Abolishing UCHL1's hydrolase activity exacerbates ischemia-induced axonal injury and functional deficits in mice.

Ubiquitin C-terminal hydrolase L1 (UCHL1) is a neuronal protein important in maintaining axonal integrity and motor function and may be important in the pathogenesis of many neurological disorders. UCHL1 may ameliorate acute injury and improve recovery after cerebral ischemia. In the current study, the hypothesis that UCHL1's hydrolase activity underlies its effect in maintaining axonal integrity and function is tested after ischemic injury. Hydrolase activity was inhibited by treatment with a UCHL1 hydrolase inhibitor or by employing knockin mice bearing a mutation in the hydrolase active site (C90A). Ischemic injury was induced by oxygen-glucose deprivation (OGD) in brain slice preparations and by transient middle cerebral artery occlusion (tMCAO) surgery in mice. Hydrolase activity inhibition increased restoration time and decreased the amplitude of evoked axonal responses in the corpus callosum after OGD. Mutation of the hydrolase active site exacerbated white matter injury as detected by SMI32 immunohistochemistry, and motor deficits as detected by beam balance and cylinder testing after tMCAO. These results demonstrate that UCHL1 hydrolase activity ameliorates white matter injury and functional deficits after acute ischemic injury and support the hypothesis that UCHL1 activity plays a significant role in preserving white matter integrity and recovery of function after cerebral ischemia.

Deletion of Sigmar1 leads to increased arterial stiffness and altered mitochondrial respiration resulting in vascular dysfunction.

Sigmar1 is a ubiquitously expressed, multifunctional protein known for its cardioprotective roles in cardiovascular diseases. While accumulating evidence indicate a critical role of Sigmar1 in cardiac biology, its physiological function in the vasculature remains unknown. In this study, we characterized the expression of Sigmar1 in the vascular wall and assessed its physiological function in the vascular system using global Sigmar1 knockout (Sigmar1-/-) mice. We determined the expression of Sigmar1 in the vascular tissue using immunostaining and biochemical experiments in both human and mouse blood vessels. Deletion of Sigmar1 globally in mice (Sigmar1-/-) led to blood vessel wall reorganizations characterized by nuclei disarray of vascular smooth muscle cells, altered organizations of elastic lamina, and higher collagen fibers deposition in and around the arteries compared to wildtype littermate controls (Wt). Vascular function was assessed in mice using non-invasive time-transit method of aortic stiffness measurement and flow-mediated dilation (FMD) of the left femoral artery. Sigmar1-/- mice showed a notable increase in arterial stiffness in the abdominal aorta and failed to increase the vessel diameter in response to reactive-hyperemia compared to Wt. This was consistent with reduced plasma and tissue nitric-oxide bioavailability (NOx) and decreased phosphorylation of endothelial nitric oxide synthase (eNOS) in the aorta of Sigmar1-/- mice. Ultrastructural analysis by transmission electron microscopy (TEM) of aorta sections showed accumulation of elongated shaped mitochondria in both vascular smooth muscle and endothelial cells of Sigmar1-/- mice. In accordance, decreased mitochondrial respirometry parameters were found in ex-vivo aortic rings from Sigmar1 deficient mice compared to Wt controls. These data indicate a potential role of Sigmar1 in maintaining vascular homeostasis.

Ion transporter cascade, reactive astrogliosis and cerebrovascular diseases.

Cerebrovascular diseases and their sequalae, such as ischemic stroke, chronic cerebral hypoperfusion, and vascular dementia are significant contributors to adult disability and cognitive impairment in the modern world. Astrocytes are an integral part of the neurovascular unit in the CNS and play a pivotal role in CNS homeostasis, including ionic and pH balance, neurotransmission, cerebral blood flow, and metabolism. Astrocytes respond to cerebral insults, inflammation, and diseases through unique molecular, morphological, and functional changes, collectively known as reactive astrogliosis. The function of reactive astrocytes has been a subject of debate. Initially, astrocytes were thought to primarily play a supportive role in maintaining the structure and function of the nervous system. However, recent studies suggest that reactive astrocytes may have both beneficial and detrimental effects. For example, in chronic cerebral hypoperfusion, reactive astrocytes can cause oligodendrocyte death and demyelination. In this review, we will summarize the (1) roles of ion transporter cascade in reactive astrogliosis, (2) role of reactive astrocytes in vascular dementia and related dementias, and (3) potential therapeutic approaches for dementing disorders targeting reactive astrocytes. Understanding the relationship between ion transporter cascade, reactive astrogliosis, and cerebrovascular diseases may reveal mechanisms and targets for the development of therapies for brain diseases associated with reactive astrogliosis.

Joint transformer architecture in brain 3D MRI classification: its application in Alzheimer's disease classification.

Alzheimer's disease (AD), a neurodegenerative disease that mostly affects the elderly, slowly impairs memory, cognition, and daily tasks. AD has long been one of the most debilitating chronic neurological disorders, affecting mostly people over 65. In this study, we investigated the use of Vision Transformer (ViT) for Magnetic Resonance Image processing in the context of AD diagnosis. ViT was utilized to extract features from MRIs, map them to a feature sequence, perform sequence modeling to maintain interdependencies, and classify features using a time series transformer. The proposed model was evaluated using ADNI T1-weighted MRIs for binary and multiclass classification. Two data collections, Complete 1Yr 1.5T and Complete 3Yr 3T, from the ADNI database were used for training and testing. A random split approach was used, allocating 60% for training and 20% for testing and validation, resulting in sample sizes of (211, 70, 70) and (1378, 458, 458), respectively. The performance of our proposed model was compared to various deep learning models, including CNN with BiL-STM and ViT with Bi-LSTM. The suggested technique diagnoses AD with high accuracy (99.048% for binary and 99.014% for multiclass classification), precision, recall, and F-score. Our proposed method offers researchers an approach to more efficient early clinical diagnosis and interventions.

The Transition of Sociodemographic and Substance Abuse Characteristics, Pairwise Co-occurrences and Factors Associated with Polysubstance Use Among US Adolescents and Young Adults.

Background: Substance abuse by adolescents and young adults is a major public health issue. This study aimed to (i) show the transition of sociodemographic and substance abuse characteristics from 1992 to 2017 among US adolescents and young adults, (ii) evaluate the likelihood of co-occurrence of substances, and (iii) identify significant sociodemographic characteristics in association with polysubstance abuse. Methods: This study extracted data for adolescents and young adults from 1992 and 2017 Treatment Episode Data Set-Admission (TEDS-A) datasets. The extracted sample included 337858 admissions in 1992 and 333322 in 2017. Findings: Both years experienced significant admissions. A significant transition in 2017 compared to 1992 was evident in education, living status, and ethnicity. Substance-specific transition showed alcohol was dominant in 1992, while marijuana/ hashish was dominant in 2017. Also, heroin, other opiates/synthetics, and methamphetamine experienced an increase, while cocaine/crack decreased. The pairwise co-occurrences exhibited a considerable variation in the likelihood of using one substance given another one. The odds ratios (ORs) obtained from generalized ordered logit models showed significantly higher odds of one or more substances with age, while education showed the opposite scenario. A mixed effect of gender was evident in 1992, whereas females were significantly less likely with one or more substances than males in 2017. Other significant vulnerable groups were those not in the labor force, homeless, white, and Mexican Americans. Conclusion: The findings may help to understand the overall changes between 1992 and 2017 and take necessary measures to reduce the burden of this public health problem.

Effect of successive recycling and reuse of acid liquor for the synthesis of graphene oxides with higher oxygen-to-carbon ratios.

Graphene has recently drawn exponential attention due to its surprising physicochemical properties and diversified field of applications. Although graphene oxides (GOs), itself is an exclusive material, it is also an intermediate product for the production of reduced graphene oxides (rGOs), graphene and their derivatives, which are other more superficial materials. In this study, GOs with higher oxygen to carbon ratios were synthesized following the Tour method, where the excess feed acid liquor (FAL) of mixed concentrated sulfuric and orthophosphoric acids at a ratio of 90:10 was recovered from the reaction slurries by applying the centrifugation technique. About 80-90 % of the FAL was recycled and reused as feed for the subsequent batches. The changes in the properties of FAL for the five consecutive recycling and reuse were studied. The properties of recycled FALs were investigated by measuring density, moisture content, pH, and ion concentration. The consecutive recycling of FALs tends to increase the moisture content about 0.5% in each recycles. Ion-chromatography (IC) was used to measure the variation in SO42- and PO43- ions in the FALs. The H2SO4 reacts with KMnO4 and crystalized out from the recovered FAL faster than the phosphoric acid. So, sulfuric acid content in the makeover FALs must be greater than primary FAL. The product GOs were characterized using FT-IR, FT-Raman, UVVis, STA, SEM, XPS, Zeta-potential, and particle size analyzers. The variation of the properties of GOs with the changes in the reaction parameters such as temperature and time were investigated and correlated with the product yield. It was observed that the effect of temperature on the reaction rate was found to be negatively and positive with the reaction time. The oxygen-to-carbon atomic ratio from XPS analysis was found 66.7%, which supported the increase in product yields 66.9% in the experimental results. The effect of acid concentration, reaction temperature, and time on the GOs properties were satisfactory, correlated, and easily controllable with the reaction conditions. A higher extent of oxidation and enhanced product yields 65-70% were observed at 60-70 °C and 14-18 h. A mixture of nano- and macro-molecular GOs was obtained, and their compositions were easily controllable and separable by controlling the reaction conditions. A correlation was made among the properties of synthesized GOs, FAL, and recycled FAL and reaction conditions.

SPAK inhibitor ZT-1a attenuates reactive astrogliosis and oligodendrocyte degeneration in a mouse model of vascular dementia.

BACKGROUND: Astrogliosis and white matter lesions (WML) are key characteristics of vascular contributions to cognitive impairment and dementia (VCID). However, the molecular mechanisms underlying VCID remain poorly understood. Stimulation of Na-K-Cl cotransport 1 (NKCC1) and its upstream kinases WNK (with no lysine) and SPAK (the STE20/SPS1-related proline/alanine-rich kinase) play a role in astrocytic intracellular Na+ overload, hypertrophy, and swelling. Therefore, in this study, we assessed the effect of SPAK inhibitor ZT-1a on pathogenesis and cognitive function in a mouse model of VCID induced by bilateral carotid artery stenosis (BCAS). METHODS: Following sham or BCAS surgery, mice were randomly assigned to receive either vehicle (DMSO) or SPAK inhibitor ZT-1a treatment regimen (days 14-35 post-surgery). Mice were then evaluated for cognitive functions by Morris water maze, WML by ex vivo MRI-DTI analysis, and astrogliosis/demyelination by immunofluorescence and immunoblotting. RESULTS: Compared to sham control mice, BCAS-Veh mice exhibited chronic cerebral hypoperfusion and memory impairments, accompanied by significant MRI DTI-detected WML and oligodendrocyte (OL) death. Increased activation of WNK-SPAK-NKCC1-signaling proteins was detected in white matter tissues and in C3d+ GFAP+ cytotoxic astrocytes but not in S100A10+ GFAP+ homeostatic astrocytes in BCAS-Veh mice. In contrast, ZT-1a-treated BCAS mice displayed reduced expression and phosphorylation of NKCC1, decreased astrogliosis, OL death, and WML, along with improved memory functions. CONCLUSION: BCAS-induced upregulation of WNK-SPAK-NKCC1 signaling contributes to white matter-reactive astrogliosis, OL death, and memory impairment. Pharmacological inhibition of the SPAK activity has therapeutic potential for alleviating pathogenesis and memory impairment in VCID.

Interactions between integrin α9ß1 and VCAM-1 promote neutrophil hyperactivation and mediate poststroke DVT.

ABSTRACT: Venous thromboembolic events are significant contributors to morbidity and mortality in patients with stroke. Neutrophils are among the first cells in the blood to respond to stroke and are known to promote deep vein thrombosis (DVT). Integrin α9 is a transmembrane glycoprotein highly expressed on neutrophils and stabilizes neutrophil adhesion to activated endothelium via vascular cell adhesion molecule 1 (VCAM-1). Nevertheless, the causative role of neutrophil integrin α9 in poststroke DVT remains unknown. Here, we found higher neutrophil integrin α9 and plasma VCAM-1 levels in humans and mice with stroke. Using mice with embolic stroke, we observed enhanced DVT severity in a novel model of poststroke DVT. Neutrophil-specific integrin α9-deficient mice (α9fl/flMrp8Cre+/-) exhibited a significant reduction in poststroke DVT severity along with decreased neutrophils and citrullinated histone H3 in thrombi. Unbiased transcriptomics indicated that α9/VCAM-1 interactions induced pathways related to neutrophil inflammation, exocytosis, NF-κB signaling, and chemotaxis. Mechanistic studies revealed that integrin α9/VCAM-1 interactions mediate neutrophil adhesion at the venous shear rate, promote neutrophil hyperactivation, increase phosphorylation of extracellular signal-regulated kinase, and induce endothelial cell apoptosis. Using pharmacogenomic profiling, virtual screening, and in vitro assays, we identified macitentan as a potent inhibitor of integrin α9/VCAM-1 interactions and neutrophil adhesion to activated endothelial cells. Macitentan reduced DVT severity in control mice with and without stroke, but not in α9fl/flMrp8Cre+/- mice, suggesting that macitentan improves DVT outcomes by inhibiting neutrophil integrin α9. Collectively, we uncovered a previously unrecognized and critical pathway involving the α9/VCAM-1 axis in neutrophil hyperactivation and DVT.

Imaging the Breakdown and Restoration of Topological Protection in Magnetic Topological Insulator MnBi2 Te4.

Quantum anomalous Hall (QAH) insulators transport charge without resistance along topologically protected chiral 1D edge states. Yet, in magnetic topological insulators to date, topological protection is far from robust, with zero-magnetic field QAH effect only realized at temperatures an order of magnitude below the Néel temperature TN , though small magnetic fields can stabilize QAH effect. Understanding why topological protection breaks down is therefore essential to realizing QAH effect at higher temperatures. Here a scanning tunneling microscope is used to directly map the size of exchange gap (Eg,ex ) and its spatial fluctuation in the QAH insulator 5-layer MnBi2 Te4 . Long-range fluctuations of Eg,ex are observed, with values ranging between 0 (gapless) and 70 meV, appearing to be uncorrelated to individual surface point defects. The breakdown of topological protection is directly imaged, showing that the gapless edge state, the hallmark signature of a QAH insulator, hybridizes with extended gapless regions in the bulk. Finally, it is unambiguously demonstrated that the gapless regions originate from magnetic disorder, by demonstrating that a small magnetic field restores Eg,ex in these regions, explaining the recovery of topological protection in magnetic fields. The results indicate that overcoming magnetic disorder is the key to exploiting the unique properties of QAH insulators.

Identification of new major histocompatibility complex-B Haplotypes in Bangladesh native chickens.

OBJECTIVE: The major histocompatibility complex in chicken demonstrates a great range of variations within varities, breeds, populations and that can eventually influence their immuneresponses. The preset study was conducted to understand the major histocompatibility complex-B (MHC-B) variability in five major populations of Bangladesh native chicken: Aseel, Hilly, Junglefowl, Non-descript Deshi, and Naked Neck. METHODS: These five major populations of Bangladesh native chicken were analyzed with a subset of 89 single nucleotide polymorphisms (SNPs) in the high-density MHC-B SNP panel and Kompetitive Allele-Specific polymerase chain reaction genotyping was applied. To explore haplotype diversity within these populations, the results were analyzed both manually and computationally using PHASE 2.1 program. The phylogenetic investigations were also performed using MrBayes program. RESULTS: A total of 136 unique haplotypes were identified within these five Bangladesh chicken populations, and only one was shared (between Hilly and Naked Neck). Phylogenetic analysis showed no distinct haplotype clustering among the five populations, although they were shared in distinct clades; notably, the first clade lacked Naked Neck haplotypes. CONCLUSION: The present study discovered a set of unique MHC-B haplotypes in Bangladesh chickens that could possibly cause varied immune reponses. However, further investigations are required to evaluate their relationships with global chicken populations.

Green synthesis of zinc oxide nano particles using Allium cepa L. waste peel extracts and its antioxidant and antibacterial activities.

Synthesis of nanoparticles through the green approach using plant and vegetable extracts has gained popularity since they are thought to be efficient and cost-effective materials. This study is designed to synthesize zinc oxide nanoparticles (ZnO-NPs) from onion waste peel extract (Allium cepa L.) via the green synthesis approach. The synthesized ZnO-NPs were characterized by utilizing the UV-Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), Energy Dispersive X-ray (EDX), Field Emission Scanning Electron Microscopy (FE-SEM) and X-ray Powder Diffraction (XRD)techniques. The nanoparticles formation was confirmed by the UV-Vis sharp absorption spectra at 318 and 322 nm. The synthesized ZnO-NPs size and shape was revealed by the XRD and SEM respectively. Smallest nanoparticle average crystallite size was found 57.38 nm with hexagonal shape. The bioactive functional groups that are in charge of capping and stabilizing the ZnO-NPs was assured by the FTIR data. Further, prepared ZnO-NPs were used to assess their possible antioxidant and antibacterial properties. DPPH test for free radical scavenging showed potential antioxidant properties of the synthesized ZnO-NPs. The antibacterial activity were studied against three clinical strains: P. aeruginosa, E. coli, and S. aureus with the maximum zone of inhibition 13.17 mm, 22.00 mm and 12.35 mm respectively at 100 µg/mL subsequently minimum inhibitory concentration was found 50 µg/mL for P. aeruginosa, and S. aureus whereas 100 µg/mL for E. coli. Antioxidant and antibacterial activity tests appear bio-resource based ZnO-NPs from Allium cepa L. extract have effects on free radical and growth of microorganisms.Therefore, it could be a promising candidates for agricultural and food safety applications as an effective antimicrobial agent against pathogenic microorganisms and also can address future biomedical applications after complete in vivo study.

An enhanced Swin Transformer for soccer player reidentification.

The re-identification (ReID) of objects in images is a widely studied topic in computer vision, with significant relevance to various applications. The ReID of players in broadcast videos of team sports is the focus of this study. We specifically focus on identifying the same player in images taken at any given moment during a game from various camera angles. This work varies from other person ReID apps since the same team wears very similar clothes, there are few samples for each identification, and image resolutions are low. One of the hardest parts of object ReID is robust feature representation extraction. Despite the great success of current convolutional neural network-based (CNN) methods, most studies only consider learning representations from images, neglecting long-range dependency. Transformer-based model studies are increasing and yielding encouraging results. Transformers still have trouble extracting features from small objects and visual cues. To address these issues, we enhanced the Swin Transformer with the levering of CNNs. We created a regional feature extraction Swin Transformer (RFES) backbone to increase local feature extraction and small-scale object feature extraction. We also use three loss functions to handle imbalanced data and highlight challenging situations. Re-ranking with k-reciprocal encoding was used in this study's retrieval phase, and its assessment findings were provided. Finally, we conducted experiments on the Market-1501 and SoccerNet-v3 ReID datasets. Experimental results show that the proposed re-ID method reaches rank-1 accuracy of 96.2% with mAP: 89.1 and rank-1 accuracy of 84.1% with mAP: 86.7 on the Market-1501 and SoccerNet-v3 datasets, respectively, outperforming the state-of-the-art approaches.

Antagonistic activity of Bacillus amyloliquefaciens subsp. amyloliquefaciens against multidrug resistant Serratia rubidaea.

Serratia rubidaea is an opportunistic Gram-negative pathogen that has developed antimicrobial resistance to a variety of commercial antibiotics. The spread of this multidrug-resistant pattern predicts that it will get harder and harder to treat S. rubidaea infections in the future. For this perception, antimicrobial proteins might represent a safe, effective, and biodegradable alternative because their site of action is on cyclic peptides. In this study, one candidate Bacillus amyloliquefaciens subsp. amyloliquefaciens was isolated from the soil of Sundarban mangrove forest, and its identification was confirmed both using the PCR (Polymerase chain reaction) method and the BIOLOG™ microbial identification system. The antibacterial protein, which has a molecular mass of about 50 kDa, was isolated from B. amyloliquefaciens subsp. amyloliquefaciens. Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) was used to confirm the extracted protein's purity. This potential protein was discovered to develop and exhibit antagonistic activity throughout a broad temperature, pH, and salinity range. At doses ranging from 300 to 400 µg/ml, this protein has antagonistic activity against multidrug resistant S. rubidaea and a wide range of other resistant pathogenic bacteria such as Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and so on. The research provides new insights to develop bio-control agents that can be applied for prevent, treat, and control infectious diseases caused by multidrug resistant S. rubidaea, as well as other pathogenic bacteria.

Methamphetamine-associated pulmonary arterial hypertension: data from the national biological sample and data repository for pulmonary arterial hypertension (PAH Biobank).

OBJECTIVE: This study compares the clinical and haemodynamic severity of methamphetamine-associated pulmonary arterial hypertension (MA-PAH) with idiopathic pulmonary arterial hypertension (IPAH) and connective tissue-associated pulmonary arterial hypertension (CTD-PAH). It also examines sex differences in clinical and physiological parameters among those with MA-PAH. DESIGN: This is a cross-sectional study using clinically derived data from the National Biological Sample and Data Repository for Pulmonary Arterial Hypertension (PAH biobank), a US-based registry, to compare clinical and physiological characteristics between males and females with MA-PAH. POPULATION: The analysis included 1830 patients enrolled in the PAH biobank, with a diagnosis of MA-PAH (n=42), IPAH (n=1073), or CTD-PAH (n=715). MAIN OUTCOME MEASURES: The study assessed and compared the clinical and haemodynamic parameters of patients with MA-PAH, IPAH and CTD-PAH. RESULTS: Among the patients analysed, 42 had MA-PAH, with 69.1% being female. There were no statistically significant differences in functional class among patients with MA-PAH, IPAH and CTD-PAH. The per cent predicted 6-min walk distance (6MWD) was comparable between the three groups. Patients with MA-PAH had similar mean pulmonary artery pressure and pulmonary vascular resistance to patients with IPAH but higher compared with patients with CTD-PAH. Male patients with MA-PAH exhibited a worse functional class and lower per cent predicted 6MWD, but no significant differences in haemodynamic findings were observed between the sexes. CONCLUSION: There were no differences in haemodynamic between MA-PAH and IPAH but we found that MA-PAH differed from CTD-PAH. The study did not find evidence of sex differences in MA-PAH. Further research is necessary to identify risk factors and underlying mechanisms of MA-PAH, particularly considering the increasing prevalence of methamphetamine use. Such investigations will contribute to the development of effective prevention and treatment strategies for this condition.

Transient ischemic stroke triggers sustained damage of the choroid plexus blood-CSF barrier.

Neuroinflammation is a pathological event associated with many neurological disorders, including dementia and stroke. The choroid plexus (ChP) is a key structure in the ventricles of the brain that secretes cerebrospinal fluid (CSF), forms a blood-CSF barrier, and responds to disease conditions by recruiting immune cells and maintaining an immune microenvironment in the brain. Despite these critical roles, the exact structural and functional changes to the ChP over post-stroke time remain to be elucidated. We induced ischemic stroke in C57BL/6J mice via transient middle cerebral artery occlusion which led to reduction of cerebral blood flow and infarct stroke. At 1-7 days post-stroke, we detected time-dependent increase in the ChP blood-CSF barrier permeability to albumin, tight-junction damage, and dynamic changes of SPAK-NKCC1 protein complex, a key ion transport regulatory system for CSF production and clearance. A transient loss of SPAK protein complex but increased phosphorylation of the SPAK-NKCC1 complex was observed in both lateral ventricle ChPs. Most interestingly, stroke also triggered elevation of proinflammatory Lcn2 mRNA and its protein as well as infiltration of anti-inflammatory myeloid cells in ChP at day 5 post-stroke. These findings demonstrate that ischemic strokes cause significant damage to the ChP blood-CSF barrier, contributing to neuroinflammation in the subacute stage.

Hypoxia increases persulfide and polysulfide formation by AMP kinase dependent cystathionine gamma lyase phosphorylation.

Hydropersulfide and hydropolysulfide metabolites are increasingly important reactive sulfur species (RSS) regulating numerous cellular redox dependent functions. Intracellular production of these species is known to occur through RSS interactions or through translational mechanisms involving cysteinyl t-RNA synthetases. However, regulation of these species under cell stress conditions, such as hypoxia, that are known to modulate RSS remain poorly understood. Here we define an important mechanism of increased persulfide and polysulfide production involving cystathionine gamma lyase (CSE) phosphorylation at serine 346 and threonine 355 in a substrate specific manner, under acute hypoxic conditions. Hypoxic phosphorylation of CSE occurs in an AMP kinase dependent manner increasing enzyme activity involving unique inter- and intramolecular interactions within the tetramer. Importantly, both cellular hypoxia and tissue ischemia result in AMP Kinase dependent CSE phosphorylation that regulates blood flow in ischemic tissues. Our findings reveal hypoxia molecular signaling pathways regulating CSE dependent persulfide and polysulfide production impacting tissue and cellular response to stress.

Social-geographic disparities in suicidal ideations among methamphetamine users in the USA.

IMPORTANCE: Methamphetamine use is a growing public health concern nationwide. Suicide is the second leading cause of death in 2019 for US citizens aged 10-14 years and 25-34 years and is also a significant public health concern. Understanding the intersection of methamphetamine use and suicidal ideation (SI) is necessary to develop public health and policy solutions that mitigate these ongoing severe public health issues. OBJECTIVE: Our objective was to examine SI in methamphetamine users to allow us to determine prevalence and trends by age, sex, race, and geographical region. DESIGN, SETTINGS, AND PARTICIPANTS: Using data collected between 2008 and 2019 from the National Inpatient Sample (NIS) database, we identified hospital admissions (HA) of patients ≥18 years of age with a primary or secondary diagnosis of SI who were also diagnosed as methamphetamine users. Those who used other substances with methamphetamine were excluded from the analysis. MAIN OUTCOME AND MEASURES: To determine the trend and prevalence of hospital admissions due to SI and SI among methamphetamine users, we used trend weights to calculate the national estimates and performed design-based analysis to account for complex survey design and sampling weights on data collected between 2008 and 2019 in the US. RESULTS: The prevalence ratio (PR) of hospitalizations with concurrent SI and methamphetamine use increased 16-fold from 2008 to 2019. The most significant increase occurred between 2015 and 2016; the PR doubled from 6.07 to 12.14. The PR of hospitalizations with concurrent SI and methamphetamine use was highest in patients aged 26-40 (49.08%) and 41-64 (28.49%). Patients aged 41-64 showed the most significant increase from 2008 to 2019 (15.8-fold). While non-Hispanic White patients comprised most of these hospitalizations (77.02%), non-Hispanic Black patients showed the highest proportional increase (39.1-fold). The Southern and Western regions in the US showed the highest PR for these hospitalizations (34.86% and 34.31%, respectively). CONCLUSION AND RELEVANCE: Our findings indicate that SI in methamphetamine users has been increasing for some time and is likely to grow. In addition, our results suggest that these patients are demographically different. Both conditions are associated with a lesser likelihood of seeking and receiving care. Therefore, when addressing increased SI or methamphetamine use, learning more about patients who share both conditions is necessary to ensure proper care.

Short-term Outcome of Peroral Endoscopic Myotomy Performed by the Same Endoscopist on Achalasia and Nonachalasia Esophageal Motility Disorders.

BACKGROUND: Peroral endoscopic myotomy (POEM) is a relatively new but increasingly therapeutic option for achalasia. In recent years, POEM has been used for nonachalasia esophageal motility disorders (NAEMDs), such as diffuse esophageal spasm, esophagogastric junction outlet obstruction, and hypercontractile disorder, with some clinical success. No studies thus far compare the outcomes of these two groups. We perform the first head-to-head comparison of outcomes after POEM in patients with achalasia and NAEMD. PATIENTS AND METHODS: A retrospective analysis of all patients undergoing POEM at one university hospital by a single expert endoscopist from July 2021 to December 2022 was performed. All patients were symptomatic, and the presence of esophageal motility disorders was confirmed using multiple diagnostic modalities. These patients were then divided into 2 groups, achalasia and NAEMD, based on the underlying diagnosis. Statistical analysis of different clinical outcomes, including effectiveness and safety, was performed. RESULTS: Thirty-seven patients (mean age: 59.55, females: 22) underwent POEM in the study period. Twenty patients had achalasia and 17 patients had NAEMD. The median myotomy length was 5.5 cm for the achalasia group and 10 cm for the NAEMD group. This excluded patients with esophagogastric junction outlet obstruction in which the median myotomy length was 3 cm. The procedure time, the duration of hospital stays, the rates of same-day discharge, and complications were similar between the two. Short-term outcomes of POEM for the two groups were similar with improvement in 94% of patients in the achalasia group and 93.75% in the NAEMD group. CONCLUSION: Contrary to prior observations, our study highlights that POEM is equally effective in achieving clinical improvement in patients with NAEMD as achalasia over 6 months of follow-up. In addition, POEM has a comparable safety profile in both patient groups making it a feasible therapeutic option for these debilitating and challenging disorders.

Schistosomus reflexus dystocia in a crossbred dairy cow.

Key Clinical Message: Schistosomus reflexus (SR), an unusual congenital defect in calves, can be diagnosed grossly by exposed viscera and curved spine with hindquarters twisted up toward the head. SR is typically associated with dystocia and fetal deaths in cows. Hence, cattle breeding programs must be aware of these anomalies to avoid losses from abnormal, non-viable calves. Abstract: Schistosomus reflexus (SR) is a rare and fatal congenital malformation in bovines from autosomal recessive disorders. We report a typical case of SR in a non-viable calf after the cesarean section of a crossbred Friesian cow. It was characterized by the inversion of the spinal column and a pronounced ventral curvature causing the cranium to be positioned near the sacrum and tail, along with exposed thoracic and abdominal viscera, limb ankylosis, and tongue protrusion. The postoperative management of the cow, along with the outcome, is also described here.

A new hybrid algorithm for intelligent detection of sudden decline syndrome of date palm disease.

Date palm is an important domestic cash crop in most countries. Sudden Decline Syndrome (SDS) causes a huge loss to the crop both in quality and quantity. The literature reports the significance of early detection of disease towards preventive measures to improve the quality of the crop. The number of prevailing detection methods limits to consideration of a certain aspect of disease identification. This study proposes a new hybrid fuzzy fast multi-Otsu K-Means (FFMKO) algorithm integrating the date palm image enhancement, robust thresholding, and optimal clustering for significant disease identification. The algorithm adopts a multi-operator image resizing cost function based on image energy and the dominant color descriptor, the adaptive Fuzzy noise filter, and Otsu image thresholding combined with K-Means clustering enhancements. Besides, we validate the process with histogram equalization and threshold transformation towards enhanced color feature extraction of date palm images. The algorithm authenticates findings on a local dataset of 3293 date palm images and, on a benchmarked data set as well. It achieves an accuracy of 94.175% for successful detection of SDS that outperforms the existing similar algorithms. The impactful findings of this study assure the fast and authentic detection of the disease at an earlier stage to uplift the quality and quantity of the date palm and boost the agriculture-based economy.