Protective factors of psychological vulnerability in Rescue 1122 workers with vicarious traumatization.

OBJECTIVES: This study aimed to determine the protective factors of psychological vulnerability in Rescue 1122 workers and to find out the difference in work mattering, coping, grittiness, and psychological vulnerability between rescue workers of fire service and ambulance service department with vicarious traumatization. METHOD: A cross-sectional design was used in this study. A sample of 112 male rescue workers was collected from Rescue 1122 department, including participants from the ambulance service (n = 56) and fire service (n = 56) departments through a purposive sampling technique. Rescue workers who experienced vicarious trauma were enrolled in this study after screening through the secondary traumatic stress tool. Work mattering scale, coping strategies questionnaire, short grit scale, and the four-dimensional symptom questionnaire were used. RESULTS: Age, marital status, spouse age, and father's age were significantly positively correlated with distress. Colleagues becoming a target of violence and death of a colleague during duty were significantly positively correlated with somatization. The number of children was a significant positive predictor, and members requiring financial support were a significant negative predictor of psychological vulnerability. Interpersonal mattering, active focused, and active distracting coping emerged as significant negative predictors of distress, anxiety, and depression after controlling for covariates. A significant difference was found in active distraction coping between the fire service and ambulance service departments. CONCLUSION: Rescue workers who considered that their work mattered used religious coping and distraction or adopted a practical approach toward dealing with stress, and those who were grittier were less vulnerable to psychological symptoms. So, these can be considered as protective factors of psychological vulnerability.

Abdominal distention, immunopositivity, and aggressive nature: A rare Ewing's sarcoma of the adrenal gland.

This case report describes a 32-year-old Pakistani male patient with an Ewing sarcoma (ES) of the adrenal gland. Presenting complaints were abdominal distention, pain, low-grade fever, and weight loss. Initial studies, including imaging and tumor markers, ruled out any other possible origins of the mass. A percutaneous biopsy verified the tumor's neuroendocrine origin. Extensive involvement of nearby anatomical structures was discovered through exploratory laparotomy, rendering total resection difficult. Based on the presence of malignant, round, blue cells that were positive for specific immunostaining markers, the histopathology report supported the diagnosis of an ES with a staging of T3N0M0. Chemotherapy, in accordance with the VAC-IE protocol, was administered after debulking surgery. Subsequent imaging and close monitoring revealed no metastatic or residual tumors. Adrenal ES is an uncommon, aggressive tumor that mandates prompt diagnosis and management. This case report highlights the value of early detection and multimodal therapy in enhancing patient outcomes for this rare malignancy.

Perfectionism, mattering and loneliness in young adulthood of Generation-Z.

Introduction: Young adulthood is a transitional period where adults are faced with new social and psychological roles. So, in order to matter and to form relationship with others, they become vulnerable to set exaggerated high standards for themselves and others, which can eventually lead them to experience loneliness. Objectives: The present study aimed to determine the relationship of perfectionism, mattering with loneliness in young adults of Gen-Z after controlling for covariates. It was also aimed to find out gender differences on perfectionism, mattering and loneliness in young adults. Method: Correlational research design was used. A sample of 320 students with age ranging from 18 to 24 years, was collected from seven different government and private universities of Lahore through purposive sampling. The sample comprised of 160 male students and 160 female students. Multidimensional perfectionism scale, Mattering scale and UCLA loneliness scale-3 were administered to measure perfectionism, mattering and loneliness respectively. Results: Pearson product moment correlation showed that closer relationship of young adults with father (p < .01), mother (p < .01) and friends (p < .05) had a significant negative relationship with loneliness. Results of hierarchical regression analysis showed that age was significant negative predictor of loneliness. Self-oriented, other-oriented and socially prescribed perfectionism were significant positive predictors of loneliness. Mattering was significant negative predictor of loneliness. Independent sample t-test showed no significant differences between male and female students on perfectionism, mattering and loneliness. Conclusion: Perfectionist individuals tend to set stringent standards for themselves and others as well. The more they engage in perfectionism, the more they tend to feel that they do not matter to others. Feeling of not mattering to others can possibly lead the person to experience loneliness.

Construction and validation of ShaMaq developmental screening tool.

INTRODUCTION: The diagnosis of developmental delay and early intervention ameliorates long-term sequelae. There is a need for an appropriate, regionally adapted and reliable developmental screening tool to be used in low and middle-income countries with scarce resources. AIM: The aim of this research is to construct and validate a screening tool for identifying developmental delay in Pakistani children. METHOD: ShaMaq developmental screening tool (SDST) was developed consisting of five proformas to be administered at different age groups: 6-8 weeks (Group 1), 6-10 months (Group 2), 18-24 months (Group 3), 3-3.5 years (Group 4), and 4.5-5.5 years (Group 5). On an average, Groups 1-3 took 10-15 min, whereas Groups 4 and 5 took 20-25 min. We sampled children between the ages of 6 weeks to 5.5 years and tested them all within their designated age groups. Internal consistency was assessed by Cronbach's alpha. Interobserver testing was done for reliability and concurrent validity was undertaken by using the senior consultant developmental paediatrician's final diagnosis as the gold standard. RESULTS: Out of 550 healthy children, 8-19% in the five groups were found to have some form of developmental delay using SDST. Approximately 50% of the families were in the low-to-moderate income bracket, and nearly 93% lived in a joint family system. Internal consistency of items in the five groups ranged from 0.784 to 0.940, whereas both interobserver reliability and concurrent validity ranged from 0.737 to 1.0. SDST showed 94.4% sensitivity and 92.9% specificity. CONCLUSION: SDST is an effective tool for identifying delay in healthy children with good internal consistency, reliability, and validity.

Hyperhomocysteinemia as a Cause of Acute Ischemic Stroke in a Four-Year-Old Child: A Report of a Rare Case.

Homocysteine is a type of amino acid that isn't genetically encoded by the human body. This amino acid is capable of causing oxidative damage to the endothelial cells, leading to the onset of thrombosis. Moreover, it can also inflict harm to neurons by activating pro-apoptotic factors, causing DNA damage, and inducing oxidative stress, as observed in various animal models and cell cultures. This case report highlights a four-year-old girl who exhibited signs of an ischemic stroke. The neurological examination revealed several symptoms, including anisocoria, decreased tone, decreased power, absent reflexes on the right upper and lower extremity, and hyper extensor plantar response, accompanied by upper motor neuron seventh cranial nerve palsy. An MRI scan further confirmed the presence of an ischemic stroke in the left middle cerebral artery territory. After a thorough evaluation, the probable cause of this condition was identified as severe homocysteine elevation.

Post-surgical Outcomes of Different Surgical Techniques in Hirschsprung's Disease: A Literature Review.

Hirschsprung's disease (HD) is a rare condition that affects newborns and is characterized by the lack of ganglion cells in the colon. Typical symptoms include difficulty passing stool, vomiting, and trouble feeding. Various surgical methods are available to manage the condition. The aim of the study is to investigate and compare the post-surgical outcomes of different surgical techniques used in the treatment of HD. A thorough literature search was conducted using various electronic databases to identify relevant studies to be referred to. Double-blinded screening of the identified articles led to the final selection of 40 out of 440 HD, including transanal endorectal pull-through (TERPT), laparoscopic approaches, and modified techniques. Several studies have investigated surgical procedures for HD, including TERPT, laparoscopic methods, and modified techniques. These have shown positive outcomes, with fewer complications, improved bowel function, and favorable cosmetic results. Individual patient characteristics and surgeon expertise should guide procedure selection. Surgery for HD aims to restore normal bowel function, but post-surgical outcomes can include constipation or fecal incontinence. Complications like enterocolitis, anastomotic stricture, and sphincter damage may occur. Laparoscopic approaches have shorter hospital stays. However long-term follow-up is essential to assess quality of life, psychological well-being, and potential side effects.

Experimental and in silico evaluation of Carthamus tinctorius L. oil emulgel: a promising treatment for bacterial skin infections.

Purpose: The current study aimed to develop a topical herbal emulgel containing Carthamus tinctorius L. (CT) oil extract, which has been scientifically proven for its antibacterial and antioxidant activities for the ailment of bacterial skin infections. Method: The CT emulgel was formulated by response surface methodology (RSM) and was evaluated by various parameters like extrudability, spreadability, pH, viscosity, and antibacterial and antioxidant activities. Molecular docking was also performed using AutoDock. Results: Among all formulated CT emulgels, F9 and F8 were optimized. Optimized formulations had shown good spreadability and extrudability characteristics. Sample F8 had % inhibition of 42.131 ± 0.335, 56.720 ± 0.222, and 72.440 ± 0.335 at different concentrations. Sample F9 had % inhibition of 26.312 ± 0.280, 32.461 ± 0.328, and 42.762 ± 0.398 at concentrations of 250 µg/ml, 500 µg/ml, and 1,000 µg/ml, respectively, which shows that both samples F8 and F9 have significant antioxidant potential. Optimized CT emulgels F8 and F9 had significant antibacterial activity against Staphylococcus aureus and Escherichia coli at p-value = 0.00, the Emulgel-F8 shows zone of inhibition of 24 mm for E-coli and 19 mm for S-aureus. Emulgel-F9 shows zone of inhibition of 22 mm for E-coli and 15 mm for S-aureus while pure CT- Oil extract shows zone of inhibition of 25 mm for E-coli and 20 mm for S-aureus and ciprofloxacin used as standard shows 36mm zone of inhibition against both E-coli and S-aureus. The comparative investigation through molecular docking binding affinities and interactions of ligands with various target proteins provides insights into the molecular processes behind ligand binding and may have significance for drug discovery and design for the current study. Conclusion: The current study suggests that C. tinctorius L.-based emulgel has good antioxidant and antibacterial activities against E. coli for the treatment of bacterial skin infections.

Ethnopharmacological basis and pharmacodynamics prospectives for folkloric claims of Rosa webbiana wall. Ex. Royle in diarrhea and asthma via In vitro, In vivo and In silico techniques.

ETHNOPHARMACOLOGICAL RELEVANCE: Rosa webbiana (Family: Rosaceae) is used by South Asian herbalists to treat gastrointestinal and respiratory disorders. AIM OF THE STUDY: This research aimed at multiple targets to verify R. webbiana for treating diarrhea and asthma. In vitro, in vivo, and in silico experiments were planned to demonstrate the antispasmodic and bronchodilator potential of R. webbiana. MATERIALS AND METHODS: The bioactive compounds of R. webbiana were identified and quantified through LC ESI-MS/MS and HPLC. These compounds were predicted for muti-mechanisms of bronchodilator and antispasmodic potential in network pharmacology and molecular docking. In vitro methods (isolated rabbit trachea, bladder, and jejunum tissues) confirmed these multi-mechanisms for antispasmodic and bronchodilator effects. Antiperistalsis, antidiarrheal, and antisecretory experiments were conducted in in-vivo experiments. RESULTS: The phytochemical analysis indicates the presence of rutin (742.91 µg/g), kaempferol (726.32 µg/g), and quercitrin (688.20 µg/g) in Rw. EtOH. These bioactive compounds in network pharmacology interfere with the pathogenic genes of diarrhea and asthma, which are the members of calcium-mediated signaling pathways and showed the stronger binding affinity towards voltage-gated L-type calcium channels, myosin light chain-kinase, Calcium calmodulin-dependent-kinase, Phosphodiesterase-4, and phosphoinositide phospholipase-C in molecular docking. Rw. EtOH elicited a spasmolytic response in isolated jejunum, trachea, and urine preparations by relaxing K+ (80 mM) and CCh (1 µM) spastic contractions. Additionally, it suppressed calcium concentration-response curves to the right, like verapamil. Like dicyclomine, it caused a rightward parallel shift of the CCh curves, followed by a non-parallel shift at higher concentrations with suppression of the maximal response. Like papaverine, it also caused isoprenaline-induced inhibitory CRCs to shift to the left. Verapamil did not potentiate isoprenaline-induced inhibitory CRCs, although it was more efficacious against K+ (80 mM) than CCh (1 µM)-induced contractions. R. webbiana EtOH extract exhibited complete antiperistalsis (21.55%), antidiarrheal (80.33%), and antisecretory (82.59±0.60) activities in vivo experiments at the dose of 300 mg/kg. CONCLUSION: Thus, Rw. EtOH modulated multiple pathways, produced calcium antagonistic, anticholinergic, and phosphodiesterase inhibitory actions, and had antidiarrheal and bronchodilator effects.

A Case of Extraskeletal Ewing Sarcoma Treated With Wide Local Excision With Latissimus Dorsi Flap and Systemic Therapy.

Extraskeletal Ewing sarcoma (EES) is a rare tumor of the soft tissue that looks the same as skeletal Ewing sarcoma (ES). A male in his 50s was diagnosed with extraskeletal Ewing sarcoma (EES) of the right shoulder, which had infiltrated the muscles around the shoulder joints. Although uncommon, all members of the ES family of tumors, including EES, were treated following the same general protocol for sarcoma tumors. Due to the significant tumor size in this patient and local invasion, wide local excision and a latissimus dorsi flap were required. This case highlighted the management of EES, including the surgical removal of the mass on the right shoulder, followed by chemotherapy, which led to a successful outcome.

Effects of visual aid on state anxiety, fear and stress level in patients undergoing endoscopy: a randomized controlled trial.

OBJECTIVES: The present study aimed to calculate the estimated size and confidence interval for the effects of adding visual aid to counselling on anxiety, stress and fear of patients undergoing upper gastrointestinal endoscopy. The secondary aim was to calculate confidence interval for endoscopy-related variables that predict which patients are likely to benefit from visual aids. METHOD: In a randomized, single-blind, two arm, parallel group, superiority trial, 232 consecutive patients who were scheduled to undergo either gastroscopy or colonoscopy were randomly divided into two intervention groups; counselling with video of endoscopic procedure and counselling with no-video (n = 116 in each group). Primary outcome was anxiety and secondary outcomes were stress and fear. RESULTS: One-way ANCOVA showed that there was significant between group differences of anxiety, stress and fear after controlling for the effect of covariates. Planned contrasts revealed that counselling along with visual aid of endoscopy procedure significantly decreased anxiety [Mean difference at post; -4.26 (-4.47, -4.05), p < .001, partial η2 = 0.88], stress [-5.35 (-5.63, -5.07), p < .001, partial η2 = 0.86] and fear [-2.82 (-2.97, -2.67), p < .001, partial η2 = 0.86] compared to counselling alone. Linear regression showed that gender, nature of complaints and concern over seniority of endoscopist were significant negative predictors, however, satisfaction on briefing of endoscopy procedure was significant positive predictor of outcome variables in visual aid condition. CONCLUSION: The increase in anxiety, acute stress and fear related to endoscopic procedures can be alleviated with psychological counselling coupled with visual aids before the procedure. Visual aid could lead to supplementary benefits in reducing anxiety scores. TRIAL REGISTRATION: ClinicalTrial.gov Number: NCT05241158. Registered 16/11/2022; https://clinicaltrials.gov/ct2/show/NCT05241158KEY MESSAGESCounselling along with visual aid of endoscopy procedure significantly decreased anxiety, stress and fear as compared to counselling alone.Male patients were less stressed after visual aid intervention as compared to female patients. Patients who had chronic GI symptoms were less stressed after visual aid intervention as compared to those who had acute GI symptoms. Patients who had concern over seniority of endoscopist were less stressed after visual aid intervention as compared to those who had no concerns over seniority.Satisfaction on briefing of endoscopy procedure was significant positive predictor of stress and fear.

Preventive practices and parents' psychological health of children with disabilities after COVID-19 lockdown in Pakistan.

AIM: To find out differences in mental health outcomes between parents of children with different disabilities due to COVID-19 by determining the relationship between preventive practices, fear and stress in parents of disabled children. METHODS: A sample of 213 parents, whose children with disabilities (age range 1-16 years) were previously on regular follow-up before pandemic but did not take therapy for 1 year or more during COVID-19 lockdown and resumed sessions after a gap period, was surveyed. Perceived stress scale, fear and adherence to preventive measures questionnaire (developed by researchers) were used to measure stress, fear response of parents due to COVID-19 and preventive measures practiced by disabled children respectively. RESULTS: Parents who had financial difficulties and believed their disabled children had more chance of getting COVID-19 were more stressed. Parents who received any help from community/government were less stressed. One-way analysis of variance showed parents of cerebral palsy (CP) children reported more stress of COVID-19 as compared to parents of autism spectrum disorder (ASD), global developmental delay (GDD) and intellectual disability (ID). Parents of ID children reported more stress than ASD. Parents of CP children had more fear of loss of family members or getting infected with COVID-19 than GDD parents. ASD, GDD and CP children adhered more to preventive measures than ID children; however, CP children adhered more to preventive measures than GDD children. CONCLUSION: COVID-19 lockdown has persisting impact on mental health of parents of disabled children. Those parents experienced increased levels of stress and fear but reported adherence to preventive measures depending on the child's disability.

Mechanistic insights of Cucumis melo L. seeds for gastrointestinal muscle spasms through calcium signaling pathway-related gene regulation networks in WGCNA and in vitro, in vivo studies.

BACKGROUND: In addition to the nutritional benefits of Cucumis melo L., herbalists in Pakistan and India employ seeds to treat various ailments. This study aimed to determine the regulatory role of C. melo seeds in calcium-mediated smooth muscle contraction. METHODS: We identified and quantified the phytochemicals of C. melo with LC ESI-MS/MS and HPLC, then conducted in vitro and in vivo tests to confirm the involvement in smooth muscle relaxation. Then, diarrhea-predominant irritable bowel syndrome gene datasets from NCBI GEO were acquired, DEGs and WGCNA followed by functional enrichment analysis. Next, molecular docking of key genes was performed. RESULTS: The quantification of C. melo seeds revealed concentrations of rutin, kaempferol, and quercetin were 702.38 µg/g, 686.29 µg/g, and 658.41 µg/g, respectively. In vitro experiments revealed that C. melo seeds had a dose-dependent relaxant effect for potassium chloride (80 mM)-induced spastic contraction and exhibited calcium antagonistic response in calcium dose-response curves. In in vivo studies, Cm.EtOH exhibited antidiarrheal, antiperistaltic, and antisecretory effects. The functional enrichment of WGCNA and DEGs IBS-associated pathogenic genes, including those involved in calcium-mediated signaling, MAPK cascade, and inflammatory responses. MAPK1 and PIK3CG were identified as key genes with greater binding affinity with rutin, quercitrin, and kaempferol in molecular docking. CONCLUSIONS: The bronchodilator and antidiarrheal effects of C. melo were produced by altering the regulatory genes of calcium-mediated smooth contraction.

Cardioprotective and hypotensive mechanistic insights of hydroethanolic extract of Cucumis melo L. kernels in isoprenaline-induced cardiotoxicity based on metabolomics and in silico electrophysiological models.

Background: Cardiovascular diseases (CVD) continue to threaten health worldwide, and account for a significant portion of deaths and illnesses. In both developing and industrialized nations, they challenge their health systems. There are several traditional uses of Cucurbitaceae seeds in Pakistan, India, Iran, and China, including treating cardiovascular, neurological, and urogenital diseases. Methods: In the present work, integrated techniques of metabolomics profiling and computational cardiomyocyte stimulation were used to investigate possible mechanisms of C. melo in isoprenaline (ISO)-induced myocardial infarction. In vitro, vasoconstrictions, paired atria, and in vivo invasive blood pressure measurement models were performed to explore the mechanism of action of C. melo hydroethanolic seed extract (Cm-EtOH). Results: Results showed that Cm-EtOH demonstrates NO-based endothelium-derived relaxing factor (EDRF) vasorelaxant response, negative chronotropic and inotropic response in the atrium, and hypotensive effects in normotensive rats. Results also revealed that Cm-EtOH decreases cardiomyocyte hypertrophy and reverts the altered gene expressions, biochemical, and metabolites in ISO-induced myocardial infarction (MI) rats. The extract additionally reversed ISO-induced MI-induced oxidative stress, energy consumption, and amino acid metabolism. Moreover, C. melo seeds increased EDRF function, energy production, and antioxidant capacity to treat myocardial and vascular disorders. In computational cardiomyocyte simulation, gallic acid reduced action potential duration, upstroke velocity (dV/dtmax), and effective refractory period. Conclusion: This study highlights the therapeutic potential of C. melo seeds to treat cardiovascular diseases and provides mechanistic insight into its antihypertensive and cardioprotective activities.

Integrated Mechanisms of Polarity-Based Extracts of Cucumis melo L. Seed Kernels for Airway Smooth Muscle Relaxation via Key Signaling Pathways Based on WGCNA, In Vivo, and In Vitro Analyses.

The present study aimed to determine the mechanisms responsible for calcium-mediated smooth muscle contractions in C. melo seeds. The phytochemicals of C. melo were identified and quantified with the aid of Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometric (LC/ESI-MS/MS) and high-performance liquid chromatography (HPLC), and then tested in-vitro and in vivo to confirm involvement in smooth muscle relaxation. Allergic asthma gene datasets were acquired from the NCBI gene expression omnibus (GEO) and differentially expressed gene (DEG) analysis, weighted gene co-expression network analysis (WGCNA), and functional enrichment analysis were conducted. Additionally, molecular docking of key genes was carried out. Kaempferol, rutin, and quercetin are identified as phytochemical constituents of C. melo seeds. Results indicated that C. melo seeds exhibit a dose-dependent relaxant effect for potassium chloride (80 mM)- induced spastic contraction and calcium antagonistic response in calcium dose-response curves. The functional enrichment of WGCNA and DEG asthma-associated pathogenic genes showed cytokine-mediated pathways and inflammatory responses. Furthermore, CACNA1A, IL2RB, and NOS2 were identified as key genes with greater binding affinity with rutin, quercitrin, and kaempferol in molecular docking. These results show that the bronchodilator and antidiarrheal effects of C. melo were produced by altering the regulatory genes of calcium-mediated smooth muscle contraction.

A Rare Case of a Non-strangulated Bladder Pantaloon Hernia.

A pantaloon hernia occurs when an indirect and direct hernia develop at the same time. The urinary bladder is a rare component of pantaloon hernias. There is a lack of literature regarding an ipsilateral pantaloon with a herniated urinary bladder. Clinically, it has a vague presentation associated with abdominal pain and urinary retention symptoms. The best diagnostic modality is an abdominal CT scan. Surgery is the treatment of choice, rendering a good prognosis. Untreated bladder hernia may lead to strangulation and necrosis of the urinary bladder. We present a rare case of a right-sided pantaloon hernia with a bladder herniation in a 65-year-old man.

Surgical Conundrum: A Case of Giant Renal Angiomyolipoma Abutting Inferior Vena Cava With Haemorrhage.

Renal angiomyolipoma (AML) is not only uncommon but often an accidental diagnosis, as it is frequently asymptomatic and affects females disproportionately. Although they may exhibit symptoms of tuberous sclerosis complex and lymphangioleiomyomatosis, the vast majority are sporadic. Due to its vascular nature, AML is prone to bleeding, and AML that bleeds typically belongs to the tuberous sclerosis complex. AMLs are mostly benign, but they can proliferate and invade locally, necessitating a strict management strategy. We hereby delineate the manifestations of a 32-year-old man who complained of increased abdominal size and pain without any history of injury. On examination, abdominal distension was demonstrated, and a palpable mass was detected in the right hypochondrium and right lumbar area. All findings from various diagnostic methods indicated that it was a classic kind of renal AML. We are keeping track of this case because it is rare and quite uncommon in males. The case presented a challenging time for the surgeons to plan the line of treatment.

Cranioplasty for a Growing Fracture of the Skull: A Case Report.

Pediatric growing skull fractures are complications that usually occur due to delays in management. In this report, we present the case of a three-year-old girl who was brought to the outpatient department with a complaint of swelling in her scalp. The patient had a history of swelling after suffering a head injury at the age of six months. There was no history of specific neurological impairments or seizures, despite the swelling being reported to have grown gradually in size. The current case is being reported since early evaluation of pediatric patients with a head injury, regardless of any neurological shortfalls, should be thoroughly worked up to prevent any progressively growing cranial defects. The subtlety of these pediatric head injury cases tends to cause misdiagnosis, which can delay management and can cause complications, as with this patient. Extended observation, intensive supportive care, and neurosurgery are considered when dealing with these seemingly innocuous cases.

Possible Mechanisms Underlying the Antispasmodic, Bronchodilator, and Antidiarrheal Activities of Polarity-Based Extracts of Cucumis sativus L. Seeds in In Silico, In Vitro, and In Vivo Studies.

Apart from the nutritional value, Cucumis sativus L. has also been used in the traditional medicine of Iran, Pakistan, and India. Its seeds are used by herbalists to treat gastrointestinal, respiratory, and urinary problems. However, more investigations are required to explain its mechanisms for treating GI, respiratory, and urinary diseases. Accordingly, the aim of the present work was to investigate the antispasmodic, bronchodilator, and antidiarrheal activities of C. sativus seeds extracts and the underlying mechanisms of action. For this purpose, sequential extracts of C. sativus seeds were prepared in n-hexane, dichloromethane, ethanol, and water. Bioactive compounds in C. sativus seed extracts were identified and quantified by utilizing LC ESI-MS/MS and HPLC. Moreover, network pharmacology and molecular docking were employed to examine the antispasmodic and bronchodilator effects of the bioactive substances in the extracts. In vitro and in vivo experiments were also conducted to validate the mechanistic insights gained from the in silico analysis. Results indicated the presence of kaempferol with a concentration of 813.74 µg/g (highest concentration) in the seed extract of C. sativus, followed by quercetin (713.83 µg/g), narcissin (681.87 µg/g), and orientin (676.19 µg/g). In silico investigations demonstrated that the bioactive chemicals in C. sativus seeds inhibited the expression of the target genes involved in smooth muscle contraction and calcium-mediated signaling. Sequential seed extracts of C. sativus caused a dose-dependent relaxant response for spasmolytic reaction and resulted in a relaxation of K+ (80 mM) spastic contraction. In animal models, C. sativus seed extracts exhibited partial or complete antiperistalsis, antidiarrheal, and antisecretory actions. By modulating the contractile response through calcium-mediated signaling target proteins, C. sativus seeds generated bronchodilator, antispasmodic, and antidiarrheal therapeutic effects.

Health Risk Factors among Doctors, Psychologists and Nurses of Pakistan during COVID-19 Pandemic.

The present study aimed to find out differences in health risk factors of COVID-19 among doctors, nurses and psychologists by determining the relationship of cognitive appraisal, coping styles, stress and fear among health professionals. Cross-sectional research design was used. Sample comprised of 3 groups; doctors, nurses and psychologists (n = 145 in each group) working in tertiary care hospitals. Stress appraisal measure, Brief COPE inventory, Perceived stress scale and Fear contracting COVID-19 questionnaire were used to assess cognitive appraisal, coping, stress and fear respectively. Results showed that nurses had high uncontrollable, stressfulness and primary appraisal, used more avoidant emotional and problem focused coping, were more stressed and fearful as compared to doctors and psychologists. Psychologists had a high appraisal of control-self and control-others as compared to doctors and nurses and were more fearful than doctors. Doctors and psychologists used more coping of humor as compared to nurses. Moreover, primary appraisal and avoidant emotional coping positively predicted stress whereas control-self appraisal negatively predicted stress among health professionals. Uncontrollable and stressfulness appraisal positively correlated with fear. This study will direct the administrative authorities to take effective measures to improve psychological wellbeing and to deal with fear and stress of health professionals.

Drug-dependent inhibition of nucleotide hydrolysis in the heterodimeric ABC multidrug transporter PatAB from Streptococcus pneumoniae.

The bacterial heterodimeric ATP-binding cassette (ABC) multidrug exporter PatAB has a critical role in conferring antibiotic resistance in multidrug-resistant infections by Streptococcus pneumoniae. As with other heterodimeric ABC exporters, PatAB contains two transmembrane domains that form a drug translocation pathway for efflux and two nucleotide-binding domains that bind ATP, one of which is hydrolysed during transport. The structural and functional elements in heterodimeric ABC multidrug exporters that determine interactions with drugs and couple drug binding to nucleotide hydrolysis are not fully understood. Here, we used mass spectrometry techniques to determine the subunit stoichiometry in PatAB in our lactococcal expression system and investigate locations of drug binding using the fluorescent drug-mimetic azido-ethidium. Surprisingly, our analyses of azido-ethidium-labelled PatAB peptides point to ethidium binding in the PatA nucleotide-binding domain, with the azido moiety crosslinked to residue Q521 in the H-like loop of the degenerate nucleotide-binding site. Investigation into this compound and residue's role in nucleotide hydrolysis pointed to a reduction in the activity for a Q521A mutant and ethidium-dependent inhibition in both mutant and wild type. Most transported drugs did not stimulate or inhibit nucleotide hydrolysis of PatAB in detergent solution or lipidic nanodiscs. However, further examples for ethidium-like inhibition were found with propidium, novobiocin and coumermycin A1, which all inhibit nucleotide hydrolysis by a non-competitive mechanism. These data cast light on potential mechanisms by which drugs can regulate nucleotide hydrolysis by PatAB, which might involve a novel drug binding site near the nucleotide-binding domains.