Background: Various vitamins and minerals have been implicated in the aetiology of depression. Objective: To estimate the effects of micronutrient exposures on major depressive disorder (MDD) and recurrent depression (rMDD) using Mendelian randomization (MR). Methods: We undertook a comprehensive bidirectional MR study of multiple micronutrient exposures on MDD and rMDD. Summary statistics were obtained from the Psychiatric Genomics Consortium (PGC) genome wide association studies (GWASs) of MDD (cases = 116,209; controls = 314,566), and rMDD (cases=17,451; controls=62,482). Results: None of the micronutrients with available genetic instruments were strongly associated with MDD or rMDD using traditional MR methods. However, using methods to increase analytical power by accounting for genetically correlated variants (e.g. cIVW), highlighted five micronutrients with possible causal effects. Point estimates for rMDD were the largest magnitude, with three micronutrients suggestive of a protective effect: serum iron (OR_cIVW 0.90 per SD increase; 95% CI 0.85- 0.95; p=0.0003); erythrocyte copper (OR_cIVW 0.97; 95% CI 0.95- 0.99; p=0.0004); and 25(OH) vitamin D (OR_cIVW 0.81; 0.66- 0.99; p=0.04). Apparent adverse effects of increased selenium on the risk of MDD (OR_cIVW 1.03; 95% CI 1.02-1.05; p=0.0003) and rMDD (OR_cIVW 1.08; 95% CI 1.00-1.08; p=0.06), and serum magnesium on rMDD (OR_cIVW 1.21; 1.01- 1.44; p=0.04); were less consistent between methods and may be driven by pleiotropy. Conclusions: Our results suggest weak evidence for a protective effect of iron, copper and 25(OH)D on major depressive outcomes, with mixed evidence for selenium and magnesium. There was no evidence to support a causal effect of any other micronutrients on MDD or rMDD, although genetic instruments were lacking, with insufficient power to detect small but important effects. Future micronutrient supplementation trials should ensure ample statistical power given modest causal effect estimates, and consider potential risks of supplementation, as some micronutrient effect estimates suggested potential harm in excess.

Antidepressants are among the most used medications in the US, with significant deleterious effects on people’s well-being. At any given time, depression impacts approximately 1 in 10 Americans, causing wide and broad societal costs. Interest is developing for non-pharmacological treatments and preventative measures. We summarize the literature on non-invasive dietary and lifestyle approaches for treating depression, including recent work with the psychedelic treatment of depression. This review aims to inform future research and treatment programs for depression. This review provides an evidentiary summary of integrative therapeutic approaches for depression.

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

In 2011, it was reviewed that there is a strong co-occurrence between major depression and chronic fatigue syndrome (CFS), with fatigue and physio-somatic symptoms being key symptoms of depression, and depressive symptoms appearing during the course of CFS. Moreover, the comorbidity between both conditions may in part be explained by activated immune-inflammatory pathways, including increased translocation of Gram-negative bacteria and increased levels of pro-inflammatory cytokines, such as interleukin (IL)-1. Nevertheless, the possible involvement of activated microglia in this comorbidity has remained unclear. This paper aims to review microglial disturbances in major depression, CFS and their comorbidity. A comprehensive literature search was conducted using the PubMed / MEDLINE database to identify studies that are relevant to this current review. Depressed patients present neuroinflammatory alterations, probably related to microglial activation, while animal models show that a microglial response to immune challenges including lipopolysaccharides is accompanied by depressive-like behaviors. Recent evidence from preclinical studies indicate that activated microglia have a key role in the onset of fatigue. In chronic inflammatory conditions, such as infections and senescence, microglia orchestrate an inflammatory microenvironment thereby causing fatigue. In conclusion, based on our review we may posit that shared immune-inflammatory pathways and activated microglia underpin comorbid depression and CFS and that activated microglia are the main orchestrators of this comorbidity. As such, microglial activation and neuro-inflammation may be promising targets to treat the overlapping manifestations of both depression and CFS.

Tourette syndrome is a complex neuropsychiatric condition that manifests in childhood and is often associated with other psychiatric comorbidities. This case describes a young male with Tourette syndrome with major depressive disorder and attention deficit hyperactivity disorder (ADHD), who experienced troublesome side-effects due to his existing medications (escitalopram, risperidone and methylphenidate). In order to control his tics, ameliorate depressive symptoms, and eliminate side-effects of stiffness and sedation, risperidone was switched to cariprazine, a third-generation antipsychotic medication with D3-D2 partial agonism. In addition, the antidepressant dose was also increased. With the new combination, the patient reported good control of his tics, together with significant improvement in depressive symptoms and no side-effects. Based on this case and the reviewed literature, cariprazine might be a viable option for patients with Tourette syndrome with other comorbid illnesses, whom are prone to side effects of medication.

Objective-Most women stop using hormonal contraceptives due to changes in their mood. The evidence regarding the association of hormonal contraception with depression shows mixed results. Therefore, we aim to establish the association between the use of hormonal contraception and depressive symptoms. Method- This cross-sectional study was conducted on 326 women of reproductive age using hormonal contraceptives for a week to one year referred to as "hormonal contraceptive (HC) users" (n=165), and those using non-hormonal methods and not using contraceptives referred to as "HC non-users" (n=161). Beck's depression inventory (BDI-II) was used to measure depression. Result-There was no discernible difference in mean Beck's depression inventory score and degree of depression between the two groups. However, individual symptoms of depression such as sadness(p=0.01), reduced libido(p=0.0002) feelings of pessimism (p=0.02), and failure (p=0.003) were found to be significantly high in the HC user group. Conclusion- We conclude that there was no significant difference in mean depression scores between groups. However, few individual symptoms of depression were high in HC users suggesting depression as a potential side effect of hormonal contraceptive use.

The work analyses the way in which symptoms and life themes manifest in middle-aged adults diagnosed with major recurrent depression. Specifically, the relationships between symptoms, life themes, and life themes - symptoms have been analyzed. For this purpose, Spearman correlation, and the methods of Latent Semantic Indexing (LSI) were used. Seven symptoms and twenty-six life themes were identified in the patients analyzed as well as similarities of symptoms/life themes (at patient level), the ranking of the importance of symptoms on each life theme (at the level of the group of patients), the rankings of the similarities of life themes in relation to different symptoms or various groups of symptoms (at the level of the group of patients), and dysfunctional cycles of symptoms and life themes (at patient level). The findings only refer to the patients analyzed. Although our findings cannot be generalized, there is a possibility that some of them may also be encountered in other patients. However, the design of the work can be used to initiate other similar studies.

Background. Fibromyalgia (FM) is a complex condition marked by increased pain sensitivity and central sensitization. Studies often explore the link between FM and depressive-anxiety disorders, but few focus on dysthymia or persistent depressive disorder (PDD), which can be more disabling than major depression (MD). Objective. To identify clinical scales and subscales of the Personality Assessment Inventory (PAI) that effectively describe and differentiate the psychological profile of PDD, with or without comorbid MD, in FM patients with PDD previously dimensionally classified by the Millon Clinical Multiaxial Inventory III (MCMI-III). Method. An observational, cross-sectional study was conducted with 66 women (mean age 49.18, SD=8.09) from Hospital del Mar. The PAI, the MCMI-III, and Fibromyalgia Impact Questionnaire (FIQ) were used to assess the sample. Results. The PAI showed strong discriminative ability in detecting PDD, characterized by high scores in cognitive and emotional depression, and low scores in identity alteration, dominance, and grandeur. High scores in cognitive, emotional, and physiological depression, identity alteration, cognitive anxiety, and suicidal ideation, along with low scores in dominance and grandeur, were needed to detect MD with PDD. Discriminant analysis could differentiate 69.6-73.9% of the PDD group and 84.6% of the PDD+MD group. Group comparisons showed that 72.2% of patients with an affective disorder by PAI were correctly classified in the MCMI-III affective disorder group, and 70% without affective disorder were correctly classified. Conclusions. The PAI effectively identifies PDD in FM patients and detects concurrent MD episodes, aiding in better prognostic and therapeutic guidance.

Depression is one of the most severe sequelae of COVID-19, with major depressive disorder often characterized by disruption in white matter (WM) connectivity , stemming from changes in brain myelination. This study aimed to quantitatively assess brain myelination in clinically diagnosed post-COVID depression using recently proposed MRI method, macromolecular proton fraction (MPF) mapping. The study involved 63 recovered COVID-19 patients (52 mild, 11 moderate, 2 severe) at 13.5±10.0 months post-recovery, with matched controls without prior COVID-19 history (n=19). A post-COVID depression group (PCD, n=25) was identified based on psychiatric diagnosis, while a comparison group (noPCD, n=38) included participants with neurological COVID-19 complications, excluding clinical depression. Fast MPF mapping revealed extensive demyelination in PCD patients, particularly in juxtacortical WM (predominantly occipital lobe and medial surface), WM tracts (inferior fronto-occipital fasciculus (IFOF), posterior thalamic radiation, external capsule, sagittal stratum, tapetum), and grey matter (GM) structures (hippocampus, putamen, globus pallidus, and amygdala). The noPCD group also displayed notable demyelination but with less magnitude and propagation. Multiple regression analysis highlighted IFOF demyelination as the primary predictor of PCD presence and severity according to Hamilton scores. The number of post-COVID symptoms was a significant predictor of PCD presence while the number acute of symptoms was a significant predictor of PCD severity. This study, for the first time, reveals extensive demyelination in numerous WM and GM structures in PCD, outlining IFOF demyelination as a key biomarker.

Current lines of research into mood disorders indicate that immune mediators participating in the pathophysiology of chronic somatic disorders have potent influences on brain functions, even when these mediators are produced in peripheral tissues. Elevated levels of circulating immune molecules have been consistently associated with depressive symptoms in a number of clinical populations and experimental models, to the extent that major depressive disorder (MDD) is now seen, at least in part, as a disorder of immunity. This paradigm has brought to the fore the use of anti-inflammatory therapies as adjunctive to standard antidepressant therapy with the hope to improve treatment efficacy, particularly in those cohorts that do not respond well to standard medication. Such new practice requires the availability of biomarkers to tailor these new therapies to those most likely to benefit but also clear mechanisms of action describing the interaction between peripheral immunity and brain function. These mechanisms are generally studied in preclinical models that try to recapitulate the human disease through peripherally induced sickness behaviour as the model for immune-induced MDD. After an appraisal of the data in rodent models and their adherence to the data in clinical cohorts, we propose a modified model of periphery-brain interaction that goes beyond the currently established view of interaction between peripheral cytokines and microglia cells as the driver of depression. Instead, we suggest that brain barriers are primary actors in the communication between body and brain and, as a consequence, in the pathophysiology of the disease. This model suggests novel biomarkers, novel targets for therapies as well as a novel mechanism for resistance to standard treatments.

Major depressive disorder (MDD) and substance use disorder (SUD) are of immense medical and social concerns. Although significant progress on neuronal involvement in mood and reward circuitries has been achieved, only relatively recently the role of glia in these disorders have attracted attention. Detail understanding of the glial function in these devastating diseases could offer novel interventions. Here, following a brief review of circuitries involved in mood regulation and reward perception, specific contribution of the neurotrophic factors, neuroinflammation and gut microbiota to these diseases are highlighted. In this context, the role of specific glial cells (e.g., microglia, astroglia, oligodendrocytes and synantocytes) on phenotypic manifestation of MDD or SUD are emphasized. In addition, potential use of this knowledge in developing novel therapeutics is touched upon.

Objective: The aim of the current study was to examine whether and to what extent mood disorders, comprising major depression and bipolar disorder, are accompanied by structural changes in the brain as measured using voxel-based morphometry (VBM). Methods: We have performed a VBM study using a 3Т MRI system (GE Discovery 750w) in patients with mood disorders (n=50), namely 39 with major depression and 11 with bipolar disorder, compared to 42 age, sex and education matched healthy controls. Results: Our results show that depression was associated with significant decreases in grey matter (GM) volume restricted to regions located in medial frontal and anterior cingulate cortex on the left side and middle frontal gyrus, medial orbital gyrus, inferior frontal gyrus (triangular and orbital parts), and middle temporal gyrus (extending to the superior temporal gyrus) on the right side. When the patient group was separated into bipolar disorder and major depression the reductions remained significant only for the patients with major depressive disorder. Conclusions: Using VBM the present study was able to replicate decreases in GM volume restricted to frontal and temporal regions in patients with mood disorders mainly major depression, as compared with healthy controls.

Background: Temporal lobe epilepsy (TLE) is the most common focal epilepsy subtype in adults and is frequently accompanied by depression, anxiety and psychosis. Aberrations in total paraoxonase (PON)1 status may occur in TLE and those psychiatric conditions. Methods: We examined paraoxonase (PON)1 status, namely Q192R PON1 genotypes and PON1 enzymatic activities, in 40 normal controls and 104 TLE patients, 27 without comorbidities, and 77 with comorbidities including mood disorders (n=25), anxiety disorders (n=27) and psychosis (n=25). Outcomes: CMPAase and arylesterase activities were significantly lower in TLE and mesial temporal sclerosis (MTS) with and without psychiatric comorbidities than in normal controls. The areas under the ROC curve of CMPAase were 0.893 (0.037) for TLE and 0.895 (±0.037) for MTS. Partial Least Squares (PLS) path analysis showed that there were specific indirect effects of PON1 genotype on TLE severity (p<0.0001) and psychopathology (p<0.0001), which were both mediated by lowered CMPAase activity, while arylesterase activity was not significant. The severity of TLE was significantly associated with psychopathology scores. Furthermore, PON1 CMPAase activity was inversely associated with Mini Mental State Examination scores. Interpretation: The severity of TLE and comorbidities are to a large extent explained by lowered PON1 enzyme activities and by effects of the Q192R genotype which are mediated by lowered CMPAase activity. Total PON1 status plays a key role in the pathophysiology of TLE, MTS and psychiatric comorbidities by increasing the risk of oxidative toxicity. PON1 enzyme activities are new drug targets in TLE to treat seizure frequency and psychiatric comorbidities.

Depression and cognitive impairment are recognized complications of COVID-19. This study aimed to assess cognitive performance in clinically diagnosed post-COVID depression (PCD) patients using neuropsychological testing. The study involved 71 post-COVID patients, with matched control groups: recovered COVID-19 individuals without complications (n=18) and individuals without prior COVID-19 history (n=19). A post-COVID depression group (PCD, n=25) was identified based on psychiatric diagnosis, a comparison group (noPCD, n=46) included participants with neurological COVID-19 complications, excluding clinical depression. The PCD patients showed significantly less scores in the MoCA test, decreased immediate memory recall in the Word Memory Test, decreased processing speed and higher accuracy in the Trail Making Test, and near to significant worse executive control and processing speed in the Stroop task compared to controls and the noPCD patients. The number of post-COVID symptoms negatively correlated with immediate word memory recall and processing speed among all post-COVID patients. In PCD patients, negative correlations between number of post-COVID symptoms and delayed recall, between time after recovery and immediate recall, and positive correlation between the number of acute symptoms and processing speed in the incongruent condition of the Stroop task were found. No differences between groups in Sniffin’s stick olfactory test was found. Overall, our study revealed cognitive impairment in PCD patients similar to those in major depressive disorder.

Depression is the commonest mental disorder worldwide. Both antidepressants and psychotherapy are effective in treating depression, but response to these treatments is often incomplete. Yoga-based interventions (YBIs) have emerged as a promising adjunctive treatment for depression. Recent research has attempted to identify the biological mechanisms associated with the antidepressant actions of YBIs. In this scoping review, conducted according to the PRISMA-ScR guidelines, the PubMed and Scopus databases were searched to retrieve research on biomarkers of response to YBIs in patients with depression. Eleven studies were included in the review. Based on these studies, YBIs may improve depression through beneficial effects on systemic inflammation, stress axis regulation, cardiac autonomic functioning, and possibly reductions in oxidative stress-related cellular damage. Increases in brain-derived neurotrophic factor (BDNF) may represent a final common pathway upon which these processes converge. Though these results are theoretically plausible, they should be interpreted with caution due to certain methodological limitations in the existing research. Replication of these results and improvements in study methodology, and the evaluation of other biomarkers relevant to the pathophysiology of depression, could further elucidate the mechanism of action of YBIs in this disorder, and identify which patients would benefit most from this treatment approach.

The co-occurrence of depression and obesity has become a significant public health concern worldwide. Recent studies have shown that metabolic dysfunction, which is commonly observed in obese individuals and characterized by inflammation, insulin resistance, leptin resistance, and hypertension, is a critical risk factor for depression. This dysfunction may induce structural and functional changes in the brain, ultimately contributing to depression's development. Given that obesity and depression mutually increase each other's risk of development by 50-60%, there is a need for effective interventions that address both conditions. The comorbidity of depression with obesity and metabolic dysregulation is thought to be related to chronic low-grade inflammation, characterized by increased circulating levels of pro-inflammatory cytokines, and C-reactive protein (CRP). As pharmacotherapy fails in at least 30-40% of cases to adequately treat major depressive disorder, a nutritional approach is emerging as a promising alternative. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are a promising dietary intervention that can reduce inflammatory biomarkers, particularly in patients with high levels of inflammation, including pregnant women with gestational diabetes, patients with type 2 diabetes mellitus, and overweight individuals with major depressive disorder. Further effort directed to implement these strategies in clinical practice could contribute to improved outcomes in patients with depression and comorbid obesity and/or metabolic dysregulation.

Rationale: Major depressive disorder (MDD) is characterized by signaling aberrations in interleukin (IL)-6, IL-10, beta-endorphins as well as mu (MOR) and kappa (KOR) opioid receptors. Here we examined whether these biomarkers may aid in the classification of unknown subjects into the target class MDD.Methods: The aforementioned biomarkers were assayed in 60 first-episode, drug-naïve depressed patients and 30 controls. We analyzed the data using joint principal component analysis (PCA) performed on all subjects to check whether subjects cluster by classes; support vector machine (SVM) with 10-fold validation; and linear discriminant analysis (LDA) and SIMCA performed on calibration and validation sets and we computed the figures of merit and learnt from the data. Results: PCA shows that both groups were well separated using the first three PCs, while correlation loadings show that all 5 biomarkers have discriminatory value. SVM and LDA yielded an accuracy of 100% in validation samples. Using SIMCA there was a highly significant discrimination of both groups (model-to-model distance=87.5); all biomarkers showed a significant discrimination and modeling power, while 10% of the patients were identified as outsiders and no aliens could be identified.Discussion: We have delineated that MDD is a distinct class with respect to neuro-immune and opioid biomarkers and that future unknown subjects can be authenticated as having MDD using this SIMCA fingerprint. Precision psychiatry should employ SIMCA a) to authenticate patients as belonging to the claimed target class and identify other subjects as outsiders, members of another class or aliens; and b) to acquire knowledge through learning from the data by constructing a biomarker fingerprint of the target class.

Recently, the relationship between emotional arousal and depression has been studied. Focusing on this relationship, we first developed an arousal level voice index (ALVI) to measure arousal levels using the Interactive Emotional Dyadic Motion Capture database. Then, we calculated ALVI from the voices of depressed patients from two hospitals (Ginza Taimei Clinic [GTC] and National Defense Medical College hospital [NDMC]) and compared them with the severity of depression as measured by the Hamilton Rating Scale for Depression (HAM-D). Depending on the HAM-D score, the datasets were classified into a no depression (HAM-D&lt;8) and a depression group (HAM-D≥8) for each hospital. A comparison of the mean ALVI between the groups was performed using the Wilcoxon rank-sum test and a significant difference at the level of 10% (p = 0.094) at GTC and 1% (p = 0.0038) at NDMC was determined. The area under the curve (AUC) of the receiver operating characteristic was 0.66 when categorizing between the two groups for GTC, and the AUC for NDMC was 0.70. The relationship between arousal level and depression severity was indirectly suggested via ALVI.

Background. Rheumatoid arthritis (RA) is a chronic inflammatory and autoimmune disorder which affects the joints in the wrists, fingers, and knees. RA is often associated with depressive and anxiety symptoms as well as chronic fatigue syndrome (CFS)-like symptoms.Aim. To examine the association between depressive symptoms (measured with the Beck Depression Inventory, BDI), anxiety (Hamilton Anxiety Rating Scale, HAMA), and CFS-like (Fibro-fatigue Scale) symptoms and immune-inflammatory, autoimmune, and endogenous opioid system (EOS) markers, and lactosylceramide in RA. Methods. The serum biomarkers were assayed in fifty-nine RA and fifty-nine patients without increased psychopathology (PP) and fifty healthy controls.Results. There were highly significant correlations between the BDI, FF, and HAMA scores and severity of RA, as assessed with the DAS28-4, clinical and disease activity indices, the number of tenders and swollen joints, and patient and evaluator global assessment scores. A common latent vector (reflective model) could be extracted from the PP and RA-severity scales, which showed excellent psychometric properties. Partial least squares analysis showed that 69.7% of the variance in this common core underpinning PP and RA symptoms could be explained by the regression on immune-inflammatory pathways, rheumatoid factor, anti-citrullinated protein antibodies, CD17, and mu-opioid receptor levels. Conclusions. Depression, anxiety, and CFS-like symptoms due to RA are reflective manifestations of the phenome of RA and are mediated via the effects of the same immune-inflammatory, autoimmune, and EOS pathways and lactosylceramide that underpin the pathophysiology of RA. These PP symptoms are clinical manifestations of the pathophysiology of RA.

Background. There is strong comorbidity between atherosclerosis (ATS) and depression which is attributed to increased atherogenicity, insulin resistance (IR), and immune and oxidative stress.Aim of the study. To examine the role of the above pathways and mu opioid receptor (MOR), β-endorphin, zinc, copper, vitamin D3, calcium, and magnesium in depression due to ATS / unstable angina (UA).Methods. Biomarkers were assayed in 58 controls and 120 ATS patients divided into those with moderate and severe depression according to the Beck Depression Inventory (BDI)-II score > 19 and > 29, respectively. Results. Neural network and logistic regression models showed that severe depression due to ATS/UA was best predicted by IL-6, UA, MOR, zinc, β-endorphin, calcium and magnesium and that moderate depression was associated with IL-6, zinc, MOR, β-endorphin, UA, atherogenicity, IR, and calcium. These neural networks yielded a significant discrimination of severe and moderate depression with an area under the ROC curve of 0.831 and 0.931, respectively. Using Partial Least Squares analysis, 66.2% of the variance in a latent vector extracted from the ATS/UA clinical features, BDI-II scores, atherogenicity, and IR could be explained by the regression on IL-6, IL-10, zinc, copper, calcium, MOR, and age. The BDI-II scores increased from controls to ATS to UA class III to UA class IV.Conclusions. Depression due to ATS/UA is a reflective manifestation of increased atherogenicity and IR, which are modulated by immune activation, aberrations in the endogenous opioid system, antioxidants, trace elements, and macrominerals.

Parkinson’s disease and Alzheimer’s disease are the most commonly diagnosed neurodegenerative disorders. Though these disorders differ in terms of their underlying pathophysiology as well as in their clinical features and course, there is a certain degree of overlap between them. This overlap may be partly related to α-synuclein-mediated neuropathological changes. Recent evidence has found that depression is associated with an increased subsequent risk of both these neurological disorders, and that α-synuclein may also play a pathogenic role in depression. The current study examines epidemiological, population genetic and environmental exposure data in relation to the estimated prevalence of depressive disorders, Parkinson’s disease and Alzheimer’s disease using a cross-sectional, country-level analysis. The results of this study are consistent with a significant relationship between depressive disorders and neurodegenerative disorders, a possible shared genetic vulnerability related to functional polymorphisms of the α-synuclein gene SNCA, and potential gene-environment interactions involving fine particulate matter pollution. The significance of these results is discussed in the light of existing translational, clinical and epidemiological research on the links between these disorders.

Background: Social skills deficits are present in 43.3% of major depressed patients and significantly impact health-related quality of life. However, studies concerning social deficits as state-dependent markers of depression are limited. Objective: To delineate the effects of severity of depression, personality characteristics, family support satisfaction and self-esteem on social skills in clinical depression. Methods: We recruited 150 patients with major depressive disorder or persistent depressive disorder and assessed 1) Beck Depression Inventory-II (BDI-II), 2) Social Skill Inventory (SSI), 3) Family Adaptation, Partnership, Growth, Affection, Resolve (APGAR) Questionnaire 4) Rosenberg Self-Esteem Scale (RSES) and 5) Maudsley Personal Inventory (MPI). Results: Social skills deficits were significantly associated with female gender, age < 40 years, depression severity, introvert / neurotic personality, and lowered family support satisfaction and self-esteem. A large part of the variance (47.2%) in social skills deficits was predicted by satisfaction of family support, introvert personality, and low self-esteem. Exploratory Factor Analysis showed that a bifactorial model best fitted the data with a) a general factor loading highly on BDI-II, SSI emotional and social, APGAR, RSES, MPI_introvert and MPI_neurotic scores, and b) a single-group factor loading on both SSI, RSES, and MPI introvert scores. Conclusion: In clinical depression, social skills deficits covary with increasing severity of depression and thus constitute a state marker of depression, and independently from severity of depression covary with introvert personality features. As such, remission of social skills deficits may emerge as a novel objective for the treatment of depression and prevention of new episodes.

Background: In this secondary analysis of the Supporting the Modification of Lifestyle In Lowered Emotional States (SMILES) randomised controlled trial, we investigated if the beneficial effects of a dietary intervention on clinical depression were driven, in part, by reducing the consumption of foods classified as ultra-processed.Methods: The SMILES trial enrolled 67 adults with major depressive disorder, randomly assigning them to either a 12-week modified Mediterranean dietary intervention or a social support control. Our analysis included 44 participants with non-missing dietary data and at least one valid Montgomery–Åsberg Depression Rating Scale (MADRS) assessment at 12 weeks of follow-up. The Nova food classification system was used to estimate the proportion of ultra-processed foods in the overall diet (percentage of grams) based on data from seven-day food diaries. We fitted linear regression models under blinded conditions to determine whether ultra-processed food intake-change from baseline to 12 weeks moderated the dietary intervention effects on depressive symptoms. We estimated mean differences in depressive symptoms along with ninety-five per cent confidence intervals (95%CIs).Results: For participants in the dietary intervention, there was an additional 2.5-point improvement in MADRS scores for each 10% reduction in the dietary share of ultra-processed foods compared to participants in the control group (between-group mean differences in depressive symptoms: −2.46, 95%CIs −4.71 to −0.20, p=0.039, η _p ² of 0.10).Conclusions: These preliminary findings suggest that the therapeutic benefit of a dietary intervention for depression may stem, at least in part, from reductions in the dietary share of ultra-processed foods.

Detecting suicidal ideation in adults with major depression is crucial for timely intervention and prevention of self-harm. As suicide is influenced by various biological, socio-cultural and psychological factors, traditional screening methods have accuracy and efficiency limitations. In certain cultures, societal stigma and marginalization can compel individuals with depression to conceal their suffering. Such individuals often turn to online social media platforms and share their experiences with peers under the protection of anonymity. Our research explored the potential of machine learning detection of suicidal ideation among Romanian adults with major depression that contributed to a web-based depression support forum. A trained algorithm (C4.5 decision tree) analyzed 125 posts fed to on a free access online support forum over 5 years (2014 – 2018) and classified them based on suicidal ideation content. 32 texts (25%) were identified as having a high probability of suicidal ideation content. 65% of the authors were male, with a mean age of 36.7±10.3 years and an average duration of illness of 3.4±1.4 years. Texts indicating positive suicidal ideation were generally shorter and elicited more general responses but fewer professional responses compared to those without suicidal ideation content. The study's main limitations include the relatively small number of classified texts, the absence of prospective information and the lack of qualitative evaluation of the excerpts' content. As socio-demographic and linguistic actuarial results were comparable to data reported by real life studies, we may consider basic text mining techniques as a screening tool that is able to detect suicidal ideation in texts written in unstructured Romanian language.

Background: Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is an emerging technique in trauma care for managing severe hemorrhage when conventional resuscitation is inadequate. Methods: We report a case involving a 45 yo female patient who sustained multiple traumatic injuries—including thoracic, pelvic, and aortic damage—after a fall from approximately 5 meters. The timely insertion of a REBOA device provided critical hemodynamic support, allowing for temporary stabilization in the emergency department according to the principles of Damage Control Resuscitation. Results: This intervention facilitated her subsequent transfer to a Level 1 Trauma Center for definitive surgical intervention.Although the patient's prognosis remained poor due to the severity of her injuries, the use of REBOA illustrated its potential utility in improving hemodynamic stability in critically injured patients. Conclusions: Our findings suggest that REBOA can be a valuable adjunct in trauma management, offering a life-saving option in critical hemorrhagic cases where traditional methods are insufficient. Further research is warranted to refine REBOA application, particularly concerning optimal balloon positioning and integration with imaging techniques.

Healthy diet interventions have been shown to improve depressive symptoms, but there is a need for randomized controlled trials (RCTs) that are double-blind and investigate biological mechanisms. The primary objectives of this randomized controlled pilot trial were to test the palatability of the meals and acceptability of the intervention in preparation for a future 8-week RCT which will investigate whether a healthy Nordic diet improves depressive symptoms in individuals with major depressive disorder, and associated biological mechanisms. Depressed (n=10) and non-depressed (n=6) women and men were randomized to receive either a healthy Nordic diet (ND) or a control diet (CD) for 8 days. Participants were blinded to diet allocation and study hypotheses. Health questionnaires were completed before and after the intervention, and, throughout the study, questionnaires assessed ratings of liking and sensory properties of the meals, adherence, and open-ended feedback. In the ND group, 75% of participants consumed no non-study foods, compared to 50% of CD participants. The meals of both diets, on average, received good ratings for liking and sensory properties, though the ND ratings were somewhat higher. Overall, results were positive and informative, indicating that the planned RCT will be feasible and well-accepted, with some proposed modifications.

The purpose of this study is to investigate the effect of academic advising on changing or maintaining majors in university degrees. It is also a goal of the study to determine which semester of the course study is most likely or less likely witness the change of major and whether advising contributes to that change. Through this correlational study, the researchers explored students’ perceptions about the academic advising they received and the relationship of its absence on students’ major change. The participants were 1725 undergraduate students from all year levels. One survey is used to collect the data for this study: Influences on Choice of Major Survey. Based on the findings, it is found that university advisors have a very poor effect on students' decisions to select their majors as 45.6% of the 1725 participants indicate NO influence of advising in their survey answers. Whereas career advancement opportunities, students' interests, and job opportunities indicate a strong effect on their majors’ selections as they score the highest means of 3.76, 3.73, 3.64 respectively. In addition, findings show that students are most likely changing their majors in their second year and specifically in the second semester. Second year major change scored 36.9% in the second semester and 30.9% in the first semester. More importantly, results indicate that there is a positive significant correlation between college advisor and change major in the second year (p = 0.000). It is to researchers understanding based on the findings that when students receive enough academic advising in the first year of study and continues steadily to the next year, the possibilities of students changing their majors decreases greatly.

Choosing a college major is a crucial issue for twelfth-grade students. Many students feel confused and influenced by their surroundings when making this decision. This can have negative consequences if it does not align with the students interests and talents. This research proposes a web application as a solution, providing introductory information for each major. We employed a design and developement approach to create an application that assists prospective students in identifying majors based on their interests. The primary objective is to alleviate students discomfort during their studies, which often leads to decreased performance. With this application, students can avoid selecting majors solely due to peer pressure or parental coercion.

Our previous studies showed that in patients with brain diseases neurotrophic factors in lacrimal fluid (LF) may change more prominently than in blood serum (BS). Since glial cell line-derived neurotrophic factor (GDNF) is involved in control of neuronal networks in epileptic brain, we aimed to assess GDNF levels in LF and BS as well as BDNF, hypothalamic-pituitary-adrenocortical and inflammation indices in BS of patients with focal epilepsy (PWFE), epilepsy and comorbid depression (PWFE+MDD) compared with major depressive disorder (PWMDD) and healthy controls (HC). GDNF levels in BS were similar in patients and HC and higher in PWFE taking valproates. GDNF levels in LF were significantly lower in all patient groups compared to controls, and independent of drugs used. LF and BS GDNF concentrations positively correlated in HC, but not patient groups. BDNF level was lower in BS of patients compared with HC and higher in PWFE+MDD taking valproates. Logistic regression models demonstrated that GDNF decrease in LF may be an important predictor of focal epilepsy. Probability of focal epilepsy can be evaluated using GDNF in LF and BDNF in BS; MDD - GDNF in LF, cortisol and TNF-α in BS; epilepsy with MDD - GDNF in LF, TNF-α and BDNF in BS.

Periodontal diseases and Thalassemia Major (TM), which are two chronic inflammatory diseases, are associated with increased levels of proinflammatory cytokines in bio-fluids. Interleukin (IL)-6 and IL-8 have been identified as potent proinflammatory biomarkers in periodontal diseases as well as in patients with β-thalassemia (TM-β). This suggests that patients with TM-β and gingival inflammation have two chronic inflammatory conditions, each of which may affect the other. The objective of this pioneer research was to evaluate the effect of oral hygiene maintenance and care on serum levels of IL-6 and IL-8. 31 participants selected after screening and were given Non-surgical periodontal therapy(NSPT). IL-6 and IL-8 were evaluated by enzyme linked immunohistochemistry assay (ELISA) at baseline and compared at 6 weeks after NSPT. Statistical analysis was done with SPSS v23. The comparison from the baseline to 6-weeks follow-up for both IL-6 and IL-8 was done using Wilcoxon Signed rank test. The descriptive statistics are represented as median and inter quartile range (IQR). Highly significant improvement (p-&lt;0.000) was found for IL-6 and IL-8 when compared at 6 weeks from baseline. Results provide a gateway to new modality in lowering systemic burden of the disease, thereby reducing morbidity, via local measures or oral care.

Understanding how and why cells cooperate to form multicellular organisms is a central aim of evolutionary biology. Multicellular groups can form through clonal development (where daughter cells stick to mother cells after division) or by aggregation (where cells aggregate to form groups). These different ways of forming groups directly affect relatedness between individual cells, which in turn influences the degree of cooperation and conflict within the multicellular group. It is hard to study the factors that favoured multicellularity by focusing only on obligately multicellular organisms, like complex animals and plants, because the factors that favour multicellular cooperation cannot be disentangled, as cells cannot survive and reproduce independently. We propose bakers yeast, Saccharomyces cerevisiae, as an ideal model for studying the very first stages of the evolution of multicellularity. This is because it can form multicellular groups both clonally and through aggregation and uses a family of proteins called ‘flocculins’ that determine the way in which groups form, making it particularly amenable to lab experiments. We briefly review current knowledge about multicellularity in S. cerevisiae and then propose a framework for making predictions about the evolution of multicellular phenotypes in yeast based on social evolution theory. We finish by suggesting outstanding questions and potentially fruitful avenues for future research.

Background. Oral anticoagulants (OACs) reduce stroke and systemic embolism (SE) in patients with atrial fibrillation (AF) but increase the risk of major bleeding (MB). No study has addressed the incidence and outcomes of bleeding in AF patients in the Middle East (ME). The Jordan AF study evaluated clinical profiles and one-year outcomes of AF patients who sustained bleeding events. Methods. Patients in 29 hospitals and clinics (May 2019 - December 2020) were enrolled and followed up for one year. Demographics and one-year events were compared in patients with or without bleeding. Results. Of 2018 patients enrolled; 166 patients sustained MB or clinically relevant non-major (CRNM) bleeding (8.2 events per 100 patient-years), including 47 patients who had MB (2.3 events per 100 patient-years). Compared with 1852 (91.8%) patients who did not have bleeding, patients with MB were older and had a higher prevalence of hypertension, diabetes mellitus (DM), heart failure, and malignancy, More patients with MB than those with no bleeding were using OACs (93.6% vs. 78.9%, p=0.02). Patients with MB had significantly higher one-year rates of stroke/SE (23.4% vs. 3.6%, p<0.0001) and all-cause mortality (31.9% vs 11.6%, p=0.001). Independent predictors of MB were stroke/SE (OR 10.8, 95% CI 5.3-21.9, p<0.0001), malignancy (3.4, 1.3-8.5, p=0.01), use of OACs (4.4, 1.3-14.7, p=0.02) and DM (1.9, 1.0-3.5, p=0.04). Conclusions. MB and CRNM bleeding occurred in (≈8%) of patients with AF at one year. Patients with MB (≈2%) had worse baseline clinical profiles and one-year prognosis compared with those who did not have bleeding. Keywords: Atrial fibrillation; Major bleeding events; Clinically-relevant non-major bleeding; Oral anticoagulants; Middle Eastern population; Prognosis. Clinical studies registration: the study is registered on clinicaltrials.gov (unique identifier number NCT03917992).

Major depressive disorder (MDD) is a serious mental illness with a heavy social burden, but its underlying molecular mechanisms remain unclear. Mass spectrometry (MS)-based metabolomics is providing new insights into the heterogeneous pathophysiology, diagnosis, treatment, and prognosis of MDD by revealing multi-parametric biomarker signatures at the metabolite level. In this comprehensive review, recent developments of MS-based metabolomics in MDD research are summarized from the perspective of analytical platforms (liquid chromatography-MS, gas chromatography-MS, supercritical fluid chromatography-MS, etc.), strategies (untargeted, targeted, and pseudotargeted metabolomics), key metabolite changes (monoamine neurotransmitters, amino acids, lipids, etc.), and antidepressant treatments (both western and traditional Chinese medicines). Depression sub-phenotypes, comorbid depression, and multi-omics approaches are also highlighted to stimulate further advances in MS-based metabolomics in the field of MDD research.

Aggregative multicellularity occurs when dispersed cells join together to form a highly cooperative unit, in contrast to clonal multicellular organisms formed by cells that remain in contact after descent from a single cell. Because aggregative groups may include non-relatives, aggregative multicellular organisms should be particularly vulnerable to the rise of cheater cells that take advantage of social goods without paying the costs, reducing cooperation, and even threatening extinction. We review the key mechanisms by which aggregative multicellular organisms control cheaters with a focus on the best studied aggregative organisms, Myxococcus xanthus and Dictyostelium discoideum. These include various passive and active mechanisms to maintain high relatedness within aggregates, to enforce cooperation on aggregate members, and the costs of cheating on other key functions. Ultimately, aggregative multicellular organisms are not that different from clonal organisms descended from a single cell.

Transporter proteins, P-glycoprotein (P-gp) and P4ATPase-CDC50, are responsible for the transport of Miltefosine drug across cell membrane of a protozoan parasite Leishmania major. Mutations or change in activity of these proteins may lead to emergence of resistance in the parasite. Owing to the structural and functional importance of these transporter proteins, in this ppaper, we have tried to decipher the evolutionary divergence of these Miltefosine transporter proteins across different forms of life including Protists, Fungi, Plants and Animals. We retrieved 96, 207, and 189 sequences of P-gp, P4ATPase and CDC50 proteins respectively, across diverse variety of organisms for the conserved analysis. Phylogenetic trees were constructed for these three transporter proteins based on Bayesian posterior probability inference. The evolutionary analysis concluded that these proteins remain highly conserved throughout the species diversity but still substantial differences in the proteins for host (Homo sapiens) and parasite (L. major) were observed which have led in targeting these Miltefosine transporter proteins in a parasite specific manner.

This study to assess the Physical Land Suitability Analysis for Cultivation of Selected Cool Weather Cereal Crops, Misha District, Hadiya Zone, South Central Ethiopia of major cereal crops of barley and teff in Misha district. Each of the criteria was separately reclassified and analyzed for their suitability for supporting barley and teff crops based on the FAO crop requirements specified for them. The major data sources were climatic data, soil, LGP and topographic data as well as key informant interview, questioner observation of crop requirements which have been considered to undertake suitability assessments of the study area. The factor maps like land use /land cover, temperature, rain fall, soil type and altitude were classified based on suitability evaluation methods of FAO and experts’ opinion. At final stage these were reclassified and standardized in GIS software extension tools, which led to the preparation of suitability analysis map of the major crops plant suitability classes. As part of spatial MCDM, AHP pair wise comparison module was used to derive internal and external weights for each individual factors and parameters respectively. Consequently, suitability analysis was done and weighted overlay suitability map was visualized with integration of GIS. The findings show that among total area of land suitability maps for both barley and teff cops were using weighted overlay techniques. The suitability map of teff crop shows that 12,038.22 hectare of the investigated area are highly suitable (S1), 19,646.07 hectare moderately suitable (S2) and 4,501.71 hectare marginally suitable (S3) and 112 hectare not suitable. On the other hand, the suitability map of barley crop shows that 7,898.52 hectare of the investigated area are highly suitable (S1), 22,830.08 hectare moderately suitable (S2), and 5,466.4 hectare marginally suitable (S3) and 103 hectare not suitable for economic reasons (N1). This was done for barley and Teff crops separately. Results of the study revealed that most of the lands in the study area are suitable for the cultivation of the selected crops and other crops. Based on finding, it could be recommended that this work would be used as policy guide for planners; investment could be successful in the District, further suitability research works should be carried out in order to optimize the major crop cultivation and production.

Objective: About a third of schizophrenia patients are treatment-resistant to antipsychotic therapy. No studies established the fingerprints or pathway-phenotypes of treatment-resistant schizophrenia. The present study aimed to delineate the pathway-phenotypes of non-responders (NRTT) and partial responders (PRTT) to treatment using machine learning. Methods: We recruited 115 schizophrenia patients and 43 healthy controls and measured schizophrenia symptom dimensions, neurocognitive tests, plasma CCL11, interleukin-(IL)-6, IL-10, Dickkopf protein 1 (DKK1), high mobility group box-1 protein (HMGB1), κ- and µ-opioid receptors (KOR and MOR, respectively), endomorphin-2 (EM-2), and β-endorphin. Results: Machine learning showed that the NRTT group is a qualitatively distinct class and is significantly discriminated from PRTT with an accuracy of 100% using a neuro-immune-opioid-cognitive (NIOC) pathway-phenotype with as main determinants list learning, controlled word association, and Tower of London test scores, CCL11, IL-6, and EM2. The top-5 symptom domains separating NRTT from PRTT were in descending order: psychomotor retardation, negative symptoms, psychosis, depression, and mannerism. Moreover, a NIOC pathway also discriminated PRTT from healthy controls with an accuracy of 100% while all PRTT and controls were authenticated as belonging to their respective classes. Conclusion: A non-response to treatment with antipsychotics is determined by increased severity of specific symptom profiles coupled with deficits in executive functions, and episodic and semantic memory, and aberrations in neuro-immune and opioid pathways. No patients showed complete remission after treatment indicating that non-remitting in PRTT is attributable to increased HMGB1 and residual deficits in attention, executive functions, and semantic memory.

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

Nanoparticles offer available tools for MDD research. In this assay, we applied CBR1 (cannabinoid receptor 1) knockout (CB1-/-) mice to study whether functionalized solid lipid nanoparticles loading with curcumin and dexanabinol (Cur/SLNs-HU-211) exhibited anti-depressant outcomes through CBR1. Wild-type (CB1+/+) animals together with CBR1 knockout (CB1-/-) animals received daily injections of Corticosterone (CORT) for 3 weeks to obtain MDD mice model, and then the therapeutic action of Cur/SLNs-HU-211 were evaluated, respectively. Our work show that Cur/SLNs-HU-211 nanoparticles in the existence of CBR1 facilitate an efficient motor function improvement in CORT-induced MDD mice model. Cur/SLNs-HU-211 nanoparticles alleviated symptoms on CB1+/+ MDD mice and resulted in dopamine and norepinephrine recovery following CORT-induced neurotoxicity. In conclusion, the possible mechanisms underlying the antidepressant effect of Cur/SLNs-HU-211 might be the induction of CB1 expression and downstream RASGEF1C and Egr1 expression, together with a significantly upregulation of neuron-specific genes in CB1+/+ mice only. In conclusion, CBR1 is necessary during the process of antidepressant activities of Cur/SLNs-HU-211 nanoparticles. This study confirms that Cur/SLNs-HU-211 nanoparticles based CBR1 in vivo targeting would be a potentially feasible and safe way to motivate future therapeutic strategies of Major Depressive Disorder.

This study introduces an integrated methodology that incorporates vessel motion dynamics into the evaluation of operations and maintenance (O&M) costs for floating offshore wind turbines (FOWTs). By combining UWiSE, a discrete-event simulation tool, with SafeTrans, a voyage simulation software, the methodology accounts for vessel motion effects during offshore operations. The approach was demonstrated through a numerical case study at two wind farm sites, Marram Wind and Celtic Sea C, with a fictive wind farm layout of 100 × 15 MW NREL turbine on a UMaine VolturnUS-S platform. Three Major Component Replacement (MCR) strategies were assessed: Tow-to-Port (T2P), Floating-to-Floating (FTF), and Self-Hoisting Crane (SHC). The T2P strategy resulted in the highest O&M costs—94 k€/MW/year at Marram Wind and 97 k€/MW/year at Celtic Sea C—due to extended MCR durations (90-180 days), leading to lower availability (90%-94%). In contrast, the FTF and SHC strategies, which are still under development, demonstrate significantly lower costs and reduced downtime. The SHC strategy, in particular, has proven to be the most cost-effective, achieving up to a 64% reduction in costs while increasing availability to 97%-98%. The integrated approach incorporates vessel dynamics, accounting for factors such as wave direction, wave period, and vessel response to varying sea states. This allows for greater flexibility in setting operational limits, potentially permitting higher limits in favorable conditions where vessel motion impact is reduced. However, in scenarios where dynamic vessel responses lead to increased motions—such as when waves approach from the side or when the wave period is close to the vessel's natural roll period—more restrictive limits may be necessary, even if significant wave heights are lower. This flexibility or restriction highlights the importance of incorporating motion-based dynamics for emerging technologies in the evolving FOWT O&M market.

This review provides a comprehensive analysis of the pelvic plexus and its regulation across various mammalian species, including rats, cats, dogs, and pigs. The pelvic and hypogastric nerves play crucial roles in regulating pelvic functions such as micturition, defecation, and erection. The anatomical organization of these nerves varies, forming either well-defined ganglia or complex plexuses. Despite these variations, the neurons within these structures are consistently regulated by key neurotransmitters—norepinephrine and acetylcholine. These neurons also possess receptors for testosterone and prolactin, particularly in rats, indicating the significant role of these hormones in neuronal function and development. Moreover, neuropeptides such as vasoactive intestinal peptide (VIP), substance P, neuropeptide Y (NPY), somatostatin (SOM), galanin (GAL), and calcitonin gene-related peptide (CGRP) are co-released with neurotransmitters to modulate pelvic functions. This review highlights the complex interplay between neurotransmitters, neuropeptides, and hormones in regulating pelvic physiology and emphasizes the importance of hormonal regulation in maintaining the functionality and health of the pelvic plexus across different species.

Background: Galectin-3 (Gal-3) is a biomarker involved in a wide range of diseases including cardiac remodeling following acute myocardial infarction (AMI). Identification of prognostic markers in patients with AMI can guide strategies towards improved survival and the quality of life. Methods: Our study included 59 patients with AMI and preserved ejection fraction. We determined the Gal-3 plasma concentration within 24 hours of chest pain onset from aortic root, femoral/radial artery, coronary sinus and cubital vein. Major adverse cardiovascular events (MACE) were evaluated at six months follow-up. Results: MACE at six months post-AMI was recorded in 20 patients (34%). The Gal-3 plasma concentration from aortic root and the femoral/radial artery were independent predictors of MACE at six months follow-up after the first AMI (OR 1.228; 95%CI: 1.011-1.491; p=0.038; OR 3.438; 95%CI: 1.275-9.265; p=0.015). ROC analysis identifies the Gal-3 plasma concentration from aortic root as a better predictor of MACE or death (cut-off &gt;10.86 ng/ml; AUC 0.858; 95%CI: 0.744-0.973; p&lt;0.001) than Gal-3 plasma concentration from femoral/radial artery (cut-off &gt;10.18 ng/ml; AUC 0.742; 95%CI: 0.596-0.888; p=0.006). Conclusion: The Gal-3 plasma concentration in patients with AMI determined during coronary angiography, especially from the aortic root, within 24 hours after chest pain onset is a valuable biomarker of prognosis at six months follow-up.

The climate change is likely to modify the freezing-thawing cycles in soils and surface waters of permafrost-affected and subarctic regions. Yet, the change of solution chemical composition during ice formation and evolution of remaining fluids remain very poorly known. Towards better understanding of dissolved (&lt; 0.45 µm) organic carbon, major and trace elements behavior in permafrost peatland environments, here we performed laboratory freezing of peat leachates, from complete freezing to complete thawing in order to quantify the partitioning of solutes between the aqueous solution and the remaining ice. We hypothesized the existence of two main groups of solutes, behaving conservatively or non-conservatively during freezing depending on their incorporation into the ice or ability to coagulate in the form of insoluble minerals or amorphous materials in the fluid phase. An unexpected result of this work was that, despite sizable degree of element concentration in the remaining fluid and possible coagulation of organic, organo-mineral and inorganic compounds, the freezing and subsequent thawing produced the final concentrations of most solutes which were not drastically different from initial concentrations in starting leachates, prior freezing. This demonstrates high stability of dissolved (&lt; 0.45 µm) OC, Fe, Al and some trace metals to repetitive freezing and thawing of surface waters in permafrost peatlands.

Leishmaniasis is a vector-borne parasitic infection caused by the bite of female Phlebotomine sandflies. World Health Organization (WHO) estimates 100,000 cases to be reported annually on a global scale, moreover, 13 million people were infected between 2010 and 2015 worldwide. Treatment of leishmaniasis by conventional synthetic compounds is met by challenges pertaining to adverse effects which call for the discovery of newer anti-leishmanial molecules. This study was performed to evaluate the effect and modes of action of a sesquiterpene alcoholic molecule Farnesol on Leishmania major, the causative agent of Zoonotic Cutaneous leishmaniasis. The cytotoxic effect of Farnesol against L. major promastigotes, amastigotes and macrophages was assessed by MTT test and counting. The IC50 on promastigotes by Farnesol on L. major was evaluated by flow cytometry. In the findings, Promastigotes were reduced at 167 µM/mL & the mean numbers of L. major amastigotes in macrophages were significantly decreased in exposure to Farnesol at 172 µM/ml. In addition, Farnesol demonstrated no cytotoxicity on macrophages as the IC50 value was 945 µM/ml; it induced significant apoptosis dose-dependent on L. major promastigotes. In silico protein-ligand binding analyses indicated the effect of Farnesol in perturbation of the ergosterol synthesis pathway of Leishmania with attributes suggesting inhibition of Lanosterol-α-demethylase, the terminal enzyme of ergosterol synthesis machinery. Findings from flow cytometry reveal the role of farnesol in apoptosis-induced killing in promastigotes. Farnesol was effective at very lower concentrations when compared to Paromomycin. Further studies are crucial to evaluate the therapeutic potentials of Farnesol alone and in combination with other conventional drugs using clinical settings.

Psychiatry remains in a permanent state of crisis, which fragmented psychiatry from the field of medicine. The crisis in psychiatry is evidenced by the many different competing approaches to psychiatric illness including psychodynamic, biological, molecular, pan-omics, precision, cognitive and phenomenological psychiatry, folk psychology, mind-brain dualism, descriptive psychopathology, and postpsychiatry. The current “gold standard” DSM/ICD taxonomies of mood disorders and schizophrenia are unreliable and preclude to employ a deductive reasoning approach. Therefore, it is not surprising that mood disorders and schizophrenia research was unable to revise the conventional classifications and did not provide more adequate therapeutic approaches. The aim of this paper is to explain the new nomothetic network psychiatry (NNP) approach, which uses machine learning methods to build data-driven causal models of mental illness by ensembling risk-resilience, adverse outcome pathways (AOP), cognitome, brainome, symptomatome, and phenomenome latent scores in a causal model. The latter may be trained, tested and validated with Partial Least Squares (PLS) analysis. This approach not only allows to compute pathway-phenotypes or biosignatures, but also to construct reliable and replicable nomothetic networks, which are, therefore, generalizable as disease models. After integrating the validated feature vectors into a well-fitting nomothetic network, clustering analysis may be applied on the latent variable scores of the R/R, AOP, cognitome, brainome, and phenome latent vectors. This pattern recognition method may expose new (transdiagnostic) classes of patients which if cross-validated in independent samples may constitute new (transdiagnostic) nosological categories.

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.

Plantago major L. is a worldwide available plant that has been used traditionally for several medical application due to its properties such as wound healing, anti-inflammatory, antimicrobial etc. This work aimed to develop and evaluate nanostructured PCL electrospun dressing with P. major extract encapsulated in nanofibers for application in wound healing. The extract from leaves was obtained by extraction in a mixture of water:ethanol= 1:1 of the freeze-dried extract presented a minimum inhibitory concentration (MIC) for Staphylococcus Aureus susceptible and resistant to methicillin of 5.3 mg/mL, a high antioxidant capacity, but a low content of total flavonoids. Electrospun mats without defects were successfully produced using two P. major extract concentrations based on MIC value. The extract incorporation in PCL nanofibers was confirmed by FTIR and contact angle measurements. The PCL/P. major extract was evaluated by DSC and TGA demonstrating that incorporation of the extract decreases the thermal stability of the mats as well as the degree of crystallinity of PCL-based fibers. The P. major extract incorporation on electrospun mats produced a significant swelling degree (more than 400%) and increased the capacity of adsorbing wound exudates and moisture, important characteristics for skin healing. The extract-controlled release evaluated by in vitro study in PBS (pH, 7.4) shows that P. major extract delivery from the mats occurs in the first 24 h, demonstrating their potential capacity to be used in wound healing.

Background. We investigated, for the first time, whether there are any sex differences in retrospective self-reported childhood maltreatment (CM) in Italian adult patients with major depressive disorder (MDD) or bipolar disorder (BD). Furthermore, the potential impacts of patients’ age on the CM self-report was investigated. Methods. This retrospective, cross-sectional study used the data documented in the electronic medical records of patients who were hospitalized for a 4-week psychiatric rehabilitation program. The CM was assessed using the 28-item Childhood Trauma Questionnaire (CTQ), which evaluates emotional, physical, and sexual abuse, as well as emotional and physical neglect. The linear and logistic regression models were used (α = 0.01). Results. Three hundred thirty five patients with MDD (255 women and 80 men) and 168 with BD (97 women and 71 men) were included. In both samples, considerable CM rates were identified, but no statistically significant sex differences were detected in the variety of CTQ-based CM aspects. There was a significant association, with no sex differences, between the increasing patients’ age and a decreasing burden of CM. Conclusion. Both women and men with MDD or BD experienced a similar and considerable CM burden. Our findings support the routine CM assessment in psychiatric clinical practice.

In order to reconstruct the origin and pathways of variola virus (VARV) dispersion, we analyzed 47 VARV isolates available in public databases and their SNPs. The mean substitution rate of the whole genomes was 9.41x10-6 (95%HPD:8.5-11.3x10-6) substitutions/site/year. The time of the tree root was estimated to be a mean 68 years (95%HPD:60.5–75.9). The phylogeographical analysis showed that the Far East and India were the most probable locations of the tree root and of the inner nodes, respectively, whereas for the outer nodes it corresponded to the sampling locations. The Bayesian Skyline plot showed that the effective number of infections started to grow exponentially in 1915-1920, peaked in the 1940s, and then decreased to zero. Our results suggests that the VARV major strains circulating between 1940s-1970s probably shared a common ancestor originated in the Far East; subsequently moved to India, which became the center of its dispersion to eastern and southern Africa, and then to central Africa and the Middle East, probably following the movements of people between south-eastern Asia and the other places with a common colonial history. These findings may help to explain the controversial reconstructions of the history of VARV obtained using long- and short- term calibrations.

Objective: A previous study showed that schizophrenia is accompanied by lowered levels of trace/metal elements including cesium. There are no data whether changes in cesium, rubidium and rhenium are associated with activated immune-inflammatory pathways, cognitive impairments, and the symptomatology of schizophrenia. Methods: This study measured cesium, rubidium, and rhenium, cognitive impairments (using the Brief Assessment of Cognition in Schizophrenia) and the cytokines/chemokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and CCL11 (eotaxin) in 120 schizophrenia patients and 54 healthy controls. Severity of illness was assessed using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the Fibromyalgia and Chronic Fatigue Syndrome Rating (FF) Scale and the Hamilton Depression Rating Scale (HAM-D). Results: Serum cesium was significantly lower in schizophrenia patients as compared with controls. Serum cesium was significantly and inversely associated with CCL11 and TNF-α, but not IL-1β. Moreover, there were significant inverse associations between serum cesium levels and the BPRS, FF, HAM-D and SANS scores and positive correlations between cesium and neurocognitive probe results including the Tower of London, Symbol Coding, Controlled Word Association, Category Instances, Digit Sequencing Task, and List Learning tests. Conclusion: The results suggest that lowered serum cesium levels may play a role in the pathophysiology of SCZ, specific symptom domains including negative, depressive and fatigue symptoms, neurocognitive impairments (spatial working, episodic and semantic memory and executive functions) and neuro-immune pathways as well.

Although, staging models gained momentum to stage define affective disorders, no attempts were made to construct mathematical staging models using clinical and biomarker data in patients with major depression and bipolar disorder.The aims of this study were to use clinical and biomarker data to construct statistically-derived staging models, which are associated with early lifetime traumata (ELTs), affective phenomenology and biomarkers.In the current study, 172 subjects participated, 105 with affective disorders (both bipolar and unipolar) and 67 controls. Staging scores were computed by extracting latent vectors (LVs) from clinical data including ELTs, recurring flare ups and suicidal behaviors, outcome data such as disabilities and health-related quality of life (HR-QoL), and paraoxonase (PON)1 actvities and nitro-oxidative stress biomarkers.Recurrence of episodes and suicidal behaviors could reliably be combined into a LV with adequate composite reliability (the “recurrence LV”), which was associated with female sex, the combined effects of multiple ELTs, disabilities, HR-QoL and impairments in cognitive tests. All those factors could be combined into a reliable “ELT-staging LV” which was significantly associated with nitro-oxidative stress biomarkers. A reliable LV could be extracted from serum PON1 activities, recurrent flare ups, disabilities and HR-QoL.Our ELT-staging index scores the severity of a relevant affective dimension, shared by both major depression and bipolar disorder, namely the trajectory from ELTs, a relapsing course and suicidal behaviors to progressive disabilities. Patients were classified into three stages, namely an early stage; a relapse-regression stage; and a suicidal-regression stage. Lowered lipid-associated antioxidant defenses may be a drug target to prevent the transition from the early to the later regression stages.

Patients with Peripheral-artery-disease (PAD) are prone to risks of major-adverse-limb-events (MALE), and major-adverse-cardiovascular-events (MACE). CHA2DS2-VASc is a prognostic score for Atrial fibrillation stroke risk, however, no study exists that evaluated its predictability for MALE and MACE in PAD patients. In this study, patients with PAD were stratified into four risk groups based on CHA2DS2-VASc score. Cox-proportional hazards models,10-fold cross-validation and Receiver operating characteristic (ROC) analyses were utilized to evaluate the predictability of CHA2DS2-VASc for predicting MALE, MACE, and MALE+MACE. Kaplan-Meier analysis estimated the survival-probability of risk-groups. CHA2DS2-VASc was found to be a significant predictor of MACE (hazard ratio (95% confidence interval; P) = 3.47 (0.99 - 12.18; 0.052), 4.12 (1.19 - 14.14; 0.024), and 5.06 (1.48 – 17.28; 0.009), for moderate-, high- and very-high-risk groups, respectively, while for MALE and MALE+MACE significance was achieved only for high-risk group. MACE demonstrated AUC > 0.8, good-discrimination (c-index > 0.8) and good-calibration. However, MALE and MALE+MACE models failed to achieve good performances. Based on all findings, CHA2DS2-VASc could potentially serve as a risk stratification score for predicting MACE in patients with PAD but failed to qualify as a good predictor for MALE.

Neurological disorders such as Autism Spectrum Disorder (ASD), Schizophrenia (SCH), Bipolar Disorder (BD), and Major Depressive Disorder (MDD) affect millions of people worldwide, yet their molecular mechanisms remain poorly understood. This study applied the Comparative Analysis of Shapley values (CASh) to transcriptomic data from nine datasets associated with these complex disorders, demonstrating its effectiveness in identifying differentially expressed genes (DEGs). CASh, which integrates Game Theory with Bootstrap resampling, offers a robust alternative to traditional statistical methods by evaluating the contribution of each gene within the broader context of the entire dataset. Unlike conventional approaches, CASh is highly effective at detecting subtle but meaningful molecular patterns that are often missed. These findings highlight the potential of CASh to enhance the precision of transcriptomic analysis, providing deeper insights into the molecular signatures of these disorders and establishing a solid basis for improving diagnostic techniques and developing more targeted therapeutic interventions.

Immunofluorescent methods in vitro have been widely used to characterize the distribution and extent of colocalization of molecules located in various intracellular compartments. These are key processes to better understand the role of those molecules in physiological and pathological conditions.In the brain, interactions of astrocytes with neurons are fundamental for the establishment and proper functioning of neuronal circuits. Among these, the phagocytosis of synapses that need to be removed is a process known as synaptic pruning. When this process is dysregulated, it might lead to the development of several brain disorders. Here, we describe the adaptation of a method to characterize the astrocyte-mediated synaptic phagocytosis and evaluate astrocytic (dys)functions in healthy cells and cells derived from an animal model of major depressive disorder (MDD).

Background: Many clinical conditions are affected by meteorological factors and climate changes. Psychiatric disorders are large contributors to the global disease burden, but the literature on the impact of climate changes on mental health is limited. The aim of this study is to investigate the correlation between rising temperatures and admissions for acute exacerbations of psychiatric disorders. Methods: Data were collected for summer months of years 2013 to 2022. Mean monthly tempera-tures were obtained from the meteorological station of the Department of Physics of the Universi-ty of Turin. Data on patients admitted to the acute psychiatric unit of San Luigi Gonzaga Univer-sity Hospital (Turin, Italy) were extracted from the hospital registry. Linear regression analyses were used to investigate the correlation between temperature and number of admissions. Results: A total of 1600 admissions to our psychiatric ward were recorded. Mean monthly temper-ature and monthly number of admissions were directly correlated (P = 0.0020). The correlation between temperature and admissions was significant for the subgroup of admissions due to Bipo-lar Disorders (BD) (P=0.0011), but not for Schizophrenia (P=0.6070) (SCZ) or Major Depressive Disorder (MDD) (P=0.0588). Conclusions: These results confirm the impact of meteorological factors on mental disorders, and in particular on the course of BD. This provides new insights into etiopathological mechanisms and can contribute to improved follow up and relapse prevention.

Under the development mode of deep blending of emerging technologies, major projects are important for enhancing China's comprehensive national strength and independent innovation capability. Based on the social benefits of major projects, and considering the influence of reputation factors, an evolutionary game model composed of a general contractor and subcontractor of major projects is established. This paper studies the influence of various factors including the income distribution coefficient of collaborative innovation, and MATLAB simulation software is analyzed the influence of factors on an evolutionary path. The results show that a reasonable income distribution coefficient can promote the game behavior of both parties to the direction of active collaborative innovation; The reduction of innovation cost and the improvement of spillover technology absorption capacity can make innovation subjects tend to choose active collaborative innovation strategies. In addition, reputation loss above a specific threshold can effectively inhibit free-riding behavior and encourage innovation subjects to choose active collaborative innovation strategies. The research results provide reference for promoting major projects' technology innovation.

The population parameters of the ecologically important mud shrimp Upogebia major were analyzed from 2012 to 2015 in tidal flats in Seonjaedo and Jugyo on the West coast of Korea. The shrimp density averaged 265/m2 in Seonjaedo and 118/m2 in Jugyo. The sex ratio varied monthly, often male-biased, but by size, males were significantly dominant, with a carapace length (CL) over 30 mm. Although the shrimp settled almost annually, only a single size-group was observed from 2012 to 2014. The recruitment in Jugyo in 2014 was notably successful, resulting in two cohorts persisting until 2015. Many shrimp were parasitized at varying local rates: 6.0% in Seonjaedo and 37.1% in Jugyo. The growth curves revealed that the shrimp grew annually after settlement, reaching CLs of 11.90, 18.24, and 23.02 mm in Seonjaedo and 13.73, 20.86, and 25.82 mm in Jugyo. Annual mortality was 77.2% in Seonjaedo and 67.4% in Jugyo. The estimated lifespan (tmax) was 10 years in Seonjaedo and 8 years in Jugyo, whereas the 2010 cohort in Jugyo largely disappeared in 5 years. Ovigerous females appeared from November to June and benthic juveniles between June and September. The shrimp’s growth was slower relative to other East Asian populations, likely due to colder sea water temperatures and altered food conditions from a higher shrimp density.

Assuming that climate warming in the WSL will lead to a northward shift of the forest and permafrost boundaries, a “substituting space for time” approach predicts an increase in concentration of DIC and labile major and trace elements and a decrease of the transport of DOC and low soluble trace metals in the form of colloids in the main stem of the Ob River. However, an unknown factor is the change in hydrochemistry of the largest southern tributary, the Irtysh River, which is impacted by permafrost-free steppe and forest-steppe zone. Overall, seasonally-resolved transect studies of large riverine systems of western Siberia are needed to assess the hydrochemical response of this environmentally-important territory to on-going climate change.

The rapid increase in population along with the economic activities led to rapid depletion of natural resources. Land use studies help us analyze the impacts of urban development on environment. Given the political upheavals in Afghanistan, this study aims to analyze how urban development evolved from 1978 to 2018 in six major cities- Kabul, Kandahar, Kunduz, Herat, Mazar-e Sharif and Jalalabad- in Afghanistan using Landsat Satellite Images. This study is based on quantitative approach. ArcGIS 9.4 software was used to synchronize the Landsat Satellite Images within the area of study. The results of the study show that the Annual rate of urban land expansion in Afghanistan was the lowest (average 1.07 square kilometers per year) during the military presence of Soviet Union in Afghanistan while it was the highest (3.35 square kilometers per year) from 2001 to 2018 due to the military presence of US-led NATO forces, relative security and rapid economic activities in Afghanistan. The authors believe that this study could be further explored if other inter-connected factors, e.g., the role of culture, literacy, immigration etc., are incorporated into the study of urban development processes in Afghanistan.

Planetary waves in the mesosphere are studied using observational data and models to establish their origin, as there are indications of their generation independently of waves in the stratosphere. The quantitative relationships between zonal wave numbers m = 1 (wave 1) and m = 2 (wave 2) were studied with a focus on the mid-latitude mesosphere at 50N latitude. Aura Microwave Limb Sounder measurements were used to estimate wave amplitudes in geopotential height during the 2020–2021 winter major sudden stratospheric warming. The moving correlation between the wave amplitudes shows that, in comparison with the anticorrelation in the stratosphere, wave 2 positively correlates with wave 1 and propagates ahead of it in the mesosphere. A positive correlation r = 0.5–0.6, statistically significant at the 95% confidence level, is observed at 1–5-day time lag and in the 75–91 km altitude range, which is the upper mesosphere–mesopause region. Wavelet analysis shows a clear 8-day period in waves 1 and 2 in the mesosphere at 0.01 hPa (80 km), while in the stratosphere–lower mesosphere the period is twice as long at 16-days; this is statistically significant only in wave 2. Possible sources of mesospheric planetary waves are discussed.

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

There are frequently interactions between active folds and major rivers (mean annual water discharges > 70 m³s^-1). The major river may incise across the fold, to produce a water gap across the fold, or a bevelling (or lateral planation) of the top of the fold. Alternatively, the major river may be defeated to produce a diversion of the river around the fold, with wind gaps forming across the fold in some cases, or ponding of the river behind the fold. Why a river incises or diverts is often unclear, though influential characteristics and processes have been identified. A new scheme for investigating fold-river interactions has been devised, involving a short description of the major river, climate, and structural geology, and 13 characteristics of river and fold geomorphology: 1) Channel width at location of fold axis, w, 2) Channel-belt width at location of fold axis, cbw, 3) Floodplain width at location of fold axis, fpw, 4) Channel sinuosity, Sc, 5) Braiding index, BI, 6) General river course direction, RCD, 7) Distance from fold core to location of river crossing, C-RC, 8) Distance from fold core to river basin margin, C-BM, 9) Width of geological structure at location of river crossing, Wgs, 10) Estimate of erosion resistance of surface sediments/rocks and deeper sediments/rocks in fold, ERs, ERd, 11) Channel water surface slope at location of fold axis, s, 12) Average channel migration rate, Rm, 13) Estimate of fold total uplift rate, TUR. The first 10 geomorphological characteristics should be readily determinable for nearly all major rivers using widely available satellite imagery and fine scale geological maps. The last 3 characteristics should be determinable for most major rivers where other data sources are available. This study demonstrates the methodology of this scheme, using the example of the major rivers Karun and Dez interacting with active folds in the foreland basin tectonic setting of lowland south-west Iran. For the rivers Karun and Dez (mean annual water discharges 575 m³s^-1 and 230 m³s^-1, respectively), it was found that geomorphological characteristics Nos. 2, 3 and 7 had statistically significant differences (p-value ≤ 0.05) between the categories of river incision across a fold and river diversion around a fold. For river incision, at the fold axis, channel-belt width was always < 2.7 km, and floodplain width was generally (80 % of cases) < 5.7 km; whereas for river diversion, at the projection of the fold axis, these two characteristics had a wide range of values. For river incision, the distance from the fold core to the location where the river channel crossed the fold axis, was generally (80 % of cases) ≤ 8.5 km; whereas for river diversion, this distance was always > 22 km. Since it is highly likely that different characteristics will be important for other major rivers interacting with other folds, it is recommended that this scheme is now used to investigate a variety of major rivers from across the globe. By comparing the same parameters for different major rivers, a better understanding of fold-river interactions should be achieved.

According to their nutritional value, their ability to adapt to the various environmental conditions, and their versatility, cereals are among the most cultivated plants in the world. However, the ongoing climate changes subject crops to important environmental stress that for some varieties leads to high production losses. Therefore, selection of species and varieties more versatile and adaptable to different environmental conditions can be important. However, the characteristics of some cereals are not completely known, this is a priority before to improve their cultivation. The aim of this study is to characterize select species of potential suitable for local environmental conditions, nutritional value.

Background: The major histocompatibility complex (MHC) plays a key role in the adaptive immune response to pathogens due to its extraordinary polymorphism. However, the spatial patterns of MHC variation in the striped hamster remain unclear, particularly regarding the relative contribution of balancing selection in shaping MHC population and diversity compared to neutral forces. Methods: In this study, we investigated the immunogenic variation of the striped hamster in four wild populations in Inner Mongolia, which experience heterogeneous parasitic stress. Our goal was to identify local adaptation by comparing the genetic structure at MHC with that at seven microsatellite loci, taking into account neutral processes. Results: We observed significant variation in parasite pressure among sites, with parasite burden showing a correlation with temperature and precipitation. Molecular analysis revealed a similar co-structure between MHC and microsatellite loci. We observed lower genetic differentiation at MHC loci compared to microsatellite loci, and no correlation was found between the two. Conclusions: Overall, these results suggest a complex interplay between neutral evolutionary forces and balancing selection in shaping the spatial patterns of MHC variation. Local adaptation was not detected at a small scale but may be applicable at a larger scale.

The Asian weaver ant Oecophylla smaragdina is a natural enemy (predator) used as a biological control agent in Australia and several Southeast Asian nations against the most destructive and economically important oriental fruit fly Bactrocera dorsalis. For biological control of the invasive bagworm species Metisa plana in oil palm plantations, the composition of the colony's social structure was investigated to ensure its efficacy. On two colonies, all castes were examined stereo microscopically after nest collection and dissection. The head's width, head, thorax, abdomen, and body lengths of workers were evaluated during the morphology analysis. All colonies with more than a thousand eggs comprise of a founding egg-laying queen, reproductive winged green and newly emerged yellow queens, as well as adult drone males and workers. Future queens, males, and workers' pupae and larvae comprised immature individuals. It is the first study to characterise one caste of minor workers, two previously unidentified castes of intermediate workers, and two castes of major workers. The lengths of the body and abdomen are proposed as differentiating factors for workers. The discovery of a polymorphic size frequency distribution model contrasts with the consistently reported existence of archetypical bimodal systems in ants. Intermediate workers foraging outside the nest revealed reconnaissance and aggressive behaviours that aided major workers in their daily tasks. Due to their short lifespan and segregated nests, it is difficult to successfully sample adult males in wide plantations. An entire year's worth of reproductive individuals are produced by stable, three-year-old colonies, with a decrease in population size correlated with a significant decline in rainfall interception.

In order to understand the evolution of multicellularity, we must understand how and why selection favors the first steps in this process: the evolution of simple multicellular groups. Multicellularity has evolved many times in independent lineages with fundamentally different ecologies, yet no work has yet systematically examined these diverse selective drivers. Here we review recent developments in systematics, comparative biology, paleontology, synthetic biology, theory, and experimental evolution, highlighting ten selective drivers of simple multicellularity. Our survey highlights the many ecological opportunities available for simple multicellularity, and stresses the need for additional work examining how these first steps impact the subsequent evolution of complex multicellularity.

Transport of carbon, major and trace element by rivers in permafrost-affected regions is one of the key factor of circumpolar aquatic ecosystem response to climate warming and permafrost thaw. While seasonal and annual export fluxes (yields) of carbon (C) and inorganic solutes are fairly well known for all large Arctic rivers, spatial variations in elementary concentration along the river length and among its tributaries remain poorly understood. Moreover, the landscape factors controlling riverine element concentration in permafrost-affected regions are still poorly constrained. This is especially true for the largest river of Eastern Siberia, the Lena River, which drains through continuous permafrost zones with highly variable lithology and vegetation. Here we present the results of C, major and trace element measurements over a 2600-km transect of the Lena River main stem (upper and middle reaches) including its 30 tributaries, conducted at the peak of the spring flood. There were two main group of solutes in the main stem depending on their spatial pattern: i) elements that decreased their concentrations downstream, from SW to NE (Cl, SO4, DIC, Li, B, Na, Mg, K, Ca, As, Sr, Mo, Sb, Ba and U), which probably reflected a decrease in the proportion of carbonate rocks in the watershed and the degree of groundwater feeding, and ii) elements that increased their concentrations downstream (Al, Ti, Cr, Fe, Ga, Rb, Y, Zr, Nb, Cs, REEs, Hf and Th), which was tentatively linked to an increase in organic C stock in soils, larch forest coverage and enhanced mobilization of lithogenic elements from silicate soil minerals. Based on landscape parameters of Lena tributaries, we tested the impact of major environmental factors on major and trace element spatial pattern. Among all the variables, the proportion of sporadic permafrost on the watershed strongly controlled concentrations of soluble highly mobile elements (Cl, B, DIC, Li, Na, K, Mg, Ca, Sr, Mo, As and U). Another important factor of element concentration control in the Lena River tributaries was the coverage of watershed by light (B, Cl, Na, K, U) and deciduous (Fe, Ni, Zn, Ge, Rb, Zr, La, Th) needle-leaf forest (pine and larch). The latter, however, could also reflect the DOC-enhanced transport of low-soluble trace elements in the NW part of the basin. This part of the basin is dominated by silicate rocks and continuous permafrost, as compared to carbonate rock-dominated and groundwater-affected SW part of the Lena River basin. Overall, the impact of rock lithology and permafrost on major and trace solutes of the Lena River basin during the peak of spring flood was mostly detected at the scale of the main stem. Such an impact for tributaries was much less pronounced, because of the dominance of surface flow and lower hydrological connectivity with deep groundwater in the latter. Future changes in the river water chemistry linked to climate warming and permafrost thaw at the scale of the whole river basin are likely to be linked to changes in spatial pattern of dominant vegetation, rather than to the permafrost regime. We argue that comparable studies of large, permafrost-impacted rivers during most contrasting seasons, including winter baseflow, should allow efficient prediction of future changes in riverine ‘inorganic’ hydrochemistry induced by permafrost thaw.

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

Current diagnoses of mood disorders are not cross validated. The aim of the current paper is to explain how machine learning techniques can be used to a) construct a model which ensembles risk/resilience (R/R), adverse outcome pathways (AOPs), staging, and the phenome of mood disorders, and b) disclose new classes based on these feature sets. This study was conducted using data of 67 healthy controls and 105 mood disordered patients. The R/R ratio, assessed as a combination of the paraoxonase 1 (PON1) gene, PON1 enzymatic activity, and early life time trauma (ELT), predicted the high-density lipoprotein cholesterol – paraoxonase 1 complex (HDL-PON1), reactive oxygen and nitrogen species (RONS), nitro-oxidative stress toxicity (NOSTOX), staging (number of depression and hypomanic episodes and suicidal attempts), and phenome (the Hamilton Depression and Anxiety scores and the Clinical Global Impression; current suicidal ideation; quality of life and disability measurements) scores. Partial Least Squares pathway analysis showed that 44.2% of the variance in the phenome was explained by ELT, RONS/NOSTOX, and staging scores. Cluster analysis conducted on all those feature sets discovered two distinct patient clusters, namely 69.5% of the patients were allocated to a class with high R/R, RONS/NOSTOX, staging, and phenome scores, and 30.5% to a class with increased staging and phenome scores. This classification cut across the bipolar (BP1/BP2) and major depression disorder classification and was more distinctive than the latter classifications. We constructed a nomothetic network model which reunited all features of mood disorders into a mechanistically transdiagnostic model.

This work evaluates the surface water quality in terms of physico-chemical parameters of the Brahmani River, Odisha using statistical analysis involving the calculation of correlation coefficient and regression equation. Besides this, the work also highlights and draws attention towards the “Water Quality Index” in a simplified format which may be used at large and could represent the reliable picture of water quality. Surface water quality data is taken from OSPCB of various location i.e. Panposh D/S, Rourkela D/S, Rengali, Talcher U/S, Kamalanga D/S, Bhuban, Pattamundai and was assessed for summer, monsoon, winter for the years 2011, 2012, 2013, 2014 and 2015. Average of values, minimum of values and maximum of values of water quality parameters were obtained seasonally over the above mentioned years. Besides this, the standard deviation for the water quality parameters was also obtained for water quality parameters namely pH, Temperature, DO, TDS, Alkalinity, EC, Na+, Ca2+, Mg2+, K+, F-, Cl-, NO3-, SO42- and PO42-. Seasonal changes in various physical and chemical parameters were analysed.The values obtained were compared with the guideline values for drinking water by Bureau of Indian Standard (BIS). A systematic correlation and regression study is carried out for three seasons, showed linear relationship among different water quality parameters. This provides an easy and rapid method of monitoring water quality. Highly significant (0.8< r <1.0), moderately significant (0.6< r <0.8) and significant (0.5< r <0.6) correlations between the parameters have been worked out. High correlation coefficient has been observed between TDS,EC-Na+, Ca2+, Cl-, SO42- ; Na+- Cl-. From the collected quantities, certain parameters were selected to derive WQI for the variations in water quality of each designated sampling site. WQI of Brahmani River ranged from 36.7 to 44.1 which falls in the range of good quality of water.Panposh D/S and Rourkela D/S showed poor water quality in summer and winter season. It is shown that WQI may be a useful tool for assessing water quality and predicting trend of variation in water quality at differentlocations in the Brahmani River.

Major Depression Disorder (MDD) is accompanied by an immune response characterized by increased levels of pro-inflammatory and immune-regulatory cytokines and cytokine-induced stimulation of indoleamine-2,3-dioxygenase (IDO). There is also some evidence that anti-inflammatory drugs may have a clinical efficacy in MDD.The aim of this study is to examine the clinical effects of an eight-week combinatorial treatment of ketoprofen (a nonsteroidal anti-inflammatory drug) combined or not with sertraline, on serum levels of IDO, interferon (IFN)-γ, interleukin (IL)-4 and transforming growth factor (TGF)-β1 in association with changes in the Beck-Depression Inventory-II (BDI-II). The study included 140 MDD patients and 40 normal controls. The pre-treatment serum levels of IDO, IFN-γ, TGF-β1 and IL-4 were significantly higher in MDD patients compared with the control group. Treatment with sertraline with or without ketoprofen significantly reduced the increased baseline production of all 4 biomarkers to levels which were similar as those of normal controls. Ketoprofen add-on had a significantly greater effect on IDO and BDI-II as compared with placebo. The reductions in IDO, IL-4 and TGF-β1 during treatment were significantly associated with those in the BDI-II.In conclusion, the clinical efficacy of both sertraline + ketoprofen may be ascribed at least in part to attenuated IDO levels and immune-inflammatory responses in MDD. Moreover, add-on treatment with ketoprofen may augment the efficacy of sertraline by attenuating IDO. However, these treatments may also significantly reduce the more beneficial properties of T helper-2 and T regulatory (Treg) immune subsets. Future research should develop immune treatments that target the immune-inflammatory response in MDD, while enhancing the compensatory immune-regulatory system (CIRS).

The paper presents the results of the theoretical and practical research on developing the infrastructure for assessment of overall risk (explosion / occupational / terrorist attack) associated with unwanted events such as major accidents that can occur at explosive storehouses for civilian use. The scientific research outlined in this article was carried out within the Nucleu Project PN 16 43 02 15 - “Research on increasing safety levels at technical facilities for storage of explosives for civil use”.

The growing emphasis on carbon considerations and the pursuit of net-zero emissions have brought about a paradigm shift in project management. To successfully facilitate the transition towards net-zero emissions, major projects must not only adapt existing systems but also embed carbon targets into their core strategies. While several studies have investigated carbon integration during the procurement phase, limited attention has been given to the construction project manager (PM) perspective. This study aims to bridge this research gap by exploring the challenges and barriers faced by construction PMs when integrating carbon targets and metrics into major Architectural, Engineering and Construction (AEC) projects, as well as evaluating the readiness of project teams to deliver on these. The study deployed a qualitative exploratory research design, where semi-structured interviews were conducted with 17 AEC project professionals actively engaged in the planning and execution of major projects in the UK. Thematic analysis of the data revealed a range of challenges and barriers faced by PM teams delivering these projects. The research findings contribute to the field of construction PM by enhancing the understanding of the challenges faced by project managers and project teams when integrating carbon requirements into the delivery of major projects. It uncovers a series of challenges and prevalent practices in major projects that have the potential to impede progress towards the net-zero transition.

Based on functional magnetic resonance imaging and multilayer dynamic network model, the quantified temporal stability of brain network has shown potentials in predicting altered brain functions. The present review focuses on summarizing current knowledge on the commonly-used measures of brain network’s temporal stability and the clinical research progress on them. There are a variety of widely used measures of temporal stability such as the variance/standard deviation of dynamic functional connectivity strengths, the temporal variability, the flexibility (switching rate), and the temporal clustering coefficient, while there is no consensus to date that which measure is the best. The temporal stability of human brain networks may be associated with several factors such as sex, age, cognitive functions, head motion, and data preprocessing/analyzing strategies, which should be considered in the clinical studies. Multiple common psychiatric diseases such as schizophrenia, major depressive disorder, and bipolar disorder have been found to be related to altered temporal stability, especially during the resting state; generally, both excessively decreased and increased temporal stabilities were thought to reflect disease-related brain dysfunctions. However, the measures of temporal stability are still far from applications in clinical diagnoses for neuropsychiatric diseases partly because of the divergent results, and further studies are warranted.

In this work, the effect of reaction time and biomass-to-H2O ratio on the structural evolution of hydro-char and kinetic of by hydrothermal processing of corn Stover with hot compressed H2O, have been systematically investigated. The experiments were carried out at 250 °C, heating rate of 2.0 °C/min, biomass-to-H2O ratio of 1:10, and reaction times of 60, 120, and 240 minutes, and at 250 °C, 240 minutes, heating rate of 2.0 °C/min, and biomass-to-H2O water ratio of 1:10, 1:15, and 1:20, using a pilot scale stirred tank reactor of 5 gallon. The characterization of solid phase products performed by thermo-gravimetric analysis, scanning electron microscope, energy dispersive X-ray spectroscopy, X-ray diffraction, and elemental analysis (C, N, H, S). The physical-chemistry properties of solid phase analyzed in terms of dry matter (DM), total organic content (TOC), and ash. The yields of solid and gas phases decrease linearly with decreasing biomass-to-H2O ratio, while that of liquid phases increases linearly. For constant biomass-to-H2O ratio, the yields of solid, liquid, and gaseous reaction products varied between 52.97 and 35.82% (wt.), 44.84 and 54.59% (wt.), and 2.19 and 9.58% (wt.), respectively. The yield of solids decreases exponentially by decreasing the reaction time, while the yields of liquid and gas phases increase exponentially. For constant biomass-to-H2O ratio, TG/DTG curves shows that reaction time of 60 minutes was not enough to carbonize corn Stover. For constant reaction time, TG/DTG curves shows that increasing the H2O-to-biomass ratio worse the carbonization of corn Stover. For constant biomass-to-H2O ratio, the SEM images show the main morphological structure of the corn Stover remains practically unchanged, while for constant reaction time, SEM images show that plant microstructure retains part of its original morphology, demonstrating that a decrease on biomass-to-H2O ratio worse the carbonization of corn Stover. For constant biomass-to-H2O ratio, the EDX analysis shows that the carbon content in hydro-char increases with reaction time, while for constant reaction time, the carbon content decreases with increasing biomass-to-H2O ratio. The kinetic of corn Stover degradation was correlated with a pseudo-first order exponential model, exhibiting a root-mean-square error (r2) of 1.000, demonstrating that degradation kinetics of corn Stover with hot compressed H2O, expressed as hydro-char formation, is well described by an exponential decay kinetics.

The Asian longhorned beetle (ALB), Anoplophora glabripennis is a forestry pest found worldwide. ALB causes serious harm because of the lack of natural enemies in the invaded areas. Dastarcus helophoroides and Dendrocopos major are important natural enemies of ALB. MaxEnt was used to simulate the distribution of D. helophoroides and D. major in China and Xinjiang, and their suitable areas were superimposed to evaluate the pest control ability of D. helophoroides and D. major. The results showed that, with climate change, the suitable areas of D. helophoroides and D. major migrated northward; the centroid shift of ALB was greater than that of D. helophoroides and D. major, which would lead to fewer natural enemies encountered by ALB during migration, reduce the control ability of natural enemies, and increase the risk of disastrous outbreaks in the invaded areas. We found that the damage caused by ALB was not serious in the areas with natural enemies and very serious in the areas without natural enemies. We suggest that natural enemies should be included in the model used for predicting suitable areas for invasive pests, as this is more conducive to assessing the risks of invasive organisms to the local ecological environment.

The diversification of life-histories is mediated by cooperation, innovations of biological information, modularity, and heterochrony in developmental processes. These processes are defined, contextualized, and exemplified, studying the evolution of coloniality (i.e. life-history involving modularization of the multicellular individual) in the family of benthic tunicates Styelidae. This study proposes that in these colonial tunicates there is an inter-generational division of labor, where one generation is feeding, a second is developing by morphogenetic processes, and a third is aging by programmed cell death and phagocytosis. The communication system developed in these colonies is mediated, by changes in proportion, location, and gene expression of specialized blood cells. Colonial life-history in animals is related to the reduction of individual size; development of extra-corporeal tissues to interconnect zooids; the inter-generational division of labor; and the reduction of zooid’s individuality. Processes analogous with the widely accepted major evolutionary transitions (METs), suggesting that coloniality could be studied as a MET. The understanding of colonial life-histories could provide information about key mechanisms for life diversification.

The disruption of brain energy metabolism, leading to alterations in synaptic signaling, neural circuitry, and neuroplasticity, has been implicated in severe mental illnesses such as schizophrenia, bipolar disorder, and major depressive disorder. The therapeutic potential of ketogenic interventions in these disorders suggests a link between metabolic disturbances and disease pathology; however, the precise mechanisms underlying these metabolic disturbances and the therapeutic effects of metabolic ketogenic therapy remain poorly understood. In this study, we conducted an in silico analysis of transcriptomic data to investigate perturbations in metabolic pathways in the brain across severe mental illnesses via gene expression profiling. We also examined dysregulation of the same pathways in rodent or cell culture models of ketosis, comparing these expression profiles to those observed in the disease states. Our analysis revealed significant perturbations across all metabolic pathways, with the greatest perturbations in glycolysis, the tricarboxylic acid (TCA) cycle, and the electron transport chain (ETC) across all three disorders. Additionally, we observed some discordant gene expression patterns between disease states and ketogenic intervention studies, suggesting a potential role for ketone bodies in modulating pathogenic metabolic changes. Our findings highlight the importance of understanding metabolic dysregulation in severe mental illnesses and the potential therapeutic benefits of ketogenic interventions in restoring metabolic homeostasis. This study provides insights into the complex relationship between metabolism and neuropsychiatric disorders and lays the foundation for further experimental investigations aimed at appreciating the implications of the present transcriptomic findings as well as developing targeted therapeutic strategies.

The therapeutic applicability of mesenchymal stem cells (MSC) for a range of conditions has garnered increasing interest. This study aimed to evaluate the mean major adverse cardiac and cerebrovascular event (MACCE)-free period in a population of 2,504 patients (age, 54.09 ± 11.65 years) receiving MSC therapy (mean dose, 1.49 ± 0.75 billion cells) for various indications (over two-thirds [n=1,700, 67.89%] received MSC therapy as an anti-ageing therapy) and evaluate for potential risk factors for MACCE development in this cohort. In multivariate Cox proportional hazards regression analysis, age, but not sex and MSC dose, was significantly associated with MACCE risk (hazard ratio=1.127; 95% confidence interval=1.0418, 1.219; p=0.0029). The adverse event rate was 0.8%, and none of the reported adverse events were severe. In conclusion, our study showed that stem cell therapy was safe in a large cohort of individuals and was associated with a low rate of MACCE.

Astrocytes, the most abundant glial cells in the brain, are an integral part of the synaptic compartment and contribute to synaptic pruning, a key process for refining neural circuits during early postnatal development (PND). Dysregulations in this process are implicated in various neuropsychiatric disorders, including major depressive disorder (MDD). To investigate astrocyte functions in a physiologically relevant context, organotypic brain slice cultures (OBSCs) offer a powerful model, reproducing more closely in vivo conditions than traditional cell cultures and preserving complex brain architecture and interactions. Here, we present OBSCs as an ex vivo culturing method to provide a platform to explore astrocyte-mediated synaptic pruning dynamics in the rat prefrontal cortex (PFC) during PND. Our approach is based on assessing the role of MEGF10, a key protein involved in synaptic pruning, alongside the synaptic markers synaptophysin and PSD95, using Western blotting to analyse the expression levels of these markers in the cortex of developing rat pups. Additionally, we combine immunofluorescence staining with confocal imaging and IMARIS 9.8 software-assisted analysis to investigate the co-localization of the lysosomal marker LAMP1 with synaptic and astrocytic markers to evaluate the precise rate of synaptic engulfment. The methods presented here allow a deeper examination of an astrocyte-mediated synaptic remodelling in healthy and pathophysiological conditions.

Background: Non-surgical organ preservation protocols have known a large diffusion worldwide in the last decades. Their oncological and functional effectiveness in a real-world setting has been recently ques-tioned, also because of the high morbidity of salvage procedures. The aim of this study is to review the outcomes of post irradiation salvage total laryngectomy (STL) and reconstruction with pectoralis major flap. Methods: This retrospective observational study included 37 cases of STL in the period going from January 2015 to December 2021. Data for each patient were extracted from the hospital information system and reviewed. Results: The 3-year overall and disease specific survival are respectively 28% and 51%. All patients with recurrences died from the disease. Only 7 recurrences and 7 consequent deaths for cancer were rec-orded. The other 14 deaths derived from comorbidities, being diabetes the most significant predictive parameter for overall survival. Also low-er postoperative albumin levels were associated with a higher risk of death. Conclusions: Overall survival after STL and reconstruction with PMMF is low but most deaths are due to comorbidities and not to cancer progression or recurrence.

Keywords: underground engineering; numerical simulation; excavation length effect, major principal stress; displacement; damage initiation; CPU time

This study aimed to identify new drug molecules against Leishmania parasites, leishmaniasis's causal agent, using Pistacia atlantica leaves as source. The evaluation of the anti-leishmania potential against the promastigote form of Leishmania. infantum and Leishmania. major was performed. A new in silico study was accomplished using molecular docking, with Autodock vina program, to find the binding affinity of two important phytochemical compounds from this plant (Masticadienonic acid, 3-Methoxycarpachromene) towards the trypanothione reductase as target drugs, responsible for defence mechanism against oxidative stress and virulence of this parasites. Results: Several concentrations showed a significant decrease in cell viability (P<0.0001), with IC50 values of 0.3 mg/ mL for L. infantum and 0.12 mg/ mL L. major; The molecular docking confirms the significant relationship between Leishmania survival and the inhibition of this crucial enzyme. There were promising and new positive results on binding modes of selected ligands and the trypanothione reductase for the first time. Through this work, we propose 3-Methoxycarpachromene and Masticadienonic acid as anti Trypanosomatidae species drug.

Innovation is an essential key factor in the technology development history. Past research on innovation focused more on the innovation behavior of technology, but seldom described knowledge assets which also influence innovation behavior greatly. The effect of knowledge assets attribute and result on disruptive innovation is therefore regarded as the research topic in this study, where disruptive innovation is divided into outbound and inbound to combine combination-embeddednessandmajor business specificityof knowledge assets as the research model. Manufacturing enterprises in China are proceeded the questionnaire survey, and 173 valid copies are collected. The empirical analysis shows that combination-embeddedness of knowledge assets presents significantly positive effects on major business specificity and outbound innovationof an enterprise but reveals remarkably negative effects on inbound innovation. Enterprises are suggested to constantly accumulate knowledge assets with low major business specificity before disruptive innovation in order to reduce ineffective inbound innovation.

Exosomes, natural nanovesicles that contain a cargo of biologically active molecules such as lipids, proteins, and nucleic acids, are released from cells to the extracellular environment. They then act as autocrine, paracrine, or endocrine mediators of communication between cells by delivering their cargo into recipient cells and causing downstream effects. Exosomes are greatly enriched in miRNAs, which are small non-coding RNAs that act as cytoplasmic posttranscriptional repression agents, modulating the translation of mRNAs into proteins, as well as nuclear transcriptional gene activators. Neuronal exosomal miRNAs have important physiologic functions in the Central Nervous System (CNS), including cell-to-cell communication, synaptic plasticity, and neurogenesis, as well as modulating stress and inflammatory responses. Stress-induced changes of exosomal functions include effects on neurogenesis and neuroinflammation, which can lead to the appearance of various neuropsychiatric disorders, such as schizophrenia, major depression, bipolar disorder, and Alzheimer's and Huntington’s's diseases. The current knowledge regarding the roles of exosomes in the pathophysiology of common mental disorders is discussed in this review.

The planetary wave activity in the stratosphere–mesosphere during the Arctic major Sudden Stratospheric Warming (SSW) in February 2018 is discussed on the basis of the microwave radiometer (MWR) measurements of carbon monoxide (CO) above Kharkiv, Ukraine (50.0° N, 36.3° E) and the Aura Microwave Limb Sounder (MLS) measurements of CO, temperature and geopotential heights. From the MLS data, eastward and westward migrations of wave 1/wave 2 spectral components were differentiated, to which less attention was paid in previous studies. Abrupt changes in zonal wave spectra occur with the zonal wind reversal near 10 February 2018. Eastward wave 1 and wave 2, observed before the SSW onset, disappear during the SSW event, when westward wave 1 becomes dominant. Wavelet power spectra of mesospheric CO variations show statistically significant periods in a band of 20–30 days using both MWR and MLS data. Approximately 10-day periods appear only after the SSW onset. Since the propagation of upward planetary waves is limited in the easterly zonal flow in the stratosphere after the zonal wind reversal during SSW, forced planetary waves in the mid-latitude mesosphere may exist due to the instability of the zonal flow.

In solid cancer surgery, oxidative stress (OS) is of particular interest because both the malignancy itself and the surgical intervention are major contributors to the modulation of OS levels. This study aimed to investigate the effects of solid cancer surgery on OS levels. Because solid cancer is often accompanied by intense cell death, the study specifically focused on the pathway leading to uric acid formation, (i.e. adenosine deaminase (ADA) and xanthine oxidase (XO). Ische-mia-modified albumin (IMA), a recognized marker of oxidative stress, and plasma redox poten-tial (RP) were also measured. Thirty-six patients undergoing major solid cancer surgery (median age 68 years (58-76), 23 men and 13 women) and thirty controls (62 years (51-80)) were included. During the surgical procedure, serum ADA levels did not change significantly (10.4 International Units (IU) (6.9 – 13.7) vs. 8 IU (6 – 12); p = 0.47). In contrast, XO (IU), IMA (Arbitrary Units(AU)) and redox potential (mV) decreased significantly (22.5 IU (11 – 63) vs. 8.4 IU (5 – 27); p = 0.0041, 89 AU (69 – 105) vs. 74 AU (66 – 80); p = 0.01 and 98 mV (78 – 118) vs. 79 mV (65 – 101); p = 0.033). The correlation between XO and IMA or redox potential was positive (Spearman’s r = 0.32 ; p = 0.007, and r = 0.58; p < 0.001, respectively). XO was negatively correlated with ADA (r = -0.26; p = 0.03). Redox potential was positively correlated with IMA (r = 0.26; p = 0.04) and nega-tively correlated with ADA (r = -0.25 ;p = 0.04). We found that a major source of OS in solid cancer could be the result of an increase in xanthine oxidase activity and that the global effect of solid cancer surgery is a significant decrease in OS levels. We also found that ADA and XO were inversely correlate, suggesting the existence of a negative retrocontrol between the production of free radicals and the production of their sub-strate. Finally, our study highlights the potential value of XO inhibitors as adjuvant therapy in solid tumor surgery.

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

Background: Kidney transplantation is considered the first-choice therapy in ESRD patients. Despite recent improvements in terms of outcomes and graft survival in recipients, postoperative complications still concern health-care providers involved in the management of those patients. Particularly challenging are cardiovascular complications. Perioperative goal-directed fluid-therapy (PGDT) and hemodynamic optimization are widely used in high-risk surgical patients, and are associated with a significant reduction in postoperative complication rates and length of stay (LOS). The aim of this work is to compare the effects of perioperative goal-directed therapy (PGDT) with conventional fluid therapy (CFT), and to determine whether there are any differences in major postoperative complications rates and delayed graft function (DGF) outcomes. Methods: Prospective study with historical controls. Two groups, a PGDT- and a CFT- group were used: the stroke volume (SV) optimization protocol was applied in PGDT group throughout the procedure. Conventional fluid therapy with fluids titration at a central venous pressure (CVP) 8-12 mmHg and mean arterial pressure (MAP) >80mmHg was applied to the control-group. Postoperative data collection including vital signs, weight, urinary output, serum creatinine, blood urea nitrogen, serum potassium, and assessement of volemic status and the signs and symptoms of major postoperative complications occurred at 24h, 72h, 7 days and 30 days after transplantation. Results: Among the 66 patients enrolled, 33 were in each group and both groups had similar physical characteristics. Good fuctional recovery was evident in the 94% of patients. The statistical analysis has showed a difference in postoperative complications as follows: significant reduction of cardiovascular complications, DGF episodes (p<0.05) and surgical complications (p<0.01). There were no significant differences in pulmonary or other complication. Conclusions: PGDT and SV optimization effectively influenced the rate of major postoperative complications, reducing the overall morbidity and thus the mortality in patients receiving kidney transplantation.

Background: Systemic-to pulmonary collaterals (SPC) are common in congenital heart disease (CHD). Particularly in single ventricle anatomy and Fontan circulation, SPC can both complicate the postoperative course and lead to clinical deterioration in the long term. Treatment of SPC is controversial. The aim of our study was (1) to analyze retrospectively patients who underwent SPC embolization using Concerto™ Helix nylon-fibred microcoils (CHM) and (2) to describe the interventional technique. Methods: In this a single-center retrospective observational cohort study, we analyzed clinical and imaging data of all patients who underwent transcatheter embolization of SPC using CHM from January 2016 to December 2023. Results: In 38 consecutive patients (65.8 % male, median age 41 months, range 2 – 490), a total number of 141 CHM had been implanted into 64 SPC in 49 procedures. The majority were arterial SPC (n = 59/64) originating from the thoracic aorta or its branches; 5/64 were veno-venous SPC. Primary closure succeeded in all procedures. The CHM diameters ranged from 3 to 8 mm, with 5 mm being the most commonly used diameter. The mean coil / SPC ratio was 2.6 (range 1.3 – 5.3). CHM implantation was performed via 4 French sheaths. Both detachment and stable positioning was simple and safe. Neither non-target embolization nor coil migration occurred. One complication occurred with a minor vascular injury without clinical relevance. Conclusion: CHM are easy to use and appropriate for SPC embolization in all age groups, including infants, with a low complication rate. The coils are particularly suitable for closure of collaterals with small diameter or tortuous course.

Cemented rock fill (CRF) is commonly used in cut-and-fill stoping operation in underground mining. This allows for the maximum recovery of ore. Backfilling can improve stope stability in underground workings, and then improve ground stability of the whole mine site. Backfilling step scenarios vary from site to site. This paper presents the investigation of five different backfilling step scenarios and their impacts on the stability of stopes at four different mining levels. A comprehensive comparison of displacements, major principal stress and stress concentration factor (SCF) was conducted. The results show that different backfilling step scenarios have little influence on the final displacement for displacement in the stopes. Among the five backfilling scenarios, the major principal stress and stress concentration factor (SCF) have almost the same final results. The backfilling scenario SCN-1 is the optimum option among these five backfilling scenarios. It can immediately prevent the increase of the displacement and reduce the sidewall stress concentration, thereby preventing possible failures. Using the same strength of CRF can achieve same effects among the four mining levels. Applying backfilling CRF of the same strength at different mining depths is acceptable and feasible to improve the stability of the stopes.

Sous-vide is a process in which food is vacuum-sealed and prepared in a water bath, heated to a precise temperature, and circulated in a sous-vide machine. This cooking technique is increasingly common in homes and catering establishments due to its simplicity and affordability. However, manufacturers' and chefs' recommendations for low-temperature and long-term sous-vide cooking in media raise food safety concerns, particularly when preparing beef tenderloin. In this study, Salmonella enterica was found to be inactivated by heat and sage essential oil (EO) in beef tenderloin from musculus psoas major that had undergone sous-vide processing. To determine whether heat treatment was likely to increase the sous-vide efficiency, S. enterica and sage EO were mixed. After being vacuum-packed and injected with S. enterica, the samples were cooked sous-vide for the prescribed time at 50, 55, 60, or 65 °C. On days 1, 3, and 6, the amounts of S. enterica, total bacteria, and coliform bacteria were measured in both groups of sous vide beef tenderloin. Mass spectrometry was used to identify bacterial strains on various days and categories. Each day that was measured, the test group exposed to a temperature of 50 °C for 5 minutes had a higher number of all microbiota. The most isolated microorganisms from the control and treated groups were Pseudomonas fragi, and in the treated group also S. enterica. It has been shown that adding sage essence oil (EO) in combination with the sous-vide gastronomic method leads to the stabilization and safety of beef tenderloin.

Mood disorders are among the commonest mental disorders worldwide. Epidemiological and clinical evidence suggests that there are close links between infectious diseases and mood disorders, but the strength and direction of these association remain largely unknown. Theoretical models have attempted to explain this link based on evolutionary or immune-related factors, but these have not been empirically verified. The current study examined cross-sectional and longitudinal associations between the incidence of infectious diseases and mood disorders, while correcting for climate and economic factors, based on data from the Global Burden of Disease Studies, 1990-2019. It was found that major depressive disorder was positively associated with lower respiratory infections, while bipolar disorder was positively associated with upper respiratory infections and negatively associated with enteric and tropical infections, both cross-sectionally and over a period of thirty years. These results suggest that a complex, bidirectional relationship exists between these disorders. This relationship may be mediated through the immune system as well as through the gut-brain and lung-brain axes. Understanding the mechanisms that link these groups of disorders could lead to advances in the prevention and treatment of both.

Mitochondrial malfunction is supposed to be involved in the etiology and pathology of major depressive disorder (MDD). Here, we aimed to identify and characterize the molecular pathomechanisms related to mitochondrial disfunction in adult human skin fibroblasts which were derived from MDD patients or non-depressive control subjects. We found that MDD fibroblasts showed significantly impaired mitochondrial functioning: basal and maximal respiration, spare respiratory capacity, non-mitochondrial respiration and ATP-related oxygen consumption was lower. Moreover, MDD fibroblasts harbor lower ATP levels and showed hyperpolarized mitochondrial membrane potential. To investigate cellular resilience, we challenged both groups of fibroblasts with hormonal (dexamethasone) or metabolic (galactose) stress for one week, and found that both stressors increased oxygen consumption but lowered ATP content in MDD as well as in non-depressive control fibroblasts. Interestingly, the bioenergetic differences between fibroblasts from MDD or non-depressed subjects, which were observed under non-treated conditions, could not be detected after stress. Our findings support the hypothesis that altered mitochondrial function causes a bioenergetic imbalance which is associated with the molecular pathophysiology of MDD. The observed alterations in OXPHOS and other mitochondria-related properties represent a basis for further investigations of pathophysiological mechanisms and might open new ways to gain insight into antidepressant signaling pathways.

Snakebite envenoming represents a critical global health challenge, particularly prevalent in regions with limited access to healthcare resources, where venomous snakes pose a significant threat to human populations. Antivenom therapy which mainly rely on antibody production by immunization of large animals with venom components is labour intensive, time consuming and associated with various ethical concerns. Consequently, access to quality and affordable antivenom remains limited in many affected regions with high mortality associated with snakebites. In traditional medicine, many plant species have been ethnobotanically reported for their antivenom properties and are used to neutralize animal toxins. Ribosome-inactivating proteins (RIPs) are a diverse group of toxins found in various organisms, including plants that possess the ability to inhibit protein synthesis by irreversibly damaging the ribosomes. Even though considered to be harmful, the biological role of RIPs has gained increasing attention in recent years due to their potential therapeutic implications. With these insights, this review underscores the potential of RIPs as promising candidates for adjunct treatments in snakebite management strategies. In silico analysis by molecular docking of RIPs with major snake venom proteins resulted in effective binding and shows the interface residues involved in the interaction. This integrative approach enhances our understanding of snakebite pathophysiology, accelerating the development of novel next-generation antivenom therapies that are safer and more effective.

The dominant paradigm holds that spontaneous and therapeutically induced anti-tumor responses are mediated mainly by CD8 T cells and directed against tumor-specific antigens (TSAs). The presence of specific TSAs on cancer cells can only be proven by mass spectrometry analyses. Bioinformatic predictions and reverse immunology studies cannot provide this type of conclusive evidence. Most TSAs are coded by unmutated non-canonical transcripts that arise from cancer-specific epigenetic and splicing aberrations. When searching for TSAs, mass spectrometry analyses must therefore interrogate not only the canonical reading frame of annotated exome but all reading frames of the entire translatome. The majority of aberrantly expressed TSAs (aeTSAs) derive from unstable short-lived proteins that are good substrates for direct MHC I presentation but poor substrates for cross-presentation. This is an important caveat because cancer cells are poor antigen-presenting cells and the immune system therefore depends on cross-presentation by dendritic cells (DCs) to detect the presence of TSAs. We therefore postulate that, in the untreated host, most aeTSAs are undetected by the immune system. We present evidence suggesting that vaccines inducing direct aeTSA presentation by DCs represent an attractive strategy for cancer treatment.

Rice blast, caused by Magnaporthe oryzae, poses significant threat to rice production. Rice blast susceptibility has been observed in Japanese rice varieties with excellent eating quality. Enhancing blast resistance is essential to ensure minimal use of agricultural chemicals. Two types of blast resistance are observed: true resistance, which is a type of qualitative resistance expressed by a major gene, and field resistance, which is a type of quantitative resistance expressed by multiple micro-acting genes. ‘Resistance collapse’, in which a variety with a true resistance gene becomes diseased by blast fungus races compatible with the resistance gene, has been observed. Varieties carrying blast-resistance genes, such as Pb1 (panicle blast resistance 1), have been developed through DNA marker-assisted selection. In this review, we focus on the Pb1, which expresses strong quantitative resistance to panicle blast and has been widely used in Japan without showing ‘resistance collapse’ for 40 years. Pb1 is an ‘adult plant resistance gene’ that does not exert strong selection pressure on the blast population during the leaf blast stage, thus preventing the selective multiplication of Pb1-compatible blast strains. This epidemiological mechanism prevents ‘resistance collapse’. Interdisciplinary research and breeding are required to sustainably use genes that induce high field resistance.

Psychiatric disorders are mental, behavioral or emotional disorders. These conditions are prevalent, one in four adults suffer from any type of psychiatric disorders world-wide. It has always been observed that psychiatric disorders have a genetic component, however new methods to sequence full genomes of large cohorts have identified with high precision genetic risk loci for these conditions. Psychiatric disorders include, but are not limited to, bipolar disorder, schizophrenia, autism spectrum disorder, anxiety disorders, major depressive disorder, and attention-deficit and hyperactivity disorder. Several risk loci for psychiatric disorders fall within genes that encode for voltage-gated calcium channels (Ca_Vs). Calcium entering through Ca_Vs is key for multiple neuronal processes. In this review, we will summarize recent findings that link Ca_Vs and their auxiliary subunits to psychiatric disorders. First, we will provide a general overview of Ca_Vs structure, classification, function, expression and pharmacology. Next, we will summarize tools and databases to study risk loci associated with psychiatric disorders. We will examine functional studies of risk variations in Ca_V genes when available. We will review pharmacological evidence of the use of Ca_V modulators to treat psychiatric disorders. Our review will be of interest for those studying pathophysiological aspects of Ca_Vs.

Current theories of autoimmunity are diverse, sometimes contradictory, and suffer from incompleteness. Although substantial evidence exists that adaptive and innate immunity, sex, genetic predisposition, and the microbiome all play essential roles in autoimmune disease etiologies and pathogenesis, and that antigen processing is altered during disease induction, no existing theory integrates all of these factors through a single, coherent mechanism. In an attempt to focus the field on the need to elucidate such an integrative mechanism, I propose one possibility here that, if nothing else, helps to identify the nature of the problems that need to be addressed. My theory is that autoimmune diseases are induced by normal immunological responses to unique pairs of complementary antigens, at least one of which is a molecular mimic of a host target. Each antigen in the complementary pair induces a complementary immune response (T or B cell); although each immune response is idiotypic in origin, the antigenic complementarity results in what appears to be an idiotype-anti-idiotype relationship between the responses. Additionally, because of the antigenic complementarity, each immune response mimics one of antigens, abrogating the distinction between self and non-self. If at least one of the antigens mimics a host antigen, then the resulting immunological civil war spreads to a host tissue. Complementary antigens also alter antigen processing so that antigens that would normally be proteolytically digested are presented by the major histocompatibility complex (MHC) to T and B cell receptors inducing a cross-reactive immune response. The resulting civil war is supported by the innate immune system due to the complementarity of the initiating antigens.. Complementary antigens stimulate synergistic toll-like receptors (TLR) and/or nucleotide-binding oligomerization receptors (NOD) resulting in up-regulation of cytokine production and further stimulation of the adaptive immune response. Because the immune responses (e.g., antibodies) mimic the initiating antigens, this synergistic activation of innate immunity becomes chronic. Additionally, TLR and NOD function are highly sensitive to sex hormones, some becoming up-regulated and some down-regulated in the presence of either testosterone or estrogens. This sensitivity explains how sex modifies susceptibility to autoimmune diseases. Genetic mutations in TLR, NOD and MHC further alter antigen presentation and the degree to which antigens stimulate an immune response explaining how genetics also modifies susceptibility. Finally, sex hormones also alter the host microbiome, which in turn modulates autoimmune disease risk by shaping the immunological nature of self and by mediating susceptibility to microbial infection. Moreover, it appears that the microbiome camouflages itself from the immune system by mimicking the host antigenic repertoire; the mimicry between the antigens of the microbiome and the host results in selective attacks on microbiome constituents concomitant with any autoimmune attack on host tissues. This antigenic complementarity theory thereby integrates all major elements known to affect, or be affected by, autoimmune diseases and provides a set of testable implications.