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The urease enzyme is recognized as a valuable therapeutic agent for treating the virulent Helicobacter pylori bacterium because of its pivotal role in aiding the colonization and growth of the bacterium within the gastric mucosa. In order to control the harmful consequences of bacterial infections, urease inhibition presents itself as a promising and effective approach. The current research aimed to synthesize pyridylpiperazine-based carbodithioate derivatives 5a–5n and 7a–7n that could serve as potential drug candidates for preventing bacterial infections through urease inhibition. The synthesized carbodithioate derivatives 5a–5n and 7a–7n were explored to assess their ability to inhibit the urease enzyme after their structural explication by gas chromatography–mass spectrometry (GC-MS). In the in vitro evaluation with thiourea as a standard drug, it was observed that all the synthesized compounds exhibited significant inhibitory activity compared to the reference drug. Among the compounds tested, 5j (bearing an o-tolyl moiety) emerged as the most effective inhibitor, displaying strong urease inhibition with an IC50 value of 5.16 ± 2.68 μM. This IC50 value is notably lower than that of thiourea (23 ± 0.03 μM), indicating the significantly most potent potential of inhibition. In molecular docking of 5j within the active site of urease, numerous noteworthy interactions were identified.

Background and objectives: A tetrahydro anthraquinone derivative, 4-dehydroxyaltersolanol A, has been obtained from Nigrospora oryzae, which was isolated from Uncaria borneensis Havil as an endophytic fungus. This is a recently described compound whose stereochemistry was assumed from biogenetic considerations. However, using ECD spectral analysis in combination with TD-DFT calculations, its stereochemistry could be determined unambiguously. Method: In the current research, the selected TH1P45 culture was analysed using semi-preparative HPLC, which led to the isolation of six secondary metabolites, including 4-dehydroxyaltersolanol A (1). We have further presented full evidence of the stereochemistry of compound 1. With the help of quantum calculations, we also determined the mechanism by which this compound degrades in solution. Results: The analysis of TH1P45 culture led to the isolation of six secondary metabolites, including 4-dehydroxyaltersolanol A, three anthraquinone derivatives (macrosporin, bostrycin and altersolanol B), and two pyrones (pestalopyrone and hydroxypestalopyrone). Conclusion: A full evidence of the stereochemistry of compound 1 with the help of the combination of X-ray crystallography, ECD, and TD-DFT quantum calculations, allowed unambiguously assigning the absolute stereochemistry of 4 dehydroxyaltersolanol A as 1S,2R,3S as correctly assumed by Proksh and collaborators from biogenetic considerations.

Abstract Background The precise choice of specialty is of paramount importance in a physician’s career. Several factors play a role in deciding the specialty, such as intelligence, motivation, clinical experience, personality, and socioeconomic factors. Our hypothesis is whether personality profiles differ based on specialty choice. Therefore, we investigated the association between personality traits and specialty choice. Results A cross-sectional study was conducted among 379 undergraduate medical students. Big five personality inventory was used to determine the personality traits among medical students. The most chosen speciality among both male and females was Surgery. Comparing the groups depending on their preferred specialties revealed no differences in three of five personality traits of Big five personality inventory. Students who selected psychiatry specialty scored highest on openness (p = 0.007) and lowest on extraversion (p = 0.018), indicating a substantial difference between the traits of extraversion and openness to experience. Conclusions The differences in personality features could not be attributed to a predilection for a particular speciality. However, medical students who scored higher on openness (intellect/imagination) and less on extraversion scales were more likely to choose psychiatric specialty. Numerous other factors affect specialization preference even if there are no differences in personality features between various specialties.

Urease, a nickel-dependent enzyme found in various life forms, catalyzes urea breakdown, concluding nitrogen metabolism by generating ammonia and carbamate. This process causes a rise in pH, supports the survival of pathogens, and can lead to infections such as gastric disorders like ulcers and cancer in humans. Helicobacter pylori employs urease for survival in the acidic environment of the stomach and in protein synthesis. To treat such infections and inhibit the growth of pathogens, it is mandatory to obstruct urease activity; therefore, derivatives of 1-(3-nitropyridin-2-yl)piperazine were synthesized (5a-o; 7a-k). All these newly synthesized compounds were investigated for urease inhibition by in vitro inhibition assays. The results showed that 5b and 7e are the most active inhibitors, having IC50 values of 2.0 ± 0.73 and 2.24 ± 1.63 µM, respectively. These IC50 values are lower than the IC50 value of the standard thiourea, which was 23.2 ± 11.0 µM. The hemolysis potential of 5b, 5c, 5i, 7e, and 7h was also determined; 7e and 7h exhibited good biocompatibility in human blood cells. Through in silico analysis, it was shown that both these potent inhibitors develop favorable interactions with the active site of urease, having binding energies of −8.0 (5b) and −8.1 (7e) kcal/mol. The binding energy of thiourea was −2.8 kcal/mol. Moreover, 5b and 7e have high gastrointestinal permeability as predicted via computational analysis. On the other hand, the IC50 value and binding energy of precursor compound 3 was 3.90 ± 1.91 µM and −6.1 kcal/mol, respectively. Consequently, 5b and 7e can serve as important inhibitors of urease.

Introduction. Hormonal contraceptives (HCs) are used for birth control, menstrual disturbances, and premenopausal syndrome. Most women stop using hormonal contraceptives due to changes in their mood. The evidence regarding the association of hormonal contraception with depression shows mixed results. Therefore, we aim to establish the association between the use of hormonal contraception and depressive symptoms. Methods. A cross-sectional study was conducted on 326 women of the reproductive age group (15–49 years) attending the family planning unit of the obstetrics and gynecology department of a medical college in Saudi Arabia. Their sociodemographic and medical details along with the current use of any contraceptives (hormonal, nonhormonal, or not using any) with duration were collected. Beck depression inventory-II (BDI-II) was applied to the women to assess for depression along with its severity, and a BDI score of >16 was taken to denote clinical depression. Women were stratified by type of contraceptive used, and its association with depression category was assessed. Results. A total of 326 consenting eligible women in the age group of 15–49 years were enrolled in the study of which 165 (50.6%) were currently using a hormonal contraceptive and 49 (15.0%) were using a nonhormonal contraceptive and the rest 112 (34.4%) were not using any contraceptives. There was no significant difference in the mean BDI scores (p=0.79) and degrees of depression (p=0.06) between the HC users and HC nonusers. However, individual symptoms of depression such as sadness (p=0.01), reduced libido (p=0.0002), feelings of pessimism (p=0.02), and failure (p=0.003) were found to be significantly higher in the HC users than non-HC users. Conclusion. We conclude that there was no significant difference in mean depression scores between groups. However, a few individual symptoms of depression were high in HC users suggesting depression as a potential side effect of hormonal contraceptive use.

Background: The diagnosis of depression in dementia patients leads to an increase in the burden of the disease. To treat depression in this patient group, antidepressants are frequently used; however, there is not any proof of their therapeutic effectiveness, and their use may be potentially harmful. This narrative review aims to summarize the existing evidence regarding the role of antidepressants in treating depression in dementia patients. Main text: A search was conducted in the PubMed, Excerpta Medica database (EMBASE), and Cochrane databases for randomized controlled trials and meta-analyses wherein antidepressants were given to dementia sufferers to address depression. Fifteen randomized controlled trials and seven meta-analyses were identified. Most well-designed blinded placebo-controlled trials reported a lack of effectiveness of antidepressants in treating depression in dementia patients. Among the seven metanalyses, two reported good efficacy of Selective serotonin reuptake inhibitors (SSRIs). However, two major Cochrane reviews reported little or no effectiveness and increased side effects of antidepressants in dementia patients. Conclusion: There is robust evidence regarding the lack of efficacy of antidepressants in treating depression in dementia patients. However, further well-designed Randomized controlled trials (RCTs,) using scales with good validity and reliability to diagnose depression in dementia patients, sufficient sample sizes, and detailed adverse effect profiles may help determine the rationale for their use.

Abstract Introduction Coronavirus disease 2019 (COVID-19) pandemic has continued relentlessly for over one and half years now, causing a threat to life, fear of falling sick, helplessness, anxiety, depression and, pessimism about the future. There has been an increasing concern over student mental health in higher education. Our study was designed to measure current mental health status and its relationship with sociodemographic variables and level of knowledge about COVID-19 in Saudi Arabia. Method A cross-sectional survey was conducted among laboratory medicine students of Makkah city, Saudi Arabia from October, 2020 to January, 21. A semi-structured questionnaire was circulated through mail and What’s App. Data collected included sociodemographic details and level of knowledge towards the COVID-19 among the students. Depression anxiety and stress-21 item (DASS 21) was used to assess psychological status. Result Our study reported 51.4% depressive symptoms, 57.9% anxiety symptoms, and 48.5% stress in the study participants. History of being hospitalized with COVID-19 and ICU reported high anxiety (p = 0.0003) and depression scores (p = 0.04). Respiratory droplet as a mode of transmission revealed higher scores on anxiety subscale (p = 0.007), whereas surface contamination reported high score of stress (p = 0.004) and anxiety (p = 0.002). Knowing that COVID-19 can also clinically present with gastrointestinal symptoms was found to show high stress (p = 0.005) and anxiety (p = 0.01) scores than any other way of clinical presentation. Conclusion COVID-19 is likely to cause negative effect on the psychological health of students.

Abstract Background Autism-spectrum disorder is a neurodevelopmental disorder with heterogeneity in etiopathogenesis and clinical presentation. Neuroanatomical and neurophysiological abnormalities may represent neural endophenotypes for autism spectrum disorders which may help identify subgroups of patients seemingly similar in clinical presentation yet different in their pathophysiological underpinnings. Furthermore, a thorough understanding of the pathophysiology of disease can pave the way to effective treatments, prevention, and prognostic predictions. The aim of this review is to identify the predominant neural endophenotypes in autism-spectrum disorder. The evidence was researched at the following electronic databases: Pubmed, PsycINFO, Scopus, Web of Science, and EMBASE. Results Enlarged brain, especially frontotemporal cortices have been consistently reported by structural neuroimaging, whereas functional neuroimaging has revealed frontotemporal dysconnectivity. Conclusions Regrettably, many of these findings have not been consistent. Therefore, translating these findings into neural endophenotype is by far an attempt in its budding stage. The structural and functional neuroimaging changes may represent neural endophenotypes unique to autism-spectrum disorder. Despite inconsistent results, a clinically meaningful finding may require combined efforts of autism-spectrum-disorder researchers focused on different aspects of basic, genetic, neuroimaging, and clinical research.

Abstract Background The coronavirus disease 2019 pandemic has shown a significant impact on the psychological well-being of health care workers. The aim of the study was to evaluate the impact of the COVID-19 pandemic on the psychological health of health care workers in the Kingdom of Saudi Arabia. During the months of November and December, 283 health care workers completed a survey containing measures of depression, anxiety and stress (using Depression Anxiety and Stress-21 scale [DASS-21]) and questions regarding potential predictors such as the role of COVID-19 perception, availability of mental health support and work-related factors. Pearson X 2 test revealed factors associated with the presence of significant psychiatric symptoms. Result Among the participants, 17.3% screened positive for depression, 26.2% for anxiety and 17.3% for stress. Nurses reported significantly more depression, anxiety and stress than doctors. Those who received mental health support reported significantly lesser depression, anxiety and stress. Those who felt that quality of life was heavily impacted due to COVID-19 reported significantly high depression, anxiety and stress. Conclusions Poor psychological well-being was prevalent in health care workers; however, mental health measures have been shown to significantly reduce the mental health burden in health care workers.

Background:Beta-thalassemia is an autosomal recessivehemoglobinopathy with frequent skeletal complications, often debilitating in adolescent patients. We aim to evaluate the bone mineral density (BMD) by dual-energy x-ray absorptiometry (DEXA) and ascertain osteoporosis/osteopenia frequency in patients with β-thalassemia major. Methodology:In this cross-sectional study, 36 adolescent patients with β-thalassemia major were enrolled from June 2015 to March 2017. BMD was measured in the anteroposterior lumbar spine (L1-L4) and femoral neck by DEXA. For the biochemical estimations, blood and urine samples were obtained and analyzed. The results of a bone density test were presented as T and Z scores. Results:There were 20 male and 16 female patients with a mean age of 21.33 ± 3.7 years. The mean bone mineral content (BMC) was 20.10 ± 6.0 gm, and the mean BMD was0.65 ± 0.07 gm/cm2. The mean T score was -3.17 ± 1.04, and the Z score was -3.06 ± 1.06. All patients had low BMD, as depicted by their T or Z scores. The reported frequency of osteoporosis and osteopenia was 77.7% and 22.2%, respectively. Conclusion:All Beta-thalassemia major patients had low BMD with a remarkable incidence of osteoporosis. It is recommended to perform an annual BMD among thalassemic patients to prevent fatal consequences and achieve an optimal bone density among such patients.

Ficus deltoidea Jack (Moraceae) is a well-known medicinal plant used in customary medication among the Malay people to reduce and mend sicknesses such as ulcers, psoriasis, cytotoxicity, cardioprotective, inflammation, jaundice, vitiligo, hemorrhage, diabetes, convulsion, hepatitis, dysentery injuries, wounds, and stiffness. Ficus deltoidea contains a wide variety of bioactive compounds from different phytochemical groups such as alkaloids, phenols, flavonoids, saponins, sterols, terpenes, carbohydrates, and proteins. The genus Ficus has several hundreds of species, which shows excellent therapeutic effects and a wide variety of helpful properties for human welfare. Searching information was collected by using electronic databases including Web of Science, Science Direct, Springer, SciFinder, PubMed, Scopus, Medline, Embase, and Google Scholar. This review is, therefore, an effort to give a detailed survey of the literature on its pharmacognosy, phytochemistry, phytochemical, and pharmacological properties of Ficus and its important species. This summary could be beneficial for future research aiming to exploit the therapeutic potential of Ficus and its useful medicinal species.

The COVID-19 pandemic is rapidly spreading, and health care systems are being overwhelmed with the huge number of cases, with a good number of cases requiring intensive care. It has become imperative to develop safe and effective treatment strategies to improve survival. In this regard, understanding the pathogenesis of COVID-19 is highly important. Many hypotheses have been proposed, including the ACE/angiotensin-II/angiotensin receptor 1 pathway, the complement pathway, and the angiotensin-converting enzyme 2/mitochondrial assembly receptor (ACE2/MasR) pathway. SARS-CoV-2 binds to the ACE2 on the cell surface, downregulating the ACE2, and thus impairs the inactivation of bradykinin and des-Arg9-bradykinin. Bradykinin, a linear nonapeptide, is extensively distributed in plasma and different tissues. Kininogens in plasma and tissue are the main sources of the two vasoactive peptides called bradykinin and kallidin. However, the role of the dysregulated bradykinin pathway is less explored in the pathogenesis of COVID-19. Understanding the pathogenesis of COVID-19 is crucial for the development of new effective treatment approaches which interfere with these pathways. In this review, we have tried to explore the interaction between SARS-CoV-2, ACE2, bradykinin, and its metabolite des-Arg9-bradykinin in the pathogenesis of COVID-19.

Abstract Background Medically unexplained oropharyngeal dysphagia (MUNOD) is a rare condition. It presents without demonstrable abnormalities in the anatomy of the upper aero-digestive tract or swallowing physiology. The aim of this case report is to discuss the unique presentation of OCD as chronic dysphagia. Case presentation A 65-year-old woman was admitted with dysphagia and weight loss in surgical department with history of undergoing repeated upper GI endoscopies and laryngoscopies. The patient was finally diagnosed to be suffering from chronic obsessive-compulsive disorder with poor insight and comorbid depression after 3 years of suffering and moving from hospital to hospital. The atypical presentation and poor insight were the major reasons for diagnostic difficulty in this particular case. The patient was given 60 mg fluoxetine and 2 mg risperidone which improved the patient’s symptoms by 40%. Conclusion This case explains the possibility of obsessive-compulsive disorder in patients presenting with unexplained somatic symptoms. It also demonstrated the importance of a timely psychiatric diagnosis and treatment and highlights the importance about awareness of psychiatric illness in doctor community which can reduce patient suffering and unnecessary invasive procedures.

Abstract Background Many international studies have reported a high prevalence of psychiatric comorbidity in alcohol-dependent individuals and highlighted the clinical, prognostic, and treatment implications of such findings. However, there is a paucity of such information within the context of India. This study investigates the prevalence of psychiatric comorbidity in treatment-seeking alcohol-dependent individuals and its relationship with the severity of this dependence. Result This was a prevalence study conducted for a period of 1 year. Patients were identified from Mahbubnagar, a local area in rural south India, and recruited at outpatient deaddiction clinic of SVS hosital. Application for research ethics approval was approved. A consecutive sample of 100 inpatients diagnosed with alcohol dependence syndrome was recruited. The Mini-International Neuropsychiatric Interview was used to assess psychiatric comorbidity 2 weeks after detoxification. The severity of dependence was judged using the Severity of Alcohol Dependence questionnaire. One-hundred (male, n = 65; female, n = 35) alcohol-dependent patients were recruited. The mean age of participants was 41.9 (SD = 9.3) years. Participants (n = 33, 33%) had a co-occurring psychiatric disorder, the commonest being mood disorder (n = 18), which sub-divided into major depressive disorder (n = 8), dysthymia (n = 5), manic episode (n = 3), and hypomanic episode (n = 2), followed by anxiety disorders (n = 11) and then psychotic disorder (n = 4). The comorbid psychiatric disorders were significantly associated with the severity of dependence (p = 0.001) and longer duration of alcohol (p = 0.003) use. Conclusion This result emphasizes the need to thoroughly assess patients for possible under-identified dual diagnosis and provide treatments accordingly.

To find out effective anticancer compounds we synthesized (1–30) derivatives of 4-isopropylbenzoylhydrazone and evaluated for anticancer potential. The compounds 3, 9, 12, 23, 26 and 28 showed better activities ranging (0.39–1.1 µg/ml) than the standard (1.53 ± 0.01 µg/ml). In line with this, compounds 2, 6, 24, 25 and 29 exhibited better activities compared to the second standard (5FU 4.60 ± 0.01 µg/ml). The best molecular docked complex between the BRCA1 structure and the 1–30 derivatives were analyzed based on the Glide docked score and binding orientation for both the SP and XP mode. The 2D-QSAR analysis reflected a significant correlation between the experimental and the predicted biological activities. The above-mentioned compounds were also assessed by various spectroscopic techniques. Keywords: 4-Isopropylbenzohydrazones, Anticancer, Molecular docking, QSAR studies, Synthesis

Calotropis procera (family Apocynaceae) is a valuable medicinal plant as it contains many valuable phytochemicals such as glycosides (mostly cardenolides), flavonoids, triterpenes, alkaloids, steroids, saponins, proteins and enzymes. Multiparous biological activities such as anti-inflammatory, antioxidant, anticancer, wound healing and wideranging antimicrobial activities of C. procera have been well investigated and reported. The main aim of this review was to present the encompassing information regarding antimicrobial activities of C. procera latex, different crude extracts and some isolated compounds which have been tested for antimicrobial property. Comprehensive data extracted from earlier as well as recently published original articles regarding antibacterial, antifungal, anti-protozoal and antiviral properties of C. procera were discussed and summarised in tabular forms. The compiled data comprised of plant parts, geographical origin, type of tested extracts/fractions, test model, used doses, tested microorganisms, obtained results and relevant references. In addition, the isolated antimicrobial pure compounds of C. procera are also discussed in a separate section. The analysis and information presented in this review identified the existing critical knowledge gaps in the research and also explored the future perspectives and further research opportunities of C. procera.

Diabetes mellitus (DM), a complicated metabolic disorder, is due to insensitivity to insulin function or reduction in insulin secretion, which results in postprandial hyperglycemia. α-Glucosidase inhibitors (AGIs) and α-amylase inhibitors (AAIs) block the function of digestive enzymes, which delays the carbohydrate hydrolysis process and ultimately helps to control the postprandial hyperglycemia. Diversified 2-(3-(3-methoxybenzoyl)-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl)-N-arylacetamides were synthesized and evaluated for their in vitro inhibitory potential against α-glucosidase and α-amylase enzymes. The compounds with chloro, bromo and methyl substituents demonstrated good inhibition of α-glucosidase enzymes having IC50 values in the range of 25.88–46.25 μM, which are less than the standard drug, acarbose (IC50 = 58.8 μM). Similarly, some derivatives having chloro, bromo and nitro substituents were observed potent inhibitors of α-amylase enzyme, with IC50 values of 7.52 to 15.06 μM, lower than acarbose (IC50 = 17.0 μM). In addition, the most potent compound, N-(4-bromophenyl)-2-(4-hydroxy-3-(3-methoxybenzoyl)-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl)acetamide (12i), was found to be a non-competitive and competitive inhibitor of α-glucosidase and α-amylase enzymes, respectively, during kinetic studies. The molecular docking studies provided the binding modes of active compounds and the molecular dynamics simulation studies of compound 12i in complex with α-amylase also showed that the compound is binding in a fashion similar to that predicted by molecular docking studies.

Orthosiphon stamineus Benth. (Lamiaceae) is a valued medicinal plant in traditional folk medicine. Many pharmacological studies have demonstrated the ability of this plant to exhibit antimicrobial, antioxidant, hepatoprotection, antigenotoxic, antiplasmodial, cytotoxic, cardioactive, antidiabetic, anti-inflammatory activies. This review is a comprehensive summary of the presently available chemical, pharmacological investigations as well as the traditional and therapeutic uses of this plant. Important and different experimental data have been addressed along with a review of all phytochemicals identified in this plant, including flavonoids, terpenoids, and essential oils. O. stamineus has wide traditional and pharmacological uses in various pathophysiological conditions. Therefore, it is an attractive subject for further experimental and clinical investigations.

Objective: The aim of this study was to evaluate the frequency of iron deficiency anemia among the blood donors. Methods: A prospective, single center cross-sectional study was conducted in the Department of Blood Transfusion Services, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad, Pakistan, from February 2017 to June 2017. A total of 528 blood donors who donated blood without prior screening for hemoglobin levels were enrolled for this study. Blood samples were tested for six hematological and five biochemical parameters including hemoglobin level, red cell count, packed cell volume, mean cell volume, mean cell hemoglobin, mean cell hemoglobin concentration, serum ferritin, iron, total iron binding capacity, transferrin saturation, and unsaturated iron binding capacity. Results: Of 528 blood donors, 251 (47.53%) were first-time donors, 203 (38.44%) had donated twice previously but not in the past 12 months, and 74 (14.01%) were regular donors with minimum three donations per year. All of the donors were males with a mean age of 29.2 years (range = 18–56 years). Of these, the regular donors showed the reduction in mean values of the parameters studied. Conclusion: The blood bank management needs to review the donor selection criteria for donation. Regular voluntary donors should be given an iron supplement to prevent the depletion of iron stores.

Vitamin D is a neurosteroid hormone that regulates neurotransmitters and neurotrophins. It has anti-inflammatory, antioxidant, and neuroprotective properties. It increases neurotrophic factors such as nerve growth factor which further promotes brain health. Moreover, it is also helpful in the prevention of amyloid accumulation and promotes amyloid clearance. Emerging evidence suggests its role in the reduction of Alzheimer’s disease hallmarks such as amyloid-beta and phosphorylated tau. Many preclinical studies have supported the hypothesis that vitamin D leads to attentional, behavioral problems and cognitive impairment. Cross-sectional studies have consistently found that vitamin D levels are significantly low in individuals with Alzheimer’s disease and cognitive impairment compared to healthy adults. Longitudinal studies and meta-analysis have also exhibited an association of low vitamin D with cognitive impairment and Alzheimer’s disease. Despite such evidence, the causal association cannot be sufficiently answered. In contrast to observational studies, findings from interventional studies have produced mixed results on the role of vitamin D supplementation in the prevention and treatment of cognitive impairment and dementia. The biggest issue of the existing RCTs is their small sample size, lack of consensus over the dose, and age of initiation of vitamin D supplements to prevent cognitive impairment. Therefore, there is a need for large double-blind randomized control trials to assess the benefits of vitamin D supplementation in the prevention and treatment of cognitive impairment.

α-Glucosidase inhibitors (AGIs) are used as medicines for the treatment of diabetes mellitus. The α-Glucosidase enzyme is present in the small intestine and is responsible for the breakdown of carbohydrates into sugars. The process results in an increase in blood sugar levels. AGIs slow down the digestion of carbohydrates that is helpful in controlling the sugar levels in the blood after meals. Among heterocyclic compounds, benzimidazole moiety is recognized as a potent bioactive scaffold for its wide range of biologically active derivatives. The aim of this study is to explore the α-glucosidase inhibition ability of benzimidazolium salts. In this study, two novel series of benzimidazolium salts, i.e., 1-benzyl-3-{2-(substituted) amino-2-oxoethyl}-1H-benzo[d]imidazol-3-ium bromide 9a–m and 1-benzyl-3-{2-substituted) amino-2-oxoethyl}-2-methyl-1H-benzo[d] imidazol-3-ium bromide 10a–m were screened for their in vitro α-glucosidase inhibitory potential. These compounds were synthesized through a multistep procedure and were characterized by 1H-NMR, 13C-NMR, and EI-MS techniques. Compound 10d was identified as the potent α-glucosidase inhibitor among the series with an IC50 value of 14 ± 0.013 μM, which is 4-fold higher than the standard drug, acarbose. In addition, compounds 10a, 10e, 10h, 10g, 10k, 10l, and 10m also exhibited pronounced potential for α-glucosidase inhibition with IC50 value ranging from 15 ± 0.037 to 32.27 ± 0.050 µM when compared with the reference drug acarbose (IC50 = 58.8 ± 0.12 μM). A molecular docking study was performed to rationalize the binding interactions of potent inhibitors with the active site of the α-glucosidase enzyme.

Diabetes mellitus (DM) is a chronic disorder and has affected a large number of people worldwide. Insufficient insulin production causes an increase in blood glucose level that results in DM. To lower the blood glucose level, various drugs are employed that block the activity of the α-glucosidase enzyme, which is considered responsible for the breakdown of polysaccharides into monosaccharides leading to an increase in the intestinal blood glucose level. We have synthesized novel 2-(3-(benzoyl/4-bromobenzoyl)-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl)-N-arylacetamides and have screened them for their in silico and in vitro α-glucosidase inhibition activity. The derivatives 11c, 12a, 12d, 12e, and 12g emerged as potent inhibitors of the α-glucosidase enzyme. These compounds exhibited good docking scores and excellent binding interactions with the selected residues (Asp203, Asp542, Asp327, His600, Arg526) during in silico screening. Similarly, these compounds also showed good in vitro α-glucosidase inhibitions with IC50 values of 30.65, 18.25, 20.76, 35.14, and 24.24 μM, respectively, which were better than the standard drug, acarbose (IC50 = 58.8 μM). Furthermore, a good agreement was observed between in silico and in vitro modes of study.

Introduction: The significance of appropriate completion of blood request forms (BRFs) is frequently underrated by the clinicians which results in wastage and increased risk of inappropriate therapy. The judicious use of blood components can be assessed by the crossmatch-to-transfusion ratio (C:T), transfusion probability (%T), and transfusion index (TI). The current study assessed the standard of completion of BRFs and blood components utilization at a Tertiary Care Hospital Blood Bank. Materials and Methods: This was a cross-sectional, prospective study conducted at the Department of Blood Transfusion Services, Shaheed Zulfiqar Ali Bhutto Medical University Hospital, Islamabad, from January to April 2016. A total of 5957 BRFs received between January and April 2016 were reviewed. The data were entered in SPSS version 20.0 (IBM SPSS Statistics for Windows, IBM Corp., Armonk, NY, USA) and analyzed for completeness, legibility, and blood component utilization through calculation of key indicators including C:T ratio, transfusion probability (%T), and TI. Results: Out of the 5957 request forms reviewed, only 12.7% forms were completed in full. The overall C:T ratio, %T, and TI were 1.52, 65.38, and 0.65, respectively. The same indicators for the Maternal and Child Health Centre (MCHC) were 10.7, 9.32, and 0.09. Conclusion: Incomplete blood transfusion request forms create difficulties for the blood bank staff in comprehending the requests which may compromise patient safety. Similarly, the efficiency of MCHC blood transfusion services is far from optimum. The Hospital Transfusion Committee can play a key role in solving this problem and thus improving the standards of Patient Blood Management.

Background: Donor deferral owing to anemia is one of the major causative factors of temporary donor rejection, which is preventable and treatable. The basic knowledge about frequency, types, and severity of anemia among donors will help plan a strategy to promote donor recruitment and overall national health. Objective: The objective of this study was to provide the predonation deferral rate of the healthy blood donors based on peripheral blood counts and second to determine the types of anemia along with its severity. Materials and Methods: Prospective records of all the reported donors were collected from January 2014 to December 2015 at Liaquat National Hospital, Karachi, Pakistan. Donor samples were analyzed on an automated hematology analyzer. Results: Overall, 36,954 potential donors reported to the blood bank, out of which 33,853 were selected and 3101 were deferred, which makes the deferral rate of 8.39%. Majority of donors (n = 2663 [7.20%]) were deferred based on peripheral blood counts. Based on peripheral count, anemia (91.8%) represents the major cause of deferral, followed by raised total leukocyte count (3.7%) and polycythemia (3.3%), and thrombocytopenia (1.0%) was the least potential cause. Microcytic-hypochromic anemia was found in 58.5% of the donors followed by normocytic and macrocytic anemia in 38.9% and 2.4%, respectively. Mild anemia was seen in 78.2% followed by moderate and severe anemia in 20.5% and 1.18%, respectively. Conclusion: A high prevalence of anemia among blood donors signifies deteriorating health status not only in donor population but also in general population. This situation calls for more concerted efforts as otherwise it would lead to decreased blood donor pool.

Introduction. Complex partial seizures are focal (CPS) (i.e., start in one area of the brain) and associated with impairment in consciousness. Most of them arise in the temporal region and are characterized by aura, impaired consciousness, and automatisms. CPS that arise in temporal region are most often misdiagnosed as primary psychiatric illness. Case Report. A 25-year-old male presented with fluctuations in consciousness, aggressive behaviour, hallucination, and delusions of grandeur lasting a few hours. He was diagnosed with acute and transient psychotic disorder according to ICD10 criteria and was treated with intramuscular haloperidol 10mg BID followed by oral olanzapine 10mg. Computed tomography of brain and electroencephalogram were normal. After 15 days he presented again to the outpatient department with complaints of aggressive behaviour and sensory misinterpretations. Video electroencephalogram was recommended, which was not done due to financial constraints. The diagnosis was reconsidered and he was started on oral carbamazepine due to high clinical suspicion, of complex partial seizures, in spite of lack of EEG evidence. He responded well to antiepileptic and symptom remission has maintained well. Conclusion. Patients presenting with psychosis need careful diagnostic evaluation for other possibilities.

Objectives: Fragmented blood transfusion services along with an unmotivated blood donation culture often leads to blood shortage. Donor retention is crucial to meet the increasing blood demand, and adverse donor reactions have a negative impact on donor return. The aim of this study was to estimate adverse donor reactions and identify any demographic association. Methods: We conducted a prospective study between January 2011 and December 2013. A total of 41,759 healthy donors were enrolled. Professionally trained donor attendants drew blood and all donors were observed during and following donation for possible adverse events for 20 minutes. Blood donors were asked to report if they suffered from any delayed adverse consequences. Results: Out of 41,759 blood donors, 537 (1.3%) experienced adverse reactions. The incidence was one in every 78 donations. The mean age of donors who experienced adverse events was 26.0±6.8 years, and all were male. Out of 537 donors, 429 (80%) developed vasovagal reaction (VVR), 133 (25%) had nausea, 63 (12%) fainted, 35 (6%) developed hyperventilation, 9 (2%) had delayed syncope, and 9 (2%) developed hematoma. Arterial prick, nerve injury, cardiac arrest, and seizures were not observed. Donors aged less than < 30 years and weighing < 70 kg were significantly associated with VVR, hyperventilation, and nausea (p < 0.005). Undergraduates and Urdu speaking donors also had a significant association with fainting and nausea, respectively (p < 0.05). Conclusion: The prevalence of adverse events was low at our tertiary center. A VVR was the predominant adverse reaction and was associated with age and weight. Our study highlights the importance of these parameters in the donation process. A well-trained and experienced phlebotomist and pre-evaluation counseling of blood donors could further minimize the adverse reactions.

Leukopenia secondary to leukocytic agglutination is caused by an ethylene diamine tetra acetic acid (EDTA) which may appear in both benign and malignant states. Ethylene diamine tetra acetic acid induced platelets clumping in peripheral blood has been well established, but invitro leukocytic aggregation is very rarest hematological finding. Pseudo-leukopenia resulting from leukoagglutinins has been reported in the cirrhotic state, infections, autoimmune disorders, uremia, in immunosuppressed state or in various malignancies. Though the condition seems to be benign but very important to be detected as these artifactual findings lead to unnecessary investigations and remarkably changed the overall management plan. Here we report the case of a young patient with this rare finding who was admitted to our hospital with progressive labor pains. The analysis of ethylene diaminetetraacetic acid (EDTA), anticoagulated blood was done on automated hematology analyzer reveals leukopenia. The peripheral smear examination revealed multiple aggregates of leukocytes. On repeat sampling in citrate anticoagulant, the complete blood count showed total leukocytic count of 16.5x109/L with absolute neutrophilic count of 11.5x109/L. This is a rare case of spurious leukopenia secondary to in-vitro leukocytic agglutination provoked by EDTA anticoagulant.

The anti-inflammatory drug predinisolone (1) was reduced to 20β-hydroxyprednisolone (2) by the marine endophytic fungus Penicilium lapidosum isolated from an alga. The structural elucidation of 2 was achieved by 1D- and 2D-NMR, MS, IR data. Although, 2 is a known compound previously obtained through microbial transformation, the data provided failed to prove the C20 stereochemistry. To solve this issue, DFT and TD-DFT calculations have been carried out at the B3LYP/6–31+G (d,p) level of theory in gas and solvent phase. The absolute configuration of C20 was eventually assigned by combining experimental and calculated electronic circular dichroism spectra and 3JHH chemical coupling constants.

Objective: Many studies have reported an association between chronic immune thrombocytopenia and Helicobactor pylori infection. Significant improvement in platelet count is seen after eradication therapy. We looked for the frequency of H. pylori infection in immune thrombocytopenia and clinico-hematological features. Material and Method: A prospective case-control study was conducted from January 2009 to December 2011. One hundred and ten chronic immune thrombocytopenic patients and 40 control subjects were enrolled. H. pylori infection was documented by H. pylori stool antigen enzyme immunoassay method. Results: H. pylori infection in immune thrombocytopenic patients was seen in 45 cases (40.9%) and in 24 (60%) controls; not significant statistically. No significant differences were seen in H. pylori positive and negative patients with respect to maternal characteristics and clinical features except for mean platelet count, which was lower in H. pylori negative group (P = 0.035). Conclusion: Unlike many related studies, we found no significant difference between the frequencies of cases versus controls. Degree of thrombocytopenia appears more marked in H pylori negative patients.

OBJECTIVE: To determine the prevalence of Hepatitis-B, Hepatitis-C and Human Immunodeficiency infections in replacement blood donors. METHODS: From January 2004 to December 2011, 108,598 apparently healthy donors donated blood at our Blood Bank. Screening was done by Microparticle Enzyme Immuno Assay (MEIA) method on Axsym System (Abbott Diagnostic, USA) and in year 2011 by Chemiluminescent Immunoassay (CIA) method on Architect i2000 (Abbott Diagnostic, USA). From 2010 onward, HIV reactive donors were advised for confirmatory tests and reported back with the results. RESULTS: Of the 108,598 total donors, 108,393 (99.8%) were replacement donors with a mean age of 28.92 (17-55) years. Of this, only 164 (0.15%) were females. Among the replacement donors, 4,906 (4.5%) were found to be reactive for Hepatitis-B, C and Human Immunodeficiency Virus. All the reactive patients, except one, were males. HbsAg was positive in 2,068 (1.90%) and anti-HCV in 2832 (2.61%) donors, while 111 (0.10%) were positive for Human Immunodeficiency Virus. Co-infectivity was observed in 103 (0.09%) cases. The prevalence appeared to be higher in younger age group (17-30 yrs). Only 16.6% cases should be patients returned with results of the confirmatory tests for HIV and were found positive. CONCLUSION: Hepatitis-B and C sero-prevalence in our series of replacement donors appears high compared to most studies from neighboring countries and relatively low in comparison to earlier studies from Pakistan. Prevalence of HIV, however, appears low and turn out of HIV positive cases for confirmatory tests is low.

The title compound, C22H32O4, a fungal-transformed metabolite of medroxyprogesterone, comprises one cyclohexanone ring, two cyclohexane rings and one cyclopentane ring fused together. The cyclohexanone ring has a half-chair conformation, while the cyclohexane rings possess chair conformations and the cyclopentane ring has a twisted conformation on the fused C—C bond. In the crystal, molecules are linked by strong O—H...O and also C—H...O hydrogen bonds, creating a two-dimensional network parallel to (10-1).

Objectives. Skeletal complications in β-homozygous thalassemic patients are uncommon but often debilitating, even amongst children and adolescent patients with well maintained transfusion and chelation therapy. The aim is to evaluate the biochemical markers of bone turnover in regularly transfused thalassemic patients and its possible correlations with demographic data and hematological and biochemical markers. Methods. In this prospective cross-sectional study, 36 β-thalassemia major patients were enrolled from March 2012 to March 2014. All patients underwent complete blood counts, LFTs, serum ferritin, serum calcium, phosphorus, serum albumin, alkaline phosphatase, 25-OH vitamin D, and parathormone (PTH) levels. Results. There were 17 males and 19 females with mean age of 12.56 ± 5.9 years. Hypocalcemia and hypophosphatemia were seen in 66.6% and 19.4%, respectively, while 25-OH vitamin D deficiency was present in 72.2% of thalassemic children and adolescents. Hypoparathyroidism was seen in 13.8% while hyperparathyroidism was detected in 8.3% of patients. There was direct correlation between serum phosphorus and ferritin levels (P0.05). Conclusions. Biochemical profile is significantly altered in patients with β-thalassemia major and bone associated biochemical abnormalities like hypocalcaemia, 25-OH vitamin D deficiency, and hypophosphatemia are not uncommon in Pakistani patients with thalassemia major.

Pure white cell aplasia (PWCA) is an exceedingly rare hematological disease of unknown origin exemplified by agranulocytosis, virtually lack of all granulocytic spectrums (from myeloblast to neutrophils) in the bone marrow with normal erythroid and megakaryocytic lineages. It has been associated with underlying autoimmune disorders, thymomas, chronic lymphocytic leukemia and drug induced or may be idiopathic. Here we report the case of a patient with this rare finding, who was admitted to our hospital with septicemia having agranulocytosis, multiple oral candidiasis, perianal abscess and right arm cellulitis. Bone marrow examination revealed absolute absence of all myeloid precursors cells. All diagnostic workup for secondary underlying cause were found to be negative and diagnosed as idiopathic PWCA. Immunosuppression with methylprednisolone pulse therapy was failed to induce neutrophils recovery. PWCA is a benign disorder, but have serious consequences due to threatening febrile neutropenia, disseminated fungal infection and septicemia. Needs urgent management depending upon underlying etiology.

Abstract Background: Many studies have reported an association between Chronic Immune Thrombocytopenia and Helicobactor Pylori infection. Significant improvement in platelet count is seen after eradication of Helicobactor Pylori infection. Objective: We looked for the frequencies of Helicobactor Pylori infection in patients with Chronic Immune Thrombocytopenia and clinico-hematological differences in two groups. Methods: A cross sectional descriptive study was conducted from January 2009 to December 2011. 110 chronic Immune thrombocytopenic patients and 40 control subjects were enrolled. Helicobactor Pylori infection was documented by Helicobactor pylori stool antigen (HpSA) enzyme immunoassay method (EIA). Frequencies were calculated. Chi-square test was used for comparison. P-value of less than 0.05 was considered significant. Results: Helicobactor Pylori infection in Chronic Immune Thrombocytopenic patients was seen in 45 cases (40.9%) and in 24 (60%) control subjects; the difference is not significant statistically. No significant differences were seen in H-Pylori positive and negative patients with respect to maternal characteristics and clinical features except for mean platelet count which was lower in Helicobactor Pylori negative group (P=0.035). Conclusion: Unlike many related studies, we found no significant difference between the frequencies of the cases versus controls. Low mean platelet count is seen in Helicobactor Pylori negative patients.

The title compound, C12H8ClFN2OS, is a hydrazide derivative adopting an E conformation with an azomethine N=C double bond length of 1.272 (2) Å. The molecular skeleton is approximately planar; the terminal five- and six-membered rings form a dihedral angle of 5.47 (9)°. In the crystal, molecules are linked by N—H...O and C—H...O hydrogen bonds into zigzag chains propagating in [100].

The title phenylhydrazine derivative, C16H16N2O4, has a crystallographically imposed centre of symmetry. Except for the methyl group, all non-H atoms are almost coplanar (r.m.s. deviation = 0.0095 Å). Intramolecular O—H...N hydrogen bonds are observed, generating S(6) graph-set ring motifs.

Abstract This study presents a novel privacy-preserving self-supervised (SSL) framework for COVID-19 classification from lung CT scans, utilizing federated learning (FL) enhanced with Paillier homomorphic encryption (PHE) to prevent third-party attacks during training. The FL-SSL based framework employs two publicly available lung CT scan datasets which are considered as labeled and an unlabeled dataset. The unlabeled dataset is split into three subsets which are assumed to be collected from three hospitals. Training is done using the Bootstrap Your Own Latent (BYOL) contrastive learning SSL framework with a VGG19 encoder followed by attention CNN blocks (VGG19 + attention CNN). The input datasets are processed by selecting the largest lung portion of each lung CT scan using an automated selection approach and a 64 × 64 input size is utilized to reduce computational complexity. Healthcare privacy issues are addressed by collaborative training across decentralized datasets and secure aggregation with PHE, underscoring the effectiveness of this approach. Three subsets of the dataset are used to train the local BYOL model, which together optimizes the central encoder. The labeled dataset is employed to train the central encoder (updated VGG19 + attention CNN), resulting in an accuracy of 97.19%, a precision of 97.43%, and a recall of 98.18%. The reliability of the framework’s performance is demonstrated through statistical analysis and five-fold cross-validation. The efficacy of the proposed framework is further showcased by showing its performance on three distinct modality datasets: skin cancer, breast cancer, and chest X-rays. In conclusion, this study offers a promising solution for accurate diagnosis of chest X-rays, preserving privacy and overcoming the challenges of dataset scarcity and computational complexity.

Abstract This study aims to identify and analyze the barriers to Green Supply Chain Management (GSCM) in the footwear industry of Bangladesh, which is essential for improving sustainability and gaining a potential benefit in the global market. Despite the growth of Bangladesh’s footwear industry, environmental challenges and a lack of green practices have hindered its ability to meet international standards. The study employs a hybrid multi-criteria decision-making approach, combining Stepwise Weight Assessment Ratio Analysis (SWARA) and Interpretive Structural Modelling (ISM) with MICMAC (Cross-Impact Matrix Multiplication Applied to Classification) analysis. Using literature reviews and expert opinions from industry professionals, 19 barriers were initially identified, which were narrowed down to 12 for further analysis. SWARA was used to rank these barriers, while ISM-MICMAC was applied to assess the interrelationships between them. The findings reveal that the most significant barriers to GSCM implementation are insufficient training and poor supplier commitment, followed by a lack of knowledge and experience. The ISM-MICMAC analysis highlights the interdependencies among these barriers, suggesting that addressing one may impact others. This research is novel in its application of a hybrid SWARA-ISM-MICMAC approach to the footwear industry, a sector in Bangladesh that has not been extensively studied in the context of GSCM. The study provides practical implications for managers and policymakers by offering insights into the most critical barriers and their interrelations, guiding targeted interventions. By addressing these barriers, the footwear industry can enhance its sustainability practices, improve market competitiveness, and meet growing environmental demands.

Purpose: To study the treatment and outcomes of children with retinoblastoma (RB) with extraocular tumor extension (RB-EOE) and compare them with RB without extraocular tumor extension (RB-w/o-EOE). Design: Multicenter intercontinental collaborative prospective study from 2017 to 2020. RB-EOE cases included those with overt orbital tumor extension in treatment-naive patients. Cases with microscopic orbital extension detected postenucleation were excluded from the study. Participants: A total of 319 children with RB-EOE and 3116 children with RB-w/o-EOE. Intervention: Chemotherapy, enucleation, exenteration, radiotherapy. Main Outcome Measures: Systemic metastasis and death. Results: Of the 3435 RB patients included in this study, 309 (9%) were from low-income countries (LIC), 1448 (42%) from lower-middle income, 1012 (29%) from upper-middle income, and 666 (19%) patients from high-income countries. There was an inverse relationship between the percentage of RB-EOE and national income level, with 96 (31%) patients from LIC, 197 (6%) lower-middle income, 20 (2%) upper-middle income, and 6 (1%) patients from high-income countries (P = 0.0001). The outcomes were statistically significant for RB-EOE compared with RB-w/o-EOE: systemic metastasis (32% vs. 4% respectively; P = 0.0001) and metastasis-related death (63% vs. 6% respectively; P = 0.0001). Multimodal treatment was the most common form of treatment (n = 177; 54%) for RB-EOE, with most cases undergoing a combination of intravenous chemotherapy and enucleation (n = 97; 30%). Adjuvant external beam radiotherapy (EBRT) after surgery (enucleation/orbital exenteration) was given in only 68 (21%) cases. Kaplan–Meier analysis for systemic metastasis and metastasis-related death in RB-EOE was 28% and 57% at 1 year, 29% and 60% at 2 years, and 29% and 61% at 3 years, respectively. Cox regression analysis revealed that the risk of death from RB-EOE was greater in patients aged >4 years than