The mTORC1-eIF4F axis controls paused pluripotency.

Mouse embryonic stem cells (mESCs) can self-renew indefinitely and maintain pluripotency. Inhibition of mechanistic target of rapamycin (mTOR) by the kinase inhibitor INK128 is known to induce paused pluripotency in mESCs cultured with traditional serum/LIF medium (SL), but the underlying mechanisms remain unclear. In this study, we demonstrate that mTOR complex 1 (mTORC1) but not complex 2 (mTORC2) mediates mTOR inhibition-induced paused pluripotency in cells grown in both SL and 2iL medium (GSK3 and MEK inhibitors and LIF). We also show that mTORC1 regulates self-renewal in both conditions mainly through eIF4F-mediated translation initiation that targets mRNAs of both cytosolic and mitochondrial ribosome subunits. Moreover, inhibition of mitochondrial translation is sufficient to induce paused pluripotency. Interestingly, eIF4F also regulates maintenance of pluripotency in an mTORC1-independent but MEK/ERK-dependent manner in SL, indicating that translation of pluripotency genes is controlled differently in SL and 2iL. Our study reveals a detailed picture of how mTOR governs self-renewal in mESCs and uncovers a context-dependent function of eIF4F in pluripotency regulation.

Determination of histological and genotoxic parameters of Nile Tilapia, Oreochromis niloticus exposed to lead (Pb).

This study investigates the hazardous effects of lead on the histological and genotoxic parameters of the fish, Oreochromis niloticus. Present work was conducted in a series of three steps. In first step, acute toxicity, LC50 and lethal lead concentration were measured using Probit analysis method. LC50 value and lethal concentration for O. niloticus was measured as 77.673 mgL-1 and 150.924 mgL-1, respectively. In second step, histological changes were assessed by preparing slides of tissues of the gills, liver and kidney of both control and Pb-stressed O. niloticus and examining the respective tissues under the light microscope. The inferences showed significant histological alterations (p<0.05) in the gills of Pb-exposed fish including necrosis, edema, vascular congestion, shortening and curling and lifting of the epithelium of secondary lamella in gills. The cellular degeneration and dilation of sinusoids in liver and loss of hemopoietic tissue, necrosis and edema in kidney was observed. Histomorphometry of the liver showed a decrease in diameter of the central vein and hepatocyte along with an increase in width of sinusoids. The histomorphometry of kidney showed an increase in the diameter of renal corpuscle, glomerulus, proximal and distal convoluted tubules. The nuclear anomalies were studied in the RBCs of fish. Non-parametric Mann-Whitney U-test was conducted to compare nuclear abnormalities and the frequency of micronuclei among the control and lead-treated fish groups. Results declared an increased micronucleus, notched and de-shaped nuclei frequency, in RBCs of fish exposed to lead as compared to control group.

NLR and PLR Ratios - Accessible and Affordable Predictors of Disease Severity in COPD.

COPD is currently the fourth leading cause of death the world but is projected to be 3rd leading cause of death by 2020. It is characterized by limitation of airflow which is not fully transformable to normal along with increased long term inflammatory response in airways of the tracts of lungs. Acute exacerbations of COPD (AECOPD) are the most common causes of hospitalization and death among COPD patients. CRP, leukocytes, IL-6, IL-8 and fibrinogen are associated with COPD. However, while these biomarkers may be helpful, many of them are time consuming with extra cost, and some of the tests are not readily clinically available. Neutrophil-to-Lymphocyte Ratio (NLR) and platelet lymphocyte ratio (PLR) are effortless and basic parameters that are readily obtained from the simplest and easily obtainable complete blood count, even in peripheral hospitals. Material: Study was conducted at NMCH &RC, Raichur, patients attending NMCH for a duration of 18 months. 100 patients with a confirmed diagnosis of COPD confirmed with pulmonary function test according to GOLD criteria were included in the study. Observation: Mean age of the study population was 67.14±8.03 years. Males were predominant with male to female ratio as 9:1.Mean NLR of the AECOPD patients from stage 1 was 3.73±0.18, stage 2 was 6.07±1.27, stage 3 was 6.02±1.14 and stage 4 was 8.19±2.66. When we compared the mean NLR of the patients between different stages of COPD, the difference was found to be statistically significant (p<0.05). It means mean NLR was higher in stage 4 as compared to other groups. Mean PLR of the AECOPD patients from stage 1 was 12690.48±3978.45, stage 2 was 22219.93±7797.9, stage 3 was 19158.73±5070.88 and stage 4 was 19544.87±10207.59. When we compared the mean PLR of the patients between different stages of COPD, the difference was found to be statistically significant (p<0.05). It means mean PLR was higher in stage 2 followed by stage 4 as compared to other groups Conclusion: The NLR and PLR may be used as a useful and easily accessible tool for evaluating the ongoing inflammation during stable period and the disease severity during acute exacerbations in COPD patients. NLR ratio is more specific to severity of COPD compared to PLR ratio.

Blunt abdominal trauma patients presenting to a tertiary care facility of Pakistan: A three years' experience.

Blunt abdominal trauma (BAT) refers to injuries without wounds entering the peritoneal cavity due to road traffic accidents (RTA) and falls, as a result of collision or counter collision. The objective of the present study was to determine the frequency of patients with visceral injuries in blunt abdominal trauma. This study was carried out in the Department of Surgery, including ward-3 of Jinnah Post Graduate Medical Centre, Karachi, from November 2017 till November 2020. The study design was descriptive case series. During the study period, the data of 112 patients was collected, which comprised of 102 males and 10 females. All the patients between 12 to 65 years of age (mean age:31.84±13.14 years) presenting to the emergency with < 24 hours of abdominal trauma, were included in the study. Organs involved during blunt abdominal trauma were observed and frequency was recorded. Liver injuries were found in 48(42.28%) patients, intestinal injuries in 40(35.7%), splenic injuries in 32(28.5%), kidney injuries in 24(21.4%), pancreatic injuries in 8(7.1%) and stomach injuries in 4(3.5%) patients. Grade 4 liver injury was found in 80(71%) patients, Grade 2 and 3 splenic injuries in 56(50%) patients whereas 47(42%) patients had grade 1 kidney injury. Liver was found to be the most frequent organ involved, followed by intestine and spleen.

Treatment of leachate through constructed wetlands using Typha angustifolia in combination with catalytic ozonation on Fe-zeolite A.

Leachate control and management is a major challenge faced during solid waste management as it may pollute surface and groundwaters. In the current research, constructed wetlands (CWs) vegetated with Typha angustifolia plant in combination with catalytic ozonation by ferrous (Fe)-coated zeolite A was studied for the treatment of leachate. The CWs treatment with 9 days detention reduced the chemical oxygen demand (COD) and biochemical oxygen demand (BOD) up to 75.81% and 69.84%, respectively. Moreover, total suspended solids (TSS), total dissolved solids (TDS), and total kjeldahl nitrogen (TKN) removal of 91.16%, 33.33%, and 25.22% were achieved, respectively. The Fe-coated zeolite A catalytic ozonation further reduced the COD up to 90.7%. Comparison of the processes showed the effective performance of the combined process (CW/O3/Fe-zeolite) with 97.76% COD reduction of leachate. It is, therefore, concluded that the studied combined process (CW/O3/Fe-zeolite A) was more efficient as compared with single ozonation and CW alone, hence it can be implied for the leachate treatment in real conditions.

Inhibition of mouse embryonic stem cell proliferation and induction of differentiation by natural products isolated from Rhazya stricta Decne.

Embryonic stem cells provide an ideal system to study various therapies for serious human diseases such as juvenile diabetes, neurodegenerative diseases, heart diseases and cancer. Synthetic or natural compounds that affect cell proliferation and/or differentiation of embryonic stem cells are of great value. Focus of the current project was upon the isolation and evaluation of natural components from a medicinal plant; Rhazya stricta on proliferation/ differentiation potential of embryonic stem cells. For this purpose, after a series of fractionation and purification steps, 7 compounds named as RS1-RS7 were isolated from aerial parts of the plant. The effects of these compounds were evaluated on the morphology and rate of cell proliferation of mouse naive embryonic stem cells. Only RS7 inhibited the proliferation of cell and reduced the induction of differentiation of cell. The qPCR analysis confirmed that the expression of the selected pluripotency markers (Oct4, Nanog and Sox2) was down regulated by RS7 treatment as compared to control. Furthermore, upon withdraw of Leukemia inhibitory factor (lif) from medium; effect of RS7 to promote differentiation was enhanced. Through structure elucidation studies, RS7 was found to be ursolic acid. This study first time shows the effect of natural compounds of Rhazya stricta Decne. on mouse embryonic stem cells.

Comparative therapeutic efficacy of Phyllanthus emblica (Amla) fruit extract and procaine penicillin in the treatment of subclinical mastitis in dairy buffaloes.

To investigate the comparative therapeutic efficacy of Phyllanthus emblica (Amla) fruit extract and procaine penicillin in the treatment of subclinical mastitis, a total of 30 subclinical mastitis positive buffaloes out of 194 lactating buffaloes were divided into 3 equal groups viz. A, B and C. Group A was treated with procaine penicillin, group B was treated with Phyllanthus emblica fruit extract and group C was served as control for 5 days respectively. The collected milk samples were subjected to the treatment trials before and after the treatment at day 0, 7th and 14th day aseptically. The evaluation parameters were bacteriological cure rate, milk pH, milk yield. The percentage cure rate of sub-clinically mastitic quarters in group A, B and C were 80.95%, 64.7% and 22.22% at day 14 respectively. The quarter based bacteriological cure rate was highest in group A (80.95%) followed by group B (64.7%) and group C (22.22%). The pH was significant (P > .05) in group A, B and C at day 0, 7 and 14. It is concluded that Phyllanthus emblica fruit extract is an inexpensive source in the treatment of subclinical mastitis in dairy buffaloes and can be used as an alternative to antibiotic therapy as for procaine penicillin.

Odontogenic cyst with diverse histopathological features: report of an unusual case.

OBJECTIVE: It is a well established fact that all inflammatory and developmental cysts of odontogenic origin have squamous epithelial linings. They may show various forms of metaplasia from a stratified squamous to more highly differentiated ciliated columnar or mucous cells. Dentigerous cyst represents is the most common developmental odontogenic cyst usually associated with an impacted tooth after complete formation of the crown. A dentigerous cyst encloses is seen attached to the neck of the tooth at the cementoenamel junction associated with an unerupted/ impacted tooth and grows by expansion of the dental follicles. We report a similar case of dentigerous cyst associated with an impacted tooth, histologically demonstrates the characteristics of a glandular odontogenic cyst with pseudo- stratified ciliated columnar epithelium lining with goblet cells and mucous cells.

Aspergillus ochraceopetaliformis SSP13 modulates quorum sensing regulated virulence and biofilm formation in Pseudomonas aeruginosa PAO1.

Pseudomonas aeruginosa is an opportunistic nosocomial pathogen causing the majority of acute and persistent infections in human beings. The ability to form biofilm adds a new dimension to its resistance to conventional therapeutic agents. In the present study, down-regulation of quorum sensing regulated virulence and biofilm development resulting from exposure to Aspergillus ochraceopetaliformis SSP13 extract was investigated. The in vitro results inferred impairment in the production of LasA protease, LasB elastase, chitinase, pyocyanin, exopolysaccharides and rhamnolipids. In addition, motility and biofilm formation by P. aeruginosa PAO1 was significantly altered. The in vitro results were further supported by molecular docking studies of the metabolites obtained from GC-MS analysis depicting the quorum sensing attenuation by targeting the receptor proteins LasR and RhlR. The in vitro and in silico studies suggested new avenues for the development of bioactive metabolites from A. ochraceopetaliformis SSP13 extract as potential anti-infective agents.

Antimicrobial susceptibility patterns of clinical isolates of Pseudomonas aeruginosa isolated from patients of respiratory tract infections in a Tertiary Care Hospital, Peshawar.

OBJECTIVE: This study aims to determine the prevalence and susceptibility pattern of Pseudomonas aeruginosa and multidrug-resistant (MDR) isolates in patients suffering from respiratory tract infection. METHODS: A cross sectional study was conducted from January to December 2014 in Northwest General Hospital and Research Centre, Peshawar. A total of 615 sputum samples were collected from both in and out-patients. Sputum samples were collected as per standard procedure and were inoculated on Blood, MacConkey and Chocolate agar. The isolates were identified by standard protocols using biochemical tests. The antibiotic susceptibility pattern of each isolate was checked as per Clinical and Laboratory Standards Institute (CLSI) guidelines using Kirby-Bauer's disc diffusion method. RESULTS: Out of 615 sputum samples, 354 (57.56%) were culture positive. Out of these a total of 71 (20.05%) strains of Pseudomonas were isolated, where 54.93% was from males and 45.07% were from females (Mean age was 44.29 ± 22.72:). Highest sensitivity was seen to Amikacin (92.86%) followed by Meropenem (91.55%) while lowest sensitivity was seen to Cefoperazone + Sulbactam (16.9%). There were 39.44% MDR strains, out of which 25% were Extensively Drug Resistant (XDR) and 10.71% were Pan Drug Resistant (PDR). In vitro susceptibility of MDR isolates showed highest sensitivity to Amikacin (82.14%) followed by Carbapenems (78.57%). All MDR isolates were resistant to Cefoperazone + Sulbactam. Resistance to Piperacillin + Tazobactam was 96.43%. CONCLUSION: Pseudomonas aeruginosa is one of the commonly isolated organisms and it is becoming more resistant to commonly used antibiotics. Carbapenems and aminoglycosides were the two classes of drugs that showed highest activity against Pseudomonas aeruginosa.

Evaluation of Ajuga bracteosa for antioxidant, anti-inflammatory, analgesic, antidepressant and anticoagulant activities.

BACKGROUND: Ajuga bracteosa has been extensively used traditionally for the treatment of a variety of diseases. The aim of the study was to scientifically validate the wide-scale exploitation of A. bracteosa in folk medicine various in vitro and in vivo assays. Moreover, these activities were related to the intrinsic biologically active phytoecdysteroids of A. bracteosa. METHODS: Aerial and root parts of A. bracteosa were first extracted separately with chloroform (AbCA and AbCR) and the residue was again extracted with methanol (AbMA and AbMR). Total flavonoid and phenolic contents were assayed as quercetin (QE) and gallic acid equivalents (GAE), respectively. These extracts were analyzed for in vitro antioxidant assessment including DPPH and H2O2 (% inhibition of free radicals), and reducing power and phosphomolybdenum methods (ascorbic acid equivalents AAE mg/g DW). Further, these extracts were assayed in vivo in separate groups of Sprague-Dawley rats for carrageenan induced rat paw edema inhibition, hotplate antinociception, forced swim antidepression and anticoagulation. Dose of each crude extract and standard drug given to rats was 200 mg/Kg- and 10 mg/10 mL/Kg body weight respectively. Plant extracts and standard drugs were administered orally, 60 min prior to the conduction of assays. Moreover, biologically active phytoecdysteroids were screened in A. bracteosa with the help of RP-HPLC. RESULTS: AbMA represented highest values of flavonoids (QE 1.98 % DW) and phenolic contents (GAE 5.94 % DW), significantly scavenged DPPH radicles (IC50 36.9) and reduced ferric ions with 718.4 mg ascorbic acid equivalent/g (AAE). Highest total antioxidant capacity was expressed by AbMR (927 mg AAE) with an IC50 value 19.1 µg/mL. The extracts which were found potent anti-oxidants, were also good at in vivo activities. AbMA significantly reduced edema in all the three hours of treatment (67.9, 70.3 and 74.3 %). AbMA also showed maximum nociceptor suppression in analgesic assay by delaying the time to start licking of paws in rats (57.7 ± 4.9 s). In addition, maximum anti-coagulation was also exhibited by AbMA (89.3 s), while all extracts were found strong antidepressants (≤15.66 s immobility time). Screening of biologically active phytoecdysteroids revealed the presence of 20-hydroxyecdysone (20-HE), makisterone (MKA), cyasterone (CYP) and ajujalactone (AJL). Total phytoecdysteroid content found in A. bracteosa was 1232.5 µg/g DW and 20-HE was most abundant (1232.5 µg/g DW) as compared to other phytoecdysteroids. CONCLUSION: Based on the tested in vitro and in vivo activities, AbMA was found to be a promising bioactive extract. These activities can be attributed to the intrinsic polyphenols and phytoecdysteroids contents of A. bracteosa.

Association of APO B gene polymorphisms with the development of myocardial infarction in Pakistani population.

Myocardial infarction (MI) is when a blood clot in the coronary artery obstructs blood flow to a specific part of the heart, leading to the death of myocardium in that area. The development of MI is influenced by various environmental factors, genetic components, and their interactions, even though the exact cause has not been fully established. This is the first case-control study examining the possible association between the human Apo B gene and MI in the Punjab region of Pakistan. The study included 100 patients and 50 healthy individuals. Genomic DNA was isolated from blood samples using manual extraction methods. Subsequently, primers were optimized, and genotyping was performed using PCR, followed by DNA sequencing and RFLP analysis. The research focused on two specific APO B gene SNPs, codon 4154 G/A (rs1801701) and codon 2488 G/A (rs1042031). Both SNPs involved the substitution of guanine with adenine. It was found that individuals carrying the minor allele A of SNP rs1801701 (p < 0.001) and the minor allele A of rs1042031 (p < 0.001) had a significantly higher risk of developing MI. Additionally, haplotype analysis revealed that the AA haplotype (comprising both rs1801701 and rs1042031 SNPs) was associated with a substantially increased risk of MI (OR = 3.845). In conclusion, the study provides evidence supporting the association between specific mutations in the APOB gene and the risk of myocardial infarction in the Pakistani population.

Vitamin C Alleviates the Negative Effects of Heat Stress on Reproductive Processes by Regulating Amino Acid Metabolism in Granulosa Cells.

Heat stress-induced biochemical alterations in ovarian follicles compromise the function of granulosa cells (GCs) and the developmental competence of oocytes. Summer heat stress can have a far-reaching negative impact on overall fertility and reproductive success. Together with the heat stress, the rise of assisted reproductive technologies (ART), potential confounding hazards of in vitro handling and the absence of systemic body support in ART makes it imperative to study the heat stress ameliorative effects of vitamin C under in vitro conditions. Using in vitro heat stress treatment of 43 °C for two hours in bovine GCs, we studied the effects of vitamin C on cell growth, oxidative stress, apoptosis and cell cycle progression together with a comprehensive metabolomics profiling. This study investigates the molecular milieu underlying the vitamin C (VC)-led alleviation of heat-related disruptions to metabolic processes in bovine GCs. The supplementation of VC ameliorated the detrimental effects of heat stress by reducing oxidative stress and apoptosis while restoring cell proliferation. Normal cell function restoration in treated GCs was demonstrated through the finding of significantly high levels of progesterone. We observed a shift in the metabolome from biosynthesis to catabolism, mostly dominated by the metabolism of amino acids (decreased tryptophan, methionine and tyrosine) and the active TCA cycle through increased Succinic acid. The Glutathione and tryptophan metabolism were important in ameliorating the inflammation and metabolism nexus under heat stress. Two significant enzymes were identified, namely tryptophan 2,3-dioxygenase (TDO2) and mitochondrial phenylalanyl-tRNA synthetase (FARS2). Furthermore, our findings provide insight into the significance of B-complex vitamins in the context of heat stress during VC supplementation. This study underscores the importance of VC supplementation in heat stress and designates multiple metabolic intervention faucets in the context of ameliorating heat stress and enhancing reproductive efficiency.

Salivary transforming growth factor beta in oral submucous fibrosis: A diagnostic and predictive marker.

CONTEXT: Growth factors and cytokines like transforming growth factor beta (TGF-ß) play a key role in the pathogenesis of oral submucous fibrosis. AIMS: To elucidate the role of Salivary TGF-ß isoforms as a predictive and diagnostic marker for oral submucous fibrosis. SETTINGS AND DESIGN: A total of 30 OSMF and 10 control patients were included in this study, and their clinic-epidemiological data was recorded. METHODOLOGY: The expression of TGF-ß genes-TGF-ß1, TGF-ß2, TGF-ß3-was studied by a real-time polymerase chain reaction in tissue and saliva. Patients were given medicinal intervention for 12 weeks along with jaw-opening exercises. Expression of salivary TGF-ß genes was studied at 12 weeks. STATISTICAL ANALYSIS USED: SPSS software version 20. RESULT: Expression of salivary TGF beta isoforms in OSMF was more than in the control group. There was an increase in salivary TGF-ß1, ß2, ß3 expressions with increasing clinical grades of OSMF and advancing the stage of the disease. Expression of all the TGF beta isoforms was decreased after treatment with statistically significant results. Statistically significant correlations were found between the mean difference of TGF-ß1 and the mean difference between mouth opening and tongue protrusion. CONCLUSION: Salivary TGF-ß isoforms may be used in diagnosis, risk assessment, and screening of the entire population at risk of OSMF after its clinical validation. However, adequate sample size and segmental assessment of the expression of TGF-ß isoforms are needed for further evaluation.

Multi-Locus Microsatellite Typing of Colonising and Invasive Aspergillus fumigatus Isolates from Patients Post Lung Transplantation and with Chronic Lung Disease.

Aspergillus fumigatus can cause different clinical manifestations/phenotypes in lung transplant (LTx) recipients and patients with chronic respiratory diseases. It can also precipitate chronic lung allograft dysfunction (CLAD) in LTx recipients. Many host factors have been linked with the severity of A. fumigatus infection, but little is known about the contribution of different A. fumigatus strains to the development of different phenotypes and CLAD. We used multi-locus microsatellite typing (MLMT) to determine if there is a relationship between strain (i.e., genotype) and phenotype in 60 patients post LTx or with chronic respiratory disease across two time periods (1 November 2006-31 March 2009 and 1 November 2015-30 June 2017). The MLMT (STRAf) assay was highly discriminatory (Simpson's diversity index of 0.9819-0.9942) with no dominant strain detected. No specific genotype-phenotype link was detected, but several clusters and related strains were associated with invasive aspergillosis (IA) and colonisation in the absence of CLAD. Host factors were linked to clinical phenotypes, with prior lymphopenia significantly more common in IA cases as compared with A. fumigatus-colonised patients (12/16 [75%] vs. 13/36 [36.1%]; p = 0.01), and prior Staphylococcus aureus infection was a significant risk factor for the development of IA (odds ratio 13.8; 95% confidence interval [2.01-279.23]). A trend toward a greater incidence of CMV reactivation post-A. fumigatus isolation was observed (0 vs. 5; p = 0.06) in LTx recipients. Further research is required to determine the pathogenicity and immunogenicity of specific A. fumigatus strains.

Exploring the long-term disability outcomes in Trauma patients: study protocol.

OBJECTIVES: Trauma registries are essential tools for improving trauma care quality and efficiency, but many fail to capture long-term patient-reported outcome measures (PROMs). Focusing on these outcomes is crucial for understanding the extent of disability patients experience and identifying potential post-discharge interventions to optimize recovery. Studies reflecting the experience from low- and middle-income countries in this area are limited. Therefore, we aim to develop a digital trauma registry in Pakistan to prospectively capture patient-reported outcome measures at one, three, six, and twelve months post-injury. METHODS: We will develop and implement a digital trauma registry at two tertiary care facilities in Karachi, Pakistan: Aga Khan University Hospital and Jinnah Postgraduate Medical Center. The registry will include all admitted adult trauma patients (≥ 18 years). Data collection will be conducted digitally using tablets, with mortality, level of disability, functional status, and quality of life as primary outcomes. Follow-up data will be collected through telephone interviews with patients and caregivers. We will employ descriptive statistics to summarize participant's socio-demographic and clinical characteristics. Additionally, we will perform survival analysis using Kaplan-Meier curves and Cox proportional hazard models and utilize mixed-effects linear regression to adjust for potential confounders for primary outcomes. DISCUSSION: The trauma registry will fill the current gap in knowledge regarding long-term outcomes among trauma patients in low- and middle-income countries (LMICs). This study will delineate future direction for capturing post-discharge data, enhancing our understanding of recovery, and informing the design of interventions aimed at improving long-term outcomes.

Phenotypic, Electrophysiologic, and Imaging Spectrum of Hirayama Disease from Northern India.

BACKGROUND AND OBJECTIVES: Cervical flexion-induced myelopathy, also known as Hirayama disease (HD), is a lower motor neuron disorder seen mainly in adolescents and young adults, affecting the C7-T1 myotomes, presenting as asymmetric weakness with wasting of one or both the distal upper limbs. We aimed to describe the clinical features, electrophysiology, and radiologic features of HD in a tertiary care institute in northern India. METHODS: One hundred and forty patients between 2017 and 2022 with clinical and imaging features consistent with HD were retrospectively reviewed from the All India Institute of Medical Sciences-Comprehensive Neuromuscular Diseases center database. RESULTS: Majority were males with the mean age of onset of illness being 17.8 years. The median duration of the symptoms was 3 (1.5-4) years. Sixty-nine (49%) patients had unilateral involvement, and the disease was actively progressing in 88 (63%) patients at presentation. Two families had history of HD in two (1.4%) siblings. Electromyography showed abnormal findings in the clinically involved limb in all the patients and in the clinically uninvolved limb in 17/50 (34%) patients. Flexion magnetic resonance imaging (MRI) demonstrated forward dural displacement in 134 (96%) patients and asymmetric cord flattening in 124 (88.5%) patients. Disability was graded as mild, moderate, and severe; 12 (13%) had severe disability. The majority were managed conservatively, and four underwent surgery for HD. CONCLUSION: A high index of suspicion of HD needs to be kept in a young male presenting with distal upper limb weakness and atrophy. Dynamic MRI of the cervical spine in young adults presenting with hand wasting is inevitable. This disease needs to be managed aggressively and early to prevent serious dysfunction and loss of productivity.

A spatiotemporal atlas of mouse liver homeostasis and regeneration.

The mechanism by which mammalian liver cell responses are coordinated during tissue homeostasis and perturbation is poorly understood, representing a major obstacle in our understanding of many diseases. This knowledge gap is caused by the difficulty involved with studying multiple cell types in different states and locations, particularly when these are transient. We have combined Stereo-seq (spatiotemporal enhanced resolution omics-sequencing) with single-cell transcriptomic profiling of 473,290 cells to generate a high-definition spatiotemporal atlas of mouse liver homeostasis and regeneration at the whole-lobe scale. Our integrative study dissects in detail the molecular gradients controlling liver cell function, systematically defining how gene networks are dynamically modulated through intercellular communication to promote regeneration. Among other important regulators, we identified the transcriptional cofactor TBL1XR1 as a rheostat linking inflammation to Wnt/ß-catenin signaling for facilitating hepatocyte proliferation. Our data and analytical pipelines lay the foundation for future high-definition tissue-scale atlases of organ physiology and malfunction.

Total zinc absorption from a diet containing either conventional rice or higher-zinc rice does not differ among Bangladeshi preschool children.

Information is needed on zinc absorption from grain cultivars having higher zinc content. Total absorbed zinc (TAZ) from mixed diets containing high-zinc rice (HZnR), conventional rice (CR), or CR plus zinc fortificant (CR+Zn) was measured. Forty-two nonmalnourished preschool-aged children were enrolled in 1 of 2 groups. Using a crossover design, children in group A (n = 22) received for 1 d each a mixed diet containing 150 g CR or HZnR. Children in group B (n = 20) received HZnR on 1 d and CR+Zn on the other day. Fractional zinc absorption (FZA) was measured during each dietary period by using a dual-isotope tracer ratio technique; TAZ was calculated as the product of zinc intake [total dietary zinc (TDZ)] and FZA. TDZ was 3.83, 4.83, and 6.03 mg/d when the children were fed the CR, HZnR, and CR+Zn-containing diets, respectively. Mean FZA from the CR diet was greater than from the HZnR diet (25.1 vs. 20.1%, P < 0.001), and the mean FZA from the CR+Zn diet (18.8%) was less than from both the CR diet (P < 0.001) and the HZnR diet (P = 0.014). The mean TAZ was 0.96 ± 0.16, 0.97 ± 0.18, and 1.13 ± 0.20 mg/d from the CR, HZnR and CR +Zn diets, respectively. TAZ was not different for the CR and HZnR diets (P = 0.99) but was significantly greater from the CR+Zn diet compared with the other 2 diets (P < 0.001). Rice cultivars with higher zinc and/or lower phytate content are needed to increase TAZ by young children consuming this amount of rice.

Greening for greater good: investigating the critical factors for customer satisfaction with sustainable e-banking.

This study investigated the impact of efficiency, reliability, responsiveness, safety, and security on customer satisfaction with sustainable e-banking. The study used a quantitative methodology, with data collected from customers of commercial banks in South Punjab, Pakistan. A Likert scale questionnaire was used to collect cross-sectional data. A sample of 350 was analyzed using the Statistical Package for the Social Sciences (SPSS) for testing descriptive statistics, correlation analysis, and regression results. The study's results revealed that efficiency, reliability, responsiveness, safety, and security significantly impacted customer satisfaction with e-banking services. Efficiency and reliability were the most crucial factors influencing customer satisfaction, followed by safety, security, and responsiveness. The research findings have important implications for commercial banks, as they highlight the critical role of these factors in the development of sustainable e-banking practices. Overall, the study provides valuable insights for commercial banks seeking to improve their e-banking services and ensure customer satisfaction. Commercial banks can enhance their competitiveness and achieve sustainable growth in the highly competitive e-banking sector by prioritizing efficiency, reliability, responsiveness, and safety and security.