Synthesis of Sugar and Nucleoside Analogs and Evaluation of Their Anticancer and Analgesic Potentials.

Chemical modification of sugars and nucleosides has a long history of producing compounds with improved selectivity and efficacy. In this study, several modified sugars (2-3) and ribonucleoside analogs (4-8) have been synthesized from α-d-glucose in a total of 21 steps. The compounds were tested for peripheral anti-nociceptive characteristics in the acetic acid-induced writhing assay in mice, where compounds 2, 7, and 8 showed a significant reduction in the number of writhes by 56%, 62%, and 63%, respectively. The compounds were also tested for their cytotoxic potential against human HeLa cell line via trypan blue dye exclusion test followed by cell counting kit-8 (CCK-8) assay. Compound 6 demonstrated significant cytotoxic activity with an IC50 value of 54 µg/mL. Molecular docking simulations revealed that compounds 2, 7, and 8 had a comparable binding affinity to cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. Additionally, the bridged nucleoside analogs 7 and 8 potently inhibited adenosine kinase enzyme as well, which indicates an alternate mechanistic pathway behind their anti-nociceptive action. Cytotoxic compound 6 demonstrated strong docking with cancer drug targets human cytidine deaminase, proto-oncogene tyrosine-protein kinase Src, human thymidine kinase 1, human thymidylate synthase, and human adenosine deaminase 2. This is the first ever reporting of the synthesis and analgesic property of compound 8 and the cytotoxic potential of compound 6.

Ibuprofen-loaded centrifugally spun microfibers for quick relief of inflammation in rats.

The conventional dosage forms (tablets, capsules) of ibuprofen have less potential in the suppression of pain and inflammation due to their slow dissolution rates and lower bioavailability. The aim of this study was to fabricate fibrous solid dispersion of ibuprofen for improved dissolution rate and quick therapeutic action. Drug-loaded microfibers were fabricated using centrifugal melt spinning (CMS) technique from the physical mixture of sucrose, ibuprofen and a hydrophilic polymer, PVP. These fibers were characterized by SEM, PXRD, DSC, and FTIR spectroscopy. The selected formulation was also pressed into tablets by direct compression method followed by its in vitro and in vivo characterization. The production yield of fibers was 75 ± 2% with an average diameter of 15 ± 5 µm. The drug loading efficiency (DLE) was 85 ± 5%. The tablets dissolved rapidly (<40 s). In vitro dissolution studies have shown >85% of ibuprofen dissolved from tablet within first 2 min which was ∼5 times quicker than drug alone. Dissolution efficiency has improved from 0.63 of ibuprofen to 0.95 of that in fibers with ∼7 times reduction in mean dissolution time. PXRD, and DSC have shown the amorphous state of ibuprofen in the formulation and FTIR spectra demonstrated no interaction of drug with excipients. In vivo anti-inflammatory studies using rabbits revealed a significant (p < 0.05) reduction in paw volume (mm) in the groups treated with fibrous formulation. This study concludes that microfibers produced by centrifugal melt spinning have improved dissolution rates and bioavailability of ibuprofen. Incorporation of polymer in the formulations improves the production yield and drug loading efficiency of microfibers.

Nanoencapsulation of betamethasone valerate using high pressure homogenization-solvent evaporation technique: optimization of formulation and process parameters for efficient dermal targeting.

Betamethsone valerate (BMV), a medium potency topical corticosteroid, is one of the most commonly employed pharmacological agents for the management of atopic dermatitis in both adults and children. Despite having remarkable pharmacological efficacy, these agents have limited clinical implication due to poor penetration across the startum cornum (SC). To mitigate issues related to targeted delivery, stability, and solubility as well as to potentiate therapeutic and clinical implication, the nanodelivery systems have gained remarkable recognition. Therefore, this study was aimed to encapsulate BMV into the chitosan nanoparticles (CS-NPs) for optimum dermal targeting and improved penetration across the SC. The prepared NPs were characterized for particle size, zeta potential, polydispersity index, entrapment efficiency, loading capacity, crystallinity, thermal behavior, morphology, in vitro release kinetics, drug permeation across the SC, and percentage of drug retained into various skin layers. Results showed that optimized BMV-CS-NPs exhibited optimum physicochemical characteristics including small particle size (< 250 ± 28 nm), higher zeta potential (+58 ± 8 mV), and high entrapment efficiency (86 ± 5.6%) and loading capacity (34 ± 7.2%). The in vitro release study revealed that BMV-CS-NPs displayed Fickian-diffusion type mechanism of release in simulated skin surface (pH 5.5). Drug permeation efficiency and the amount of BMV retained into the epidermis and the dermis were comparatively higher in case of BMV-CS-NPs compared to BMV solution. Conclusively, we anticipated that BMV-CS-NPs could be a promising nanodelivery system for efficient dermal targeting of BMV and improved anti-AD efficacy.

A qualitative and quantitative analysis of radiation dose and image quality of computed tomography images using adaptive statistical iterative reconstruction.

Image quality is a key issue in radiology, particularly in a clinical setting where it is important to achieve accurate diagnoses while minimizing radiation dose. Some computed tomography (CT) manufacturers have introduced algorithms that claim significant dose reduction. In this study, we assessed CT image quality produced by two reconstruction algorithms provided with GE Healthcare's Discovery 690 Elite positron emission tomography (PET) CT scanner. Image quality was measured for images obtained at various doses with both conventional filtered back-projection (FBP) and adaptive statistical iterative reconstruction (ASIR) algorithms. A stan-dard CT dose index (CTDI) phantom and a pencil ionization chamber were used to measure the CT dose at 120 kVp and an exposure of 260 mAs. Image quality was assessed using two phantoms. CT images of both phantoms were acquired at tube voltage (kV) of 120 with exposures ranging from 25 mAs to 400 mAs. Images were reconstructed using FBP and ASIR ranging from 10% to 100%, then analyzed for noise, low-contrast detectability, contrast-to-noise ratio (CNR), and modulation transfer function (MTF). Noise was 4.6 HU in water phantom images acquired at 260 mAs/FBP 120 kV and 130 mAs/50% ASIR 120 kV. The large objects (fre-quency < 7 lp/cm) retained fairly acceptable image quality at 130 mAs/50% ASIR, compared to 260 mAs/FBP. The application of ASIR for small objects (frequency >7 lp/cm) showed poor visibility compared to FBP at 260 mAs and even worse for images acquired at less than 130 mAs. ASIR blending more than 50% at low dose tends to reduce contrast of small objects (frequency >7 lp/cm). We concluded that dose reduction and ASIR should be applied with close attention if the objects to be detected or diagnosed are small (frequency > 7 lp/cm). Further investigations are required to correlate the small objects (frequency > 7 lp/cm) to patient anatomy and clinical diagnosis.

Leg Ulceration with Infected Calcinosis Cutis Mimicking Osteomyelitis: A Case Report.

Calcified tissue exposed in a leg ulcer can become infected and develop into a nidus of infection leading to sepsis. This case details a patient with a leg wound secondary to skin biopsy. This leg ulceration did not heal due to an underlying calcified mass and led to five hospital admissions for sepsis. She was diagnosed as having calcinosis cutis, which was suspected to be the source of her infections. The calcified mass was resected, and she healed uneventfully without further infections. Calcified soft-tissue masses should be considered in nonhealing leg ulcers and ulcers with multiple recurrent infections. Radiographs can be used to diagnose this condition, and surgical excision can be considered in cases of infection.

Pregnenolone derivatives for the treatment of Alzheimer's disease: synthesis, and in vitro inhibition of amyloid ß1-42 peptide aggregation, acetylcholinesterase and carbonic anhydrase-II.

The amyloid state, which is a specific conformation of proteins, offers valuable information about both functional protein structures and the pathological assemblies associated with various diseases. One of the major hallmarks of Alzheimer's disease includes primarily the extracellular build-up of a peptide known as amyloid-ß, which has a sequence consisting of 39 to 42 amino acid residues, and the formation of intracellular neurofibrillary tangles mostly consisting of hyperphosphorylated tau protein. Drugs that are expected to reduce Aß production, prevent Aß aggregation, and promote Aß clearance are promising approaches for treating AD. Current work is focused on identifying the compounds that have balanced even mild biological activities against multiple targets instead of finding one-target compound with high potency. We synthesized pregnenolone derivatives and evaluated their potential against inhibition of eeAChE/eqBChE, hCA-II and self-mediated Aß1-42 peptide aggregation. Our synthesized derivatives 23, and 25-27 exhibited concomitant inhibition of all the tested macromolecular targets. All the active compounds were found to be BBB penetrants in the PAMPA assay. Furthermore, these selected compounds were found to be non-neurotoxic in the MTT assay on neuroblastoma SH-SY5Y cells. Docking studies support dual binding site (PAS and CAS) inhibition of AChE which showed Aß1-42 aggregation and AChE inhibition. Moreover, docking studies carried out on the 3D crystallographic structure of Aß1-42 peptide (PDB ID = 1IYT) showed significant interactions with amino acid residues Asp 23 and Lys 28, and hydrophobic interactions with the Phe19, Phe20, and Ala 30 effectively impeding the formation of ß-sheet structures.

Antimalarial prophylaxis failure: Malaria in a returning traveler despite mefloquine prophylaxis.

This case report presents a perplexing case of Plasmodium malariae breakthrough infection despite prophylaxis with appropriate antimalarial prophylactic regimen of mefloquine in a compliant patient. A 78-year-old missionary who travels each year to the African subcontinent for multiple weeks to months, over 25 years, adheres to stringent antimalarial prophylaxis with Mefloquine as prescribed, starting prior to the trip and continuing after the return to the U.S.A. She gave no prior history of malaria during her 25 years of travel to Africa and back. Since she had no prior history of malaria and due to her excellent compliance with antimalarial regiment, despite her presentation which were suggestive of malaria, neither the patient nor her providers recognized the onset of malaria in this case. Infectious diseases physicians approached this case with an open mind, investigated appropriately, requested appropriate tests, found the presence of malarial parasite, identified as P. malariae species thereafter. She was started on antimalarial treatment in a timely fashion and showed an excellent response. This intriguing recovery of malarial parasite and response to treatment despite the patient being on antimalarial prophylaxis raised the possibility of mefloquine failure as an antimalarial prophylactic agent against P. malariae species.

Observational Study of the Clinical Impact of E-scooter Injuries at a Major Trauma Centre.

Background Due to the increased use of e-scooters in the UK, associated injuries have increased, and its cost has increased as well. Worldwide data on injuries related to e-scooter use are relatively limited, owing to the short duration since their first introduction to the public.  Aim There has been an increase in using e-scooters as a method of transport recently. It was noticed that the severity and frequency of its injuries are increasing as well. This study focuses on the frequency of e-scooter-associated injuries, especially open fractures, and to evaluate its burden on the health system. Methods Data on e-scooter injuries were extracted from our trauma database from November 2017 to July 2022. Patients' notes and images were reviewed. Outcome measures were the type of injuries: site of bony fractures, closed vs. open fracture (using Anderson and Gustilo classification), number of operations, complications, and length of hospital stay. Results The number of patients enrolled was 104. The mean age was 34.3 years, and 78.8% (n = 82) were male. The main mechanism of injury was riding (91%, n = 95) vs. hitting by an e-scooter (9%, n = 9). Injured patients were more likely not to wear helmets (82% of total injured patients). Patients with bony injuries were 65.4% (n = 68), with 22.1% (n = 15) of them being open fractures. The most common bony injuries were lower limb-only fractures at 45.6% (n = 31), then upper limb-only injuries at 39.7% (n = 27). Combined upper and lower limb cases were 8.8% (n = 6), and pelvic injuries were 5.9% (n = 4). Head and neck injuries composed 23.1% (n = 24) of the reported injuries, including intracranial haemorrhages (9.6%, n = 10), extensive traumatic brain injury (3.8%, n = 4), haematoma/lacerations (3.8%, n = 4), cervical spine fractures (1.9%, n = 2), and skull fractures (1.9%, n = 2). The mean duration of hospital stay was 8.6 days, and 9.6% (n = 10) of patients needed intensive therapy unit (ITU) admission. The number of patients presented as trauma calls was 55.8% (n = 58). Patients who needed surgical intervention either under orthopaedics or other specialties were 52.9% (n = 55) and 21.2% (n = 22) of total patients had complications either due to surgical intervention or a long hospital stay.  Conclusion E-scooter riding can lead to serious injuries that can end with limb- or life-threatening conditions. The most common demographic characteristics were adults in their early 30s. There should be more emphasis on wearing protective gear like wrist and elbow guards in addition to helmets. Future prospective studies with larger cohorts across multiple regions and hospitals are necessary to truly characterize the nature and cost of e-scooter injuries.

Exploitation of the multitarget role of new ferulic and gallic acid derivatives in oxidative stress-related Alzheimer's disease therapies: design, synthesis and bioevaluation.

Monoamine oxidases (MAOs) inhibitors could decrease reactive oxygen species (ROS) generation, enhance mono-aminergic neural transmission, and have major therapeutic benefits for the treatment of Alzheimer's disease (AD). Following the conjunction of ferulic acid (FA)/gallic acid (GA) with sulfonamide, alanine and 2-aminobenzothiazole, we planned to assess the radical scavenging and antioxidant properties of synthesized analogs by using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and ferric ion reducing antioxidant power (FRAP) assays. GA analog 28 was identified as the most potent antioxidant compound with IC50 values of 1.77 µM and 2.06 µM in DPPH and ABTS assays respectively. In the in vitro enzyme inhibition assays, synthesized derivative 23 emerged as a potent multitarget inhibitor of hMAO-B, eeAChE. COX-2 and 5-LOX with IC50 values of 0.037 µM, 0.071 µM, 14.3 µM and 0.59 µM, respectively. Moreover, selected compounds 23, 25, 26 and 28 displayed good to moderate inhibition of self-mediated amyloid ß1-42 peptide aggregation. More importantly, compounds 23, 25, 28 and 29 showed no neurotoxicity on SH-SY5Y cells and also showed excellent neuroprotective effects against H2O2-induced SH-SY5Y cells. In the in vivo experiment, antioxidant enzymes superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-Px) were studied in the brain of male BALB/c mice at the dose of 5 mg kg-1. All the tested compounds, except 29, have shown good to in vivo antioxidant potential. Docking studies on 3D crystallographic structures of AChE and MAO-B showed significant interactions with catalytic amino acid residues. In conclusion, the current study showed that FA/GA derivatives could be further exploited for their multitarget role in oxidative stress-related AD therapies.

Coupling negative pressure wound therapy with instillation and split-thickness skin graft for a large chronic venous leg ulceration: a case report.

INTRODUCTION: Chronic VLUs are quite challenging to heal with many currently available treatment methods. The timing and combination of treatment methods is integral to successful wound healing. OBJECTIVE: This case combined NPWTi coupled with biofilm killing solution, hydrosurgical debridement to prepare the wound bed, and STSG to achieve epithelialization. To the knowledge of the authors of the present study, no previously published case report has combined these methods for treatment of a chronic VLU. CASE REPORT: This case report highlights a chronic VLU on the anteromedial ankle that healed in 2 months using NPWTi and STSG. CONCLUSION: The combination of NPWTi, hydrosurgery, and STSG to treat this patient resulted in successful wound healing, greatly reduced time to healing compared with standard of care, and allowed the patient to return to her normal lifestyle.

Pathergy After Endovenous Ablation for Lower-Extremity Venous Disease: A Case Report of an Unexpected Complication.

A 64-year-old woman presents with wounds to her left ankle. Although her soft-tissue cultures and arterial Doppler and duplex studies were unremarkable, her venous reflux studies showed right and left small saphenous vein insufficiency. After 8 weeks of standard treatment, her wounds to the left ankle did not improve, and she developed a wound to her right anterior leg. Her left ankle wound healed 8 months after initial presentation, and her right leg wound healed in 3 months. Thereafter she underwent an endovenous ablation of her left small saphenous vein, without apparent complications. Two weeks after surgery, she developed an incision site scab that worsened and ulcerated. This case report highlights pathergy from endovenous ablation for lower-extremity venous disease.

A Case of Concurrent Tricuspid Valve, Mitral Valve, and Device Endocarditis.

Endocarditis involving multiple valves is a relatively rare phenomenon, and much about its etiology, prognosis, and best practices for treatment remains uncharacterized. Currently, the treatment of multiple-valve endocarditis is similar to that of single-valve endocarditis. However, limited data suggest that patients may potentially benefit from different treatment approaches not yet clearly defined. Here, we present a unique case of a 22-year-old female with a history of aortic coarctation repair and a ventricular septal defect (VSD) patch repair who presented to the emergency department (ED) after acute onset of fever, chills, nausea, vomiting, and diarrhea. The patient was admitted to the ICU with septic shock and was found to have concurrent mitral valve, tricuspid valve, and VSD patch endocarditis. We discussed her hospital course and treatment as well as current treatment approaches to multiple-valve endocarditis.

Clinical outcomes of selective plantar fascia release for hallux interphalangeal joint ulcers.

BACKGROUND: Plantar hallux IPJ ulcers are common and challenging to manage, with many available treatments. One newer technique called SPFR has been used in the management of plantar forefoot ulcers. OBJECTIVE: This case series reports the clinical results of SPFR for treatment of strictly plantar hallux IPJ ulcers. MATERIALS AND METHODS: A retrospective chart review was conducted on patients that underwent SPFR procedure by a single foot and ankle surgeon from 2018 to 2023. The primary study outcome was to identify the rate and time of healing associated with SPFR for hallux IPJ ulcers. Only the initial surgery was evaluated for time of healing for the ulcer, healing rate, and complications. Subsequent surgeries were reviewed as well. Patient charts were further reviewed to determine the presence or absence of a postoperative complication. RESULTS: A total of 17 feet from 17 patients were studied. The hallux IPJ ulcers healed in an average of 3.0 months. The average follow-up time was 26.9 months. Fifteen patients (88.2%) healed after the SPFR procedure. Five patients (29.4%) developed transfer lesions, and 7 patients (41.2%) developed postoperative complications. CONCLUSIONS: The authors believe that SPFR can be utilized in the treatment of hallux IPJ ulcers if both surgeons and patients are aware of the potential complications and limitations of this procedure. Further research is warranted to evaluate the efficacy and reproducibility of these results.

Myocarditis Presenting as ST-Elevation Myocardial Infarction.

When evaluating a patient with ST-segment elevation on ECG and acute chest pain, providers often rapidly arrive at the diagnosis of ST-elevation myocardial infarction (STEMI). As myocardial infarction is deadly and time is of the essence in establishing reperfusion, it is reasonable to place it at the top of the differential. However, doing so should not come at the expense of conducting a thorough clinical evaluation, considering all causes of ST-segment elevation, and creating a comprehensive differential. Myocarditis, in particular, can present similarly to myocardial infarction and misdiagnosis can lead to unnecessary and sometimes harmful interventions such as thrombolytic therapy, vasodilator therapy, or coronary angiography. We present a case of myocarditis mimicking STEMI and discuss diagnosis and treatment of myocarditis.

Density functional theory, molecular docking, In vitro and In vivo anti-inflammatory investigation of lapachol isolated from Fernandoaadenophylla.

Medicinal plants are the main source of active chemical constituents responsible for curing or mitigating various ailments. To discover new, safe, and effective drug candidates the isolation and screening of natural products are essential. In the current research work, lapachol was isolated from Fernandoa adenophylla, which was evaluated for anti-inflammatory effect followed by molecular docking. The isolated compound was tested for anti-inflammatory effects using in vitro (HRBC assay) and in vivo (xylene-induced ear edema) experimental models. Various concentrations of lapachol demonstrated anti-inflammatory effects with a percent potential of 77.96 at 100 µM. Different concentrations of Lapachol demonstrated a dose-dependent anti-edematous effect with a maximum percent effect of 77.9 % at a higher dose. The histopathological study revealed that the application of xylene led to a significant increase in ear thickness, along with clear signs of ear edema and infiltration of inflammatory cells, as well as epidermal hyperplasia of the dermis when compared to the control group. However, treatment with the investigated compound showed a significant reduction in ear thickness and pathological differences comparable to those observed in the group treated with diclofenac. Density functional theory calculations are accomplished to gain insight into structural and spectroscopic properties. Geometry optimization, FMO, and MEP analyses are performed. Overall, the molecular docking results indicate that lapachol has potential as a COX inhibitor by binding to the active sites of both COX-1 and COX-2 enzymes.

Molecular docking, DFT studies, and anti-inflammatory evaluation of peshawaraquinone isolated from Fernandoa adenophylla.

In recent years, there has been growing interest in exploring natural compounds with anti-inflammatory properties for potential therapeutic applications. This study focuses on investigating the anti-inflammatory potential of peshawaraquinone (PAQ), a compound isolated from Fernandoa adenophylla, which is known for its local use in pain relief. We aim to evaluate the efficacy of peshawaraquinone in both in vitro and in vivo models and gain insights into its mode of action. In the in vitro Human red blood cell (HRBC) assay, various concentrations of peshawaraquinone were tested for their ability to inhibit the hemolysis of red blood cells, a well-established indicator of anti-inflammatory activity. The results demonstrated a maximum percent inhibition of 79.69 at a concentration of 100 µM, indicating significant anti-inflammatory potential. Furthermore, the in vivo xylene-induced ear edema model was employed to assess the compound's efficacy in reducing inflammation. Xylene was topically applied to the ear to induce edema, and peshawaraquinone was administered to evaluate its inhibitory effects. The findings revealed a substantial 74.19% reduction in ear edema, accompanied by decreased ear thickness and histopathological improvements, such as inhibited cell infiltration and epidermal hyperplasia. To gain further insights into the compound's mechanism of action, density functional theory (DFT) calculations were performed to investigate its spectroscopic characteristics and geometric properties. Additionally, docking studies were conducted on key targets involved in inflammation, including COX-1 and COX-2. In conclusion, this study showcases the significant anti-inflammatory potential of peshawaraquinone, offering promising prospects for its use as a natural anti-inflammatory agent. The results from both in vitro and in vivo models, as well as the mechanistic insights gained from computational analyses, provide a solid basis for further exploration of peshawaraquinone's therapeutic applications.Communicated by Ramaswamy H. Sarma.

Knowledge, Adherence, and Perception of Patients on Maintenance Hemodialysis to Treatment Regimens at a Tertiary Care Hospital in Pakistan.

Background The management of end-stage renal disease (ESRD) demands meticulous adherence to treatment regimens, encompassing hemodialysis (HD) sessions, medication protocols, dietary guidelines, and fluid restrictions. The intricate interplay of factors impacting treatment adherence warrants comprehensive exploration, particularly within Pakistan. Objective To assess knowledge, adherence, and perception regarding the treatment regimens and their determinants among ESRD patients. Methodology Employing a nonprobability, consecutive sampling method, this prospective, cross-sectional study was conducted in July and August 2023 at Lahore General Hospital, Lahore, Pakistan. It exclusively enrolled adult patients with a minimum three-month history of hemodialysis. Thorough demographic data were collected, followed by the meticulous administration of a translated version of the End Stage Renal Disease-Adherence Questionnaire (ESRD-AQ) through face-to-face interviews in the native language. IBM SPSS Statistics for Windows, Version 26 (released 2019; IBM Corp., Armonk, New York, United States) was used to acquire descriptive statistics, as well as Pearson's and Spearman's correlations and univariate and multivariate regression analysis. Results The study encompassed 119 patients, with a mean age of 43.13 ± 14.99 years. Adherence scores revealed means of 921.83 ± 28.37 for males and 865.18 ± 28.81 for females, out of 1200. Notably, only 10.1% demonstrated good adherence, 31.9% displayed moderate adherence, and 58% exhibited poor adherence. A statistically significant association emerged between better adherence and access to personal transportation (ß=-0.225; 95% CI -178.24 to -20.77, p=0.014), with no other demographic factors predicting adherence. Conclusion The study underscores the sobering reality of minimal optimal adherence. Chief impediments include anxiety, alongside challenges such as fistula complications, financial constraints, transportation barriers, and inadequate counseling and motivation. Evidently, robust patient education, sustained motivation, and unwavering support from healthcare providers and institutional entities are imperative to surmount the multifaceted barriers that compromise treatment adherence.

Study protocol of DIVERGE, the first genetic epidemiological study of major depressive disorder in Pakistan.

INTRODUCTION: Globally, 80% of the burdenof major depressive disorder (MDD) pertains to low- and middle-income countries. Research into genetic and environmental risk factors has the potential to uncover disease mechanisms that may contribute to better diagnosis and treatment of mental illness, yet has so far been largely limited to participants with European ancestry from high-income countries. The DIVERGE study was established to help overcome this gap and investigate genetic and environmental risk factors for MDD in Pakistan. METHODS: DIVERGE aims to enrol 9000 cases and 4000 controls in hospitals across the country. Here, we provide the rationale for DIVERGE, describe the study protocol and characterise the sample using data from the first 500 cases. Exploratory data analysis is performed to describe demographics, socioeconomic status, environmental risk factors, family history of mental illness and psychopathology. RESULTS AND DISCUSSION: Many participants had severe depression with 74% of patients who experienced multiple depressive episodes. It was a common practice to seek help for mental health struggles from faith healers and religious leaders. Socioeconomic variables reflected the local context with a large proportion of women not having access to any education and the majority of participants reporting no savings. CONCLUSION: DIVERGE is a carefully designed case-control study of MDD in Pakistan that captures diverse risk factors. As the largest genetic study in Pakistan, DIVERGE helps address the severe underrepresentation of people from South Asian countries in genetic as well as psychiatric research.

Synthesis, characterization and in vitro, in vivo, in silico biological evaluations of substituted benzimidazole derivatives.

A series of substituted benzimidazole derivatives were synthesized by reacting O-phenylenediamine with various aromatic aldehydes or glycolic acid using various inexpensive reagents in aqueous media. Synthesized compounds were characterized and elucidated by IR, 1H NMR, ESI-MS spectra. Resultant compounds were screened for in vitro antimicrobial, cytotoxic, antioxidant, lipid peroxidation and cholinesterase inhibitory activities, in vivo analgesic and anti-inflammatory, and in silico anti-acetylcholinesterase and anti-butyrylcholinesterase activities. Among the synthesized compounds, compound 3b showed most promising central analgesic effect (46.15%) compared to morphine (48.08%), whereas compounds 6, 3c and 3a showed significant peripheral analgesic activity at two different dose levels (25 mg/kg and 50 mg/kg). Compounds 3b and 3a at the dose of 100 mg/kg showed significant anti-inflammatory effects from the first hour and onward, whereas compounds 6 and 3b showed moderate cytotoxic activities. In addition, compound 3a showed significant antioxidant activity having IC50 value of 16.73 µg/ml compared to 14.44 µg/ml for the standard BHT. Compound 6, 3a and 3b exhibited mild to moderate cholinesterase inhibitory activity. In silico studies revealed that compound 3a and 3b might be suitable for cholinesterase inhibitory activity. A comprehensive computational and experimental data suggested compounds 3b and 3a as the best possible candidates for pharmacological activity. All the experimental data were statistically significant (p < 0.01 level).

Literacy and stigma of suicide in Bangladesh: Scales validation and status assessment among university students.

BACKGROUND: Increased suicide literacy and reduced stigma toward suicide facilitate the care-seeking for suicidal behavior. However, no attempt has been identified to determine these two vital aspects in Bangladesh. OBJECTIVES: We aimed to validate the literacy of suicide scale and stigma of suicide scale into Bangla along with the determination of the level of suicide literacy and stigma toward suicide. METHODS: We conducted this study between April and June 2021. Data were collected from medical school and university students by Google form. We used a questionnaire consisting of four segments (i.e., sociodemographic questionnaire, a questionnaire for suicidal behavior, Bangla literacy of suicide scale [LOSS-B], and Bangla stigma of suicide scale [SOSS-B]) for data collection. We tested the psychometric properties of the scales in a sample of 529 students and examined factors associated with suicide stigma and literacy. RESULTS: The mean age of the students was 22.61 ± 1.68 (range 18-27) years, 274 (51.8%) were males, 476 (89.9%) were graduate students, and 490 (92.6%) were unmarried. The mean score of LOSS was 4.27 ± 1.99 ranging from 0 to 10. Factor analysis revealed acceptable psychometric properties of SOSS-B. The literacy was significantly higher in females, students of medicine, having a family history of suicidal attempts, and a history of student nonfatal attempts, while stigma was significantly lower among the females and a history of past attempts. CONCLUSIONS: This study revealed the level of literacy and stigma and culturally tested the psychometric properties of the LOSS-B and SOSS-B among university students in Bangladesh.