Patients with metastatic epidural spinal cord compression (MESCC) and favorable survival prognoses may benefit from radiation doses exceeding 10 x 3.0 Gy. In a multi-center phase 2 trial, patients receiving 15 x 2.633 Gy (41.6 Gy10) or 18 x 2.333 Gy (43.2 Gy10) were evaluated for local progression-free survival (LPFS), motor/sensory functions, ambulatory status, pain, distress, toxicity, and overall survival (OS). They were compared (propensity score adjusted Cox regression) to a historical control group (N=266) receiving 10 x 3.0 Gy (32.5 Gy10). In the phase 2-cohort, 50 (of 62 planned) patients were evaluable for LPFS. Twelve-month rates of LPFS and OS were 96.8% and 69.9%, respectively. Motor and sensory functions improved in 56% and 57.1% of patients, and 94.0% were ambulatory following radiotherapy. Pain and distress decreased in 84.4% and 78.0% of patients. Ten and two patients experienced grade 2 and 3 toxicities, respectively. Phase 2 patients showed significantly better LPFS than the control group (p = 0.039) and a trend for improved motor function (p = 0.057). Ambulatory and OS rates were not significantly different. Radiotherapy with 15 x 2.633 Gy or 18 x 2.333 Gy was well tolerated and appeared superior to 10 x 3.0 Gy.

Familial Alzheimer’s disease (FAD) can be caused by mutations in PSEN1 that encodes presenilin-1, a component of the gamma-secretase complex that cleaves amyloid precursor protein. Alterations in calcium (Ca2+) homeostasis and glutamate signaling are implicated in the pathogenesis of FAD, however it has been difficult to assess in humans whether or not these phenotypes are the result of amyloid or tau pathology. This study aimed to assess early calcium and glutamate phenotypes of FAD by measuring the Ca2+ response of induced pluripotent stem cell (iPSC)-derived neurons bearing PSEN1 mutations to glutamate and the ionotropic glutamate receptor agonists NMDA, AMPA and kainate compared to isogenic control and healthy lines. The data shows that in early neurons, even in the absence of amyloid and tau phenotypes, FAD neurons exhibit increased Ca2+ responses to glutamate and AMPA, but not NMDA or kainate. Together this suggests that PSEN1 mutations alter Ca2+ and glutamate signaling as an early phenotype of FAD.

Adenoviruses (Ads) have been extensively manipulated for the development of cancer selective replication, leading to cancer cell death or oncolysis. Clinical studies using E1-modified oncolytic Ads have shown that this therapeutic platform was safe, but with limited efficacy, indicating the necessity of targeting other viral genes for manipulation. To improve the therapeutic efficacy of oncolytic Ads, we treated the entire Ad genome repeatedly with UV-light and have isolated AdUV which efficiently lyses cancer cells as reported previously [1]. In this report, we show that no mutations were observed in the early genes (E1 or E4) of AdUV while several mutations were observed within the Ad late genes which have structural or viral DNA packaging functions. This study also reported the increased release of AdUV from cancer cells. In this study, we found that AdUV inhibits tumor growth following intratumoral injection. These results indicate the potentially significant role of the viral late genes, in particular the DNA packaging genes, to enhance Ad oncolysis.

This study aims to evaluate the patient’s dose exposure from Computed Tomography Pulmonary Angiography (CTPA) examination and to estimates the cancer risk induced from the examinations based on the patient’s size. One hundred patients were recruited, and data information was collected retrospectively. A multi-detector (MDCT) (Philips Brilliance 128, USA) scanner were utilized for the CTPA examination, and dose data were obtained from the system. The effective diameter of each subjects’ image was measured for the Size-specific dose estimates (SSDEs). All subjects divided into Group 1 (19 – 25 cm), Group 2 (25-28 cm) and Group 3 (28-38 cm), where the association between gender were analysed. Effective dose (E), SSDE, organ dose and cancer risk of each group were evaluated and compared statistically using independent t-test and one-way ANOVA. The range of mean CTDI_vol, DLP and E values were (6.44 – 17.42 mGy), (239 – 631 mGy), (5.19 – 13.90 mSv), respectively. In respective with the patient’s effective diameter, the mean SSDE value for Group 1, Group 2 and Group 3 were 9.93 ± 3.89 mGy, 13.70 ± 9.04 mGy and 22.29 ± 7.35 mGy. The organ dose and cancer risk attained for breast, lung and liver were 17.05 ± 10.40 mGy (194 per one million procedure), 17.55 ± 10.86 mGy (192 per one million procedure) and 15.04 ± 9.75 mGy (53 per one million procedure), respectively. Lung and breast with more massive patient’s effective diameter received the highest dose exposure which increases the probability of the cancer risk. CTDI_vol was found to be underestimated, and SSDE provides more accurate in describing the radiation dose and cancer risk. Body effective diameter found to be significant on the estimation except for gender. Therefore, it is essential to apply optimised protocols in order to reduce patient’s exposure during CTPA examination.

Background and Objectives: This study aimed to evaluate the histological and biochemical ef-fects of capsaicin on implant osseointegration and oxidative stress. Materials and Methods: Male Wistar albino rats weighing between 250 and 300 grams were used in this study. Twenty-four rats were randomly divided into three equal groups: implant + control (n= 8), implant + capsai-cin-1 (n= 8), and implant + capsaicin-2 (n= 8). 2.5 mm diameter and 4 mm length titanium im-plants were surgically integrated into the corticocancellous bone parts of the femurs. In the treatment groups, rats were injected intraperitoneally with 25 mg/kg (implant + capsaicin-1) and 50 mg/kg (implant + capsaicin-2) of capsaicin. No additional applications were made in the con-trol group. Three rats in totally were died during and after the experiment, as a result of the an-alyzes performed on 21 animals. Results: The highest total antioxidant status value was found in capsaicin dose 2, according to the analysis. The control group had the highest total oxidant status and oxidative stress index values, while group 2 of capsaicin had the lowest. After analysis, we found that there was no observed positive effect on osteointegration in this study (p> 0.05), alt-hough the bone implant connection was higher in the groups treated with capsaicin. Conclusi-ons: A positive effect on osteointegration was not observed in this study. This may be due to os-teaclast activation. However it was found that it has a positive effect on oxidative stress. Osteo-clast activation may be the cause of this phenomenon. Capsaicin was found to have a positive effect on oxidative stress (p

The association between normal-range triglycerides and diabetes mortality remains unclear. This cohort study aimed to elucidate this relationship by examining 19,010 US adult participants with fasting serum triglycerides below 150 mg/dL. Cox proportional hazards models were employed to estimate mortality hazard ratios (HRs) and 95% confidence intervals (CIs). Participants were followed up for a mean of 15.3 years, during which 342 diabetes deaths were recorded. A 1-natural-log-unit increase in triglycerides was associated with a 57% higher risk of diabetes mortality (adjusted HR, 1.57; 95% CI, 1.04–2.38). Comparable results were obtained when triglycerides were analyzed in quartiles. Receiver operating characteristic curve analysis identified an optimal triglyceride cutoff of 94.5 mg/dL for diabetes mortality; individuals with triglyceride levels above this threshold faced a greater risk of diabetes mortality (adjusted HR, 1.43; 95% CI, 1.12–1.83). Further investigation revealed a positive association between normal triglyceride levels and all-cause mortality, though no association was observed between normal triglycerides and mortality from hypertension or cardiovascular disease. In conclusion, elevated triglycerides within the normal range were associated with an increased risk of diabetes mortality. Individuals with triglyceride levels of 95 mg/dL or higher may require vigilant monitoring for diabetes and its associated complications.

Worldwide, approximately 15 million people per year suffer from stroke. With about 5 million deaths, stroke is the second most common cause of death and a major cause of long-term disability. It is estimated that about 25% of people older than 85 years will develop stroke. Cannabis sativa and derived cannabinoids are used for recreational and medical purposes for many centuries. However, due to past legal status, research faced restrictions and cannabis use was stigmatized for potential negative impacts on health. With the legalization of cannabis in many countries of the world, cannabis and cannabis-derived substances such as cannabinoids and terpenes have gained more interest in medical research. Several medical effects of cannabis have been scientifically proven and potential risks were identified. In the context of stroke, the role of cannabis is controversial. Negative impact of cannabis use on stroke has been reported through anecdotal case reports and some population-based studies. However, potential beneficial effects of specific cannabinoids are described in animal studies under certain conditions. In this review, the existing body of evidence regarding the negative and positive impacts of cannabis use prior to stroke will be critically appraised.

Radiotherapy is a crucial treatment for head and neck malignancies, but it usually leads to sensorineural hearing loss (SNHL). Changes in the immune microenvironment and sensorial neuroepithelium of the inner ear after radiation exposure remain poorly understood. This study investigated cochlear morphology and macrophages in the inner ear after high-dose irradiation. The heads of 8-week-old Cx3cr1GFP/+ heterozygous male mice were irradiated with 30Gy X-rays and biological samples were taken on the 1st, 7th, and 10th days after irradiation. Auditory brainstem responses were used to assess auditory function in mice. The changes of basal membrane hair cells, spiral ganglion (SGN), and inner ear macrophages were observed using hematoxylin-eosin (HE) staining and immunofluorescence staining. The expression of inflammatory mediators in the inner ear was detected by reverse transcription-polymerase chain reaction (RT-PCR) in cochlear tissue. As a result, there was no significant hair cell loss after high doses of radiation, but the mice developed full-frequency hearing loss on day 10 when HE staining revealed SGN atrophy and immunofluorescence revealed decreased neurofilament expression. The number of macrophages in the inner ear decreased over time. RT-PCR showed that cochlear inflammatory factors and chemokines were briefly up-regulated on the first day after irradiation and then decreased over time. In summary, high-dose irradiation causes acute SNHL that does not involve hair cell loss and may be associated with SGN changes. Radiation-induced SNHL is accompanied by a reduction in cochlear macrophages and changes in the immune microenvironment, but the relationship between the two has yet to be explored.

(1) Background: After the discovery and application of Chlamydomonas reinhardtii channelrhodopsins, the optogenetic toolbox has been greatly expanded with engineered and newly discovered natural channelrhodopsins. However, channelrhodopsins of higher Ca2+ conductance or more specific ion permeability are still in demand. (2) Methods: In this study, we mutated the conserved aspartate of the transmembrane helix 4 (TM4) within Chronos (Stigeoclonium helveticum channelrhodopsin = ShChR) and PsChR (Platymonas subcordiformis channelrhodopsin) and compared them with published ChR2 (C. reinhardtii channelrhodopsin-2) aspartate mutants. (3) Results: We found that the ChR2 D156H mutant (XXM) showed enhanced Na+ and Ca2+ conductance, which was not noticed before, while the D156C mutation (XXL) influenced the Na+ and Ca2+ conductance only slightly. Furthermore, the D173H mutant of PsChR showed a much improved photocurrent, compared to wildtype, and even higher Na+ selectivity to H+ than XXM. PsChR D173H also showed a strongly enhanced Ca2+ conductance, more than 2-fold that of the calcium translocating L132C of ChR2 (CatCh). (4) Conclusions: We found that mutating the aspartate of the TM4 to histidine influences the ion selectivity of channelrhodopsins. With the large photocurrent and enhanced Na+ selectivity and Ca2+ conductance, XXM and PsChR D139H are promising powerful optogenetic tools, especially for Ca2+ manipulation.

Antiretroviral therapy has effectively suppressed HIV infection and replication and prolonged the lifespan of HIV-infected individuals. In the meantime, various complications including type 2 diabetes associated with long-term antiviral therapy have shown steady increases. Metformin has been the front-line anti-hyperglycemic drug of choice and the most widely prescribed medication for the treatment of type 2 diabetes. However, little is known about the effects of Metformin on HIV infection and replication. In this study, we showed that Metformin treatment enhanced HIV gene expression and transcription in HIV-transfected 293T and HIV-infected Jurkat and human PBMC. Moreover, we demonstrated that Metformin treatment resulted in increased CREB expression and phosphorylation, and TBP expression. Furthermore, we showed that Metformin treatment increased the recruitment of phosphorylated CREB and TBP to the HIV LTR promoter. Lastly, we showed that inhibition of CREB activation significantly abrogated Metformin-enhanced HIV gene expression. Taken together, these results demonstrated that Metformin treatment increased HIV transcription, gene expression, and production though increased CREB phosphorylation and recruitment to the HIV LTR promoter. These findings may help design the clinical management plan and HIV cure strategy of using metformin to treat type 2 diabetes, a comorbidity with an increasing prevalence, in people living with HIV.

SARS-CoV-2 breakthrough infections, associated with waning immunity, increase systemic antibody levels. In this study, we analyzed the impact of the infection timing on the magnitude of the systemic humoral response and whether breakthrough infections also boost antibody levels in the salivary compartment. We observed that the combination of infection plus vaccination, regardless of infection timing, produced a sharp increase of systemic antibodies, being higher in subjects infected after third doses. Moreover, despite high systemic antibody levels, breakthrough infections after dose 3 occurred and boosted antibody levels in the salivary compartment. These results lead to rethink the current vaccination strategies against COVID-19 and the use of salivary anti-SARS-CoV-2 antibodies for disease surveillance and vaccination follow-up.

The swelling behavior of titanium-modified austenitic stainless steel 15-15Ti was investigated by pre-implantation of He at room temperature followed by Ni irradiation at 580 °C to peak doses of 120, 240 and 400 dpa. Relatively smaller cavities were observed in the zone of helium implantation while large cavities appeared in the region near the damage peak. A correction formula of the dpa curve was proposed and applied for samples with large swelling. It is found that the steady-state swelling rate of 15-15Ti keeps at ~1% /dpa even to high doses. By comparing the swelling data of the helium-implanted and helium-free regions at same doses, 70 dpa and 122 dpa, the suppression of excessive helium on swelling can be deduced at such doses.

SARS-CoV-2 infection can lead to life-threatening clinical manifestations. Patients with cardiovascular disease (CVD) are at higher risk for severe courses of COVID-19. However, strategies to predict the course of SARS-CoV-2 infection in CVD patients at the time of hospital admission are still missing. Here, we investigated whether this prediction is achievable by prospectively analysing the blood immunophenotype of 94 participants, including 20 uninfected and 37 acutely SARS-CoV-2-infected CVD patients and 37 healthy donors, using a 36-colour spectral flow cytometry panel. Unsupervised data analysis revealed little differences between healthy donors and CVD patients, whereas the distribution of the cell populations changed dramatically in SARS-CoV-2-infected CVD patients. The latter had more mature NK cells, activated monocyte subsets, central memory CD4+ T cells, and plasmablasts but fewer dendritic cells, CD16+ monocytes, innate lymphoid cells, and CD8+ T cell subsets. Moreover, we identified an immune signature characterised by mucosal-associated invariant T (MAIT) cells, intermediate effector CD8+ T cells, and natural killer T (NKT) cells that is predictive for CVD patients with a severe course of COVID-19. Thus, intensified immunophenotype analyses can help identify patients at risk of severe COVID-19 at hospital admission, improving clinical outcomes through specific treatment.

Background: Hypertension, atherogenicity and insulin resistance are major risk factors of cardiovascular disorder (CVD), which shows a strong comorbidity with major depression (MDD) and bipolar disorder (BD). Activated oxidative and nitrosative stress (O&NS), inflammatory pathways, and increased atherogenicity are shared pathways underpinning CVD and mood disorders. Methods: The current study examined the effects of lipid hydroperoxides (LOOH), superoxide dismutase (SOD), nitric oxide metabolites (NOx), advanced oxidation protein products (AOPP), and malondialdehyde (MDA) on systolic (SBP) and diastolic (DBP) blood pressure in 96 mood disordered patients and 60 healthy controls. Results: A large part of the variance in SBP (31.6%) was explained by the regression on a z unit-weighted composite score (based on LOOH, AOPP, SOD, NOx) reflecting nitro-oxidative stress toxicity (NOSTOX), coupled with highly sensitive C-reactive protein, body weight and use of antihypertensives. Increased DBP was best predicted (23.8%) by body mass index and NOSTOX. The most important O&NS biomarkers predicting an increased SBP were in descending order of significance: LOOH, AOPP and SOD. Higher levels of the atherogenic index of plasma, HOMA2 insulin resistance index and basal thyroid-stimulating hormone also contributed to increased SBP independently from NOSTOX. Although there were no significant changes in SBP/DBP in mood disorders, the associations between NOSTOX and blood pressure were significant in patients with mood disorders but not in healthy controls. Conclusions: Activated O&NS pathways including increased lipid peroxidation and protein oxidation, which indicates hypochlorous stress, are the most important predictors of an increased BP, especially in patients with mood disorders.

The amount of outdoor particles that indoor environments receive depends on the particle infiltration factors (Fin), peculiar of each environment, and on the outdoor aerosol concentrations and size distributions. The respiratory doses received, while residing indoor, will change accordingly. This study aims to ascertain to what extent such doses are affected by the vertical distance from the traffic sources. Particle number size distributions have been simultaneously measured at street level and at about 20 m height in a street canyon in downtown Rome. The same Fin have been adopted to estimate indoor aerosol concentrations, due to the infiltration of outdoor particles and then the relevant daily respiratory doses. Aerosol concentrations at ground floor were more than double than at 20 m height and richer in ultrafine particles. Thus, although aerosol infiltration efficiency was on average higher at 20 m height than at ground floor, particles more abundantly infiltrated at ground level. On a daily basis, this involved a 2.5-fold higher dose at ground level than at 20 m height. At both levels, such doses were greater than those estimated over the period of activity of some indoor aerosol sources, therefore they represent an important contribution to the total daily dose.

There is remarkable morphologic and genetic heterogeneity in acute myeloid leukemia (AML). In a small percentage of cases of AML, increased eosinophils and/or basophils are present in the bone marrow and sometimes in the peripheral blood. This is often a puzzling diagnostic situation but also an important finding that requires special investigation. Unique chromosomal rearrangements have been correlated with an increased number of eosinophils and basophils in AML. Identification of the underlying genetic lesion that promotes eosinophilia and basophilia can dramatically change both the prognosis and the treatment of the patient. Thus clinicians must be vigilant in searching for the cause of eosinophilia and/or basophilia in patients with AML, since the different causes may lead to different treatments and survival outcomes. In this article we examine the significance of increased eosinophils and/or basophils in the context of AML, provide guidance that simplifies the differential diagnosis, and prognostic and therapeutic information about specific subtypes of AML associated with eosinophilia and/or basophilia. Evidence supporting personalized (molecularly targeted) therapy for these patients is also presented.

Ferroptosis, a regulated form of cell death characterized by iron-dependent lipid peroxide accumulation, plays a pivotal role in various pathological conditions, including neurodegenerative diseases. While reasonable evidence for ferroptosis exist e.g. in Parkinson’s disease or Alzheimer’s disease, there are only few reports on amyotrophic lateral sclerosis (ALS), a fast progressive and incurable neurodegenerative disorder characterized by progressive motor neuron degeneration. Initial studies, however, highlight that ferroptosis might be significantly involved in ALS. Key features of ferroptosis include oxidative stress, glutathione depletion, mitochondrial and dysfunction alterations in mitochondrial morphology, mediated by proteins such as GPX4, xCT, ACSL4 FSP1, Nrf2 and TfR1. Induction of ferroptosis involves small molecule compounds like erastin and RSL3, which disrupt system Xc- and GPX4 activity, respectively, yielding in lipid peroxidation and cellular demise. Mutations in Fused in Sarcoma (FUS) are associated with familial ALS. Pathophysiological hallmarks of FUS-ALS involve mitochondrial dysfunction and oxidative damage, implicating ferroptosis as putative cell death pathway in motor neuron demise. However, mechanistic understanding of ferroptosis in ALS, particularly FUS-ALS, remains limited. Here, we investigated ferroptosis vulnerability in a FUS-ALS cell model, revealing mitochondrial disturbance and increased susceptibility for ferroptosis in cells harboring the mutant FUS variant. This was accompanied by altered expression of ferroptosis-associated proteins, particularly by dramatic reduction of xCT expression, leading to cellular imbalance of the redox system and increased lipid peroxidation. Iron chelation with deferoxamine as well as inhibition of the mitochondrial calcium uniporter (MCU) significantly alleviated ferroptotic cell death and lipid peroxidation. These findings suggest a link between ferroptosis and FUS-ALS, offering potential therapeutic targets.

The mRNA vaccines for SARS-CoV-2 have demonstrated efficacy and immunogenicity in the re-al-world setting. However, most of the research on vaccine immunogenicity has been centered on characterizing the antibody response, with limited exploration into the persistence of spike-specific memory B cell response. Here we monitored the durability of the memory B cell response and characterize the trajectory of spike-specific B cell phenotypes in healthy individuals who have received two doses of the BNT162b2 vaccine up to 9 months post-vaccination. To profile the spike-specific B cell response we applied the tSNE and Cytotree automated approaches. Our data showed the induction of spike-specific IgA+ and IgG+ plasmablasts and IgA+ activated cells 7 days after the second dose which disappeared 3 months later, while subsets of spike-specific IgG+ resting memory B cells became predominant 9 months after vaccination, and they were capable to differentiate into spike-specific IgG secreting cells when in vitro restimulated. Other subsets of spike-specific B cells, such as IgM+ or unswitched IgM+IgD+ or IgG+ double negative/atypical cells, were also elicited by the BNT162b2 vaccine and persisted up to month 9. The analysis of circulating spike-specific IgG, IgA and IgM was in line with the plasmablasts observed. The longitudinal analysis of the antigen-specific B cell response elicited by mRNA-based vaccines provides valuable insights into our understanding of the immunogenicity of this novel vaccine platform destined to a future widespread use, and it is crucial in guiding future decisions and vaccination schedules.

Lime application with other complementary sustainable management practices increases crop yield, but liming is modestly applied in Serbia. This study investigated the influence of liming (1000 kg/ha) combined with the common application of mineral fertilizers on maize yield and the chemical properties of Pseudogley soil. The experiment was conducted near Kraljevo, Western Serbia, on maize hybrid ZP 606, sown in a two-year monoculture. The experiment had three treatments: fertilizer, fertilizer+lime, and control treatment. The soil is acid, poor in humus, and contains an increased content of mobile aluminum. There was a significant increase in yield under the fertilizer and lime+fertilizer treatments, compared with the control. The yield of maize in the limed treatment was 4.4–9% higher than in the fertilizer treatment. The positive effects of liming on soil are related to an increase in pH, base saturation, and available phosphorus and a decrease in available aluminum. In the fertilizer treatment, there was a small decrease in pH and base saturation, whereas the amount of aluminum remained high, indicating that further application of fertilizers without lime can increase the aluminum content and foster its toxicity. The long-term sustainability of maize production in Serbia should include liming as a regular management practice on Pseudogley soil, with the utilization of smaller doses of lime because of the potential CO2 effects. To improve soil health, food, and environmental security, and incorporate new crops, developing a framework promoting liming as a sustainable management practice is of high importance.

Tomato (Solanum lycopersicum L.) has almost 190 million tonnes produced in 2023. Tomato fruit suffer losses of up to 50% during harvest and transport, which causes financial hardship, reduces the amount of food available and causes environmental harm. Calcium plays an important role in cell wall strength. This work assessed the use of a calcium transport stimulants (MCAS) to increase the firmness of tomato fruit in the laboratory and the foliar application to tomato plants. Then handling damage was simulated. In the laboratory, the calcium with MCAS significantly increased the fruit firmness compared to the untreated and calcium without MCAS, which were not significantly different. When calcium with MCAS was applied to tomato plants foliarly before harvest, the calcium with MCAS treated fruit were significantly firmer than the untreated or calcium without MCAS treated fruit for up to 10 weeks after harvest, and this was achieved by applying only 0.91 kg ha-1 calcium. Finally, when fruit were exposed to a simulated drop, the calcium with MCAS treated fruit remained firmer than the undamaged fruit or dropped fruit with calcium without MCAS. Calcium with MCAS could significantly increase the fruit firmness and increase the shelf-life of tomatoes while applying less calcium.

Crop genetic diversity is most for the long-term sustainable production system. The breeding and production strategies of developing and growing uniform and homogenous varieties have created many different problems. Such populations are static and very sensitive to unpredictable stresses. In Nepal, more than 80% of seed system is informal s which has contributed greatly to creating and maintaining genetic diversity within the field particularly contributing to landrace diversity. This paper aims to assess and present the approaches and advantages of increased crop genetic diversity in the fields. The paper is developed based on experiences of implementing on-farm conservation activities carried out in Nepal since last two decades. Some of the evidences have been derived from on-going evolutionary plant breeding project being implemented in Nepal. The information is supplemented with field assessment, focus group discussion, and literature review. The major approaches to increase crop genetic diversity are evolutionary plant breeding, cultivar mixture, landrace enhancement, informal seed system, bulk method, diversifying the sources, participatory plant breeding, open pollination, etc. EPB and cultivar mixture are very simple and effective approaches to increase crop genetic diversity at field level. The involvement of farmers in these approaches helps to accelerate the population improvement particularly for landraces. The major advantages of increased crop genetic diversity are: seed maintenance by farmers themselves, minimal risk of crop failure, resilience to unpredictable stresses, increased amount of diversified nutrition, production increment each year, ease to produce organically, etc. However, there are some issues and problems associated with mixtures and diverse varieties, for example, not being able to harvest by machine, mature at a different date, difficulty in maintaining seeds and registration, etc. Crop genetic diversity should be considered for a climate-resilient and self-dependent production system. The higher the genetic diversity in farming land, the more chance of getting the multiple benefits in the agriculture system (Vernooy 2022).

Background. The main impetus behind the worldwide Covid-19 vaccination campaign in 2021 was to reduce the mortality attributed to SARS-CoV-2 infection in the preceding year. Nevertheless, rigorous analyses of the mortality benefits conferred by this massive vaccination effort have been lacking. Methods Statistics offers us an essential methodological approach for measuring the impacts of Covid-19 vaccination on public health. The mathematical relation between vaccinated-alive groups can be repeated between vaccinated-dead groups with relatively high statistical reliability because of the large population numbers involved. This method also confers greater statistical usefulness because it eliminates the Simpson effect. Results Calculations were performed for each of the following five(5) four-week intervals: weeks 35-38 (2021), weeks 39-42 (2021), weeks 43-46 (2021), weeks 47-50 (2021), and weeks 50(2021)-1(2022). The results obtained confirm that the mortality of the vaccinated coronavirus-infected groups was 14.5% higher on average than the mortality of non-vaccinated coronavirus-infected groups. Conclusions Vaccinated infected groups appear to have higher average mortality than their non-vaccinated infected counterparts. The findings suggest the legitimacy of extending the statistics between vaccinated living and vaccinated dead individuals for different age groups. Calculating the impact of Covid-19 vaccination on the mortality rate is a necessary step towards satisfying the first principle of medicine: “Primum non nocere”, “Do no harm”.

Plant hormones regulate the adaptive responses to various biotic and abiotic stress factors. Applied exogenously they trigger the natural plant defense mechanisms, a feature that could be implemented in strategies for supporting crop resilience. The potential of exogenous cytokinin-like acting compound (kinetin), the auxin analogue 1-naphtyl acetic acid (NAA), abscisic acid (ABA) and the ethylene-precursor 1-aminocyclopropane-1-carboxylic acid (ACC) to mitigate dehydration was tested on Lactuca sativa (lettuce) grown on 12% polyethylene glycol (PEG). Priming with different blends containing these plant growth regulators applied in bioequivalent concentrations was evaluated through biometric measurements and biochemical analyses. The combined treatment with the four plant hormones exhibited the best dehydration protective effect. The antioxidative enzyme profiling of the PGR-primed individuals revealed increased SOD, catalase and peroxidase activity in the leaves. Immunodetection of higher levels of the rate-limiting enzyme for proline biosynthesis (delta-pyroline-5-carboxylate synthase) in the primed plants coincided with a significantly higher content of the amino acid measured in the leaves. These plants also accumulated particular dehydrin types, which may have contributed to the observed stress-relieving effect. The four-component hormonal mix applied by spraying or through the roots exerted similar stress-mitigating properties on soil-grown lettuce subjected to moderate drought.

(1) The study using the quails of the Manchurian golden breed was aimed at the efficacy of the food supplement based on micro-incapsulated phytase of Obessumbacterium proteus in the recombinant yeast producer Yarrowia lipolytica at a dose of 500 FYT/kg of the feed. (2) The effect of the supplement in the poultry diets on the productivity of young and adult quails was assayed; (3) It was found that the keeping the quails on the diets using the microencapsulated phytase O. proteus provided the highest live weight, the highest intensity of egg production, and the slaughter yield of animals, the lowest feed conversion compared to those in control groups and the groups getting a commercial phytase supplement based on Aspergillus ficuum. Taken together the data obtained in our experiments indicate a high degree of assimilation of phytate-containing products by the quails when using the encapsulated phytase compared to both the control and commercial preparation of phytase of the PhyA class. It can be concluded that it is a highly expedient and promising supplement based on the microencapsulated phytase of class D for feeding, which shows the best kinetic features compared to the phytases of PhyA and PhyC classes when working in the chyme of the poultry.

The small intestinal villus is covered with a thick layer of mucus that is secreted by goblet cells and functions primarily to first barrier from damage by toxic substance. Recent studies showed that goblet cells and mucins involved in complex immune function. Lipopolysaccharide (LPS) is widespread in the housing of livestock, which can induce bacterial infection symptoms and immunological stress within a short of time. Therefore, we aimed to study the effects of long-term exposure to different doses of LPS on intestinal mucus layer and immune barrier. The result showed that mucus layer thickness and goblet cell functions were significantly increased after low doses of LPS. The intestinal mucosal barrier can block the bacteria of the lumen, but LPS can penetrate this barrier into the blood, putting the body in a state of chronic low-grade inflammation and reducing the body’s immune function. However, after long-term exposure to high doses of LPS, a large number of lysosomes in goblet cells caused loss of function, and mucus layer thickness was significantly decreased. A large amount of LPS stuck to the mucus, leading to normal LPS and inflammatory cytokines level of plasma. The intestinal tissue morphology was damaged, and a number of immune cells were necrosis in the intestine. Collectively, long-term exposure to low doses of LPS lead to chronic low-grade inflammation in the body. Long-term exposure to high doses of LPS can be directly linked to the severity of the immunosuppression in the body.

Chronic fatigue and fibromyalgia symptoms frequently occur in major depressive disorder (MDD). The pathophysiology of these symptoms may in part, be ascribed to activated immune pathways, although it is unclear whether muscular factors play a role in their onset. The aim of the present study is to examine the role of muscle proteins in major depression in association with symptoms of chronic fatigue and fibromyalgia. We measured serum levels of agrin, talin-2, titin, and creatine phosphokinase (CPK) as well as the FibroFatigue (FF), the Hamilton Depression Rating Scale (HAM-D) and the Beck Depression Inventory (BDI-II) in 60 MDD patients and 30 healthy controls. The results show a significant increase in agrin and talin-2 in MDD patients as compared with controls. There were highly significant correlations between agrin and HAM-D, BDI-II and FF scores. Agrin, but not talin or titin, was significantly and positively associated with all 12 items of the FF scale. We found that a large part of the variance in HAM-D (47.4%), BDI-II (43.4%) and FF (43.5%) scores was explained by the regression on agrin, smoking, female sex (positively associated) and education (inversely associated). CPK was significantly and inversely associated with the total FF score and with muscle and gastro-intestinal symptoms, fatigue, a flu-like malaise, headache and memory, autonomic and sleep disturbances. These results suggest that aberrations in neuromuscular (NMJs) and myotendinous junctions may play a role in MDD and that the aberrations in NMJs coupled with lowered CPK may play a role in symptoms of chronic fatigue and fibromyalgia in MDD. Moreover, the increase of agrin in MDD probably functions as part of the compensatory immune-regulatory system (CIRS).

Earthquakes often entail alterations in the groundwater flow regime, in the phreatic level, in the surge and loss of springs, and discharge in brooks and springs. As for the latter, there are diverse feasible mechanisms, so there is a variety of theoretical approaches to elucidate the post-earthquake effects on spring discharge. This study adopts a conceptual approach, primarily presenting various methods for estimating water released by earthquakes by calculating discharge surpluses in springs. This study delves into refined techniques rooted in groundwater hydraulics, displaying applications of analytical and simulation methodologies to quantify seismic-induced groundwater discharge in springs. Investigating springs as natural indicators, this research applies mathematical precipitation-runoff models, specifically the CREC model, for simulating hydrographs in post-earthquake scenarios. We apply analytical procedures or mathematical simulation techniques employed in groundwater hydraulics for natural aquifer recharge calculations. Firstly, we briefly describe the methods based on the analysis of depletion curves of hydrographs in spring discharge. Additionally, certain mathematical rainfall-runoff models utilized in simulating hydrographs of karstic springs, along with derived analytical approximations, are adapted for this scenario. These hydraulic calculations involve the depletion coefficient and hydrodynamic volumes of aquifers, parameters that reveal certain aspects of the relation between groundwater and earthquakes, such as: a) Acknowledging faults as the primary geological structures in transmitting pore pressures due to earthquakes. b) Clarifying mechanisms of permeability enhancement during earthquakes. c) Highlighting the substantial volumes in motion within the Earth's interior, which, for instance, could constitute a significant source for the origin of mineral deposits. The findings highlight diverse features of the complex interplay between hydrogeological and tectonic processes at challenging spatial and temporal scales.

Background Epidemiological studies have associated plasma galectin-4 (Gal-4) levels with prevalent and incident diabetes, and with increased risk of coronary artery disease, but data regarding possible associations with stroke are lacking. Methods We tested Gal-4 association with prevalent stroke in a population-based cohort, and whether Gal-4 increases after ischemic stroke in mice fed a high-fat diet (HFD). Results Gal-4 was higher in subjects with compared to without prevalent ischemic stroke, and was associated with prevalent ischemic stroke (odds ratio 1.52; 95% confidence interval 1.01-2.30; p=0.048) adjusted for age, sex and covariates of cardiometabolic health. Plasma Gal-4 increased after stroke in both controls and HFD-fed mice, but HFD exposure was devoid of impact in Gal-4 levels. Conclusions This study demonstrates higher plasma Gal-4 levels in both a stroke mouse model and individuals with prevalent stroke.

Background—In 2011, Miller and Goldman published a study in Human and Experimental Toxicology that found a counterintuitive, positive correlation, r = 0.70 (r² = 0.49, p < .0001), demonstrating that as nations require more vaccine doses for their infants, infant mortality rates (IMRs) tend to increase (worsen). The dataset (n = 30) included the United States, a nation that required the most vaccines for their infants, and all nations with better IMRs than the United States. Dr. E. Bailey, a professor at BYU, and her students, recently read the Miller-Goldman study and found it "troublesome that this manuscript is in the top 5% of all research outputs" and falsely claimed that its findings were due to "inappropriate data exclusion," i.e., failure to analyze the "full dataset" of all 185 nations. The "Bailey reanalysis," titled Infant vaccination does not predict increased infant mortality rate: correcting past misinformation, was posted to the medRxiv preprint server on September 10, 2021 (version 1) and October 5, 2021 (version 3) and Europe PMC preprint server on September 10, 2021. Objective—This present study examines the various claims postulated by the Bailey reanalysis and assesses the robustness of their methodology, analyses, and reported results and conclusions. Methods—Data discussed in this paper are based on the previously mentioned study by Miller and Goldman and the Bailey reanalysis. Results—Linear regression analysis of IMR and the number of vaccine doses for each country yield a statistically significant positive correlation of r = 0.70 (p < .0001) for the top nations (n = 30) chosen by Miller-Goldman and r = 0.16 (p < .04) for the "entire dataset" chosen by Bailey et al (n = 185). Bailey also conducted linear regression analyses (for the year 2019) of IMRs as a function of vaccination rates for each of eight different vaccines and reported statistically significant inverse correlations for 7 of 8 vaccines over the entire range of vaccination rates. However, Miller and Goldman reanalyzed the Bailey analyses for nations with vaccination rates below 60% and found no statistically significant correlation for six vaccines (DPT, Hib, hepatitis B, polio, rotavirus, and measles) and statistically significant positive correlations for tuberculosis (r = 0.8, p < .005) and pneumococcal (r = 0.6 p < .023) vaccines. Conclusions—Bailey’s reanalysis corroborates a statistically significant positive correlation originally reported by Miller and Goldman. However, Bailey’s reported correlation (r = +0.16, p < .04) is small, likely due to poor methodology (failing to account for covariates, i.e., disparities among numerous socioeconomic factors that add uncertainty to their conclusion). The r-value reported by the Bailey reanalysis demonstrates an effect size that is about one-fourth (0.16/0.70) that reported by Miller-Goldman—underscoring how critically important it is for Bailey's reanalysis to eliminate confounding variables. Moreover, Bailey’s linear regression analyses of IMR as a function of vaccination rates for each of eight different vaccines demonstrate that some countries with low vaccination rates have low IMRs, while other countries with high vaccination rates have high IMRs. Rather than supporting a strong inverse correlation, the Bailey reanalysis demonstrates high vaccination rates are neither necessary nor sufficient to cause low IMR.

The BNT162b2 vaccine is globally used for preventing morbidity and mortality related to COVID-19. Cancer patients have had priority for receiving the vaccine due to their diminished immunity. This study reports the response of administering the 3rd and 4th vaccine doses to can-cer patients receiving active anti-neoplastic treatment. 142 patients have received two doses of the mRNA-based BNT162b2 COVID-19 vaccine, while 76 and 25 patients have received three and four doses, respectively. The efficacy of the humoral response following two vaccine doses was diminished in cancer patients, especially in the group of patients receiving chemotherapy. In a multivariate analysis, patients after three and four BNT162b2 vaccine doses were more likely to have antibody titers in the upper tertile compared to patients after two doses of the vaccine (odds ratio (OR) 7.62 (95% CI 1.38-42.12), p=0.02 and 17.15 (95% CI 5.01-58.7), p<0.01, respective-ly). Unlike the response after two doses, the 3rd and 4th BNT162b2 vaccine booster doses, had an increased efficacy of 95-100% in cancer patients while on active treatment. This result could be explained by different mechanisms including the development of memory B cells.

Background and Aims: Metabolic Syndrome (MetS), a global problem, predisposes to an increased risk for Type 2 diabetes and premature cardiovascular disease. While MetS is associated with central obesity, there is scanty data on adipocyte hypertrophy, increased fat cell size (FCS), in MetS. The aim of this study was to investigate FCS status in gluteal adipose tissue biopsy of patients with nascent MetS without the confounding of diabetes, cardiovascular disease, smoking or lipid therapy . Methods and Results: Fasting blood and subcutaneous gluteal adipose tissue (SAT) biopsy were obtained in MetS (n=20) and controls (n=19). Cardio metabolic features, FFA levels, hsCRP and HOMA-IR were significantly increased in patients with MetS. Waist-circumference adjusted-FCS was significantly increased in patients with MetS and increased with increasing severity of MetS. Furthermore, there were significant correlations between FCS with glucose, HDL-C and the ratio of TG: HDL-C. There were significant correlations between FCS and FFA, endotoxin and monocyte TLR4 abundance. Also, FCS correlated with readouts of NLRP3 Inflammasome activity. Most importantly, FCS correlated with markers of fibrosis and angiogenesis. Conclusions: In conclusion, in patients with nascent MetS, we demonstrate WC-adjusted increase in FCS from gluteal AT that correlated with cellular inflammation, fibrosis and angiogenesis. While these preliminary observations were in gluteal fat, future studies are warranted to confirm these findings in visceral and other fat depots.

Food security is a matter of global concern, as the supply of food is one of the basic needs, ensuring the survival of the species. The trend of globalization and development of the global economy has shifted the responsible, local consumption patterns towards an increased homogeneity of diets, with food products being disconnected from their source, leading to two major results: (1) increased global consumption, driven by the extensive availability of affordable seasonal foods throughout the year and (2) increased uncertainty in the supply chain – susceptible to disruptions, causing food insecurity. To determine what the nutritional model is in the case of the present study – Romania – we developed a questionnaire of 32 questions and distributed it to 1,053 respondents from Romania. The survey was conducted during 2021 and 2022, both in urban and rural areas with the aim of investigating the consumption pattern of the population. The analysis of the questionnaire data reveals overconsumption of animal products, starchy vegetables and bread and pastry products. This nutritional pattern with a high intake in animal protein, correlated with a lack of diversification, is extremely unsustainable, having a negative impact on human health and environmental health.behaviour towards a careful approach to food, environment and personal health, aims to identify consumption patterns that have the potential to increase the sustainability of the food system and a positive correlation with food security. Adopting sustainable dietary patters, based on short supply chains and mindful consumption, has great potential in restoring food security and resilience to adversity.

Antibiotic resistant Pseudomonas aeruginosa infections are the primary cause of mortality in people with cystic fibrosis (CF). Yet it has only recently become appreciated that resistance mutations can also increase P. aeruginosa virulence, even in the absence of antibiotics. Moreover, the mechanisms by which resistance mutations increase virulence are poorly understood. In this study we tested the hypothesis that mutations affecting efflux pumps can directly increase P. aeruginosa virulence. Using genetics, physiological assays, and model infections, we show that efflux pump mutations can increase virulence. Mutations of the mexEF efflux pump system increased swarming, rhamnolipid production, and lethality in a mouse infection model, while mutations in mexR that increased expression of the mexAB-oprM efflux system increased virulence during an acute murine lung infection without affecting swarming or rhamnolipid gene expression. Finally, we show that an efflux pump inhibitor, which represents a proposed novel treatment approach for P. aeruginosa, increased rhamnolipid gene expression in a dose-dependent manner. This finding is important because rhamnolipids are key virulence factors involved in dissemination through epithelial barriers and cause neutrophil necrosis. Together, these data show how current and proposed future anti-Pseudomonal treatments may unintentionally make infections worse by increasing virulence. Therefore, treatments that target efflux should be pursued with caution.

2003 it is shown that after the Chernobyl accident, childhood leukemia by single age and year of birth in the 0-4y cohort increased significantly in Wales and Scotland combined in the period 1986-1990 compared with controls born 1970-1985 and 1991-1994. Relative risk RR = 1.41; 95% CI 1.20<RR<1.65; p = 0.00004. These exposure periods were chosen because whole body Caesium-137 monitoring had demonstrated that internal exposures persisted for more than 4 years. The dose-response exhibits saturation and reversal, interpreted as biological censoring effects in the developing individual.

Employing data supplied by the Oxford-based UK Childhood Cancer Research Group in 2003 it is shown that after the Chernobyl accident, childhood leukemia by single age and year of birth in the 0-4y cohort increased significantly in Wales and Scotland combined in the period 1986-1990 compared with controls born 1970-1985 and 1991-1994. Relative risk RR = 1.41; 95% CI 1.20<RR<1.65; p = 0.00004. These exposure periods were chosen because whole body Caesium-137 monitoring had demonstrated that internal exposures persisted for more than 4 years. The dose-response exhibits saturation and reversal, interpreted as biological censoring effects in the developing individual.

Indoor crop cultivation systems such as vertical farms or plant factories necessitate artificial lighting. Light spectral quality can affect plant growth and metabolism and, consequently, the amount of biomass produced and the value of the produce. Conflicting results on the effects of light spectrum in different plant species and cultivars make it critical to implement a singular lighting solution. In this study we explored the response of green and red leaf lettuce cultivars (’Aquino’, CVg, or ‘Barlach’, CVr, respectively) to long-term blue-enriched light application (WB). Plants were grown for 30 days in a growth chamber with optimal environmental condi-tions (temperature: 20°C, relative humidity: 60%, ambient CO2, Photon Flux Density (PFD) of 260 µmol m-2 s-1 over an 18-h photoperiod). At 15 days after sowing (DAS) white spectrum LEDs (WW) were compared to WB (λPeak = 423 nm) maintaining the same PFD of 260 µmol m-2 s-1. At 30 DAS, both lettuce cultivars resulted adapted to the blue light variant, though the adaptive re-sponse was specific to the variety. Rosette weight, light use efficiency and maximum operating efficiency of PSII photochemistry in the light, Fv/Fm’, were comparable between the two light treatments. Significant light quality effect was detected on stomatal density and conductance (20% and 17% increase under WB, respectively, in CVg) and, on the modified anthocyanin re-flectance index (mARI) (40% increase under WB, in CVr). Net photosynthesis response was gen-erally stronger in CVg compared to CVr; e.g. net photosynthetic rate, Pn, at 1000 µmol m-2 s-1 PPFD increased from WW to WB by 23% in CVg, compared to 18% in CVr. Results obtained suggest the occurrence of distinct physiological adaptive strategies in green and red pigmented lettuce cultivars to adapt to the higher proportion of blue light environment.

Measurements of copper and zinc in transfusion-dependent thalassemia (TDT) show contradictory results.Aim of the study: To examine serum levels of these minerals in TDT in relation to iron overload indices and erythron variables. Methods: This study recruited 60 children with TDT and 30 healthy children aged 3-12 years old.Results: Zinc was significantly higher in TDT children than in control children, whilst copper and the copper to zinc ratio were significantly lowered in TDT. Serum zinc was significantly associated with the number of blood transfusions and iron overload variables (including serum iron and TS%) and negatively with erythron variables (including hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin). Serum copper was significantly and negatively associated with the same iron overload and erythron variables. The copper to zinc ratio was significantly correlated with iron, TS%, ferritin, hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin. Albumin levels were significantly higher in TDT children than in control children. Conclusion: Our results suggest that the increase in zinc in children with TDT may be explained by iron loading anemia and hemolysis and the consequent shedding of high amounts of intracellular zinc into the plasma. Increased albumin levels and treatment with Desferral may further contribute towards higher zinc levels in TDT. We suggest that the elevations in zinc in TDT are a compensatory mechanism protecting against infection, inflammation, and oxidative stress. Previous proposals for prophylactic use of zinc supplements in TDT may not be warranted.

This brief report presents a comparative analysis to examine differences in the mean dose of nitrate supplementation between studies with positive and negative results on exercise performance. Protocols of at least six days that had positive results used lower nitrate doses (~7.7 mmol), whereas those with negative results used higher doses (~10.2 mmol), showing a statistically significant difference (p < 0.05). These findings suggest long-term supplementation with higher doses (~10.2 mmol) may not improve exercise performance. Further research is essential to understand the underlying mechanisms.

Since the beginning of the mass immunization with COVID-19 vaccines of patients with multiple sclerosis, many data on the efficacy and safety of these vaccines have been produced. Considering that MS is an autoimmune disease whose pathology can be explained by an altered immune system and that some DMTs seem to be able to decrease the antibody response against COVID-19 vaccines, we carried out this retrospective study with the aim to evaluate the safety in terms of AEFIs occurrence and the antibody response after the third dose of COVID-19 vaccines in people with MS. Third doses were administered from October 2021 to January 2022. Two hundred and ten patients (64.8% female; mean age: 46 years) received the third dose of the mRNA-based COVID-19 vaccine and were included in the study. The majority of patients (n=193) were diagnosed with RRMS and EDSS values were ≤3.0 in 72.4% of them. DMTs most commonly used by included patients were interferon Beta 1-a, dimethyl fumarate, natalizumab and fingolimod. Overall, 160 patients (68.8% female) experienced 294 AEFIs, of which about 90% were classified as short-term, while 9.2% were classified as long-term. The most commonly reported following the booster dose were pain at the injection site, flu-like symptoms, headache, fever and fatigue. Regarding the immune response, consistently with literature data, we found that patients receiving ocrelizumab and fingolimod had lower IgG titer than patients receiving other DMTs.

Metabolic syndrome is a growing global health problem. Evidence suggests that diets rich in phytochemical-containing herbs and spices can contribute to reduced risk of chronic disease. This review assesses the scope of evidence supporting the use of herbs and spices in the diet for prevention or treatment of metabolic syndrome and associated health conditions. A search of PubMed and Scopus databases was carried out to assess the available clinical or cohort evidence for culinary doses of commonly used herbs and spices. Trials that were measuring health factors related to metabolic disorders or the health of individuals with metabolic syndrome or associated diseases were included. Out of a total of 1742 papers identified, there were 146 relevant studies on black pepper, chilli, cardamom, cinnamon, coriander, cumin, fennel, fenugreek, garlic, ginger, Nigella seed, rosemary, sage and turmeric. No relevant research was found for cloves, mint, oregano, parsley or thyme. Cinnamon, fenugreek and ginger were the herbs/spices with the most published trials on them and showed promise for glycaemic control. Cardamom appears to have potential to reduce inflammatory markers, and cinnamon, ginger and turmeric for blood lipids. Patients with type 2 diabetes were the population most likely to be included in studies, but the preventative benefits of herbs/spices in healthy populations were also investigated, particularly for chilli, ginger and cinnamon. There is evidence for the beneficial effect of culinary doses of many common herbs/spices in the prevention and treatment of metabolic syndrome and associated disorders.

The difficulty in obtaining commercial fertilizers by smallholder farmers in sub-Saharan Africa makes it very important to optimize the use of local organic resources. In VilanKulo, Mozambique, a study was carried out on okra (Abelmoschus esculentus) over two growing seasons in a haplic Lixisol, a loamy-sand textured soil, applying both bat guano and biochar prepared by an artisanal process. Bat guano was applied at two rates (5 and 10 t ha−1), one month and just before sowing. Biochar was also used at two rates (5 and 10 t ha−1) applied close to sowing. Mixtures of biochar and guano at two rates (1 and 4 t ha−1, and 2 and 8 t ha−1, respectively) were also used along with a non-fertilized control. Field trials were arranged in a completely randomized design with three replicates. The treatments receiving high rates of guano tended to show significantly higher fruit yields (&gt; 10 t ha−1, being the two-year average) in comparison to the control, which showed the lowest average okra fruit yield (6.21 t ha−1). In guano treatments, the apparent recovery by okra of some important nutrients, such as nitrogen (N), was greater than the amount of nutrient contained in the guano itself. This result, together with many others related to tissue nutrient concentration, soil properties and residual fertilizing value in guano plots, indicates a strong mineralization of guano during the growing season, probably due to its low carbon (C)/N ratio and favourable environmental conditions for the mineralization process, such as high temperature and well-aerated soil. The result also suggests some kind of manuring effect, i.e., a fertilizing effect of guano beyond what can be explained by the nutrient supply. The use of biochar increased total organic C in the soil and cation exchange capacity (CEC) compared to the control, but did not affect variables related to plant performance, such as tissue nutrient concentration or plant growth and yield.

Food security is a matter of global interest, as the provision of food resources is the primary determinant of human existence. Food is one of the basic needs, ensuring the survival of the species. The trend of globalization and development of the global economy has shifted the responsible local consumption patterns to an increased homogeneity of diets, food products being disconnected from their source. This disconnection led to two major results: (1) increased global consumption, with seasonal foods now available throughout the year, and a decrease in food prices on the global market, and (2) increased uncertainty in the supply chain, susceptible to disruptions, as was the case during the Covid-19 pandemic. The present study, based on the research and analysis of third-party data on food security, sustainable diets, consumption patterns and recommended actions to change the current unsustainable consumer behaviour towards a careful approach to food, environment and personal health, aims to identify consumption patterns that have the potential to increase the sustainability of the food system and a positive correlation with food security. Adopting sustainable dietary patters, based on short supply chains and mindful consumption, has great potential in restoring food security and resilience to adversity.

This study demonstrates the orientation and the ‘shape factor’ have pronounced effects on the development of the localized pressure fields inside of the helmet. We used anatomically accurate headform to evaluate four modern combat helmets under blast loading conditions in the shock tube. The Advanced Combat Helmet (ACH) is used to capture the effect of the orientation on pressure under the helmet. The three modern combat helmets: ECH, Ops-Core, and Airframe, were tested in frontal orientation to determine the effect of helmet geometry. Using the unhelmeted headform data as a reference, we characterized pressure distribution inside each helmet and identified pressure focal points. The nature of these localized “hot spots” is different than the elevated pressure in the parietal region of the headform under the helmet widely recognized as the under-wash effect also observed in our tests. It is the first experimental study which indicates that the helmet presence increased the pressure experienced by the eyes (as evidenced by the pressure sensors in the H8 and H9 locations), and the forehead (denoted as H1 location). Pressure fingerprinting using an array of sensors combined with the application of principle component analysis (PCA) helped elucidate the subtle differences between helmets.

Biphasic bone substitutes (BBS) are nowadays established biomaterials. Through their constant development even natural components like hyaluronic acid (HY) are added to improve both their handling and also their regenerative properties. However, low knowledge exists regarding the consequences of the HY addition for their biocompatibility and the inflammatory tissue reactions. Thus, the present study was conducted aiming to analyze the influence of two different amounts of high molecular weight HY (HMWHY) combined with a BBS on the in vitro biocompatibility and the in vivo tissue reaction. Established in vitro procedures using L929 cells were used for cytocompatibility analyses under the test conditions of DIN EN:ISO 10993-5. For the in vivo study part, calvarial defects were created in 20 Wistar rats and subsequently filled with the BBS and the BBS combined with two different HMWHY amounts, i.e., BBS+HY(L) and BBS+HY(H). As controls empty defects were used. Established histological, immunohistochemical and histomorphometrical methods were applied to analyze the tissue reactions to the three different materials, including the induction of pro- and anti-inflammatory macrophages and multinucleated giant cells (BMGCs). The in vitro results showed that none of the materials or compositions caused biological damages to the L929 cells and can considered to be non-toxic. The in vivo results showed that only the addition of high doses of HY to a biphasic bone substitute significantly decreases the occurrence of proinflammatory macrophages (* p < 0.05) comparable to the numbers found in the control group, while no significant differences within the three study groups for M2-macrophages nor BMGCs were detected. In conclusion, the addition of different amounts of HMWHY does not seem to affect the inflammation response to the BBS while improving the material handling properties.

Background: This longitudinal study aimed to investigate the relationship between self-reported chewing status and increases in waist circumference (WC) after 1 year in 10,870 Japanese adults who had received health checkups. Subsequently, 8,068 participants were included in the final analysis at follow-up. Methods: Chewing status was evaluated using a self-reported questionnaire at baseline; 1,080 (13%) respondents were diagnosed as having poor chewing status. We defined an increase in WC of ≥ 5 cm after 1 year as an unhealthy increase; in total, 613 (7.5%) respondents met this criterion. Results: After adjusting for age, gender, WC, body mass index (BMI), and chewing status, an increase in WC ≥ 5 cm was found to be positively associated with gender (females: odds ratios [ORs]: 1.206; 95% confidence intervals [CIs]: 1.008–1.443), WC (ORs: 0.967; 95% CIs: 0.954–0.981), BMI (≥ 25 kg/m2; ORs: 2.194; 95% CIs: 1.715–2.808), and chewing status (poor; ORs: 1.356; 95% CIs: 1.084–1.697). Conclusions: These findings suggest that self-reported poor chewing status is associated with increases in WC after 1 year in Japanese adults.

The COVID-19 virus is spread to the respiratory system by minute airborne particles in contrast to large particle fomite transmission. Yet, an often-repeated health directive during the COVID-19 pandemic was to improve handwashing to limit the spread of the virus. Persistent handwashing can aggravate obsessive-compulsive disorder (OCD), diminishing mental health. Given that handwashing is unlikely to control the spread of COVID-19, it is pertinent to determine if the directive for handwashing to eradicate the COVID-19 virus increased the incidence of OCD and, as such, promoted negative mental health. This scoping review of the parameter, “handwashing, mental health, COVID-19, OCD”, conducted during July 2023, searched six relevant databases. The result was that negative mental health related to increased handwashing was evident both for those already diagnosed with OCD and regarding new cases of OCD throughout the duration of the pandemic. The conclusion is that health officials should update details of their health directives as information becomes available during a pandemic and, concerning COVID-19, the directive to concentrate on handwashing should have been relaxed once it was known that spread of the virus by fomite transmission was improbable. This likely would have reduced the incidence of OCD and improved mental health.

The study presents a novel approach of programing pain inhibition in chronic pain patients based on the hypothesis that pain perception is modulated by dysfunctional dorsal medial nucleus tractus solitarii (dmNTS) reflex arcs that produce diminished baroreflex sensitivity (BRS) resulting from a conditioned response. This study tested whether administration of noxious and non-noxious electrical stimuli synchronized with the cardiac cycle resets BRS, reestablishing pain inhibition. 30 pain-free normotensives controls (NC) and 32 normotensives fibromyalgia (FM) patients received two, ≈8 minute-epochs of cardiac-gated, peripheral electrical stimuli. Non-painful and painful electrical stimuli were synchronized to the cardiac cycle as the neuromodulation experimental protocol (EP) with 2 control conditions (CC1, CC2). BRS, heart-rate-variability (HRV), pain threshold and tolerance, and clinical pain intensity were assessed.Reduced BRS in FM at baseline increased by 41% during two, ≈8 minute-epochs of stimulation. Thresholds in FM increased significantly during the experimental protocol (all Ps<0.001) as did HRV. FM levels of clinical pain significantly decreased by 35.52% during the experimental protocol but not during control stimulations (P<0.001). Baroreceptor training may reduce FM pain by BRS-mediated effects on intrinsic pain regulatory systems and autonomic pain modulation. These processes seem to be linked by classical and operant conditioning.

Glioblastoma (GBM) is often resistant to conventional and targeted therapeutics. ERBB4 is expressed throughout normal brain and is an oncogene in several pediatric brain cancers; therefore, we investigated ERBB4 as a prognostic marker and therapeutic target in GBM. Using RT-qPCR, we quantified mRNA encoding total ERBB4 and known ERBB4 variants in GBM and non-neoplastic normal brain (NNB) samples. Using immunohistochemistry, we characterized the localization of total and phosphorylated ERBB4 (p-ERBB4) and EGFR protein in archived GBM samples and assessed their association with patient survival. Furthermore, we evaluated the effect of ERBB4 phosphorylation on angiogenesis and tumorigenicity in GBM xenograft models. Total ERBB4 mRNA was significantly lower in GBM than NNB samples, with the JM-a and CYT-2 variants predominating. ERBB4 protein was ubiquitously expressed in GBM but was not associated with patient survival. However, high p-ERBB4 in 11% of archived GBM samples, independent of p-EGFR, was associated with shorter patient survival (12.0±3.2 months) than was no p-ERBB4 (22.5±9.5 months). Increased ERBB4 activation was also associated with increased proliferation, angiogenesis, tumorigenicity and reduced sensitivity to anti-EGFR treatment in xenograft models. Despite low ERBB4 mRNA in GBM, the functional effects of increased ERBB4 activation identify ERBB4 as a potential prognostic and therapeutic target.

A 24 week-controlled trial was conducted in menopausal women (mean age:61.5) to assess serum 25-hydroyvitaminD (s25OHD) evolution in relation to three interdependent determinants: doses of supplemented (Suppl.) vitamin D₃ (VitD₃); baseline status; seasonality. Participants were randomized into 3 groups (Gr): Gr.Suppl.0, time-controls maintaining dietary habits; Gr.Suppl.5 and Gr.Suppl.10 consuming one and two 125 g servings of VitD₃-fortified yogurts with 5 and 10 µg daily doses, respectively. The 16 intervention-weeks lasted from early-January to mid-August, the 8 follow-up-weeks from late-August to mid-October. Before enrollment, subjects were randomized into two s25OHD strata: “Low stratum (LoStr)“: 25-50 nmol/L; “High stratum (HiStr)“: >50-75 nmol/L. All enrolled participants remained compliant until study end: Gr.Suppl.0 (n=45), Gr.Suppl.5 (n=44) Gr.Suppl.10 (n=44). Over the 16 intervention and 8 follow-up weeks, s25OHD increased in both supplemented groups, more in Gr.Suppl.10 than Gr.Suppl.5. The constant rate of s25OHD per supplemental VitD₃ microgram was greater in LoStr than HiStr. s25OHD increase was greater with late (mid-March) than early (mid-January) inclusion. In conclusion, this randomized trial demonstrates: -a dose-dependent s25OHD improvement related to fortified yogurt consumption; -an inversely baseline-dependent increase in s25OHD; -a seasonal effect that highlights the importance of vitamin D₃ supplementation during winter, even at 5µg/d, in healthy menopausal women.

Intra-abdominal pressure (IAP) elevation during capnoperitoneum can cause adverse cardiovascular and respiratory effects. This study aimed to determine if a sequentially increased IAP affects cardiovascular and respiratory variables in anesthetized dogs and evaluate the effects of constant rate infusion of dexmedetomidine (Dex) on cardiovascular and respiratory variables with increased IAP. Five dogs were anesthetized, instrumented, and the Veress needle was equipped to adjust the IAP using a carbonic anhydrase insufflator. Stabilization was conducted for 1 h, and physiological variables were measured in IAPs of 0, 5, 10, 15, and 20 mmHg and after desufflation. After the washout period, the dogs underwent similar procedures along with constant rate infusion of dexmedetomidine. Cardiovascular effects of increased IAP up to 20 mmHg were not significant in healthy beagle dogs and those administered with dexmedetomidine. In the control group, the arterial pressure slightly increased, but not statistically significant, at an IAP of 20 mmHg compared with that at baseline (mean arterial blood pressure, p = 0.399; systolic arterial blood pressure, p = 0.293; diastolic arterial blood pressure, p = 0.141). When comparing the control and dexmedetomidine groups, overall significant effects of dexmedetomidine were noted on heart rate, cardiac output, and systemic vascular resistance during the experiment. Respiratory effects were not affected by abdominal insufflation when compared between different IAPs and between the two groups. Overall, an increased IAP of until 20 mmHg did not significantly affect cardiovascular and respiratory variables in both control and dexmedetomidine groups. This study suggests that dexmedetomidine infusion administration is applicable in laparoscopic procedures in healthy dogs.

Background: Hepatic erythrophagocytosis is augmented in NASH and amplifies inflammation and fibrosis. Although various pro-phagocytic signals have been identified on erythrocytes of NASH patients, the role of bound thrombospondin-1 (TSP-1), which acts as an “eat-me” signal, arginase-1, which regulates the levels of nitric oxide in erythrocytes, and phosphatidylethano-lamine (PE) which can amplify erythrophagocytosis and hepatic inflammation have not been explored. Hence, we sought to investigate the levels of arginase-1 and TSP-1 in erythrocyte lysate and PE in erythrocyte membranes of NASH patients. Methods: Twenty-four patients and 14 healthy controls participated in our study. The levels of TSP-1 and arginase were quantified by ELISA in erythrocyte lysates, and the levels of PE in erythrocyte membranes by thin layer chro-matography. Results: Erythrocytes of NAFLD patients exhibit lower levels of arginase-1 and TSP-1 (p<0.01). Erythrocyte-bound TSP-1 levels correlated with the levels of erythrocyte surface CD47. Phosphatidylethanolamine was increased in erythrocytes of NASH patients and was accompanied by increased release, indicating exposure. Conclusion: Our results imply reduced TSP-1 binding by erythrocytes which could allow free TSP-1 molecules to act on macrophages, enhancing erythrophagocytosis. Increased PE which could amplify inflammation after efferocytosis, while downregulation of arginase-1 could lead to defective efferocytosis.

Background: There is now evidence that schizophrenia and deficit schizophrenia are neuro-immune conditions and that oxidative stress toxicity (OSTOX) may play a pathophysiological role. Aims of the study: To compare OSTOX biomarkers and antioxidant (ANTIOX) defenses in deficit versus non-deficit schizophrenia. Methods: We examined lipid hydroperoxides (LOOH), malondialdehyde (MDA), advanced oxidation protein products (AOPP), sulfhydryl (-SH) groups, paraoxonase 1 (PON1) activity and PON1 Q192R genotypes, total radical-trapping antioxidant parameter (TRAP) as well as immune biomarkers in patients with deficit (n=40) and non-deficit (n=40) schizophrenia and healthy controls (n=40). Results: Deficit schizophrenia is characterized by significantly increased levels of AOPP and lowered -SH, and PON1 activity, while no changes in the OSTOX/ANTIOX biomarkers were found in non-deficit schizophrenia. An increased OSTOX/ANTIOX ratio was significantly associated with deficit versus non-deficit schizophrenia (Odds ratio=3.15, p<0.001). Partial least squares analysis showed that 47.6% of the variance in a latent vector extracted from psychosis, excitation, hostility, mannerism, negative symptoms, psychomotor retardation, formal thought disorders, and neurocognitive test scores was explained by LOOH+AOPP, PON1 genotype + activity, CCL11, tumor necrosis factor (TNF)-α, IgA responses to neurotoxic tryptophan catabolites (TRYCATs), whereas -SH groups and IgM responses to MDA showed indirect effects mediated by OSTOX and neuro-immune biomarkers. Discussion: Our findings indicate that with increasing overall severity of schizophrenia, neuro-immune and neuro-oxidative (especially protein oxidation indicating chlorinative stress) toxicities become more prominent and together with lowered antioxidant defenses and impairments in innate immunity-associated resilience against neurotoxic processes shape a distinct nosological entity, namely deficit schizophrenia.

Prolylcarboxypeptidase (PRCP, PCP, Lysosomal Pro-X-carboxypeptidase, Angiotensinase C) controls angiotensin - and kinin- induced cell signaling. Elevation of PRCP appear to be activated in chronic inflammatory diseases (cardiovascular disease (CVD), diabetes) in proportion to severity. Vascular endothelial cell senescence and mitochondrial dysfunction have consistently been shown in models of CVD in aging. The cellular senescence, a driver of age-related dysfunction, can differentially alter the expression of lysosomal enzymes due to lysosomal membrane permeability. There is a lack of data demostrating the effect of age-related dysfunction on the expression and function of PRCP. To explore the changes in PRCP, PRCP-dependent prekallikrein (PK) pathway was charcterized in early – and late-passage human pulmonary artery endothelial cells (HPAECs). Detailed kinetic analysis of cells treated with high molecular weight kininogen (HK), a precursor of bradykinin (BK), and PK revealed a mechansim by which senescent HPAECs activate the generation of kallikrein upon the assembly of the HK-PK complex on HPAECs in parallel with an upregulation of PRCP and endothelial nitric oxide (NO) synthase (eNOS) and NO formation. The NO production and expression of both PRCP and eNOS increased in early-passage HPAECs while decreased in late-passage HPAECs. Low activity of PRCP in late passage HPAECs was associated with rapid decreased telomerase reverse transcriptase mRNA levels. We also found that, with an increase in the passage number of HPAECs, reduced PRCP altered respiration rate. These results indicated that aging dysregulates PRCP protein expression, and further studies will shed light into the complexity of PRCP-dependent signling pathway in aging.

The pathophysiology of many mood disorders is closely related with abnormal stress response associated with the dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis and cortisol overproduction. The hippocampus, key structure of the limbic system responsible for both cognitive and emotional spheres, is selectively vulnerable to excess of glucocorticoids (GCs) inducing neuroinflammation and neurodegeneration. The antiGC therapy of psychiatric diseases, in particular depressive disorders, may be a useful additional treatment. Among other approaches, targeting glucocorticoid receptors, abounded in the hippocampus, is regarded as highly promising. However, though the preclinical data provide firm evidence to the concept of antiGC therapy for stress-related diseases, clinical studies still are at the proof-of-concept stage. Noteworthy, chronic GC excess is associated not only with mood diseases, but also with cognitive decline, metabolic disorders, diabetes. Potentially, antiGC (HPA axis modifying) therapy may alleviate affective symptoms, cognitive disturbances, GC and insulin resistance and adverse side effects of conventional drugs through beneficial effects on hippocampal dysfunction and neurodegeneration, neuroinflammation, and neurogenesis. Since stress/GC-associated neuroinflammation-mediated pathology of the limbic system and, specifically, the hippocampus, is a general feature typical for many brain diseases, the concept of antiGC therapy may be extended, tested and validated in a wider spectrum of cerebral pathologies.

Introduction The COVID-19 virus was initially reported in Dec 2019 as the causative agent of a pneumonia breakout in Wuhan China. This virus rapidly spread from China to Europe and the East Coast of the United States eventually reaching the South West United States and indigenous tribes in mid -March. Since, then the indigenous tribes have been devasted by the virus which the Governor of New Mexico has likened as an existential threat. Methodology A PubMed search was performed utilizing the words: Navajo Indian, Indigenous Indian, Wuhan Virus, COVID-19, SARs coronavirus, ACE2, S protein, virulence, clinical presentation, epidemiology, genome, treatment, structure, MERs, pathogenesis and/or pathology alone and in combination with other terms. Each paper was evaluated by three content experts for quality, reproducibility, credibility and reputation of the journal Results: Navajo’s and other indigenous peoples may have elevated levels of ACE2 receptors in their lungs and other tissues allowing greater susceptibility to the COVID-19 virus. Increased levels of diabetes and protein nutrition are directly related to increased morbidity and mortality in this group while obesity, COPD, and heart diseas are not. The increased morbidity and mortality is exasperated by an inability to test for COVID-19 Conclusion: The infectivity rate of Navaho’s on the reservation is 22 times higher than the national average with a death rate near 4%. Comorbidites account for some of the increased morbidity and mortality while lack of access to adequate health care unnecessarily magnifies the poor outcome. The threat to indigenous tribes in the Southwest of COVID-19 is dire.

The purpose of the present study was to investigate the effects of psychological pressure on corticospinal excitability, the spinal reflex, lower limb muscular activity, and reaction times during a task involving dominant leg movements. Ten healthy participants performed a simple reaction time task by raising the heel of their dominant foot from a switch. After 20 practice trials, participants performed 20 non-pressure and 20 pressure trials in a counterbalanced order. Stress responses were successfully induced, as indexed by significant increases in state anxiety, mental effort, and heart rates under pressure. Significant increases in motor evoked potential (MEP) amplitude of the tibialis anterior muscle (TA) occurred under pressure. In terms of task-related EMG amplitude, the co-contraction rate between the soleus (SOL) and TA muscles significantly increased along with SOL and TA EMG amplitudes under pressure. Hoffmann reflexes for SOL and reaction times did not change under pressure. These results indicate that corticospinal excitability and leg muscle-related EMG activity increase homogeneously during lower limb movements that are performed under psychological pressure.

: Alluvial soils naturally possess abundant soil nutrients. Nevertheless, excessive nitrogen addition and inappropriate use of nitrogen fertilizers lead to conditions where soil nutrients become immo-bilized, ultimately reducing productivity. This study investigates the potential of natural nano-material zeolite which is important land resources to improve nutrient utilization efficiency and mitigate the harmful effects of excessive fertilizer application. Specifically, the research ex-plores the incorporation of clinoptilolite zeolite and processed sewage sludge blends, alongside reduced recommended nitrogen fertilizer doses, to evaluate their impact on soil quality and plant growth. A greenhouse experiment was conducted (three-year study), comprising eight treatments with varying proportions of zeolite and sewage sludge. The efficacy of these treatments in en-hancing soil carbon pools, nutrient indices, and plant growth responses was assessed. Results in-dicate that a combination of 50% recommended fertilizer dose, 4-6% zeolite, and 5-10% sewage sludge significantly improved multiple aspects of plant growth, including leaves, tillers, culms, and panicles, leading to increased straw and grain yields. The addition of 6% zeolite in conjunc-tion with sewage sludge positively influenced plant tillering capacity. Certain treatment combina-tions exhibited a greater impact on plant height at different growth stages. For example, the treatment with 75% recommended fertilizer dose, 4% zeolite, and 5% sewage sludge significantly affected plant height at 40 and 55 days after treatment. Additionally, the combination of 50% recommended fertilizer dose, 6% zeolite, and 10% sewage sludge promoted plant height, carbon levels, and various yield parameters in later stages. Principal component analysis effectively dis-tinguished treatments incorporating zeolite and sewage sludge based on plant responses. The combination of 6% zeolite and 10% sewage sludge, along with a 50% recommended fertilizer dose, positively influenced soil carbon fractions, nutrient levels, and the growth response of rice plants.

Oral cancer is a major public health burden worldwide. The lack of biomarkers for early diagnosis has increased the difficulty in managing this disease. Recent studies have reported that neutrophil gelatinase-associated lipocalin (NGAL), a secreted glycoprotein, is upregulated in various tumors. In our study we found that NGAL was significantly downregulated in primary malignant and metastatic tissues of oral cancer compared to normal tissues. The downregulation of NGAL was strongly correlated with the degree of differentiation and stage (I-IV), and can serve as a prognostic biomarker for oral cancer. Tobacco carcinogens were also found to be involved in the downregulation of NGAL. Mechanistic studies revealed that knockdown of NGAL increased oral cancer cell proliferation, survival, and migration, and also induced resistance against cisplatin. Silencing of NGAL activated mTOR signaling and reduced autophagy by the LKB1-AMPK-p53-Redd1 signaling axis. Moreover, cyclin-D1, Bcl-2, and MMP-9 were upregulated, and caspase-9 was downregulated, suggesting that silencing of NGAL increases oral cancer cell proliferation, survival, and migration. Thus, from our study it is evident that downregulation of NGAL activates the mTOR pathway and helps in the progression of oral cancer.

We conducted this study to determine the potential cryopreservative effects of different hesperidin (vitamin P; HSP) doses on ram semen after freeze-thawing. Semen samples were obtained from Sönmez rams by an artificial vagina. The samples were divided into six groups: control, 10, 50, 100, 250, and 500 µg/mL HSP (C, HSP10, HSP50, HSP100, HSP250, and HSP500, respectively). At the end of the study, sperm motility and kinetic parameters, plasma membrane acrosome integrity (PMAI), high mitochondrial membrane potential (HMMP), viability, lipid peroxidation levels (LPL), chromatin damage, oxidant parameters, and antioxidant parameters were assayed. None of the doses of HSP added to the semen extender showed any enhancing effect on progressive motility compared to C (p>0.05). In fact, HSP500 had negative effects (p<0.05). Moreover, PMI activities were the highest at the HSP10 dose, while LPL values were the lowest (p<0.05). The doses of HSP10 and HSP50 added to the Tris extender medium showed positive effects on spermatozoon chromatin damage. Consequently, we can say that HSP doses used in this study are not effective on semen progressive motility, but the HSP10 dose is effective on PMAI and chromatin damage by reducing LPL.

1) Background: The Aicardi-Goutières syndrome (AGS) is a rare congenital disease which courses with severe psychomotor delay in neurodevelopment. We studied a 3-years and 4-months old child with very important growth and weight affectation, microcephaly and loss of his developmental skills from 16-months of age, in which previous metabolic and genetic studies discarded any abnormality. Therefore diagnosis was cerebral palsy of unknown etiology. He presented spastic paraparesia, poor fine motricity, cognitive impairment and absence of oral communication. One year after discharge, a de novo mutation was detected in a single nucleotide in the gene IFIH1: c.2317G>C, being then diagnosed of AGS. 2) Methods: Blood analysis showed very low IGF-1 and slightly elevated liver transaminases. Treatment consisted in GH (0.04 mg/kg/day), melatonin (20 mg/day, and after 3-months 50 mg/day), and daily intense neurorehabilitation (5 days/week). Tests for evaluating childhood developmental milestones (GMFM-88, BDIST and the WeeFim test) were carried out every 3-months. 3) Results: The equivalent age at admission (10-months) increased to 24-months at discharge. There were clear improvements in spasticity, fine motor function, swallowing, cognition and autonomy as well as in communication, growth and weight. 4) Conclusion: Most likely melatonin blocked or decreased the interferon signature, allowing GH and neurorehabiltation to act on neurodevelopment.

A novel concept of a finned piston system is presented and analyzed where the compression heat is continuously extracted from the compression chamber. The resulting compression characteristic moves in direction of an isothermal process, reducing so the temperature of the compressed fluid in the compression chamber and reducing the necessary mechanical work for the process. The finned piston concept consists in an integrated heat exchanger inside of the chamber and being constituated of imbricated flat fins placed on the stator part and on the mobile piston. The internal heat exchange surface is strongly increased in comparison with a classical piston/cylinder. The energetic performance of the new system is evaluated with the help of simulation. Pressures, forces and temperature of the compressed gas are simulated as well as the mechanical work needed. The different curves are compared with adiabatic and isothermal characteristics.

This study explored the potential synergism within chlorhexidine-silver nanoparticles conjugates against Influenza type A, Staphylococcus aureus, Escherichia coli, and Candida albicans. Silver nanoparticles (SN) were obtained by the reduction of silver ions with green tea total phenolic extract and conjugated with chlorhexidine (Cx). The particles were characterized by UV-Vis and FTIR spectroscopies, dynamic light scattering, X-ray diffraction, and transmission electron microscopy. A stable negatively-charged nano-silver colloid (ζ=-50.01) was obtained with an average hydrodynamic diameter of 92.34 nm. In the presence of chlorhexidine, the spectral data and the shift of the zeta potential to positive values (ζ=+44.59) revealed the successful sorption of the drug onto the silver surface. The conjugates (SN-Cx) demonstrated potentiation in the effects against S. aureus and C. albicans, and synergism against E. coli with minimal inhibitory concentrations of SN 5.5 µg/mL+Cx 8.8 µg/mL. The SN showed excellent, increasing with time, virucidal properties, and low toxicity. The coupling of the cationic chlorhexidine with nano-silver, however, did not reduce its intrinsic cytotoxicity on various cell lines (MDCK, BJ, and А549). The newly-synthesized antimicrobial agent presented with an extended and promising therapeutic spectrum and needs to be further evaluated on relevant to the designated route of administration three-dimensional cell models (e.g., nasal, bronchial, dermal, ocular, etc.).

Three carbon-chain extension genes associated with fatty acid synthesis in cotton, namely GhKAR, GhHAD, and GhENR, play important roles in oil accumulation in cotton seeds. In the present study, these three genes were cloned and characterized. The expression patterns of GhKAR, GhHAD and GhENR in the high seed oil content cultivars 10H1007, 10H1014, and 10H1041 differed somewhat compared with those of 2074B with low seed oil content at different stages of seed development. GhKAR showed all three cultivars showed higher transcript levels than that of 2074B at 10, 40 and 45 DPA. The expression pattern of GhHAD showed a lower transcript level than that of 2074B at both 10 and 30 DPA but higher transcript level than that of 2074B at 40 DPA. GhENR showed a lower transcript level than that of 2074B at both 15 and 30 DPA. The highest transcript levels of GhKAR and GhENR were detected at 15 DPA in 10H1007, 10H1014, and 10H1041 compared with 2074B. From 5 to 45 days post anthesis (DPA) cotton seed, the oil content accumulated continuously in the developing seed. Oil accumulation reached the peak at 40 DPA to 45 DPA and slightly decreased in mature seed. In addition, GhKAR and GhENR showed different expression patterns in fiber and ovule development processes, in which they showed high expression levels at 20 DPA during fiber elongation stage, but their expression level peaked at 15 DPA during ovule development processes. These two genes showed the lowest expression levels at the late seed maturation stage, while GhHAD showed peak at 10 DPA of fiber development. Compared to 2074B, the oil contents of GhKAR and GhENR overexpression lines increased 1.05~1.08 folds. These results indicated that GhHAD, GhENR and GhKAR were involved in both seed oil synthesis and fiber elongation with dual biological functions in cotton.

Due to urban warming, energy demand for cooling buildings is rising. The current study used CitySim to estimate the cooling energy requirements for 40 buildings in Downtown, Dubai using high-resolution climate data from weather research and forecasting (WRF) coupled with single layer urban canopy model (SLUCM). Simulating the four mitigation scenarios allowed for the examination of the reduction in cooling load caused by the addition of greenery at a rate ranging from 25% to 100%. The insulated building's cooling demand reduced by a maximum of 13.89% under 100% GI (M4). Scenario M4 resulted in a reduction of 4.6 kWh/m2 and 3.1 kWh/m2 for the non-insulated and insulated low-rise residential buildings, respectively, while the high-rise buildings saw a reduction of 3.09-4.91 kWh/m2 for the non-insulated and 2.07-3.09 kWh/m2 for insulated buildings. This study offered a potential remedy to deal with the problem of urban heating in subtropical environments.

Conclusions: Meningiomas with histopathological CNS invasion show a higher proliferative activity.

Sonic Hedgehog (Shh) is a prototypical angiogenic agent with a crucial role in the regulation of angiogenesis. Experimental studies have shown that Shh is upregulated in response to ischemia. Also, Shh may be found on the surface of circulating microparticles (MPs) and MPs bearing Shh (Shh+ MPs) have shown the ability to contribute to reparative neovascularization after ischemic injury in mice. In this study, the plasma number of Shh+ MPs in patients with peripheral artery disease (PAD) and control subjects without PAD. We found significantly higher number of Shh+ MPs in plasma of subjects with PAD, compared to controls, while the global number of MPs – produced either by endothelial cells, platelets, leukocytes, and erythrocytes – was not different between PAD patients and controls. Interestingly, the concentration of Shh protein unbound to MPs – which was measured in MP-depleted plasma – was not different between subjects with PAD and controls, indicating that, in the setting of PAD, the call for Shh recapitulation does not lead to secretion of protein into the blood but to binding of the protein to the membrane of MPs. These findings provide novel insights on the mechanisms through which the Shh signaling is reactivated during ischemia in humans, with potentially important fundamental and clinical implications.

Background: Lung cancer is one of the leading causes of morbidity and mortality worldwide with 25% of deaths due to lung cancer occurring in Europe. This study therefore sought to assess the burden of lung cancer by country and to evaluate the magnitude of fine Particulate Matter (PM2.5) and cigarette smoking by country in Europe. Methods: An ecological study nested on the World Health Organization air pollution database 2016 was conducted. We sampled 30 European Countries, with a total of 1625 mean annual samples of Particulate Matter (PM2.5) collected from 1625 designated sites (n = 1625). We further used the ‘World Health Disease Rankings’ database to extract Lung Cancer Morbidity and Mortality Rate by country. We used SAS version 9.4 to indicate the distribution of PM2.5 and Lung Cancer Mortality Rate. Results: Lung cancer Relative Risk (RR) was 1.0 in all never- smokers. RR for Ex-smokers for Adeno carcinoma was 3.5 in males and 1.1 in females, small cell carcinoma was 16.2 in males and 3.8 in females. RR for current smokers for Adeno carcinoma was 8.0 in males and 4.1 in females, small cell carcinoma was 57.9 in males and 18.2 in females. Mean annual PM2.5 by country ranged from 6.01 to 37.28µg/m3 whereas lung cancer mortality rate by country ranged from 19.67 to 54.26 deaths per 100,000 population. Conclusion: Cigarette smoking and exposure to both second hand smoke and high concentration of PM2.5 resulted into increased burden of lung cancer in Europe. Countries should re-strategize to reduce the burden of lung cancer in Europe.

Purpose: This study investigated the hypotensive effect of RKI-1447, a Rho kinase inhibitor, in a porcine ex vivo pigmentary glaucoma model. Methods: Twenty-eight porcine anterior chambers were perfused with medium supplemented with 1.67 × 10⁷ pigment particles/mL for 48 hours before treatment with RKI-1447 (n = 16) or vehicle control (n = 12). Intraocular pressure (IOP) was recorded and outflow facility was calculated. Primary trabecular meshwork cells were exposed to RKI-1447 or vehicle control; effects on the cytoskeleton, motility, and phagocytosis were evaluated. Result: Compared to baseline, the perfusion of pigment caused a significant increase in IOP in the RKI-1447 group (P = 0.003) at 48 hours. Subsequent treatment with RKI-1447 significantly reduced IOP from 20.14 ± 2.59 mmHg to 13.38 ± 0.91 mmHg (P = 0.02). Pigment perfusion reduced the outflow facility from 0.27 ± 0.03 at baseline to 0.18 ± 0.02 at 48 hours (P < 0.001). This was partially reversed with RKI-1447. RKI-1447 caused no apparent histological changes in the micro- or macroscopic TM appearance. RKI-1447-treated primary TM cells showed significant disruption of the actin cytoskeleton both in the presence and absence of pigment (P < 0.001) but no effect on TM migration was observed. Pigment-treated TM cells exhibited a reduction in TM phagocytosis, which RKI-1447 reversed. Conclusion: RKI-1447 significantly reduces IOP by disrupting TM stress fibers and increasing TM phagocytosis. These features may make it useful for the treatment of secondary glaucomas with an increased phagocytic load.

In most industrialized countries, screening programs for cervical cancer have shifted from cytology (Pap smear or ThinPrep) alone on clinician-obtained samples to the addition of screening for human papillomavirus (HPV), its main causative agent. For HPV testing, self-sampling instead of clinician-sampling has proven to be equally accurate, in particular for assays that use nucleic acid amplification techniques. In addition, HPV testing of self-collected samples in combination with a follow-up Pap smear in case of a positive result is more effective in detecting precancerous lesions than a Pap smear alone. Self-sampling for HPV testing has already been adopted by some countries, while others have started trials to evaluate its incorporation into national cervical cancer screening programs. Self-sampling may result in more individuals willing to participate in cervical cancer screening, because it removes many of the barriers that prevent women, especially those in low socioeconomic and minority populations, from participating in regular screening programs. Several studies have shown that the majority of women who have been underscreened but who tested HPV-positive in a self-obtained sample, will visit a clinic for follow-up diagnosis and management. Additionally, a self-collected sample can also be used for vaginal microbiome analysis, which can provide additional information about HPV infection persistence as well as vaginal health in general.

Background: Aberrations in endothelial cells, immune and oxidative pathways are associated with atherosclerosis (ATS) and unstable angina (UA). The role of trace elements, minerals, and the endogenous opioid system (EOS) in UA are less well established. Methods: We measured lipid, insulin resistance (IR), and immune, trace element (copper and zinc), mineral (magnesium, calcium), EOS (β-endorphin and mu-opioid receptor (MOR)) and antioxidant (vitamin D3) biomarkers in patients with ATS (n=60) and UA (n=60) and healthy controls (n=58). Results: ATS patients showed increased atherogenic and IR indices, IL-6, IL-10, β-endorphin, copper and magnesium, and lower zinc than healthy controls. Logistic regression showed that UA was significantly discriminated from ATS without UA with an accuracy of 85.5% using calcium, IL-10, β-endorphin, MOR, triglycerides, IR (all positively), and copper and vitamin D3 (inversely). Neural networks showed that UA was discriminated from ATS without UA with an area under the ROC curve of 0.942 using MOR, β-endorphin, calcium, insulin resistance, vitamin D3 and copper as input variables. We found that 50.0% of the variance in IR was explained by the regression on copper, IL-10, IL-6 (all positively), and zinc (inversely), while 32.9% of the variance in the atherogenic index of plasma was explained by copper, IL-10 (both positively), and magnesium (inversely). Conclusion: UA is not only mediated by insulin resistance, atherogenicity, and immune disorders, but also by aberrations in the endogenous opioid system and trace elements as well as lowered antioxidant levels. Copper appears to play a key role in IR and atherogenicity.

The artificial intelligence chatbot ChatGPT can answer questions and solve tasks posed by the user within seconds. Using an exemplary task, this study investigates the reliability and con-sistency of the answers given by ChatGPT. For this purpose, it was analyzed whether the an-swers differ when a question is asked repeatedly and whether selected content categories and associated word combinations coincide with those from scientific literature. ChatGPT was asked 400 times, how the connectedness between humans and nature can be increased. The responses were classified into a categorization system and the most frequently occurring word combina-tions for each category were extracted. These word combinations were used for a search of re-lated scientific literature. In addition, the Normalized Mutual Information (NMI) between the 400 individual responses was calculated. The results show that the phrases used by ChatGPT within the categories are also found in the scientific literature, however, the number of mentions between scientific literature and ChatGPT differs. In addition, the NMI suggested that there are large differences between the categories mentioned in the individual answers. These results in-dicate that ChatGPT currently still has difficulties in answering complex questions and cannot yet replace scientific literature research or academic writing.

Background and Objectives: Acculturation is associated with excessive weight gain among immigrants to the U.S. Whether dietary factors mediate this association is unclear. This study aimed to examine whether overall diet quality or specific component(s) of diet quality mediate the association between acculturation and Body Mass Index (BMI) among Mexican American (MA) men and women. Material and Methods: This is a secondary data analysis using dietary intake data from 24-hour dietary recalls, measured height and weight, and self-reported acculturation from the National Health and Nutrition Examination Survey (NHANES) cycles 1999-2000 to 2011-2012. A total of 6848 MA adults (≥20 yrs) with reliable dietary recall status and body measures were included in the study. Path analyses was performed in Mplus with complex survey design effects adjusted. Results: HEI components of whole grains and sodium were found to play meditating roles in the acculturation-BMI association, and their effects on BMI were opposing [indirect effect were -0.01 (SE 0.00) and 0.02 (0.01), respectively]. In gender-specific analysis, sodium [0.01 (0.00)] was a significant mediator only in MA men; whereas, whole grains [-0.01 (0.00)] was a significant mediator only in MA women. Conclusions: HEI components of whole grains and sodium appeared to be significant dietary mediators in the acculturation-BMI association. Understanding the variations of dietary components and their relationship with acculturation as well as BMI is useful for developing dietary interventions and obesity reduction.

Using a randomized, double-blinded, placebo-controlled, parallel group design, this investigation determined if the combination of 2-weeks flavonoid supplementation (329 mg/day, quercetin, anthocyanins, flavan-3-ols mixture) and a 45-minute walking bout (62.2±0.9% VO_2max) enhanced the translocation of gut-derived phenolics into circulation in a group of walkers (N = 77). The walkers (flavonoid, placebo groups) were randomized to either sit or walk briskly on treadmills for 45 minutes (thus four groups: placebo-sit, placebo-walk, flavonoid-sit, flavonoid-walk). A comparator group of runners (N = 19) ingested a double flavonoid dose for 2 weeks (658 mg/day) and ran for 2.5 h (69.2±1.2% VO_2max). Four blood samples were collected (pre- and post-supplementation, immediately-post- and 24-h post-exercise/rest). Of the 76 metabolites detected in this targeted analysis, 15 increased after the 2.5-h run, and when grouped were also elevated post-exercise (versus placebo-sit) for the placebo- and flavonoid-walking groups (P < 0.05). A secondary analysis showed that pre-study plasma concentrations of gut-derived phenolics in the runners were 40% higher compared to walkers (P = 0.031). These data indicate that acute exercise bouts (brisk walking, intensive running) are linked to an increased translocation of gut-derived phenolics into circulation, an effect that is amplified when combined with a 2-week period of increased flavonoid intake or chronic training as a runner.

Diabetes is a chronic condition that worsens living conditions and causes significant problems, particularly in the vascular system. Many different treatment options are used to prevent these negative effects of diabetes. The most important of these is changing living conditions and exercising regularly.This study aimed todetermining the impacts of a 6-week anaerobic exercise protocol on the blood glucose levels and Glut4 gene expression in the muscle tissues of streptozocin (STZ)-induced diabetic rats. A total of 45 rats were separate control, sedentary, and exercise groups (n=15 each). The STZ used to induce diabetes in rats was applied once with a single intraperitoneal injection. No diabetes was created in the control group, and no exercise was performed, whereas in the sedentary group, diabetes was induced, and no exercise was applied. It was determined that the Glut4 gene expression in the muscle tissue of the exercise group was importantly increased when compared with the sedentary diabetes group.Glut4 gene is an important gene involved in blood glucose regulation and anaerobic exercise significantly increased the expression level of this gene in our study.

Fossil-based emissions can be avoided through using wood in place of non-renewable raw materials as energy and materials. However, increasing wood harvest influences forest carbon stocks. This effect may reduce the overall climate benefit of wood use significantly but is widely overlooked. We carried out a systematic review of simulation studies and compared differences in forest carbon and amount of wood harvested between more and less intensive wood harvest scenarios for three different time perspectives; short (1-30 years), mid (31-70 years) and long (71-100 years). Out of more than 450 reviewed studies 44 provided adequate data. Our results show that increased harvesting reduced carbon stocks over 100 years in temperate and boreal forests roughly 1.6 (stdev 0.9) t_C per t_C harvested. The value proved to be robust when outliers explicitly influenced by other factors than change in harvest rate, such as increase in fertilization or forest area, were removed. Interestingly, no significant difference in carbon impacts was found for average values of boreal and temperate forests or between short and long time-horizons. However, impacts tend to be greatest in the mid-term. This carbon balance indicator that we estimated can be interpreted as carbon debit of wood harvest in forests. It is significant compared with the typical GHG credits in technosphere generated by avoiding fossil emissions in substitution and increase in carbon storage in harvested wood products, and should not be ignored. Our estimates provide default values that can directly be included in GHG balances of products or assessment of mitigation policies and measures related to wood use. However, more systematic scenarios and transparent data in which different factors influencing forest carbon stocks are separately studied are clearly required to provide better constrained estimates for specific forest types.

Background: Increase of collagen I (COL I)/COL III ratio enhances vessel wall stiffness and renders vessels less resistant to blood flow and pressure changes. We hypothesized that COL I/COL III ratio is increased in the brain arteriovenous malformations (bAVMs), which is associated with bAVM hemorrhage. Method: Surgically resected human bAVM samples and mouse bAVMs induced in three transgenic mouse lines with activin receptor-like kinase 1 or endoglin deletion in the endothelial cells or in the brain focally. Colony-stimulating factor receptor inhibitor was used to transiently deplete microglia. COL I and COL III levels, hemorrhage, and gene expression in bAVMs were analyzed. Results: The COL I and COL III levels and the COL I/COL III ratio were higher on human and mouse bAVMs than controls, which was associated with bAVM hemorrhage. Col I and Col III mRNAs were also increased in mouse bAVMs. The degree of microhemorrhage in mouse bAVMs was positively correlated with Col I/Col III ratios. Transient depletion of microglia reduced Col I/Col III ratio and microhemorrhage in mouse bAVMs. Conclusion: COL I/COL III ratio are increased in bAVM vessels, which is associated with bAVM hemorrhage. Depletion of microglia reduces Col I/Col III ratio and hemorrhage in mice bAVMs.

Background: The coexistence of a high IgE level and transient hypogammaglobulinemia of infancy ( THI ) with atopic dermatitis (AD) is well known, but the coexistence with a marked serum IgE level ≥ 1000 IU/mL is a rare finding. Literature is scarce regarding IgE levels in patients with THI and AD after treatment with immunoglobulin (Ig). The present article is the first to describe a finding of marked IgE elevation (> 1000 IU/mL) after treatment with intravenous immunoglobulin (IVIG). This paper also reviews previous related reports and series. Case presentation and review: We reported on a female infant 8 months old, with THI and severe AD. She was treated with IVIG infusion after the failure of conventional therapy. Initially, serum levels of IgE were high, and serum levels of IgG were low. After 4 weeks of treatment with IVIG, the patient showed clinically improved AD in parallel with elevated IgG level but increased IgE level to a higher level. We also review previous results of IgE levels reported in cases with THI and AD before and after Ig therapy. The mean increment in IgE levels was 227.5 IU/mL (SD = 164.2). The review showed that the IgG is directly related to IgA and IgM in addition to IgE. Results also showed that IgA and IgM also have a direct relation with IgE. Conclusion: We report a case of marked IgE level in a THI patient with AD after IVIG treatment. Also, there were increased levels of IgA and IgM. A similar finding was observed in other reviewed cases.

Background: There is a strong comorbidity between mood disorders and metabolic syndrome (MetS). Increased levels of reactive oxygen and nitrogen species (RONS) and nitro-oxidative stress toxicity (NOSTOX) partially underpin this comorbidity.Aims: To examine the associations of RONS/NOSTOX biomarkers with MetS after adjusting for the significant effects of mood disorders (major depression, and bipolar type 1 and 2), generalized anxiety disorder (GAD), tobacco use disorder (TUD), and male sex.Methods: The study included subjects with (n=65) and without (n=107) MetS and measured levels of superoxide dismutase 1 (SOD1), lipid hydroperoxides (LOOH), nitric oxide metabolites (NOx), malondialdehyde (MDA), and advanced oxidation protein products (AOPP) and computed z unit-weighted composite scores which reflect RONS/NOSTOX. The study included 105 patients with mood disorders, 46 with GAD, and 95 with TUD.Results: MetS was associated with increased levels of MDA and AOPP, independently from mood disorders, TUD, sex and GAD. Atherogenicity and insulin resistance (IR) were significantly associated with a NOSTOX composite score. Mood disorders, TUD, GAD, male sex and MetS independently contribute to increased RONS/NOSTOX. The RONS/NOSTOX profile of MetS was different from that of GAD, which showed increased SOD1 and NOx levels. TUD was accompanied by increased SOD1, LOOH and MDA, and male sex by increased LOOH and AOPP.Conclusions: MetS is characterized by increased lipid peroxidation with aldehyde formation and chlorinative stress, and atherogenicity and IR are strongly mediated by RONS/NOSTOX. Partially shared RONS/NOSTOX pathways underpin the comorbidity of MetS with mood disorders, GAD, and TUD.

Cryptococcal meningitis remains a significant opportunistic infection among HIV-infected patients, contributing 15%-20% of HIV-related mortality. A complication of initiating Antiretroviral therapy (ART) following opportunistic infection is Immune Reconstitution Inflammatory Syndrome (IRIS). IRIS afflicts 10-30% of HIV-infected patients with cryptococcal meningitis (CM), but its immunopathogenesis is poorly understood. We compared circulating T cell memory subsets and cytokine responses among 17 HIV-infected Ugandans with CM: 11 with and 6 without CM-IRIS. At meningitis diagnosis, stimulation with cryptococcal capsule component, glucuronoxylomannan (GXM) elicited consistently lower frequencies of CD4⁺ and CD8⁺ T cell memory subsets expressing intracellular cytokines (IL-2, IFN-γ and IL-17) among subjects who subsequently developed CM-IRIS. After ART initiation, T cells evolved to show a decreased CD8⁺ central memory phenotype. At the onset of CM-IRIS, stimulation more frequently generated polyfunctional IL-2⁺/IL-17⁺ CD4⁺ T cells in patients with CM-IRIS. Moreover, CD8⁺ central and effector memory T cells from CM-IRIS subjects also demonstrated more robust IL-2 responses to antigenic stimulation vs. controls. Thus, ART during CM elicits distinct differences in T cell cytokine production in response to cryptococcal antigens both prior to and during the development of IRIS, suggesting an immunologic foundation for the development of this morbid complication of CM infection.

Circulating microparticles (MPs) are novel potential biomarkers in cancer patients. Their role in hepatocellular carcinoma (HCC) is under intensive investigation. In this study we tested the hypothesis that MPs expressing the antigen HepPar1 are increased in the blood of subjects with HCC and may serve as markers of early recurrence after liver resection (LR). We studied fifteen patients affected by HCC undergoing LR and used flow cytometry to assess the number of circulating HepPar1+ MPs. Ten subjects without HCC (five with liver cirrhosis and 5 with healthy liver) were used as controls. After LR, HCC patients were followed-up for early recurrence, which occurred in seven cases. The number of circulating HepPar1+ MPs was significantly higher in subjects affected by HCC, compared to individuals without cancer (p<0.01). We also found that, among HCC patients, the number of circulating HepPar1+ MPs, measured before LR, was significantly higher in those who displayed early recurrence compared to those without recurrence (p=0.02). Of note, other types of circulating MPs, such as those derived from endothelial cells (CD144+) or those produced by the activated endothelium (CD144+/CD62+) were not associated with HCC, neither could predict HCC recurrence. HepPar1+ MPs deserve further investigation as novel biomarkers of disease and prognosis in HCC patients.

This study investigates the potential benefits of integrating coarser particle size distributions (PSDs) of 45-106 µm into laser-based powder bed fusion of metals (PBF-LB/M), aiming to reduce costs while maintaining quality standards. Despite the considerable advantages of PBF-LB/M in producing intricate geometries with high precision, the high cost of metal powders remains a barrier to widespread adoption. By exploring the use of coarser PSDs, particularly from electron beam-based powder bed fusion of metals (PBF-EB/M), significant cost-saving opportunities are identified. Through comprehensive powder characterization, process analysis, and mechanical property evaluation, this study demonstrates that PBF-LB/M can effectively utilize coarser powders while achieving comparable mechanical properties to those produced with 20-53 µm PSD. Adaptations in process parameters enable the successful processing of coarser powders, maintaining high-relative density components with minimal porosity. Additionally, market surveys reveal substantial cost differentials between PBF-LB/M and PBF-EB/M powders, indicating 40 % cost reduction potential by integrating coarser PSDs into PBF-LB/M. Overall, this study provides valuable insights into the economic and technical feasibility of printing with coarser powders in PBF-LB/M, offering promising avenues for cost reduction without compromising quality, thus enhancing competitiveness and adoption of the technology in manufacturing applications.

Current research suggests that polycystic ovary syndrome (PCOS) might originate in utero and implicates the placenta in its pathogenesis. Kisspeptin (KISS1) and neurokinin B (NKB) are produced by the placenta in high amounts, and they have been implicated in several pregnancy complications associated with placental dysfunction. However, their placental expression has not been studied in PCOS. We isolated mRNA after delivery from the placentae of 31 PCOS and 37 control women with term, uncomplicated, singleton pregnancies. The expression of KISS1, NKB, and neurokinin receptors 1, 2, and 3 was analyzed with real-time polymerase chain reaction, using β-actin as the reference gene. Maternal serum and umbilical cord levels of total testosterone, sex hormone binding globulin (SHBG), free androgen index (FAI), androstenedione, dehydroepiandrosterone sulfate (DHEAS), Anti-Mullerian hormone (AMH), and estradiol were also assessed. NKB placental mRNA expression was higher in PCOS versus controls in pregnancies with female offspring. NKB expression depended on fetal gender, being higher in pregnancies with male fetuses. NKB was positively correlated with umbilical cord FAI and AMH, and KISS1 with cord testosterone and FAI; there was also a strong positive correlation between NKB and KISS1 expression. Women with PCOS had higher serum AMH and FAI and lower SHBG than controls. Our findings indicate that NKB might be involved in PCOS-related placental dysfunction, and warrant further investigation. Studies assessing the placental expression of NKB should take fetal gender into consideration.

Curdlan is a water-insoluble polymer that has structure and gelling properties useful in a wide variety of applications such as in medicine, cosmetics, packaging and the food and building industries. The capacity to produce curdlan has been detected in certain soil-dwelling bacteria of various phyla, although the role of curdlan in their survival remains unclear. One of the major limitations of the extensive use of curdlan in industry is the high cost of production during fermentation, partly because production involves specific nutritional requirements such as nitrogen limitation. Engineering of the industrially relevant curdlan-producing strain Agrobacterium sp. ATTC31749 is a promising approach that could decrease the cost of production. Here, during investigations on curdlan production, I found that curdlan was deposited as a capsule. Curiously, only a part of the bacterial population produced a curdlan capsule. This heterogeneous distribution appeared to be due to the activity of Pcrd, the native promoter responsible for the expression of the crdASC biosynthetic gene cluster. To improve curdlan production, Pcrd was replaced by a promoter (PphaP) from another Alphaproteobacterium, Rhodobacter sphaeroides. Compared to Pcrd, PphaP was stronger and only mildly affected by nitrogen levels. Consequently, PphaP dramatically boosted crdASC gene expression and curdlan production. Importantly, the genetic modification overrode the strict nitrogen depletion regulation that presents a hindrance for maximal curdlan production and from nitrogen rich, complex media, demonstrating excellent commercial potential for achieving high yields using cheap substrates under relaxed fermentation conditions.

There is high confidence that climate change has increased the probability of concurrent temperature-precipitation extremes, changed their spatial-temporal variations, and affected the relationships between drivers of such natural hazards. However, the extent of such changes has been less investigated in Australia. Daily weather data (131 years, 1889-2019) at 700 grid cells (1◦ × 1◦) across Australia was obtained to calculate annual and seasonal mean daily maximum temperature (MMT) and total precipitation (TPR). A nonparametric multivariate copula framework was adopted to estimate the return period of compound hot-dry (CHD) events based on an ‘And’ hazard scenario (hotter than a threshold ‘And’ drier than a threshold). CHD extremes were defined as years with joint return periods of larger than 25 years. Mann-Kendall nonparametric tests was used to analyse trends in MMT and TPR as well as in the frequency of univariate and CHD extremes. A general cooling-wetting trend was observed over 1889-1989. Significant increasing trends were detected over 1990-2019 in the frequency and severity of hot extremes across the country while trends in dry extremes were mostly insignificant (and decreasing). Results showed a significant increase in the association between temperature and precipitation at various temporal scales. The frequency of CHD extremes was mostly stable over 1889-1989, but significantly increased between 1990 and 2019 at 44% of studied grid cells, mostly located in the north, south-east and south-west. Spatial homogeneity (i.e. connectedness) and propagation of extreme events from one grid cell to its neighbouring cells was investigated across Australia. It can be concluded that this connectedness has not significantly changed since 1889.

Arbutus unedo L. is a small Ericaceae tree with a circum-Mediterranean distribution. It has a huge ecological impact on southern Europe forests and a great economic importance, as a source of phytochemicals with bioactive properties and for fruit production. On the foreseen climate change context, breeding towards drought tolerance is necessary in order to ameliorate plant performance. The aim of this work was therefore to study the reproduction mechanisms of strawberry tree, obtain new genetic combinations by hybridization and select genotypes more tolerant to drought stress. A morphological analysis of flowers and pollen was carried out, and controlled pollinations performed both in vitro and ex vitro. The very first approach on strawberry tree breeding by means of hybridization is also presented. Several physiological parameters were evaluated on 26 genotypes submitted to a water deficit regime. Plant behavior under drought greatly varied among genotypes, which showed a high phenotype plasticity. Three genotypes that were able to cope with water restriction without compromising net CO2 assimilation were identified as highly tolerant to drought stress. The results obtained elucidate the reproduction mechanisms of strawberry tree and open the way for a long-term breeding program based on the selection of drought tolerant plants.

Binder jet printed components typically have low overall density in the green state and high shrinkage and deformation after heat treatment. It has previously been demonstrated that, by including nanoparticles of the same material in the binder, these properties can be improved as the nanoparticles can fill the interstices and pore throats between the bed particles. The beneficial effects from using these additive binder particles can be improved by maximising the binder particle size, enabling the space within the powder bed to be filled with a higher packing efficiency. The selection of maximum particle size for a binder requires detailed knowledge of the pores and pore throats between the powder bed particles. In this paper, a raindrop model is developed to determine the critical radius at which binder particles can pass between pores and penetrate the bed. The model is validated against helium pycnometry measurements and binder particle drop tests. It is found that the critical radius can be predicted, with acceptable accuracy, using a linear function of the mean and standard deviation of the particle radii. Percolation theory concepts have been employed in order to generalise the results for powder beds that have different mean particle sizes and size distributions. The results of this work can be employed to inform the selection of particle sizes required for binder formulations, to optimise density and reduce shrinkage in printed binder jet components.

A phase 1-2, prospective, multicenter, randomized, open-label clinical trial (Code RPCEC00000382, https://rpcec.sld.cu/trials/RPCEC00000382-En/), with parallel groups, involving 1161 participants was designed to assess safety and immunogenicity of two Cuban COVID-19 vaccines (Mambisa and Abdala) in boosting COVID-19 immunity of convalescent adults after receiving one dose of either vaccine. The main safety outcome was severe vaccination adverse events occurring in &lt;5% of vaccinees. Main immunogenicity success endpoints were ≥4-fold anti-RBD IgG seroconversion or ≥20% increase in ACE2-RBD inhibitory antibodies in &gt;55% of vaccinees in Phase 1 and &gt;70% in Phase 2. Neutralizing antibody titers against SARS-CoV-2 variants were evaluated. Both vaccines were safe; no deaths or severe adverse events occurred. Mild intensity adverse events were the most frequent (&gt;73%); headache predominated for both vaccines. Phase 1 responders were 83.3% (p = 0.0018) for Abdala. Mambisa showed similar results. Phase 2 responders were 88.6% for Abdala (p &lt;0.0001) and 74.2% for Mambisa (p = 0.0412). In both phases, anti-RBD IgG titers, inhibition percentages and neutralizing antibody titers increased significantly after the booster dose. Both vaccines were safe and their immunogenicity surpassed the study endpoints.

Abstract: This article reports the results of an ecological study of cancer incidence rates by state in the US for the period 2016-2020. The goals of this study were to determine the extent to which solar UVB doses still reduced cancer risk compared to findings reported in 2006 for cancer mortality rates for the periods 1950–1969 and 1970-1794 as well as cancer incidence rates for the period 1998–2002 and to determine which factors were recently associated with cancer risk. The cancer data for non-Hispanic white (European American) men and women were obtained from the Centers for Disease Control and Prevention. Indices were obtained for solar UVB at the surface for July 1992, and alcohol consumption, and diabetes and obesity prevalence near the 2016–2020 period. Lung cancer incidence rates were also used in the analyses as a surrogate for smoking, diet, and air pollution. The cancers for which solar UVB is significantly associated with reduced incidence are bladder, brain (males), breast, corpus uteri, esophageal, gastric, non-Hodgkin’s lymphoma, pancreatic, and renal cancer. Lung cancer was significantly associated with colorectal, laryngeal, and renal cancer. Diabetes was also significantly associated with breast, liver, and lung cancer. Obesity prevalence was significantly associated with breast, colorectal and renal cancer. Alcohol consumption was associated with bladder and esophageal cancer. Thus diet has become a very important driver of cancer incidence rates. The role of solar UVB in reducing risk of cancer has been reduced due to people spending less time outdoors, wearing sunscreen that blocks UVB but not UVA radiation, and population increases in overweight and obesity, which lowers 25-hydroxyvitamin D concentrations and generates systemic inflammation, a risk factor for cancer. The dietary approach that would reduce the risk of diabetes, obesity, lung cancer, and, therefore cancer, would be one based mostly on whole-plants and restrictions on red and processed meats and ultraprocessed foods. Solar UVB exposure for a few minutes before applying sunscreen and taking vitamin D supplements would also help reduce risk of cancer.Keywords: alcohol consumption; cancer incidence;

Nitrogen is the most commonly managed mineral nutrient in olive groves because it is essential for plant growth. The precise management of N fertilization in olive cultivation is still not fully clarified, but it is now essential for providing sustainable production. A nitrogen fertilizer ex-periment with olive trees (cv. Kalinioti) was carried out over a six-year period. Seven levels of nitrogen fertilizer given as ammonium nitrate (control, 1, 2, 3, 4, 5, and 6 kg/tree) were annually applied in order to determine the effect of nitrogen on vegetative growth, fruit set, fruit weight, yield, maturation index and leaf N,P, and K concentrations. The results indicate that, under these conditions, application of up to 4 kg NH4NO3/tree significantly increased yield to 62.5 kg/tree compared to the control. The positive effect was attributed to the initial and final fruit set increases (7.63 and 3.73%, respectively). However, the weight of 100 olives (337 g) at the same fertilizer rate was considerably lower compared to the control. Higher nitrogen rates decreased yield while increasing overall shoot growth. Nitrogen fertilization did not significantly influence the oil content of olive fruit. Fruit weight, maturation index and concentration of oil reached maximum levels in the beginning of December, indicating a suitable start to olive harvesting with reduced yield losses due to unfavorable weather conditions. With increasing fertilizer levels from 0 to 6 kg NH4NO3,/tree concentration of N in olive leaves also increased from 1.23% to 2.38%. Maximum yield was achieved at a level of 6 kg NH4NO3/tree, which corresponded to 2.01% N in leaves. The results suggest that application of 3 kg NH4NO3/tree can be recommended for table olive pro-duction due to the fact that fruit weight was not decreased, while fertilization with 4 kg NH4NO3/tree was suitable for oil olives.

Oxidative stress toxicity (OSTOX), as well as lowered antioxidant defenses (ANTIOX), play a role in temporal lobe epilepsy (TLE). Nevertheless, the associations between OSTOX/ANTIOX and psychiatric comorbidities in TLE are largely unknown.Thus, this study examines plasma malondialdehyde (MDA), lipid hydroperoxides (LOOH), advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), total radical trapping antioxidant parameter (TRAP) and sulfhydryl (-SH) groups in Depression due to TLE (n=25); Anxiety Disorders due to TLE (n=27); Psychotic Disorder due to TLE (n=25); “pure TLE” (n=27); and healthy controls (n=40).TLE and mesial temporal sclerosis (MTS) were characterized by significant increases in OSTOX (MDA, AOPP, LOOH) and lowered ANTIOX (-SH groups, TRAP). The discrimination of pure TLE from controls yielded a significant area under the ROC curve for MDA (0.999), AOPP (0.851), -SH groups (0.899) and the OSTOX/ANTIOX ratio (0.996). Seizure frequency is significantly associated with increased MDA and lowered LOOH and NOx levels. Increased MDA was associated with the severity of depressive and physiosomatic symptoms, whilst increased AOPP levels predicted suicidal ideation. Depression and anxiety disorders co-occurring with TLE showed significantly lower MDA levels than TLE without any comorbidities. The psychotic and negative symptoms of TLE are associated with increased MDA levels and excitation with increased LOOH and lowered TRAP levels.These results indicate that oxidative stress toxicity especially protein oxidation and aldehyde formation coupled with lowered -SH groups play a key role in the pathophysiology of TLE/MTS. Increased aldehyde formation also impacts psychopathology, psychosis, as well as negative and depressive symptoms.

The use of interspecific hybrids during the industrial fermentation process has been well established, positioning the frontier of advancement in brewing to capitalize on the potential of Saccharomyces hybridization. Interspecific yeast hybrids used in modern monoculture inoculations benefit from a wide range of volatile metabolites that broaden the organoleptic complexity. This is the first report of sake brewing by Saccharomyces arboricola and its hybrids. S. arboricola x S. cerevisiae direct-mating generated cryotolerant interspecific hybrids which increased yields of ethanol and ethyl hexanoate compared to parental strains, important flavor attributes of fine Japanese ginjo sake rice wine. We used hierarchical clustering heatmapping with principal component analysis for metabolic profiling and found that the low levels of endogenous amino/organic acids clustered S. arboricola apart from the S. cerevisiae industrial strains. In sake fermentations, hybrid strains showed a mosaic profile of parental strains, while metabolic analysis suggested S. arboricola had a lower amino acid net uptake than S. cerevisiae. Additionally, we found an increase in ethanolic fermentation from pyruvate and increased sulfur metabolism. Together, our results suggest S. arboricola is poised for in-depth metabolomic exploration in sake fermentation.

Background: The increased vascular risk associated to Varicella- Zoster Virus (VZV) reactivation is extensively established in the general population. This retrospective cohort study investigates whether this observation holds true for People Living With HIV (PLWH), a group already con-fronting heightened cardiovascular risk. Methods: Among PLWH who initiated antiretroviral therapy (ART) at our center and have been under our care for > 24 months since January 1st, 2005, individuals with a history of Herpes Zoster (HZ) were identified and compared their features with those of PLWH with no history of HZ. The prevalence of ischemic events (Deep Venous Thrombosis, Stroke, Acute Myocardial Infarction) was calculated and compared using Chi Square. Odds Ratios (O.R.) with 95% Confidence Intervals (C.I.) for ischemic events following HZ were evaluated through univariate and multivariate logistic regression. Results: Overall, 45/581 PLWH reported HZ. Ischemic events followed HZ significantly more often than the other group (13% vs. 5%, p=0.01). Both positive serology for VZV and HZ correlated with increased ischemic risk (O.R. 4.01, 95% C.I. 1.38-11.6, p=0.01 and O.R. 3.14, 95% C.I. 1.12-7.68, p=0.02, respectively), though pre-existing heart disease demonstrated stronger predictive value in multivariate analysis(O.R. 8.68, 95% C.I. 2.49-29.50, p=0.001). Conclusions: VZV potentially exacerbates vascular risk for PLWH, particularly in the presence of other predisposing factors. Further research is needed to confirm our data.

Aborycin is a type I lasso peptide with a stable interlocked structure, offering a favorable framework for drug development. The aborycin biosynthetic gene cluster gul from marine sponge-associated Streptomyces sp. HNS054 was cloned and integrated into the chromosome of S. coelicolor hosts with different copies. The 3-copy gul-integration strains S. coelicolor M1346::3gul showed better production than one-copy or 2-copy gul-integration strains, and the total titer reached approximately 10.4 mg/L, i.e., 2.1 times that of the native strain. Then, five regulatory genes, phoU (SCO4228), wblA (SCO3579), SCO1712, orrA (SCO3008) and gntR (SCO1678), which were reported to have negative effects on secondary metabolism, were further knocked out from the M1346::3gul genome by CRISPR/Cas9 technology. While the ΔSCO1712 mutant showed a significant decrease (4.6 mg/L) and the ΔphoU mutant showed no significant improvement (12.1 mg/L) in aborycin production, the ΔwblA, ΔorrA and ΔgntR mutations significantly improved the aborycin titers to approximately 23.6 mg/L, 56.3 mg/L and 48.2 mg/L, respectively, which were among the highest heterologous yields for lasso peptides in both Escherichia coli systems and Streptomyces systems. Thus, this study provided important clues for future studies on enhancing antibiotic production in Streptomyces systems.

Anxiety, chronical stress and depression during pregnancy are considered to affect the offspring, presumably through placental dysregulation. We have studied the term placentae of pregnancies clinically monitored with the Beck’s Anxiety Inventory (BAI) and Edinburgh Postnatal Depression Scale (EPDS). A cutoff threshold for BAI/EPDS of 10 classed patients into an Index group (>10, n=23) and a Control group (<10, n=23). Cortisol concentrations in hair (HCC) were periodically monitored throughout pregnancy and delivery. Expression differences of main glucocorticoid pathway genes: i.e. corticotropin-releasing hormone (CRH), 11β-hydroxysteroid dehydrogenase (HSD11B2), glucocorticoid receptor (NR3C1), as well as other key stress biomarkers (Arginine Vasopressin, AVP and O-GlcNAc transferase, OGT) were explored in medial placentae using real-time qPCR and western blotting. Moreover, gene expression changes were considered for their association with HCC, offspring, gender and birthweight. A significant dysregulation of gene expression for CRH, AVP and HSD11B2 genes was seen in the Index group, compared to controls, while OGT and NR3C1 expression remained similar between groups. Placental gene expression of the stress-modulating enzyme 11β-hydroxysteroid dehydrogenase (HSD11B2) was related to both hair cortisol levels (Rho= 0.54; p<0.01) and the sex of the newborn in pregnancies perceived as stressful (Index, p<0.05). Gene expression of CRH correlated with both AVP (Rho= 0.79; p<0.001) and HSD11B2 (Rho= 0.45; p<0.03), and also between AVP with both HSD11B2 (Rho= 0.6; p<0.005) and NR3C1 (Rho= 0.56; p<0.03) in the Control group but not in the Index group; suggesting a possible loss of interaction in the mechanisms of action of these genes under stress circumstances during pregnancy.

Despite significant research efforts, the question of whether rising atmospheric CO₂ concentrations (C_a) affect leaf respiration remains unanswered. Here, I reanalyse published hydrogen isotope abundances in starch glucose of sunflower leaves. I report that, as C_a increases from 450 to 1500 ppm, respiration by the oxidative pentose phosphate pathway in chloroplasts increases from 0 to ≈ 5% relative to net carbon assimilation. This is consistent with known regulatory properties of the pathway. Summarising recent reports of metabolic fluxes in plant leaves, a picture emerges in which mitochondrial processes are distinctly less important for overall respiration than the oxidative pentose phosphate pathways in chloroplasts and the cytosol. Regulatory properties of these pathways are consistent with observations of lower-than-expected stimulations of photosynthesis in response to increasing C_a. Reported advances in understanding leaf respiratory mechanisms may enable modelling and prediction of respiration effects (inter alia) on biosphere-atmosphere CO₂ exchange and plant performance under climate change.

Rural electrification rate (RER) in Africa is still low to date. Several countries in Sub-Saharan Africa have tried to address this problem using conventional single-phase two-wire or three-phase three-wire systems, however at large costs due to the nature of dispersed rural load centers, low load demand, and low population density. Another solution of off-grid generation creates associated health problems. Therefore, this paper undertakes a review of a single wire earth return (SWER) network as a RER improvement solution. The paper undertakes intensive literature review to elucidate challenges and solutions to the implementation of SWER technology. Advantages of SWER technology discussed make it the choice for RER improvement in Sub-Saharan African countries. After that, a case study is selected in rural Tanzania, and a preliminary SWER network design is undertaken.

BACKGROUND: We investigated whether immigrants from Southeast Europe (SE) and Swiss patients have different reasons for visiting the emergency department (ED). METHODS: Our retrospective data analysis for the years 2013-2017 describes the pattern of ED consultations for immigrants from SE living in Switzerland (Canton Bern), in comparison with Swiss nationals, with a focus on type of referral and reason for admission. RESULTS: A total of 153,320 Swiss citizens and 12,852 immigrants from SE were included in the study. The mean age was 51.30 (SD=21.13) years for the Swiss patients and 39.70 (SD=15.87) years for the SE patients. For some countries of origin (Albania, Bosnia and Herzegovina, and Turkey), there were highly statistically significant differences in sex distribution with the predominance for male. SE immigrants had a greater proportion of patients in the lower triage level (level 3: SE: 67.3% vs. Swiss: 56.0%) and a greater proportion of patients in the high triage level than the Swiss population (level 1: SE: 3.4% vs. Swiss: 8.8%,). SE patients of working age (16-65 years) were six times more often admitted by ambulance than older (≥65 years) SE patients, whereas in the Swiss population this ratio was similar. In both groups, fast track service was primarily used for patients of working age (<65) and more than three times more often in the SE than the Swiss group (SE: 39.1%, Swiss: 12.6%). CONCLUSION: We identified some indications in access to primary care in Emergency Department for immigrants highlighting the need for attention to the role of organizational characteristics of primary health care in the Switzerland. The authors have highlighted the need for professional support to improve the quality of healthcare for immigrants. In the future, more primary care services and general practitioners will need to be provided with a migrant background.

Seed germination and seedling growth represent two vulnerable stages in a plant life cycle and it is important to determine how they will be affected by environmental changes associated with climate change. This study examines the impact of salinity levels (0, 50, 100, and 150 mM) at each of three temperatures (15, 25, and 35˚C) on seed germination and radicle growth for three dormant and three non-dormant varieties of conventional, glyphosate resistant, or reduced lignin alfalfa. The genetic basis and phenotypic plasticity for seed germination and seedling growth in response to salinity and temperature were determined. Both traits were phenotypically plastic with respect to temperature and salinity. Seed germination was 87.0% ± 1.7 at 25˚C, 0mM (no salinity), but decreased to 33.9% ± 3.9 germination at 35˚C and 150mM. Radicle length went from 36.7 ± 1.5 mm after four days at 25˚C, 0mM, to 10.5 ± 0.7 mm at 35˚C, 150mM. The phenotypic response brought seed germination and radicle length away from their optimum, but we detected standing genetic variation for both seed germination and radicle length. Selection to increase both traits at high temperature and salinity would facilitate alfalfa establishment under climate change.

Leucine-rich α-2 glycoprotein1 (LRG1) is a member of the leucine-rich repeat (LRR) family that was implicated in multiple diseases including cancer, aging and heart failure as well as diabetes and obesity. LRG1 plays a key role in diet-induced hepatosteatosis and insulin resistance by mediating the crosstalk between adipocytes and hepatocytes. LRG1 also promotes hepatosteatosis by upregulating de novo lipogenesis in the liver and suppressing fatty acid β oxidation. In this study, we investigated the association of LRG1 with obesity markers including leptin and other adipokines in adolescents (11-14 years; n=425). BMI-for-age classification based on WHO growth charts was used to define obesity. Plasma LRG1 was measured by ELISA while other markers were measured by multiplexing assay. Median (IQR) of LRG1 levels was higher in obese [30 (25, 38) µg/mL] and overweight [30 (24, 39) µg/mL] adolescents, compared to normal-weight participants [27 (22, 35) µg/mL]. The highest tertile of LRG1 had an OR [95%CI] of 2.55 [1.44, 4.53] for obesity. LRG1 was positively correlated to plasma levels of HsCRP (R=0.2), Leptin (R=0.2) and Chemerin (R=0.24) with p<0.001. Additionally, it was positively associated with plasma level of IL6 (R=0.17) and IL10 (R=0.14) but not TNF-α. In conclusion, LRG1 levels are increased in obese kids and associate with increased levels of adipogenic markers. These results suggest the usefulness of LRG1 as an early biomarker for obesity and its related pathologies in adolescents.

Exposure to predator scent (PS) has been used as a model of stress associated with danger to life and body integrity. We tested the hypothesis that repeated PS exposure alters the excitability of serotonin (5-HT) neurons of the dorsal raphe nucleus. To study the mechanisms involved, we approached serum and adrenal corticosterone and aldosterone concentrations, as well as cortical brain-derived neurotrophic factor (BDNF) expression. Adult male Sprague-Dawley rats were exposed to PS for ten minutes daily for ten consecutive days. Two weeks after the last exposure, electrophysiological and biochemical assessments were performed. Measurements by in vivo electrophysiology showed increased spontaneous firing activity of 5-HT neurons in rats exposed to PS. PS exposure resulted in reduced serum corticosterone and aldosterone concentrations. Concentrations of both corticosteroids in the adrenal glands, as well as the relative weight of the adrenals, were unaffected. The gene expression of hippocampal BDNF of rats exposed to PS remained unaltered. In conclusion, repeated exposure of rats to PS leads to enhanced firing activity of 5-HT neurons accompanied by reduced serum, but not adrenal aldosterone and corticosterone concentrations. Reduced corticosteroid concentrations in the blood appear to be the result of increased metabolism and/or tissue uptake rather than altered steroidogenesis. The decrease in circulating corticosterone in rats experienced repeated PS may represent part of the mechanisms leading to increased excitability of 5-HT neurons. The increase in 5-HT neuronal firing activity might be an important compensatory mechanism designated to diminish the harmful effects of the repeated PS exposure on the brain.