With the inclusion of Internet Gaming Disorder (IGD) in both the DSM-5 and ICD-11, understanding the prevalence and diagnostic discrepancies is crucial for developing appropriate interventions. This study presents a meta-analysis of the prevalence of IGD based on two diagnostic criteria. We systematically searched PubMed, Web of Science databases. 17 studies were included in the final analysis, The analysis incorporated studies employing the DSM-5 and ICD-11 criteria and focused on the impact of various factors, including study location, sample size, and quality score, on the reported prevalence rates using a random-effects model. Heterogeneity and publication bias were analyzed using an I2 test and Galbraith plots , The prevalence of IGD varied among the selected studies, with a general pooled prevalence of 5% (95% CI: 3%–7%). Subgroup analysis indicated that the prevalence rates of IGD (DSM-5 criteria) and GD (ICD-11 criteria) do not show significant differences. DSM-5-based scales yielded varied results, while heterogeneity among the studies was high (I2 = 98.50). In contrast, ICD-11-based scales produced more consistent and less variable findings. Our findings highlight that assessment scales, not diagnostic criteria, impact IGD prevalence. This underscores the importance of adopting standardized methodologies to guide public health interventions. However, given the limited research based on ICD-11 diagnostic criteria, further investigation is necessary to determine the variations in prevalence rates of IGD under different diagnostic standards.

(1) Background: Various cutaneous adverse drug reactions (ADRs) are observed with the development of mRNA COVID-19 vaccines. To gain insight into the clinicopathologic features, we analyzed the correlation of histological and clinical data in 48 patients with these ADRs.; (2) Methods: Single-center retrospective study in patients with ADRs post-mRNA COVID-19 vaccination (mRNA-1273 and BNT162b2 vaccines).; (3) Results: Distant generalized ADRs prevailed (91%), often appearing clinically as spongiotic dermatitis or maculo-papular exanthema. Histopathological analysis revealed spongiotic changes (46%) and dermal superficial perivascular lympho-histiocytic infiltrates (17%). Eosinophils were found in 66% of biopsies, neutrophils in 29%, and plasma cells only in 8% of biopsies. Most ADRs occurred post-second vaccine dose (44%). Histologically spongiotic changes were associated with clinical features of spongiotic dermatitis in only 50% and maculo-papular exanthema in the remaining patients. ADRs represented an aggravation of preexisting skin disease in 23% of patients. ADRs regressed within 28 days or less in 53% of patients and persisted beyond a month in the remaining patients.; (4) Conclusions: Our study demonstrates a diverse spectrum of generalized ADRs, revealing correlations between histology and clinical features but also instances of divergence. The majority of ADRs are self-limited with a few extending beyond a month.

Hox gene clusters are crucial in Embryogenesis. It was observed that some Hox genes are located in order along the telomeric to centromeric direction of the DNA sequence: Hox1, Hox2, Hox3…. These genes are expressed in the same order in the ontogenetic units of the Drosophila embryo along the Anterior-Posterior axis. The two entities (genome and embryo) differ significantly in linear size and in-between distance. This strange phenomenon was named Spatial Collinearity (SP). Later, it was observed that, particularly in the Vertebrates, a Temporal Collinearity (TC) coexists: first is Hox1 expressed, later Hox2 and even later Hox3,…,. According to a Biophysical Model (BM), pulling forces act at the anterior end of the cluster while a cluster fastening applies at the posterior end. Hox clusters are irreversibly elongated along the force direction. During Evolution, the elongated Hox clusters are broken at variable lengths thus split clusters may be created. An Empirical Rule was formulated distinguishing development due to a complete Hox cluster from development due to split Hox clusters. BM can ‘explain’ this Empirical Rule. In a spontaneous mutation where the cluster fastening is dismantled, a minimal pulling force can automatically shift the cluster inside the Hox activation domain. This cluster translocation can probably explain the absence of Temporal Collinearity in Drosophila.

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

Recent research has suggested that working memory training interventions may benefit children with Developmental Language Disorder (DLD). The current study investigated a short and engaging adaptive working memory intervention that targeted executive skills and aimed to improve both language comprehension and working memory abilities in children with DLD. Forty-seven 6- to 10-year-old children with DLD were randomly allocated to an executive working memory training intervention (n=24) or an active control group (n=23). A pre-test/intervention/post-test/9-month-follow-up design was used. Outcome measures included assessments of language (to evaluate far transfer of the training) and working memory (to evaluate near transfer of the training). Hierarchical multiple regression analyses controlling for pre-intervention performance and age found group to be a significant predictor of sentence comprehension and of performance on six untrained working memory measures at post-intervention and 9-month follow-up. Children in the intervention group showed significantly higher language comprehension and working memory scores at both time points than children in the active control group. The intervention programme showed potential to improve working memory and language comprehension in children with DLD and demonstrated several advantages: it involved short sessions over a short period; caused little disruption in the school day; and was enjoyed by children.

In this communication, we present a new simulated in situ lab/on-deck incubator, light spectrum replicator (LSR), and method to simulate the measured in situ HOCR light spectrum curves in incubation chambers. Carbon flux studies require detailed knowledge of primary and secondary production, including an understanding of temporal and spatial scales of variation. Interpretation of the processes involved during measurements continues to be difficult [1] since the incubation of the samples does not permit the study of rapid variations in carbon assimilation. Further, the significance of Dissolved Organic Matter of DOM in primary production is gaining attention as many autotrophic species are known for using organic substrates for growth, even in the dark [2–4] and since a significant portion of DOM can be accounted for from active release of intracellular metabolites by microbial consortia [5]. On the other hand, the major uncertainties in bacterial production measurements lie with the conversion factors used to calculate bacterial production (BP). For a given thymidine incorporation rate, estimates of BP can range by a factor of more than 20 [6,7]. Even though various new analytical tools have emerged [8], understanding of complex patterns of interactions within the microbial loop remains an open question.

It is urgent to find new antibiotic classes to replenish the empty development pipeline of antibiotics. Recently, pyrrolobenzodiazepines (PBDs) with a C8-linked aliphatic-heterocycle have been identified as a new broad spectrum antibiotic class with activity against Gram-negative bacteria. The active imine moiety of the reported lead pyrrolobenzodiazepine compounds was replaced with amide to obtain the non-DNA binding and non-cytotoxic dilactam analogues to further understand the structure activity relationship and improve the safety potential of this class. The synthesized compounds were tested against panels of multidrug resistant Gram-positive and Gram-negative bacteria, including WHO priority pathogens. Minimum inhibitory concentrations for the dilactam analogues ranged from 4 – 32 mg/L for MDR Gram-positive bacteria, compared to 0.03 to 2 mg/L for the corresponding imine analogues while they were found to be inactive against MDR Gram-negative bacteria, with an MIC >32 mg/L, compared to an MIC of 0.5 to 32 mg/L. A molecular modelling study suggests the lack of imine functionality also affects the interaction of PBDs with DNA gyrase. This study suggests the presence of N10-C11 imine moiety is crucial for broad spectrum activity of pyrrolobenzodiazepines.

A distributed bragg reflector is designed to get an optical reflectance on visible electromagnetic spectrum i.e. ~800 nm in this work. Device is realized based on Abele’s matrix for TE mode.

All RNA viruses deliver their genomes into target host cells through processes distinct from normal trafficking of cellular RNA transcripts. The delivery of viral RNA into most cells hence triggers innate antiviral defenses that recognize viral RNA as foreign. In turn, viruses have evolved mechanisms to subvert these defenses, allowing them to thrive in target cells. Therefore, drugs activating defense to exogenous RNA could serve as broad-spectrum antiviral drugs. Here we show that transcriptional signatures associated with cellular responses to the delivery of a non-viral exogenous RNA sequence into human cells predict small molecules with broad-spectrum antiviral activity. In particular, transcriptional responses to the delivery of Cas9 mRNA into human hematopoietic stem and progenitor cells (HSPCs) highly matches those triggered by small molecules with broad-spectrum antiviral activity such as emetine, homoharringtonine, pyrvinium pamoate and anisomycin, indicating that these drugs are potentially active against other RNA viruses. Furthermore, these drugs have been approved for other indications and could thereby be repurposed to novel viruses. We propose that the antiviral activity of these drugs to SARS-CoV-2 should therefore be determined as they have been shown as active against other coronaviruses including SARS-CoV-1 and MERS-CoV. Indeed, two of these drugs- emetine and homoharringtonine- were independently shown to inhibit SARS-CoV-2 as this article was in preparation. These drugs could also be explored as potential adjuvants to COVID-19 vaccines in development due to their potential effect on the innate antiviral defenses that could bolster adaptive immunity when delivered alongside vaccine antigens.

Arthropod-borne flaviviruses represent human pathogens of global medical importance, against which no effective small molecule-based antiviral therapy is currently available. Arbidol (umifenovir) is a broad spectrum antiviral compound approved in Russia and China for prophylaxis and treatment of influenza. This compound showed activity against numerous DNA and RNA viruses. Its mode of action is based predominantly on the impairment of critical steps of virus-cell interaction. Here we demonstrate that arbidol possesses a micromolar inhibition activity (EC50 values ranging from 10.57 ± 0.74 to 19.16 ± 0.29 µM) in Vero cells infected with Zika virus, West Nile virus, and tick-borne encephalitis virus, three medically important representatives of arthropod-borne flaviviruses. Interestingly, no antiviral effect of arbidol is observed in porcine stable kidney cells (PS), human neuroblastoma cells (UKF-NB-6), human hepatoma cells (Huh-7 cells) indicating that the antiviral effect of arbidol is strongly cell-type dependent. Arbidol presents a significant increasing in cytotoxicity profiles when tested in various cell lines in the order: Huh-7 < HBCA < PS < UKF-NB-6 < Vero with CC50 values ranging from 18.69 ± 0.1 to 89.72 ± 0.19 µM. Antiviral activity and acceptable cytotoxicity profiles suggest that arbidol could be a promising candidate for further investigation as a potential therapeutic agent in treating flaviviral infections.

Substance use disorder (SUD) is a global health crisis that is becoming increasingly prevalent among younger generations and impacting the overall health of millions of people worldwide. Traditional treatment methods, including cognitive-behavioral therapies and medicinal-assisted treatments, often face limitations such as inconsistent efficacies and varying degrees of accessibility. Thus, there is a clear need for a new and innovative treatment strategy. Music therapy has recently gained attention through research as a promising non-pharmacological supplement to strengthen conventional SUD treatment methods. This review explores the potential benefits of music therapy in reducing substance cravings, alleviating depressive symptoms, and improving emotional expression among patients in the rehabilitation phase of SUD recovery. We review evidence from various studies and clinical trials to evaluate the efficacy of music therapy in improving standard treatment outcomes, with the results indicating that music therapy could be an effective complement to traditional treatment methods while noting that its efficacy could vary depending on the individual and type of intervention provided. The benefits of music therapy include accessibility of treatment for diverse patient groups and the potential for highly individualized care, although more research is needed to compare the efficacies of specific music treatment types for certain conditions and patient populations. Further research is also needed to validate the neurobiological mechanisms of music therapy, as well as increased communication between music therapists worldwide to enforce consistency in treatment methods and share learnings in this growing field.

Background Posttraumatic stress disorder (PTSD) is a complex condition that represents a significant burden in terms of individual disability and societal costs. Despite decades of research investigating treatment options, PTSD remains a major cause of quality-of-life impairment. We hypothesized that patients with PTSD might benefit from peripheral somatosensory stimulation (PSS) therapy. Methods Six adult patients with clinically diagnosed PTSD were enrolled to undergo daily PSS therapy over a 4-week period. Patients completed two surveys evaluating satisfaction with treatment and overall well-being (Survey 1) and severity of PTSD symptoms (Survey 2). Survey 1 was completed weekly during the course of the study. Survey 2 was based on the 9-question National Stressful Events Survey PTSD Short Scale (NSESSS) and was completed as a baseline prior to initiation of therapy and then at the conclusion of the trial. All data were analyzed by an independent statistician. Results Six male patients were enrolled in the study; all completed the trial. All patients demonstrated a decrease in symptoms within one week of initiation of therapy. This benefit was sustained and appeared to further improve over the course of the trial. For Survey 1, the overall median scores demonstrated a significant time-dependent improvement across measurement times (p < 0.001). For Survey 2, patients had statistically significant improvements from baseline regarding feelings of being emotionally upset and being overly alert. Results from a cumulative link mixed model demonstrated that treatment yielded a 38.2-fold higher likelihood of transitioning from a higher PTSD score at baseline to a lower (improved) score at week 4. No adverse events were described by the patients. Conclusions PSS stimulation appeared to improve symptoms in all six patients with PTSD symptoms in this trial. Patients had unanimous and clinically meaningful improvement in overall PTSD symptoms with treatment. By week 4, all patients responded that they enjoyed the treatment and would like to keep their device. We suggest that further investigation into the potential usefulness of PSS therapy in patients with PTSD is warranted.

Background: Alzheimer's disease causes great changes, with the prefrontal cortex be-ing frequently damaged zones, affecting physical and cognitive behavioural and compromising autonomy and quality of life. Objective: To evaluate the effectiveness of feedback-based tech-nology on the improvement of physical-cognitive capacities in Alzheimer. Methods: Forty pa-tients with Alzheimer were recruited from the Santa Elena Alzheimer's Association, Seville, of which 15 ended up being pilot participants, divided randomly into controls (8) and experi-mental (7). They were evaluated with: Cognitive Mini-Examination Scale, Oddball Test and At-tention Network, Berg Scale, Tinetti, Timed up and Go and Geriatric Deterioration Scale. The experimental group was treated with feedback-based technology under the supervision of physiotherapists, during 16 thirty-minute sessions, twice a week. The control group performed their usual care. Result: A significant improvement was observed in the experimental group (Cognitive Mini-Examination and Tinetti). In the group of control, a worsening of physical and motor skills was evidenced because of the degenerative disease. Discussion/Conclusion: This treatment could be a strategy to keep the patient in early stages for longer, and improve quali-ty of life delaying dependency. It creates intergenerational bonds and use at home to promote treatment adherence.

Marine sponges, a well documented prolific source of natural products, harbors numerous microbial communities believed to possess N-acyl homoserine lactones (AHLs) mediated Quorum sensing (QS) as one of the mechanisms of interaction. Bacteria and eukaryotic organisms are known to produce molecules that can interfere with QS signaling, thus affecting microbial genetic regulation and function. In the present study, we established the potential for production of both QS signal molecules as well as QS interfering molecules (QSI) in the same sponge species Sarcotragus spinosulus. A total of eighteen saturated acyl chain AHLs were identified along with six putative unsaturated acyl chain AHLs. Bioassay guided purification led to the isolation of two brominated metabolites with QS-interfering activity. The structures of these compounds were elucidated by comparative spectral analysis of 1HNMR and HR-MS data and was identified as 3-Br-N-methyltyramine (1) and 5,6-dibromo-N,N-dimethyltryptamine (2). The QSI activity of compounds 1 and 2 were evaluated using reporter gene assays for long- and short-chain signals (E. coli pSB1075 and E. coli pSB401) and was confirmed by measuring dose dependent inhibition of proteolytic activity and pyocyanin production in P. aeruginosa PAO1. The obtained results showed the co-existence of QS and QSI in S. spinosulus, a complex network which may mediate the orchestrated function of the microbiome within the sponge holobiont.

Myeloid neoplasms and acute leukemias include different entities that have been recently re-classify taking into account molecular and clinicopathological features. The myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) category comprises a heterogeneous group of hybrid neoplastic myeloid diseases characterized by the co-occurrence of clinical and pathologic features of both myelodysplastic and myeloproliferative neoplasms. The most frequent entity in this category is chronic myelomonocytic leukemia (CMML) which is, after acute myeloid leukemia (AML), the main myeloid disorder prone to develop cutaneous manifestations. Skin lesions associated with myelodysplastic and myeloproliferative neoplasms include a broad clinical, histopathological and molecular spectrum of lesions, poorly understood and without a clear-cut classification in the current medical literature. The aim of this review is to describe and classify the main clinical, histopathological and molecular patterns of cutaneous lesions in the setting of MDS/MPN in order to improve the diagnostic skills of dermatologists, hematologist and pathologist who deal with these patients.

.The emergence and spread of antimicrobial resistance genes and resistant bacteria does not recognized animal, human or geographic borders. Addressing this threat requires a combination of multidisciplinary approach involving human, animal and environmental health (One Health). Because antimicrobial agents used in veterinary medicine maybe the same or like those in human medicine. Extended-spectrum beta lactamase (ESBL) E. coli is a growing public health problem worldwide, and the Agri-Food industry is constantly becoming sources of clinically important ESBL bacteria. Accordingly, the aim of this study was to investigate the occurrence and characteristics of ESBL-producing E. coli from dairy cattle, milk, and the farm environment. E. coli isolates were identified by their 16sRNA and their ESBL production was confirmed by ESBL-CHROMagar media and double disk diffusion method. Genotypes of ESBL producers were characterised using mPCR assay. Among the examined samples, 18(4.8 %) were positive for ESBL-producing E. coli. Of these, 66.7% were from milk, 27.8% and 5.5% were from farm environment and faecal samples respectively. Predominant ESBL Genotype identified were a combination of both TEM and CTX-M in eight out of 18 (44.4%) isolates. Four (22.2%) isolates produced CTX-M gene, two (11.1%) isolates produced TEM gene and four (22.2%) remaining isolates produced ESBL genes other than TEM, SHV, CTX-M and OXA. The SHV and OXA gene were not detected in all 18 isolates. The occurrence of these genotype in indicator organisms from dairy cattle, milk, and farm environment further re-enforced the potentials of food-animals as sources of infection for humans via the food chain. Thus, consolidating the need for the adoption of tripartite One Health approach in surveillance and monitoring antimicrobial resistance

In this paper, I present a comprehensive theoretical framework for understanding surface-enhanced Raman scattering (SERS) measurements in both solution and thin film setups, focusing on electromagnetic enhancement principles. Two prevalent types of SERS substrates found in the literature are investigated: plasmonic colloidal particles, including spherical and spheroid nanoparticles, nanoparticle diameters, and thin-film-based SERS substrates like ultra-thin substrates, bundled nanorods, plasmonic, and porous thin films. The investigation explores the impact of analyte adsorption, orientation, and the polarization of the excitation laser on effective SERS enhancement factors. Notably, it considers the impact of analyte size on the SERS spectrum, by examining scenarios where the analyte is significantly smaller or larger than the hot-spot dimensions. The analysis also incorporates optical attenuations arising from the optical properties of the analyte and the SERS substrates. The findings provide possible explanations for many observations made in SERS measurements, such as variations in relative peak intensities during SERS assessments, reductions in SERS intensity at high analyte concentrations, and the occurrence of significant baseline fluctuations. The study offers valuable guidance for optimizing SERS substrate design, enhancing SERS measurements, and improving the quantification of SERS detection.

The current recommendation to avoid non-steroidal anti-inflammatory drugs (NSAIDs) in management of dengue virus disease is, as it was adopted earlier in COVID-19, scientifically considered of very low to low certainty. In this perspective I argue, for the first time globally, basing on real-life practice that NSAIDs might be lifesaving in early management of dengue virus disease as I originally argued and proved rightful in COVID-19. Moreover, I also argue that the Egyptian immune-modulatory Kelleni’s protocol, including nitazoxanide as an integral component, can be safely and effectively used to early manage COVID-19, human metapneumovirus, dengue virus disease, Zika virus separate or co-infections similar to what has already been experienced and published with separate or conjoined infections with SARS CoV-2, influenza, RSV and Norwalk viruses without the need of prior serological or molecular investigations to determine the causative agent.

Keywords: Cystic fibrosis, Cystic Fibrosis Transmembrane Conductance Regulator gene, CFTR, Next Generation Sequencing, Cystic fibrosis carriers

Management of Juvenile idiopathic arthritis (JIA) has improved tremendously in recent years due to the introduction of new drug therapies but remains complex also in terms of non-pharmaceutical issues. In order to determine the direction of scientific progress by characterizing the current spectrum of ongoing clinical research in JIA, we analyzed all ongoing studies in the field of JIA registered in clinicaltrials.gov and clinicaltrialsregister.eu concerning sponsoring, enrollment, duration, localization, and particularly objectives. Close of database was 7 January 2021. After identifying doubled-registered studies, N=72 went into further analysis. Of these, 61.1% were academia-sponsored and 37.5% by pharma industry. The majority of studies was of interventional type (77.8%), while others (22.2%) were observational. Median planned enrollments were 100 participants (interventional studies) and 175 participants (observational studies), respectively. Duration differed remarkably from one month to more than 15 years with a median of 42.5 months. 61.1% of studies were located in a single country, 38.9% were in several. Europe and North America clearly dominated study localizations. Study objectives were DMARDs (56.9%), followed by diagnostics and disease activity measurement (18.1%), and medication other than DMARD (12.5%), besides others. Studies on DMARDs were mainly sponsored by industry, predominantly interventional studies on established and novel biologics, with several on specific issues like systemic JIA and others. The spectrum of registered studies is currently centered on drug therapy and diagnostics, while other issues in JIA play a subordinated role.

Sleep-related eating disorder (SRED) is a non-REM parasomnia with potentially significant negative effects on general health (dangerous activities during night eating episodes, obesity, or metabolic syndrome, for example). Although the history of SRED encompasses more than six decades, public awareness and even the awareness of the mental health specialists of this disorder is very limited, a phenomenon that hinders the development of research in this field. Therefore, an updated review, based on a narrative methodology, explored the available evidence for SRED found in four electronic databases (PubMed, Cochrane Collaboration, Google Scholar, and Clarivate/Web of Science). A number of 94 primary and secondary reports were retrieved, investigating aspects regarding the risk factors, epidemiology, clinical data and differential diagnosis, epidemiology, structured evaluation, and treatment of SRED. Based on the results of these reports, Z-drugs, but also certain benzodiazepines, antidepressants, antipsychotics, and psychostimulants may trigger the onset of SRED. Psychiatric and neurologic disorders have also been associated with SRED, either as risk factors or comorbid conditions. Cerebral glucose metabolism dysfunctions, neurotransmitter dysfunctions, and genetic factors have been invoked as pathogenetic contributors. Structured assessment of SRED is possible, but there is a dearth of instruments dedicated to this purpose. Data on the prevalence and treatment of SRED exist, but good-quality epidemiological studies and clinical trials are still missing. In conclusion, future research is expected to address the shortcomings of SRED exploration by creating the conditions for better quality and larger group clinical research. The need for such investigation is granted by the importance of this pathology and its negative functional consequences.

Rapid eye movement sleep behavior disorder (RBD) is often prodromal to Parkinson’s disease (PD). Thus there should be detectable in vivo functional signatures shared between RBD and PD that aid in disease classification. To assess common in-vivo phenotypes, resting state data was collected on a 3T clinical MRI platform and a novel functional connectivity magnetic resonance imaging (fcMRI) approach, which combined independent component analysis (ICA) and graph theory, was used to evaluate deficits in interconnectivity among 15 PD, 14 RBD and 13 control participants. Whole brain and network-level analyses revealed the largest deficits in network connectivity in PD compared with controls, with less severe differences between RBD and controls. Importantly, the network-level analysis demonstrated decreased network interconnectivity, with the greatest aberrant networks in PD, and a subset in RBD. Additionally, a disease classification algorithm predicted PD cases by being trained on RBD cases with 0.87 sensitivity and 0.68 specificity. The functional alterations in cortical networks in RBD extended beyond the brainstem. These findings demonstrate progressive reductions in connectivity between brain networks, with less severe deficits in RBD than PD. Moreover, RBD phenotypes can be used to predict PD status in a cross-sectional sample, which suggests RBD is an intermediate phenotype.

Keywords: Wall-like RC columns; Strengthening; FRP; NSM rebars; Steel plates; Testing; FE modeling; Preloading.

What does the way autistics bypass, learn, and eventually master language tell us about humans’ genetically encoded linguistic ability? In this theoretical review, we argue that autistic non-social acquisition of language, as well as autistic savant abilities, provide a strong argument for an innate, human-specific orientation toward (and mastery of) complex embedded structures. Autistic non-social language learning may represent a widening of the material processed during development beyond oral language. Structure detection and manipulation and generative production of non-linguistic embedded and chained material (savant abilities in calendar calculation, musical composition and interpretation, three-dimensional drawing) may thus represent an application of such innate mechanisms to non-standard materials. Typical language learning through exposure to the child’s mother tongue may represent but one of many possible achievements of the same capacity. The deviation from typical language development in autism may ultimately allow access to oral language, sometimes in its most elaborate forms, but also explains the possibility of the absence of its development when applied exclusively to non-linguistic structured material. Such an extension of human capacities beyond, or in parallel to, their usual limits call into question what we consider to be specific or expected in humans and, therefore, does not necessarily represent a genetic “error”. Regardless of the adaptive success or failure of non-social language learning, it is up to science and ethical principles to strive to maintain autism as a human potentiality to further foster our vision of a plural society.

The World Health Organization recently proposed the Tricycle Protocol for harmonized surveillance of extended-spectrum beta lactamase-producing E. coli (ESBL-Ec) as a proxy for AMR among humans, animals, and the environment. We implemented the Tricycle Protocol with ceftriaxone (CRO) to screen for ESBL-Ec using membrane filtration (TBX-CRO) and Colilert Quanti-Tray (CQT-CRO) workflows in parallel applied to water samples collected from four lakes. ESBL-Ec and E. coli abundance and prevalence, and ESBL-Ec to E. coli ratios were significantly higher in the two highly impacted lakes (receiving sewage treatment plant effluent, open defecation site adjacent to informal settlements) compared to less impacted lakes (wildlife sanctuary, recreational site). The cumulative burden of antibiotic compounds was also higher in the highly impacted lakes. Even in the “pristine” lake in a bird sanctuary, ESBL-Ec and an antibiotic compound were present. Overall, the CQT-CRO format yielded reasonable qualitative (K = 0.603) and quantitative agreement (intra-class correlation coefficient = 0.849) and linearity (r² = 0.785) with the TBX-CRO format adapted from the Tricycle Protocol. However, CQT-CRO doubled the prevalence of ESBL-Ec in settings with decreased E. coli abundance. Consistent with observations for other third-generation cephalosporins, CRO performed poorly for screening the ESBL phenotype. Further, confirmed ESBL-Ec isolates were not associated with an increased number of resistance phenotypes compared with non-ESBL isolates. Instead, the number of resistance phenotypes was associated with the lake from which the sample was collected. In high-burden settings, AMR surveillance efficiency could be increased by directly testing generic E. coli isolates for ESBL phenotype and antibiotic susceptibility. Our experience also suggests that sequencing ESBL-Ec will likely be required to determine epidemiologically appropriate risk mitigation strategies where ESBL-Ec are prevalent. Resource limitations could jeopardize the relevance of the Tricycle Protocol for changing the trajectory of AMR in high-burden low-resource settings globally.

In order to explore more spectrum resources to support sensors and its related applications, cognitive wireless sensor networks (CWSNs) have emerged to identify available channels being underutilized by the primary user (PU). To improve the detection accuracy of the PU signal, cooperative spectrum sensing (CSS) among sensors paradigm is proposed to make a global decision about the PU status for CWSNs. However, CSS is susceptible to Byzantine attack from malicious sensor nodes due to its open nature, resulting in wastage of spectrum resources or causing harmful interference to PUs. To suppress the negative impact of Byzantine attack, this paper proposes a beta distribution function (BDF) for CSS among multiple sensors, which includes a sequential process, beta reputation model, and weight evaluation. Based on sequential probability ratio test (SPRT), we integrate the proposed beta reputation model into SPRT, while improving and reducing the positive and negative impacts of reliable and unreliable sensor nodes on the global decision, respectively. Finally, the numerical simulation results demonstrate that compared to SPRT and weighted sequential probability ratio test (WSPRT), the proposed BDF has outstanding effects in terms of the error probability, and average number of samples under various attack ratios and probabilities.

Cellular therapies have started an important new therapeutic direction for Autistic Spectrum Disease (ASD), and the ample diversity of ASD pathophysiology and the different types of cell therapies need an equally ample effort for studying the applicable ASD causes and the specific benefits of cell therapies via clinical studies.CORDUS Clinical Study is a crossover study in which autologous cord blood was administered intravenously to 56 patients between January 2019 and July 2023, and has compared its efficacy versus an individualized combination of supplements; both treatments were administered in a different sequence to all participants. Treatment efficacy was evaluated pre- and post- treatments by an independent psychotherapist with ATEC, Q-CHAT and a 16-item comparative table score, after interviews with the children’s parents and therapists.Cord blood was beneficial in the group of 3–7-year-old children (n=28; 3 out of 4 children – 78.57% - improved scores), but was much less effective in kids older than 8 years or with body weight of more than 35 kg (n=28; 1 out of 10 children improved scores). Individualized supplements were more efficacious than cord blood in 5 cases out of 28, while in 23 kids cord blood brought more improvement than supplements; 6 kids registered minor or no improvement. Statistically significant improvements were seen after cord blood infusion on areas such as verbalization and social interaction, but not on irritability or aggressive behavior; also ample individual differences were noted. No serious adverse reactions were noted during and after cord blood or supplement administration.

Among the number of hurdles that the vaccines based in modRNA platforms have been facing, there is now another critical one: immune imprinting which decreases even more the effectiveness of the modRNA Covid vaccines.

The resonance spectrum of surface resistance derivative in quasi-two dimensional layered organic conductors has been calculated numerically for the out-of-plane and in-plane magnetic field. Not all but some of the resonances in a given series of transitions are present in the spectra. They are observed at the positions corresponding to the maxima in the surface resistance derivative curve and are in a good agreement with previously calculated magnetic field resonance positions. For tilted magnetic fields, there are more resonances present in the spectrum than in the case of a non-tilted field. Apart from the resonances corresponding to the transitions between the adjacent surface states there also appear resonances involving the transitions between the more distant surface states. This is correlated with the specific topology of Fermi surface of the organic conductors. The presented calculations will allow correct interpretation of the experimental curves for the resonance spectrum, and also to obtain information on the surface properties of these materials for their possible implementation in fabrication of devices based on organic molecular conductors.

Reconstruction of acoustic relaxation absorption curve is a powerful approach to ultrasonic gas sensing, but requires known of a series ultrasonic absorption at various frequencies around effective relaxation frequency. Ultrasonic transducer is a most widely deployed sensor for ultrasonic wave propagation measurement and works only at a fixed frequency or specific environment like water, so a large number of ultrasonic transducers operating at various frequencies are required to recover an acoustic absorption curve with a relative large bandwidth, which cannot suit for large-scale practical applications. This paper proposes a wideband ultrasonic sensor using a distributed Bragg reflector (DBR) fiber laser for gas concentration detection through acoustic relaxation absorption curve reconstruction. With a relative wide and flat frequency response, the DBR fiber laser sensor measures and restores a full acoustic relaxation absorption spectrum of CO2 using a decompression gas chamber between 0.1 and 1 atm to accommodate the main molecular relaxation processes, and interrogates with a non-equilibrium Mach-Zehnder (M-Z) interferometer to gain a sound pressure sensitivity of -45.4 dB. The measurement error of the acoustic relaxation absorption spectrum is less than 1.32%.

Looking at different operating climatic conditions, the electrical behavior predicting photovoltaic modules gets very important. For the estimation of output power from photovoltaic (PV) plants this is a very essential and basic aspect. In this paper, the relationship between the I-V curve and the irradiation spectrum is discussed by combining the single diode model. An explicit elementary analytical model with two defined shape parameters is discussed and improved with three approximations and second order Taylor expansion. Then, the explicit elementary analytical model is investigated under varying conditions leveraging the four parameters I_ph, I₀, R_s and R_sh from the single diode model. The relationship between the physical parameters and the condition parameters are discussed and applied to extract the shape parameters at different scenarios. Considering the aging effect, the process of calculation to predict the I-V curve under different splitting spectra is simplified as follow: (1) two shape parameters are gotten from the I-V data at measurement reference conditions (MRC); (2) the short circuit current, open circuit voltage and shape parameters under any splitting spectrum can be calculated based on the relationship provided in article; (3) the performance of PV panel can be predicted with parameters. The validation of this model was experimentally proven leveraging monocrystalline silicon photovoltaic module with different splitting films. Results showed that the model accurately predicts the I-V characteristics for the examined PV modules at different irradiance spectra and cell temperatures. Moreover, the presented model performs superior compared to other investigated models when looking at accuracy and simplicity.

Introduction: This study aims to verify if elderly patients with mixed anxiety-depressive disorder are more prone to euthanasia and identify factors that interfere with their satisfaction with health and capacity for well-informed decisions. Material and Methods: The study applied a paper questionnaire composed of a sociodemographic section and a battery of scales (to assess depression, anxiety, cognitive performance, suicide risk, therapeutic adhesion, functionality, loneliness, attitude towards euthanasia, decision pattern, personality, empathy and health status) in the Psychogeriatric Unity of Senhora da Oliveira Hospital in Portugal. The sample was collected by convenience to include patients and controls of the same age. Six months later, a reassessment was done. Patients and controls were compared using descriptive statistics and a multiple-regression model.Results: A total of 114 patients and 25 controls were included. Eighty-one point six per cent of patients had four or fewer years of schooling. Contrary to controls, they presented mild depressive and anxiety symptoms, loneliness feelings, worse cognitive performance, a more fragile personality, higher personal distress and a poorer health state. No statistically significant differences were found between controls and patients regarding their attitudes towards euthanasia. Patients more favourable to euthanasia had higher empathic concern, conscientiousness and fantasy and lower personal distress.Discussion and Conclusion: When addressing euthanasia in these patients, it is crucial to ensure they are fully self-determinate and that all the necessary treatment and support are available. It may not be the case when the educational level is low and mild disease persists, significantly affecting their well-being and cognitive performance.

This study aimed to compare procedural learning skills between Spanish-speaking preschool children (ages 4 years to 4 years, 11 months) with Developmental Language Disorder (DLD) and their typically developing (TD) peers. Using the Serial Reaction Time task, participants (30 DLD and 30 TD children) respond to visual stimuli in a sequenced manner over four blocks, followed by a random order block. The task assessed reaction time (RT) and accuracy. Results showed a significant interaction between group and block for reaction time (RT) and accuracy, with children with DLD exhibiting longer RTs and accuracy deficits across blocks. In contrast, the TD group showed higher RT efficiency and accuracy in the sequential blocks and as expected, decreased performance in the random block according to the experimental manipulation. Overall, the results of this investigation suggest that there was no implicit learning in the DLD group, as indicated by the SRT task paradigms of procedural memory. These findings align with the Procedural Deficit Hypothesis (PDH), suggesting that linguistic deficits in the TD population may derive from a general dysfunction of the procedural memory system domain in the Spanish context.

The objective of this literature review was to provide an up-to-date overview, and an analysis of the current knowledge on narcolepsy. A systematic search was conducted in different databases to identify relevant studies on various aspects of narcolepsy. The search terms included "narcolepsy," "excessive daytime sleepiness," "cataplexy," and related terms. The search was limited to studies published up until 2022. The initial screening of studies was performed based on titles and abstracts to identify potentially relevant articles. Full-text assessment was then conducted to determine the eligibility of each study for inclusion in the review. Studies were included if they provided information on the symptoms, classification, genetic aspects, impact on daily life, and gaps in knowledge regarding narcolepsy. The review reveals several important findings regarding narcolepsy: 1. the classification of narcolepsy - Type 1 narcolepsy, previously known as narcolepsy with cataplexy, and Type 2 narcolepsy, also referred to as narcolepsy without cataplexy. 2. the genetic component of narcolepsy and the complex nature of the disorder, which is characterized by excessive daytime sleepiness, disrupted sleep patterns, and potential impacts on daily life activities and social functioning. 3. the important implications for clinical practice in the management of narcolepsy. Healthcare professionals should be aware of the different types of narcolepsies and their associated symptoms, as this can aid in accurate diagnosis and treatment planning. The review underscores the need for a multidisciplinary approach to narcolepsy management, involving specialists in sleep medicine, neurology, psychiatry, and psychology. Clinicians should consider the impact of narcolepsy on a person's daily life, including their ability to work, study, and participate in social activities, and provide appropriate support and interventions. There are several gaps in knowledge regarding narcolepsy. Future research should focus on further elucidating the genetic causes of narcolepsy and exploring potential biomarkers for early detection and diagnosis. Long-term studies assessing the effectiveness of different treatment approaches, including pharmacological interventions and behavioural therapies, are needed. Additionally, there is a need for research on strategies to improve the overall well-being and quality of life of individuals living with narcolepsy, including the development of tailored support programs and interventions.

Personality disorders (PD) are described as enduring patterns of markedly deviant and pervasive inner experiences and behaviors, with onset in adolescence, which lead to severe distress or impairment. Patients suffering with major depressive disorder (MDD) display higher rates of comorbidity with personality disorders, often complicating the treatment, and worsening the outcome. Borderline personality disorder (BPD) is the most common of PD and is frequently associated with MDD, with which shares several features. The most part of research agrees on the fact that comorbid BPD in MDD patients quite double the poor response to treatments. Moreover, no treatment strategy stands out currently to emerge as more effective in these cases, thus urging the call for the need of a new approach. Herein, we revise the current literature on BPD, its neurobiology and comorbidity with MDD, as well as the more recent treatment strategies used. Then, based on its pharmacology, we propose a possible role of trazodone as a valuable tool to approach underlying BPD in MDD

Background: Currently, completed suicide, suicide ideation, suicide behavior, and suicide attempts are major public health problems worldwide. Major Depressive Disorder (MDD) is one of the most common mental disorders associated with an increased risk of suicide. Since the relationship between suicide and cholesterol levels is still controversial, in this study, we explore the association between SNPs rs754203 and rs4900442 of CYP46A1 with suicide risk in Mexican patients with major depressive disorder. Methods: We evaluated 188 unrelated suicide completers and compared them to 144 non-suicidal individuals (controls) and 126 MDD patients. Genotypes were analyzed using the Real Time-polymerase chain reaction method and two allele-specific probes to detect specific SNP targets. A chi-square test was used to identify a possible risk genotype or allele type for suicide. Results: Statistical analysis showed significant differences between completed suicide and controls in their allelic and genotypic frequencies in rs754203 SNP. The genotype G/G of CYP46A1 rs754203 was significantly associated with suicide. Also, the G allele was associated with an increased risk of suicide (OR= 1.370, 95% CI= 1.002-1.873). No differences in either genotype distribution or allele frequencies of CYP46A1 rs4900442 were observed. Conclusions: The results of the current study report the first association between G allele carriers (A/G + G/G) of rs754203 and increased risk for suicide, especially in males.

HIV-associated neurocognitive disorder (HAND) is an array of neurocognitive changes associated with HIV infection, and the roles of microRNAs in HAND are not completely revealed yet. Based on published data and publicly available databases, we constructed an integrated miRNA-mRNA network involved in HAND. Bioinformatics analyses, including gene ontology, network analysis, and KEGG pathway analysis, were applied for further study of the network and the genes of the network. The axon guidance KEGG pathway, three genes NTNG1, EFNB2, CXCL12, and 17 miRNAs which regulates them, are spotlighted in our study. This study provides new perspectives to the knowledge of miRNAs’ roles in the process of HAND, and our findings provided potential therapeutic targets and clues of HAND.

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.

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

This study investigated the presence, distribution, and antimicrobial resistance profiles of extend-ed-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in a dairy herd located in Northern Italy. A questionnaire was administered, and the feces of clinically healthy pre-weaned dairy calves, their mothers, and the cows treated for mastitis, waste milk, water, and environmental samples, were collected and inoculated on Chromagar ESBL™ medium. The questionnaire identi-fied several risk factors including administration of waste milk to male calves, lack of routine cleaning of calf feeding and housing equipment, and blanket dry cow therapy. Escherichia coli was identified by MALDI-TOF MS in the feces of 28 of 37 (75.67%) calves, 2 of 3 (66.67%) treated cows, 8 of 14 (57.15%) environmental samples, and the waste milk. Six of 14 (42.85%) environmental samples were also positive for ESBL Acinetobacter baumannii, while all fecal samples were negative. ESBL production was confirmed for all E. coli isolates based on the double disk susceptibility test (DDST), while none were carbapenemase producers. Upon minimal inhibitory concentration (MIC) analysis, all of them showed multiple resistances and were categorized as multi-drug resistant (MDR). This study confirms the widespread presence of MDR, ESBL-E. coli in dairy calves and highlights their diffusion in the farm environment.

Abstract: The EMU(electric multiple units) traction motors are powered by converters. The PWM(pulse width modulation) voltage increases the voltage stress borne by the motor insulation system, making the ITSC(inter-turn short-circuit) fault more prominent. An index based on short-circuit thermal power was proposed in the article to evaluate the non-metallic ITSC faults degree. The apFFT(all phase FFT) time-shift phase difference correction with double Hanning-windows is used to calculate the fundamental frequency of the traction motor's ZSVC（zero se-quence voltage component）, the fundamental amplitudes of ZSVC and three-phase current. The five parameters are used as fault features to train the SVM (support vector machine)fault diagnosis model. The SVM hyper-parameters C and g are optimized by K-CV (K fold cross-validation) and grid search methods. The experimental verification was carried out by the EMU electric traction simulation experimental platform. According to the non-metallic degree index proposed in this article, the experimental samples were divided into three categories, normal, incipient and serious fault samples. The ITSC fault diagnosis accuracy was 100% on the training data set and 93.33 % on the test data set. There was no misclassification between normal and serious ITSC fault samples.

Nuclear protein of testis (NUT), a protein product of the NUTM1 gene (located on the long arm of chromosome 15) with highly restricted physiologic expression in post-meiotic spermatids, is the oncogenic driver of a group of emerging neoplasms when fused with genes involved in transcription regulation. Although initially identified in a group of lethal midline carcinomas in which NUT forms fusion proteins with bromodomain proteins, NUTM1-rearrangement has since been identified in tumors at non-midline locations, with non-bromodomain partners and with varied morphology. The histologic features of these tumors have also expanded to include sarcoma, skin adnexal tumors, and hematologic malignancies that harbor various fusion partners and are associated with markedly different clinical courses varying from benign to malignant. Most of these tumors have nondescript primitive morphology and therefore should be routinely considered in any undifferentiated neoplasm. The diagnosis is facilitated by the immunohistochemical use of the monoclonal C52 antibody, fluorescence in situ hybridization (FISH), and, recently, RNA-Sequencing. The pathogenesis is believed to be altered expression of oncogenes or tumor suppressor genes by NUT-mediated genome-wide histone modification. NUTM1-rearranged neoplasms respond poorly to classical chemotherapy and radiation therapy. Targeted therapies such as bromodomain and extraterminal domain inhibitor (BETi) therapy are being developed. This current review provides an update of NUTM1-rearranged neoplasms, focusing on the correlation between basic sciences and clinical aspects.

In South Western Indian ocean (IO), Extended-Spectrum β-Lactamase producing Enterobacteriaceae (ESBL) are a main public health issue. In livestock, ESBL burden was unknown. The aim of this study was estimating the prevalence of ESBL on commercial farms in Reunion, Mayotte and Madagascar and genes involved. Secondly, risk factors of ESBL occurrence in broiler, beef cattle and pig farms were explored. In 2016-2017, commercial farms were sampled using boot swabs and samples stored at 4°C before microbiological analysis for phenotypical ESBL and gene characterization. A semi-directive questionnaire was performed. Prevalences observed in all production types and territories were elevated, except for beef cattle in Reunion which differed significantly. The most common ESBL gene was the CTX-M-1 subtype. Generalized linear models explaining ESBL occurrence varied between livestock production sectors and allowed identifying main protective (e.g., water quality control and detergent use for cleaning) and risk factors (e.g., recent antibiotic use, other farmers visiting the exploitation, pet presence). This study is the first to explore tools for antibiotic resistance management in IO farms. It provides interesting hypothesis to explore about antibiotic use in IO and ESBL transmission between pig, beef cattle and humans in Madagascar.

Abstract: (1) Background: The occurrence of youth aggression has aroused widespread concern, and we would like to explore the reasons for it from both the family and individual sides of the youth. This study constructed a chain mediation model based on Bandura's Social Learning Theory to explore the mechanism of internet gaming disorder and avatar identification in it; (2) Methods: We conducted a randomized survey involving 973 adolescents from various middle schools in China. We used the Harsh Parenting Scale, the Online Gaming Disorder Scale, the Incarnate Identity Scale, and the Buss-Perry Aggression Scale to conduct a randomized survey. Empirical analyses were conducted using SPSS 25.0 and Amos 24.0 software to examine the mediating role of online gaming barriers and avatar identity; (3) Results: There was a two-by-two significant positive correlation between harsh parenting, internet gaming disorder, avatar identification and aggression. The me-diation model between harsh parenting, internet gaming disorder, avatar identification and ag-gression was well fitted ( χ2/df=7.268, GFI=0.961, AGFI=0.923, IFI=0.970, CFI=0.970, TLI=0.951, RMSEA=0.080).; (4) Conclusions: Parental harsh parenting affects adolescent aggression not only through the separate mediating roles of internet gaming disorder and avatar identification, but also through the chain mediating roles of internet gaming disorder and avatar identification.

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.

In this paper, the deformation and phase transformation of disorder α phase at (α + γ) two phase region in as-forged Ti-44Al-8Nb-(W, B, Y) alloy are investigated by hot compression and hot packed rolling. Detailed microstructural evolution demonstrates that the as-deformed microstructure is significantly affected by deformation conditions. The mircrostructure differences are mainly due to temperature drop and strain rate. The evolution of α lamelae into α grains is detailed descripted. Moreover, the disorder α lamellae can also be decomposed into some new α grains by the assisted decomposition mechanism of γ grains. Microstructure evolution model of current TiAl alloy at 1250 °C during hot rolling is built.

Great Himalayan range with regions namely, Jammu & Kashmir, Ladakh and high altitude parts of north eastern states inherently experience high solar exposure, cold, arid climate and significantly challenging geography. With a scarcity of affordable public housing projects in these regions a grid enabled low energy residential prototype is proposed having the capability to operate on nearly zero consumption of heating and cooling energy with the application of indigenous and contemporary energy efficient passive design techniques. Preliminary study, development of design and reading of simulation results were applied for the performance and benefit analysis of the low energy building prototype. Analysis of the climatic zone further classified and narrowed the design criterion by confirming upon beneficial architectural components proven to be energy efficient. These architectural components include, optimization of direct solar gain and orientation of building envelope, modified trombe wall system, traditional sunrooms, solar chimney with openable vents, efficient spatial planning and compliance of relevant parameters such as window-wall-ratio (WWR). The proposed low energy housing for the economically weaker section is estimated to save nearly 50% of active fuel based household heating energy. Site has been planned in such a way that about 100% of required electricity can be generated from on site renewable energy for the proposed infrastructure, it is proven more beneficial if additional electricity is generated to offset the power supply and result in lower or subsidized electricity bills. Design is compliant to different codes relevant to energy conservation and low-income housing with an embodied carbon of about 1.2 kgCO2/m2 per dwelling unit giving ‘A’ grade in cradle to gate impacts. The findings and performance of this prototype can serve as a guideline for energy efficient design in low income group housing situated in severe cold and arid regions of India such as Ladakh (U.T.).

The clustering methods of Software Defined Networking (SDN) gained popularity due to their ability to offer improved scalability, consistency, dependability, and load balancing within overlay networks and SDN partitions. This paper delved into the effects of increasing the number of OpenFlow-enabled southbound devices on the establishment and coordination of SDN-Controller clusters. Specifically, we examined the volume of east-west cluster packet communication concerning the number of southbound devices within the topology. Many research studies focused on bandwidth and the number of bytes in East-West communication. While bandwidth referred to the maximum rate at which data could be transferred, and the number of bytes reflected the volume of data being transmitted, the number of packet communications directly influenced the efficiency and responsiveness of network operations. Our investigation encompassed the impact of SDN controllerto- controller communication within the cluster concerning the rising number of OpenFlow switches connected to various topologies, including tree (star-bus network), linear, and torus configurations. This study presented data on communication patterns within Open Network Operating Systems (ONOS) and OpenDaylight (ODL) clusters, revealing differing levels of controller communication with southbound network expansions. We evaluated the scalability of ODL and ONOS controllers by scrutinising the effect of increasing the number of southbound devices on control communication volume. Our analysis revealed varied communication patterns within ONOS and ODL clusters, resulting in different volumes of control communication with southbound expansions. The findings indicated that in small to medium-sized SDNs, ODL outperformed ONOS, notably with faster cluster discovery. Conversely, ONOS demonstrated greater efficiency in larger networks owing to its centralised communication architecture. Finally, we provided recommendations for selecting the most suitable controllers based on the size of southbound networks, aiming to provide practical guidelines for optimal network performance.

Immune-cell reprogramming driven by mitochondria-derived reactive electrophilic immunometabolites (mt-REMs—e.g., fumarate, itaconate) is an emerging phenomenon of major biomedical importance. Despite their localized production, mt-REMs elicit significantly-large local and global footprints within and across cells, through mechanisms involving electrophile signaling. Burgeoning efforts are being put into profiling mt-REMs’ potential protein-targets and phenotypic mapping of their multifaceted inflammatory behaviors. Yet, precision indexing of mt-REMs’ first-responders with spatiotemporal intelligence and locale-specific function assignments remains elusive. Highlighting the latest advances and overarching challenges, this perspective aims to stimulate thoughts and spur interdisciplinary innovations to address these unmet chemical-biotechnological needs at therapeutic immuno-signaling frontiers.

In the present paper, we efficiently solve the two-body problem for extreme cases such as those with high eccentricities. The use of numerical methods, with the usual variables, cannot maintain the perihelion passage accurately. In previous articles, we have verified that this problem is treated more adequately through temporal reparametrizations related to the mean anomaly through the partition function. The biparametric family of anomalies, with an appropriate partition function, allows a systematic study of these transformations. In the present work, we consider the elliptical orbit as a meridian section of the ellipsoid of revolution, and the partition function depends on two variables raised to specific parameters. One of the variables is the mean radius of the ellipsoid at the secondary, and the other is the distance to the primary. One parameter regulates the concentration of points in the apoapsis region, and the other produces a symmetrical displacement between the polar and equatorial regions. The three most used geodesy latitude variables are also studied, resulting in one not belonging to the biparametric family. However, it is in the one introduced now, which implies an extension of the biparametric method. The results obtained by the method presented here now allow a causal interpretation of the operation of numerous reparametrizations used in the study of orbital motion.

Abstract: Placenta accreta spectrum (PAS) is a severe complication of pregnancy associated with excessive invasion of cytotrophoblast cells at the sites of the endometrial-myometrial interface and the myometrium itself in cases of adherent (creta) and invasive (increta and percreta) forms, respectively. Despite advancements in ultrasound protocols and found associations of alpha-fetoprotein, PAPP-A, hCG, PLGF, sFlt-1, IL-8, and IL-33 peripheral blood levels with PAS, the condition remains undiagnosed before delivery because of the lacking clear evaluation criteria for each of the three grades of PAS. This leads to a high risk of massive blood loss, maternal hysterectomy, and preterm birth. While using deep sequencing, miRNA signatures of placental tissue, myometrium, and blood plasma from women with PAS in the third trimester of pregnancy, as well as miRNA profile in exosomes from the blood serum of women in the first trimester with physiologically progressing pregnancy, complicated by PAS or preeclampsia, were obtained. Two logistic regression models were constructed, both featuring statistically significant parameters related to the levels of miR-26a-5p, miR-17-5p, and miR-101-3p quantified by real-time PCR in native blood serum. These models demonstrated 100% sensitivity in detecting PAS during the first pregnancy screening. These miRNAs were identified as specific markers for PAS, showing significant differences in their blood serum levels during the first trimester in the PAS group compared to those in physiological pregnancies, early- or late-onset preeclampsia groups. Furthermore, these miRNAs exhibited differential expression in the PAS placenta and/or myometrium in the third trimester and, according to literature data, control angiogenesis. Significant correlations were found between extracellular hsa-miR-101-3p and nuchal translucency thickness, hsa-miR-17-5p and uterine artery pulsatility index, and hsa-miR-26a-5p and hsa-miR-17-5p with PLGF. The developed test system for early non-invasive PAS diagnosis based on the blood serum level of extracellular miR-26a-5p, miR-17-5p, and miR-101-3p can serve as an auxiliary method for 1st trimester screening pregnant women, subject to validation on independent test samples.

We analyze the expected arrival time spectrum of supernova neutrinos using simulated luminosity and computing the expected number of events in future detectors such as the DUNE Far Detector and Hyper-Kamiokande. We develop a general method using minimum square statistics that can compute the sensitivity to any variable affecting neutrino time of flight. We apply this method in two different situations: First, we compare the time spectrum changes due to different neutrino mass values to put limits in electron (anti)neutrino effective mass. Second, we constrain Lorentz Invariance Violation through the mass scale, MQG, at which it would occur. We consider two main neutrino detection techniques: 1. DUNE-like liquid argon TPC, for which the main detection channel is νe+40Ar→e−+40K*, related to the supernova neutronization burst, and 2. HyperK-like water Cherenkov detector, for which ν¯e+p→e++n is the main detection channel. We consider a fixed supernova distance of 10 kpc and two different masses of the progenitor star: (i) 15 M⊙ with neutrino emission time up to 0.3 s and (ii) 11.2 M⊙ with neutrino emission time up to 10 s. The best mass limits at 3σ are of O(1) eV. For νe, the best limit comes from a DUNE-like detector if the mass ordering happens to be inverted. For ν¯e, the best limit comes from a HyperK-like detector. The best limit for the Lorentz Invariance Violation mass scale at 3σ level, considering superluminal or subluminal effect, is MQG≳1013 GeV (MQG≳5×105 GeV) for linear (quadratic) energy dependence.

Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is a serious-global public health issue. A total of 292 E. coli isolates obtained from fecal samples of pigs in Central (n = 103) and Northeastern (n = 189) provinces of Thailand were included in this study. Eighty-six E. coli isolates were phenotypically confirmed to be β-lactamase producers (29.5%) and screened for the presence of β-lactamase genes. The genes in CTX-M family was most frequently found (90.7%). The blaCTX-M-15 gene (59.3%) was predominantly identified CTX-M genotype, followed by blaCTX-M-14 (31.4%) and blaCTX-M-4 (25.6%). The blaTEM-1 gene was prevalent (75.6%). The blaCTX-M-4 and blaCTX-M-14 genes were located on conjugative plasmid. The results highlight healthy pigs as reservoirs of ESBL-producing E. coli carrying ESBL genes that could be horizontally transferred.

In the present work, we provide an electronic structure based method for the “on-the-fly” deter- mination of vibrational sum frequency generation (v-SFG) spectra. The predictive power of this scheme is demonstrated at the air-water interface. While the instantaneous fluctuations in dipole moment are obtained using the maximally localized Wannier functions, the fluctuations in polar- izability are approximated to be proportional to the second moment of Wannier functions. The spectrum henceforth obtained captures the signatures of hydrogen bond stretching, bending, as well as low-frequency librational modes.

The image performance of acoustic and ultrasound sensors depends on several fundamental parameters such as depth of focus or spatial resolution. There are currently two different type of acoustic diffractive lenses: those which form a diffraction-limited spot with a shallow depth of focus (zone plates) and lenses which form an extended focus (quasi-Bessel beams). In this paper, we investigate a pupil-masked Soret zone plate which allows the tunability of a normalized angular spectrum. It is shown that the depth of focus and the spatial resolution can be modified, without changing the lens structure, by choosing the size of the amplitude pupil mask. This effect is based on the transformation of spherically converging waves into quasi-conical waves, due to the apodization of the central part of the zone plate. The theoretical analysis is verified with both numerical simulations and experimental measurements. A Soret zone plate immersed in water with D/2F=2.5 and F=4.5$\lambda$, changes its depth of focus from 2.84$\lambda$ to 5.9$\lambda$ and the spatial resolution increases from 0.81$\lambda$ to 0.64$\lambda$ at a frequency of 250 kHz, by modifying the pupil mask dimensions of the Soret zone plate.

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

This paper addresses the grammatical challenges associated with the development of clause complexity, focusing on the performance of a group of monolingual Spanish-speaking schoolchildren with Specific Language Impairment/Developmental Language Disorder (SLI/DLD) in a longitudinal corpus of oral narrative samples. The study examines the presence of interclause relations of subordination and equivalence (hypotaxis and parataxis) in language samples of two groups: an experimental group made up of 24 schoolchildren with SLI/DLD and a control group made up of 24 schoolchildren with typical development (TD). The results show that while both groups use parataxis as the most common relation between clauses in all school grades, there is a significant decrease in paratactic relations and a significant increase in hypotactic relations from first to fourth grade of primary education. Although the development patterns are highly similar, the SLI/DLD group shows greater difficulties in mastering more complex (hypotactic) relations in fourth grade compared to the control group, indicating that they are less sophisticated in the use of these types of complex relations. These findings suggest that focused support on the most complex structures is needed towards the fourth grade of primary education, given the demands of the school academic register from 6 and 7 years of age, and the potential problems that the development of clause complexity can cause in school-age children.

While shoulder injuries represent the musculoskeletal disorders (MSDs) most encountered in physical therapy, there is no consensus on their management. As attempts to provide standardized and personalized treatment, a robot-ic-assisted device combined with EMG biofeedback specifically dedicated to shoulder MSDs has been developed. The aim of this study was to determine the efficacy of an 8-week rehabilitation program (≈3 sessions a week) using a ro-botic-assisted device combined with EMG biofeedback (RA-EMG group) in comparison with a conventional program (CONV group) in patients presenting with shoulder MSDs. This study is a retrospective cohort study including data from 2010 to 2013 on patients initially involved in a physical rehabilitation program in a private clinic of Chicoutimi (Canada) for shoulder MSDs. Shoul-der flexion strength and range of motion were collected before and after the rehabilitation program. Forty-four patients participated in a conventional pro-gram using dumbbell (CONV group) while 72 of them completed a program on robot-assisted device with EMG and visual biofeedback (RA-EMG group), whereby both programs consisted in 2 sets of 20 repetitions at 60% of maximal capacity. Results showed that the RA-EMG had significantly greater benefits than the Conv group for shoulder flexion strength (+103.1% vs 67%, p = 0.016) and range of motion (+14.4% vs 6.1%, p = 0.046). The current retrospective co-hort study showed that a specific and tailored rehabilitation program with constant effort by automatic adjustment of the level of resistance was able to potentiate strength and range of motion shoulder flexion after an 8-week reha-bilitation period in comparison with a conventional approach in patients with shoulder MSDs. This study provides new insight on shoulder MSD rehabilita-tion and future research should be pursued to determine the added potential of this approach for abduction and external rotation with a randomized controlled design.

Background. 46,XX disorders of sex development are rare. Approximately, 90% of XX males are SRY-positive, while testicular development in the absence of SRY takes place in a minority. Methods: A boy with 46,XX karyotype (SRY-negative; absence of SOX9 duplications) was investigated by targeted Next Generation Sequencing (NGS), Multiplex ligation-dependent probe amplification (MLPA), and Comparative Genomic Hybridization array (CGH-array). Results: The boy had normal male phenotype and normal prepubertal values of testicular hormones. He presented a heterozygous duplication of 49.626 bp, encompassing exons 2 and 3 of DMRT1. The result was arr[GRCh37] 9p24.3(845893_895518)x3. Since both breakpoints are harbored in the intronic regions, the duplication does not stop or shift the coding frame. Additional known pathogenic or uncertain variants in pro-testis gene cascade were not identified. Conclusions: This study report a boy with 46,XX testicular disorder of sex differentiation, showing a de novo partial intragenic duplication of DMRT1. This intragenic duplication may result in a gain of function, acting as primary pro-testis gene (or anti-ovary gene) in a 46,XX human foetus and permitting normal pre-pubertal endocrine testis function.

The present study aimed to investigate the effect of a motor skills training program in children with DCD considering their gender. The Movement Assessment Battery for Children (MABC-2) classified the children and assessed skill changes over time. The study was implemented at four kindergartens in the Khorezm region of Uzbekistan. In the study, all children had DCD (5.17 ± 0.70 years; 10 girls), and all indicators on MABC-2 were less than 16 percent. Participants were divided into an experimental group (n=17) receiving ten weeks of motor skills training program for 45 min twice per week, the control group (n=7) proceeded with exercises of everyday living. All children in the experimental group had a significant increase in total percentile rank of MABC-2 and concerning each domain (manual dexterity; throwing and catching; balance). In the control group, a significant decrease in the total percentile rank of MABC-2 and each domain of MABC-2 was observed. The effectiveness of the intervention program was similar across both genders. The study supports that a period of 10 weeks of a motor skills training program can increase the quality of children's motor coordination and represent a valuable procedure for physical education specialists to enhance motor skills for children with DCD.

It is not new in medical history to propose a global concern to be classified as a disease. Defining a concern into disease allows to assign ethical responsibilities to develop powerful and effective interventions. It also allow to appropriate distribute the resources uniformly economically and morally. In 2003, World Health Organization report stated that 30-50 % of patients do not take their medications as prescribed associated with morbidity, mortality and health cost. It was considered a global concern, however, irrespective of decades of researches conducted on medication adherence, we are still unable to state that medication adherence issues are being resolved. In this review, we have described few apprehensions in current understandings of medication adherence that have limited its research. We have also proposed medication adherence as disorder and provided its’ definition and classification

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.

Disorders associated with substance abuse are a major public health crisis with few treatment options. According to World Health Organization (WHO) ethanol is the most widely used drug in the world, and it represents a risk factor for the advent of disease, disability, and eventually death. Foetal Alcoholic Spectrum Disorders (FASD) is a diagnostic term to describe the range of effects that can occur in an individual whose mother drank alcohol during pregnancy. These effects encompass both physical, mental, behavioural and further lifelong disabilities. Besides, ethanol can harm the gut microbiota. Gut microbiome is firstly acquired from the mother and it is crucial for intestinal homeostasis during hosts’ lifetime. It is responsible for producing metabolites that benefits and protects the host from harm microbial colonization. Knowledge about the interactions between human gut microbes and the developing nervous system is still scarce. Nevertheless, animal models have shown that gut bacteria and microbial metabolites are strongly associated with Central Nervous System (CNS) homeostasis. Endotoxins such as Lipopolysaccharides (LPS) are hypothesized to have a major role in neurodegeneration, however, conclusions must be taken with care due to differences in sensitivity between humans and mice. In this review we focus on the role of gut microbiota on the neurodevelopment of mice when ethanol consumption is one of the major stressors during prenatal period. We detail the range of the endotoxin hypothesis in describing endotoxins’ contribution to neurodegeneration and the influence that kynurenine pathway has on the process.

Microbial diseases have been declared one of the main threats to humanity, which is why, in recent years, great interest has been generated in the development of nanocomposites with antimicrobial capacity. In the present work, two magnetic nanocomposites, based on Graphene Oxide (GO) and Multiwall Carbon Nanotubes (MWCNTs) were studied. The synthesis of these magnetic nanocomposites consisted of three phases: first, the synthesis of Iron Magnetic Nanoparticles (MNPs) was carried out in the presence of MWCNTs and GO using the Co-precipitation method. The second phase consisted of the adsorption of photosensitizer menthol-Zinc phthalocyanine (ZnMintPc) into MWCNTs and GO, and the third phase was the encapsulation in poly (N-vinylcaprolactam-co-poly(ethylene glycol diacrylate)) poly (VCL-co-PEGDA) polymer VCL/PEGDA a biocompatible hydrogel, in order to obtain the magnetic nanocomposites: VCL/PEGDA-MNPs-MWCNTs-ZnMintPc and VCL/PEGDA-MNPs-GO-ZnMintPc. In vitro studies were carried out using Escherichia coli and Staphylococcus aureus bacteria and the Candida albicans yeast based on the PTT/PDT effect. This research describes the optical, morphological, magnetic and photophysical characterizations of nanocomposites and their application as antimicrobial agents. It was evaluated the antimicrobial effect of magnetics nanocomposites based on the Photodynamic/Photothermal (PDT/PTT) effect; for this purpose, doses of 65 mW cm-2 at 630 nm of light were used. The VCL/PEGDA-MNPs-GO-ZnMintPc nanocomposite was able to eliminate colonies of E. coli and S. aureus, while VCL/PEGDA-MNPs-MWCNTs-ZnMintPc nanocomposite was able to eliminate the three types of microorganisms; consequently, the latter is considered a broad-spectrum of antimicrobial agent in PDT and PTT.

While the importance of continuous monitoring of electrocardiographic (ECG) or photoplethysmographic (PPG) signals to detect cardiac anomalies is generally accepted in preventative medicine, there remain major barriers to its actual widespread adoption. Most notably, current approaches tend to lack real-time capability, exhibit high computational cost, and be based on restrictive modeling assumptions or require large amounts of training data. We propose a lightweight and model-free approach for the online detection of cardiac anomalies such as ectopic beats in ECG or PPG signals based on the change detection capabilities of Singular Spectrum Analysis (SSA) and nonparametric rank-based cumulative sum (CUSUM) control charts. The procedure is able to quickly detect anomalies without requiring the identification of fiducial points such as R-peaks and is computationally significantly less demanding than previously proposed SSA-based approaches. Therefore, the proposed procedure is equally well suited for standalone use and as an add-on to complement existing (e.g. heart rate (HR) estimation) procedures.

We report a facile route for the green synthesis of trimethylchitosan nitrate-capped silver nanoparticles (TMCN-AgNPs) with positive surface charge. In this synthesis, silver nitrate, glucose, and trimethyl chitosan nitrate (TMCN) were used as silver precursor, reducing agent, and stabilizer, respectively. The reaction was carried out in a stirred basic aqueous medium at room temperature without the use of energy-consuming or expensive equipment. We investigated the effects of the concentrations of NaOH, glucose, and TMCN on the particle size, zeta potential, and formation yield. The AgNPs were characterized by UV-visible spectroscopy, photon correlation spectroscopy, laser Doppler anemometry, transmission electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The catalytic activity of the TMCN-AgNPs was studied by the reduction of 4-nitrophenol using NaBH₄ as a reducing agent. We evaluated the antibacterial effects of the TMCN-AgNPs on Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus using the broth microdilution method. The results showed that both gram-positive and gram-negative bacteria were killed by the TMCN-AgNPs at very low concentration (< 6.13 μg/mL). Moreover, the TMCN-AgNPs also showed high antibacterial activity against clinically isolated multidrug-resistant A. baumannii strains, and the minimum inhibitory concentration (MIC) was ≤ 12.25 μg/mL.

In this study, in order to develop the composition ceramics for the application of ultrasonic transducer device for temporomandibular joint disorder pain relief and facial skin massage, Pb0.88(La0.6Sm 0.4)0.08(Mn 1/3 Sb 2/3)0.02 Ti 0.98 O3 ceramics were manufactured using CuO as sintering aids, and their piezoelectric ,and resonant properties were investigated. At the specimen sintered at 1200 [℃], the excellent values of piezoelectric properties appeared, respectively: the dielectric constant (εr) of 202, piezoelectric constant (d33) of 56[pC/N], first and third overtone electromechanical coupling factor kt of 0.548, kt3 of 0.219, and then first and third overtone mechanical quality factor Qmt1 of 345, Qmt3 of 292 were suitable for the device application such as ultrasonic transducer, respectively. When the length of one side was 7.7 mm, first and third overtone electromechanical coupling factor kt1 of 0.555, kt3 of, 0.196, and then first ,third overtone mechanical quality factor Qmt1 of 381, Qmt3 of 393 , and the first dynamic ratio(D.R) and third overtone dynamic ratio(D.R) of 63.7(dB),and 37.7(dB) were suitable for the device application such as ultrasonic transducer ,respectively .

Background: Dual disorders (DD) involve the coexistence of substance use disorder (SUD) with another mental illness, often from psychotic and affective categories. This study explores the ef-fectiveness of brexpiprazole, a third-generation antipsychotic, in individuals diagnosed with schizophrenia spectrum disorder (DSM-V) and comorbid AUD/SUD (DSM-V). Methods: Eighteen enrolled patients underwent psychometric assessments at baseline and one month into brexpiprazole treatment administered at a mean dosage of 2 mg/day. Results: Brexpiprazole demonstrated significant reductions in psychopathological burden (PANSS total score, p=0.004), improved CGI total score (p=0.042), and decreased MOAS total score (p=0.012). Quality of life improved in SF-36 subscales (p<0.05). Substance craving reduction, though observed, did not reach statistical significance. Conclusions: This study provides initial evidence supporting brexpiprazole's efficacy and safety with positive effects on psychopathology and quality of life, emphasizing the need for tailored, comprehensive treatment strategies in this complex patient population.

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.

(1) Background: donor-derived circulating free DNA (dd-cfDNA) is an innovative biomarker with great potential for the early identification and prevention of graft damage; (2) Methods: Prospective study to analyze dd-cfDNA plasma levels in 30 kidney transplant patients during their post-transplant follow-up (15 days, 3, 6 and 9 months), to determine if the result could be of interest in the identification of possible adverse events, specially allograft rejection. In addition, the aim is also to verify the obtained data on sensitivity, specificity, NPV and PPV; (3) Results: Plasma levels of dd-cfDNA could be considered a novel biomarker of graft rejection after first term post-transplant up to several months before its clinical presentation, mainly in TCMR or ABMR. In this study, it appears to have no positive predictive value for borderline rejection or TCMR IA. Our results show a low NPV of the technique because other pathologies or biological post-transplant complications can also affect dd-cfDNA levels and they must be considered in the interpretation of the result.; (4) Conclusions: dd cfDNA could allow, together with other additional biomarkers in the context of a future score, avoid invasive biopsies in most cases, mainly in the case of suspected TCMR or ABMR.

Background: Little is known about the decisional background of choosing an appropriate disease model. Therefore, this paper aims, (1) to identify a spectrum of reasons for choosing between animal and non-animal disease models and (2) provides an ethical analysis of these reasons. Methods: 13 researchers from basic and preclinical research were interviewed, the interviews were analyzed qualitatively and the results were categorized. The ethical analysis was based on the principlism approach and a value judgement model. Results: This paper presents 66 reasons why researchers use animal (41 %) or alternative, non-animal disease models (59 %). Most of the reasons were be assigned to the work environment (29 reasons) and scientific standards (22 reasons). Other reasons were assigned to personal attitudes (11 reasons) and animal welfare (4 reasons). Qualitative relevant normative differences are presented in the ethical analysis. Even if few reasons can be rejected outright from an ethical point of view, there are good reasons to give some more weight than others. Conclusions: The spectrum of reasons and its ethical assessment provide a framework for reflection for researchers who may have to choose between animal models and (investing in) alternatives. This can help to reflect on and justify decisions.

Aims: The lack of information about the inter variability of the test results obtained by CLSI and EUCAST requires further clarifications to interpret antimicrobial susceptibility patterns better. This study aimed to compare the CLSI and EUCAST interpretations of the antimicrobial susceptibility test results of the ESBL–producing uropathogenic Escherichia coli and Klebsiella pneumonia strains. Methods: After obtaining 157 ESBL-producing E. coli and 95, ESBL-producing K. pneumonia isolates from the urine specimens of the patients, Kirby-Bauer’s disc diffusion method was used for conducting antimicrobial susceptibility test. The test procedures and the interpretation of the results were carried out according to the year 2017 versions of both of the two guidelines. For the statistical comparison of concordance between the two guidelines, the Kappa coefficients and the concordance rates were calculated. Results: The results were graded in the range from perfect to poor agreement. For E. coli, interpretations of the AST results revealed a moderate to perfect agreement between both methods. Weighted Kappa agreement scores in the range from 0.42 to 1. The agreement for AMC, TPZ30/6, ceftazidime 10, meropenem, and aztreonam was poor without any inconsistencies. For Klebsiella, the kappa agreement score was in the range from 0.25 to 1. It was incompatible with AMC, TPZ 30/6, ceftazidime 10, aztreonam; there was poor agreement for cefepime, amikacin and ertapenem. Conclusions: Our results showed agreement between the two guidelines for uropathogenic extended-spectrum ß-lactamase producing Escherichia coli and Klebsiella pneumoniae but also showed inconsistencies between two guidelines. Therefore, the results of our study contribute to the comparison of these guidelines for interpreting antibiotic susceptibilities.

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

Rett syndrome (RTT) is mainly caused by mutations in methyl CpG-binding protein 2, cyclin-dependent kinase-like 5, or forkhead box protein G1. These RTT-causing proteins harbor an intrinsically disordered region (IDR) whose conformation exhibits spatiotemporal heterogeneity, which not only confer versatility to the protein, but also implicates them in diseases. The IDR generally evolves more rapidly than an ordered structure. In this study, we examined the relationship between pathogenic RTT-associated point mutations in RTT-causing proteins and the evolutionary dynamics of sequence features including structural order–disorder, phosphorylation sites, and evolutionary rates. We also analyzed the molecular properties and evolution of proteins that interact with RTT-causing proteins in terms of phylogenetic profiles, tissue specificity, subcellular localization, expression level, and functions. The results indicate that constrained IDRs may function by forming contacts with other regions in the protein sequence causing pathogenic missense mutations likely to arise in the rapidly evolving IDR and affect molecular networks, leading to disease. The results also provide novel insights into the genetic basis for RTT and the evolution of the neocortex in higher vertebrates.

: Poultry products in Zambia form an integral part of the human diet in many households, as they are cheap and easy to produce. The burden of poultry diseases has, however, remained a major challenge. Growing consumer demand for poultry products in Zambia has resulted in non-prudent antimicrobial use on farms, intending to prevent and treat poultry diseases for growth optimization and maximising profits. This cross-sectional study aimed to identify the different types of bacteria causing diseases in chickens in Lusaka and to detect the extended-spectrum-lactamase (ESBL)-encoding genes. We collected 215 samples from 91 diseased chickens at three post-mortem facilities and screened them for gram-negative bacteria. Of these samples, 103 tested positive for various clinically relevant Enterobacteriaceae, including Enterobacter (43/103, 41.7%), Escherichia coli (20/103, 19.4%), Salmonella (10/103, 9.7%), and Shigella (8/103, 7.8%). Other isolated bacteria included Yersinia, Morganella, Proteus, and Klebsiella, which accounted for 21.4%. E. coli, Enterobacter, Salmonella, and Shigella were subjected to antimicrobial susceptibility testing. The results revealed that E. coli, Enterobacter, and shigella were highly resistant to tetracycline, ampicillin, amoxicillin, and trimethoprim-sulfamethoxazole, while Salmonella showed complete susceptibility to all antibiotics. The observed resistance patterns correlated with antimicrobial usage estimated from sales data from a large-scale wholesale and retail company. Six (6/14, 42.9%) E. coli isolates tested positive for bla_CTX-M, whilst eight (8/14, 57.1%) Enterobacter samples tested positive for bla_TEM. Interestingly, four (4/6, 66.7%) of the E. coli isolates carrying bla_CTX-M-positive strains were also positive for bla_TEM. Sanger sequencing of the PCR products revealed that five (5/6,83.3%) of the abovementioned isolates possessed the bla_CTX-M-15 allele. The results suggest the presence of potentially pathogenic ESBL-producing Enterobacteriaceae in poultry, threatening public health. Keywords:. Enterobacteriaceae, bla_CTX-M, bla_TEM

This paper addresses the problem of non-cooperative spectrum sensing in very low signal noise ratio (SNR) conditions. In our approach, detecting an unoccupied bandwidth consists to detect the presence or absence of a communication signal on this bandwidth. Major well known communication signals may contain hidden periodicities, we use the Recurrence Quantification Analysis (RQA) to reveal the hidden periodicities. RQA is very sensitive to a reliable estimation of the phase space dimension m or the time delay τ. In view of the limitations of algorithms proposed in the literature, we have proposed a new algorithm to estimate simultaneously the optimal values of m and τ. The new proposed optimal values allow the states reconstruction of the observed signal and then the estimation of the distance matrix. This distance matrix has particular properties which we have exploited to propose the Recurrence Analysis based Detector (RAD). RAD can detect a communication signal in a very low SNR condition. Using Receiver Operating Characteristic curves, our experimental results corroborate the robustness of our proposed algorithm comparing to classical widely used algorithms.

Enterovirus 71 (EV71) is an etiological agent of hand foot and mouth disease and can also cause neurological complications in young children. However, there are no approved drugs to treat EV71 infections. In this study, we conducted an antiviral drug screening by using a Food and Drug Administration (FDA)-approved drug library. We identified five drugs that showed dose-dependent inhibition of viral replication. Sertraline was further characterized because it exhibited the most potent antiviral activity with the highest selectivity index among the five hits. The antiviral activity of sertraline was noted for other EV serotypes. The drug’s antiviral effect is not likely associated with its approved indications as an antidepressant and its mode-of-action as a selective serotonin reuptake inhibitor. The time-of-addition assay revealed that sertraline inhibited an EV71 infection at the entry stage. We also showed that sertraline partitioned into acidic compartments, such as endolysosomes, to neutralize the low pH levels. In agreement with the findings, the antiviral effect of sertraline could be relieved greatly by exposing virus-infected cells to extracellular low-pH culture media. Together, we have identified an FDA-approved antidepressant with the new indication for the broad-spectrum EV inhibition by blocking viral entry through the alkalization of the endolysosomal route.

The term deviation frequency denotes the boundary between the variable part of the amplitude and phase scintillation spectrum and the part of uninformative noises. We suggested the concept of the “characteristic deviation frequency” during the observation period which is defined as the most probable value of the deviation frequency under current local conditions. This work is a case study of the characteristic deviation frequency (fd) registered for GPS, GLONASS, Galileo and SBAS signals under quiet and weakly disturbed geomagnetic conditions in April 2021 at the mid-latitude GNSS station. Our results demonstrated that the fd value for all signal components of GPS, GLONASS and GALILEO signals varied within 15-22 Hz. The characteristic deviation frequency was 20 Hz for the mentioned GNSS signals. In difference, the deviation frequency was limited within 13-20 Hz for SBAS with the lower characteristic deviation frequency at 18 Hz. We assume that the concept of the characteristic deviation frequency can be used to determine the optimal sampling rate of the GNSS carrier phase data for the ionospheric studies. The characteristic deviation frequency can also characterize the state of the regular trans-ionospheric radio channel.

Learning disorders (LD) are diagnosed in children impaired in the academic skills of reading, writing and/or mathematics. Children with LD usually show a slower resting-state electroencephalogram (EEG), with EEG patterns corresponding to a neurodevelopmental lag. LD-children also show a consistent cognitive impairment in working memory (WM), including an abnormal task-related EEG with an overall slower EEG activity of more delta and theta power, and less gamma activity in posterior sites; task-related EEG patterns considered indices of an inefficient neural resource management. Neurofeedback (NFB) treatments aimed at normalizing the resting-state EEG of LD-children have shown improvements in cognitive-behavioral indices and diminished EEG abnormalities. Given the typical findings of a WM impairment in LD-children; we aimed to explore the effects of a NFB treatment in the WM of children with LD, by analyzing the WM-related EEG power-spectrum. We recruited 18 children with LD (8-10 years old). They performed a Sternberg-type WM-task synchronized with an EEG of 19 leads (10-20 system) twice in pre-post treatment conditions. They went through either 30 sessions of a NFB treatment (NFB-group, n= 10); or through 30 sessions of a placebo-sham treatment (Sham-group, n= 8). We analyzed the before-after treatment group differences for the behavioral performance and the WM-related power-spectrum. The NFB group showed faster response times in the WM-task post-treatment. They also showed an increased gamma power at posterior sites and a decreased beta power. We explain these findings in terms of NFB improving the maintenance of memory representations coupled with a reduction of anxiety.

Background: The extended-spectrum beta-lactamase (ESBL) Klebsiella pneumoniae is one of the leading causes of health-associated infections (HAI), whose antibiotic treatments have been severely reduced. Besides, HAI bacteria may harbor pathogenic factors such as siderophores, enzymes, or capsules, which increase the virulence of these strains. Thus, new therapies such as antimicrobial photodynamic inactivation (aPDI) are needed. Method: A collection of 118 clinical isolates of K. pneumoniae were characterized susceptibility and virulence through the determination of the minimum inhibitory concentration (MIC) of Amk, Cfx, Cfz, Imp, Mer, and Pip-taz, and by PCR, the frequency of the virulence genes, K2, magA, rmpA, entB, ybtS, and allS. Susceptibility to innate immunity, such as human serum, macrophages, and polymorphonuclear cells, was tested. All the strains were tested for sensitivity to the photosensitizer PSIR-3 (4µg/mL) in a 17µW/cm2 for 30 min aPDI. Results: A significantly higher frequency of virulence genes in ESBL than non-ESBL bacteria were observed. The isolates of the genotype K2+, ybtS+, and allS+ display enhanced virulence since they showed higher resistance to human serum as well as to phagocytosis. All strains are susceptible to the aPDI with PSIR-3 decreasing viability in 3log10. The combined treatment with Cfx improved the aPDI to 6log10 for the ESBL strains. The combined treatment is synergistic as it showed an FIC index value of 0.15. Conclusions: The aPDT effectively inhibits clinical isolates of K. pneumoniae, including the more risky strains of ESBL-producing bacteria and the K2+, ybtS+, and allS+ genotype. The aPDI with PSIR-3 is synergistic with Cfx.

Exergames (EG) are interactive video games that require physical activity and use gamification to make exercise more engaging. EG interventions have shown various benefits for older adults, such as improved mental health, quality of life, and reduced fall risk. Enhanced cognition is thought to drive these benefits. This review aimed to identify neural correlates underlying cognitive improvements in healthy older adults and those with neurocognitive disorders. We systematically searched major databases and included 13 studies from 2,095 records. Findings revealed that EG interventions led to structural brain changes and improved functional connectivity in healthy adults, Parkinson patients, and those with mild cognitive impairment (MCI). Increased activity in the frontal, temporal, and precuneus regions during rest was specific to adults with neurocognitive disorders. Neuroplastic changes, such as elevated BDNF levels and increased neurovascular coupling, were observed in both groups. However, methodological limitations in some studies highlight the need for further high-quality research.

Objectives: The aim of this study was to determine why and how adults with attention deficit hyperactivity disorder (ADHD) experience variable impairment and identify the processes and strategies adults with ADHD use to develop positive self-regulation skills. Methods: A mixed cohort of 11 participants (6 female and 5 male) from a university, an adult ADHD clinic and an ADHD support group in the UK were interviewed online between September 2021 and February 2022. Data were collected and analysed simultaneously, inspired by constructivist grounded theory methodology. Results: Participants described a “polar awareness of difference” from others in terms of engagement and ADHD characteristics, and a “polar awareness of consciousness” experienced as the states of chaotic attention and hyperfocus, both of which impact core perceptions of self. Using an infinity paradigm, the results demonstrate unskilled attempts to self-regulate within and between these states using self-absorption or self-transcendence strategies including their inherent challenges and energetic cost. Our results further indicate that at the centre of this dynamic paradigm creative awareness strategies exist, which exemplify polarity awareness and the regulation of that awareness supported by an authentic inner compass (AIC). Conclusions: This paper presents the empirical foundation for the ADHD Creative Awareness Theory (CAT) – a new theory for understanding the experience of ADHD consciousness and environmental engagement. Practice implications are explored, and recommendations include use of the CAT as a framework for understanding and development of inherent self-regulation skills for adults with ADHD.

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

Post-traumatic stress disorder (PTSD) is a debilitating mental health disorder that causes significant dysfunction in individuals. Currently, there are many approved Pharmacotherapy and Psychotherapy treatment options for PTSD, but unfortunately, half of the patients do not respond to traditional therapies. In this article, we reviewed clinical trials and research on 3,4-methylenedioxymethamphetamine (MDMA) assisted Psychotherapy in PTSD patients, its pharmacokinetics and current treatment guidelines for PTSD. Based on the results of the efficacy of MDMA assisted Psychotherapy from six phases II Randomized controlled trials. MDMA-assisted Psychotherapy for PTSD has received the “Breakthrough Therapy” designation from the FDA. MDMA can potentially reduce PTSD symptoms even in treatment-resistant cases by increasing certain neurohormones, i.e. dopamine, serotonin, norepinephrine and oxytocin. It also modulates activities in the brain regions involved in fear and anxiety. Future research is needed to show whether the advantages outweigh the disadvantages and whether its use can be integrated into available treatment options for PTSD.

The introduction of ventricular shunts dramatically changed the outcome and quality of life of hydrocephalic patients. However, shunt surgery continues to be associated with numerous adverse events. Headache is one of the most common complications after shunt operation. It is often over a prolonged duration, the symptoms resemble migraine, and pain does not respond to medication. We propose invasive peripheral nerve stimulation as a possible solution in the treatment of patients suffering from chronic headache associated with shunted hydrocephalus. A young woman with daily holocephalic headache with diffuse pain exacerbated by lying down. Imaging revealed panventricular enlargement and possible stenosis of the aqueduct. When a ventriculoperitoneal shunt was placed, clinical symptoms resolved. Nevertheless, she gradually exacerbated after a second valve replacement due to wound infection. Imaging revealed decompressed ventricles and appropriate shunt placement. The diagnosis of chronic post-intracranial disorder headache was set. Therefore, occipital nerve stimulation was applied and considering that the patient had not a total response, bilateral parietal stimulation was added. Three months after the combined PNS she experienced total remission of headache. Combined PNS eases refractory headaches much more than occipital nerve stimulation alone and could be considered as a solution for shunted hydrocephalus associated headache.

This manuscript provides a new integrated view of the development of allergen-specific TH2 and the lack of their associated Treg cells in a unified model, justifying the need for IL-2 to correct allergy conditions.

Background: Maladaptive neuroplasticity related learned response in substance use disorder (SUD) can be ameliorated using non-invasive brain stimulation (NIBS); however, inter-individual variability needs to be addressed for clinical translation. Objective: Our first objective was to develop a hypothesis for NIBS for learned response in SUD based on competing neurobehavioral decision systems model. Next objective was to conduct computational simulation of NIBS of cortico-cerebello-thalamo-cortical (CCTC) loop in cannabis use disorder (CUD) related dysfunctional “cue-reactivity” – a closely related construct of “craving” that is a core symptom. Our third objective was to test the feasibility of our neuroimaging guided rational NIBS approach in healthy humans. Methods: “Cue-reactivity” can be measured using behavioral paradigms and portable neuroimaging, including functional near-infrared spectroscopy (fNIRS) and electroencephalogram (EEG), metrics of sensorimotor gating. Therefore, we conducted computational simulation of NIBS, including transcranial direct current stimulation(tDCS) and transcranial alternating current stimulation(tACS) of the cerebellar cortex and deep cerebellar nuclei(DCN), of the CCTC loop for its postulated effects on fNIRS and EEG metrics. We also developed a rational neuroimaging guided NIBS approach for cerebellar lobule (VII) and prefrontal cortex based on healthy human study. Results: Simulation study of cerebellar tDCS induced gamma oscillations in the cerebral cortex while tTIS induced gamma-to-beta frequency shift. Experimental fNIRS study found that 2mA cerebellar tDCS evoked similar oxyhemoglobin(HbO) response in-the-range of 5x10-6M across cerebellum and PFC brain regions (=0.01); however, infra-slow (0.01–0.10 Hz) prefrontal cortex HbO driven(phase-amplitude-coupling, PAC) 4Hz, ±2mA (max.) cerebellar tACS evoked HbO in-the-range of 10-7M that was statistically different (=0.01) across those brain regions. Conclusion: Our healthy human study showed the feasibility of fNIRS of cerebellum and PFC as well as fNIRS-driven ctACS at 4Hz that may facilitate cerebellar cognitive function via the frontoparietal network. Future work needs to combine fNIRS with EEG for multi-modal imaging.

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by a persistent pattern of inattention and/or hyperactivity-impulsivity. Neurobiologically, ADHD impairments arise from abnormalities in different circuits involving the prefrontal cortex. In face of high rates of diagnosis, alternative/complementary pharmacological therapeutic approaches for ADHD are needed. Although the number of publications that study the potential effects of caf-feine consumption on ADHD treatment have been accumulating over the last years, and caffeine has recently been used in ADHD research in the context of animal models, an updated evi-dence-based systematic review on the effects of caffeine on ADHD-like symptoms in animal stud-ies is missing. To provide insight and value at the preclinical level, a systematic review based on PRISMA guidelines was performed for all publications available up to September 1, 2021. Caffeine treatment increases attention, improves learning, memory and olfactory discrimination, without altering blood pressure and body weight. These results are supported at the neuronal level. Nonetheless, the implication of caffeine in modulating ADHD-like symptoms of hyperactivity and impulsivity is contradictory, raising discrepancies that require further clarification. Our results strengthen the hypothesis that caffeine cognitive effects found in animal models could be trans-lated to human ADHD, particularly during adolescence.

The growing emphasis on sustainability and environmental stewardship in the pharmaceutical industry necessitates innovative solutions to manage pharmaceutical waste, particularly medication bottles. This research paper explores the potential of integrating Radio Frequency Identification (RFID) and blockchain technology to enhance the traceability, accountability, and efficiency of recycling empty medication bottles. By utilizing RFID for real-time tracking and blockchain for secure, immutable data storage, this proposed system improves transparency across the supply chain and incentivizes consumer participation in recycling programs. The solution provides benefits to pharmaceutical manufacturers, regulators, and consumers, contributing to sustainability, regulatory compliance, and environmental protection.

Flomoxef (FMX) may be a potential alternative to carbapenems for dogs infected with Enterobacterales producing extended-spectrum β-lactamase (ESBL-E). However, the appropriate dosage of FMX in dogs with ESBL-E infections has yet to be established. This study was carried out to establish appropriate treatment regimens for FMX against ESBL-E infections in dogs by a pharmacokinetics–pharmacodynamics (PK–PD) approach. Five dogs received an intravenous bolus dose of FMX (40 mg/kg). Serum FMX concentrations were evaluated using high-performance liquid chromatography-tandem mass spectrometry, and PK indices were determined based on non-compartmental model. The cumulative fraction of response (CFR) was calculated based on the distribution of minimum inhibitory concentrations among wild-type ESBL-E from companion animals. As the results, the dosage regimens of 40 mg/kg q8h and q6h were estimated to achieve a CFR of &gt;90% for wild-type isolates of ESBL-producing Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis for dogs. In contrast, all regimens exhibited a CFR of &lt;80% for ESBL-producing Enterobacter cloacae. Our results indicated that dosage regimens of 40 mg/kg FMX q8h and q6h can be a non-carbapenem treatment for dogs infected with ESBL-producing isolates of Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, but not for those infected with ESBL-producing Enterobacter cloacae.

The instability of traveling pulses in nonlinear diffusion problems is inspected on the example of Gunn domains in semiconductors. Mathematically the problem is reduced to the calculation of the "energy" of the ground state in Schrödinger equation with a complicated potential. A general method to obtain the bottom-part spectrum of such equations based on the approximation of the potential by square wells is proposed and applied. Possible generalization of the approach to other types of nonlinear diffusion equations is discussed.

Multidrug resistant extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is considered a serious concern to public health worldwide including Bangladesh, and chicken meat is recognized as an important reservoir of ESBL-Ec dissemination to humans. Therefore, this study aimed to determine the prevalence, and phenotypic and genotypic antimicrobial resistance pattern of ESBL-producing Escherichia coli (ESBL-Ec) in frozen chicken meat. A total of 113 frozen chicken meat samples were purchased from 40 outlets of 9 branded supershops in five megacities in Bangladesh. Isolation and identification of Escherichia coli were done based on cultural, biochemical properties and PCR assay. The resistance pattern was determined by disk diffusion method. ESBL-encoding genes were determined by multiplex PCR. The results showed that 76.1% samples were positive for Escherichia coli, of which 86% were ESBL producers. All the isolates were multidrug-resistant (MDR). Resistance to 9–11 and 12–13 antimicrobial classes was observed in 38.4% and 17.4% isolates, respectively while only 11.6% were resistant to 3–5 classes. The possible extensively drug resistance (pXDR) was found in 2.3% isolates. The high single resistance was observed for oxytetracycline (93%) and amoxicillin (91.9%), followed by ampicillin (89.5%), trimethoprim-sulphamethoxazole and pefloxacin (88.4%), and tetracycline (84.9%). Most importantly, 89.6% of isolates were resistant to carbapenems. All the isolates were positive for blaTEM gene. However, the blaSHV and blaCTX-M-2 genes were identified in two ESBL-non producer isolates. None of the isolates were carried blaCTX-M-1 gene. This study provided evidence of wide dissemination of MDR and existence of pXDR ESBL-Ec in frozen chicken meat in Bangladesh. Our data clearly indicated that frozen chicken meat is, at the present time, the most significant known food source of ESBL-Ec to which peoples are regularly exposed.

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

Background In many African countries, clinical samples are not routinely tested for carbapenem-resistant bacteria, the resistance data remaining limited. Material and methods In March 2020 –June 2022, we collected extended spectrum β-lactamase (ESBL) -producing Enterobacterales (ESBL-PE) isolates from five hospitals in Burkina Faso. The species were identified using API20E and ESBL production confirmed by double-disc synergy test. Production of carbapenemases and AmpC-β-lactamases and phenotypic co-resistance were determined. Results Among the 473 ESBL-PE, 356 were ESBL- E. coli (ESBL-Ec) and 117 Klebsiella spp. (ESBL-K). Of the isolates, 5.3% were carbapenemase and 5.3% AmpC-β-lactamase positive Three types of carbapenemases were identified: 19 NDM, 3 OXA-48 like and 1 VIM. Two isolates produced both NDM and OXA48-like carbapenemases. Carbapenemase rates were highest among isolates in tertiary hospitals. Co-resistance rates were up to 85% for aminoglycosides, 90% for sulfonamides, 95% for fluoroquinolones and 25% for chloramphenicol, Fosfomycin resistance was 6% for ESBL-Ec and 49% for ESBL-K (49%). Conclusion Many ESBL-Ec and ESBL-K co-produced carbapenemases and/or AmpC-β-lactamases, at all healthcare levels and in various samples, with high co-resistance rates to non-betalactams. Carbapenem resistance is no longer rare, calling for testing in routine diagnostics, vigorous resistance surveillance system, and infection control within healthcare.

The conservation of the main protease in viral genomes, combined with the absence of a homologous protease in humans, makes this enzyme family an ideal target for developing broad-spectrum antiviral drugs with minimal host toxicity. GC-376, a peptidomimetic 3CL protease inhibitor, has shown significant efficacy against coronaviruses. Recently, a GC-376-based PROTAC was developed to target and induce the proteosome-mediated degradation of the dimeric SARS-CoV-2 3CLPro protein. Extending this approach, the current study investigates the application of the GC-376 PROTAC to the 3CPro protease of Enteroviruses, specifically characterizing its interaction with CVB3 3CPro through X-ray crystallography, NMR and biophysical techniques. The present structural data show that there are some changes between the binding of CVB3 3CPro and SARS-CoV-2 3CLPro, but the overall similarity is strong. The most notable variation is the orientation of the phenylmethyl ester of GC-376 with the S4 subsite of the proteases. This is linked to the flexibility of the protein structure around the region of the catalytic triad shown by our NMR data. Other structural variations include distinct ligand interactions in subsites S1 and S2, influenced by the presence of Glu71 in CVB3 3CPro. Despite these differences, the GC-376 PROTAC fits well within the binding sites of both proteases, demonstrating its potential as a broad-spectrum antiviral agent.

Deep eutectic solvents are a mixture of two or more components, that at a particular composition become liquids at room temperature. When the compounds that constitute the DES are primary metabolites, namely, amino acids, organic acids, sugars, or choline derivatives, the DES are so called natural deep eutectic solvents (NADES). NADES fully represent green chemistry principles. These solvents are highly welcome, as they are obtained from renewable resources, and gratifyingly biodegradable and biocompatible. They are an alternative to room temperature ionic liquids (RTILs). From the pharmaceutical industry point of view, they are highly desirable, but unfortunately have been rarely used despite their enormous potential. In this review, we will look at their impact on the asymmetric catalytic synthesis of key target molecules, via metal-based catalysis, biocatalysis and organocatalysis. In many cases the NADES that have been used are chiral and can even promote enantioselective reactions, this crucial and very exciting aspect will also be discussed and analysed.

ESBL-producing E. coli is a growing public problem in healthcare settings and the community. Between 2009 and 2018, a total of 187 ESBL-producing pathogenic E. coli isolates were confirmed, and clonal complex (CC) 10 was the predominant clone. This study aimed to characterize ESBL-producing pathogenic E. coli CC10 strains obtained from diarrheal patients to improve the understanding of CC10 distribution in the Republic of Korea. A total of 57 CC10 strains were selected for molecular characterizations, such as the identification of serotype, antibiotic resistance genes, genetic environments, plasmid profiles, and the genetic correlation between CC10 strains. In the CC10 isolates, the most prevalent serotype was O25:H16, followed by O6:H16. ESBL genes were identified as blaCTX-M, and the most dominant ESBL gene was blaCTX-M-15 (56%) and blaCTX-M-14 (30%). Most blaCTX-M genes were located on plasmids, and these plasmid profiles were confirmed as IncB/O/K/Z, IncF, IncI1 and IncX1. The mobile elements located up-and down-stream mainly included ISEcp1 (complete or incomplete) and IS903 or orf477 were found, respectively. Phylogenetic analysis showed that the CC10 strains were genetically diverse and divided into several distinct lineages. In this study, we found that CC10 ESBL-producing pathogenic E. coli has been steadily isolated; particularly, CTX-M-15-producing E. coli O25:H16 isolates were the major type related with distribution in CC10 clones during the last decade. Identification of ESBL-producing pathogenic E. coli CC10 isolates highlights the possibility of the emergence of resistant isolates with epidemic potential within this CC. Therefore, continuous monitoring will be conducted to prevent further spread of resistant ESBL-producing E. coli CC10 strains.

Slow-roll inflation may simultaneously solve the horizon problem and generate a near scale-free fluctuation spectrum $P(k)$. These two processes are intimately connected via the initiation and duration of the inflationary phase. But a recent study based on the latest {\it Planck} release suggests that $P(k)$ has a hard cutoff, $k_{\rm min}\not=0$, inconsistent with this conventional picture. Here we demonstrate quantitatively that most---perhaps all---slow-roll inflationary models fail to accommodate this minimum cutoff. We show that the small parameter $\epsilon$ must be $\gtrsim 0.9$ throughout the inflationary period to comply with the data, seriously violating the slow-roll approximation. Models with such an $\epsilon$ predict extremely red spectral indices, at odds with the measured value. We also consider extensions to the basic picture (suggested by several earlier workers) by adding a kinetic-dominated or radiation-dominated phase preceding the slow-roll expansion. Our approach differs from previously published treatments principally because we require these modifications to---not only fit the measured fluctuation spectrum, but to simultaneously also---fix the horizon problem. We show, however, that even such measures preclude a joint resolution of the horizon problem and the missing correlations at large angles.

Extended-spectrum β-lactamase (ESBL) mediating resistance in Enterobacterales is a global public health issue, especially in low-and middle-income countries (LMICs) such as Cameroon. ESBL-producing Enterobacterales reduce therapeutic options and lead to the use of last resort drugs such as carbapenems even in vulnerable populations like children under five years. This study aims at determining the phenotypic and genotypic characteristics of ESBL-producing Escherichia coli (ESBL-Ec) isolated from children under five years with and without diarrhoea in two health care facilities in Dschang. A cross-sectional study was conducted from 3 February to 19 May 2022 in two hospitals in the city of Dschang, Cameroon. Stool collected were cultured on Eosine Methylen Blue (EMB) medium. Enterosystem 18 R kit was used for bacterial identification. Evaluation of the resistance patterns and detection of ESBL production were performed with, the Kirby Bauer disk diffusion method and CHROMagar® ESBL medium, respectively. The genomic DNA of ESBL-Ec was extracted using the boiling method and subjected to conventional and multiplex PCRs for detection of blaSHV, blaCTX-M and blaTEM genes. Data were entered into ExcelTM 2016. Epi info and R software were used for statistical analyses with a p-value <0.05 considered statistically significant. Out of the 125 children enrolled, 67.2% (84/125) were colonized by E. coli. Among these, 57.14% (48/84) were colonized by ESBL-Ec. ESBL- Ec isolates showed high levels of resistance to amoxicillin-clavulanic acid (96.22%), cefotaxime (75.47%), ceftriaxone (73.58%), ofloxacin (67.92%), levofloxacin (56.6%) and ciprofloxacin (54.71%). Children aged between 1-3 years (47.62%, p=0.09) and those who had taken an antibiotic one week prior to collection (70.83%, p=0.04) had a higher prevalence of ESBL-Ec with statistical significance. The majority of ESBL-Ec isolates (52.83%; 28/53) were co-producers of blaCTX-M and blaTEM. Infection prevention and control measures coupled with antimicrobial stewardship strategies need to be strengthened to reduce emergence and dissemination of ESBL-Ec among this vulnerable population.

The healthy function of the vestibular system (VS) is of vital importance for individuals to carry out their daily activities independently and safely. This study carries out Tsallis entropy (TE)-based analysis on insole force sensor data in order to extract features to differentiate between healthy and VS-diseased individuals. Using a specifically developed algorithm, we detrend the acquired data to examine the fluctuation around the trend curve in order to consider the individual’s walking habit and thus increase the accuracy in diagnosis. It is observed that the TE-value increases for diseased people as an indicator of the problem of maintaining balance. As one of the main contributions of this study, in contrast to studies in the literature that focus on gait dynamics requiring extensive walking time, we directly process the instantaneous pressure values, enabling to reduce the data acquisition period significantly. The extracted feature set is then inputted into fundamental classification algorithms, with the Support-Vector-Machine (SVM) demonstrating the highest performance, achieving an average accuracy of 95%. This study constitutes a significant step of a large project aiming to identify specific VS disease together with its stage. The performance achieved in this study provides a strong motivation to further explore this topic.