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.

Diagnosis and treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in women remain insufficient. Fluctuations of reproductive hormones during the premenstrual period, postpartum period and (peri)menopause are neglected, even though they impact ADHD symptoms and as-sociated mood disorders [1]. Therefore, we created a female-specific treatment group for women with ADHD and premenstrual worsening of ADHD and/or mood symptoms. We describe the group programme and underlying rationale, offering a qualitative analysis of the participants’ evaluation. The 7 two-weekly sessions foreground the menstrual cycle and address several ADHD-specific topics in relation to this cyclical pattern: emotional regulation; impulsivity; setting boundaries, and triggers. Concurrently, women track their menstrual cycle and (fluctuating) ADHD and mood symptoms with an adjusted premenstrual calendar. In total, 18 women (25-47yrs) participated in three consecutive groups. We analysed the evaluation of the last group. Participants experienced the group as a safe and welcoming space. Recognition was valued by all. The topics discussed were deemed valuable and the structure suited them well. Completing the premenstrual calendar augmented awareness and recognition of individual cyclical symptoms. Discussing ADHD throughout the lifespan increased self-understanding. Participants took their menstrual cycle more seriously, prioritising self-acceptance and self-care in the luteal phase of the cycle. Exploring a cyclical approach in a group setting seems to be a positive addition to treatment for female ADHD.

The electronic cigarette or e-cigarette is the new alternative method to deliver nicotine. In 2007, the United States introduced vaping devices on the market. Due to their attractive taste and lack of adverse effects, these vaping devices have gained popularity among youth and adults. However, there has been increasing evidence that vaping can cause severe lung injury, and these devices release toxic chemicals into the body. E-cigarettes are recognized as a global threat to public health. Nicotine, the most prevalent chemical in vaping devices, is associated with neurological problems and cognitive decline. Long-term use of e-cigarettes can cause adverse health problems, including respiratory illnesses, asthma, bronchitis, and lung inflammation. In 2019, the Centers for Disease Control and Prevention (CDC) officially declared vaping-associated illness EVALI (e-cigarette or Vaping Product Associated Lung Injury). The US Surgeon General published an alarm in December 2016 that e-cigarette consumption among adolescents and teens in the US is a "major public health concern" and that more young people are now vaping than smoking traditional cigarettes and cigars. Since its commercial introduction in 2003, modern electronic cigarettes (or E-cigarette s) have become increasingly popular with smokers, non-smokers, and those who used to smoke who have switched to them. With such a rise in consumption, people are becoming more aware of the irritating, harmful, and perhaps cancer-causing effects on the lungs. (Chadi et al., 2019; Dinardo & Rome, 2019; Lyzwinski et al., 2022; Marrocco et al., 2022; O’Callaghan et al., 2022)

The involvement of the prefrontal cortical dopaminergic system in psychopathology of epilepsies and comorbid conditions such as autism spectrum disorder (ASD) still needs to be explored. We used autoradiography to study the D1-like (D1DR) and D2-like (D2DR) receptor binding density in the prefrontal cortex of normal Wistar rats and Wistar-derived strains with generalized convulsive and/or nonconvulsive epilepsies. WAG/Rij rats served as a model for non-convulsive absence epilepsy, WAG/Rij-AGS as a model of mixed convulsive/non-convulsive forms, and KM strain was a model for convulsive epilepsy comorbiding with ASD-like behavioral phenotype. Prefrontal cortex of rats with any of epileptic pathology studied, demonstrated profound decreases in binding densities to both D1DR, D2DR; the effects were localized in the primary and secondary anterior cingulate cortexi, and adjacent regions. The local decreased D1DR and D2DR binding densities were independent (not correlated) from each other. The particular group of epileptic rats with ASD-like phenotype (KM strain), displayed changes in the lateral prefrontal cortex and adjacent regions: D1DR were lowered, but those to D2DR elevated, in anterior dysgranular insular cortex and adjacent regions. Thus, epilepsy-related changes in the dopaminergic system of rat archeocortex were localized in the medial regions, whereas ASD-related candidates were seen in the lateral aspects. The findings point to putative local dopaminergic dysfunctions, associated with generalized epilepsies and/or ASD.

Recent brain imaging findings by using different methods (e.g., fMRI and PET) have suggested that social anxiety disorder (SAD) is correlated with alterations in regional or network-level brain function. However, due to many limitations associated with these methods, such as poor temporal resolution and limited number of samples per second, neuroscientists could not quantify the fast dynamic connectivity of causal information networks in SAD. In this study, SAD-related changes in brain connections within the default mode network (DMN) were investigated using eight electroencephalographic (EEG) regions of interest. Partial directed coherence (PDC) was used to assess the causal influences of DMN regions on each other and indicate the changes in the DMN effective network related to SAD severity. The DMN is a large-scale brain network basically composed of the mesial prefrontal cortex (mPFC), posterior cingulate cortex (PCC)/precuneus, and lateral parietal cortex (LPC). The EEG data were collected from 88 subjects (22 control, 22 mild, 22 moderate, 22 severe) and used to estimate the effective connectivity between DMN regions at different frequency bands: delta (1–3 Hz), theta (4–8 Hz), alpha (8–12 Hz), low beta (13–21 Hz), and high beta (22–30 Hz). Among the healthy control (HC) and the three considered levels of severity of SAD, the results indicated a higher level of causal interactions for the mild and moderate SAD groups than for the severe and HC groups. Between the control and the severe SAD groups, the results indicated a higher level of causal connections for the control throughout all the DMN regions. We found significant increases in the mean PDC in the delta (p = 0.009) and alpha (p = 0.001) bands between the SAD groups. Among the DMN regions, the precuneus exhibited a higher level of causal influence than other regions. Therefore, it was suggested to be a major source hub that contributes to the mental exploration and emotional content of SAD. In contrast to the severe group, HC exhibited higher resting-state connectivity at the mPFC, providing evidence for mPFC dysfunction in the severe SAD group. Furthermore, the total Social Interaction Anxiety Scale (SIAS) was positively correlated with the mean values of the PDC of the severe SAD group, r (22) = 0.576, p = 0.006 and negatively correlated with those of the HC group, r (22) = −0.689, p = 0.001. The reported results may facilitate greater comprehension of the underlying potential SAD neural biomarkers and can be used to characterize possible targets for further medication.

Background: Despite tremendous efforts to reduce neonatal mortality worldwide and in 24 Ethiopia, there is the country is one of the countries with highest neonatal morbidity and health 25 losses. Never the less, the past three decades’ national trend and subnational distribution of 26 neonatal morbidity and mortality and its health loss in Ethiopia, was not well documented. 27 Hence, this study had aimed to analyze the trend and distributions as well as health losses 28 resulting from neonatal morbidity in the past three decades in Ethiopia, 2019. 29 Objective: To assess the national trend and sub national distributions of neonatal morbidity and 30 neonatal mortality in the previous three decades by using Global Burden of Diseases, 2019 data. 31 Methods: The data sources were primary and secondary data related to risk factors, morbidity, 32 disability, deaths, Disability Adjusted Life Years, Years Lived with Disability and Years Life Lost 33 were collected form case studies and case series, household surveys, socio-demographic surveys 34 and surveillances, health facilities surveys, Health facility observations and interviews and 35 published and unpublished literatures. The prevalence, deaths and health losses were calculated 36 by using embedded model. The study period covered from 1990 to 2019. Results were presented 37 buy using texts, tables and graphs. 38 Results: Seventy percent of neonatal disorders had occurred among early neonates aged 0 to 6 39 days. Between 1990 and 2019, the national prevalence of neonatal disorders had increased by 40 47% in to 28,319 (95% UI, 25646-30,361). Bet Similarly, the highest number of neonatal deaths 41 caused by neonatal sepsis had shifted from Southern Nations Nationalities and Peoples region to 42 Oromia region while Harari remains to bear the lowest burden in the last three decades. The 43 highest and the lowest YLL as a result of neonatal disorders had occurred in Oromia 44 [(2,753,038,95% UI, 2,184,142-3,497-926) and Amhara 1,360,847 [(95% UI, 95% UI, 45 1,062,660-1,762,028)] regions respectively. Unlike other regions, Addis Ababa had the highest 46 (52%) prevalence of preterm birth in 2019 47 Conclusion and Recommendation: About seven in ten of neonatal death had occurred among 48 early neonates indicating narrowed occurrence of the event. The highest and the lowest number 49 of neonatal death and health loss had occurred in Oromia and Harari regions respectively. The 50 main causes of death were neonatal sepsis and other infections, neonatal preterm, hemolytic 51 disease and other jaundice and neonatal encephalopathy and trauma. Hence, Contextualized, 52 locally accepted innovative early neonatal care is crucial to avert the event.

A model to predict the relative levels of respiratory and fecal-oral transmission potentials of coronaviruses (CoVs) by measuring the percentage of protein intrinsic disorder (PID) of the M (Membrane) and N (nucleoprotein) proteins in their outer and inner shells, respectively, was built before the MERS-CoV outbreak. Application of this model to the 2003 SARS-CoV indicated that this virus with M_PID = 8.6% and N_PID = 50.2% falls into group B, which consists of CoVs with intermediate levels of both fecal-oral and respiratory transmission potentials. Further validation of the model came with MERS-CoV (M_PID = 9%, N_PID = 44%) and SARS-CoV-2 (M_PID = 5.5%, N_PID = 48%) falling into the groups C and B, respectively. Group C contains CoVs with higher fecal-oral but lower respiratory transmission potentials. Unlike SARS-CoV, SARS-CoV-2 with M_PID = 5.5% has one of the hardest outer shells among CoVs. This shell hardness is believed to be responsible for high viral loads in the mucus and saliva making it more contagious than SARS-CoV. The hard shell is able to resist the anti-microbial enzymes in body fluids. Further searches have found that high rigidity of outer shell is characteristic for the CoVs of burrowing animals, such as rabbits (M_PID = 5.6%) and pangolins (M_PID = 5-6%), which are in contact with the buried feces. A closer inspection of pangolin-CoVs from 2017-19 reveals that these animals provided a unique window of opportunity for the entry of an attenuated SARS-CoV-2 precursor into the human population in 2017 or earlier, with the subsequent slow and silent spread as a mild cold that followed by its mutations into the current more virulent form. Evidence of this lies in the similarity of shell disorder and genetic proximity of the pangolin-CoVs to SARS-CoV-2 (~90%). A 2017 pangolin-CoV strain shows evidence of higher levels of attenuation and higher fecal-oral transmission associated with lower human infectivity via having lower N_PID (44.8%). Our shell disorder analysis also revealed that lower inner shell disorder is associated with the lesser virulence in a variety of viruses.

A model that predicts levels of coronavirus (CoV) respiratory/fecal-oral transmission potentials based on the outer shell hardness has been built using neural network (artificial intelligence, AI) analysis of the percentage of disorder (PID) in the nucleocapsid, N, and membrane, M, proteins of the inner and outer viral shells, respectively. Based mainly on the PID of N, SARS-CoV-2 is categorized as having intermediate levels of both respiratory and fecal oral transmission potential. Related to this, other studies have found strong positive correlations between virulence and inner shell disorder among numerous viruses, including Nipah, Ebola, and Dengue viruses. There is some evidence that this is also true for SARS-CoV-2 and SARS-CoV, which have N PIDs of 48% and 50%, and are characterized by case-fatality rates of 7.1% and 10.9%, respectively. The link between levels of respiratory transmission and virulence lies in viral load of body fluids and organ respectively. A virus can be infectious via respiratory modes only if the viral loads in saliva and mucus exceed certain minima. Likewise, a person may die, if the viral load is too high especially in viral organs. Inner shell proteins of viruses play important roles in the replication of viruses, and structural disorder enhances these roles by providing greater efficiency in protein-protein/DNA/RNA/lipid binding. This paper outlines a novel strategy in attenuating viruses involving comparison of disorder patterns of inner shells of related viruses to identify residues and regions that could be ideal for mutation. The M protein of SARS-CoV-2 has one of the lowest M PID values (6%) in its family, and therefore this virus has one of the hardest outer shells, which makes it resistant to antimicrobial enzymes in body fluid. While this is likely responsible for its contagiousness, the risks of creating an attenuated virus with a more disordered M are discussed.

Arginine shows Jekyll and Hyde behavior in several respects. It participates in protein folding via ionic and H-bonds and cation-pi interactions; the charge and hydrophobicity of its side chain makes it a disorder-promoting amino acid. Its methylation in histones; RNA binding proteins; chaperones regulates several cellular processes. The arginine-centric modifications are important in oncogenesis and as biomarkers in several cardiovascular diseases. The cross-links involving arginine in collagen and cornea are involved in pathogenesis of tissues but have also been useful in tissue engineering and wound-dressing materials. Arginine is a part of active site of several enzymes such as GTPases, peroxidases, and sulfotransferases. Its metabolic importance is obvious as it is involved in production of urea, NO, ornithine and citrulline. It can form unusual functional structures such as molecular tweezers in vitro and sprockets which engage DNA chains as part of histones in vivo. It has been used in design of cell-penetrating peptides as drugs. Arginine has been used as an excipient in both solid and injectable drug formulations; its role in suppressing opalescence due to liquid-liquid phase separation is particularly very promising. It has been known as a suppressor of protein aggregation during protein refolding. It has proved its usefulness in protein bioseparation processes like ion-exchange, hydrophobic and affinity chromatographies. Arginine is an amino acid, whose importance in biological sciences and biotechnology continues to grow in diverse ways.

The prevalence of internet gaming disorders (IGD) is considerably high among youth, especially with social isolation imposed by the ongoing COVID-19 pandemic. IGD adversely affects mental health, quality of life, and academic performance. The Internet Gaming Disorder Scale (IGDS9-SF) is designed to detect IGD according to DSM-IV diagnostic criteria. However, inconsistent results are reported on its capacity to diagnose IGD evenly across different cultures. To ensure the suitability of the IGDS9-SF as a global measure of IGD, this study examined the psychometric properties of the IGDS9-SF in a sample of Sri Lankan university students (N = 322, mean age =17.2 ± 0.6, range = 16-18 years, 56.5% males) and evaluated its measurement invariance across samples from Sri Lanka, Turkey, Australia, and the USA. Among Sri Lankan students, a unidimensional structure expressed good fit, invariance across different groups (e.g., gender, ethnicity, and income), adequate criterion validity (strong correlation with motives of internet gaming, daily gaming duration, and sleep quality), and good reliability (alpha = 0.81). Males and online multiplayers expressed higher IGD levels, greater time spent gaming, and more endorsement of gaming motives (e.g., Social and Coping) than females and offline players. Across countries, the IGDS9-SF was invariant at the configural, metric, and scalar levels, albeit strict invariance was not maintained. The lowest and highest IGD levels were reported among Turkish and American respondents, respectively. In conclusion, the IGDS9-SF can be reliably used to measure IGD among Sri Lankan youth. Because the scale holds scalar invariance across countries, its scores can be used to compare IGD levels in the studied countries.

High dietary phosphate intake and poor adherence to phosphate-binding-therapy elevate the risk of hyperphosphatemia in maintenance hemodialysis (HD; MHD) patients. Therefore, chronic kidney disease-related mineral and bone disorder (CKD-MBD) indicators increase; consequently, risks of CKD-MBDs and inflammation are elevated. This double-blind, randomized control trial intervention study was designed to investigate the possibility of reducing blood CKD-MBD indicators and modulating inflammatory indicators by consuming low-phosphate (LP) meals accompanied by a minimum dose of a calcium-based phosphate binder (CaCO3). MHD patients were recruited and randomly assigned to an LP meal group (LP group) or a control group. After initial data collection, blood collection, and dietary counseling, subjects were asked to consume a washout diet for 1 week. During the washout diet period, subjects consumed their usual diet but took 1 tablet of calcium carbonate (1CaCO3) as a phosphate binder with each meal. After the washout diet period, subjects in the LP group and control group respectively consumed LP meals and regular meals twice a day for 1 week. Meat in the LP meals was boiled before the regular cooking process, but meat in control meals was not. All meals were supplied by a central kitchen so that the contents of phosphate and other nutrients could be identified. In total, 40 MHD patients completed the study program. After 1 week of the dietary intervention, the blood Ca x P product and dietary phosphate had significantly decreased in the LP group compared to the control group (p<0.05). The LP group had significantly lower variations in dietary phosphate intake, blood calcium, Ca x P product, and tumor necrosis factor (TNF)-α than the control group by comparing differences between after the dietary intervention and the baseline (△after intervention - baseline, p<0.05). The increase in dietary phosphate intake (△3rd - 2nd dietary phosphate intake) augmented the increase in the TNF-α level by 6.24-fold (odds ratio [95% confidence interval]: 6.24 [1.12~34.92], p<0.05). These results highlighted the conclusion that LP meals accompanied by a minimum dose of CaCO3 downregulated pro-inflammation by reducing CKD-MBD indicators which was triggered by decreasing dietary phosphate intake.

Post-stroke depressive disorders (PSD) and post-stroke cognitive impairments (PCI) are frequent consequences of ischemic stroke (IS). The study was focused on exploring possible associations between relative volumes of cortical and limbic brain structures during the acute period of IS, and changes in biochemical indices of hypothalamic-pituitary-adrenal, sympathoadrenal medullary and inflammatory systems, with the development of PSD or PCI after mild or moderate IS. Patients developing PSD later on had significantly smaller relative volumes of the hippocampus, entorhinal cortex, and temporal pole versus patients without depressive symptoms. PCI development was associated with significantly smaller volumes of temporal pole and supramarginal gyrus versus patients without cognitive changes. Multiple logistic regression analysis showed higher likelihood of developing PSD in patients with smaller temporal pole volume (β0=10.9; β=-4.27; p=0.04) and increased salivary α-amylase activity (β0=-3.55; β=2.68e-05; p=0.02,). PCI likelihood was higher in patients with smaller supramarginal gyrus volume (β0=3.41; β=-0.99; p=0.047), smaller temporal pole volume (β0=3.41; β=-3.12; p=0. 06), and increased hair cortisol concentration at admission (index of accumulated stress load within a month before IS; β0=3.41; β=-0.05; p=0.08). The data support the hypothesis suggesting predisposition to PSD and PCI and multi hit scenarios of their pathogenesis with IS providing a final hit.

Alcohol use disorder (AUD) is a chronically relapsing disease characterized by loss of control in seeking and consuming alcohol (ethanol) driven by recruitment of brain stress systems. However, AUD differs among the sexes: men are more likely to develop AUD, but women progress from casual to binge drinking and heavy alcohol use more quickly. The central amygdala (CeA) is a hub of stress and anxiety, with corticotropin releasing factor (CRF)-CRF1 receptor and GABAergic signaling dysregulation occurring in alcohol dependent male rodents. However, we recently showed that GABAergic synapses in female rats are less sensitive to the acute effects of ethanol. Here, we used patch clamp electrophysiology to examine the effects of alcohol dependence on the CRF-modulation of rat CeA GABAergic transmission of both sexes. We found that GABAergic synapses of naïve female rats were unresponsive to CRF application compared males, although alcohol dependence induced a similar CRF responsivity in both sexes. In situ hybridization revealed that females had less CeA neurons containing mRNA for the CRF1 receptor (Crhr1) than males, but in dependence, the percentage of Crhr1-expressing neurons in females increased, unlike males. Overall, our data provide evidence for sexually dimorphic CeA CRF system effects on GABAergic synapses in dependence.

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.

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.

The bHLH-PAS proteins are a family of transcription factors regulating expression of a wide range of genes involved in different functions, from differentiation and development control, by oxygen and toxins sensing to circadian clock setting. In addition to the well-preserved DNA-binding bHLH and PAS domains, bHLH-PAS proteins contain long intrinsically disordered C-terminal regions, responsible for their activity regulation. Our aim was to analyse the potential connection between disordered regions of the bHLH-PAS transcription factors with posttranscriptional modifications and liquid-liquid phase separation in the context of the disease-associated missense mutations. Highly flexible disordered regions, enriched in short more ordered motives, are responsible for wide spectrum of interactions with transcriptional co-regulators. Based on our in silico analysis and taking into account fact that transcription factors functions can be modulated by posttranslational modifications and spontaneous phase separation, we assume that the location of missense mutations inducing disease states, is clearly related to sequences directly undergoing these processes or to sequences responsible for their activity regulation.

Non-suicidal self-injurious behavior (NSSI), prevalent in patients with non-psychotic mental disorders (NPMD), is associated with numerous adverse outcomes. Despite active research into the clinical and psychological aspects of NSSI, the underlying biological mechanisms remain obscure. Early adverse experiences are believed to induce long-lasting changes in neuroendocrine mechanisms of stress control playing a key role in NSSI development. The aim of the study was to evaluate parameters potentially predicting development of NSSI in female patients with NPMD. Eighty female patients over 18 years with NPMD and suicidal ideation (40 with and 40 without NSSI) and 48 age matching women without evidence of mental illness (healthy controls) were enrolled. Diagnostic interviews and self-report measures were used to assess childhood maltreatment, presence, frequency, and characteristics of suicidal and self-injurious thoughts and behaviors, the Beck Depression Inventory scale to assess severity of depression. Hypothalamic-pituitary-adrenal axis markers, hormones, and neurotrophic factors were measured in blood serum. The likelihood of developing NSSI in patients with NPMD was associated with early adverse family history and elevated adrenocorticotropic hormone levels. Dysregulation of hypothalamic-pituitary-adrenal axis as a result of early chronic stress experiences may represent critical biological mechanism promoting the development of NSSI behaviors in patients with NPMD.

The Gilles de la Tourette syndrome (GTS) and Non-Coeliac Gluten Sensitivity (NCGS) may be associated. We analyse the efficacy of a gluten-free diet (GFD) in 29 patients with GTS (23 children; 6 adults) in a prospective pilot study. All of them followed a GFD for one year. The YGTSS, Y-BOCS/CY-BOCS and GTS-QOL questionnaires were compared before and after the GFD. 74% of children and 50% of adults were males, not significant (NS). At the beginning of the study, 69% of children and 100% of adults had associated OCD (NS). At baseline, the YGTSS scores were 55.0 ± 17.5 (children) and 55.8 ± 19.8 (adults) (NS), the Y-BOCS/CY-BOCS scores were 15.3 (SD = 12.3) (children) and 26.8 (9.2) (adults) (p = 0.043), and the GTS-QOL scores were 42.8 ± 18.5 (children) and 64 ± 7.9 (adults) (p = 0.000). NCGS was frequent in both groups, with headaches reported by 47.0% of children and 83.6% of adults (p = 0.001). After one year on a GFD there was a marked reduction in measures of tics (YGTSS) (p = 0.001), and the intensity and frequency of OCD (Y-BOCS/CY-BOCS) (p = 0.001), along with improved QOL (p = 0.001) in children and adults. In conclusion, a GFD maintained for one year in GTS patients led to a marked reduction in tics and OCD both in children and adults.

This review focuses on the evidence for neurotherapeutics for Attention Deficit Hyperactivity Disorder (ADHD). EEG-Neurofeedback has been tested for about 45 years with latest meta-analyses of randomised controlled trials (RCT) showing small/medium effects compared to non-active controls only. Three small studies piloted neurofeedback of frontal activations in ADHD using functional magnetic resonance imaging or near-infrared spectroscopy, finding no superior effects over control conditions. Brain stimulation has been applied to ADHD using mostly repetitive transcranial magnetic and direct current stimulation (rTMS/tDCS). rTMS has shown mostly negative findings on improving cognition or symptoms. Meta-analyses of tDCS studies targeting mostly dorsolateral prefrontal cortex show small effects on cognitive improvements with only two out of three studies showing clinical improvements. Trigeminal nerve stimulation has shown to improve ADHD symptoms with medium effect in one RCT. Modern neurotherapeutics are attractive due to their relative safety and potential neuroplastic effects. However, they need to be thoroughly tested for clinical and cognitive efficacy across settings and beyond core symptoms and for their potential for individualised treatment.

Transition between the unfolded and native states of the ordered globular proteins is accompanied by accumulation of several intermediates, such as pre-molten globule, wet molten globule, and dry molten globule. Structurally equivalent conformations can serve as native functional states of intrinsically disordered proteins. This overview captures the characteristics and importance of these molten globules in both structured and intrinsically disordered proteins. It also discusses examples of engineered molten globules. The formation of these intermediates under the conditions of macromolecular crowding and their interactions with nanomaterials are also reviewed.

The Impact of Event Scale-Revised (IES-R) is the most popular measure of post-traumatic stress disorder (PTSD), which has been recently validated in Arabic. This instrumental study aimed to determine optimal cutoff scores of the IES-R and its subscales in Arab samples of psychiatric patients (N = 168, 70.8% females) and healthy adults (N = 992, 62.7% females) from Saudi Arabia during the COVID-19 pandemic as an ongoing collective traumatic event. Based on a cutoff score of 14 of the Depression Anxiety Stress Scale 8-items (DASS-8), receiver operator curve (ROC) analysis revealed two optimal points of 39.5 and 30.5 for the IES-R in the samples (area under the curve (AUC) = 0.86 & 0.91, p values = 0.001, 95% CI: 0.80-0.92 & 0.87 to 0.94, sensitivity = 0.85 & 0.87, specificity = 0.73 & 0.83, Youden index = 0.58 & 0.70, respectively). Different cutoffs were detected for the six subscales of the IES-R, with numbing and avoidance expressing the lowest predictivity for distress. Meanwhile, hyperarousal followed by the irritability expressed stronger predictive capacity for distress than all subscales in both samples. In path analysis, pandemic-related irritability resulted from direct and indirect effects of key PTSD symptoms (intrusion, hyperarousal, and numbing). Irritability contributed to traumatic symptoms of sleep disturbance in both samples while the opposite was not true. The findings suggest usefulness of the IES-R at a score of 30.5 for detecting adults prone to trauma related distress, with higher scores needed for screening in psychiatric patients. Various PTSD symptoms may induce dysphoric mood, which represents a considerable burden that may induce circadian misalignment and more noxious psychiatric problems/ co-morbidities (sleep disturbance) in both healthy and diseased groups.