Delirium Tremens: A Review of Clinical Studies.

Delirium tremens (DT) is a severe condition resulting from alcohol withdrawal. This review highlights the challenges in diagnosing and managing DT and emphasizes the importance of early recognition and intervention to prevent complications and ensure optimal patient outcomes. The discussion of the pathophysiology of DT, focusing on the neurochemical imbalances involving the neurotransmitters gamma-aminobutyric acid and glutamate, explains how chronic alcohol dependence leads to these imbalances and contributes to the hyperexcitability seen in DT. The management of DT involves ensuring patient safety and alleviating symptoms, primarily through pharmacological approaches, such as benzodiazepines. Closely monitoring vital signs and electrolyte imbalances is necessary due to autonomic dysregulation associated with DT. The mention of the potential complexity of DT when coexisting with other conditions emphasizes the need for additional research to advance comprehension, identify predictive factors, and enhance its management.

Effects of COVID-19 on Autism Spectrum Disorder in Qatar.

Introduction: The unprecedented impact of the coronavirus pandemic (COVID-19) has had profound implications on the ASD community, including disrupting daily life, increasing stress and emotional dysregulation in autistic children, and worsening individual and family well-being. Methods: This study used quantitative and qualitative survey data from parents in Qatar (n=271), to understand the impact of the COVID-19 pandemic on autistic children and their families in Qatar. The questionnaire was a combination of open-ended (qualitative) and closed-ended (quantitative) questions to explore patterns in the experiences of the different families, as well as to contrive themes. The survey was created in a way to evaluate the psychological, academic/intervention, economic, and other impacts of the pandemic related measures on a sample of multicultural families residing in the State of Qatar during the peak period of confinement and physical distancing in 2020. Data acquisition involved the utilization of Google Forms. Subsequent quantitative analysis employed the SPSS software and chi-square analysis for numerical examination, enabling the characterization of the studied population and exploration of associations between parental stress levels and variables such as employment status, therapy accessibility, presence of hired assistance, and alterations in their childs skills. Concurrently, qualitative data from written responses underwent thorough categorization, encompassing themes such as emotional isolation, mental or financial challenges, and difficulties in obtaining support. Results: Parents expressed distress and disturbance in their daily lives, including profound disruptions to their childrens access to treatment, education, and activities. Most parents reported deteriorations in their childrens sleep (69.4%), behavioral regulation (52.8%), and acquired skills across multiple domains (54.2%). Parents also reported decreased access to family and social support networks, as well as decreased quality of clinical and community support. Qualitative analysis of parental responses revealed that child developmental regression was an important source of parental stress. Discussion and conclusion: The greater impact of the pandemic on autistic children and their families emphasizes the need for accessible and affordable health, education, and family services to manage their special needs.

Correction: Noureddine et al. Impact of the Renin-Angiotensin System on the Endothelium in Vascular Dementia: Unresolved Issues and Future Perspectives. Int. J. Mol. Sci. 2020, 21, 4268.

The authors would like to make the following correction to the publication dealing with Reference #3 [...].

Potential Alternative Receptors for SARS-CoV-2-Induced Kidney Damage: TLR-4, KIM-1/TIM-1, and CD147.

Kidney damage in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can occur even in patients with no underlying kidney disease. Signs of kidney problems can progress to a state that demands dialysis and hampering recovery. Although not without controversy, emerging evidence implicates direct infectivity of SARS-CoV-2 in the kidney. At the early stage of the pandemic, consideration was mainly on the well-recognized angiotensin-converting enzyme 2 (ACE2) receptor as being the site for viral interaction and subsequent cellular internalization. Despite the abundance of ACE2 receptors in the kidneys, researchers have expanded beyond ACE2 and identified novel viral entry pathways that could be advantageously explored as therapeutic targets. This review presents the potential involvement of toll-like receptor 4 (TLR-4), kidney injury molecule-1/T cell immunoglobulin mucin domain 1 (KIM-1/TIM-1), and cluster of differentiation 147 (CD147) in SARS-CoV-2-associated renal damage. In this context, we address the unresolved issues surrounding SARS-CoV-2 renal infectivity.

Effectiveness of full Pulpotomy compared with Root canal treatment in managing teeth with signs and symptOms indicative of irreversible pulpitis: a protocol for prospectiVE meta-analysis of individual participant data of linked randomised clinical trials (PROVE).

BACKGROUND: Full pulpotomy has been proposed as an alternative to root canal treatment in teeth with signs and symptoms indicative of irreversible pulpitis (IRP), but the evidence is limited, relying on underpowered studies with a high risk of bias. The aim of this study is to conduct a prospective meta-analysis (PMA) of individual participant data of a series of individual randomised trials to provide robust evidence on the clinical and cost-effectiveness of pulpotomy compared with root canal treatment. METHODS: Individual participant data will be obtained from a series of randomised trials designed and conducted by a consortium of multi-national investigators with an interest in vital pulp treatment. These individualised trials will be conducted using a specified protocol, defined outcomes, and outcome measures. Ten parallel-group randomised trials currently being conducted in 10 countries will provide data from more than 500 participants. The primary outcome is a composite measure defined as (1) the absence of pain indicative of IRP, (2) the absence of signs and symptoms indicative of acute or chronic apical periodontitis, and (3) the absence of radiographic evidence of failure including radiolucency or resorption. Individual participant data will be obtained, assessed, and checked for quality by two independent reviewers prior to the PMA. Pooled estimates on treatment effects will be generated using a 2-stage meta-analysis approach. The first stage involves a standard regression analysis in each trial to produce aggregate data on treatment effect estimates followed by an inverse variance weighted meta-analysis to combine these aggregate data and produce summary statistics and forest plots. Cost-effectiveness analysis based on the composite outcome will be undertaken as a process evaluation to evaluate treatment fidelity and acceptability by patients and dentists. RESULTS: The research question and trial protocol were developed and approved by investigators in all 10 sites. All sites use shared resources including study protocols, data collection forms, participant information leaflets, and consent forms in order to improve flow, consistency, and reproducibility. Each site obtained its own Institutional Review Board approval, and trials were registered in appropriate open access platforms. Patient recruitment has started in most sites, as of July 2023. DISCUSSION: PMA offers a rigorous, flexible, and efficient methodology to answer this important research question and provide results with improved generalisability and external validity compared with traditional trials and retrospective meta-analyses. The results of this study will have implications for both the delivery of clinical practice and structured clinical guidelines' development. TRIAL REGISTRATION: PROSPERO CRD42023446809. Registered on 08 February 2023.

Nicotinamide Riboside Supplementation Restores Myocardial Nicotinamide Adenine Dinucleotide Levels, Improves Survival, and Promotes Protective Environment Post Myocardial Infarction.

AIMS: Myocardial infarction (MI) is a major cause of death. Nicotinamide adenine dinucleotide (NAD+) is a coenzyme in oxidative phosphorylation and substrate of sirtuins and poly-ADP ribose polymerases, enzymes critical for cardiac remodeling post-MI. Decreased NAD+ is reported in several heart failure models with paradoxically an upregulation of nicotinamide riboside kinase 2, which uses nicotinamide riboside (NR) as substrate in an NAD+ biosynthetic pathway. We hypothesized that stimulating nicotinamide riboside kinase 2 pathway by NR supplementation exerts cardioprotective effects. METHODS AND RESULTS: MI was induced by LAD ligation in 2-3-month-old male mice. NR was administered daily (1 µmole/g body weight) over 7 days. RT-PCR showed a 60-fold increase in nicotinamide riboside kinase 2 expression 4 days post-MI with a 60% drop in myocardial NAD+ and overall survival of 61%. NR restored NAD+ levels and improved survival to 92%. Assessment of respiration in cardiac fibers revealed mitochondrial dysfunction post-MI, and NR improved complexes II and IV activities and citrate synthase activity, a measure of mitochondrial content. Additionally, NR reduced elevated PARP1 levels and activated a type 2 cytokine milieu in the damaged heart, consistent with reduced early inflammatory and pro-fibrotic response. CONCLUSION: Our data show that nicotinamide riboside could be useful for MI management.

Development and validation of an Arabic language eye-tracking paradigm for the early screening and diagnosis of autism spectrum disorders in Qatar.

Abnormal eye gaze is a hallmark characteristic of autism spectrum disorder (ASD). The primary aim of the present research was to develop an Arabic version of an objective measure of ASD, the "autism index" (AI), based on eye gaze tracking to social and nonsocial stimuli validated initially in the United States. The initial phase of this study included the translation of English language eye-tracking stimuli into stimuli appropriate for an Arabic-speaking culture. During the second phase, we tested it on a total of 144 children with ASD, and 96 controls. The AI had excellent internal consistency and test-retest reliability. Moreover, the AI showed good differentiation of ASD from control cases (AUC = 0.730, SE = 0.035). The AI was significantly positively correlated with SCQ total raw scores (r = 0.46, p < 0.001). ADOS-2 scores were only available in the ASD group and did not show a significant relationship with AI scores (r = 0.10, p = 0.348), likely due to the restricted range. The AI, when implemented using Arabic-translated stimuli in a Qatari sample, showed good diagnostic differentiation and a strong correlation with parent-reported ASD symptoms. Thus, the AI appears to have cross-cultural validity and may be useful as a diagnostic aide to inform clinical judgment and track ASD symptom levels as part of the evaluation process.

Assessing the outcomes of prescribing angiotensin converting enzyme inhibitors and angiotensin receptor blockers for COVID-19 patients.

Background: Patients with heart failure were affected severely by COVID-19. Most heart failure patients are on guideline directed medical therapy, which includes ACE inhibitors (ACEI) and ARBs. These medications were controversial at the beginning of the pandemic due to their interplay with the receptor that SARS-CoV-2 binds in the lungs. We investigated the effect that ACEI and ARB had on patients with hypertension, coronary artery disease, and heart failure. Methods: We recruited 176 patients with COVID-19 infection and cardiovascular comorbidities at the American University of Beirut Medical Center in Lebanon. Of these, 110 patients were taking ACEI or ARB and 66 were not. We collected clinical data and looked at inflammatory markers such as CRP and IL-6 and cardiac markers such as troponin T. We also reported the incidence of ARDS, sepsis, and death of each patient, and compared the 2 groups. Results: We found that patients taking ACEI and ARB had a statistically significant decrease in levels of troponin T, IL-6, and CRP compared to patients not taking these medications (p < 0.05). We found no difference in rates of ARDS, sepsis, or death between the 2 groups. Conclusion: Inhibition of the renin-angiotensin-aldosterone-system had no effect on the mortality of patients with COVID-19 and on their overall disease progression. However, it may be beneficial not to stop these medications as they decrease inflammation in the body and the levels of troponin, which are related to increased stress on the heart.

Categorical versus dimensional structure of autism spectrum disorder: A multi-method investigation.

Background: A key question for any psychopathological diagnosis is whether the condition is continuous or discontinuous with typical variation. The primary objective of this study was to use a multi-method approach to examine the broad latent categorical versus dimensional structure of autism spectrum disorder (ASD). Method: Data were aggregated across seven independent samples of participants with ASD, other neurodevelopmental disorders (NDD), and non-ASD/NDD controls (aggregate Ns = 512-16,755; ages 1.5-22). Scores from four distinct phenotype measures formed composite "indicators" of the latent ASD construct. The primary indicator set included eye gaze metrics from seven distinct social stimulus paradigms. Logistic regressions were used to combine gaze metrics within/across paradigms, and derived predicted probabilities served as indicator values. Secondary indicator sets were constructed from clinical observation and parent-report measures of ASD symptoms. Indicator sets were submitted to taxometric- and latent class analyses. Results: Across all indicator sets and analytic methods, there was strong support for categorical structure corresponding closely to ASD diagnosis. Consistent with notions of substantial phenotypic heterogeneity, the ASD category had a wide range of symptom severity. Despite the examination of a large sample with a wide range of IQs in both genders, males and children with lower IQ were over-represented in the ASD category, similar to observations in diagnosed cases. Conclusions: Our findings provide strong support for categorical structure corresponding closely to ASD diagnosis. The present results bolster the use of well-diagnosed and representative ASD groups within etiologic and clinical research, motivating the ongoing search for major drivers of the ASD phenotype. Despite the categorical structure of ASD, quantitative symptom measurements appear more useful for examining relationships with other factors.

Consanguinity as a Risk Factor for Autism.

PURPOSE: Genetic and environmental risk factors associated with Autism Spectrum Disorders (ASD) continue to be a focus of research worldwide. Consanguinity, the cultural practice of marrying within a family, is common in cultures and societies of the Middle East, North Africa and parts of Asia. Consanguinity has been investigated as a risk factor for ASD in a limited number of studies, with mixed results. We employed registry and survey data from Qatar to evaluate the role of consanguinity as a risk factor for ASD. METHODS: Data were sourced from a national registry and a population-based survey of autism recently conducted in Qatar. We selected a sample of 891 children (mean age: 8.3 years) with (N = 361) or without (N = 530) ASD. Data on consanguinity and covariates were collected through questionnaires and interviews. RESULTS: The prevalence of consanguinity in the overall sample was 41.2% with no significant difference between cases and controls (42.1% vs 41.3%; p = .836). In adjusted multiple logistic regression analyses, consanguinity was not associated with risk of ASD (aOR = 1.065; 95% CI: .751-1.509; NS). CONCLUSION: Parental consanguinity was not associated with autism risk in our study. Replication in other populations with high rates of consanguineous unions is recommended.

Cooling Down Inflammation in the Cardiovascular System via the Nicotinic Acetylcholine Receptor.

ABSTRACT: Inflammation is a major player in many cardiovascular diseases including hypertension, atherosclerosis, myocardial infarction, and heart failure. In many individuals, these conditions coexist and mutually exacerbate each other's progression. The pathophysiology of these diseases entails the active involvement of both innate and adaptive immune cells. Immune cells that possess the α7 subunit of the nicotinic acetylcholine receptor on their surface have the potential to be targeted through both pharmacological and electrical stimulation of the cholinergic system. The cholinergic system regulates the inflammatory response to various stressors in different organ systems by systematically suppressing spleen-derived monocytes and chemokines and locally improving immune cell function. Research on the cardiovascular system has demonstrated the potential for atheroma plaque stabilization and regression as favorable outcomes. Smaller infarct size and reduced fibrosis have been associated with improved cardiac function and a decrease in adverse cardiac remodeling. Furthermore, enhanced electrical stability of the myocardium can lead to a reduction in the incidence of ventricular tachyarrhythmia. In addition, improving mitochondrial dysfunction and decreasing oxidative stress can result in less myocardial tissue damage caused by reperfusion injury. Restoring baroreflex activity and reduction in renal damage can promote blood pressure regulation and help counteract hypertension. Thus, the present review highlights the potential of nicotinic acetylcholine receptor activation as a natural approach to alleviate the adverse consequences of inflammation in the cardiovascular system.

Dietary isoleucine supplementation enhances growth performance, modulates the expression of genes related to amino acid transporters and protein metabolism, and gut microbiota in yellow-feathered chickens.

This study investigated the effects of dietary isoleucine (Ile) on growth performance, intestinal expression of amino acid transporters, protein metabolism-related genes and intestinal microbiota in starter phase Chinese yellow-feathered chickens. Female Xinguang yellow-feathered chickens (n = 1,080, aged 1 d) were randomly distributed to 6 treatments, each with 6 replicates of 30 birds. Chickens were fed diets with 6 levels of total Ile (6.8, 7.6, 8.4, 9.2, 10.0, and 10.8 g/kg) for 30 d. The average daily gain and feed conversion ratio were improved with dietary Ile levels (P < 0.05). Plasma uric acid content and glutamic-oxalacetic transaminase activity were linearly and quadratically decreased with increasing dietary Ile inclusion (P < 0.05). Dietary Ile level had a linear (P < 0.05) or quadratic (P < 0.05) effect on the jejunal expression of ribosomal protein S6 kinase B1 and eukaryotic translation initiation factor 4E binding protein 1. The relative expression of jejunal 20S proteasome subunit C2 and ileal muscle ring finger-containing protein 1 decreased linearly (P < 0.05) and quadratically (P < 0.05) with increasing dietary Ile levels. Dietary Ile level had a linear (P = 0.069) or quadratic (P < 0.05) effect on the gene expression of solute carrier family 15 member 1 in jejunum and solute carrier family 7 member 1 in ileum. In addition, bacterial 16S rDNA full-length sequencing showed that dietary Ile increased the cecal abundances of the Firmicutes phylum, and Blautia, Lactobacillus, and unclassified_Lachnospiraceae genera, while decreased that of Proteobacteria, Alistipes, and Shigella. Dietary Ile levels affected growth performance and modulated gut microbiota in yellow-feathered chickens. The appropriate level of dietary Ile can upregulate the expression of intestinal protein synthesis-related protein kinase genes and concomitantly inhibit the expression of proteolysis-related cathepsin genes.

Comparative Coexpression Analysis of Indole Synthase and Tryptophan Synthase A Reveals the Independent Production of Auxin via the Cytosolic Free Indole.

Indole synthase (INS), a homologous cytosolic enzyme of the plastidal tryptophan synthase A (TSA), has been reported as the first enzyme in the tryptophan-independent pathway of auxin synthesis. This suggestion was challenged as INS or its free indole product may interact with tryptophan synthase B (TSB) and, therefore, with the tryptophan-dependent pathway. Thus, the main aim of this research was to find out whether INS is involved in the tryptophan-dependent or independent pathway. The gene coexpression approach is widely recognized as an efficient tool to uncover functionally related genes. Coexpression data presented here were supported by both RNAseq and microarray platforms and, hence, considered reliable. Coexpression meta-analyses of Arabidopsis genome was implemented to compare between the coexpression of TSA and INS with all genes involved in the production of tryptophan via the chorismate pathway. Tryptophan synthase A was found to be coexpressed strongly with TSB1/2, anthranilate synthase A1/B1, phosphoribosyl anthranilate transferase1, as well as indole-3-glycerol phosphate synthase1. However, INS was not found to be coexpressed with any target genes suggesting that it may exclusively and independently be involved in the tryptophan-independent pathway. Additionally, annotation of examined genes as ubiquitous or differentially expressed were described and subunits-encoded genes available for the assembly of tryptophan and anthranilate synthase complex were suggested. The most probable TSB subunits expected to interact with TSA is TSB1 then TSB2. Whereas TSB3 is only used under limited hormone conditions to assemble tryptophan synthase complex, putative TSB4 is not expected to be involved in the plastidial synthesis of tryptophan in Arabidopsis.

Risk of thromboembolic events in non-hospitalized COVID-19 patients: A systematic review.

The risk of thromboembolism in non-hospitalized COVID-19 patients remains uncertain and was assessed in this review to better weigh benefits vs. risks of prophylactic anticoagulation in this population. A search was performed through three databases: Medline, Embase, and Cochrane Library until 2022. Self-controlled case series, case-control and cohort studies were included, and findings summarized narratively. Meta-analyses for risk of thromboembolism including deep vein thrombosis (DVT), pulmonary embolism (PE), and myocardial infarction (MI) between COVID-19 and non-COVID-19 non-hospitalized patients were conducted. Frequency, incidence rate ratio (IRR), and risk ratio (RR) of stroke were used to assess risk in non-hospitalized COVID-19 patients considering the lack of studies to conduct a meta-analysis. Ten studies met inclusion criteria characterized by adult non-hospitalized COVID-19 patients. Risk of bias was relatively low. Risk of DVT (RR: 1.98 with 95% CI: 1.03-3.83) and PE (OR: 6.72 with 95% CI: 4.81-9.39 and RR: 4.44 with 95% CI: 1.98-9.99) increased in non-hospitalized COVID-19 patients compared to controls. Risk of MI (OR: 1.91 with 95% CI: 0.89-4.09) is possibly increased in non-hospitalized COVID-19 patients with moderate certainty when compared to controls. A trend in favor of stroke was documented in the first week following infection. Our meta-analyses support the increase in risk of DVT and PE, and likely increase of MI, in non-hospitalized COVID-19 patients. The risk of stroke appears significant in the first week following infection but drops to insignificance two weeks later. More studies are needed to establish evidence-based recommendations for prophylactic anticoagulation therapy in non-hospitalized COVID-19 patients.

Sexual dimorphism in acute myocardial infarction-induced acute kidney injury: cardiorenal deteriorating effects of ovariectomy in premenopausal female mice.

Acute kidney injury (AKI) is a common complication of cardiovascular diseases (CVDs) in both males and females, increasing mortality rate substantially. Premenopausal females appear to be more protected, suggesting a potential protective role of female sex hormones. Here, we tested the hypothesis that ovariectomy (OVX) eliminates the beneficial effect of female sex on renal protection following acute myocardial infarction (MI). Seven days post-MI, both sexes exhibited worsened kidney function and a substantial decrease in total kidney NAD levels. Unlike MI female mice, MI males showed exacerbated morphological alterations with increased proinflammatory, proapoptotic, and profibrotic biomarkers. The expression of NAD+ biosynthetic enzymes NAMPT and NMRK-1 was increased in MI females only, while males showed a substantial increase in NAD+ consuming enzyme PARP-1. OVX did not eliminate the female-sex protection of glomerular morphology but was associated with swelling of proximal convoluted tubules with MI as in males. With OVX, MI females had enhanced proinflammatory cytokine release, and a further decrease in creatinine clearance and urine output was observed. Our findings suggest that MI induced AKI in both sexes with pre-menopausal female mice being more protected. Ovariectomy worsens aspects of AKI in females after MI, which may portend increased risk for development of chronic kidney disease.

DIS3L2 Gene Mutation Causes the Perlman Syndrome of Overgrowth and Wilms Tumor Susceptibility.

The deletion of the DIS3L2 gene causes the extremely uncommon congenital overgrowth syndrome, known as Perlman syndrome, which is autosomal recessive. Polyhydramnios, macrosomia, facial dysmorphism, renal dysplasia, and several congenital abnormalities with Wilms tumor propensity are its defining features. Beckwith-Wiedemann syndrome (BWS), prune belly syndrome (PBS), and Simpson-Golabi-Behmel syndrome (SGBS1) have certain similar clinical characteristics with Perlman syndrome. The syndrome is often associated with a high neonatal mortality rate and there are few reports of long-term survivors. Here, we present a case with the classic clinical features of Perlman syndrome and a DIS3L2 gene deletion that was discovered prenatally.

Characterization of a loss-of-function NSF attachment protein beta mutation in monozygotic triplets affected with epilepsy and autism using cortical neurons from proband-derived and CRISPR-corrected induced pluripotent stem cell lines.

We investigated whether a homozygous recessive genetic variant of NSF attachment protein beta (NAPB) gene inherited by monozygotic triplets contributed to their phenotype of early-onset epilepsy and autism. Induced pluripotent stem cell (iPSC) lines were generated from all three probands and both parents. The NAPB genetic variation was corrected in iPSC lines from two probands by CRISPR/Cas9 gene editing. Cortical neurons were produced by directed, in vitro differentiation from all iPSC lines. These cell line-derived neurons enabled us to determine that the genetic variation in the probands causes exon skipping and complete absence of NAPB protein. Electrophysiological and transcriptomic comparisons of cortical neurons derived from parents and probands cell lines indicate that loss of NAPB function contributes to alterations in neuronal functions and likely contributed to the impaired neurodevelopment of the triplets.

Evaluation of thermal performance factor by hybrid nanofluid and twisted tape inserts in heat exchanger.

The thermal performance parameters of an improved heat exchanger tube fitted with various vortex generator inserts were investigated using numerical and experimental methods. The governing equations have been solved numerically by a Finite Volume approach employing the turbulence model ( κ - ε ). Two twisted tape types, which being inserted across a circular pipe (plain twisted tape) and (Double V-cut twisted tape), have been achieved. The hybrid nanofluid is prepared by using metal oxide [Al2O3+CuO] with distilled water at volume fraction range (0.6%, 1.2% and 1.8%), Reynolds number range (3560-8320) at twisted ratio (9.25). The experimental data for a plain tube, plain twisted tapes and double v-cut twisted tape are validated using the standard correlations available in the literature. The effect of such variables upon the average Nusselt number, friction factor, and thermal performance factor have been investigated and compared with a plain tube at the same conditions. As compared to plain twisted tape, the tube equipped with a double V-cut twisted tape with hybrid nanofluid displayed increased thermal performance. The greater vortex flow induced by the V-cuts results in more active thermal boundary layer disturbance, resulting in a greater heat transfer rate. The results show that thermal performance factor for hybrid nanofluid in plain circular tube at ( ∅ = 1.8 %) and Reynolds number (8320) is about (1.068), when the plain twisted tape and double v-cut twisted tape inserted with hybrid nanofluid the thermal performance factor increased to (1.33) and (1.37), respectively. The results show a similar trend for both numerical and experimental cases. The comparison between the experimental and numerical results have maximum error was (9.7)%.