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Background and Aim: Endoscopic retrograde cholangiopancreatography (ERCP) is commonly used to diagnose and treat bile duct and pancreatic disorders. Successful cannulation of the papilla is crucial for the effectiveness of ERCP; however, sometimes, it can be challenging to achieve. This study explores the relationship between net difficult ERCP cannulation with bile visibility, papilla orifice visibility, and papilla position and compares it with successful cannulation., Methods: These data were collected from the ERCP database at the Center for Liver Disease, Holy Family Hospital, Rawalpindi, between November 2019 and November 2022. IBM SPSS version 26.0 software was used for statistical analysis., Results: The study included 329 patients, with 186 (56.6%) female and 143 (43.5%) male participants. Most patients were in the 39-48 age group (28.3%), with a mean age of 51 ± 1. Bile visibility was noted in 268 (81.5%) cases, papilla orifice visibility in 296 (90%) participants, atypical papilla in 20 (6.1%), and typical papilla in 309 (93.9%) participants. Bile visibility ( P  = 0.004) and papilla orifice visibility ( P  = 0.006) were significantly associated with successful cannulation, while papilla position ( P  = 0.116) was not. Significant associations were also found between difficult cannulation and bile visibility ( P  = 0.000), papilla orifice visibility ( P  = 0.000), and papilla position ( P  = 0.000)., Conclusion: Understanding this relationship can improve success rates and reduce complications associated with difficult cannulation during ERCP procedures. Further research is needed to establish clear correlations and guidelines for endoscopists to plan appropriate strategies for challenging cases., (© 2024 The Author(s). JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Nephrotoxicity is a prominent complication of methotrexate (MTX) therapy that limits clinicians in its extensive use. MTX triggers oxidative burden and inflammation, so the nephroprotective potential of the synthetic derivative of 1,3,4-oxadiazole (5b) was explored in this research. Male Wistar rats were divided into four groups i.e., control group, MTX group, 5b (5 mg/kg) + MTX group and 5b (10 mg/kg) + MTX group, respectively. All treatments were given, intraperitoneally (i.p.) during 12 days of the animal model. The MTX-induced nephrotoxicity was evaluated by renal function markers i.e., serum creatinine (Cret), blood urea nitrogen (BUN), and albumin (Alb). Furthermore, antioxidant markers, catalase (CAT), glutathione-S-transferase (GST), and reduced glutathione (GSH), and oxidative stress, markers lipid peroxidase (LPO) and nitric oxide (NO), were analyzed. Pro-inflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), were also calculated. DNA damage was assessed by the comet assay. Histopathological staining (Hematoxylin and eosin, Masson's trichrome) was done and immunohistochemistry was performed against Caspase-3, Nrf2, HO-1, TLR-4, TNF-α, and NF-κB. A significant improvement in the serum Cret, BUN, and Alb was observed in (5b) treated groups. Antioxidant markers were elevated, oxidative stress markers and pro-inflammatory cytokines were reduced, moreover, histopathological analysis revealed less tissue damage in (5b) administered groups. Immunohistochemistry showed increased immune expression of Nrf2 and HO-1 and decreased expression of TLR-4, TNF-α, Caspase-3, and NF-κB in 5b (5 mg/kg) + MTX group and 5b (10 mg/kg) + MTX group as compared to the MTX group. Hence, the results of this study favor the use of (5b) against MTX-induced nephrotoxicity., (© 2024 Wiley Periodicals LLC.)

Ulcerative colitis (UC) is a condition characterized by inflammation and ulcer formation in the colon and rectum due to genetic and environmental factors. It is a common condition, with a global prevalence rate exceeding 0.3%. Current treatments have limited efficacy and can cause unwanted side effects, leading to a high recurrence rate and reduced quality of life for patients. This study suggests that Bacillus clausii has a beneficial role in reducing intestinal inflammation and relieving colitis symptoms in mice. The study aimed to examine B. clausii's potential to reduce the progression and pathogenesis of dextran sulphate sodium (DSS)-induced UC. Bacillus clausii was administered to mice as a pre-treatment, post-treatment and adjunct treatment with sulfasalazine for 14 days. The study found that B. clausii effectively reduced the severity of colitis in mice when used preventatively. Administering B. clausii after the onset of colitis also effectively alleviated symptoms. Combining B. clausii with standard sulfasalazine as adjunct therapy was more effective in reducing intestinal inflammation than using a single therapy alone. B. clausii has shown the potential to prevent colon damage and decrease the likelihood and severity of the disease. Immunohistochemistry results revealed a decrease in the expression of pro-inflammatory cytokines such as IL-1β, TNF-α and NFkB in colon tissue. Additionally, mice that received B. clausii showed a significant increase in anti-oxidant levels and improved haematological markers. In conclusion, it must be emphasized that B. clausii possesses the potential to alleviate the symptoms of UC., (© 2024 John Wiley & Sons Australia, Ltd.)

Background: Stress is among the most common comorbid conditions with epilepsy and a strong factor in the pathophysiology of seizures. An imbalance in neuronal circuits causes recurrent unprovoked seizures in epilepsy. Dysregulation of BDNF/VEGF expression, oxidative stress, increased levels of neuroinflammatory cytokines, and increased expression of apoptotic genes contribute to the underlying cause of the seizure., Objectives: Chrysophanol, an anthraquinone, has broad-spectrum therapeutic potential. This study evaluated the neuroprotective effect of chrysophanol with underlying pathways in PTZ-induced epilepsy with stress as a comorbid condition., Methods: Male mice were given 35 mg/kg of PTZ every other day to induce seizures. In addition, they were exposed to 120 min of daily restraint stress for 21 days to induce stress. Chrysophanol (0.1, 1, 10 mg/kg) was administered to the mice 30 min before the PTZ in the acute study. The most effective dose (10 mg/kg) was proceeded for the chronic epilepsy model. Following this, various tests were conducted, including behavioral assessments for memory impairment and stress, analysis of antioxidant levels, histopathological and immunohistochemistry examinations, measurement of cortisol levels using ELISA, and gene expression analysis using RT-PCR., Results: Chrysophanol demonstrated a notable decrease in both the intensity and frequency of seizures. Additionally, it effectively boosted the levels of important antioxidants such as GSH, GST, and CAT, while simultaneously reducing the levels of MDA and Nitric oxide. The histopathological analysis also showed improvement in overall morphology and survival of neurons. Chrysophanol treatment effectively showed an increase in the expression of BCL-2, and Nrf-2 with a decrease in BAX expression confirmed by immunohistochemistry. Dysregulation of vascular permeability factor, production of inflammatory cytokines, and apoptotic gene expression was successfully reversed after chrysophanol treatment analyzed through RT-PCR. Cortisol concentration was decreased in treatment groups analyzed through Enzyme-linked immunoassay. Molecular docking of chrysophanol with different proteins declared the binding affinity of the ligands with the target sites of proteins., Conclusion: In conclusion, chrysophanol demonstrated remarkable neuroprotective and antiepileptic effects at a dose of 10 mg/kg in stress-exacerbated PTZ-induced epilepsy following the TLR4/NFκB -Nrf2/HO-1 and BDNF/VEGF pathways., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Khan, Zainab, Rehman, Abid, Shah, Rehman and Tipu.)

Extra-articular manifestations (EAM), which are associated with rheumatoid arthritis (RA), affect the quality of life of patients and are one of the critical causes of early mortality. This study was aimed at investigating whether Bacillus subtilis NMCC-path-14 (1 × 10 8  CFU/animal/day) could serve as a valuable therapeutic agent in managing EAM using complete Freund's adjuvant (CFA) induced arthritis during acute and sub-acute phases. Arthritis was induced using intra-dermal administration of CFA in the right hind paw of mice on day 1. Dexamethasone (Dexa) (5 mg/kg/day/animal) was used as a standard treatment. Animals in Dexa and Bacillus subtilis concurrent treatment (BS-CT) received treatments on day 1. The Bacillus subtilis pre-treatment (BS-PT) group received a probiotic dose 7 days before arthritis induction. Parameters like body weight, relative organ weight, colon length, hematology, serum biochemistry, antioxidant capacity, and histopathology of liver, kidney, spleen, colon, stress-related behavioral changes, and cortisol levels were evaluated on days 7 (acute) and 14 (sub-acute). Dexa failed to manage the EAM in arthritic mice and instead exacerbated them. On the other hand, B. subtilis NMCC-path-14 significantly declined EAM with no notable side effects, highlighting its safety and effectiveness. The current data show that B. subtilis NMCC-path-14 may be an alternative option for arthritis treatment that can reduce systemic symptoms associated with arthritis. More studies are required to comprehend the underlying mechanisms of mitigating the EAM by B. subtilis NMCC-path-14., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background Empirical antibiotic therapy is facilitated by antibiograms as they provide local bacterial resistance data and patterns. Antibiograms are critical tools that offer comprehensive, institution-specific information on antimicrobial susceptibilities, enabling clinicians to make informed decisions about empirical treatment and guiding antimicrobial stewardship efforts. The rising incidence of multidrug-resistant (MDR) organisms is a significant challenge in countries like Pakistan. Objective The objective of this study was to evaluate the resistance patterns of Gram-negative and Gram-positive bacteria at Hayatabad Medical Complex (HMC) to commonly used antibiotics, with a specific focus on identifying MDR pathogens. Methods A retrospective study was conducted using antibiogram data from January to September 2022, focusing on both Gram-negative and Gram-positive organisms. Sensitivity patterns for antibiotics such as Ceftazidime, Imipenem, Meropenem, Amikacin, Oxacillin, and Teicoplanin were checked. Results Acinetobacter posed a significant challenge to treatment, displaying only 6% sensitivity to Ceftazidime. This extremely low sensitivity indicates an alarmingly high level of resistance, which is of great concern as it severely limits treatment options for Acinetobacter infections. Such high resistance to Ceftazidime, a broad-spectrum cephalosporin, suggests that infections caused by this pathogen may require the use of last-resort antibiotics or combination therapies, potentially leading to increased healthcare costs and poorer patient outcomes. Additionally, Acinetobacter showed only 37% sensitivity to Ciprofloxacin, further confirming its status as an MDR pathogen in hospital settings. Conclusion The results show the growing threat of MDR organisms at HMC, Peshawar. This underscores the urgent need for robust antimicrobial stewardship programs, enhanced infection control practices, ongoing surveillance of resistance patterns, healthcare provider education, and regional collaboration to address the challenge of antimicrobial resistance., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Hayatabad Medical Complex (Institutional Research and Ethical Board) issued approval 2208. To ensure the study was done ethically, the institutional review board granted ethical permission. Patient confidentiality was ensured by eliminating all identities and analyzing only anonymous data. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Iftikhar et al.)

Background: Epilepsy is a paroxysmal abnormal hypersynchronous electrical discharge characterized by recurrent seizures. It affects more than 50 million people worldwide. Stress is the leading cause of neurodegeneration and can produce seizures that may lead to or aggravate epilepsy. Inflammation plays a vital role in epilepsy by modulating oxidative stress, and levels of neuroinflammatory cytokines including NF-κB, TNF-α, and IL-1β., Methods: Stress-induced changes in behavior were evaluated in mice by employing behavioral assessment tests such as an elevated plus maze, light-dark box, open field test, tail suspension test, Y-maze, novel object recognition test, and Morris water maze in pentylenetetrazole (PTZ) kindled mice. Behavioral changes in all these paradigms including seizure score, latency, and frequency showed an increase in symptoms in PTZ (35 mg/kg) induced seizures in stressed mice (RS-PTZ) as compared to PTZ, Stress, and normal animals., Results: The Enzyme-linked immunosorbent assay (ELISA) results confirmed increased in serum cortisol levels. Histological examinations showed neurodegenerative changes in the hippocampus and cortex regions. The spectrophotometric evaluation showed an increase in oxidative stress by decreasing antioxidant production i.e. reduced glutathione, glutathione -s- transferase, and catalase (CAT), and increasing oxidant levels such as maloaldehyde and nitric oxide. Immunohistochemistry results showed increased expression of NF-κB, TNF-α, and IL-1β in the cortex and hippocampus of mice brains., Conclusions: Results from the study conclude that stress increases the likelihood of eliciting an epileptic attack by increasing the level of reactive oxygen species and neuroinflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

1,3,4-Oxadiazole is a fascinating heterocyclic compound with a unique five-membered ring structure containing nitrogen and oxygen atoms. It has garnered significant attention for its interactions and activities within biological systems. This versatility has led to the production of several ligands using this compound as a pharmacophore. This study evaluates the acute toxicity of three oxadiazole derivatives (1,3,4-Bromo, Chloro, and Iodo) followed by a 28 days sub-acute study involving four different doses of each derivative. The study followed the guideline, the Organization for Economic Cooperation and Development (OECD) outlined, specifically OECD Guidelines 425 for the acute toxicity study and OECD Guidelines 407 for the sub-acute study. In the acute toxicity study, a high dose of 2000 mg/kg was administered to male and female rats to establish lethal dose 50 (LD50) values, and the rats were closely monitored for 14 days. The subsequent sub-acute study involved the administration of four different doses (1.25, 2.5, 5, and 10 mg/kg) of each derivative to male and female rats for 28 days. Throughout both studies, careful monitoring for signs of toxicity and comprehensive hematological, biochemical, and histological analysis were carried out thoroughly. The results of the acute toxicity study indicated that all three derivatives had LD50 values exceeding 2000 mg/kg, and the rats did not display significant signs of toxicity. Similarly, no organ or systemic toxicity was observed in the repeated dose sub-acute study for any of the three derivatives. In conclusion, based on the findings of these studies, it was determined that the derivatives are safe for further investigation of their pharmacological activity., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Probiotics have recently gained significant interest for their possible therapeutic effects in treating numerous health conditions. Probiotics containing Bacillus subtilis have been shown to have several health benefits, most notably in preventing diarrhea and gastrointestinal problems. A novel probiotic strain, Bacillus subtilis (NMCC-path-14), isolated from the rumen of a Nilli Ravi Buffalo, was evaluated for 28-day repeated dose toxicity in Balb/c mice. The NMCC-path-14 in low dose (1 × 10 8  CFU/ml) and high dose (1 × 10 10  CFU/ml) was administered to the mice through gavage regularly. After 28 days of treatment, it was discovered that the no-observed-adverse-effect level (NOAEL) for NMCC-path-14 wasgreater than 1 × 10 10  CFU/animal/day. This study also revealed no treatment-related changes in clinical parameters, body weight, gross pathology, or histology. Food consumption, hemoglobin, hematocrit, red blood cell counts, and colon length increased, while total/differential leukocyte count and platelets remained unchanged. The administration of NMCC-path-14 also resulted in decreased bilirubin and creatinine levels. Furthermore, NMCC-path-14 also displayed a promising antioxidant potential by increasing the antioxidant enzymes (GST, GSH, and CAT) and decreasing oxidant enzyme (MDA and NO) levels in vital organs like the liver, kidneys, spleen, and colon. TheNMCC-path-14also decreased the pathogenic bacterial population while increasing the beneficial population. Given the lack of adverse effects observed after NMCC-path-14 treatment, this strain is safe and must be considered as a potential probiotic in humans., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:None declared If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The current study aimed to determine the safety and efficacy of Coag-A through in vivo analysis in CFA induced mice model. Treatment of CFA induced arthritis in mice with Coagulansin-A (10 mg/kg i.p. daily for 28 days), a withanolide obtained from Withania coagulans, as well as standard drug treatment with Dexamethasone (5 mg/kg i.p) was provided. The effect of Coag-A on body weight, relative organ weight, hematology, serum biochemistry, survival rate, oxidative stress markers, and antioxidant enzymes was evaluated. The liver and kidney histopathology were also assessed to ascertain its safety profile. Treatment of arthritic mice with Coag-A considerably improved body weight, relative organ weight of liver, kidney, and spleen, ameliorated hematology and serum biochemistry, and increased survival and antioxidant potential. Coag-A was found to be safer with fewer adverse effects showing hepato-protective, nephroprotective, and anti-inflammatory effect. It also significantly (p < 0.001) improved histopathology of CFA-induced mice when compared with Dexa. In conclusion, compared to dexamethasone, Coag-A has demonstrated a greater therapeutic benefit and fewer side effects in the treatment of arthritis against the CFA-induced model., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

To investigate and compare efficacy as well as safety of Bacillus subtilis and dexamethasone (Dexa) in complete Freund's adjuvant (CFA)-induced arthritis, we used glucocorticoid monotherapy (Dexa 5 mg/kg/day) and B. subtilis (1 × 10 8  CFU/animal/day p.o) as pre-treatment and concurrent treatment for a duration of 35 days. Specific emphasis was on chronic aspect of this study since long-term use of Dexa is known to produce undesirable side effects. Treatment with Dexa significantly attenuated the arthritic symptoms but produced severe side effects like weight loss, increased mortality, immunosuppression, and altered histology of liver, kidney, and spleen. Oxidative stress was also elevated by Dexa in these organs which contributed to the damage. Treatment with B. subtilis improved symptoms of arthritis without producing any deleterious side effects as seen with Dexa therapy. Immunohistochemistry (IHC) profile revealed decreased expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin (IL)-1β, tumor necrosis factor alpha (TNF-α), and increased nuclear factor erythroid 2-related factor 2 (Nrf-2) expression by B. subtilis and Dexa treatment in ankle joint of arthritic mice. Radiological scores were also improved by both treatments. This study concludes that B. subtilis could be an effective alternative for treating arthritis than Dexa since it does not produce life-threatening side effects on prolong treatment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To investigate the efficacy of Photobiomodulation therapy (PBMT) for the treatment of solitary rectal ulcer syndrome (SRUS). Background: SRUS is a benign disease, diagnosed by symptoms, clinical, and histological findings. PBMT has been reported for the treatment of various inflammation-based diseases including aphthous ulcer, but still no such study on the treatment of SRUS is published. Materials and methods: A 29-year Asian women, diagnosed for SRUS of 0.57 cm diameter, was treated by a laser at 635 nm through seven sessions. Laser fluence of 85 J/cm 2 was delivered to ulcer lesion during each session for 10 min. Clinical results were valued by physician with sigmoid probe throughout PBMT sessions and no medicines were prescribed to the patient. Results: After seven sessions, the lesion was completely healed with 100% clinical response. In follow-up, patient did not respond to any additional/recurring abnormality, and no side effects were observed. Conclusions: In conclusion, PBMT by using laser at 635 nm is an effective treatment for SRUS without any side effects and patient remained comfortable throughout treatment sessions. Patient registration No. H-744/23.

Introduction: Infectious disease management in intensive care units (ICUs) is becoming more difficult due to increasing antimicrobial resistance. Hence, the aim of this study was to explore the nature of pathogens mostly encountered in an ICU and determine their antibiotic susceptibility through the compilation of ICU-specific antibiogram., Methodology: A descriptive cross-sectional study of the culture and sensitivity reports of ICU patients was conducted in a tertiary care hospital. An antibiogram was created according to the Clinical Laboratory Standards Institute (CLSI) M39-A4 guidelines., Results: Of the total 597 reports, the most common specimen type were respiratory secretions (n = 174), followed by blood (n = 128), wounds (n = 108), and urine (n = 80). Out of 597 isolates, the most frequently isolated bacteria were Klebsiella species (n = 156), Pseudomonas aeruginosa (n = 117), Escherichia coli (n = 112), Enterobacter species (n = 56), Acinetobacter species (n = 52), Proteus species (n = 39), Staphylococcus aureus (n = 34) and coliform species (n = 31). An 84% multidrug resistance (MDR) rate was reported among the isolates studied, with Acinetobacter species being at the top with a 98% MDR rate., Conclusions: A substantial and alarming MDR rate was observed in our study. Furthermore, our findings demonstrated a potential interest in developing an ICU-specific antibiogram that is informative to clinicians in their clinical decision-making related to antibiotic therapy., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2023 Jehan Zeb Khan, Mohammad Ismail, Raza Ullah, Waqar Ali, Iftikhar Ali.)

Background: Rabies vaccines are conventionally given via the intramuscular (IM) route; however, switching the route of administration from IM to intradermal (ID) without affecting efficacy can be advantageous in terms of cost, dosing, and time. Hence, it is indispensable to evaluate its safety along different routes. This study was carried out to ascertain the frequency of adverse drug events (ADEs) and associated factors, as well as to compare safety based on the IM and ID routes., Methods: A prospective observational study was carried out on 184 individuals with rabies exposure. The vaccination schedules for post-exposure prophylaxis (PEP) included 0.2 milliliter (mL) of purified Vero cell rabies vaccine (PVRV) administered ID at two different sites with 0.1 mL each on days 0, 3, and 7 in first group (3-dose regimen ID) and 0.5 mL administered IM on days 0, 3, 7, 14, and 28 in the second group (5-dose regimen IM). The safety of the vaccines was determined by reviewing ADEs during physical examinations and follow-up. ADEs were characterized by local and systemic effects., Results: Of the total, 99 (53.80%) patients reported ADEs. Those who reported local and systemic ADEs were 80 (43.48%) and 59 (32.06%), respectively, while simultaneous occurrence was reported in 40 (40.40%) patients. The most frequent local ADE (76; 41.30%) reported was pain, followed by erythema (18; 9.78%). Additionally, fever had the highest proportion (25; 13.59%) for systemic effects, followed by headache (15; 8.15%). The patients reported with ADEs by the IM and ID routes were comparable ( p  >.05). Similarly, both local and systemic effects were also comparable ( p  >.05)., Conclusion: Half of the study participants reported ADEs. Almost similar proportions of local and systemic effects were observed. Likewise, the ADEs recorded were comparable for both routes. PVRV carries very low safety concerns with either route for administration.

Accurate and early diagnoses are prerequisites for prompt treatment. For coronavirus disease 2019 (COVID-19), it is even more crucial. Currently, choice of methods include rapid diagnostic tests and reverse transcription polymerase chain reaction (RT-PCR) using samples mostly of respiratory origin and sometimes saliva. We evaluated two rapid diagnostic tests with three specimen types using viral transport medium (VTM) containing naso-oropharyngeal (NOP) swabs, direct nasal and direct nasopharyngeal (NP) samples from 428 prospective patients. We also performed RT-PCR for 428 NOP VTM and 316 saliva samples to compare results. The sensitivity of the SD Biosensor Standard Q COVID-19 antigen (Ag) test kit drastically raised from an average of 65.55% (NOP VTM) to 85.25% (direct nasal samples), while RT-PCR was the gold standard. For the CareStart kit, the sensitivity was almost similar for direct NP swabs; the average was 84.57%. The specificities were ≥95% for both SD Biosensor Standard Q and CareStart COVID-19 Ag tests in all platforms. The kits were also able to detect patients with different variants as well. Alternatively, RT-PCR results from saliva and NOP VTM samples showed high sensitivities of 96.45% and 95.48% with respect to each other as standard. The overall results demonstrated high performance of the rapid tests, indicating the suitability for regular surveillance at clinical facilities when using direct nasal or direct NP samples rather than NOP VTM. Additionally, the analysis also signifies not showed that RT-PCR of saliva can be used as an choice of method to RT-PCR of NOP VTM, providing an easier, non-invasive sample collection method. IMPORTANCE There are several methods for the diagnosis of coronavirus disease 2019 (COVID-19), and the choice of methods depends mostly on the resources and level of sensitivity required by the user and health care providers. Still, reverse transcription polymerase chain reaction (RT-PCR) has been chosen as the best method using direct naso-oropharyngeal swabs. There are also other methods of fast detection, such as rapid diagnostic tests (RDTs), which offer result within 15 to 20 min and have become quite popular for self-testing and in the clinical setting. The major drawback of the currently used RT-PCR method is compliance, as it may cause irritation, and patients often refuse to test in such a way. RDTs, although inexpensive, suffer from low sensitivity due to technical issues. In this article, we propose saliva as a noninvasive source for RT-PCR samples and evaluate various specimen types at different times after infection for the best possible output from COVID-19 rapid tests.

Objectives: With COVID-19 vaccination underway, this study aimed to understand belief, attitude and intention of the people in the South Asia region towards the vaccine., Methods: We conducted a cross-sectional study using semi-structured questionnaires among 18201 individuals in four South Asian countries; Bangladesh, India, Pakistan, and Nepal between January 17 and February 2, 2021. We used the Health Belief Model (HBM) to identify the predictors related to vaccine acceptance. STATA (v16.1) was used for all analyses., Results: The percentage of respondents willing to be vaccinated against COVID-19 was 65%, 66%, 72% and 74% for Bangladesh, India, Pakistan and Nepal, respectively. Perceived destructive impact of COVID-19, positive perception of vaccines and concern about possible side effects were significant in modifying respondents' intentions.. In multivariable logistic regression, age, sex, marital status, education, comorbidities, worry about getting infected, perceived COVID-19 impact, belief regarding vaccine efficacy, positive attitude towards mandatory measures, and vaccine availability were found to be associated with vaccine acceptance across countries., Conclusion: Nearabout two-third of the respondants were willing to take COVID-19 vaccine in the four South Asia countries., Competing Interests: Conflict of Interest The authors have no conflicts of interest associated with the material presented in this paper., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Transdermal delivery system has gained significance in drug delivery owing to its advantages over the conventional delivery systems. However, the barriers of stratum corneum along with skin irritation are its major limitations. Various physical and chemical techniques have been employed to alleviate these impediments. Among all these, transfersomes have shown potential for overcoming the associated limitations and successfully delivering therapeutic agents into systemic circulation. These amphipathic vesicles are composed of phospholipids and edge activators. Along with providing elasticity, edge activator also affects the vesicular size and entrapment efficiency of transfersomes. The mechanism behind the enhanced permeation of transfersomes through the skin involves their deformability and osmotic gradient across the application site. Permeation enhancers can further enhance their permeability. Biocompatibility; capacity for carrying hydrophilic, lipophilic as well as high molecular weight therapeutics; deformability; lesser toxicity; enhanced permeability; and scalability along with potential for surface modification, active targeting, and controlled release render them ideal designs for efficient drug delivery. The current review provides a brief account of the discovery, advantages, composition, synthesis, comparison with other cutaneous nano-drug delivery systems, applications, and recent developments in this area., (© 2021. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Objective The present study aimed to assess the psychological and clinical determinants of coronavirus disease 2019 (COVID-19) and their association with the disease severity and outcomes. Methods This prospective study was conducted at Hayatabad Medical Complex, Peshawar-Pakistan. Admitted patients were screened for COVID-19 with reverse transcription-polymerase chain reaction (RT-PCR) and subsequently, 250 COVID positive patients were included in the final analysis. Data were obtained from the patient's medical chart; demographic and clinical characteristics were recorded using a structured questionnaire. Psychological determinants, including anxiety and depression, were measured using the Hospital Anxiety and Depression Scale (HADS). The predictors of disease severity and outcomes (recovery vs. mortality) were also studied. Results A total of 250 patients were included in this study; out of which, 193 patients recovered from this deadly virus and 57 died. Based on psychological assessment, 58.4% of the enrolled COVID-19 patients had poor HADS scores. Most of the patients who died (70.2%) had severe symptoms (poor HADS scores). Similarly, 49.6% of the total cases were observed with poor HADS, and 50.9% of those who died had severe depression. Conclusion It is concluded from the study results that psychological distress is frequent in COVID-19 patients. Age, hypertension, fatigue, abnormal respiratory rate, oxygen saturation, ferritin, and poor HADS sore were determined as the significant predictors of COVID-19 severity and outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Shah et al.)

Coronavirus Disease-2019 (COVID-19) quickly surged the whole world and affected people's physical, mental, and social health thereby upsetting their quality of life. Therefore, we aimed to investigate the quality of life (QoL) of COVID-19 positive patients after recovery in Bangladesh. This was a study of adult (aged ≥18 years) COVID-19 individuals from eight divisions of Bangladesh diagnosed and confirmed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) from June 2020 to November 2020. Given a response rate of 60% in a pilot study, a random list of 6400 COVID-19 patients was generated to recruit approximately 3200 patients from eight divisions of Bangladesh and finally a total of 3244 participants could be recruited for the current study. The validated Bangla version of the World Health Organization Quality of Life Brief (WHOQOL-BREF) questionnaire was used to assess the QoL. Data were analyzed by STATA (Version 16.1) and R (Version 4.0.0). All the procedures were conducted following ethical approval and in accordance with the Declaration of Helsinki. The mean scores of QoL were highest for the physical domain (68.25±14.45) followed by social (65.10±15.78), psychological (63.28±15.48), and environmental domain (62.77±13.07). Psychological and physical domain scores among females were significantly lower than the males (p<0.001). The overall quality of life was lower in persons having a chronic disease. Participants over 45 years of age were 52% less likely to enjoy good physical health than the participants aged below 26 years (AOR: 0.48, CI: 0.28-0.82). The quality of life of employed participants was found 1.8 times higher than the unemployed (AOR: 1.80, CI: 1.11-2.91). Those who were admitted to hospitals during infection had a low QoL score in physical, psychological, and socials domains. However, QoL improved in all aspect except the psychological domain for each day passed after the diagnosis. These findings call for a focus on the quality of life of the COVID-19 affected population, with special emphasis given to females, older adults, unemployed, and people with comorbidities., Competing Interests: The authors declare no competing interests.

The submicron particulate matter (PM 1 ) and fine particulate matter (PM 2.5 ) are very important due to their greater adverse impacts on the natural environment and human health. In this study, the daily PM 1 and PM 2.5 samples were collected during early summer 2018 at a sub-urban site in the urban-industrial port city of Tianjin, China. The collected samples were analyzed for the carbonaceous fractions, inorganic ions, elemental species, and specific marker sugar species. The chemical characterization of PM 1 and PM 2.5 was based on their concentrations, compositions, and characteristic ratios (PM 1 /PM 2.5 , AE/CE, NO 3 - /SO 4 2- , OC/EC, SOC/OC, OM/TCA, K+/EC, levoglucosan/K + , V/Cu, and V/Ni). The average concentrations of PM 1 and PM 2.5 were 32.4 µg/m 3 and 53.3 µg/m 3 , and PM 1 constituted 63% of PM 2.5 on average. The source apportionment of PM 1 and PM 2.5 by positive matrix factorization (PMF) model indicated the main sources of secondary aerosols (25% and 34%), biomass burning (17% and 20%), traffic emission (20% and 14%), and coal combustion (17% and 14%). The biomass burning factor involved agricultural fertilization and waste incineration. The biomass burning and primary biogenic contributions were determined by specific marker sugar species. The anthropogenic sources (combustion, secondary particle formation, etc) contributed significantly to PM 1 and PM 2.5 , and the natural sources were more evident in PM 2.5 . This work significantly contributes to the chemical characterization and source apportionment of PM 1 and PM 2.5 in near-port cities influenced by the diverse sources., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Background: Thyroid nodules are usually diagnosed using fine-needle aspiration (FNA). The sensitivity limitations of FNA result in 10-30% of nodules being classified as "indeterminate". The BRAF V600E mutation is associated with papillary thyroid carcinoma (PTC). We conducted a systemic review and meta-analysis to evaluate the diagnostic utility of the BRAF V600E mutation in indeterminate nodules., Method: PUBMED and EMBASE were searched for studies testing for the BRAF V600E involving indeterminate nodules (Thy3a, Thy3f, Thy4) and containing information on final surgical histopathology. Thirty two studies involving 3150 indeterminate nodules were included in the analysis., Results: The overall sensitivity and specificity for BRAF V600E for the diagnosis of thyroid malignancy was 0.40 (95% CI: 0.32-0.48) and 1.00 (95% CI: 0.98-1.00) respectively. The diagnostic odds ratio (DOR) was 205.4 (95% CI: 40.1-1052). With a Fagan plot, the post-test probability of thyroid cancer, given a negative mutation was 6%, but this rose to 92% with a positive result. On subgroup analysis, for Thy3a nodules, the pooled sensitivity and specificity for thyroid malignancy was 0.21 (95% CI: 0.13-0.34) and 1.00 (95% CI: 0.98-1.00). For Thy3f nodules, the pooled sensitivity and specificity was 0.09 (95% CI: 0.03-0.20) and 1.00 (95% CI: 0.05-1.00) respectively. For Thy4 nodules, the corresponding sensitivity and specificity was 0.58 (95% CI: 0.5-0.64) and 0.99 (95% CI: 0.95-1.00) respectively., Conclusions: Despite a high specificity for thyroid cancer, BRAF V600E mutation has a low overall sensitivity and therefore has a limited diagnostic value as a single screening test., (Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: The gold standard treatment for chronic hepatitis C virus (HCV) infection is pegylated interferon (PEG-IFN) in combination with ribavirin. Most patients treated with PEG-IFN achieve a sustained virological response (SVR). However host genetic factors play a vital role in the spontaneous and treatment-induced clearance of HCV infection from these infected patients. In the current study, polymorphisms of IL28B (rs8099917 and rs12979860) were analyzed and their association with the virological response to PEG-IFN alpha treatment was determined., Methods: One hundred and fifty HCV genotype 3 patients were assessed to study the correlation of IL28B with a therapeutic regimen of PEG-IFN alpha plus ribavirin. Twenty patients were excluded due to a refusal to participate in the study and 25 patients failed to meet the inclusion criteria. Of the 105 patients recruited, 49 (46.7%) were male and 56 (53.3%) were female. In order to determine single nucleotide polymorphisms of rs8099917 and rs12979860, the sample was amplified by PCR and then IL28B typing was carried out by restriction fragment length polymorphism (RFLP) followed by standard sequencing., Results: We found three types of genotype in rs8099917 of IL28B: wild-type TT in 60.0% of patients, heterozygous GT minor genotype in 36.2%, and GG in 3.8%. The frequency of the CC genotype of rs12979860 was 54.3%, CT was 37.1%, and TT was 8.6%. Overall, SVR was achieved in 68.6% of patients. A higher SVR was achieved for patients with the favorable genotype CC of rs12979860, with 84.2% as compared to 56.4% and 22.2% for minor genotype CT and TT, respectively (p=0.0001). We did not find a significant association for SVR to antiviral treatment in patients with genotype TT (rs8099917) (71.9%, p=0.36). The rapid virological response (RVR) rate was significantly higher in patients with major genotype TT (88.9%, p=0.04). These results show that IL28B polymorphism is highly associated with SVR to therapy in the Pakistani population infected with HCV genotype 3., Conclusions: HCV-infected patients carrying homozygous C/C have a higher chance of SVR. In addition, patients who carry T/T (rs8099917) have a higher chance of RVR., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)