Our hypothesis that controlled ozone applications interfere into the redox balance of the biological organism (first published in 1998 with a preclinical trial on protecting the liver from CCl4 intoxication), has been verified over the last 2 decades in reactive oxygen species (ROS)-induced mitochondrial pathologies, such as rheumatoid arthritis, osteoarthritis, aging processes, diabetes-2 and in prevention of intoxications. Low-dose ozone acts as a redox bioregulator: The restoration of the disturbed redox balance is comprehensible in a number of preclinical and clinical studies by a remarkable increase of the antioxidant repair markers, here mainly shown as glutathione increase and a reduction in oxidative stress markers, mainly malondialdehyde. The mechanism of action is shown, relevant data are displayed, evaluated and comprehensively discussed: The repair side of the equilibrium increases by 21% up to 140% compared to the non-ozone treated groups and depending on the indication; the stress markers are simultaneously reduced, the redox system regains its balance.

The best form of prevention against human infection through bacteria, viruses and other parasites is ozone disinfection of wastewater and drinking water as a highly effective, well-known method. As a therapeutic measure, various preclinical studies showed promising results, which are being revisited and reconsidered in times of pandemics and led to interesting results in recent clinical trials and reports, as presented by the example of protective measures against covid-19 in particularly vulnerable clinical personnel. In patients with rheumatoid arthritis, repeated ozone treatments have led to new findings in the "immunomodulation" through ozone. The more effective immune response is discussed as the response of innate immune memory and opens interesting aspects for complementary treatment of autoimmune diseases.

Objective. To test the hypothesis that a session of unilateral tSMS over the dominant primary motor cortex (M1) in healthy subjects produces a transient decrease in manual dexterity. Methods. A triple-blinded randomized control trial was conducted in 40 healthy participants who were allocated to real- or sham-tSMS group. Each participant underwent one session of tSMS and were assessed before, immediately after, 15 minutes, and 40 minutes after stimulation. Outcome measures were Finger Tapping Test (FTT), 5-seconds FTT, nine Hole Peg Test, and the hand grip assessment. Results: Significant differences were found between groups 15 minutes after stimulation in favor of the tSMS group in the FTT (2.2 ± 0.99; CI= .18-4.22; d= .84p=.034), and 5-second FTT (4.2 ± 1.98; CI= .199-8.2, d= .68; p=.04). In the intragroup analysis, a significantly lower number of taps 15 minutes after stimulation was observed in sham group (3.3 ± 1.01; CI= .47-6.13; d= .42; p=.015), but not in the real stimulation group. Conclusion: A unilateral session of tSMS in the M1 of the dominant hemisphere of healthy individuals does not reduce manual dexterity or grip strength. This technique could have benefits on the motor performance of the arm contralateral to the stimulated motor cortex

(1) Background: Health Care-Associated Infections (HAIs)are a significant public health problem worldwide favoring multidrug-resistant (MDR) microorganisms. The SARS-CoV-2 infection had a negative association with the increase in antimicrobial resistance, and the ESKAPE group had the most significant impact on HAIs. The study aimed to evaluate the bactericidal effect of high concentration O3 gas on some reference and ESKAPE bacteria. (2) Material and Methods: Four standard strains and four clinical or environmental MDR strains were exposed to high ozone doses at different concentrations and times. Bacterial inactivation (growth and cultivability) was investigated using colony counts and resazurin as a metabolic indicator. Scanning electron microscopy (SEM) was performed. (3) Results: The culture exposure to a high level of O3 inhibited the growth of all bacterial strains tested with a statistically significant reduction in colony count compared to the control group. The cell viability of S. aureus (MRSA) (99,6%) and P. aeruginosa (XDR) (29,2%) was reduced considerably, and SEM showed damage on bacteria after O3 treatment (4) Conclusion: High doses of ozone were able to interfere in the growth of all strains studied, evidencing that ozone-based decontamination approaches may represent the future of hospital cleaning methods.

Background: Intrauterine transfusion (IUT) of the donor and partial exchange (pET) of the recipient is a temporizing treatment for pregnancies with Twin Anemia Polycythemia Sequence (TAPS). We sought to give a detailed description of the procedural approach and outcomes for sequential donor IUT and recipient pET in TAPS. Methods: Retrospective study of spontaneous TAPS referred to the Johns Hopkins Center for Fetal Therapy treated with donor IUT followed by recipient pET utilizing a double-syringe set up. Procedure characteristics and outcomes as well as accuracy of existing transfusion formulas were analyzed and compared with the literature. Results: 5 of 78 patients with spontaneous TAPS underwent a total of 19 combined IUT/pET procedures (median first procedure to delivery interval 5.6 weeks [interquartile range IQR 1.9-6.0]). One pET was stopped for fetal decelerations. Patients delivered at 33.0 weeks [IQR 31.9-33.3] with two survivors and no neonatal transfusion requirements. IUT volumes were 48 ml [IQR 39-63 ml] and pET volumes 32 ml [IQR 20-50] utilizing aliquots of 5 – 20 mls for the latter (p=0.021). For IUTs, assumption of a fetal blood volume below 150 ml/kg underestimated required transfusion volume. For pETs, all formulas required adjustment of dilution volume based on bedside testing (p<0.05 for all). Conclusions: Donor transfusion followed by partial exchange in the recipient can prolong pregnancy in spontaneous TAPS and obviate the need for neonatal transfusion. A double-syringe setup facilitates efficient saline exchange. Because the accuracy of volume formulas is limited, bedside testing is recommended to achieve the target hemoglobin.

The variability of ozone over Egypt has been studied in this work. Higher values of coefficient of variation (COV) at eight stations occur at winter while lowest values occur at summer. The COV is function of latitude in annual, winter and spring where it decreases gradually from the north to south of Egypt. The trend analysis of ozone over the eight stations indicates negative trends over northern stations for both annual and seasonal time series with the greatest one at winter. The horizontal distribution of ozone trend values is negative over all Egypt in winter while it positive over middle and south Egypt in the other seasons. The long-term variability of the behavior of the annual ozone shows positive trend values in ozone are the dominant features during the period 1979- 1989 at the most stations. Negative trend values in ozone are the dominant features during the period 1990- 2014 at all stations. The Mann–Kendall test confirms that there is an abrupt change towards decreasing of ozone occurs in 1981, 1984, 2012, 1999, 2000, 1998 and 2010, while a change towards increasing of ozone appears in 2006, 2014, 1993 and 1989.

Background: The laryngeal mask airway Vision Mask (LMA VM) is a supraglottic airway device (SAD) with vision guidance system. The ideal head and neck position for direct laryngoscopy is known, but the ideal position for placing a LMA is not. The objective of this study is to evaluate and compare the optimal position for placement of a video laryngeal mask airway. Methods: This was a prospective observational, transversal and analytical study of 72 consecutive patients. In the same patient, laryngeal vision was first assessed with the head and neck in the sniffing position and then with the head in the neutral position. Procedures were filmed and performed by the same investigator. Assessment of the laryngeal view was performed using two classifications: modified Cormack-Lehane classification and Brimacombe classification. Device placement was considered adequate when the Cormack-Lehane rating was scored from 1 to 2 and the Brimacombe rating was from 2 to 4. Results: 72 patients were included in this study. In the assessment of the glottis using the Cormack Lehane classification for fiberoptic view, laryngeal visibility was adequate in 64 (88.89%) patients in the neutral position and in 65 (90,28%) patients in the sniffing position (p>0,05). In the fiberoptic view of the glottis, assessed using the Brimacombe classification, laryngeal visibility was adequate in 68 (93%) patients in the neutral position and in 69 (95%) patients in the sniffing position, (p>0,05). There was no statistically significant difference in the rate of success between the sniffing position (70 patients, 97.22% success rate) and the neutral position (67 patients, 93.06% success rate) during the first insertion attempt. Two patients required a second attempt in the sniffing position, while five patients required a second attempt in the neutral position. Conclusion: An adequate sniffing position did not result in a better glottic view than neutral position, and the number and type of additional maneuvers were equal in both positions.

As the world’s population age, Cognitive Frailty (CF) is becoming one of the most serious health problems and elucidating its biological mechanisms along with prevention and treatments becomes increasingly important also considering the associated health costs. This pilot study aims to investigate the potential cognitive and neuropsychological effects of a 5-week treatment with a therapy based on the regenerative properties of ozone (O3) in a cohort of patients stratified according to CF. We also study the potential effects of O3 on blood-based biomarkers indicative of specific biological systems that may be altered in CF. Seventy-five older persons have been recruited and randomly assigned to receive the active treatment (150cc of oxygen-O2-O3 mixture at the concentration of 30ug of O3 per cc of O2) or O2, or the placebo (air) for 5 weeks. The primary endpoint is a change in the scores of clinical scales from baseline (T0) to weeks 3 (T3), 9 (T9), 15 (T15) after treatment. The secondary endpoint is a change in biomarkers levels resulting from transcriptomics, proteomics and metabolomic patterns at the same times. This study will evaluate whether an intervention with the O2-O3 therapy could have potential cognitive, neuropsychological and biological effects on CF.

Obesity has increasingly become a worldwide epidemic, as demonstrated by epidemiological and clinical studies. Obesity may lead to development of a broad spectrum of cardiovascular diseases (CVDs), such as coronary heart disease (CHD), hypertension, heart failure (HF), cerebrovascular disease, atrial fibrillation (AF), ventricular arrhythmias, and sudden cardiac death (SCD). In addition to hypertension, there are other cardiometabolic risk factors (CRFs) such as visceral adiposity, dyslipidemia, insulin resistance, diabetes, elevated levels of fibrinogen, and C-reactive protein and others, all of which increase the risk of CVD events. Mechanisms involved between obesity and CVD mainly include insulin resistance, oxidative stress, inflammation, and adipokines dysregulation, which cause maladaptive structural and functional alterations of the heart, particularly left ventricular (LV) remodeling and diastolic dysfunction. Natural products of plants, provide a diversity of nutrients and different bioactive compounds, including phenolics, flavonoids, terpenoids, carotenoids, anthocyanins, vitamins, minerals, fibers, and others, which possess a wide range of biological activities including antihypertensive, antilipidemic, antidiabetic, and other activities, thus conferring cardiometabolic benefits. In this review, we discussed the main therapeutic interventions using extracts from herbs and plants in preclinical and clinical trials with protective properties targeting CRFs. Molecular mechanisms and therapeutic targets of herbs and plants extracts for the prevention and treatment of CRFs are also reviewed.

This communication explores the transition from Cognitive Behavioural Therapy (CBT) to a more holistic model, named Complex Therapy, developed by Tullio Scrimali for explaining and treating mental disorders. The Author delves into the limitations of traditional CBT and introduces an innovative framework that integrates multiple therapeutic modalities. While CBT is based on the study and modification of behaviour and cognition, Complex Therapy includes, in its focus, the theory of human relationships, the attachment theory, neuroscience, applied neuroscience, complex systems theory and ecology.Complex Therapy addresses the multifaceted nature of mental health issues by combining evidence-based techniques with personalized care strategies. The goal is to enhance patient outcomes through a tailored, comprehensive treatment plan that adapts to the evolving needs of individuals facing mental health challenges.Two innovative and original items which Scrimali has developed, which are a device for Applied Neuroscience MindLAB Set and a new botanical drug, NegEnt, are presented and discussed.The topic also describes, an original and integrated protocol, named Negative Entropy, the author has developed for treating a challenging disorder, such as schizophrenia, he renamed Entropy of Mind.

Background and Objectives: ARNE score was developed for the prediction of difficult airway for both general and ENT surgery with a universal cut-off value. We tested the accuracy of this score in the case of laryngeal surgery and provided an insight of its combination with flexible laryngoscopy. Materials and Methods: This prospective pilot clinical study included 100 patients who were being scheduled for microscopic laryngeal surgery. We have calculated ARNE score for every patient and flexible laryngoscopy was provided preoperative. Difficult intubation was assessed according to intubation difficulty score (IDS). Results: A total of 33% patients had difficult intubation according to IDS. ARNE score showed to be accurate for prediction of difficult intubation in laryngology with P<0.0001 and AUC 0.784. Flexible laryngoscopy showed to be an independent parameter with P<0.0001 and AUC 0.766. We have defined a new cut-off value of 15.50 for laryngology, according to AUC curve. After the patients were divided in two groups, according to the new cut-off value and provided cut-off value, AUC improved to 0.707 from 0.619 respectively. Flexible laryngoscopy improved the prediction model of ARNE score to AUC 0.882 and of new cut-off value to AUC 0.833. Conclusions: It is recommended to use flexible laryngoscopy together with ARNE score in difficult airway prediction in patients with laryngeal pathology. Also, universally recommended cut-off value of 11 can not be effectively used in laryngology and a new cut-off value of 15.50 is recommended.

Hepatocellular carcinoma (HCC) development is associated with altered modifications in DNA methylation, changing transcriptional regulation. Emerging evidence indicates that DNA methyltransferase 1 (DNMT1) plays a key role in carcinogenesis process. This study aimed to investigate how pirfenidone (PFD) modifies this pathway and the effect generated by the association between c-Myc expression and DNMT1 activation. Rats F344 were used for HCC development using 50 mg/kg of diethylnitrosamine (DEN) and 25 mg/kg of 2-aminofluorene (2-AAF). HCC/PFD group received simultaneous doses of 300 mg/kg of PFD. All treatments lasted 12 weeks. On the other hand, HepG2 cells were used to evaluate the effects of PFD in restoring DNA methylation in the presence of the inhibitor 5-Aza. Histopathological, biochemical, immunohistochemical, and western blot analysis were carried out and our findings showed that PFD treatment reduced the amount and size of tumors along with decreased Glipican-3, β-catenin, and c-Myc expression in nuclear fractions. Also, this treatment improved lipid metabolism by modulating PPARγ and SREBP1 signaling. Interestingly, PFD augmented DNMT1 and DNMT3a protein expression, which restores global methylation, both in our in vivo and in vitro models. In conclusion, our results suggest that PFD could slow down HCC development by controlling DNA methylation.

Renal cell carcinoma (RCC) accounts for approximately 90-95% of all kidney cancers in adults, with the clear cell RCC (ccRCC) the most frequently identified subtype. RCC is known for its responsiveness to immunotherapy, making it an area of significant research interest. Immune checkpoint (IC) molecules, which regulate immune surveillance, are established therapeutic targets in RCC. The aim of this study was to analyze the influence of polymorphisms in genes HVEM and CD160 on susceptibility to ccRCC and patient overall survival (OS) with over a ten-year period of observation. We genotyped three HVEM single nucleotide polymorphisms (SNPs): rs1886730, rs2234167, and rs8725, and two CD160 SNPs: rs744877 and rs2231375, in 238 ccRCC patients and 521 controls. Our findings indicated that heterozygosity within rs2231375 and/or rs2234167 increases ccRCC risk. Furthermore, in women, heterozygosity within additional HVEM SNPs, rs8725 and rs1886730, is associated with an increased ccRCC risk. The presence of a minor allele for rs1886730, rs2234167, rs8725, and rs2231375 was also correlated with certain clinical features of the disease. Moreover, the rs1886730 SNP was found to be associated with patients' OS. In conclusion, our study highlights an association between HVEM and CD160 polymorphisms and the risk of developing ccRCC as well as patient’s OS.

This study aimed to investigate the efficacy of manual therapy and exercise versus synchronized telerehabilitation with self-manual therapy and exercise in treating Subacromial Pain Syndrome (SAPS). Sixty individuals diagnosed with SPS, aged 18-50 years, were randomly assigned to home exercise (HE), manual therapy (MT), and telerehabilitation (TR) groups. Treatment protocols were administered over 8 weeks and included specific exercises and therapy interventions. Out-come measures included Visual Pain Scale (VAS), shoulder range of motion (ROM) via gonio-metric measurements, Quick Disability Arm-Shoulder-Hand Problems Survey (Q-DASH), and patient satisfaction. Results revealed that both MT and TR groups exhibited reduced pain, in-creased ROM, lower Q-DASH scores, and higher patient satisfaction compared to the HE group. However, no significant differences were found between MT and TR groups in pain levels, ROM, Q-DASH scores, or patient satisfaction. The study concludes that both telerehabilitation and manual therapy effectively alleviate pain and are well-received by patients with SPS. Addition-ally, manual therapy demonstrates superiority in enhancing functional levels compared to exer-cise-based interventions. (Registration: NCT05200130)

This study aimed to evaluate the impact of Candida albicans on subgingival biofilm formation on dental implant surfaces. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were used to compare biofilm structure and microbial biomass in the presence and absence of the fungus after periods of 24, 48, and 72 h. Quantitative polymerase chain reaction (qPCR) was used to quantify the number of viable and total micro-organisms for each of the biofilm-forming strains. A general linear model was applied to compare CLSM and qPCR results between control and test conditions. The biofilm developed with C. albicans at 72 h had a higher bacterial biomass, with a significantly higher cell viability (p < 0.05). After both 48 and 72 h of incubation, in the presence of C. albicans, there was a significant increase in counts of Fusobacterium nucleatum and Porphyromonas gingivalis and in the cell viability of Streptococcus oralis, Aggregatibacter actinomycetemcomitans, F. nucleatum, and P. gingivalis. Using a dynamic in vitro multispecies biofilm model, C. albicans exacerbated the development of the biofilm grown on dental implant surfaces, significantly increasing the number and cell viability of periodontal bacteria.

Background: Atopic dermatitis is a chronic condition that significantly affects the daily life of those who suffer from it, requiring complex and personalized management with active participation of the patient in the management of their disease. Objective: to describe the design and development process of a mobile application, using the Design Thinking method, for the follow-up of patients with atopic dermatitis. Methods: User-centered design and prototype creation method, differentiating the phases of the empathize, define, idea, prototype, and test. A purposive snowball sampling was used to recruit patients with atopic dermatitis, family members, and health professionals. Three two-hour workshops were held, attended by 25 people. Results: the parameters to be monitored will include objective data (physical, behavioral, treatments, environmental, integration of daily routines) and subjective data (user experience). On the other hand, it will figure out behavior patterns, set up rewards, foster a feeling of community, and use notifications and a chatbot. Conclusion: The active integration of all stakeholders at each stage of the design and development of the digital solution has improved its relevance and acceptance, resulting in a tool that is expected to significantly improve the management of atopic dermatitis.

Uterine leiomyosarcoma (LMS) is a rare and aggressive form of uterine cancer, with a poor prognosis and high number of uterine cancer-related deaths. Chimeric Antigen Receptor (CAR) T-cell therapy is an immunotherapy approach to antigen specific of cancer cell, thereby enhancing the immune system's ability to target and destroy cancer cells. This study aims to investigate the potential of targeting differentially expressed genes (DEGs) as a novel therapeutic strategy using CAR T-cell technology in LMS. Genome datasets were obtained from NCBI-GEO database, Of the five datasets, genes that experienced significant overexpression in at least three datasets were categorized as DEGs, and DEGs were evaluated for protein localization, Gene Ontology, bioactivity, interaction, and overexpression. The results identified 25 DEGs, with ten of them expressed on the plasma membrane; four of them—HMMR, KIF20A, PRC1, and ZWINT—were part of the main protein network derived from the 25 DEGs. The dominant bioactivity of these PMGs involves influencing the cell cycle, particularly processes related to chromosome segregation. In conclusion, HMMR, KIF20A, PRC1, and ZWINT are high-potential DEGs as candidates for tumor-associated antigen CAR T-cell therapy. Further research, both in vitro and in vivo, is needed to enhance the validity of these findings.

Venous leg ulcers still pose a significant medical problem worldwide. The complexity of the problem determines the need for further interdisciplinary activities that will improve the quality of life of treated patients. The study compared the quality of life of patients with venous leg ulcers who received local hyperbaric oxygen therapy or local ozone therapy procedures as a part of comprehensive treatment. The study included 129 patients (62 men and 57 women) with venous leg ulcers. Group I underwent local hyperbaric oxygen therapy (HBOT), group II - local ozone therapy (OZONE). In both groups, the patients' quality of life was assessed before the start of treatment cycle, as well as 10 weeks and 6 months after the completion of the treatment, by using the EQ-5D-5L questionnaire and the Polish shortened version of the SF-36 scale. After completing the respective therapeutic cycle, both groups showed a statistically significant (p<0.001) improvement the quality of life according to the EQ-5D-5L questionnaire and the SF-36 scale. Differences were noted between 1st examination (before treatment) and 2nd examination (10 weeks after treatment), as well as 3 examination (6 months after treatment). In the EQ-5D-5L assessment of anxiety and depression, self-care and activities of daily living 6 months after the end of treatment, better results were found in the group of patients treated with local hyperbaric oxygen therapy (p<0.001). In this group, 6 months after the end of the treatment, a statistically significantly higher result on the EQ-VAS scale was also obtained (73.09±19.8 points vs. 68.03±17.37 points, p=0.043). However, in the SF-36 assessment 6 months after the end of treatment better results - a statistically significantly lower value of the quality of life index - were recorded in the group of patients treated with local ozone therapy (103.13±15.76 points vs. 109.89±15.42 points, p<0.015). Hyperbaric oxygen therapy and local ozone therapy procedures have a beneficial effect on improving the quality of life of patients with venous leg ulcers.

In this study we focus on measurements and modeled UV index at the region of Athens, Greece, during a period of a low ozone event. During the period of 12 to 19 of May 2020, total column ozone (TOC) showed extremely low values 35-55 DU (up to 15%) decrease from the climatic mean (being lower than the -2σ). This condition favors the increase of UV erythemal irradiance, since stratospheric ozone is the most important attenuator at the UVB spectral region. A parallel intrusion of Saharan Dust aerosols in the region has masked a large part of the low ozone effect on UV irradiance. In order to investigate the event, we have used spectral solar irradiance measurements from the Precision Solar Radiometer (PSR), total column ozone from the BREWER spectrophotometer and Radiative Transfer Model (RTM) calculations. Model calculations of UV Index (UVI) showed an increase of ~30% compared to the long term normal UVI due to the low TOC while at the same time and for particular days, aerosols masked this effect by ~20%. The study points out the importance of accurate measurements or forecasts of both ozone and aerosols when deriving UVI under unusual low ozone-high aerosol conditions.

Abstract: Spinal disorders are some of the most prevalent health concerns, especially among stu-dents. Based on student demographics, this cross-sectional study evaluated the correlation be-tween functional tests (FT) and spinal range of motion (ROM). This study included 206 students from Vasile Alecsandri University of Bacău. Participants' assessments were conducted using the following tests: (i) Ott, (ii) Schober, (iii) Stibor, (iv) finger-to-floor distance, (v) lateral flexion of the cervical and lumbar spine, and (vi) flexion of the cervical spine. Correlation analyses were evaluated using Spearman correlation coefficient analysis. The results indicated a very strong re-lationship between lateral flexion of the lumbar spine on the left (LFLSL) and right (LFSR) for all departments (r = 0.85 to 0.97, p < 0.05). There was a stronger relationship between FT results and spinal ROM of physical education department students compared to students from other de-partments (n = 17, r = -0.38 to 0.93, p < 0.05). There was no statistically significant correlation be-tween FT and spinal ROM based on age (p > 0.05). The study results provide evidence of the pri-mary risk factors that predispose students to postural deviations. Practitioners and physiothera-pists can utilize these values as a reference for potential therapeutic interventions.

This study investigates the effects of home-based Kakao health care breathing exercises and stretching on respiratory function and fatigue in COVID-19 cured patients. A total of 35 participants performed four movements of home-based breathing exercise and five respiratory muscle stretching exercises four times a week for four weeks. Respiratory function was measured using FVC, FEV1, FEV1/FVC, and PEF. Fatigue was assessed using the Fatigue Severity Scale (FSS). Data analysis was performed using Independent Samples and Paired Samples T-tests in SPSS 24, with a significance level set at p &lt; 0.05. After four weeks of Home based Kakao health care Breathing Exercise, there were significant increases in respiratory FVC, FEV1, FEV1/FVC, and PEF function values observed in the training group (T.G.) after the exercise intervention (p &lt; 0.05). Such an increase was observed when comparing these values with the pre-exercise measurements. In contrast, there was no statistically significant difference in respiratory function outcomes before and after exercise in the control group (C.G.) (p &gt; 0.05). The FSS scores were statistically significant within the training group (T.G.). (p &gt;0.05). The 4-week Kakao health care Breathing Exercise was found to be capable of improving some respiratory functions in COVID-19-recovered patients, but it showed no significant improvement in fatigue levels.

The purpose of this study is to assess the concentration-response relations between conjunctivitis and exposure to ambient ozone. This retrospective study includes emergency department (ED) visits for conjunctivitis in Edmonton, Canada, for the period April 1992–March 2002. Daily average levels of ozone (range: 1.2–50.9, ppb), of temperature, and of relative humidity were estimated and used for the period of the study. For each of the considered exposure lags, (from 0 to 9 days), six different models were fitted to estimate the concentration-response function. The goodness of fit was assessed using the Akaike information criterion. During the period of the study, 17,211 ED visits for conjunctivitis were recorded and used. For all subjects together, a positive statistically significant association was obtained for the exposure lagged by 5 days. For female subjects, lags 1, 3, and 9 had positive statistically significant associations (lag 2 had negative associations). For male subjects, only lag 5 had a positive statistically significant association. The estimated non-linear concentration-response functions for the considered groups (all, males, females) and lags, revealed the associations along the exposure levels. The fitted shapes are described by algebraic functions and may have various forms. The estimated functions are useful to determine the risk associated with exposure to ground-level ozone.

Osteoarthritis and chronic pancreatitis comorbidity are insufficiently studied, and the reciprocal impact of these conditions remains poorly understood. This study aimed to investigate potential predictors for the development of osteoarthritis and chronic pancreatitis comorbidity, as well as complications associated with this comorbidity. A cohort of 150 patients was categorized into three groups: a control group (n=30), patients with osteoarthritis (n=68), and patients with comorbid osteoarthritis and chronic pancreatitis (n=52). Potential predictors for comorbidity development and associated complications were explored. The study revealed that concurrent osteoarthritis and chronic pancreatitis exacerbate each other's progression and contribute to malnutrition. Body Mass Index (BMI) emerged as a potential predictor for chronic pancreatitis development in osteoarthritis patients. In osteoarthritis patients, fecal elastase-1 levels were identified as potential predictors for exocrine pancreatic insufficiency. Factors such as WOMAC total score, fecal elastase-1, C-reactive protein (CRP), ferritin, retinol, tocopherol, 25-hydroxy vitamin D3, and BMI were found to influence comorbidity development between osteoarthritis and chronic pancreatitis. Additionally, Gastrointestinal Symptom Rating Scale-Diarrhea Syndrome (GSRS-DS), Gastrointestinal Symptom Rating Scale-Constipation syndrome (GSRS-CS), Qualitative Assessment of the Symptoms and Impact of Pancreatic Exocrine Insufficiency domain A (PEI-Q-A), retinol, tocopherol, and iron were identified as potential predictors for exocrine pancreatic insufficiency in osteoarthritis patients. In conclusion, the comorbidity of osteoarthritis and chronic pancreatitis exacerbates disease progression and complications, necessitating further investigation.

For monitoring of chimeric antigen receptor (CAR) T-cell therapies antigen-based CAR detection methods are usually applied. However, for each target-antigen a separate detection system is required. Furthermore, when monitoring CAR T-cells in the blood of patients treated with bispecific antibodies or T-cell engagers (bsAbs/BiTEs) recognize the same antigen, these methods producing false-positive results in clinical diagnostics. Anti-CAR-linker monoclonal antibodies (mAbs) targeting the linker sequence between the variable domains of the antigen binding CAR fragment, promise an universal and unbiased CAR detection. To test this, we analyzed clinical specimens of all BCMA- and CD19 targeting CAR T-cell products currently approved for clinical use. We found a highly specific and sensitive CAR detection by using anti-CAR-linker mAb in blood cells from patients treated with Ide-cel, Tisa-cel, Axi-cel, Brexu-cel, and Liso-cel. For Ide-cel and Tisa-cel the sensitivity was significant lower compared to antigen-based CAR detection assays. Strikingly, the specificity of anti-CAR linker mAb was not affected by the simultaneous presence of bispecific blinatumomab or teclistamab for Axi-cel, Brexu-cel, Liso-cel or Ide-cel, respectively. Cilta-cel (containing an monomeric G4S-CAR linker) could not be detected by anti-CAR linker mAb. In conclusion, anti-CAR-linker mAbs are highly specific and useful for CAR T-cell monitoring but not universal applicable.

Chronic obstructive pulmonary disease (COPD) patients are particularly susceptible to respiratory infections like influenza, which exacerbate symptoms and increase healthcare utilization. While smoking cessation and influenza vaccination are recommended preventive measures, their combined impact on healthcare resource utilization is underexplored. The Charlson Comorbidity Index (CCI) assesses comorbidity burden in COPD patients and may influence healthcare outcomes. We conducted a retrospective analysis of 357 COPD patients, evaluating smoking cessation success over one year and influenza vaccination receipt, stratifying patients by CCI scores. Healthcare utilization outcomes included emergency room visits, hospitalizations, and medical expenses. Results showed that 51.82% of patients quit smoking and 59.66% received influenza vaccination, with higher comorbidity prevalence in advanced COPD stages (p=0.002). Both smoking cessation and influenza vaccination independently correlated with decreased emergency room visits, hospital admissions, days, and costs. Patients who both quit smoking and received influenza vaccination exhibited the lowest healthcare utilization rates. In conclusion, smoking cessation and influenza vaccination significantly reduce healthcare resource utilization in COPD patients, with the combination yielding synergistic benefits, particularly in those with lower CCI scores. Integrating these interventions and comorbidity management in COPD strategies is essential for optimizing patient outcomes and healthcare efficiency.

Lymphocyte collection by apheresis for CAR-T production usually does not include mobilized blood using Granulocyte Colony Stimulating Factor (G-CSF) due to the widespread knowledge that it causes a decrease in the number and functionality of lymphocytes. However, it is used for stem cell transplant, which is a common treatment for hematological malignancies. The growing demand for CAR therapies (CAR-T and NK-CAR), both in research and clinic, makes necessary to evaluate whether mobilized PBSC products may be potential candidates for use in such therapies. This review collects recent work that experimentally verifies the role and functionality of T and NK lymphocytes, and the generation of CAR-T, from apheresis after G-CSF mobilization. As discussed, T cells do not vary significantly in their phenotype, the ratio of CD4+ and CD8+ remains constant and the different sub-populations remain stable. In addition, its expansion and proliferation rate are invariant regardless mobilization with G-CSF, as well as the secretion of proinflammatory cytokines and the cytotoxic ability. Therefore, cells mobilized before apheresis are postulated as a new alternative source of T cells for adoptive therapies that will serve to alleviate high demand, increase availability, and take advantage of the substantial number of existing cryopreserved products.

In this work we outline a general method for calculating Auger spectra in molecules, which accounts for the underlying symmetry of the system. This theory starts from Fano’s formulation of the interaction between discrete and continuum states and generalizes this formalism to deal with the simultaneous presence of several intermediate quasi-bound states and several non-interacting decay channels. Our theoretical description is specifically tailored to resonant autoionization and Auger processes, and includes explicitly the incoming wave boundary conditions for the continuum states and an accurate treatment of the Coulomb repulsion. This approach is implemented and applied to the calculation of the K−LL Auger and autoionization spectra of ozone, which is a C2v symmetric molecule, whose importance in our atmosphere to filter out radiation has been widely confirmed. We also show the effect that the molecular point group, and in particular the localization of the core-hole in the oxygen atoms related by symmetry operations, has on the electronic structure of the Auger states and on the spectral lineshape by comparing our results with experimental data.

Beta thalassemia is an inherited blood disorder that results in inefficient erythropoiesis due to genetic mutation that leads to reduction or absence of the hemoglobin beta-globulin protein. Approximately 8.5% of UAE residents suffer from β-thalassemia, a significant health and financial problem. The treatment options available for β-Thalassemia major are limited and associated with a wide range of complications. β-thalassemia gene therapy is emerging as a potential novel treatment option that eliminates the complications caused by the current long-term treatment modalities and the associated economic burden. This paper reviews the scientific literature related to emerging gene-therapy for β-Thalassemia by analyzing all the articles published from January 2010 to December 2023 in the English language on Databases like PubMed, Scopus, ProQuest, and CINAHL. The use of gene therapy has demonstrated promising outcomes for a permanent cure of β-Thalassemia. ZYNTEGLO (Betibeglogene autotemcel) is the only cell-based gene therapy which was approved by the FDA on 19th August, 2018. To conclude, Gene therapy is an innovative solution. It demonstrates a promising future, but does come with its own set-backs and is something that must be tackled in-order to revolutionize it in the medical world. FDA approved ZYNTEGLO is a potentially one-time curative treatment for β-Thalassemia. Although cutting-edge, its use is limited because of the high cost; a price of $2.8million per patient.

Telomeres, located at the ends of each chromosome play a vital role in determining cellular fate and aging. Accelerated shortening of telomeres may also result in accelerated aging and occurrence of age-related degenerative diseases. Anti-aging treatments may help in increasing the telomere length along with improving quality of life, reducing dependency for daily life activities, increasing life expectancy and reducing the risks associated with aging. In this study, we evaluated the effect of anti-aging integrative therapy in 36 individuals. The treatment included a combination of HBOT, ozone therapy, colon hydrotherapy, etc. Telomere length was used as a biomarker for objectively quantifying the outcome of the treatment. The effect of treatment was also assessed on various aging symptoms. At the end of the treatment, it was found that that 97.22% individuals showed an increase in telomere length with an average increase of 0.43 Kbp and 94.44% individuals showed reduced biological age with an average decrease of 3.8 years. These improvements were statistically significant. Improvements were also recorded in the majority of the symptoms. No major adverse events were observed. These results indicate that antiaging integrative therapy has the potential to reverse aging symptoms, cellular aging and improve quality of life.

Evidence suggests that COVID-19 infection can cause lasting health consequences. Multidiscipli-nary rehabilitation services have been recommended to reduce the sequalae. However, the effec-tiveness of physical exercise interventions remains insufficiently documented. The aim of this study was to develop and implement a specific and well tolerated protocol-based, intervention to reduce muscle weakness in older adults impacted by COVID-19. Forty six older adults random-ized into Intervention and Control Groups. Isometric and isokinetic strength assessments were conducted for selected muscle groups using JBA Staniak® torquemeter and Biodex System 3 dy-namometer. Functional abilities were evaluated with the Time Up and Go test and Chair Stand Tests. Men in intervention group demonstrated a significant improvement in static conditions for knee flexors (KF), trunk extensors (TE) and trunk flexors (TF) and in dynamic conditions for knee extensors (KE). Women in intervention group showed significant improvement in static condition for EF, KF, TE and TF and in dynamic for a KE and for a KF. The interaction GROUP x TESTING SESSION was significant for Chair test (s) and Chair test (n). Our results demonstrate the effec-tiveness of a well-tolerated, protocol-based approach that can be used to diminish long lasting functional deficits in post-covid survivors.

Greek roots: "phos" (φῶς) - means "light" and "dynamis" (δύναμις) - means "force" or "power". Photodynamic therapy (PDT) is an innovative treatment method based on the ability of photosensitizers to produce reactive oxygen species after exposure to light of a specific wavelength range, either in the visible or near infrared range. This process results in damage to pathological cells, such as cancer cells, while minimizing the impact on healthy tissues. PDT is a promising direction in the treatment of many diseases, with particular emphasis on the fight against cancer and other diseases asso-ciated with excessive cell growth. The power of light contributed to the creation of phototherapy, whose history dates back to ancient times. It was then noticed that some substances exposed to the sun have a negative effect on the body, while others have a therapeutic effect. This work provides a detailed review of photodynamic therapy, from its origins to the present day. It is surprising how a seemingly simple beam of light can have such a powerful healing effect, which is used not only in dermatology, but also in oncology, surgery, microbiology, virology, and even dentistry. However, despite promising re-sults, photodynamic therapy still faces many challenges. The availability of this thera-py is limited due to the small number of centers offering this type of treatment and the high costs, which may be unaffordable for many patients. Moreover, photodynamic therapy requires further research and improvement.

Hong Kong is one of the most densely populated cities in the world, with millions of people exposed to severe air pollution. (1) Background: Surface ozone, mostly produced photochemically from anthropogenic precursor gases is harmful to both human and vegetation. The phytotoxicity of ozone has been shown to damage plant photosynthesis, induce early leaf death and retard growth. (2) Methods: We use genotypes of bush bean Phaseolus vulgaris with various degrees of sensitivity to ozone to investigate the impacts of ambient ozone on the morphology and development of the bean. We use ozone-induced foliar injury index and measure the flowerings and fruit production to quantify the ozone stress on the plants. (3) Results: We expected that the ozone-sensitive genotype would suffer from a reduction of yield. Results however show that the ozone-sensitive genotype suffers higher ozone-induced foliar damage as expected but produces more pods and beans and heavier beans than the ozone-resistant genotype. (4) Conclusions: It is postulated that the high ozone sensitivity of the sensitive genotype causes stress-induced flowering and therefore results in higher bean yield. A higher-than-ambient concentration of ozone is needed to negatively impact the yield production of the ozone-sensitive genotype. This study demonstrate the usefulness of bioindicators to monitor the phytotoxic effects of ozone pollution in a subtropical city such as Hong Kong.

Spectral photon counting cone-beam CT imaging is challenged by individual pixel response behaviour, which leads to noisy projection images and subsequent image artefacts like rings. Existing methods to correct for this either use calibration measurements, like signal-to-thickness calibration (STC), or perform post-processing ring artefact correction of sinogram data or scan reconstructions, without taking the pixel response explicitly into account. Here we present a novel post-processing method (DAC-shifting), which explicitly measures the current pixel response using flat field images, and subsequently corrects the projection data. The DAC-shifting method was evaluated with a repeat series of spectral photon counting imaging (Medipix3) of a phantom with different density inserts, and in iodine K-edge imaging. The method was also compared against PMMA based STC. The DAC-shifting method was shown to be effective in correcting individual pixel response, and was robust against detector instability. On the contrary, STC correction showed varying results, which was almost as good as DAC-shifting when data was acquired just after STC calibration, but worse with larger time differences. In K-edge imaging, DAC-shifting provides a sharper attenuation peak, and more uniform CT values, which is expected to benefit iodine concentration quantification.

It is well established that the reaction cycles involving some halogenated alkanes (so-called ozone-depleting substances, ODS) contribute to the depletion of ozone in the stratosphere, thus causing the Montreal Protocol (initially signed in 1987) and later amendments. The Protocol called for the scheduled phase-out of ODS, including chlorofluorocarbons (CFC), hydrochloro-fluorocarbons (HCFC), carbon tetrachloride (CCl4), halon, methyl chloroform (CH3CCl3), me-thyl chloride (CH3Cl), and even hydrofluorocarbons (HFCs). In view of the urgent importance of ozone layer protection to the globally ecological environment, the Taiwan government took regulatory actions on reducing ODS consumption since 1993 by the joint-venture of the central competent authorities. Under the regulatory requirements and the industry’s efforts by adopt-ing the alternatives to ODS and abatement technologies, the phase-out of some ODS (i.e., CFC, CCl4, halon, and CH3CCl3) have been achieved prior to 2010. The consumptions of HCFCs and methyl chloride have been significantly declined over the past three decades (1993-2022). However, HFC emission indicated a V-type variation during the period. Due to the local pro-duction and extensive use of HFC in Taiwan, its emissions increased from 663 kilotons of carbon dioxide equivalents (CO2eq) in 1993 to 2,330 kilotons of CO2eq in 2001, and then decreased to 373 kilotons of CO2eq in 2011. Since then, the emissions of HFC largely used as the alternatives to ODS showed an upward trend, increasing to 1,555 kilotons of CO2eq in 2022. To be in compliance with the Kigali Amendment (KA-2015) to the Montreal Protocol for mitigating global warming, the Taiwan government has taken regulatory actions in reducing the consumption of some HFC substances with high global warming potential (GWP) under the authorization of the Climate Change Response Act in 2023, aiming at the baseline consumption in 2024 by 80 % reduction by 2045.

Art therapy fosters emotional healing and growth. This process can offer healthcare professionals (HCPs) novel insights into patients’ medication experiences. We developed a Metaverse Art Gal-lery of Image Chronicles (MAGIC), which depicted patients’ medication experiences symbolically as hero-villain portrayals. This gallery aimed to enhance healthcare students’ learning through re-latable insights into patients’ medication therapies. A character sheet was used to craft patients’ personifications of their medication experiences. ChatGPT, NightCafe, Canva, HeyGen and Cam-tasia were used to generate hero-villain portraits based on the character traits and mounted in MAGIC, which consisted of three virtual realms, each with a unique theme. Alpha-testing among sixteen Generation Z healthcare learners indicated that the content in MAGIC enabled them to understand the concepts of medication adherence (93.7%), art therapy (87.5%) and how patients related to their medications (81.3%). Perceived playfulness (rs=0.925, p

(1) Background: Disinfection of medical devices designed for clinical use associated or not with the growing area of tissue engineering is an urgent need. However, traditional disinfection methods are not always suitable for some biomaterials, especially those sensitive to chemical, thermal, or radiation. Therefore, the objective of this study was to evaluate the minimal concentration of ozone gas (O3) necessary to control and kill a set of sensitive or multi-resistant Gram-positive and Gram-negative bacteria. The cell viability, membrane permeability, and the levels of reactive intracellular oxygen (ROS) species were also investigated; (2) Material and Methods: Four standard strains and a clinical MDR strain were exposed to low doses of ozone at different concentrations and times. Bacterial inactivation (cultivability, membrane damage) was investigated using colony counts, resazurin as a metabolic indicator, and propidium iodide (PI). A fluorescent probe (H2DCFDA) was used for the ROS analyses; (3) Results: No reduction in the count colony was detected after O3 exposure, compared to the control group. However, the cell viability of E. coli (30%), P. aeruginosa (25%), and A. baumannii (15%) was reduced considerably. The bacterial membrane of all strains was not affected by O3 but presented a significant increase of ROS in E. coli (90 ± 14%), P. aeruginosa (62.5 ± 19%), and A. baumanni (52.6 ± 5%); (4) Conclusion: Low doses of ozone were able to interfere in the cell viability of most strains studied, and although it does not cause damage to the bacterial membrane, increased levels of reactive ROS are responsible for causing a detrimental effect in the lipids, proteins, and DNA metabolism.

Transcatheter Aortic Valve Implantation (TAVI) now represents the mainstay in the treatment of severe aortic stenosis. Owing to its exceptional procedural efficacy and safety, TAVI has been extended to include patients at lower surgical risk, thus now encompassing a diverse patient population receiving this treatment. Yet, long-term outcomes also depend on optimal medical therapy for secondary vascular prevention, with antithrombotic therapy serving as a cornerstone. Leveraging data from multiple randomized controlled trials, current guidelines generally recommend single antithrombotic therapy, with either single antiplatelet therapy (SAPT) or oral anticoagulation (OAC) alone in those patients without, or with atrial fibrillation respectively. Yet, individualization of this pattern, as well as specific case uses, may be needed based on individual-patient characteristics and concurrent procedures. This review aims to discuss the evidence supporting antithrombotic treatments in patients treated with TAVI, indications for a standardized treatment, as well as specific considerations for an individualized approach to treatment.

Knee osteoarthritis (KO) is an important health condition, affecting one third of the people aged 65 years or more. Pain is the main cause of disability. Pain management in KO includes pharmacological and non-pharmacological modalities. Patient education, lifestyle changes, physical exercise and physical agents are prescribed as a first approach for pain control. Laser therapy is part of many therapeutical protocols, with two forms, low-level laser therapy (LLLT) and high-intensity laser therapy (HILT). The paper aimed at stressing the advantages of HILT, based on a greater wavelength, higher energy delivery and deeper tissue penetration. Research on 23 published trials revealed that analgesic effect is rapid, cumulative and long lasting. Compared to sham, to LLLT or to other associations of therapeutical modalities, HILT provided significantly better results on pain reduction and functional improvement. Ultrasound examination showed reduction of intraarticular inflammation.

The use of chimeric antigen receptor (CAR) in natural killer (NK) cells for cancer therapy is gaining momentum, marking a significant shift in cancer treatment. This review aims to explore the potential of CAR-NK cell therapy in cancer immunotherapy, providing a fresh perspective. It discusses the innovative approaches in CAR-NK cell design and engineering, particularly targeting refractory or recurrent cancers. By comparing CAR-NK cells with traditional therapies, the review highlights their unique ability to tackle tumor heterogeneity and immune system suppression. Additionally, it explains how novel cytokines and receptors can enhance CAR-NK cell efficacy, specificity, and functionality. The review underscores the advantages of CAR-NK cells, including reduced toxicity, lower cost, and broader accessibility compared to CAR-T cells, along with their potential in treating both blood cancers and solid tumors.

Osteosarcoma (OS) are the most prevalent malignant bone tumors in adolescents and young adults.. OS cells grow in a permissive local microenvironment which modulates their behavior and facilitates all steps in tumor development (e.g., proliferation/quiescence, invasion/migration, drug resistance) and contributes to their intrinsic heterogeneity. The lung parenchyma is the most common metastatic site in OS, and metastatic foci are frequently associated with a poor clinical outcome. Although multiple factors may be responsible for the disease, including genetic mutations (e.g., Rb, p53), the molecular mechanism of development of OS remains unclear and the conventional treatment for OS is still based on a sequential approach that combines chemotherapy and surgery. Also, despite the increase in clinical trials, the survival rates for OS have not improved. Non-specific targeting therapies thus show poor therapeutic effects with side effects at high doses. For these reasons, many efforts have been done to characterize the complex genome of osteosarcoma thanks to the whole exome analysis with the aim to identify predictive biomarkers to give to these patients a better therapeutic option. This review aims to summarize and discuss the main recent advances in OS molecular research for precision medicine.

Metabolic-associated fatty liver disease (MASLD) is not only associated with traditional cardiovascular risk factors such as T2DM and obesity, but it is also an independent risk factor for the development of cardiovascular disease. MASLD has been shown to be independently related to endothelial dysfunction and atherosclerosis. MASLD is characterized by a chronic proinflammatory response that, in turn, may induce a prothrombotic state. Several mechanisms such as endothelial and platelet dysfunction, changes in the coagulation cascade, decreased fibrinolytic activity can contribute to induce the prothrombotic state. Platelets are players and addresses of metabolic dysregulation; obesity and insulin resistance are related to platelet hyperactivation. Furthermore, platelets can exert a direct effect on liver cells, particularly through the release of mediators from granules. Growing data in literature support the use of antiplatelet agent as a treatment for MASLD. The use of antiplatelets drugs seems to have potential clinical implication for the prevention of HCC patients with MASLD, since platelets contribute to fibrosis progression and cancer development. This review aims to summarize the main data on the role of platelets in the pathogenesis of MAFLD and its main complications such as cardiovascular events and the development of liver fibrosis. Furthermore, we will examine the role of antiplatelet therapy not only in the prevention and treatment of cardiovascular events but also as a possible anti-fibrotic and anti-tumor agent.

Glycosphingolipids (GSLs), a subtype of glycolipids containing sphingosine, are critical components of vertebrate plasma membranes, playing a pivotal role in cellular signaling and interactions. In human articular cartilage in osteoarthritis (OA), GSL expression is known notably to decrease. This review focuses on the roles of gangliosides, a specific type of GSL, in cartilage degeneration and regeneration, emphasizing their regulatory function in signal transduction. The expression of gangliosides, whether endogenous or augmented exogenously, is regulated at the enzymatic level, targeting specific glycosyltransferases. This regulation has significant implications for the composition of cell surface gangliosides and their impact on signal transduction in chondrocytes and progenitor cells. Different levels of ganglioside expression can influence signaling pathways in various ways, potentially affecting cell properties, including malignancy. Moreover, gene manipulations against gangliosides have been shown to regulate cartilage metabolism and chondrocyte differentiation in vivo and in vitro. This review highlights the potential of targeting gangliosides in the development of therapeutic strategies for osteoarthritis and cartilage injury and addresses promising directions for future research and treatment.

This case report examines the impact of a novel Combined Neuromuscular Electrical Stimulation (Comb-NMES) regimen on muscle glucose signaling, fiber type distribution, and metabolic function in a patient with acute spinal cord injury (SCI) and lower motor neuron lesions (LMNLs). A 32-year-old male with complete T9 SCI underwent a ten-session Comb-NMES intervention targeting the quadriceps. Muscle biopsies and blood samples were analyzed pre- and post-intervention to evaluate changes in muscle fiber types, key metabolic proteins, fasting insulin, glucose, and lipid profiles. The intervention led to a 74.7%, and 28.2% reduction in fasting insulin and glucose, respectively. Muscle analysis showed significant increases in CaMK II, Hexokinase II, and IRS-1, indicating improved glucose metabolism. Comb-NMES training markedly improved metabolic control and muscle glucose metabolism in a patient with acute SCI and LMNLs. Enhanced insulin sensitivity and glucose utilization were evidenced by upregulated metabolic proteins which suggests Comb-NMES is a promising intervention for improving muscle and metabolic health in SCI patients with LMNLs. Further studies are needed to confirm these benefits and explore long-term effects.

Cancer treatment is a significant focus in medicine owing to the increasing global incidence. Patients with advanced cancers that do not respond to conventional therapies have limited options and an unfavorable prognosis. Consequently, researchers are investigating complementary approaches to conventional treatments. One such approach is alkalization therapy, which aims to neutralize the acidic tumor microenvironment (TME) by increasing its pH level. The acidic TME promotes inflammation, tumor progression, and drug resistance. Alkalization therapy has been demonstrated to be effective for various cancers. In addition, natural products, such as triterpenoids, parthenolides, fulvic acid, Taxus yunnanensis, and apple pectin have the potential to alleviate symptoms, maintain physical fitness, and improve treatment outcomes of cancer patients through their anti-inflammatory, antioxidant, and anticancer properties. In this review, we focus on the effects of alkalization therapy and natural products on cancer. Furthermore, we present a case series of advanced cancer patients who received alkalization therapy and natural products alongside standard treatments, resulting in long-term survival. We posit that alkalization therapy together with the supplementation of natural products may confer benefits to cancer patients by mitigating the side effects of chemotherapy and complementing standard treatments. However, further research is warranted to validate these clinical findings.

Cancer, characterized by abnormal cell proliferation driven by genetic mutations, remains a significant health challenge. Tailoring effective therapies depends on factors like tumor location, grade, and stage, alongside patient condition. Leveraging Nano-carrier encapsulated drugs offers a promising avenue, as they accumulate preferentially at tumor sites, enhancing therapeutic efficacy while mitigating side effects. Polymeric Nano-carriers, with their customizable properties, further optimize drug delivery efficiency and specificity. Incorporating active targeting ligands such as antibodies, carbohydrates, peptides, folates, and aptamers-onto polymeric nanoparticle surfaces through techniques like functionalization, adsorption, and conjugation plays a pivotal role in directing therapeutic agents to tumor cells. Consequently, polymeric nanoparticles emerge as the carrier of choice for delivering drugs to various tumor types, including breast, colon, lung, prostate, liver, and spleen tumors.

Infection with the malaria parasite Plasmodium, remains a major cause of illness and death world-wide. The development of evasion strategies by the parasite from host immunity and its adaptability to antimalarial drugs has raised the urgency for developing new strategies to combat this disease. One promising avenue is targeting telomeres – sequences found at chromosome termini– and telomerase – the enzyme that catalysis synthesis of telomeres using an intrinsic RNA template. As telomeres shorten critically, cells undergo replicative senescence or apoptosis. Plasmodium, lacking telomerase activity in its human stages, exploits alternative mechanisms, accelerating telomere shortening, aging, and immune evasion. Chemical telomerase inhibitors show promise as antimalarials. In this review, we examine the potential of targeting this system in malaria therapy, with telomerase inhibitors offering a novel approach. A systematic search on PubMed using Boolean techniques identified 246 relevant articles from 1985 to March 31, 2024. After filtering, 43 articles met inclusion criteria, supplemented by snowball sampling. The telomerase inhibitor drug strategy is widely applicable against cancer. However, given the drugability of telomerase and the absolute requirement for active telomere maintenance in the vast majority of parasites including plasmodium, telomerase and telomere maintenance could well represent the Achilles heel of the parasite

Radio-dynamic therapy (RDT), as an emerging cancer treatment method, has attracted attention due to its remarkable therapeutic efficacy using low-dose, high-energy radiation (such as X-rays), and has shown significant potential in cancer treatment. The RDT system typically consists of scintillators and photosensitizers. Scintillators absorb X-rays and convert them to visible light, activating nearby photosensitizers to generate cytotoxic reactive oxygen species (ROS). Challenges faced by the two-component strategy, including low loading capacity and inefficient energy transfer, hinder its final effectiveness. In addition, the tumor microenvironment (TME) with hypoxia and immunosuppression limits the efficacy of RDTs. Recent advances introduce one-component RDT systems based on nanomaterials with high-Z metal elements, which effectively inhibit deep-seated tumors. These novel RDT systems exhibit immune enhancement and immune memory, potentially eliminating both primary and metastatic tumors. This review comprehensively analyzes recent advances in the rational construction of RDTs, exploring their mechanisms and its application in the treatment of deep-seated tumors. Aimed at providing a practical resource for oncology researchers and practitioners, the review offers new perspectives for potential future directions in RDT research.

To investigate the impact of electrode structure on Electrical Stimulation Therapy (EST) for chronic wound healing, this study designed three variants of flexible microelectrodes (FMs) with Ag-Cu coverings (ACCs), each exhibiting distinct geometrical configurations: hexagonal, cross-shaped, and serpentine. These were integrated with PPY@PDA/PANI (3/6) hydrogel dressings. Comprehensive animal studies, coupled with detailed electrical and mechanical modeling and simulations, were conducted to assess their performance. Results indicated that the serpentine-shaped FM outperformed its counterparts in terms of flexibility and safety, exhibiting minimal thermal effects and a reduced risk of burns. Notably, FMs with metal coverings under 3% demonstrated promising potential for optoelectronic self-powering capabilities. Additionally, simulation data highlighted the significant influence of hydrogel non-uniformity on the distribution of electrical properties across the skin surface, providing critical insights for optimizing EST protocols when employing hydrogel dressings.

In patients with primary central nervous system lymphoma (PCNSL), the choice of surgical strategy for histopathologic assessment is still controversial, particularly in terms of preoperative corticosteroid (CS) therapy. To provide further evidence for clinical decision-making, we retrospectively analyzed data from 148 consecutive patients who underwent surgery at our institution. Although patients treated with corticosteroids preoperatively were significantly more likely to require a second or third biopsy (p=0.049), it was only necessary in less than 10% of the cases with preoperative corticosteroid treatment. The choice of surgical procedure did not affect diagnostic accuracy (p&gt;0.05). Preoperative CSF sampling did not provide additional information but was associated with delayed surgery (p=0.02). Surprisingly, diagnostic accuracy was significantly lower when patients were treated with anticoagulation or dual antiplatelet therapy (p=0.015). In conclusion, preoperative CS therapy can challenge the histological diagnosis of PCNSL. At the same time, our data suggest that preoperative CS treatment only presents a relative contraindication for an early surgical intervention. The standard surgical approach is stereotactic biopsy, but other approaches can be individually considered. If a definitive diagnosis cannot be made after the first surgical intervention, the timing of a repeat biopsy after discontinuation of CS remains a case-by-case decision.

Lipid-lowering therapy (LLT) is a cornerstone of atherosclerotic cardiovascular disease prevention. Although LLT might lead to different reductions in low-density lipoprotein cholesterol (LDL-C) levels in women and men, LLT diminishes cardiovascular risk equally effectively in both sexes. Despite similar LLT efficacy, the use of high-intensity statin, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors is lower in women compared to men. Women achieve the guideline-recommended LDL-C levels less often than men. Greater cholesterol burden is particularly prominent in women with familial hypercholesterolemia. In clinical practice, women and men with dyslipidemia present with different cardiovascular risk profiles and disease manifestations. The concentrations of LDL-C, lipoprotein(a) and other blood lipids differ between women and men over a lifetime. Dissimilar levels of LLT’s target molecules partially result from sex-specific hormonal and genetic determinants of lipoprotein metabolism. Hence, to evaluate a potential need for sex-specific LLT, this comprehensive review (i) describes the impact of sex on lipoprotein metabolism and lipid profile, (ii) highlights sex differences in cardiovascular risk among patients with dyslipidemia, (iii) presents recent, up-to-date clinical trial and real-world data on LLT efficacy and safety in women, and (iv) discusses diverse medical needs of women and men with dyslipidemia and increased cardiovascular risk.

Production and transport of reactive species through plasma-liquid interactions plays a significant role in multiple applications in biomedicine, environment, and agriculture. We experimentally investigated the transport mechanisms of hydrogen peroxide H2O2 and ozone O3, as the typical plasma species, into water. We measured the solvation of gaseous H2O2 and O3 in airflow into water bulk vs. electrosprayed microdroplets while changing the gas and water flow rates, applied voltage that determines the gas-liquid interface area, and treatment time. The solvation rate of H2O2 and O3 increased with the treatment time and the gas-liquid interface area. The total surface area of the electrosprayed microdroplets was larger than that of the bulk, but their lifetime was much shorter. We estimated that only microdroplets with diameters below ~ 40 µm could achieve the saturation by O3 during their lifetime, while the saturation by H2O2 was impossible due to its depletion from air. Besides the short-lived flying microdroplets, the longer-lived bottom microdroplets substantially contributed to H2O2 and O3 solvation in water electrospray. This study contributes to a better understanding of the gaseous H2O2 and O3 transport into water as a function of different parameters and will lead to design optimization of the plasma-liquid interaction systems.

The objective of this paper is to estimate the trend of Total Ozone Column (TOC) over Togo. Multi Sensor Reanalysis-2 (MSR-2) TOC over the entire territory of Togo were used. Multiple Linear Regression (MLR) method has been applied to retrieve the interannual contributions of different forcings and the long term variability. It was found that the Annual Oscillation (AnO), the Quasi Biennial Oscillation at 30 mb (QBO30), the Solar Flux (SF), and the El Niño–Southern Oscillation (ENSO) have statistically significant influence on the interannual variability of the TOC. The strongest contribution (22 ± 1.4 DU) is allocated to the AnO while the weakest (< 1 DU) is attributed to the Semi-Annual Oscillations (SAnO). Before the peak year of Equivalent Effective Stratospheric Chlorine (EESC) in tropics in 1997 the trend is negative (- 0.3% ± 0.9% per decade) and is not statistically significant. After the peak year, a statistically significant positive trend is observed. The trend of TOC is 0.6% ± 0.2% per decade. The monthly TOC trend over Togo is positive and statistically significant during the rainy season (particularly during the monsoon period) except in April, unlike during the harmatan period (DJF) where the trend is not significant.

Abstract: Research Highlights: This study is among the first to investigate ozone levels in urban forests in China. It establishes that urban forest air quality in Yuanshan Forest Park, Shenzhen, is suitable for recreational activities and identifies spatial, seasonal, and diurnal O3 patterns and relationships with micrometeorological parameters, suggesting the possibility of manipulating relevant forest characteristics to reduce O3 levels. Background and Objectives: An understanding of O3 levels of urban forest environments is needed to assess potential effects on human health and recreational activities. Such studies in China are scarce. This study investigated urban forest O3 levels to improve understanding and support residents engaging in forest recreational activities. Materials and Methods: We monitored O3 levels in 2015–2016 for three urban forests representing common habitats (foothill, valley, and ridge) in Yuanshan Forest Park, Shenzhen, and for an adjacent square. Results: The overall mean daily and daily maximum 8-h mean (MDA8) O3 concentrations were highest for the ridge forest and lowest for the valley forest. Each forest’s O3 concentrations were highest in summer. Diurnally, forest O3 concentrations peaked between 13:00 and 17:00 and reached a minimum between 03:00 and 09:00. The correlation between forest O3 concentrations and air temperature (AT) was strongly positive in summer and autumn but negative in spring. In each season, O3 concentration was negatively correlated with relative humidity (RH). No MDA8 or hourly O3 concentrations in the forests exceeded National Ambient Air Quality Standard Grade I thresholds (100 and 160 μg m−3, respectively). Conclusions: O3 accumulation is present in ridge urban forest in all seasons. Foothill and valley urban forests have better air quality than ridge forestation. Urban forest air quality is better in spring and autumn than in summer and is better from night-time to early morning than from noon to afternoon.

In this review we aim to address the current status of phage therapy in the management of multidrug-resistant infections, from compassionate use cases to ongoing clinical trials, as well as the challenges this approach presents in the particular context of CF patients.

Recent omics technologies have revolutionized the study of molecular plant responses to air pollution, overcoming previous limitations. This review synthesizes the latest advancements in molecular plant responses to major air pollutants, emphasizing ozone (O3), nitrogen oxides (NOX) and particulate matter (PM) research. These pollutants induce stress responses common to other abiotic and biotic stresses, including the activation of reactive oxygen species (ROS)-scavenging enzymes and hormone signaling pathways. New evidence showed the central role of antioxidant phenolic compound biosynthesis via phenylpropanoids pathway in air pollution stress responses. Transcription factors like WRKY, AP2/ERF, and MYB, which connect hormones signaling to antioxidant biosynthesis, were also affected. To date, research has predominantly focused on laboratory studies analyzing individual pollutants. This review highlights the need for comprehensive field studies and the identification of molecular tolerance traits, which are crucial for the identification of tolerant plant species aimed to the development of sustainable Nature Based Solutions (NBS) to mitigate urban air pollution.

In recent years, nocturnal ozone enhancement(NOE) events have become a hot research topic in the field of atmospheric environment. By using statistically-based data analysis, we made a comparative investigation about nocturnal ozone concentrations and NOE events in 2022 and 2023, and further explored the effects of NOE events on O3 and PM2.5 at the night of the same day and the next day. The results showed that from 2022 to 2023 in Dongying, the annual average nocturnal ozone concentrations increased from 51 μg/m3 to 59 μg/m3, and the frequency of NOE events was higher in spring, summer and autumn, and lower in winter. NOE events not only had an obvious promoting effect on nocturnal O3 and Ox, and the daily maximum 8 h average concentration of O3 (MDA8-O3) of the same day (more apparent in summer and autumn), and nocturnal PM2.5 and PM2.5-bounded NO3- and SO42- (more apparent in winter), but also had a distinct influence on O3, Ox and MDA8-O3 of the next day (more apparent in summer). The results could strengthen the understanding of the phenomena of NOE events, and provide a scientific basis for the collaborative control of PM2.5 and ozone in urban areas in the Yellow River Delta, China.

Recently, there have been revolutions in the development of both gene therapy and genome surgical treatments for inherited diseases. Much of this progress has been centered around hereditary retinal dystrophies, because the eye is an immune-privileged and anatomically ideal target. Gene therapy treatments, already demonstrated to be safe and efficacious in numerous clinical trials, are benefitting from the development of new viral vectors, such as dual and triple AAVs. CRISPR/Ca9, which revolutionized the field of gene editing, is being adapted into more precise “high fidelity” and catalytically dead variants. New CRISPR endonucleases, such as CjCas9 and Cas12a, are generating excitement in the field as well. Stem cell therapy has emerged as a promising alternative, allowing human embryo derived stem cells and induced pluripotent stem cells to be edited precisely in vitro and then reintroduced into the body. This article highlights recent progress made in gene therapy and genome surgery for retinal disorders, and it provides an update on precision medicine FDA treatment trials.

The results of numerical experiments with the chemistry-climate model of the Institute of Numerical Mathematics of the Russian Academy of Sciences - Russian State Hydro-Meteorological University (INM-RSHU CCM) in comparison with the MERRA2 reanalysis data are presented. To assess the impact of sea surface temperature (SST) on stratospheric processes and the ozone layer, numerical experiments were carried out for scenarios corresponding to the El Niño and La Niña Southern Oscillation phases. It is shown that the El Niño phase contributes to the enhancement of heat and mass transfer to the polar stratosphere, which strengthen the Brewer-Dobson circulation and the flux of wave activity that affect the zonal wind. As a result, during El Niño, the probability of sudden stratospheric warming increases and the stratospheric polar vortex (SPV) weakens, re-sulting in an increase in total polar stratospheric ozone. The La Niña phase, on the contrary, is accompanied by a weakening of heat and mass transfer from the troposphere to the stratosphere, as a result of which the stratospheric polar vortex strengthens and the total column ozone decreases. It is shown that the effect associated with the Southern Oscillation is more pronounced in the Northern Hemisphere than in the Southern Hemisphere. Numerical experiments were also carried out for scenarios in which the sea surface temperature was set corresponding to the early 1980s, and the results were compared with calculations in which the SST was set corresponding to the late 2010s. This allowed us to assess the influence of the multiyear trend in the SST increase on stra-tospheric processes and the ozone layer. It was shown that the SST increase is most pronounced in the Arctic, which corresponds to the phenomenon of "Arctic amplification", and therefore, the heat and mass transfer to the stratosphere increases in the Northern Hemisphere, which contributes to some weakening of the SPV and increase of the total column ozone. But, compared to the Southern Oscillation, the influence of the SST trend on the SPV and total column ozone is much weaker and is observed mainly in the Northern Hemisphere.

This study investigates the frequency dependence of the correlation or anticorrelation of ozone and temperature in the middle atmosphere. The anticorrelation of ozone and temperature plays a role for the expected recovery or superrecovery of upper stratospheric ozone in presence of manmade cooling of the middle atmosphere due to increasing carbon dioxide emissions. The correlation between lower stratospheric ozone and temperature indicates the dependence of lower stratospheric temperature trends on the ozone evolution in addition to greenhouse gas emissions. Ozone and temperature measurements of the microwave limb sounder (MLS) on the satellite Aura from 2004 to 2021 are utilized for Bern (46.95∘N, 7.44∘E) at middle latitudes and for the equator region. The time series are bandpass filtered for periods from 2 days to 5 years. The correlation coefficient depends on the period of the oscillation in temperature and ozone. The strongest correlation and anticorrelation are found for the annual oscillation. The anticorrelation between ozone and temperature in the upper stratosphere is about −0.7 at a period of 2 days and −0.99 at a period of one year. Thus, the temperature dependence of the ozone reaction rates also leads to an anticorrelation of ozone and temperature at short periods so that ozone can be considered as a tracer of planetary waves. At the equator, a dominant semiannual oscillation and an 11 year solar cycle are found for nighttime ozone in the upper mesosphere. The SAO in ozone and temperature show a strong correlation indicating a dynamical control of the ozone SAO in the upper mesosphere. The SAO in the equatorial nighttime values of ozone and temperature is due to a semiannual modulation of vertical advection by the diurnal tide.

Repeated exposure to environmental ozone causes a chronic state of oxidative stress. This state is present in chronic degenerative diseases and induces a loss of control of the inflammatory response. The dysfunction of redox system and failures in control the inflammatory responses are involved in a vicious circle that maintains and increases the degenerative process. Intestine also responds to secondary reactive species formed by exposure to ozone doses, generating noxious stimuli that increase degenerative damage. This review aims to elucidate how environmental pollution, mainly by ozone, induces a state of chronic oxidative stress with the loss of regulation of the inflammatory response, both in the intestine and in the brain, where the functionality of both structures is altered and plays a determining role in some neurodegenerative and chronic degenerative diseases. For this purpose, we searched for information on sites like the Cochrane Library Database, PubMed, Scopus, and Medscape. Reviewing the data published, we can conclude that environmental pollutants are a severe health problem. Ozone pollution has different pathways of action, both molecular and systemic, and participates in neurodegenerative diseases such as Parkinson's and Alzheimer's disease as well in bowel diseases as Inflammatory Bowel Disease, Crohn's Disease and Irritable Bowel Syndrome.

India is one of the large sources of the anthropogenic pollutants and their increasing emission due to the recent economic growth in India. In this study we analyzed the annual and seasonal behaviors of ozone (O₃) gas using satellite remote sensing dataset from the sources Ozone Monitoring Instrument (OMI) over India region from 2006-2015. The study focuses on the seasonal behaviors of O₃ gas i.e., monthly, seasonal, annual mean variations of trace gas and also trend analysis of O₃ gas and comparison of the seasonal behavior of the ozone gas by trend analysis were assessed. In this study we also taken eleven cities to show the increment and decrement in four seasons of O₃ gas by taking 2006 as a base year and investigate the behaviors of gases during (2007-2015) years. Higher concentrations of O₃ south-to-north gradient, indicating the variations due to the impact of emissions and local meteorology. Ozone concentrations were higher during the warmer months. However, in winter season lowest concentration of O₃ seen due to the less amount of heat and due to cold days and ozone holes in the stratosphere. Instead, total O₃ concentrations rises over Delhi, Lucknow and Kolkata due to large population density, high traffic emission, highly polluted air and larger industrial activities.

Background/Objectives: This study looks at how a kinematic chain exercise regimen that targets the lower, core, and upper body affects university shot put participants' shoulder muscle strength and throwing efficiency. This study fills an apparent research void on shot put training approaches by presenting a comprehensive kinematic chain workout program. It was anticipated that this method would improve performance the most, considering the complex biomechanical require-ments of the sport. Methodology: Athletes, seventy in age (19.87 ± 1.31 years), were assigned into two groups at random: experimental (n = 35) and control (n = 35). While the control group carried on with their usual training, the experimental group participated in an 8-week kinematic chain training program, pre- and post-training evaluations were carried out to evaluate shot put throwing ability, shoulder muscle strength, and participant satisfaction with the exercise regimen. Results: demonstrated that, when compared to the control group, the athletes in the kinematic chain program had a significantly improved throwing distance (p = 0.01) and shoulder muscle strength (p = 0.01). Furthermore, there was a significant difference (p = 0.005) in the athletes' satisfaction levels with the workout program among those in the experimental group. This implies that a kinematic chain-focused strategy improves performance and emphasizes the significance this type of training is for shot put athlete performance. Conclusion: As an improvement forward in sports science, the study's finding promotes the inclusion of kinematic chain workouts in shot put training programs and calls for more research on kinematic chain-based approaches in a variety of sports.

Background Endometrial cancer is the fourth most common type of cancer in the world. Due to the prevalence and high morbidity, it is of key importance to make a quick and accurate diagnosis and effective therapy. The use of photodynamic therapy (PDT) in the treatment of endometrial cancer is a significant challenge in conducting clinical trials. PDT is non-invasive, with few side effects, damaging only neoplastic tissue, leaving healthy adjacent structures intact. Thanks to numerous experiments (also in vitro), PDT is gaining more and more recognition as a potential tool in endometrium cancer treatment. Objective The aim of the study was to analyze the effectiveness of photodynamic therapy on endometrial cancer tissue samples Methods In the in vitro experiment of PDT, sections of endometrial cancer tissue taken from female patients were subjected to. Rose Bengal was used as a photosensitizer in order to assess the usefulness of the applied PDT and to introduce these solutions into the in vivo test procedure. Results Changes on the cellular substrate, such as: chromatin condensation, disturbed structure and shape of cell nuclei were observed in all tissues subjected to PDT. Conclusions The PDT experiment in vitro offers opportunities and hopes for using the chosen procedure also in vivo. Keywords endometrial cancer; photodynamic therapy; in vitro; treatment; rose bengal

Nowadays, it is highly desired to develop highly active and humidity resistive ozone decomposition catalyst to eliminate the ozone contaminant, one of the primary pollutants in air. In this work, a series of Cu2S hollow structured materials are rapidly synthesized using different structured Cu2O templates. The Cu2S from porous Cu2O shows the highest ozone catalytic decomposition efficiency of >95% to 400 ppm ozone with a weight hourly space velocity of 480,000 cm3g-1h-1 in dry air. Importantly, the conversion still keeps >85% in a high relative humidity of 90%. The mechanism is explored by diffusive reflectance infrared spectroscopy which shows the decomposition intermediate of O22-, and the X-ray photoelectron spectroscopy reveals the dual active site of both Cu and S. All these results show the effective decomposition of ozone by Cu2S especially in harsh environments, promising for active ozone elimination.

A better understanding of background tropospheric ozone delivers multiple benefits. Robust estimates of regional background ozone assist policy makers to understand the limits to reducing ozone by controlling anthropogenic emissions alone and assist in characterising changes in the atmospheric environment and its composition. Long time series of background ozone measurements can also help quantify the influence of human activity on the global and regional atmosphere. Background tropospheric ozone measurements representative of continental air masses are however scarce in Australia, limiting our knowledge of background atmospheric composition. Here we use k-means clustering to identify a cluster of measurements from the long-term monitoring station at Oakdale, NSW which are likely to be representative of background air. The cluster is associated with NOx-limited air masses of continental origin. From this analysis we estimate background ozone representative of Eastern Australia. We find recent (2017-2022) mean ozone mixing ratios of 28.5 ppb and identify a statistically significant (α=0.05) trend in the mean of +1.8 (1.0 – 2.8) ppb/decade. Our methods demonstrate that some long-term monitoring stations within or near urban areas can provide suitable conditions and datasets for regional Global Atmosphere Watch monitoring.

The purpose of this work is to study Rossby wave parameters in total ozone over Arctic in 2000–2021. We consider the averages in the January–March period, when stratospheric trace gases (including ozone) in sudden stratospheric warming events are strongly disturbed by planetary waves. To characterize the wave parameters, we analyzed ozone data at the latitudes of 50° N (the sub-vortex area), 60° N (the polar vortex edge) and 70° N (inner region of the polar vortex). Total ozone column (TOC) measurements during 22-year time interval were used from Total Ozone Mapping Spectrometer (TOMS) / Earth Probe and Ozone Mapping Instrument (OMI) / Aura satellite observations. The total ozone zonal distribution and variations in the parameters of the Fourier spectral components with zonal wave numbers m = 1–5 are presented. Daily and interannual variations in TOC, amplitudes and phases of spectral wave components, and linear trends of the quasi-stationary wave 1 (QSW1) amplitudes are discussed. The positive TOC peaks inside the vortex in 2010 and 2018 alternate with negative ones in 2011 and 2020. The latter TOC anomalies correspond to severe depletion of stratospheric ozone over the Arctic in the strong vortex conditions due to anomalously low activity of planetary waves. Variations in TOC in sub-vortex region exhibit the statistically significant negative trend –4.8±5.4 DU decade–1 in QSW1 amplitude, while the trend is statistically insignificant at the vortex edge region due to increased TOC variability. Processes associated with polar vortex dynamics are discussed, including quasi-stationary vortex asymmetry and quasi-circumpolar migration of the wave-1 phase at the vortex edge.

Objective: To investigate whether the relationships between acute care occupational therapy (OT) and physical therapy (PT) utilization and community discharge are moderated by functional or physical performance at discharge among individuals hospitalized with traumatic brain injury (TBI). Setting: 14 acute care hospitals in the state of Colorado. Participants: We studied 5,599 adults hospitalized with TBI between June 2018 and April 2021. Design: In a secondary analysis of de-identified electronic health record (EHR) data, multivariable moderation logistic regression models were performed to calculate odds ratios (ORs) for the likelihood of community discharge among patients who utilized OT/PT services. Main Measures: Functional (activities of daily living [ADL]) and physical (mobility) performance at discharge, OT and PT utilization, and community discharge status. Results: Overall, 67% of patients discharged to the community. The mean age of the sample was 55 years (SD = 20 years). Most participants were male (64%) and non-Hispanic white (72%). Mean hospital length of stay was 6 days (SD = 6 days). Both OT and PT utilization (OT: OR= 1.21, 95% CI [1.11, 1.33]; PT: OR= 1.22, 95% CI [1.14, 1.30]) and discharge ADL and mobility scores (ADL: OR= 1.34, 95% CI [1.30, 1.39]; mobility: OR= 1.38, 95% CI [1.33, 1.42]) were significantly and positively associated with community discharge. The OT and PT utilization-by-discharge ADL and mobility interaction terms yielded slightly negative, but statistically significant moderation effects in both models (ORs= 0.99, 95% CIs [0.98, 1.00]); indicating the magnitude of the OT and PT utilization effect diminished as ADL and mobility scores increased. Several sociodemographic characteristics and clinical factors were also independently associated with community discharge in both models (p-values

Cancers, a large and heterogeneous group of malignancies, are becoming an increasingly important cause of premature mortality worldwide. 2% of these are primary CNS tumors, of which 24% are gliomas. These tumors are diverse, but what they have in common is one of the most unfavorable prognoses among all cancers. A patient's future varies depending on the grade of the diagnosed glioma. To date, however, no standard treatment for grade IV has been established. All glioblastomas eventually undergo progression or recurrence. The current standard of treatment, which includes surgical intervention, radiation therapy and chemotherapy, is therefore far from sufficient. Work is constantly underway to discover a new, effective form of glioma therapy. Photodynamic therapy (PDT) may be one of them. It involves the local or systemic application of a photosensitive compound - a photosensitizer (PS), which accumulates in the affected tissues. Photosensitizer molecules absorb light of the appropriate wavelength, initiating activation processes leading to the formation of reactive oxygen species and selective destruction of inappropriate cells. Currently, this method has been approved for the treatment of several cancers. Research focusing on the effective use of PDT in glioma therapy is already underway, with promising results. In our work, we present molecular insights into PDT of glioma. Based on the available literature, we analyze and systematize the impact of various molecules, proteins, transporters and transmitters on the efficacy of PDT and the effect of PDT on their expression. In addition, we highlight gaps in current knowledge and point out directions for future research that may contribute to the efficacy of PDT glioma.

Objective: We report a case of acute pancytopenia and liver injury after concomitant administration of low-dose methotrexate (MTX), and high-dose esomeprazole and metamizole. Case summary: A 71-year-old patient with chronic systemic idiopathic erosive arthritis was admitted after a pelvic ring fracture. After hospital admission, she received MTX in addition to esomeprazole and metamizole. Subsequent laboratory tests revealed pancytopenia and elevated liver enzymes. The follow-up clinical examinations were unremarkable, with the exception of sub-febrile temperatures. Further investigations did not detect a definitive etiology. Due to the suspicion of methotrexate-induced hematotoxicity and hepatotoxicity, antagonizing therapy with calcium folinate was administered, after which the blood counts and liver parameters normalized. Discussion: Due to the administration of high-dose metamizole immediately before the administration of low-dose MTX, the pre-existing hematotoxic pharmacodynamic effect of MTX was acutely enhanced by that of metamizole, although folic acid was administered preemptively. In addition, the concomitant administration of high-dose esomeprazole and normal dose torasemide resulted in a pharmacokinetic interaction with MTX by decreasing its renal secretion and elimination, further enhancing the concentration-dependent hematotoxic and hepatotoxic side effects of MTX. Conclusions: The relatively high demand for analgesics in patients with chronic rheumatic diseases already being treated with MTX and proton pump inhibitors necessitates that clinicians consider drug-drug interactions as potential causes of adverse drug reactions after the administration of metamizole or nonsteroidal anti-inflammatory drugs. In this category of patients, it is strongly recommended to switch to analgesics of other classes.

Background: A Morel–Lavallée lesion (MLL) is a traumatic, internal closed degloving injury that results from shearing of subcutaneous tissue away from underlying fascia, usually associated with high-velocity trauma. Case presentation: A 52-year-old man was transported to hospital for further follow-up of a superficial femoral artery injury. Examination on admission showed bruising seen around the left thigh. Contrast-enhanced computed tomography of the left thigh revealed hematoma with extravasation from a branch of the left superficial femoral artery, but no apparent aneurysms or femoral fractures. The patient was treated with compression bandages and discharged on hospital day 6. He left hospital able to walk unaided. He subsequently complained of left thigh pain with swelling and visited the hospital several times. He was treated at another outpatient clinic and was diagnosed with MLL. Single-use disposable portable negative pressure wound therapy (NPWT) was applied for about 2 months, achieving a stable wound site. Conclusion: We encountered a case of MLL successfully treated with single-use portable NPWT. This report presents the case of a patient with isolated MLL without fracture in the left thigh, in which the diagnosis was missed on initial admission. Finally, the patient received minor interventions including drainage along with tissue debridement and portable NPWT. We reviewed the relevant literature and summarize the pathogenesis, clinical manifestations, and treatment strategies for MLL. Emergency physicians require an increased understanding of MLL to avoid misdiagnosis and missed diagnosis.

The process of developing therapies to treat rare diseases is fraught with financial, regulatory, and logistical challenges that have limited our ability to build effective treatments. Recently, a novel type of therapy called antisense therapy has shown immense potential for the treatment of rare diseases, particularly through single-patient N-of-1 trials. Several N-of-1 antisense therapies have been developed recently for rare diseases, including the landmark study of milasen. In response to the success of N-of-1 antisense therapy, the Food and Drug Administration (FDA) has developed unique guidelines specifically for the development of antisense therapy to treat N-of-1 rare diseases. This policy change establishes a strong foundation for future therapy development, and addresses some of the major limitations that previously hindered the development of therapies for rare diseases.

Oritavancin is a novel long-acting lipoglycopeptide with in vitro activity against methicillin-resistant (MR) Gram-positive pathogens and a good bactericidal activity even in presence of biofilm forming bacteria. It has been approved for acute bacterial skin and skin structure infections (ABSSSI), but recent reports have demonstrated possible off-label uses, as for prosthetic joint infections (PJI), which, in more than half of cases, are caused by MR Gram positive organisms. We reported a case of a man in his eighties with a late shoulder PJI caused by methicillin resistant Staphyloccus epidermidis (MRSE) with contraindications for surgical replacement and few oral therapeutic options for a long term suppressive antibiotic therapy. The prosthesis was retained, and the patient received ten outpatient sequential doses of 1200 mg of oritavancin during 28 weeks, based on therapeutic drug monitoring (TDM) as a guide for correct timing of administration of each dose. During oritavancin administration, the patient achieved clinical cure, with disappearance of the pain and regaining pre-infection joint mobility, with no side effects reported and no further surgery or hospitalization needed. The treatment is ongoing as a long-lasting suppressive antimicrobial therapy. Oritavancin could represent an excellent solution for treating PJI caused by MR organism, especially in patients who need a long-term suppressive therapy.

The retinoblastoma (RB) transcriptional corepressor 1 (RB1) is a critical tumor suppressor gene, governing diverse cellular processes implicated in cancer biology. Dysregulation or deletion in RB1 contributes to the development and progression of various cancers, making it a prime target for therapeutic intervention. RB1's canonical function in cell cycle control and DNA repair mechanisms underscores its significance in restraining aberrant cell growth and maintaining genomic stability. Understanding the complex interplay between RB1 and cellular pathways is beneficial to fully elucidate its tumor-suppressive role across different cancer types and for therapeutic development. As a result, investigating vulnerabilities arising from RB1 deletion-associated mechanisms offers promising avenues for targeted therapy. Recently, several findings highlighted multiple methods as a promising strategy for combating tumor growth driven by RB1 loss, offering potential clinical benefits in various cancer types. This review summarizes the multifaceted role of RB1 in cancer biology and its implications for targeted therapy.

(1) Background: Cardiac resynchronization therapy (CRT) is essential for patients with heart failure and ventricular conduction abnormalities. Cardiomyopathy often includes left bundle branch block (LBBB) marked by delayed activation of the LV lateral wall and a widened QRS complex. Following CRT, patients with heart failure and LBBB have better outcomes and quality of life improvements. Various electrocardiographic and clinical parameters are thought to predict this improvement. The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a reliable tool for measuring the quality of life in these patients. (2) Methods: We performed an observational prospective study over 69 individuals diagnosed with cardiac failure and dilatative cardiomyopathy with low FE and major LBBB and analyzed the correlations between patient outcomes after the procedure and the demographic, clinical, and electrocardiographic parameters, which include systolic blood pressure, ECG morphology elements, QRS duration, QRS area and associated comorbidities. (3) Results: Following our analysis a correlation between QRS area, intraprocedural systolic blood pressure, QRS duration and CRT outcomes assessed by the KCCQ score was observed which reflected that CRT has a hemodynamic impact and also affects the severity of ventricular asynchrony.; (4) Conclusions: The significant correlations observed with the KCCQ score show how CRT therapy impacts patients' quality of life, symptom burden, and functional status.

The paper presents the observational, remote sensing and model simulation to analyze Southern Brazil Antarctic Ozone Hole influence (SBAOHI) events occurred between 2005 and 2014. To an-alyze it we use Total Ozone Column (TOC) data provide by Brewer Spectrophotometer (BS) and OMI (Ozone Monitoring Instrument) instrument satellite, besides the AURA/MLS (Microwave Limb Sounder) instrument satellite ozone profiles was utilized with DYBAL (Dynamical Barrier Localization) code in MIMOSA (Modélisation Isentrope du transport Mésoéchelle de l’Ozone Stratosphérique par Advection) model Potential Vorticity (PV) fields. TOC has 7.0 ± 2.9 DU re-ductions average in 62 events. October have more events (30.7%). Polar Tongue events are 19.3% of total, being in October more frequently observed (50% of cases), with medium intensity (58.2%) and in stratosphere medium levels (55.0%). Already Polar Filament events (80.7%) are more frequent in September (32.0%), medium intensity (42.0%) and in stratosphere medium lev-els (40.7%). ENSO index positive phase influenced 61.3% of events, having dominance in all in-tensity categories (minor 57.9%, medium 51.6%, major 58.3%), while the equilibrium dominate the QBO influence with 50% of total cases in positive phase and 50 % in negative phase.

Candida spondylodiscitis (CS) is a rare disease, for which therapeutic option are limited to fluconazole or echinocandins and the treatment should be administered up to 12 months. In case of reduced azole susceptibility, there is a scarcity of therapeutic options with adequate bone penetration and limited toxicity. We report the first case of successful use of rezafungin for a spondylodiscitis due to Candida parapsilosis with reduced susceptibility to azoles. The patient, affected by paraplegia and short bowel syndrome, was diagnosed with CS with culture on vertebral biopsy guided by a 18-FDG-PET/CT scan. He received rezafungin 200 mg weekly for 26 weeks, after 10 weeks of previous antifungal treatment. He had a full clinical, radiologic and biochemical response to the therapy with rezafungin, with no adverse effects. Rezafungin is a promising therapy for Candida osteomyelitis, especially when first line therapies are ineffective or contraindicated.

Pulmonary complications are frequently observed in patients with ulcerative colitis (UC), with large airway disease being the most prevalent manifestation. In this case study, we explore the potential for Immunosuppressant, a monoclonal antibody, to induce pulmonary hemorrhage—a side effect not previously documented with its use. The subject, a young male in his twenties with a six-year history of UC, tragically died suddenly. Found in a pool of blood without external injuries, extensive post-mortem examinations were required to determine the cause of death. The patient had been on biologic therapy, receiving Immunosuppressant intermittently over the past two years, including an infusion five days prior to death. External examination revealed bloody, pinkish foamy material expelling from his nose and mouth. An autopsy supported an atypical presentation of UC, while histopathology confirmed diffuse pulmonary hemorrhage, marked by edema and emphysematous changes. Additionally, there was a notable lymphomonocytic infiltration around the arterial walls, and signs of bronchiolitis and focal pleural fibrosis were evident. We concluded that the cause of death was Diffuse Alveolar Hemorrhage (DAH), directly associated with the recent administration of Immunosuppressant. This finding underscores the need for vigilant pulmonary monitoring in patients treated with monoclonal antibodies to promptly identify and manage potential fatal adverse reactions.

Monitoring of clients living with HIV encompasses a specific array of activities that routinely check on various aspects of ART following its initiation depending on the availability of resources in that particular state, among other factors as per guidelines from the World Health Organisation. This is a significant practice as it promotes positive health outcomes for patients and efficient utilisation of ART regimens to reduce resistance to the medication – hence it is a measure to guard avoidable costs. It also forms a basis on which decisions are made from. It can be done clinically by assessing for signs e.g., skin rash and symptoms e.g., nausea and vomiting, checking vital organ function and measuring weights across all populations, or can be also be done by assessing specimens for their respective viral loads, white blood cell count, pregnancy status or other infections such as hepatitis B. There have not been any special indications required for one to be eligible for monitoring during ART in developing countries; all qualify for routine monitoring even though some may be more frequent than others in cases of comorbidities such as renal failure where medications can be attributed to exacerbating the condition.

Purpose To investigate the effects of intra-articular glenohumeral joint triamcinolone injection in treating secondary adhesive capsulitis after breast cancer surgery.Methods This study prospectively enrolled 37 participants, 22 of the breast cancer surgery group and 15 of the idiopathic group. All participants received intra-articular glenohumeral joint injection in the affected shoulder joint and received physiotherapy for 12 week. The clinical assessment evaluated before, and 1, 3, and 6 months after the intervention. The primary outcome was the change in the Shoulder Pain and Disability Index (SPADI).Results The total SPADI(%) in both groups showed significant decrease from baseline to 1, 3, and 6 months after the intervention. There was no significant difference in the differences of the total SPADI from baseline to 1, 3, and 6 months between two groups. However, the improvement in the SPADI pain subscale and the PROM of abduction at 3 and 6 months post-injection in the breast cancer group were inferior to the idiopathic group.Conclusion Intra-articular triamcinolone injection for adhesive capsulitis after breast cancer surgery significantly improved in significant improvements of pain, shoulder function and the PROM. The effects were similar to idiopathic adhesive capsulitis, but in the breast cancer surgery group, appropriate pain and ROM management and monitoring are required even 3 months after injection. With a standardized injection protocol, intra-articular triamcinolone injection could be an effective and safe treatment option for secondary adhesive capsulitis after breast cancer surgery.

In individuals with spinal cord injury (SCI), rapid skeletal muscle atrophy and metabolic dysfunction pose profound rehabilitation challenges, often resulting in substantial loss of muscle mass and function. This study evaluates the effect of combined neuromuscular electrical stimulation (Comb-NMES) on skeletal muscle cross-sectional area (CSA) and inflammatory signaling within the acute phase of SCI. We applied a novel Comb-NMES regimen, integrating both high-frequency resistance and low-frequency aerobic protocols on the vastus lateralis muscle, to participants early post-SCI. Muscle biopsies were analyzed for CSA and inflammatory markers pre-and post-intervention. The results revealed a preservation of muscle CSA in the Comb-NMES group compared to a control group receiving transcutaneous electrical nerve stimulation and passive movements. Inflammatory signaling proteins such as TLR4 and Atrogin-1 were downregulated, whereas markers associated with muscle repair and growth were modulated beneficially in the Comb-NMES group. The study's findings suggest that early application of Comb-NMES post-SCI can attenuate inflammatory pathways linked to muscle atrophy and potentially promote muscle repair, advocating for its inclusion in early rehabilitation efforts. However, the small sample size and variability in injury characteristics emphasize the need for further research to corroborate these results across a more diverse and extensive SCI population.

Staphylococcus aureus is a gram-negative bacterium that causes superficial and deep infections that can be mild or potentially fatal. Recently, the bacterium has gained significant attention due to the increased incidence of multidrug-resistant (MDR) strains that make treatment with antibiotics dif-ficult. Owing to the MDR strains, alternative therapies such as antimicrobial photodynamic therapy (PDT) have emerged as good options to treat non-systemic infections. PDT combines a photosensi-tiser (PS) with light and oxygen to generate free radicals that destroy bacterial structures such as the plasma membrane, matrix, and genetic material. This systematic review aimed to identify the ef-fectiveness of PDT delivered using different types of hydrogels for treating wounds, burns, and contamination by S. aureus. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Bibliographic research was conducted using the PubMed, Web of Science, and Scopus databases. Only full articles published in English between 2013 and 2024 from any country of origin (without restrictions) were included. The research was carried out from 15 June 2023 to 15 June 2024 and did not use any automatic biblio-graphic search tool. The articles collected were identified using keywords and selected using in-clusion and exclusion criteria in accordance with the PRISMA protocol. Seven articles were in-cluded that presented a good set of evidence associated with the use of PDT against S. aureus in in vitro and in vivo studies. To conclude, PDT can effectively complement antimicrobial therapy against S. aureus, in the healing of wounds and burns. The effectiveness of this technique depends on the PS used, hydrogel type, and lesion location. Some studies have already demonstrated the ef-fectiveness of PDT but most were in vitro and a few in vivo. Further studies are required to demonstrate the safety and efficacy of PDT delivered via hydrogels in in vivo models of bacterial infection.

Abstract: Chronic Obstructive Pulmonary Disease (COPD) is a continually advancing respiratory disorder, characterized by enduring airflow limitation along with long-lasting inflammation in the airways. An expanding pool of evidence is emphasizing how mitochondrial dysfunction directly impacts the development and progression of COPD. This comprehensive review delves deeper into the intricate cellular and molecular biology of mitochondria within the framework of COPD, spotlighting significant alterations in structure and function that accompany mitochondrial dysfunction. In this narrative, we delve into the observed changes in mitochondrial shape, behavior, and respiratory chain complex alterations seen in individuals afflicted with COPD. The discussion includes implications on cellular signaling pathways and how this affects the natural process of programmed cellular death (apoptosis) and cellular aging, particularly in reference to COPD. Additionally, we consolidate ongoing therapeutic strategies, honing in on the management of COPD through a focus on mitochondrial dysfunction. Prominent among these strategies is the potential role of antioxidants and mitochondrial biogenesis inducers, which are emerging as promising fields of intervention. Furthermore, we embark on an overview of the possible use of mitochondrial biomarkers as innovative tools in diagnosing COPD, evaluating disease progression, and monitoring the efficacy of COPD treatments. As we unravel the rather complex interplay between mitochondrial biology and COPD, this review highlights the critical importance of formulating treatments that target mitochondrial dysfunction. The ultimate goal of these strategic interventions is to slow down the rate of COPD progression and significantly improve patient outcomes. Lastly, though our understanding of the nexus between COPD and mitochondrial dysfunction has significantly enhanced, ample scope remains for further investigation. Improved insights into the mechanisms of mitochondrial dysfunction, discovered biomarkers, and targeted therapies could encompass a revolutionary step towards comprehensive disease management. The future of COPD treatment seems to lean towards a combination of strategies, prioritizing not only the management of symptoms but also focused on preserving and restoring lung function, improving physical capacity, and enhancing quality of life for COPD patients.

Growth hormone therapy (GHT) can improve growth velocity and final height but can also accelerated the process of bone growth, which is related to structural bone modelling, both in formation and resorption. The study evaluated the capacity of bone turnover markers to predict early growth response to one year GHT in short stature children born as small for gestational age (SGA). 25 prepubertal SGA children were included. We have estimated P1NP (N-terminal procollagen type 1), CTX (C-terminal telopeptide of collagen type I), P3NP (N-terminal procollagen type III), NT-pro-CNP (amino-terminal C-type natriuretic peptide) and Ca-P metabolism using standard ECLIA, IRA and ELISA methods. A statistically significant increase in bone resorption markers (Ctx ) was found both at 6 and 12 months. P1NP bone markers increased at 6 months and after 12 months of therapy. The P3NP marker of collagen synthesis also increased after 12 months of therapy. We obtained significant increases in phosphorus levels at 6 and 12 months and similarly ALP. We have found a significant correlation between height (cm) and Ctx after 6 -12 months as well as P1NP / height (SD) after 12 months. Calcium levels significantly correlated with height (SD) after 12 months. We find a strong reaction of bone resorption and bone formation markers during growth hormone therapy that may determine their selection as prediction of GH treatment outcome in SGA children. However, the issue requires further research.

Abstract: In recent years, the concentration of fine particulate matter (PM2.5) in China has decreased significantly, whereas the concentration of surface ozone (O3) has increased. The formation regime of ozone is closely related to the ratio of volatile organic compounds (VOCs) to nitrogen oxides (NOx). To reveal the reasons for this increase in ozone, we determined the sensitivity of ozone generation by determining the regional threshold of the ratio of formaldehyde to nitrogen dioxide (HCHO/NO2) in the satellite troposphere. The different FNR(HCHO/NO2) ratio ranges indicate three formation regimes: VOC-limited, transitional, and NOx-limited. The range of the transitional regime plays a crucial role in identifying the regime of ozone formation. Currently, the key threshold for ozone generation in China remains unclear. Polynomial fitting models were used to determine the threshold range for the transitional regime in the BTH region [2.0,3.1]. The ozone formation regime in the BTH region mainly exhibited a transitional and NOx-limited regime, and the overall concentration changes of the HCHO and NO2 columns in the BTH region showed a fluctuating trend from 2019 to 2022. However, compared to 2019, the ozone precursors and FNR showed varying degrees of decline in 2022. The concentration changes of NO2 were high in winter and low in summer, whereas the trend of HCHO and FNR changes was the opposite to that of NO2, being high in summer and low in winter. The concentrations of HCHO and NO2 in the BTH region showed a trend of urban agglomeration areas>urban expansion areas>non-urban areas in different land types from 2019 to 2022, whereas the FNR showed an opposite trend in urban agglomeration areas<urban expansion areas<non-urban areas.

Objective: To evaluate the effect of rectal Ozone (O3) in severe COVID-19 pneumonia in two different cohorts differing in location (Madrid vs Zilina), ethnicity (Slovakian vs Spanish cohorts) and age. Material and Methods: In a multicenter-study, 32 severe bilateral-COVID-19-pneumonia patients and (+) RT-PCR (reverse transcriptase polymerase chain reaction) SARS-CoV-2 were evaluated (16 from each cohort). Primary outcomes: a) clinical (O2-saturation); b) biochemical (Lymphocyte-count, Fibrinogen, D-Dimer, Urea, Ferritin, LDH [lactate dehydrigenase], IL-6 and CRP [c-reactive protein]); and c) radiological improvement. Secondary outcomes: a) days-of-hospitalization, b) mortality-rate before discharge. The Ozone-protocol consisted of 10 sessions of intra-rectal Ozone, total dose 5.25 mg (150 mL volume, 35 g/ml concentration). The Standard-of-care protocol included O2 supply, antivirals (Remdesivir / Isoprinosine), corticosteroids (Dexamethasone / Metilprednisolone), monoclonal antibodies (Anakinra / Tocilizumab), antibiotics (Azytromicine), anticoagulants (Enoxaparine / Fraxiparine). Protocol was approved by Health Care Ethics Committee (Report 15/4/2020) of our Hospital and by Ethics Committee for Medical Investigation of La Princesa’s Hospital (ACTA CEIm 12/20, 28/5/20, Registry 4146). Results: Patients in Slovakian cohort were younger (53.38 vs 84.69 years). Grade of severity was worse in Spanish-cohort (4.78 vs 3.30 points). Length of stay was superior in Spanish-cohort (27.38 vs 10.07 days). Both cohorts improved O2-saturation and Lymphocyte-count. Inflammation biomarkers (Fibrinogen, D-Dimer, Urea, Ferritin, LDH, CRP and IL-6) decreased in both cohorts. In Spanish-cohort, Urea and Ferritin improvement was not significant (p>0.05), while in Slovakian-cohort, Urea, Fibrinogen and LDH were not significant (p>0.05) Radiological signs of bilateral pneumonitis decreased on both cohorts. Mortality was similar (12.5%). Conclusion: After Standard of care protocol, Rectal Ozone improved O2-saturation, decreased inflammation biomarkers and improved Taylor’s radiological scale in both cohorts. Although age, grade of severity and days of hospitalization were inferior in Slovakian cohort, mortality was similar in both cohorts, but inferior if compared to an external control cohort.

Abstract: Background: COVID-19 is associated with various changes in immunity, including signaling through the pattern-recognition receptors (PRR). However, the role of these processes is poorly understood. The present study aimed to evaluate the relationships of the serum levels of the cyclic dinucleotide 2’3’-cyclic GMP-AMP (cGAMP) marker of PRR activation with immunoglobulin G antibodies against severe acute respiratory syndrome-linked coronavirus (IgG-SARS)-positive status and endothelial dysfunction in apparently healthy subjects and in patients with coronary heart disease (CHD). Methods: The present study investigated selected groups from two cohorts, including cohort 1 of 307 healthy volunteers and cohort 2 of 218 CHD patients. COVID-19 infection was confirmed by the detection of IgG-SARS against SARS-CoV-2 S1 protein receptor-binding domain. Cohort 1 (24–69 years of age; 44.8 ± 8.6 years; 80.4% men) was examined for systematic coronary risk evaluation by European Society of Cardiology (SCORE) starting from 2019 before the onset of the COVID-19 pandemic. Cohort 2 (63±10.9 years of age, 54% men) was processed starting from 2017 (three years prior to the COVID-19 pandemic) in a hospital setting to undergo coronary angiography to assess coronary lesions as Gensini score. The levels of cGAMP and endothelial markers (nitrate and nitrite combined as NOx and endothelin-1) were assessed in the serum to evaluate the associations with IgG-SARS status, SCORE, and extent of coronary lesions by correlation and receiver operating characteristic (ROC) analyses. Results: Serum cGAMP did not discriminate between SARS-positive and SARS-negative healthy subject of cohort 1. Moreover, the level of cGAMP was not associated with endothelial biomarkers in healthy subjects. However, serum cGAMP was associated with atherosclerosis in cohort 2 in patients with CHD (area under the curve (AUC) 0.69; 95% CI 0.587-0.806; P=0.001), indicating that serum cGAMP was lower in patients with coronary stenosis compared to that in patients without coronary lesions. Conclusions: Low levels of serum cGAMP were associated with atherosclerosis and markers of endothelial dysfunction in patients with CHD. However, cGAMP was not associated with endothelial biomarkers or IgG-SASR immune status in healthy subjects, suggesting that cGAMP may be a new biomarker of coronary lesions in the context of sterile inflammation.

In this work, we examined the effect of tropospheric emissions on tropospheric ozone (O₃) by conducting three-dimensional (3D) chemistry transport model (CTM) simulations. For the control run, the CTM model simulates tropospheric O₃ levels with a complete set of anthropogenic, biomass burning, and vegetation emissions [8]. For the no-emission simulation, all anthropogenic, biomass burning, and vegetation emissions were turned off. Comparisons of results from these two simulations exhibit the emission impacts on the tropospheric O₃. In the no-emission simulation, distinctive low surface O₃ with concentrations less than 5 ppbv prevail over the Amazon basin, tropical South America, tropical South Africa, Southeast Asia. Transport of air from these land areas downwind contributes to the low O₃ over the remote marine boundary layer. In contrast, elevated O₃ levels over the extra-tropical remote marine boundary layer are less supported by the anthropogenic and biomass burning emissions but more sustained by the downward transport of O₃ from the stratosphere. These results demonstrate that the northern hemisphere continental areas (north of 30^◦N ), polar regions, and tropical continental regions are more sensitive to the tropospheric emissions. The northern hemisphere winter is mostly dominated by the stratospheric processes, while the tropospheric emissions dominate over the southern hemisphere tropical continental areas from tropics to 30^◦S latitudinal bands. The northern hemisphere continental regions are increasingly dominated by tropospheric emissions from spring, to reach maxima in summer, and started to reduce in autumn months.

The relationship between antitumor response and tumor marker changes was evaluated in patients with advanced hepatocellular carcinoma treated with durvalumab plus tremelimumab (Dur/Tre). Thirty-two patients were enrolled in this retrospective evaluation of treatment outcomes. According to Response Evaluation Criteria for Solid Tumors at 8 weeks, the objective response rate (OR) was 25% and the disease control rate (DC) was 56.3%. Median alpha-fetoprotein (AFP) ratio at 4 weeks was 0.310 in patients who achieved OR at 8 weeks (8W-OR group), significantly lower than the 1.105 in the non-8W-OR group (p=0.0020), but was 1.210 in patients who did not achieve DC at 8 weeks (non-8W-DC group), significantly higher than the 0.470 in the 8W-DC group (p=0.0006). Similarly, median des-γ-carboxy-prothrombin (DCP) ratio at 4 weeks was 0.125 in the 8W-OR group, significantly lower than the 1.225 in the non-8W-OR group (p=0.0001), but was 1.120 in the non-8W-DC group, significantly higher than the 0.480 in the 8W-DC group (p=0.0255). Early changes in tumor markers after Dur/Tre initiation were associated with antitumor response. In particular, changes in AFP and DCP at 4 weeks may offer useful biomarkers for early prediction of both response and progressive disease following Dur/Tre.

Two decades after the antiretroviral therapy (ART) introduction, several challenges still prevail in maintaining people living with HIV (PLHIV), even with "Test and Treat" and/or "Rapid Start of ART" initiatives, as well as the scale-up of ART worldwide to promote access and adherence to treatment. This review examined articles on ART adherence in Africa between 2016 and 2023, published in English and indexed in PubMed. A total of 16 articles out of 2415 were eligible and included for analyses. Overall, ART adherence rates in SSA regions ranged from 43% to 84%. Rates in the centre of the SSA region ranged from 58% to 80%, in the north from 50% to 83%, in the south from 77% to 84%, in the west from 43% to 60% and in the east from 69% to 73%. Most African countries use the self-report to assess treatment adherence, although unreliable. The main factors with negative influence on ART adherence were comorbidities, lack of motivation, socioeconomic difficulties or side effects. Conclusion: Adherence to ART is a good indicator for controlling the spread of HIV. It is important to overcome the barriers that make it difficult to comply with ART and reinforce the factors that facilitate the accession of medication.

In this review, we have included current information on the use of photodynamic therapy in the treatment of gliomas. We mainly focused on the discussion and regarding the use of photodynamic therapy in patients with genetically determined syndromes that are associated with an increased risk of glioma. The review also uses information on genetic syndromes that are associated with an increased risk of glioma.

Hypertension is a frequent risk factor for cardiovascular diseases and the prevalence rate is continuously rising. Multiple pathophysiological mechanisms are responsible for hypertension, necessitating a combination of drugs from different classes for best management. Combination therapy is five times more effective in decreasing blood pressure compared to escalating the dose of a single agent. As per the ACCOMPLISH trial analysis, coupling a renin-angiotensin system inhibitor with a calcium channel blocker is more effective than the combination of a renin-angiotensin system inhibitor with diuretics in reducing major cardiovascular events, cardiovascular-related mortality, and the progression of chronic kidney disease. The renin-angiotensin system can be suppressed by inhibiting the angiotensin-converting enzyme or angiotensin type 1 receptor (AT1R), resulting, in decreased vascular smooth muscle contraction, heart performance, and reduced aldosterone synthesis. Calcium channel blockers work by inhibiting L-type calcium channels, reducing heart performance via negative inotropic, chronotropic, and bathmotropic effects, along with reducing vascular smooth muscle contraction. Diuretics exert their antihypertensive impact by changing body fluid volume and electrolytes. Initially, hypertension treatment commences with a single medication but often, different classes of two or more antihypertensive medications are necessary for achieving the target blood pressure goal. Sometimes, for Resistant hypertension four different classes of antihypertensive medications are necessary to reach the target blood pressure goal.

Background and Objectives: Cancer as the second leading cause of death in the United States poses a huge healthcare burden. Barriers to access to advanced therapies influence the outcome of cancer treatment. In this study, we examined whether insurance types affect the quality of cancer clinical care regarding access to an important monoclonal antibody, ramucirumab. Materials and Methods: Data for 13,340 cancer patients with Purchased or Medicaid insurance from the All of Us Database were collected for this study. The Chi-square test of proportions was employed to determine the significance of patient cohort characteristics and ramucirumab usage between Purchased and Medicaid insurance groups. The independent t-test was utilized to assess the influences of other determinants on insurance types. Results: Cancer patients who are African American, with lower socioeconomic status, or with lower educational attainment are more likely to be insured by Medicaid. Analysis of survey questions demonstrated the relationship between income and education level with insurance type as Medicaid cancer patients were less likely to receive primary care and specialist physician access and more likely to request lower cost medications. In addition, those with Medicaid insurance were identified to have poorer access to expensive therapeutics like ramucirumab compared to those with Purchased insurance.  Conclusions: The inequities of the US healthcare system are observed for cancer patient care; access to physicians and therapeutics are highly varied and dependent on insurance types. Socioeconomic status determines insurance type, which unfortunately generates a significant impact on cancer treatment and disease outcome.

The increase in the rate and prevalence of diseases associated with the localized and general loss of bone mass calls for an investigation into therapeutic alternatives that largely involve the de-velopment of new biomaterials and cell therapy, converting tissue bioengineering into a prom-ising option. An experimental model of a critical mandibular lesion in rats has been used to study bone re-generation by treating the ostectomy with the biomaterials Evolution® and Gen-Os® (OsteoBiol®, Italy) combined, or not, with dental pulp stem cells (DP-MSC). The results obtained through the Micro-CT and histological study reveal the almost complete re-covery of the lesion in the group with DP-MSC. These results are supported by increases in endoglin, TGF-β, protocollagen I, parathormone, and calcitonin, generating an environment of bone generation and development when combining Evolution® and Gen-Os® (OsteoBiol®, Italy) with DP-MSC. These promising results confirm the transcendental role of DP-MSC in combina-tion with osteogenic biomaterials for bone regeneration, and warrant further studies, including its assessment in clinical trials.

Air pollution in urban centers depends directly on anthropogenic activities. The objective of the present study was to predict tropospheric ozone levels from temperature data in the city of Durango, Dgo. Temperature and tropospheric ozone values were obtained from 18 sampling points in the urban area of the city of Durango, of which 15 were obtained by collecting from the Ventusky service and the rest from three fixed monitoring stations established in the city. These values were interpolated in order to determine the spatial values for the entire city. A correlation analysis was performed for three different periods in the day established as follows (24:00-03:00-06:00, 09:00-12:00-15:00 and 15:00-18:00-21:00). Subsequently, a linear regression analysis was performed by time period. The results showed a higher positive correlation between ozone concentration and temperature from 15:00 hrs to 21:00 hrs; likewise, this period showed a higher goodness of fit in the ozone prediction (R2=0.99; RMSE: 1.12 ppbv). Temperature allows spatial prediction of ozone concentrations in urban areas with acceptable accuracy.

Ozone and fine particles (PM_2.5) are the two main air pollutants of concern in the New South Wales Greater Metropolitan Region (NSW GMR) region due to their contribution to poor air quality days in the region. This paper focuses on source contributions to ambient ozone concentrations for different parts of the NSW GMR, based on source emissions across the greater Sydney region. The observation-based Integrated Empirical Rate Model (IER) was applied to delineate the different regions within the GMR based on the photochemical smog profile of each region. Ozone source contribution is then modelled using the CCAM-CTM (Cubic Conformal Atmospheric Model-Chemical Transport Model) modelling system and the latest air emission inventory for the greater Sydney region. Source contributions to ozone varied between regions, and also varied depending on the air quality metric applied (e.g., average or maximum ozone). Biogenic volatile organic compound (VOC) emissions were found to contribute significantly to median and maximum ozone concentration in North West Sydney during summer. After commercial domestic, power station was found to be the next largest anthropogenic source of maximum ozone concentrations in North West Sydney. However, in South West Sydney, beside commercial and domestic sources, on-road vehicles were predicted to be the most significant contributor to maximum ozone levels, followed by biogenic sources and power stations. The results provide information which policy makers can devise various options to control ozone levels in different parts of the NSW Greater Metropolitan Region.

Cancer develops from abnormal cell growth in the body, causing significant mortalities every year. To date, potent therapeutic approaches have been developed to eradicate tumor cells, but intolerable toxicity and drug resistance can occur in treated patients, limiting the efficiency of existing treatment strategies. Therefore, searching for novel genes critical for cancer progression and therapeutic response is urgently needed for successful cancer therapy. Recent advances in bioinformatic and proteomic techniques have allowed the identification of a novel category of peptides encoded by non-canonical open reading frames (ncORFs) from historically non-coding genomic regions. Surprisingly, many of the ncORFs express functional microproteins that play a vital role in human cancers. In this review, we provide a comprehensive description of different ncORF types with coding capacity and technological methods in discovering ncORFs among human genomes. We also summarize the diagnostic and prognostic value of these ncORF as well as their carcinogenic role in cancer progression and underestimated potential as therapeutic targets.

Great toe strength (GTS) weakness is linked to declines in balance and mobility. Assessing GTS, particularly great toe extension strength (GTES) accurately is often neglected in clinical evaluations due to cumbersome and subjective methods. This study aims to characterize the force development curve output from the ToeScale and examine GTES variations with age, sex, BMI, and grip strength (GS) using traditional analyses and machine learning (ML). We conducted a pilot, cross-sectional feasibility study with convenience samples. We assessed GS using a hand-grip dynamometer and GTES using the ToeScale. Data analysis included descriptive statistics, correlations, independent samples t-tests, and accuracy and area under the curve (AUC) scores for three ML models. Thirty-one participants (Males: 9, Females: 22), 14 young (18-24 years), and 17 older (&gt;65 years) adults participated in the study. Males had significantly higher peak GTES than females in both age groups. Associations between GTES parameters with BMI and GS varied by age and sex. ML model accuracies and AUC scores were low-moderate but aligned with traditional analyses. Future studies with larger samples and optimized ML models are needed.

Oral candidiasis is a common problem among immunocompetent patients. The frequent resistance of Candida strains to popular antimycotics makes it necessary to look for alternative methods of treatment. The authors conducted a systematic review following the PRISMA 2020 guidelines. The objective of this review was to determine whether curcumin-mediated aPDT and blue light could be considered as an alternative treatment for oral candidiasis. PubMed, Google Scholar and Cochrane Library databases were searched using a combination of the following keywords: (Candida OR candidiasis oral OR candidosis oral OR denture stomatitis) AND (curcumin OR photodynamic therapy OR aPDT OR photodynamic antimicrobial chemotherapy OR PACT OR photodynamic inactivation OR PDI). The review included in vitro laboratory studies with Candida spp., in vivo animal studies, and randomized control trials (RCTs) involving patients with oral candidiasis or prosthetic stomatitis, published only in English. The method of elimination of Candida species in the studies was curcumin-mediated aPDT. 757 studies were identified. Following the analysis of the titles and abstracts of the studies, only 42 studies were selected for in-depth screening, after which 26 were included in this study. All studies evaluated the antifungal efficacy of curcumin-mediated aPDT against C. albicans and non-albicans Candida. In studies conducted with planktonic cells solutions, seven studies demonstrated complete elimination of Candida spp. cells. The remaining studies demonstrated only partial elimination. In all cases, experiments on single-species yeast biofilms demonstrated partial, statistically significant inhibition of cell growth and reduction of biofilm mass. In vivo, curcumin-mediated aPDT has shown good antifungal activity against oral candidiasis also in an animal model. However, its clinical efficacy as a potent therapeutic strategy for oral candidiasis requires further RCTs.

Diarrhea remains one of the leading causes of mortality worldwide, especially among children. Recent epidemiological studies conducted in developing countries identified Shigella species as the most predominant pathogenic bacteria responsible for diarrhea. Antimicrobial therapy is necessary for Shigella infections; however, the rapid emergence of resistance against existing antimicrobials in Shigella spp. poses a serious global health problem. To identify alternative antimicrobial compounds with activity against Shigella species, the pathogens responsible for bacterial diarrhea. In this study, we have applied antibacterial phenotypic screening to identify potent anti-Shigella compounds across a broad chemical diversity, including selected acetaminophen derivatives containing benzothiazoles backbone, and their combination with certain antibiotics. In continuation to our effort in searching potent antimicrobial compounds, we have found this time around that two acetaminophen derivatives containing benzothiazoles backbone (4a and 4b) could inhibit the growth of Shigella flexneri with common MIC value of 12.5 µg/ml. These compounds were established through a time-kill kinetics’ study to be bactericidal. Meanwhile, the 2-aminobenzothiazoles (1a and 1b) used for the synthesis of compounds 4 (a & b) were found to be poorly active (MIC: 100 µg/ml) against this pathogen. Combination studies of 4a and 4b with the least susceptible antibiotics (ceftriaxone and cotrimoxazole) demonstrated synergistic anti-Shigella activity. The present study demonstrates that the azobenzothiazole dyes 4 (a & b) can be repurposed as potential anti-Shigella compounds, which can serve as scaffolds for the development of new agents against infectious diarrhea caused by Shigella and other enteric pathogens, especially in developing countries.

Vancomycin is one of the ‘last-line’ classes of antibiotics used in the treatment of life-threatening infections caused by Gram-positive bacteria. Even though vancomycin was discovered in 1950s it was widely used after 1980s for the treatment of infections caused by methicillin-resistant Staphylococci as prevalence of such strains were increased. However, currently it is evident that vancomycin resistant Staphylococcusaureusandvancomycin-resistant Enterococci have been developed as a result of various reasons including use of avaparcin, which is an analog of vancomycin, as feed additive in livestock. In present day context, more attention should be paid on prevention of emergence of resistance for the antibiotics in order to keep antibiotics effective. In order to prevent emergence of resistance, proper guidance for the responsible use of antimicrobials is indispensable. Therefore, almost all stakeholders who use antibiotics should have in depth understanding on the antibiotic they use. As such, it is imperative to be aware of the important aspects of vancomycin. In the present review, efforts have been made to discussthe pharmacokinetics and pharmacodynamics, indications, emergence of resistance, control of resistance, adverse effects and alternative therapy for vancomycin.