Using analytic approach we study the effect of HPA axis secretions to the emotional variation of bipolar II disorder patient. Modified Duffing – Van der Pol oscillator was used to model the emotional variation, that was solved analytically using multiple scale perturbation to obtain an asymptotic solution. The solution was graphed to understand the effect of the variation of the cortisol to the oscillator. It was observed that the increase or decrease of the HPA hormone from the basal level in the body system, affects the mood variation of bipolar II disorder patients.

Maternal type 2 diabetes mellitus (T2DM) has been shown to result in fetal programming of the hypothalamus-pituitary-adrenal (HPA) axis, leading to adverse fetal outcomes. T2DM is preceded by prediabetes and shares similar pathophysiological complications. However, no studies have investigated the effects of maternal prediabetes on fetal HPA axis function and postnatal offspring development, hence this study. Pre-diabetic (PD) and non-pre-diabetic (NPD) female Sprague Dawley rats were mated with non-prediabetic males. After gestation, male pups born from the PD and NPD groups were collected. Markers of HPA axis function, adrenocorticotropin hormone (ACTH) and corticosterone were measured in all dams and pups. Glucose tolerance and expression of mineralocorticoid (MR) and glucocorticoid (GR) receptors were further measured in all pups at birth and their developmental milestones. The results demonstrated increased basal concentrations of ACTH and corticosterone in the dams from the PD group by comparison to NPD. Furthermore, the results show an increase in pups ACTH and corticosterone concentrations, impaired glucose tolerance and dysregulated MR and GR expression in the PD group at all developmental milestones. These observations reveal that pregestational prediabetes is associated with maternal dysregulation of the HPA axis, impacting offspring HPA axis development along with impaired glucose handling.

Obsessive–compulsive disorder (OCD) is believed to follow a waxing and waning course, often according to environmental stressors. During the COVID-19 pandemic, pre-existing OCD symptoms were reported to increase and to change from checking to washing behaviors, while new-onset symptoms were predominantly of the hoarding type. In the present study, we followed the evolution of OCD symptoms, anxiety, depression, and insight of illness in forty-six OCD patients throughout the pandemic. Clinical measures were collected at four different time points before and during the COVID-19 pandemic in Italy. Within-subject comparisons were used to compare clinical scale scores across time, and correlations were examined between patients' baseline characteristics and changes in clinical scores. We found that all clinical measures increased during the first Italian lockdown, with respect to the pre-pandemic values. Anxiety decreased during the temporary elimination of restriction provisions, whereas severity of OCD symptoms and insight returned to pre-pandemic values during the second mandatory lockdown. These results were observed only in two sub-groups of patients: those taking benzodiazepines and those with shorter illness duration. Our findings suggest the need of additional clinical attention to these specific sub-groups of OCD patients in case of particularly distressing circumstances, while pointing to a possible adaptive role of their OCD symptoms when the environment requires a higher care of hygiene and extraordinary supply of essential resources.

1) Background: Bipolar or manic-depressive disorder is a malign mental disease that frequently faces social stigma. Educational and thinking models are needed to increase people’s awareness and understanding of the disorder. The arts have potential to achieve this goal. 2) Methods: This paper builds on the recent use of heavy metal music as a thinking and education model. It emphasizes the artistic component of heavy metal and its potential to characterize the symptomatology during the episodes of (hypo)mania and depression and the recurrence of these episodes. Heavy metal music has diversified into subgenres that become allegorical to both the symptoms of episodes and the recurrence of bipolar cycles. 3) Results: Examples of songs are given that mirror distinct facets of the disorder. 4) Conclusion: Although the links drawn between art (music) and science (psychiatry) are inherently subjective, such connections might be used to trigger a learning process, facilitate judgment and decision-making, and induce affective reactions and memory formation in the listener. The approach may facilitate collaborative efforts and serve healthcare professionals and educators as a communication tool to aid the public’s comprehension of the disease and an associated social paradox: On one hand, bipolar disorder incurs substantial costs to society. On the other hand, it benefits from the creative artistic and scientific endeavors of bipolar individuals from which cultural and political gains may ensue.

Background: Mental capacity is a fundamental aspect that enables patients to fully par-ticipate in various healthcare procedures. To assist healthcare professionals (HCPs) in assessing patients' capacity, especially in the mental health field, several standardized tools have been developed. These tools include the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), and the Competence Assessment Tool for Psychiatric Advance Directives (CAT-PAD). The core dimensions explored by these tools include Understanding, Appreciation, Reasoning, and Expression of a choice. Objective: This meta-analysis aimed to investigate potential differences in deci-sion-making capacity within the healthcare context among groups of patients with bi-polar disorder (BD) and schizophrenia spectrum disorder (SSD). Methods: A systematic search was conducted on Medline/Pubmed, and Scopus. Addi-tionally, Google Scholar was manually inspected, and a manual search of emerging re-views and reference lists of the retrieved papers was performed. Eligible studies were specifically cross-sectional, utilizing standardized assessment tools, and involving pa-tients diagnosed with BD and SSD. Data from the studies were independently extracted and pooled using random-effect models. Hedges g was used as a measure for outcomes. Results: Six studies were identified, with three studies using the MacCAT-CR, two studies the MacCAT-T, and one the CAT-PAD. The participants included 189 individuals with BD and 324 individuals with SSD. The meta-analysis revealed that patients with BD performed slightly better, and the difference was statistically significant, compared to patients with SSD, particularly in the domain of Appreciation (ES=0.23, 95% CI: 0.01 to 0.04, p=0.037). There was no statistically significant difference between the two groups for Understanding (ES=0.09, 95% CI: - 0.10 to 0.27, p=0.352), Reasoning (ES=0.18, 95% CI: - 0.12 to 0.47, p=0.074), and Expression of a choice (ES = 0.23, 95% CI: - 0.01 to 0.48, p=0.60). In the sensitivity analysis, furthermore, when considering only studies involving patients in symptomatic remission, the difference for Appreciation also resulted in non-significant (ES=0.21, 95% CI: -0.04 to 0.46, p=0.102). (ES=0.21, 95% CI: -0.04 to 0.46, p=0.102). Conclusions: These findings indicate that there are no significant differences between patients with BD and SSD during remission phases, while differences are minimal during acute phases. The usefulness of standardized assessment of capacity at any stage of the illness should be considered, both for diagnostic-therapeutic phases and for research and advance directives. Further studies are necessary to understand the reasons for the overlap in capacity between the two diagnostic categories compared in this study.

Vitamin D status may impact acute affective symptomatology and the severity of symptoms in patients with bipolar disorder (BD). Therefore, this cross-sectional study analyzed 25(OH)D, 24,25(OH)2D, and the vitamin D metabolite ratio (VMR) in BD and correlated the results with clinical affective symptomatology and functionality. The inactive precursor 25(OH)D and its principal catabolite 24,25(OH)2D were measured simultaneously with a validated liquid chromatography tandem mass-spectrometry method in 170 BD outpatients and 138 healthy controls. VMR was calculated as follows: VMR=100*(24,25(OH)2D/25(OH)D). The psychometric assessment enclosed: Beck Depression Inventory-II, Hamilton Depression Rating Scale, Young Mania Rating Scale, Global Assessment of Functioning, and number of suicide attempts. We did not find a significant difference between patients and controls in the concentrations of 25(OH)D and 24,25(OH)2D. Additionally, the VMR was comparable in both groups. The calculations for the clinical parameters showed a negative correlation between the Young Mania Rating Scale and 24,25(OH)2D (r = -.154, p = .040). Based on the small effect size and the predominantly euthymic sample, further exploitation in individuals with manic symptoms would be needed to confirm this association. In addition, long-term clinical markers, and an assessment in different phases of the disease may provide available additional insights.

External stressors strongly increase cardiovascular activity and induce metabolic changes that ensure the availability of glucose and oxygen as part of a co-ordinated stress response. Exposure to stress during early life appears to have an exaggerated long-term effect on this response, leading to an increased risk or cardiometabolic disorders. Here we demonstrate that acute stress induced glucose release is impacted by the early life environment in rodent maternal deprivation and early-life infection models and this was validated in our EpiPath human early-life adversity cohort. In all three models differences in baseline blood glucose levels after ELA exposure were sex dependent. The human ELA model showed higher levels of basal glucose in females, similar to the mouse infection and rat maternal deprivation models. We anticipated that the stress induced glucose rise would be a GC dependent process. However, the kinetics of stress-induced glucose release, peaking 15-28 minutes before cortisol suggest that it is a GC-independent process. We confirmed this by administering an escalating dose of cortisol to a health human cohort, and the inability of an intravenous GC bolus induce a glucose rise in man confirms that it is a rapid, GC independent, process.In conclusion, we provide a novel perspective on the mechanisms behind stress related metabolic changes and highlights the importance of collecting early life data as a measure to understand an individual’s metabolic status in a better light.

Schizoaffective disorder and its classification have always been a topic of discrepancy among researchers. The overlapping presentations of schizoaffective disorder, schizophrenia and psychotic bipolar disorder makes it difficult to classify and diagnose. This study is a narrative review of literatures and genetic and epidemiological research evidences, done to determine the similarities and differences between schizoaffective and psychotic bipolar disorder. Beginning from the introduction of schizoaffective disorder as "schizoaffective psychosis" by Kasanin in 1933, various researchers have proposed different views regarding the diagnosis and classifications for schizoaffective disorder. DSM-III considered schizoaffective disorder as a diagnosis of exclusion as it fails to fit the definite diagnostic criteria of schizophrenia, major affective disorders, or schizophreniform disorder. DSM-V updated the criteria of schizoaffective disorder and stated it as a life time illness rather than being an episodic disorder as in DSM-IV and hence is more reliable. However, some studies show that schizoaffective disorder patients are more like schizophrenia than mood disorder. It still remains unclear whether schizoaffective disorder is a heterogenous disease, a form of schizophrenia, a form of mood disorder or a midpoint in the continuation spectrum of schizophrenia and psychotic bipolar disease.

Patients with bipolar disorder (BD) experience more frequent and intense emotions in response to environmental conditions relative to healthy subjects, which leads to mood instability. The aim of this study was to investigate the time-course of emotion regulation strategies, distraction, and reappraisal, in euthymic BD patients using electroencephalography (EEG). Fourteen BD patients and 13 matched healthy controls took part in an experiment constituted of three conditions, i.e., a passive viewing of positive, negative, and neutral pictures and two regulation conditions, one with reappraisal strategy and the other with distraction strategy. Critically, ERP results indicated that during passive viewing, the Late Positive Potential (LPP) was larger in BD patients compared with healthy controls, but only for neutral pictures. During emotion regulation, LPP amplitude was reduced in distraction condition compared with viewing one, especially for negative emotions in both patients and controls. Importantly, LPP was reduced in reappraisal condition compared with passive viewing in an early time window for negative emotions and in a later time window for positive emotions in controls but not in patients. Our findings showed that the neurochronometry of emotion regulation is faster for negative than for positive emotion in controls but not in BD patients.

The focus of this study was to investigate how individuals with bipolar disorder integrate auditory and visual speech information compared to non-disordered individuals and whether there were any differences in auditory and visual speech integration in the manic and depressive episodes in bipolar disorder patients. It was hypothesized that bipolar groups’ auditory-visual speech integration would be less robust than the control group. Further, it was predicted that those in the manic phase of bipolar disorder would integrate visual speech information more than their depressive phase counterparts. To examine these, the McGurk effect paradigm was used with typical auditory-visual speech (AV) as well as auditory-only (AO) speech perception on visual-only (VO) stimuli. Results. Results showed that the disordered and non-disordered groups did not differ on auditory-visual speech (AV) integration and auditory-only (AO) speech perception but on visual-only (VO) stimuli. The results are interpreted to pave the way for further research whereby both behavioural and physiological data are collected simultaneously. This will allow us understand the full dynamics of how, actually, the auditory and visual (relatively impoverished in bipolar disorder) speech information are integrated in people with bipolar disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by persistent deficits in social interaction and communication, repetitive movements, abnormal focusing on objects, or activity that can significantly affect the quality of life of the afflicted. Brain neuronal and glial cells have been implicated. It has a genetic component but can also be triggered by environmental factors or drugs. For example, prenatal exposure to valproic acid (VPA) or acetaminophen (APAP) or ingestion of propionic acid (PPA) can increase the risk of ASD. Recently, epigenetic influences on ASD have been brought to the forefront of investigations on the etiology, prevention, and treatment of this disorder. Epigenetics refers to DNA modifications that alter gene expression without making any changes to the DNA sequence. Although an increasing number of pharmaceuticals and environmental chemicals are being implicated in the etiology of ASD, here we specifically focus on the molecular influence of the above-mentioned drugs on epigenetic alterations in neuronal and glial cells and their potential connection to ASD. It is concluded that a better understanding of these phenomena can lead to more effective interventions in ASD.

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.

Background: Older adults with bipolar disorder (OABD) are individuals aged 50 years and older with bipolar disorder (BD). People with BD may have fewer coping strategies or resilience. A long course of the disease, such as in OABD, could impact the development of resilience strategies, but this remains under-researched in OABD. Therefore, this study aims to assess resilience levels within the OABD and explore associated factors, hypothesizing that resilience could improve psychosocial functioning, wellbeing and quality of life of OABD patients. Methods: This study sampled 33 OABD patients from the OABD cohort at the Bipolar and Depressive Disorders Unit of Hospital Clinic of Barcelona. This was an observational, descriptive and cross-sectional study. Demographic and clinical variables as well as psychosocial functioning, resilience and cognitive reserve were analyzed. Resilience was measured using the CD-RISC-10. Non-parametric tests were used for statistical analysis. Results: The average CD-RISC-10 score was 25.67 points (SD 7.87). Resilience negatively correlated with the total number of episodes (p = 0.034), depressive episodes (p = 0.001), and the FAST (p < 0.001). Participants with normal resilience had a lower FAST (p = 0.046), a higher CRASH (p = 0.026), and more EOBD (p = 0.037) compared to those with low resilience. Conclusions: OABD individuals may exhibit lower resilience levels which correlate with more psychiatric episodes, particularly the number of depressions and worse psychosocial functioning and cognitive reserve. Better understanding and characterization of resilience could aid in early identification of patients requiring additional support to foster resilience and enhance OABD management.

Background and objectives: Huntington disease (HD) is characterized by motor, cognitive and psychiatric manifestations and is caused by an expansion of CAG repeats over 35 triplets on the huntingtin (HTT) gene. However, expansions in the range 27-35 repeats (intermediate allele) can be associated with pathological phenotypes. The onset of HD is conventionally defined by the onset of motor symptoms, but psychiatric disturbances can precede the motor phase by up to twenty years. The aims of the present study are to identify HD patients in the pre-motor phase of the disease among patients diagnosed with bipolar disorders and to evaluate any differences between bipolar patients carrying normal HTT allele and patients with expanded HTT gene. Methods: We assessed the HTT genotype in an Italian cohort of 69 patients affected by bipolar disorder type 1 and type 2. Results: No patient was found to be a carrier of the pathological HTT allele, but 10% of bipolar subjects carried an intermediate allele. Carriers of the intermediate allele were older at onset of psychiatric symptoms than non-carriers. Conclusion: The pathological HTT gene was not associated with bipolar disorder, while we found a higher frequency of the intermediate allele among the bipolar population with respect to healthy controls.

The purpose of this study was to explore the association of cognition with hazardous drinking and alcohol related disorder in persons with bipolar disorder (BD). The study population included 1,268 persons from Finland with bipolar disorder. Alcohol use was assessed through hazardous drinking and alcohol related disorder including alcohol use disorder (AUD). Hazardous drinking was screened with the AUDIT-C (Alcohol Use Disorders Identification Test for Consumption) screening tool. Alcohol related disorder diagnoses were obtained from the national registrar data. Participants performed two computerized tasks from the Cambridge automated neuropsychological test battery (CANTAB) on tablet computer: the 5-choice serial reaction time task, or, reaction time (RT) test and the Paired Associative Learning (PAL) test. Association between RT-test and alcohol use was analyzed with log-linear regression, and eβ with 95% confidence intervals (CI) are reported. PAL first trial memory score was analyzed with linear regression, and β with 95% CI are reported. PAL total errors adjusted was analyzed with logistic regression and odds ratios (OR) with 95% CI are reported. After adjustment for age, education and housing status, hazardous drinking was associated with lower median and less variable RT in females while AUD was associated with a poorer PAL test performance in terms of the total errors adjusted scores in females. Our findings of positive associations between alcohol use and cognition in persons with bipolar disorder are unique.

The aim of the present trial was to evaluate the growth performance of buffalo calves fed diets characterized by different forage/concentrate ratio with or without the Saccharomyces Cerevisiae supplementation (CBS 493.94, Yea-Sacc®). Twenty-four male buffalo calves (mean age 145.1 ± 16.1 days; mean weight 108.0 ± 18.7) were assigned randomly to 4 groups, homogeneous for age, fed four different diets: diet 1 F:C ratio 50:50; diet 2 F:C ratio 30:70; diet 3 F:C ratio 50:50 + Yea-Sacc® and diet 4 F:C ratio 30:70 + Yea-Sacc®. Buffalo calves were individually weighted before the start of the experiment and the data were used as a covariate, monthly until the end of the trial. Dry matter intake (DMI), daily weight gain (DWG) and feed conversion ratio (FCR) were calculated. The differences in diets’ composition significantly (p

The incremental sheet forming represents a relatively recent technology that guarantees high customization, thanks to the layered manufacturing principle typical of rapid prototyping, and cost-effectiveness, because it does not require dedicated equipment. Research has initially shown that this process is effective in metal materials capable of withstanding plastic deformation but, in recent years, the interest in this technique has been increasing for the manufacture of complex polymer sheet components as an alternative to the conventional technologies, based on heating-shaping-cooling manufacturing routes. Conversely, incremental formed polymer sheets can suffer from some peculiar defects, for example twisting. To reduce the risk of this phenomenon and the occurrence of failures, a viable way is to choose toolpath strategies that make the tool/sheet contact conditions less severe, and this represents the main goal of the present research. Polycarbonate sheets were worked by incremental forming; in detail, cone frusta with a fixed wall angle were manufactured with a reference and a stair toolpath strategy, and both the forming forces and the twist angle were monitored. The analysis of the results highlighted that a stair toolpath involving an alternation of diagonal up and vertical down steps represents a useful strategy to mitigate the forming forces and, with them, the occurrence of the twisting phenomenon in incremental formed thermoplastic sheets.

The aim of this paper is to establish a valid procedure for better understanding all the phenomena associated with the high-speed machining of Glass Fibre Reinforced Plastic (GFRP) composites. Both rectangular and circular specimens were machined at high speeds (up to 50 m/min) in order to understand what occurred for all values of fiber orientation angles during machining operations. An innovative testing methodology was proposed and studied to investigate the phenomenon of burr formation and thus understand how to avoid it during machining operations. To this end, the forces arising during the machining process and the roughness of the resulting surface, were carefully studied and correlated with the cutting angle. Additionally, the cutting surface and chip morphology formed during cutting tests were examined using a high-speed camera. Close correlations are found between the variations of the cutting forces' signals and the trends of the roughness and the morphology of the machined surface.

Silencing of the fragile X mental retardation 1 (FMR1) gene and consequently lack of synthesis of FMR protein (FMRP) are associated with fragile X syndrome, which is one of the most prevalent inherited intellectual disabilities. FMRP is a multifunctional protein involved in many cellular functions in nearly all subcellular compartments under normal conditions and under conditions of cellular stress in both neuronal and non-neuronal cell types. This is achieved through its trafficking signals, nuclear localization signal (NLS), nuclear export signal (NES), and nucleolar localization signal (NoLS), as well as its RNA and protein binding domains, and is modulated by various post-translational modifications such as phosphorylation, ubiquitination, sumoylation, and methylation. This review summarizes recent advances in understanding the interaction networks of FMRP with a special focus on FMRP stress-related functions, including stress granule formation, mitochondrion and endoplasmic reticulum plasticity, ribosome biogenesis, cell cycle control, and DNA damage response.

Bipolar disorder is a severe mood disorder and is one of the top 20 reasons of disability in the world. It causes a huge burden on society. In this study, the prediction models of bipolar disorder were constructed based on the concept of knowledge distillation. The input data consisted of patients of bipolar disorder and matched controls, all of which were selected from the open database MIMIC. The method of kernel density estimation (KDE) was exploited to generate probability density functions (PDF) which identify distributions of input data. The PDF values referred to as the soft labels were combined with the input data to construct the prediction models of bipolar disorder using decision tree and artificial neural network respectively. According to the evaluation results, indicators for identifying positive samples of bipolar disorder were improved. Meanwhile, the indicators for identifying negative samples have also been advanced. In addition, the branching attributes selected by the decision trees can be mapped back to specific disease diagnoses, which are all associated with bipolar disorder. In conclusion, using KDE to generate the soft label information of the input data can make knowledge distillation work and has improved the performances of prediction models for bipolar disorder.

Background: Patients with bipolar disorder (BD) receive traditional Chinese Medicine (TCM) for unmet clinical needs with psychotropic medications. However, the clinical characteristics of practices and outcomes of TCM in BD are not fully understood. This cohort study investigated the clinical characteristics, principal diagnoses, TCM interventions, and TCM prescriptions in patients with BD. Methods: 12,113 patients with BD were withdrawn from Taiwan's longitudinal health insurance database 2000 (LHID 2000) between 1996 and 2013. Chi-squared test for categorical variables and independent t-test for continuous variables. A p-value less than 0.05 indicated significance. Results: One-thousand and three hundred nineteen patients who visited TCM clinics after the diagnosis of BD were in the TCM group, while those who never visited TCM were in the non-TCM group (N= 1,053). Compared to the non-TCM group, patients in the TCM group had younger average age, a higher percentage of female individuals, more comorbidities of anxiety and alcohol use disorders, and higher mood stabilizer usage rates. The TCM group exhibited pain-related indications, including joint pain, myalgia, myositis, headache, and sleep disturbances. Corydalis yanhusuo and Shu-Jing-Huo-Xue-Tang were the most useful single herb and herbal formulas. Conclusions: Physicians need to be aware of the use of TCM in Patients with BD.

Bipolar disorder (BD) is a high suicide-risk mental disorder. The purpose of this study was to identify the relationship between temperament and character traits with suicide probability, suicide attempt and perceived stress level in patients with BD. A total of 39 euthymic patients with bipolar disorder who had a history of suicide attempt and 39 euthymic patients without a history of suicide attempt were included in this study. Sociodemographic and clinical data form, Hamilton Depression Rating Scale (HDRS), Young Mania Rating Scale (YMRS), The Structured Clinical Interview for DSM-5-Clinician Version (SCID-5/CV), Temperament and Character Inventory (TCI), Perceived Stress Scale (PSS), Suicide Probability Scale were used for obtaining the data. HDRS, PSS and SPS scores of the group comprised of patients who attempted suicide were higher than the other group. There was no significant difference between the group of patients who had attempted suicide and the other group in terms of temperament characteristics. In the group of patients who had attempted suicide, self-directedness (SD) and cooperativeness (CO) scores were lower and self-transcendence (ST) score was higher than the other group. HA and ST were positively and SD negatively associated with SPS scores. In the regression analysis for suicide risk, the factors most associated with suicide risk were high HDRS and low CO score. Low SD in BD, high ST with CO may be associated with suicide attempt. Alongside low SD, high HA and ST may be associated with suicidal ideation. Treating residual depressive symptoms can reduce the risk of suicide.

Introduction: Hospitalization in a COVID-19 unit represents a significant source of stress and psychological distress for patients. Our study aims to determine the factors of psychological distress in the therapeutic and psychosocial management of patients hospitalized with a COVID-19 infection. Methods: This cross-sectional study was carried out over 8 months at the COVID-19 zone of the CHU HASSAN II of FES. 99 patients were evaluated within days of diagnosis by psychometric scales of anxiety, depression, and post-traumatic stress. In the course of this follow-up, we found the presence of psychological impacts in these patients, and we tried to find correlating factors between the occurrence of psychiatric disorders and the set of factors related to sociodemographic data, hospitalization course and treatments taken, as well as family support. Results: 35% of patients had scores in favor of post-traumatic stress disorder, 37% of the patients had definite depression and 50% had anxiety. Post-traumatic stress, depression, and anxiety were correlated with sociodemographic factors, hospitalization, treatments received, and length of stay. Conclusion: The prevalence of anxiety-depressive disorders and post-traumatic stress disorder was high in patients with COVID-19, hence the interest in providing psychological and psychosocial care in the emergency department.

To investigate effects of probiotics on cognitive function and regulation of cortisol and IL-1β in adolescents with depression. All 180 participants were randomly assigned into study group(treated by probiotics combined with sertraline hydrochloride) and control group(treated by sertraline hydrochloride). The repetitive Neuropsychological State Test (RBANS) and Hamilton Depression Scale (HAMD) were administered in MDD patients. The levels of serum cortisol and IL-1β were detected by ELISA kit. Except speech function, immediate memory, visual span, attention function, delayed memory and RBANS in the study group were significantly higher than those in the control group. The cortisol and interleukin1β in the study group were significantly downregulated than those in the control group. Except speech function, cortisol level was negatively correlated with RBANS total score and other factors in the study group. Interleukin-1β was negatively correlated with the total score of RBANS and each factor score. Cortisol and interleukin-1β were predictors of RBANS total score, which explained 46.80% of the variance. Cortisol had significant predictive effects on attention function and delayed memory, and interleukin-1β had significant predictive effects on visual span and speech function. It could concluded that probiotics can improve cognitive function in adolescents with depression by regulating cortisol and IL-1β levels.

Apicomplexan infections, such as giardiasis and cryptosporidiosis, negatively impact a considerable proportion of human and commercial livestock populations. Despite this, the molecular mecha-nisms of disease, particularly the effect on the body beyond the gastrointestinal tract, are still poorly understood. To highlight host-parasite-microbiome biochemical interactions, we utilised integrated metabolomics-16S rRNA genomics and metabolomics-proteomics approaches in a C57BL/6J mouse model of giardiasis and compared these to Cryptosporidium and uropathogenic Escherichia coli (UPEC) infections. Comprehensive samples (faeces, blood, liver, and luminal contents from duo-denum, jejunum, ileum, caecum and colon) were collected 10 days post infection and subjected to proteome and metabolome analysis by liquid and gas chromatographic mass-spectrometry, re-spectively. Microbial populations in faeces and luminal washes were examined using 16S rRNA metagenomics. Proteome-metabolome analyses indicated that 12 and 16 key pathways were sig-nificantly altered in the gut and liver, respectively, during giardiasis with respect to other infections. Energy pathways including glycolysis and supporting pathways of glyoxylate and dicarboxylate metabolism, and redox pathway of glutathione metabolism, were upregulated in small intestinal luminal contents and the liver during giardiasis. Metabolomics-16S rRNA genetics integration in-dicated that populations of three bacterial families –Autopobiaceae (Up), Desulfovibrionaceae (Up) and Akkermanasiaceae (Down) – were most significantly affected across the gut during giardiasis, causing upregulated glycolysis and short-chained fatty acid (SCFA) metabolism. In particular, the perturbed Akkermanasiaceae population seemed to cause oxidative stress responses along the gut-liver axis. Overall, the systems biology approach applied in this study highlighted that the effects of host-parasite-microbiome biochemical interactions extended beyond the gut ecosystem to the gut-liver axis. These findings form the first steps in a comprehensive comparison to ascertain the major molecular and biochemical contributors of host-parasite interactions and contribute towards the development of biomarker discovery and precision health solutions for apicomplexan infections.

Insulated Gate Bipolar Transistor (IGBT) may convey high current and sustain high breakdown voltages; it may provide high power control. In a sense, how IGBT demonstrates the capability of power control was not specifically described, and the equivalent bipolar junction transistors (BJT) activated by an applied bias to the insulated gate is intriguing. As seen in Figure 1, IGBT shows an equivalent circuit structure containing two types of BJT, (NPN-type Bipolar transistor and PNP-type Bipolar transistor), which can be modeled as diode-associated transistor. Apparently, as a bias applies to the controlling gate, the channel beneath the gate oxide gets strongly inversed and turns out to be conductive just like what happens on metal-oxide-silicon field effect transistor (MOSFET), which provides necessary igniting currents to both BJTs and thus causes high current gain flowing through them-selves from the bottom. A proposed and renewed formula provides addressing the above scenario and successfully fitting the measured data that forms the characteristic curves. Some parameters in the proposed formula, which includes size and mobility associated constant, threshold voltage, and Early-Voltage-related lambda for MOSFET, explain and explore the underlying physics. IGBT thus enjoy high input impedance and high current gain due to MOSFET (Insulated Gate) and BJT, respectively. This formula combines both merits of MOSFET and BJT in order to fit the measured data. Indeed, the formula intimately fits IGBT electrical characteristic curves, and thus may be qualified and served as a model. The new model is then advisable for designing power integrated circuit to exactly achieve power saving, power control, and power efficiency.

Keywords: retinoblastoma, RB, gastric inhibitory polypeptide receptor, GIPR, trefoil factor family peptide, TFF1, CAM, tumorigenesis, MK0893, miR5-542-5p

Optimizing the NACA0015 airfoil which is widely applied in small-scale vertical axis wind turbine to make it has a better aerodynamic performance. In the optimization process, using CST parameterization method to perturb the airfoil geometry, the thickness and camber of the airfoil are selected as the constraint, and the value of the maximum tangential force coefficient is chosen as the objective function, the genetic algorithm based on non-dominated sorting (NSGA-II)is selected as an optimization method, calculates the aerodynamic performance of the airfoil by applying the approach of combining XFOIL program and Viterna-Corrigan post-stall mode ,and establishes the optimizing process by the optimization software modefrontier for NACA0015 airfoil’s muti-point optimization, validate the airfoil’s performance with CFD finally. The result illustrates that, by comparing with the NACA0015 airfoil, the optimized airfoil’s lift to drag ratio is improved over a wide range of attack angles, the stall performance is more gentle. The maximum lift coefficient, the maximum lift-drag ratio and the maximum tangential force coefficient are increased by 7.5%,9 and 8.87%, respectively. The optimized airfoil has a wide variable condition performance, more suitable for the operating conditions of a vertical axis wind turbine. Finally, predict the rotor efficiency with optimized airfoil and NACA0015 airfoil for different tip speed ratios and different solidities with multiple streamtube model, the result shows the rotor with optimized airfoil has a higher efficiency.

The focus of this article is the evaluation of the quality and the degree of community engagement in an expert-based, public-health communicative intervention for Alcohol Use Disorder (AUD). In 2023 the Canadian Alcohol Use Disorder Society collaborated with a grass-roots community health group, a regional health authority, and an academic participatory researcher to organize a working group to mount a social-marketing campaign to increase community support for AUD medical treatment in family-practice settings in a rural community in British Columbia. The partnership working group conducted a series of activities in the school system, the town council, and the community. This article covers the formative evaluation and the summative evaluation of the working group's effectiveness. The formative evaluation ("lessons learned" and "recommendations") consists of consensus evaluations of the quality of each activity using a variety of data sources. The formative evaluation followed improvement science methods and used consensus meetings to provide and reflect on formal and informal feedback. Formative results reflect the consensus of the participants in the working group and they record the reactions in the community. The summative evaluation measures evidence of community engagement found in transcribed text from meeting minutes. The summative evaluation used theory-based frameworks and text data visualization to assess the engagement dynamics of the working group. The summative evaluation helps to put the formative evaluation into perspective as communicative action. The summative evaluation validates the formative evaluation by revealing the communicative dynamics of engagement which resulted in the community’s increased capacity to understand and support Alcohol Use Disorder Treatment options. The working group and the entire intervention was seen by the participants and the public as a success and capable of replication. In a small community, it instilled new understandings and attitudes, bringing an emerging awareness of medication as an optional health mitigation strategy for Alcohol Use Disorder. Our study furthers this overall assessment by using theoretical constructs and analysis of communicative records to trace engagement characteristics of interest to researchers, societies, and community groups contemplating similar interventions in the future. The study also validates the effectiveness of communicative analysis as a measure of social-marketing for expert-based public health interventions.

A growing body of research has identified fetal risk factors associated with adult diseases that form the basis for the Developmental Origins of Health and Disease (DOHaD) hypothesis. This theory proposes a critical developmental period during which the fetus is highly susceptible to specific environmental influences that significantly impact health from short to long term. Maternal stress and T2DM during pregnancy are among these influences, likely leading to fetal overexposure to glucocorticoids and suggesting a shared pathway between maternal dysregulated HPA axis and fetal environmental insults. Studies demonstrate that prenatal glucocorticoid exposure alters fetal HPA axis function, affecting brain function, tissue glucocorticoid availability, and fetal growth in utero. These programmed changes, such as altered HPA axis function and reduced fetal growth, contribute to metabolic disorders persisting into adulthood. T2DM is preceded by a prediabetic state, often asymptomatic, which shares similar pathophysiological complications with T2DM, including HPA axis dysregulation observed in animals. Therefore, investigating prediabetes during pregnancy alongside maternal HPA axis function and its effects on fetal outcomes is crucial, as these areas remain understudied. This review aims to synthesize existing literature on pre-existing T2DM during pregnancy, its links to fetal programming via HPA axis changes, and possible links to pregestational prediabetes.

Text mining is a technological trend often highlighted in the continuous exchange of information through interconnected media. Its applicability goes beyond private organizations, as the public sector also requires it to treat textual information regarding services offered. Within this scenario, public security emerges as a prominent user of text mining that seeks to ensure the construction of data and knowledgebases to support decision-making about law enforcement actions to ensure citizen welfare. The primary objectives of this article are: (i) to develop a survey to identify text mining applications, techniques, opportunities, and challenges in public security, and (ii) to outline research directions concerning these topics and provide insights so that interested researchers can develop new studies. The literature was searched within four databases: Scopus, IEEE Xplore, ACM Digital Library, and Web of Science. A filtering process was applied to extract the works most aligned with the target theme, resulting in the selection of 194 of the most relevant works for a literature review. There were identified nineteen key applications of text mining related to public security and the most recurrent techniques and technologies reported between 2014 to 2021, supporting outlining three axes for future directions: one with possible expansion of objectives for new research; another on changes and adaptations in scopes for the methodological context; and the last one on expansions and changes in application scenarios based on the literature.

The epithelial cell tight junction structure is the site of the transepithelial movement of solutes and water between epithelial cells (paracellular permeability). Paracellular permeability can be divided into two distinct pathways, the Pore Pathway mediating the movement of small ions and solutes and the Leak Pathway mediating the movement of large solutes. Claudin proteins form the basic paracellular permeability barrier and mediate the movement of small ions and solutes via the Pore Pathway. The Leak Pathway remains less understood. Several proteins have been implicated in mediating the Leak Pathway, including occludin, ZO proteins, tricellulin, and actin filaments, but the proteins comprising the Leak Pathway remain unresolved. The properties of the Leak Pathway, such as its molecular mechanism, its regulation, and whether or not it has a size limit, remain controversial. This review will trace the evolution of the Leak Pathway concept from its origins, will discuss the current information about the properties of the Leak Pathway, and will discuss recent research suggesting a possible molecular basis for the Leak Pathway. Based on these findings, we propose a model for the molecular mechanism underlying the Leak Pathway and its regulation.

This article presents a new input device for spastic patients and others with similar symptoms. The sensor consists of a disc used to determine positions and can replace standard joysticks in medical devices such as electric-powered wheelchairs. Using a standard joystick while operating a powered wheelchair can result in dangerous situations when spastic movements occur and extremities cramp making them uncontrollable. To avoid this, a disc was developed that can be controlled with any body part. By shifting weight (x- and y-axis) the disc can tilt in any direction creating a proportional output signal and can also be pushed down in the center (z-axis) to open a menu on a screen for example. When spasms occur it is impossible for users to get stuck on the input device because the disc is flat and can be mounted within a control panel. Body parts coming into contact with the disc would merely slide across the disc without triggering unintentional actions. The sensor presented here is also adaptive and can be adjusted to fit a user’s strength and range of motion. This proposal aims to develop an input device that enables spastic patients to operate sensitive systems safely.

There is now evidence that, based on cytokine profiles, bipolar disorder (BD) is accompanied by simultaneous activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS), and that both components may be associated with the staging of illness. Nevertheless, no BD studies have evaluated the IRS/CIRS ratio using CD (cluster of differentiation) molecules expressed by peripheral blood activated T effector (Teff) and T regulatory (Treg) subpopulations. This study examined T cell subsets both before and after ex vivo anti CD3/CD28 stimulation using flow cytometric immunophenotyping in 25 euthymic BD patients and 21 healthy controls as well as human cytomegalovirus (HCMV)-specific IgG antibodies. BD is associated with a significantly lowered frequency of baseline (unstimulated) CD3+CD8+CD71+ and CD4+CD25+FOXP3 and increased CD4+CD25+FOXP3+CD152+ frequencies and with lowered stimulated frequencies of CD3+CD8+CD71+, CD4+CD25+FOXP3+CD152+ and CD4+CD25+FOXP3+GARP cells and, consequently, by an increased stimulated Teff/Treg ratio. Moreover, the number of manic, but not hypomanic or depressive episodes, is significantly and negatively associated with the stimulated proportions of CD3+CD4+CD154+, and CD69+ and CD71+ expression on CD4+ and CD8+ cells, while duration of illness (≥ 10 years) is accompanied by a depleted frequency of stimulated CD152+ Treg, and CD154+ and CD71+ CD4+ T cells. BD and anti-human cytomegalovirus (HCMV) IgG levels significantly interact to decrease the expression of CD4+CD25+FOXP+GARP T phenotypes. In conclusion, BD is characterized by deficits in immune-regulatory functions while the staging of illness is characterized by additional impairments is Teff and Treg activation. HCMV seropositivity may contribute to an immune-risk phenotype associated with BD.

Two interesting compounds such as quaternary ammonium lignin(QAL) and 2-ethylhexyl phosphoric acid mono-2-ethylhexyl ester (P507) were synthesized as ionic liquids(QP-ILs) for the extraction of metal ions. The extraction behavior of Co(II) and Ni(II) from chloride solution was compared between QP-ILs and P507. The results showed that the extraction rates of Co(II) and Ni(II) in the two solutions varied with the extraction conditions, but QP-ILs has stronger extractability for cobalt than P507, while Ni is on the contrary. Under the same conditions, the Co/Ni separation performance(βCo/Ni) in QP-ILs is superior to that in p507. At pH4.0, 55℃, concentration of 20%, extraction time of 10 minutes, the βCo/Ni of QP-ILs reached to 2703, while that of P507 was only 164. In conclusion, QP-ILs was more efficient than P507 for separating Co from mixed solutions.

Major depression is accompanied by increased IgM-mediated autoimmune responses to oxidative specific epitopes (OSEs). Nevertheless, these responses have not been examined in bipolar disorder type 1 (BP1) and BP2. IgM responses to malondialdehyde (MDA), phosphatidinylinositol, oleic acid, and azelaic acid were determined in 35 healthy controls, and 101 mood disorder patients, namely 47 major depressed (MDD), 29 BP1, and 25 BP2 patients. We also measured serum total peroxides, IgG to oxidized LDL (oxLDL), IgM to nitroso-adducts, and IgM/IgA directed to lipopolysaccharides (LPS). IgM responses to OSEs were significantly higher in MDD and BP1 as compared with controls and higher in MDD than in BP2. Partial Least Squares (PLS) analysis showed that 57.7% of the variance in the clinical phenome of mood disorders was explained by number of episodes, IgM directed to OSEs and nitroso-adducts, IgG to oxLDL, and peroxides. There were significant specific indirect effects of IgA/IgM to LPS on the clinical phenome, which were mediated by peroxides, IgM OSEs, and IgG oxLDL. Using PLS we have constructed a data-driven nomothetic network which ensembled causome (increased plasma LPS load), adverse outcome pathways (namely neuro-affective toxicity), and clinical phenome features of mood disorders in a data-driven model. Based on those feature sets, cluster analysis discovered a new diagnostic class characterized by increased plasma LPS load, peroxides, autoimmune responses to OSEs and nitroso-adducts, and increased phenome scores. Using the new nomothetic network approach, we constructed a mechanistically transdiagnostic diagnostic class indicating neuro-affective toxicity in 74.3% of the mood disorder patients.

Major depression (MDD) is accompanied by higher serum IgM/IgA responses to LPS of Gram-negative bacteria, suggesting increased bacterial translocation and gut dysbiosis. Gut dysbiosis may occur in bipolar disorder (BD) and there are differences between MDD and BD type 1 (BP1) and -2 (BP2) in nitro-oxidative stress biomarkers associated with leaky gut. This study examines serum IgM/IgA responses directed to LPS of 6 Gram-negative bacteria in 29 BP1, 37 BP2, 44 MDD and 30 healthy individuals. MDD plus BD was best discriminated from controls by increased IgM/IgA responses to Pseudomonas aeruginosa. BP1 patients showed higher IgM responses to Morganella morganii as compared with MDD and BP2 patients. Patients with melancholia showed higher IgA responses to Citrobacter koseri as compared to controls and non-melancholic depression. The total score on the Hamilton Depression Rating Scale was significantly associated with IgA responses, especially C. koseri. IgG responses to oxidized low-density lipoprotein were significantly associated with signs of increased bacterial translocation. In conclusion, not only MDD but also BP1 and BP2 are accompanied by an immune response due to the increased load of plasma LPS of gut commensal bacteria while these aberrations in the gut-brain axis are most pronounced in BP1 and patients with melancholic features. Activated oxidative stress pathways and autoimmune responses to oxidative specific epitopes in mood disorders may be driven by a breakdown in gut paracellular, transcellular and/or vascular pathways. If replicated, drugs that protect the integrity of the gut barrier may offer novel therapeutic opportunities for BP1 and MDD.

Approximately 20% of the world's population resides in coastal areas at risk of rising sea levels due to climate change. This could lead to severe weather events and ecological impact on critical infrastructure. To combat the effects of water-based environmental forces on the land, hard engineering methods such as seawalls have been utilized. However, a more sustainable solution is emerging in nature-based engineering, which involves growing vegetation. This approach can help extend the lifespan of existing technology and provide climate change adaptation and resilience for coastal and riverine communities. The following paper will review seaweed farms as an advanced nature-based mitigation approach. The paper also outlines the findings of experiments at RWTH Aachen University's hydraulic laboratory. These tests involved using seaweed as a natural solution to dampen waves in a model system to test a hypothesis. One result involving a system with two lines of seaweed revealed 15 percent wave damping. Using seaweed as a nature-based solution, a gentle engineering approach to designing future vegetated protection systems can extend the design life of existing coastal infrastructure. This can also provide protection against climate-induced sea level rise, promote coastal risk mitigation, restore ecosystems, and foster blue bio-economic development.

Bipolar neutrosophic set is an important extension of bipolar fuzzy set. This set is a hybridization of bipolar fuzzy set and neutrosophic set. Every element of a bipolar neutrosophic set consists of three independent positive membership functions and three independent negative membership functions. In this paper, we develop cross entropy measures of bipolar neutrosophic sets and prove its properties. We also define cross entropy measures of interval bipolar neutrosophic sets and prove its properties. Thereafter, we develop two novel multi-attribute decision making methods based on the proposed cross entropy measures. In the decision making framework, we calculate the weighted cross entropy measures between each alternative and the ideal alternative to rank the alternatives and choose the best one. We solve two illustrative examples of multi-attribute decision making problems and compare the obtained result with the results of other existing methods to show the applicability and effectiveness of the developed method. In the end, the main conclusion and future scope of research are summarized.

Protein tyrosine phosphatase receptor type E (PTPRE) is a member of the “classical” protein tyrosine phosphatase subfamily and regulates a variety of cellular processes in a tissue-specific manner by antagonizing the function of protein tyrosine kinases. PTPRE plays a tumorigenic role in different human cancer cells, but its role in retinoblastoma (RB), the most common malignant eye cancer in children, remains to be elucidated. Etoposide resistant RB cell lines and RB patients display significant higher PTPRE expression levels compared to chemosensitive counterparts and the healthy human retina, respectively. PTPRE promotor methylation analyses revealed that PTPRE expression in RB is not regulated via this mechanism. Lentiviral PTPRE knockdown (KD) induced a significant decrease in growth kinetics, cell viability, and anchorage independent growth of etoposide resistant Y79 and WERI RB cells. Caspase-dependent apoptosis rates were significantly increased and a re-sensitization for etoposide could be observed after PTPRE depletion. In vivo chicken chorioallantoic membrane (CAM) assays revealed decreased tumor formation capacity as well as reduced tumor size and weight following PTPRE KD. Expression levels of miR631 were significantly downregulated in etoposide resistant RB cells and patients. Transient miR631 overexpression resulted in significantly decreased PTPRE levels and concomitantly decreased proliferation and increased apoptosis levels in etoposide resistant RB cells, impacts mirroring PTPRE KD effects and indicating PTPRE regulation via this miR. Additionally, PTPRE KD led to altered phosphorylation of protein kinase SGK3 and - dependent on the cell line - also AKT and ERK1/2, suggesting potential PTPRE downstream signaling pathways. In summary, these results indicate an oncogenic role of PTPRE in chemoresistant retinoblastoma.

Copper(II), nickel(II) and zinc(II) complexes of various peptide fragments of tau protein were studied by potentiometric and spectroscopic techniques. All peptides contained one histidyl residue and represented the sequences of tau(91-97) (Ac-AQPHTEI-NH2), tau(385-390) (Ac-KTDHGA-NH2) and tau(404-409) (Ac-SPRHLS-NH2). Imidazole-N donors of histidine were the primary metal binding sites for all peptides and all metal ions but in case of copper(II) and nickel(II) the deprotonated amide groups were also involved in metal binding by increasing pH. The most stable complexes were formed with copper(II) ion but the presence of prolyl residues resulted in significant changes in the thermodynamic stability and speciation of the systems. It was also demonstrated that nickel(II) and especially zinc(II) complexes have relative low thermodynamic stability with these peptides. Copper(II) catalyzed oxidation of the peptides was also studied. In the presence of H2O2 the fragmentation of peptides can be detected in all cases. In the simultaneous presence of of H2O2 and ascorbic acid the extent of the fragmentation of the peptide is less preferred, and the formation of 2-oxo-histidine also occurs.

This work compared the performance of three methods for constructing a regional ensemble prediction system (EPS) for wind speed forecasts: dynamical downscaling, breeding of growth modes (BGM), and blending method. The Weather Research and Forecasting (WRF) model was used to downscale the European Centre for Medium-range Weather Forecast (ECMWF) EPS. In addition, as the BGM method needs observation data for generating scaling factors, an alternative method for generating scaling factors was proposed to eliminate dependence on observation data. One-month tests between October 1st and October 30th, 2020, were implemented to evaluate the performance of three methods in the Gansu province of China. The results demonstrate that the blending method outperforms the other two methods. Furthermore, the difference in performance is evident mainly in early forecast lead time and becomes negligible as forecast time increases.

The chemotactic cytokine fractalkine (FKN, chemokine CX3CL1) has unique properties resulting from the combination of chemoattractants and adhesion molecules. The soluble form (sFKN) has chemotactic properties and potently attracts T cells and monocytes. The membrane-bound form (mFKN) facilitates diapedesis and is responsible for cell-to-cell adhesion, especially by promoting the strong adhesion of leukocytes (monocytes) to activated endothelial cells with the subsequent formation of an extracellular matrix and angiogenesis. FKN signaling occurs via CX3CR1, which is the only known member of the CX3C chemokine receptor subfamily. Signaling within the FKN-CX3CR1 axis plays an important role in many processes related to inflammation and the immune response, which often occur simultaneously and overlap. FKN is strongly upregulated by hypoxia and/or inflammation-induced inflammatory cytokine secretion, and it may act locally as a key angiogenic factor in the highly hypoxic tumor microenvironment. The importance of the FKN/CX3CR1 signaling pathway in tumorigenesis and cancer metastasis results from its influence on cell adhesion, apoptosis and cell migration. This review presents the role of the FKN signaling pathway in the context of angiogenesis in inflammation and cancer. The mechanisms determining the pro- or anti-tumor effects are presented, which are the cause of the seemingly contradictory results that create confusion regarding the therapeutic goals.

The COVID-19-medical emergency has ended worldwide, yet there is still a need to evaluate the psychological impact of these years of unprecedented changes on students’ life. Methods: This study aims to assess and compare COVID-19-related stressors (Relationships-and-Academic-Life; Isolation; Fear-of-Contagion) and psychophysical symptoms reported by university students in April-2020, April 2021, and April 2022. The predictive role of COVID-19-related stressors on psychophysical symptoms within each time was also tested. Data were collected among 637 university students in April-2020 (n = 197), April-2021 (n = 200), April-2022 (n = 240). Results: In April-2022, perceived Isolation and Fear-of-Contagion decreased from the peak registered in April-2021, but stress related to Relationships-and-Academic-Life remained noteworthy high. A sharp and ongoing increase in psychophysical symptoms was found, with more than 50% of students reporting clinical levels of Sleep-Disorders, Depression, Psychoticism, and Interpersonal-Sensitivity. In April-2022, students still perceiving stress related to Relationships-and-Academic-Life and Isolation were at risk for Anxiety, Somatization, and Sleep-Disorders, while those still perceiving stress related to Fear-of-Contagion were also at risk for Depression, Obsessive-Compulsive, and Psychoticism. Conclusion: Findings emphasized the long-lasting detrimental effects of the COVID-19-related stress. Interventions must pinpoint the complex post-pandemic adjustment process and their effects on university students' psychophysical health.

(1) Background: Heavy and chronic alcohol intake causes altered gut-permeability and dysfunction; and exhibits a unique pro-inflammatory state. Thyroid-associated hormones and proteins may be dysregulated by alcohol administration; however, the impact of altered gut-derived changes on thyroid function is unclear. This study investigated the role of gut-dysfunction and pro-inflammatory activity on thyroid function in patients with alcohol use disorder (AUD). (2) Methods: Male and female AUD patients (n=44) were grouped as Gr.1 with normal thyroid stimulating hormone (TSH) levels (n=28, 0.8≤TSH≤3 mIU/L); and Gr.2 with clinically elevated TSH levels (n=16, TSH&gt; 3 mIU/l). Demographics, drinking measures, comprehensive metabolic panel, and candidate thyroid markers (TSH, circulating triiodothyronine [T3] and free thyroxine [fT4]) were tested. Plasma-derived gut-dysfunction associated markers (lipopolysaccharide [LPS], LPS-binding protein [LBP], and LPS-induced pathogen-associated protein [CD14]), and cytokine profile (IL1-β, TNF-α, IL-6, IL-8, MCP-1, PAI-1) were analyzed and compared with the thyroid, demographic, and drinking markers. (3) Results: Both groups presented with a borderline overweight category of BMI. Gr.2 presented with numerically higher level of chronic and heavy drinking patterns vs Gr.1. fT4 levels were elevated while T3 was within normal limits in both the groups. Gut-dysfunction markers LBP and CD14 were numerically elevated in Gr.2 vs Gr.1 suggesting subtle ongoing changes; however, the difference was not statistically significant. All pro-inflammatory cytokines were significantly elevated in Gr.2 among IL1-, MCP-1, and PAI-1. Gr.2 showed a strong and statistically significant effect of gut-immune-pituitary response (r=0.896, p=0.002) on TSH levels in a multivariate regression model with LBP, CD14, and PAI-1 levels as upstream variables; this assessment was not significant in Gr.1. In addition, AUROC analysis demonstrated that many of the cytokines strongly predicted TSH in Gr.2, including IL-6 (area=0.774, p&lt;0.001) and TNF- (area=0.708, p=0.017) among others. This was not observed in Gr.1. Gr.2 demonstrated elevated fT4 as well as TSH, which suggests that there was subclinical thyroiditis with underlying CNS dysfunction and lack of a negative feedback loop. (4) Conclusions: These findings reveal the toxic effects of heavy and chronic drinking that play a pathological role in thyroid gland dysregulation employing the gut-brain axis. These results also strongly emphasize potential directions to strongly consider thyroid dysregulation in the overall medical management of AUD.

Homotopy perturbation and analysis methods have been widely used to obtain both approximate and exact so- lutions to nonlinear problems. In general, these two methods are based on the Taylor series with respect to an embedding parameter. Many researchers have compared the two methods and raised more concerns on the homo- topy perturbation method (HPM) because the homotopy analysis method (HAM) contains a convergence-control parameter ~: For this reason, in this article, a more general form of HPM is introduced as the -homotopy per- turbation method (-HPM), which contains a control parameter : The introduction of parameter  in this new modi cation gives a better way to adjust and control the convergence region and the rate of the series solution. We con rm through the given examples in this study that the HPM is a special case of the -HPM. The error and convergence analysis of this proposed method are also presented

This paper presents a non-perturbative method for solving eigenproblems. This method applies to almost all potentials and provides non-perturbative approximations for any energy level. The method converts an eigenproblem into a perturbation problem, obtains perturbation solutions through standard perturbation theory, and then analytically continues the perturbative solution into a non-perturbative solution.

COX II containing a dual core CuA active site is one of the three core subunits of mitochondrial Cco, which plays a significant role in the physiological process. In this report, the full-length cDNA of COXⅡ gene was cloned from Sitophilus zeamais, which had an ORF of 684 bp encoding 227 amino acids residues. The predicted COXⅡ protein had a molecular mass of 26.2 kDa with pI value of 6.37, and multiple sequence alignment and phylogenetic analysis indicated that Sitophilus zeamais COXⅡ had high sequence identity 78.51% with the COXⅡ of other insect species, especially similarity to sitophilus oryzae. This gene was subcloned into the prokaryotic expression vector pET-32a, and induced by IPTG in E.coli Transetta (DE3) expression system. Finally the COXⅡ with 6-His tag was purified using affinity chromatography with Ni²⁺-NTA agarose. WB showed the recombinant COXⅡ was about 44 kD, and the concentration of fusion protein was 50μg/mL. UV-spectrophotometer and infrared spectrometer analysis showed that recombinant COXⅡ could catalyze the oxidation of substrate Cytc, and influenced by AITC. It was found that AITC could form a hydrophobic region with COXⅡ protein via molecular docking, besides, a sulfur atom of AITC structure could form a length of 2.9 Å hydrogen bond with Leu-31. These results will provide valuable information for elucidating the role of COXⅡ in Sitophilus zeamais responses to AITC, meanwhile, it will helpful to carry out a point mutation in AITC binding sites for the future research.

Chronic kidney disease patients treated by hemodialysis present a high cardio-vascular morbidity and mortality. There is an imperative need for novel biomarkers in identifying and to offer possible therapeutically intervention in these patients. We performed a prospective observational cohort study on 77 patients in the period October 2021 – October 2023. We measured serum plasma levels of Interleukin 1-Beta, Galectin 3, human suppression of tumorigenicity factor 2, bone morphogenetic protein 2 and fibroblastic growth factor 23 at the inclusion. We evaluated the correlations of these biomarkers with cardiac function and structure evaluated by echocardiography. Mean age was 61.02 (±11.81) years, 45 (56.2%) males and with a dialysis vintage of 4.95 (2.4-7.8) years. Median ejection fraction was 51 (43-54 %) and more than two thirds of the patients presented valvular calcifications. Overall mortality was 22%. Interleukin 1-Beta correlated positively with ejection fraction and global longitudinal strain and negatively with left atrium diameter and left ventricle tele systolic diameter. Galectin 3 values negatively correlated with aortic valve fibrosis and mitral valve calcifications and human suppression tumorigenity factor 2 negatively correlated with mitral valve calcifications. Some of these novel biomarkers could be used to better asses the cardio-vascular disease in patients on maintenance hemodialysis.

Background: The purpuse was to investigate the influence induced by magnesium chloride (MgCl2) and zinc gluconate (ZnG) supplementation on liver and kidney injuries experimentally-induced with acetaminophen (AAPh) and potentiated by ciprofloxacin addition in rats. Material and methods: The experiment was performed on 5 animals groups: group 1 – control, treated for 6 weeks with normal saline, 1mL/kg; group 2 – AAPh, treated for 6 weeks with AAPh, 100 mg/ kg/day; group 3 – AAPh+C, treated AAPh 100 mg/kg/ day for 6 weeks and ciprofloxacin, 50mg /kg/day, only in the last 14 days of the experiment; group 4 – AAPh+C+Mg, with the same treatment as group 3, but, and in the last 14 days, MgCl2 10 mg/ kg/day was added; group 5 – AAPh+C+Zn, with the same treatment as group 3, but, and in the last 14 days, zinc gluconate (ZnG),10 mg/kg/day was added. All administrations were performed by oral gavage. At the end of the experiment, the animals were sacrificed and blood samples were collected for biochemistry examinations. Results: Treatment with AAPh for 6 weeks determined an alteration of the liver function (increases in alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase and, and gamma-glutamyl transferase) and of renal function (increases in serum urea and creatinine) (P < 0.001 group 2 vs. group 1 for all mentioned parameters). Also, the antioxidant defense capacity was impaired in group 2 vs. group 1 (superoxide dismutase and glutathione peroxidase activity decreased in group 2 vs. group 1, 0.001 < P < 0.01, respectively 0.01 < P < 0.05). The addition of ciprofloxacin, 50 mg/kg/day during the last 14 days resulted in further increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea and creatinine (0.01 < P < 0.05, group 3 vs. group 2). MgCl2 provided a slight protection against liver enzymes increase and a more pronounced protection against the increase in serum urea and creatinine (0.001 < P < 0.01 group 4 vs. group 3). MgCl2 provided a slight protection against the decrease in superoxide dismutase (0.01 < P < 0.05 group 4 vs. group 3), but not against decrease of glutathione peroxidase. The improvement of mentioned parameters could also be seen in case of ZnG, to a higher extent especially in the case of alanine aminotransferase and lactic dehydrogenase (0.01 < P < 0.05 group 5 vs. group 4). Conclusions: This study represents a furthermore proof for beneficial effect of magnesium and zinc salts against toxicity induced by different agents, including antibacterials added to the analgesic and antipyretic acetaminophen; the protection is proven on the liver and kidney’s function; the antioxidant profile improvement has a key role, especially in case of zinc gluconate.

Instead of the conventional 0 and 1 values, bipolar reasoning uses -1, 0, +1 to describe double-sided judgements in which neutral elements are halfway between positive and negative evaluations (e.g., “uncertain” lies between “impossible” and “totally sure”). We discuss the state-of-the-art in bipolar logics and recall two medieval forerunners, i.e., William of Ockham and Nicholas of Autrecourt, who embodied a bipolar mode of thought that is eminently modern. Starting from the trivial observation that “once a wheat sheaf is sealed and tied up, the packed down straws display the same orientation”, we work up a new theory of the bipolar nature of networks, suggesting that orthodromic (i.e., feedforward, bottom-up) projections might be functionally coupled with antidromic (i.e., feedback, top-down) projections via the mathematical apparatus of presheaves/globular sets. When an entrained oscillation such as a neuronal spike propagates from A to B, changes in B might lead to changes in A, providing unexpected antidromic effects. Our account points towards the methodological feasibility of novel neural networks in which message feedback is guaranteed by backpropagation mechanisms endowed in the same feedforward circuits. Bottom-up/top-down transmission at various coarse-grained network levels provides fresh insights in far-flung scientific fields such as object persistence, memory reinforcement, visual recognition, Bayesian inferential circuits and multidimensional activity of the brain. Implying that axonal stimulation by external sources might backpropagate and modify neuronal electric oscillations, our theory also suggests testable previsions concerning the optimal location of transcranial magnetic stimulation’s coils in patients affected by drug-resistant epilepsy.

Type II grass carp reovirus (GCRV-II) with high pathogenicity and infectivity causes severe hemorrhagic disease, which leads to extensive death in the grass carp and black carp aquaculture. However, the early invasion portal remains unclear. In this study, we explored the invasion portal, time, and pathway of GCRV-II by immersion infection in grass carp. Through the detection of the infected grass carp external body surface tissues, most of them could be detectable to carry GCRV-II within 45 minutes except for the skin covered by scales. Further shortening the duration of infection, we proved that GCRV-II rapidly invades through the nostril (especially), gill, and skin on head at only 5 min post immersion, rather than merely adhesion. Subsequently, visual localization investigations of GCRV-II were conducted on the nostril, olfactory system (olfactory bulb and olfactory tract), and brain by immunofluorescence microscopy and transmission electron microscopy. We found that few viruses were located in the nostril at 5 min post immersion infection, while significantly increased viruses were distributed in all these tissues at 45 min. Furthermore, semi-qRT-PCR and western blotting results of different infection time confirmed that GCRV-II invades grass carp via nostril-olfactory system-brain axis and then unfolds viral replication. These results revealed the infection mechanism of GCRV-II on the invasion portal, time, and pathway in grass carp. This study aims to understand the invasion mode of GCRV-II in grass carp, which provides theoretical support for the prevention and control strategies of hemorrhagic disease.

The Solvency II regulatory framework specifies procedures and parameters for determining solvency capital requirements (SCRs) for insurance companies. The proposed standard SCR calculations involve two steps. The Value–at–Risk (VaR) of each risk driver is measured and, in a second step, all components are aggregated to the company’s overall SCR, using the Standard Formula. This formula has two inputs: the VaRs of the individual risk drivers and their correlations. The appropriate calibration of these input parameters has been the purpose of various Quantitative Impact Studies that have been conducted during recent years. This paper demonstrates that the parameter calibration for the equity–risk module—overall, with about 25%, the most significant risk component—is seriously flawed, giving rise to spurious and highly erratic parameter values. As a consequence, an implementation of the Standard Formula with the currently proposed calibration settings for equity–risk is likely to produce inaccurate, biased and, over time, highly erratic capital requirements.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterised by poor social interaction and communication, as well as restricted and stereotyped interests. Due of the high prevalence of gastrointestinal disorders in individuals with ASD, researchers have investigated the gut microbiota as a potential contributor to its aetiology. The relationship between the microbiome, gut, and brain (microbiome-gut-brain axis) has been acknowledged as a key factor in modulating brain function and social behaviour, but its connection to the aetiology of ASD is not well understood. Recently, there has been increasing attention on the relationship between the immune system, gastrointestinal disorders, and neurological issues in ASD, particularly in relation to the loss of specific species or a decrease in microbial diversity. It focuses on how gut microbiota dysbiosis can affect gut permeability, immune function, and microbiota metabolites in ASD. Although a very complete study suggests that dysbiosis is a consequence of the disease and that it has practically no effect on autistic manifestations. This is a review of the relationship between the immune system, microbial diversity, and the microbiome-gut-brain axis in the development of autistic symptoms severity and, a proposal of a novel role of gut microbiome in ASD, where dysbiosis is a consequence of ASD-related behaviour and where dysbiosis in turn accentuates the autistic manifestations of the patients via microbiome-gut-brain axis in a feedback circuit.

Aiming at the development of the application of massive and heterogeneous LEO constellations, the influence of typical perturbation forces on the orbit prediction of LEO satellites at different altitudes is analyzed. Firstly, the main perturbation force model of LEO satellites is introduced. Then experiments for analyzing the influence of orbit prediction on LEO satellites at different altitudes are designed. Finally, the influence of typical perturbation forces on the orbit prediction under different prediction durations by numerical analysis is assessed systematically, and the orbit prediction of LEO satellites with different non-spherical gravitational field orders, ocean tide orders and atmospheric density models were compared and calculated. The research results show that different orders of non-spherical gravitational fields should be considered when the altitude of satellites is different, the reasonable gravitational field orders for LEO satellites at 500km, 1000km, 1500km and 2000km under 1-hour forecast time are 140x140, 80x80, 60x60 and 40x40 orders, the reasonable orders of ocean tide perturbation for 1500km and 2000km satellites are 20x20 orders. Under the 24-hour forecast time, atmospheric resistance has a great influence on the precision of LEO satellites at orbit altitude below 1,000km. The forecast deviation of the LEO satellites orbit at 500km reaches 8751.576m. The difference of orbit precision between different atmospheric density models is in the meter level. The orbit deviation by the Standard Atmosphere 1976 and NRLMSISE 2000 atmospheric models respectively reaches 25.494m. Relevant conclusions provide support for the optimization and selection of dynamical models in high precision orbit determination and fast orbit prediction of LEO satellites.

Beyond factors such as smoking and obesity, the risk of getting gastrointestinal cancer is passed down from parents to offspring, inherited by a gene mutation, predisposing them to develop cancer in their lifetime. Here we describe the clinical history of family members affected by gastrointestinal pathologies often leading to cancer. In the epidemiological study, the cohort of members of this family shared a high risk of developing gastrointestinal diseases. The subjects were monitored from May 2006 to December 2017 by collecting periodically clinical and endoscopic data, and determining both auto-modification of lymphocyte Poly(ADP-ribose)Polymerase as early signal of DNA damage, and erythrocyte membrane lipid composition (Fat Profile). Both biomarkers were demonstrated to be non invasive and easy tools, to monitor over time family members, first the oldest members (nine siblings), and thereafter their offspring, whose cell status evolved from physiological even to cancerous one. All subjects developed gastrointestinal pathologies of different kind and seriousness. Some diseases evolved to cancer, sometimes as a sudden and lethal event. The results of the two molecular approaches, agreed and even predicted the clinical and imaging paths. This cohort study supported the hypothesis that both noninvasive molecular analyses can predict altered cell states and support clinical and imaging tests.

Music has the innate potential to reach all parts of the brain, stimulates certain brain areas which are not achievable through other modalities. Music Therapy (MT) is being used for more than a century to treat individuals who needs personalized care. MT optimizes motor, speech and language responsibilities of the brain and improves cognitive performance. Pervasive developmentdisorder (PDD) is a multifaceted, neuro developmental disorder and autism spectrum disorder (ASD) comes under PDD, which is defined by deficiencies in three principal spheres: social connection with others, communicative and normal movement skills. The conventional imaging studies illustrate reduced brain area connectivity in people with ASD, involving selected parts of the brain cortex. People with ASD express much interest in musical activities which engages the brain network areas and improves communication and social skills.The main objective of this review is to analyze the potential role of MT in treating the neurological conditions, particularly ASD. Evidence based studies have reported the extensive therapeutic application of music on various part of the brain in a nonverbal child with autism through hearing or making music.Hence we hypothesized that MT intervention can improve the communication capacity in people with ASD, than customary neurorestoration therapy alone.

Since general relativity (GR) has already established that matter can simultaneously have two different values of mass depending on its context, we argue that the missing mass attributed to non-baryonic dark matter (DM) actually obtains because there are two different values of mass for the baryonic matter involved. The globally obtained "dynamical mass'' of baryonic matter can be understood as a small perturbation to a background spacetime metric even though it's much larger than the locally obtained "proper mass". Having successfully fit the SCP Union2.1 SN Ia data without accelerating expansion or a cosmological constant, we employ the same ansatz to compute dynamical mass from proper mass and explain galactic rotation curves (THINGS data), the mass profiles of X-ray clusters (ROSAT and ASCA data) and the angular power spectrum of the cosmic microwave background (Planck 2015 data) without DM. We compare our fits to modified Newtonian dynamics (MOND), metric skew-tensor gravity (MSTG) and scalar-tensor-vector gravity (STVG) for each data set, respectively, since these modified gravity programs are known to generate good fits to these data. Overall, we find our fits to be comparable to those of MOND, MSTG and STVG. While this favorable comparison does not establish the validity of our proposition, it does provide confidence in using the fits to pursue an underlying action. Indeed, the functional form of our ansatz reveals an interesting structure in these fits.

Anaemia is the most prevalent nutritional deficiency in the World and is associated with long-lasting developmental effects in children. Anaemia weakens the immune system and im-pairs cognitive development of children. Anaemia is multifactorial; therefore, anaemia’s pre-ventive/control measures should be evidence-based. This paper aimed to investigate the preva-lence and correlates of anaemia in preschool aged children at individual, maternal/household and community level in the Democratic Republic of Congo (DRC). Retrospective, nationally representative cross-sectional data, the 2013-2014 DRC Demographic and Health Survey (DHS) was used. Three -levels random intercept logistics regression models were fitted to the data using the outcome anaemia in children, defined as a haemoglobin concentration below 11dl with potential risk factors grouped at individual, maternal/household and community levels. Anaemia in children is a severe public health issue in the DRC, 63% of school-aged children are anaemic. Anaemia is highly prevalent amongst males, children with infections (fever/malaria and intestinal parasites), whose mothers are anaemic, from the poorest household, and whose drinking source of water is unclean, and who reside in provinces with recent/previous armed forces attacks. Results from this paper highlight the need for a clean and safe environment for children’s growth.

In February 2004, the Food and Drug Administration (FDA) was the first to approve the combination of cisplatin (CDDP) and pemetrexed (PEM) as standard first-line chemotherapy for untreated, unresectable malignant pleural mesothelioma (MPM). However, after that approval, no progress was made in the standard first-line treatment of MPM for almost 15 years. Positive results from a phase 3 study (Mesothelioma Avastin Cisplatin Pemetrexed Study: MAPS) verifying the effect of bevacizumab, an anti-angiogenesis agent added to CDDP/PEM for unresectable MPM, were published in The Lancet in December 2015; however, this did not lead to approval by national drug regulatory agencies. Furthermore, no second-line treatment was established for cases refractory to CDDP/PEM. In August 2018, the Pharmaceuticals and Medical Devices Agency of Japan was the first in the world to approve monotherapy with nivolumab, an immune checkpoint inhibitor (ICI), for previously unresectable, advanced, or recurrent MPM. Following Japan, in October 2020, the FDA approved the combination of nivolumab and ipilimumab for the treatment of previously untreated, unresectable MPM. In this article, we review the transition of drug treatment for MPM, in light of the historical background, focusing on the benefits of ICIs.

Objective: Major depression (MDD) and a lifetime history of MDD are characterized by increased nitrosylation, while bipolar disorder type 1 (BP1), but not BP2, is accompanied by highly increased levels of oxidative stress and nitric oxide (NO) production. Nevertheless, it is unknown whether nitrosylation is involved in BP and whether there are differences in nitrosylation between BP1 and BP2.Methods: Serum IgM antibodies directed against nitroso (NO)-adducts were examined in MDD, BP1, BP2 and healthy controls, namely IgM responses to NO-cysteine, NO-tryptophan (NOW), NO-arginine and NO-albumin (SBA) in association with IgA/IgM responses to Gram-negative bacteria, IgG responses to oxidized low-density lipoprotein (oxLDL) and serum peroxides.Results: Serum IgM levels against NO adducts were significantly higher in BP1 and MDD as compared with healthy controls, whereas BP2 patients occupied an intermediate position. IgM responses to NO-albumin were significantly higher in BP1 and MDD than in BP2 patients. There were highly significant associations between the IgM responses to NO-adducts and IgG responses to oxLDL and IgA/IgM responses to Gram-negative bacteria.Conclusions: BP1 and MDD are characterized by an upregulation of the nitrosylome (the proteome of nitrosylated proteins), and increased IgM responses to nitrosylated conjugates. Increased nitrosylation may be driven by increased bacterial translocation and is associated with lipid peroxidation processes. Innate like (B1 and marginal zone) B cells and increased nitrosylation may play a key role in the major affective disorders through activation of immune-inflammatory and oxidative pathways, cardiovascular comorbidity and impairments in antioxidant defenses, neuro-glial interactions, synaptic plasticity, neuroprotection, neurogenesis, etc.

Hydroxamic acid (HA) derivates displayed antibacterial and antifungal activities. HA with various numbers of carbon atoms (C2, C6, C8, C10, C12 and C17), complexed to different metal ions Fe(II/III), Ni(II), Cu(II) and Zn(II) were evaluated for their antimycobacterial activities and their anti-biofilm activities. Some derivates, among others HA12Fe2, inhibited the development of Mycobacterium tuberculosis, Mycobacterium bovis BCG and Mycobacterium marinum biofilms and could even attack pre-formed Pseudomonas aeruginosa biofilm. Proteomic profiles showed that the potential targets of HA10FeCl were mainly related to mycobacteria stress adaptation, involving cell wall lipid biosynthesis, drug resistance and tolerance, siderophore metabolism. This study provides new insights regarding the antimycobacterial activities of the HA and their complexes, especially about their potential antibiofilm activities.

Heart failure (HF) management in type 1 diabetes (T1D) is particularly challenging due to its increased prevalence and the associated risks of hospitalization and mortality, driven by diabetic cardiomyopathy. Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) offer a promising avenue for treating HF, specifically the preserved ejection fraction variant most common in T1D, but their utility is hampered by the risk of euglycemic diabetic ketoacidosis (DKA). This review investigates the potential of SGLT2-i in T1D HF management, alongside the emergent Continuous Ketone Monitoring (CKM) technology as a means to mitigate DKA risk, through a comprehensive analysis of clinical trials, observational studies, and reviews. The evidence suggests SGLT2-i significantly reduce HF hospitalization and enhance cardiovascular outcomes. However, their application in T1D patients remains limited due to DKA concerns. CKM technology emerges as a crucial tool in this context, offering real-time monitoring of ketone levels, which enables the safe incorporation of SGLT2-i into treatment regimes by allowing for early detection and intervention in the development of ketosis. The synergy between SGLT2-i and CKM has the potential to revolutionize HF treatment in T1D, promising improved patient safety, quality of life, and reduced HF-related morbidity and mortality. Future research should aim at clinical trials directly assessing this integrated approach, potentially guiding new management protocols for HF in T1D.

Wastewater-based epidemiology (WBE) has emerged as a key method for continuous monitoring of COVID-19 prevalence including circulating SARS-CoV-2 lineages. WBE addresses limitations of traditional clinical COVID-19 surveillance such as clinical test availability, fluctuating testing rates and increased reliance on rapid antigen tests. Our study in Perth, Western Australia, found a significant positive correlation between SARS-CoV-2 concentrations in wastewater and clinical PCR positivity rates (rs = 0.772; p < 0.001) over an 18-month period that included four successive COVID-19 waves. A strong positive correlation was apparent between the proportions of SARS-CoV-2 lineages in wastewater and clinical cases within the same region (rs = 0.728; p < 0.001), including earlier detection of Omicron and recombinant lineages in wastewater before clinical case confirmation. The successful integration of WBE with healthcare data underscores its critical role in enhancing public health decision-making and pandemic management. This approach not only demonstrates the value of WBE in current global health surveillance efforts but also highlights the potential of WBE to address future public health challenges, as a comprehensive disease monitoring and response approach.

The capacitated team orienteering problem with time windows (CTOPTW) is a NP-hard combinatorial optimization problem. In the CTOPTW, a set of customers is given each with a profit, a demand, a service time and a time window. A homogeneous fleet of vehicles is available for serving customers and collecting their associated profits. Each vehicle is constrained by a maximum tour duration and a limited capacity. The CTOPTW is concerned with the determination of a preset number of vehicle tours that begin and end at a depot, visit each customer no more than once while satisfying the time duration, time window and vehicle capacity constraints on each tour. The objective is to maximize the total profit collected. In this study we propose an iterated local search (ILS) algorithm to deal with the CTOPTW. ILS is a single solution based meta-heuristic that successively invokes a local search procedure to explore the solution space. A perturbation operator is used to modify the current local optimum solution in order to provide a starting solution for the local search procedure. As different problems and instances have different characteristics, the success of the ILS is highly dependent on the local search procedure, the perturbation operator(s) and the perturbation strength. The basic ILS uses a single perturbation operator and the perturbation strength remains the same during the optimization process. To address these issues, we use three different perturbation operators and a varying perturbation strength which changes as the algorithm progresses. The idea is to assign a larger perturbation strength in the early stages of the search in order to focus on exploring the search space. The perturbation strength is gradually decreased so that we focus more on exploitation. The computational results show that the proposed ILS algorithm is able to generate high quality solutions on the CTOPTW benchmark instances taken from the scientific literature, demonstrating its efficiency in terms of both the solution quality and computational time. Moreover, the proposed ILS produces 21 best known results and 5 new best solutions.

Logic gates made of pairs of NPN and PNP bipolar transistors, similar to CMOS logic gates, have been proposed and patented long ago but did not find any practical application until now. Other bipolar technologies (TTL, TTL-S, ECL), once the technologies of choice for digital systems, were abandoned and superseded by CMOS. In this paper it is shown that now, when truly com-plementary pairs of bipolar transistors can be made, properly biased bipolar gates similar to CMOS gates are feasible, can be thermally stable and find practical applications.

Silybin is a natural compound extensively studied for its hepatoprotective, neuroprotective and anti-cancer properties. Envisioning the enhancement of silybin potential by suitable modifications in its chemical structure, here, a series of new 7-O alkyl silybins derivatives were synthesized by Mitsunobu reaction starting from the silybins and tyrosol-based phenols, such as tyrosol (TYR, 3), 3-methoxytyrosol (MTYR, 4) and 3-hydroxytyrosol (HTYR, 5). This research sought to explore the antioxidant and anticancer properties of new eighteen derivatives and their mechanisms. In particular, the antioxidant properties of new derivatives outlined by DPPH assay, showed a very pronounced activity depending on the tyrosyl moiety (HTYR&gt;MTYR&gt;&gt;TYR). A significant contribution of the HTYR moiety was observed for silybins and 2,3-dehydro-silybin based derivatives. According to the very potent antioxidant activity, 2,3-dehydro-silybin derivatives 15ab, 15a and 15b exerted the most potent anticancer activity in human prostate cancer PC-3 cells. Furthermore, flow cytometric analysis for cell cycle and apoptosis revealed that 15ab, 15a and 15b induce strong G1 phase arrest and increase late apoptotic population in PC-3 cells. Additionally, western blotting for apoptotic marker cleaved caspase-3 confirmed apoptosis induction by these silybin derivatives in PC-3 cells. These findings hold significant importance in the investigation of anticancer properties of silybin derivatives and strongly encourage swift investigation in pre-clinical models and clinical trials.

Azobenzene photoswitches are fundamental components in contemporary approaches aimed at light-driven control of intelligent materials. Significant endeavors are directed towards enhancing the light-triggered reactivity of azobenzenes for such applications and obtaining water-soluble molecules able to act as crosslinkers in a hydrogel. Here, we report the rational design and the synthesis of azobenzene/alginate photoresponsive hydrogels endowed with fast reversible sol-gel transition. We started with the synthesis of three cationic azobenzenes (AZO A, B, and C) and then incorporated them in sodium alginate (SA) to obtain photoresponsive supramolecular hydrogels (SMHGs). The photoresponsive properties of the azobenzenes were investigated by UV-Vis and ¹H NMR spectroscopy. Upon irradiation with 365 nm UV light, the azobenzenes demonstrated efficient trans-to-cis isomerization, with complete isomerization occurring within seconds. The return to the trans form took several hours, with AZO C exhibiting the fastest return, possibly due to higher trans isomer stability. In the photoresponsive SMHGs, the minimum gelation concentration (MGC) of azobenzenes was determined for different compositions, indicating that small amounts of azobenzenes could induce gel formation, particularly in 5 wt% SA. Upon exposure to 365 nm UV light, the SMHGs exhibited reversible gel-sol transitions, underscoring their photoresponsive nature. This research offers valuable insights into the synthesis and photoresponsive properties of cationic, water-soluble azobenzenes, as well as their potential application in the development of photoresponsive hydrogels.

ADHD, one of the most prevalent diseases during childhood, we still do not know its precisely origin, although oxidative/nitrosative stress and the hypothalamic-pituitary-adrenal axis are suggested contributors. Methylphenidate, among others, is the main drug used in these patients, but its effects on relevant markers and structures remain unclear. This study, involving 59 patients diagnosed with ADHD according to DSM-5 criteria, aimed to assess changes in cortisol levels (using cortisol awakening response, CAR) and oxidative/nitrosative status with the treatment. Blood samples before and 3 months after treatment with methylphenidate were used to measure oxidative and inflammatory markers, and the endogenous antioxidant activity, while saliva samples tracked cortisol awakening response (CAR). The results show a treatment-related improvement in the redox profile, with the reduction of advanced oxidation protein products (AOPP), lipid peroxidation (LPO), and nitrite plus nitrate (NOx) levels, and the increase of the enzymatic activities of glutathione reductase (GRd) and catalase (CAT). Moreover, the area under the curve (AUC) of CAR increased significantly, indicating increased reactivity of the HPA axis. These result support by the first time the involvement of the endogenous antioxidant system in the pathophysiology of ADHD.

Artificial Intelligence (AI) is rapidly transforming the field of medicine, announcing a new era of innovation and efficiency. Among AI programs designed for general use ChatGPT holds a prom-inent position using an innovative language model developed by OpenAI. Thanks to the use of deep learning techniques, ChatGPT stands out as an exceptionally viable tool, renowned for gen-erating human-like responses to queries. Various medical specialties, including rheumatology, oncology, psychiatry, internal medicine, and ophthalmology, have been explored for ChatGPT in-tegration, with pilot studies and trials revealing each field's potential benefits and challenges. However, the field of genetics and genetic counseling, as well as that of rare disorders, represents an area suitable for exploration, with its complex data sets and the need for personalized patient care. In this review, we synthesize the wide range of potential applications for ChatGPT in the medical field, highlighting its benefits and limitations. We pay special attention to rare and genetic disorders, aiming to shed light on the future roles of AI-driven chatbots in healthcare. Our goal is to pave the way for a healthcare system that is more knowledgeable, efficient, and centered around patient needs.

Small and micro hydropower represents an attractive solution for electricity generation, with low cost and low environmental impact. The pump-as-turbine (PAT) approach has promise in this application owing to its low purchase and maintenance costs. In this paper, a new method to predict the inverse characteristic of industrial centrifugal pumps is presented. This method is based on results of simulations performed with commercial three-dimensional CFD software. Model results have been first validated in pumping mode using data supplied by pump manufacturers. Then, results have been compared to experimental data for a pump running in reverse condition. Experimentation has been performed on a dedicated test bench installed in the Department of Civil Construction and Environmental Engineering of the University of Naples Federico II. Three different pumps, with different specific speeds, have been analyzed. Using the model results, the inverse characteristic and the best efficiency point have been evaluated. Finally, results of this methodology have been compared to prediction methods available in the literature.

Urea cycle disorders (UCDs) are common inborn errors of metabolism, with an incidence of one in 30,000 births. They are caused by deficiencies in any of six enzymes and two carrier proteins, the most common being Ornithine Transcarbamylase Deficiency (OTCD). OTCD results in impairment to excrete nitrogen, causing toxic buildup of ammonia with resultant encephalopathy. Hyperammonemia (HA) induces the conversion of glutamate to glutamine in the brain. Excess glutamine in the brain causes osmotic changes cerebral edema, changes in astrocyte morphology, and cell death. Acute symptoms of HA include vomiting, hyperventilation, seizures, and irritability. Long-term neurological changes include deficits in working memory and executive function. To date, there are no predictors of prognosis of infants with neonatal onset OTCD outside of plasma ammonia level at presentation and duration of hyperammonemic coma. We provide a comprehensive analysis of a 16-year-old male with neonatal onset of OTCD as an example of how brain biomarkers may be useful to monitor disease course and outcome. This male presented at 8 days post natal with plasma ammonia and glutamine of 677 and 4024 micromol/L and had a missense mutation in Exon 4 (p.R129H). Treatment included protein restriction, sodium benzoate, and citrulline, arginine, and iron. He suffered recurrent acute hyperammonemic episodes despite compliance, triggered by infections or catabolic stressors. We discuss the long-term effects of the hyperammonemic episodes by following MRI based disease biomarkers.

We hypothesis that large earthquakes generate Horndeski-like Gravitational Wave (GW). We find that such a Horndeski-like GW propagates with the speed of sound. The sound waves generated by an earthquake make a local and temporal change to the Earth’s diagravitational medium; therefore, they modify the GW speed in a standard, Alternative-Theory-of-Gravity (ATG) sense. The quantum of the Horndeski-like GW is a massless scalar quasiparticle and cannot exist outside of the propagation region of the P-field. The Horndeski-like GW may be detectable by future GW detectors with a sensitivity of 10−15 Hz^−1/2 in the region of 0.1–1 Hz.

Introduction: Substance-induced psychotic disorder (SIPD) is a mental health condition linked to the use of a psychotropic substance whose pathogenesis has not been totally clarified. The present retrospective observational study has the objective to identify differences in clinical features and peripheral biomarkers in SIPD patients according to the main substance of abuse.Methods: A total sample of 218 patients was divided in 3 groups according to the type of consumed substance: alcohol, cannabis and psychostimulants. The 3 groups were compared for continuous variables by one-way analyses of variance (ANOVAs) and for qualitative variables by χ² tests. After removing alcohol-induced psychotic disorder group, the same analyses were repeated. Statistically significant variables from these latter analyses were included in a binary logistic regression model to confirm their reliability as predictors for cannabis- or psychostimulants-induced psychotic disorders. Results: Psychotic cannabis abusers were younger (p<0.01) and had an earlier age at onset (p<0.01). On the contrary, alcohol consumers resulted to have a longer duration of illness (p<0.01), more previous hospitalizations (p=0.04), more frequent medical comorbidity (p<0.01), higher mean Modified Sad Person Scale scores (p<0.01). Finally, psychostimulant abusers had more frequently a lifetime history of poly-substance use disorders (p<0.01). Binary logistic regression revealed that higher mean Brief Psychiatric Rating Scale scores (p<0.01) higher sodium (p=0.012) and haemoglobin(p=0.040) plasma levels were predictors of cannabis misuse in SIPD patients.Conclusions: Different clinical factors and biochemical parameters con be associated to SIPD according to the main substance of abuse, thus requiring a specific management by clinicians.

Sleep is essential for health. Indeed, poor sleep is consistently linked to the development of systemic disease, including depression, metabolic syndrome, and cognitive impairments. Further evidence has accumulated suggesting a role for sleep in cancer initiation and progression (primarily breast cancer). Indeed, patients with cancer and cancer survivors frequently experience poor sleep, manifested as insomnia, circadian misalignment, hypersomnia, somnolence syndrome, hot flushes, and nightmares. These problems are associated with a reduction in patients’ quality of life and increased mortality. Due to the heterogeneity among cancers, treatment regimens, patient populations, and lifestyle factors, the etiology of cancer-induced sleep disruption is largely unknown. Here, we discuss recent advances in understanding the pathways linking cancer and the brain and how this leads to altered sleep patterns. We describe a conceptual framework where tumors disrupt normal homeostatic processes, resulting in aberrant changes in physiology and behavior that are detrimental to health. Finally, we discuss how this knowledge can be leveraged to develop novel therapeutic approaches for cancer-associated sleep disruption, with special emphasis on host-tumor interactions.

In the last decades synthetic jet actuators have gained much interest among the flow control techniques due to their short response time, high jet velocity and absence of traditional piping, that matches the requirements of reduced size and low weight. A synthetic jet is generated by the diaphragm oscillation (generally driven by a piezoelectric element) in a relatively small cavity, producing periodic cavity pressure variations associated with cavity volume changes. The pressured air exhausts through an orifice, converting diaphragm electrodynamic energy into jet kinetic energy. This review paper faces the development of various lumped-element models (LEMs) as practical tools to design and manufacture the actuators. LEMs can quickly predict device performances such as the frequency response in terms of diaphragm displacement, cavity pressure and jet velocity, as well as the efficiency of energy conversion of input Joule power into useful kinetic power of air jet. The actuator performance is analyzed also by varying typical geometric parameters such as cavity height and orifice diameter and length, through a suited dimensionless form of the governing equations. A comprehensive and detailed physical modeling aimed to evaluate the device efficiency is introduced, shedding light on the different stages involved in the process. Overall, the influence of the coupling degree of the two oscillators, the diaphragm and the Helmholtz’s one, on the device performance is discussed throughout the paper.

Background: The Liver Imaging Reporting and Data System (LI-RADS) combines standardized terminology with a classification system for imaging findings in patients with HCC, therefore rendering diagnostic biopsy unnecessary in many cases. This retrospective study included 23 patients with a biopsy diagnosis of HCC, performed either before or after local interventional procedures, in order to evaluate the histopathologic changes induced by previous procedures and their potential influence on the response to immune therapy. Material and Methods: The study encompassed a cohort of patients diagnosed with Hepatocellular Carcinoma (HCC). Diagnosis was established through contrast-enhanced computer tomography or magnetic resonance imaging that identified LI-RADS-5 nodules in conjunction with historical liver disease and elevated alpha-fetoprotein (AFP) levels, or through histological examination confirming positivity for glypican3, heat shock protein70, and glutamine synthetase. The study detailed the liver disease etiology, LI-RADS scores, characteristics and dimensions of HCC nodules, serum AFP concentrations, Edmondson-Steiner grading, and the expression of programmed cell death ligand 1 (PD-L1) in the tumor cells. Results: Among the study's cohort of Hepatocellular Carcinoma (HCC) patients, a portion had not received any prior treatments, while the remainder experienced local HCC recurrence following trans-arterial chemoembolization or radiofrequency ablation. Observations indicated elevated alpha-fetoprotein (AFP) levels in those who had not undergone any previous interventions, showing statistical significance. The Edmondson-Steiner classification predominantly identified grade III differentiation across patients, irrespective of their treatment history. Furthermore, an increase in intra-tumoral programmed cell death ligand 1 (PD-L1) expression was noted in patients who had not been subjected to previous therapies. Conclusion: Liver biopsy offers valuable insights for patients with Hepatocellular Carcinoma (HCC), assisting in the tailoring of immune therapy strategies, particularly in cases of recurrence following prior local interventions.

Limited understanding exists regarding the intricate dynamics between the levels of social inhi-bition exhibited by both wives and husbands concerning their perceived family support and de-pressive symptoms, particularly within couples who are parents of children diagnosed with au-tism spectrum disorder (ASD). This study used the actor-partner, interdependence mediation model to analyze data collected from 397 pairs of Chinese parents with children diagnosed with ASD. The findings of the study revealed significant indirect actor effects, indicating that the levels of social inhibition exhibited by both wives and husbands were associated with their own de-pressive symptoms through their respective perceptions of family support. In general, the study did not find significant partner effects, except for some indirect effect (IE) of wives on their hus-bands' depressive symptoms through the wives' perceived social support. This observation sug-gests that cultural norms and role expectations within the family context may influence these dy-namics. These results underscore the potential importance of interventions aimed at addressing social inhibition and enhancing perceived family support to alleviate depressive symptoms in this population. Additionally, interventions targeting fathers should emphasize the importance of their involvement in parenting and collaboration with their partners in caring for children with ASD. Such collaborative efforts may contribute to improved outcomes for both parents and chil-dren within families affected by ASD.

Chenodeoxycholic acid (CA) is a naturally occurring bile acid that is produced in the liver from cholesterol. Three CA complexes using Zn(II), Mg(II), and Ca(II) ions were synthesized to examine the chelation tendencies of CA towards these metal ions. The complexation reaction of CA with the metal ions under investigation was conducted with a 1:1 molar ratio (CA to metal) at 60-70°C in natural media (pH 7-8), which consisted of a binary solvent of MeOH and H2O (1:1). The resulting CA complexes were characterized using analytical data (metal, H, C, and Cl, analysis) and spectral data (UV-visible, FT-IR, and 1H NMR) to elucidate the complexes’ structures. The results suggested that CA in anion form utilized oxygen atoms of the carboxylate group (-COO−) to capture Zn(II), Mg(II), and Ca(II) ions. This produced complexes with the general compositions of [Zn(CA)(H2O)Cl], [Mg(CA)(H2O)Cl]H2O, and [Ca(CA)(H2O)Cl]2H2O, respectively. The Kirby-Bauer disc diffusion assay was then used to explore the bioactivity of the CA complexes toward three fungal species, three Gram-positive bacteria, and two Gram-negative bacteria. The Ca(II) and Mg(II) complexes exhibited marked inhibitory effects on the cell growth of the fungal species Aspergillus niger with potency equal to 127% and 116% of the activity of the positive control, respectively. The Zn(II) and Ca(II) complexes strongly inhibited the growth of Penicillium sp., while the Zn(II) and Mg(II) complexes showed strong growth inhibition towards the Gram-negative species Pseudomonas aeruginosa.

[Co(AMPY)(DAPY)Cl2(H2O)].H2O (1) [Cu(AMPY)(DAPY)Cl2(H2O)].H2O (2) [Zn(AMPY)(DAPY)Cl2(H2O)] (3) were prepared from the ligands; AMPY = 2-amino-4-methylpyrimidine (L1), DAPY = 2,3-diaminopyridine (L2) and CoCl2.6H2O, CuCl2.2H2O and ZnCl2 in water/ethanol solutions and the three products characterized by elemental analysis, ultraviolet-visible spectroscopy (UV–Vis), Fourier-transform infrared spectroscopy (FT-IR), magnetic susceptibility, molar conductivity methods, and TGA analysis. The X-ray powder diffraction of the Co(II), Cu(II), and Zn(II) compounds showed that the geometry of monoclinic and SEM analysis revealed their morphology with a smooth surface. Molecular modeling was performed for all compounds using the density functional method DFT/B3LYP to study the structures and the frontier molecular orbitals (HOMO and LUMO). We have used Gaussian09 software for the calculations. In this study, different complexes were tested against Gram negative and Gram positive bacterial species to give insight into their broad-spectrum effects. The used pathogenic strains were two Gram positive species "Staphylococcus aureus and Micrococcus luteus" and two Gram negative species "Salmonella thyphimurium and Escherichia coli. The antifungal activity was evaluated against a pathogenic reference strain of the yeast Candida albicans. The antimicrobial and antioxidant assay results demonstrate that the tested compounds are effective against Gram positive and negative bacteria. Additionally, the compounds have an antifungal effect against Candida albicans with a maximum inhibitory zone of 2.5cm. The results demonstrated high antioxidant potential for the Zn(II) complex with a DPPH scavenging of 91.5%, however, the Cu(II) complex was low (16.5%). The data of docking with tyrosyl-tRNA synthetase presented that all compounds fit very well in the catalytic pockets of the proteins of the receptor.

The weight coefficients of the diaphragm spring depend on experiences in the traditional optimization. However, this method not only cannot guarantee the optimal solution but it is also not universal. Therefore, a new optimization target function is proposed. The new function takes the minimum of average compress force changing of the spring and the minimum force of the separation as total objectives. Based on the optimization function, the result of the clutch diaphragm spring in a car is analyzed by the non-dominated sorting genetic algorithm (NSGA-II) and the solution set of Pareto is obtained. The results show that the pressing force of the diaphragm spring is improved by 4.09%by the new algorithmand the steering separation force is improved by 6.55%, which has better stability and steering portability. The problem of the weight coefficient in the traditional empirical design is solved. The pressing force of the optimized diaphragm spring varied slightly during the abrasion range of the friction film, and the manipulation became remarkably light.

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

In a recent paper, we have shown how gravity and information can be related. The relation is based on the thermodynamic extension of the gravitational system under consideration using the holographic principle. Using this idea, we were able to derive the Gullstrand-Painlevé (GP) metric. In this short paper, we re-derive the GP metric using information. However, we now extend the spacetime to 5D with the fifth dimension being time, that is, the (3+1)D spacetime is now promoted to (3+1+1)D spacetime. We also comment on the possible Braneworld interpretation of this model.

Intrinsically Disordered Proteins (IDPs) play crucial roles in signal transduction, cell differentiation, and transcriptional regulation. Many disrupted genes associated with mental disorders are identified as IDPs, and emerging evidence suggests the functional role of IDPs in neuropsychiatric disorders. However, few studies comprehensively explore the functional association between protein disorder properties and different mental diseases. To address this gap, we collected disrupted gene sets for seven mental diseases (MDD, SCZ, BP, ID, AD, ADHD, ASD) and a control gene set from normal brains using DisGeNET and GeneCards databases. The state-of-the-art predictor IUPred2A was then utilized to calculate the disorder properties , followed by a thorough comparison between the disordered proteins in mental diseases and healthy controls. Functional enrichment analysis and protein-protein interaction networks were conducted to investigate the IDPs’ functional roles in psychiatric diseases. Additionally, we demonstrated the role of IDPs in protein binding formations through a case study of alpha-synuclein using protein docking. Our findings reveal that differentially expressed proteins in mental disorders, especially in ASD and ADHD, exhibit more IDPs than those in healthy controls. IDPs in psychiatric disorders are significantly enriched in neurodevelopmental pathways and play an important role in in gene expression regulation. Our results indicate distinct functional patterns of disorder proteins among mental diseases and healthy controls. When comparing the IDPs between ASD and ADHD, we observed that IDPs in ADHD are more likely linked to the synaptic signaling and regulation, while IDPs in ASD are more tendentiously related to diverse and complex biological processes. Our work offers valuable insights into the important functions of IDPs in psychiatric disorders, enhancing our understanding of the molecular mechanisms involved in psychiatric disorders.

Various formulations of the exact renormalization group can be compared in the perturbative domain, in which we have reliable expressions for regularization-independent (universal) quantities. We consider the renormalization of the $\lambda\phi^4$ theory in three dimensions and make a comparison between the sharp-cutoff regularization method and other more recent methods. The former gives considerably better results, while the other methods are far from optimal in the perturbative domain. In addition, these methods present theoretical problems that are already manifest in the renormalization of mass.

The article presents the potential of liposomal cannabidiol in the treatment of Panic Disorder, when used in integration with Complex Cognitive Psychotherapy. The advantages of the integrated treatment, developed by the Author, and based on the use of liposomal cannabidiol combined with cognitive psychotherapy, are discussed. A new and original tool is presented and described, developed, and tested for the first time by the Author and called NegEnt Panic Blocker.

Gestational diabetes mellitus (GDM) pathophysiology comprises clinical and genetic factors. In fact, GDM has been associated with several single nucleotide polymorphisms (SNPs). This study aimed to build a prediction model of GDM combining clinical and genetic risk factors. A total of 1588 pregnant women from the San Carlos Cohort participated in the present study, 1069 (67.3%) Caucasian (CAU) and 519 (32.7%) Latin American (LAT), 255 (16.1%) with GDM. The incidence of GDM was similar in both groups (16.1% CAU and 16.0% LAT). Genotyping was performed by IPLEX Mass ARRAY PCR selecting 110 SNPs based on literature references. The SNPs showing the strongest likelihood of GDM development were the rs10830963, rs7651090 and rs1371614 in CAU and rs1387153 and the rs9368222 in LAT. Clinical variables including age, pre-pregnancy body mass index and fasting plasma glucose (FPG) at 12 gestational weeks predicted the risk of GDM (AUC 0.648, 95%CI 0.601-0.695 in CAU; AUC 0.688, 95%CI 0.628-9.748 in LAT) and adding the SNPs modestly improved prediction (AUC 0.722, 95%CI 0.680-0.764 in CAU; AUC 0.769, 95%CI 0.711-0.826 in LAT). In conclusion, adding genetic variants enhanced the prediction model of GDM risk in CAU and LAT pregnant women. An RCT is underway to demonstrate its usefulness

A new method for multi-shot reconstruction of high-energy photon distributions in the context of studying the interaction between a beam and a plasma in plasma wakefield acceleration (PWFA) experiments is presented. The study investigates the effects of beam perturbations on betatron radiation and analyzes how these perturbations can lead to hosing, a transverse instability that can degrade the quality of the beam. The potential of betatron radiation spectroscopy as a non-invasive diagnostic technique for PWFA experiments is also emphasized.

Physics of high-Tc superconducting cuprates is obscured by the effect of strong electronic correlations. One way to overcome the problem is to seek for an exact solution at least within the small cluster and expand it to the whole crystal. Such an approach is in the heart of the cluster perturbation theory (CPT). Here we develop CPT for the dynamic charge and spin susceptibilities (spin-CPT), within which the correlation effects are explicitly taken into account by the exact diagonalization. We apply spin-CPT to the effective two-band Hubbard model for the cuprates obtained from the three-band Emery model and calculate one- and two-particle correlation functions, namely, spectral function and spin and charge susceptibilities. Doping dependence of the spin susceptibility was studied within spin-CPT and CPT-RPA that is the CPT generalization of the random phase approximation (RPA). Both methods produce the low energy response at four incommensurate wave vectors in qualitative agreement to the results of the inelastic neutron scattering on overdoped cuprates.

Pollen tubes grow by spatially and temporally regulated expansion of new material secreted into the cell wall at the tip of the tube. A complex web of interactions among cellular components, ions and small molecule provides dynamic control of localized expansion and secretion. Cross-correlation studies on oscillating lily (Lilium formosanum Wallace) pollen tubes showed that an increase in intracellular calcium follows an increase in growth, whereas the increase in the alkaline band and in secretion both anticipate the increase in growth rate. Calcium, as a follower, is unlikely to be a stimulator of growth, whereas the alkaline band, as a leader, may be an activator. To gain further insight herein we reversibly inhibited growth with potassium cyanide (KCN), and followed the re-establishment of calcium, pH and secretion patterns as growth resumed. While KCN markedly slows growth and causes the associated gradients of calcium and pH to sharply decline, its removal allows growth and vital processes to fully recover. The calcium gradient reappears before growth restarts, however it is preceded by both the alkaline band and secretion, in which the alkaline band is slightly advanced over secretion. Thus the pH gradient, rather than the tip-focused calcium gradient, may regulate pollen tube growth.

To explore the relevant factors that affect the efficacy of consciousness-regaining therapy (CRT)for prolonged disorder of consciousness(pDOC),a retrospective analysis was conducted on the case data of 114 patients with pDOC admitted to department of functional neurosurgery of Tianjin Huanhu Hospital from January 2019 to January 2022. Basic information on the cases,data on pDOC disease assessment, consciousness-regaining therapy methods, and efficacy evaluation were collected. A total of 114 patients were grouped and compared based on the efficacy at the end of treatment. Among them, there were 61 cases in the ineffective group and 53 cases in the effective group. There was no statistically significant difference (P&gt;0.05) between the two groups in terms of gender, age, etiology, acute cerebral herniation, emergency craniotomy surgery, emergency decompressive craniectomy, time from onset to start of consciousness-regaining therapy , and duration of consciousness-regaining therapy(P&gt;0.05). However, there were statistically significant differences (P&lt;0.05) in terms of secondary hydrocephalus, , consciousness-regaining therapy methods, CRS-R grading before treatment, and GOSE score at 6 months after treatment. Binary logistic regression analysis showed that the type of therapy (OR=0.169, 95% CI: 0.057-0.508) was a related factor affecting the efficacy of consciousness-regaining therapy (P&lt;0.05).Compared with non-invasive therapy, personalized awakening therapy using various invasive consciousness-regaining therapy methods can help improve the efficacy of therapy for pDOC.

Academic stress affects students' psychological and physiological well-being. Dental undergraduate programs are known for their demanding curriculum, leading to significant stress symptoms. Objective was to determine if salivary cortisol levels were higher in students exposed to academic stress, assess the relationship between stress severity/temperament and cortisol values, and explore relaxation technique effects. Salivary cortisol was measured at two time points for all participants: before exams and during a relaxation period after summer break. A third measurement was conducted for students with high pre-test cortisol levels who received instructions on progressive muscle relaxation(PMR) before subsequent exams. Additionally, participants completed two questionnaires: Perceived Stress Scale(PSS) and Fisher's Temperament Questionnaire. The group analysis based on the PSS indicated that 39 participants reported high stress. Women demonstrated significantly higher stress than men(p=0.042054). A significant difference in stress levels was observed between Director and Builder temperament types(p=0.029276). Cortisol levels showed a significant decrease from the first measurement to the second measurement, and the third measurement after implementing PMR. The grade in the "Dermatovenereology" course correlated with stress level according to the PSS(k=0.578467). Pre-test cortisol levels correlated with the frequency of using PMR guidelines during winter test periods(k=0.416138). Stress negatively affects the immune system and poses health risks. Implementing stress reduction techniques in dental/medical education could benefit students and the healthcare system.

The search of DNA polymorphisms useful for the genetic improvement of dairy farm animals lasts more than 40 years with relevant findings in cattle for milk traits, where the best combination of alleles for dairy processing have been found in casein genes and in the DGAT1. Nowadays, similar results are not reached yet in river buffaloes despite advanced genomic technologies and accurate phenotype records are available. The aim of the present study was to investigate and validate in a larger buffalo population the effect on six milk traits of four single nucleotide polymorphisms (SNP) in the CSN1S1, CSN3, SCD and LPL genes, previously reported to be associated with or affect dairy traits in smaller populations often belonging to one farm. A total of 800 buffaloes were genotyped. Daily milk yield (dMY, kg), protein yield (dPY, kg) and fat yields (dFY, kg), fat and protein contents (dFP, % and dPP, %), somatic cell count (SCC, 103cell/ml) and urea (mg/dl) were individually recorded in each month for the whole lactation from 2010 to 2021. A total of 15,742 individual milk test day records (2,496 lactations) were available on 680 buffalo cows with 3.6±1.7 parity (from 1 to 13) and 6.1±1.2 test day records per lactation on average. Three out four SNP in CSN1S1, CSN3 and LPL were associated with at least one of analyzed traits. In particular, the CSN1S1 (AJ005430:c.578C&gt;T) gave favorable associations with all yield traits (dMY, p=0.022; dPY, p=0.014 ; dFY, p=0.029) and SCS (p=0.032), whereas the CSN3 (HQ677596: c.536C&gt;T) positively associated with SCS (p=0.005) and milk urea (p=0.04). Favorable effect on dMY (p=0.028), dFP (p=0.027) and dPP (p=0.050) were observed for the LPL. Conversely, SCD did not show any association with milk traits. This is the first example of confirmation study carried out in the Mediterranean river buffalo for genes of economic interest in dairy field and it represents a very important indication for the preselection of young bulls destined to breeding programs in the view of a more sustainable dairy production.

Psychosis can be defined as a combination of psychopathological symptoms including delusions and/or hallucinations without insight. Psychotic disorders may configure a primary psychiatric illness or represent the result of a functional/structural brain damage induced by substance use, neurological diseases or other medical conditions. They are multifactorial disorders in which genetic, environmental and gene-environment interaction factors contribute to the expressiveness of the symptoms. Among the environmental factors, psychotropic substances represent the most important removable facilitators of psychosis. In our study, we compared the prevalence of substance induced psychosis between a sample of patients affected by cannabis use disorder and a sample of patients affected by cocaine use disorder analyzing retrospectively the data of outpatients with no personal or family history of psychiatric illnesses.

The gastrointestinal (GI) tract is innervated by the enteric nervous system (ENS), an extensive neuronal network that traverses along its walls. Due to local reflex circuits, the ENS is capable of functioning with and without input from the central nervous system. The functions of the ENS range from the propulsion of food to nutrient handling, blood flow regulation and immunological defense. Records of it first being studied emerged in the early 19th century when the submucosal and myenteric plexuses were discovered. This was followed by extensive research and further delineation of its development, anatomy, and function during the next two centuries. The morbidity and mortality associated with the underdevelopment, infection or inflammation of the ENS highlights its importance and the need for us to completely understand its normal function. This review will provide a general overview of the ENS to date and connect specific GI disorders such as short bowel syndrome with neuronal pathophysiology. Exciting opportunities in which the ENS could be used as a therapeutic target for common GI diseases will also be highlighted, as the further unlocking of such mechanisms could open the door to more therapy-related advances, and ultimately change our approach to GI disorders.

Hormone changes across women's menstrual cycle may lead to changes in perception of chemical signals and hormonal responses to these cues. The aim of the present study was to determine the role of menstrual cycle phase on the effects of extracts of male axillary secretions (EMAS) in women. We tested healthy reproductive age and premenopausal women (n=29). EMAS/control solution was applied once in two hours either in the follicular or luteal phase, while collecting saliva samples for LH and cortisol monitoring. LH and cortisol concentrations were analyzed using EIA technique. PANAS and VAS were used to assess the mood. We observed a significant increase in the number of LH peaks (p=0.0447) and their amplitude (p=0.0469) when EMAS was applied in the follicular phase. The same application in the luteal phase lowered the amplitude of LH peaks (p=0.0382). EMAS application increases salivary cortisol level in reproductive age women relative to premenopausal women (p=0.0032). PANAS revealed changes in positive and negative affect after EMAS application. Our data indicate the significance of the menstrual cycle phase for EMAS effects on LH secretion, mood, but not on cortisol secretion in women.

Aim: This study aimed to investigate the relationship between dental caries, dental anxiety, and salivary cortisol levels in children visiting pediatric dental clinics and their implications on pediatric oral health. Materials and Methods: A cross-sectional study was conducted at a dental university in the UAE. A total of 60 children, aged 4-12 years, were included. Salivary cortisol levels were measured using an Enzyme-Linked Immunosorbent Assay (ELISA) kit. Dental caries status was evaluated, and dental anxiety levels were assessed using the Modified Dental Anxiety Scale (MDAS). Statistical analyses, including Mann-Whitney U test and Pearson's correlation coefficient, were performed to determine significant differences and associations. Results: The study group showed significantly higher salivary cortisol levels compared to the control group (p<0.0001). A strong positive correlation was found between salivary cortisol levels and dental caries status (p<0.001). However, no significant difference in dental anxiety levels was observed between the study and control groups (p=0.85). A strong positive correlation was found between dental anxiety levels and dental caries status (p<0.001). Conclusion: The findings indicate a significant association between salivary cortisol levels and dental caries, suggesting that higher cortisol levels are associated with active caries. Dental anxiety levels were positively correlated with dental caries. Understanding the relationship between these variables can contribute to better oral health strategies and interventions for children, emphasizing the importance of managing dental anxiety and stress in pediatric dental care. Clinical Significance: This study highlights the potential of salivary cortisol as a biomarker for assessing stress and its impact on oral health in children. By addressing dental anxiety and stress, dental professionals can provide child-friendly dental care, enhance preventive measures, and improve oral health outcomes in pediatric patients.

New research points to a possible link between Autism Spectrum Disorder and the gut microbiota as many autistic children have co-occurring gastrointestinal problems. This review focuses on specific alterations of gut microbiota mostly observed in autistic patients. Particularly, the mechanisms through which such alterations may trigger the production of the bacterial metabolites or leaky gut in autistic people are described. Various altered metabolite levels were observed in autistic children, many of those were of bacterial origin such as short chain fatty acids (SCFAs), indoles and lipopolysaccharides. A less integrative gut-blood-barrier is abundant in autistic individuals. This explains the leakage of bacterial metabolites into the patients triggering new body responses or altered metabolism. Some other co-occurring symptoms such as mitochondrial dysfunction, oxidative stress in the cells, altered tight junctions in the blood brain barrier and structural changes in cortex, hippocampus, amygdala and cerebellum were detected. Moreover, this paper suggests that autism is associated with an unbalanced gut microbiota (dysbiosis). Although the cause-effect relationship between autism and gut microbiota is not yet well established, consumption of specific probiotics may represent a powerful tool to re-establish gut homeostasis and promote gut health. Diagnostic and therapeutic value of new biomarkers leading to the perturbation in the phenylalanine metabolism will be discussed.

Due to the retrognathic mandible, an orthodontist frequently observes skeletal class II malocclusion in growing patients. The preferred technique for analyzing and monitoring the temporomandibular joint alterations caused by the functional device is magnetic resonance imaging [MRI]. The study aimed to assess and compare changes in the articular disc's dimension and location before and following the use of various class II correctors to correct the class II molar relation using MRI technology. Methods: 39 adolescent patients aged 15-23 years old [24 girls and 15 boys] who were diagnosed with skeletal Class II division 1 malocclusion based on clearly defined criteria underwent treatment with either the power scope II [PS], Sabbagh Advanced Repositioning Appliance [SARA] and or Dynaflex [DF] with fixed appliances. For fixed functional treatment, the average length of treatment was 5-7 months. The changes in the articular disc dimension and position and condylar position were assessed. The study was done at the Department of Orthodontics at the College of Dentistry, Hawler Medical University in Erbil City. Results: Group DF has a significant effect on the condylar position index and posterior joint space on the closed mouth and disc length on both open and close mouth techniques, and in the group SARA, disc position, and condylar position index on closed mouth technique have shown that significant differences were observed. Conclusion: Class II malocclusions can be effectively corrected by fixed functional appliances. The statistical significance forward movement of the condyle in the glenoid fossa and the posterior movement of the articular disc concerning the condylar head was observed. The mechanism of action of functional appliances appears to include the forward migration of the C-GF complex.

In the tissue regeneration field, stem cell transplantation and the control of their differentiation represent a promising therapeutic strategy. The second aspect can be achieved using electrical stimulation. This study aims to characterize the effect of a microsecond electrical stimulation on MSCs and iNSCs, in the context of the RISEUP FET-OPEN project (n. 964562) that seeks to control these cells differentiation for the spinal cord injury treatments. Here, the effect of a specific microsecond electric pulses stimulation, characterized by bipolar pulses of 100 µs + 100 µs, delivered for 30 minutes at an intensity of 250 V/cm, on i) cell proliferation, ii) cell cycle, iii) gene expression and iv) apoptosis was evaluated. Results show that the stimulation does not affect cell proliferation, cell cycle, and apoptosis, but induced some variations in gene expression, in particular in EGR1, FOS, and POU5F1. These ob-servations led us to deeply investigate the cell proliferation until 72h from the stimulation observing an increase in the iNSCs. The main outcome of this study is that the chosen stimulation protocol is safe and not toxic for MSCs and iNSCs. The observed variations in the gene expression need to be deeply investigated to assess the molecular mechanisms involved.