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Background: Immunoglobulin A Nephropathy (IgAN) is a heterogeneous disorder. Multiple ethnicities conducted studies to assess the effectiveness of the Oxford classification of IgAN in prognostication. However, there is no study on the Pakistani population. We aim to identify its prognostic effectivity in our patients., Methods: We retrospectively reviewed the medical records of 93 biopsy-proven cases of primary IgAN. We collected the clinical and pathological data at baseline and on follow-ups. The median follow-up period was 12 months. We defined the renal outcome as a ≥ 50% decline in eGFR or end-stage renal disease (ESRD)., Results: Of 93 cases, 67.7% were males with a median age of 29. Glomerulosclerosis was the most prevalent lesion (71%). The median MEST-C was 3. On follow-up, median serum creatinine worsened from 1.92 to 2.2 mg/dL, and median proteinuria reduced from 2.3 g/g to 1.072 g/g. The reported renal outcome was 29%. T and C scores and MEST-C scores above 2 were significantly associated with pre-biopsy eGFR. On Kaplan-Meier analysis, the T and C scores' association was significant with the renal outcome (p-value 0.000 and 0.002). In univariate and multivariate analyses, the association of T-score (p-value 0.000, HR 4.691), total MEST-C score (p-value 0.019), and baseline serum creatinine (p-value 0.036, HR 1.188) were significant with the outcome., Conclusion: We validate the prognostic significance of the Oxford classification. T and C scores, baseline serum creatinine, and total MEST-C score significantly affect the renal outcome. Furthermore, we recommend the inclusion of the total MEST-C score in determining the IgAN prognosis., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background and Aims: Extracorporeal shock wave lithotripsy (ESWL) is performed to fragment large main pancreatic duct (MPD) stones in symptomatic patients. Subsequent endoscopic retrograde cholangiopancreatography (ERCP) is often performed to clear the stone fragments. Edema of surrounding tissue after ESWL theoretically affects the ability to perform ERCP. However, the optimal timing of ERCP after ESWL is not clearly defined. The aim of this study is to determine the efficacy and safety of same-day ERCP after ESWL and to determine if the timing of ERCP after ESWL affects outcomes., Methods: This is a retrospective study of consecutive patients from January, 2013 to September, 2019 who received ESWL for MPD stones at our center. Included patients received subsequent same-day ERCP under the same general anesthesia session or later session ERCP (1-30 days after ESWL). Demographics, anatomical findings, history, and outcomes were collected. Success was defined as complete or near complete (> 80%) stone fragmentation with clearance., Results: 218 patients were treated with ESWL and subsequent ERCP. 133 (61.0%) received ERCP on the same day immediately after ESWL, while 85 (39.0%) returned for ERCP at a later day (median 3.0 days after ESWL). Baseline characteristics demonstrated patients who received same-day ERCP had a higher rate of pain at baseline (94.7% vs 87.1%, p = 0.045). Main outcomes demonstrated an overall successful MPD stone clearance rate of 90.4%, with similar rates between same-day ERCP and later session ERCP (91.7% vs 88.2%, p = 0.394). Additionally, successful cannulation at ERCP, adverse events, and post-procedure admission rates were similar., Conclusions: Delaying ERCP to allow peripancreatic tissue recovery after ESWL does not affect outcomes. Same-day ERCP after ESWL is safe and effective., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction Obesity, a complex and multifactorial disease, is defined by a body mass index (BMI) greater than 30 kg/m². When the BMI exceeds 40 kg/m², it is classified as morbid obesity. This condition leads to excessive fat accumulation, which impairs normal body function and metabolism. For individuals grappling with morbid obesity and those who have faced significant hurdles in their quest for substantial weight loss, bariatric surgery emerges as a vital option. Purpose The study aims to explore the dynamics of bariatric surgical tourism in Pakistan, shedding light on factors influencing the choice of Pakistan as a destination for bariatric tourism. Materials and methods A retrospective cross-sectional study design was adopted. Data were gathered from the medical records database, including all patients who had undergone bariatric surgery from 2018 until 2022. The data collection process involved comprehensive patient outreach, where investigators conducted phone interviews and collected patient satisfaction assessments. During these phone interviews, valuable information was gathered by posing questions. These inquiries encompassed various aspects, including the patient's overall satisfaction with the surgical experience, their countries of origin, the specific bariatric procedures they underwent, the motivating factors behind their decision to travel abroad for surgery, their postoperative follow-up routines, and any complications they may have encountered. Results One hundred and nine patients traveled to Pakistan for bariatric surgery from 2018 to 2022. Out of 109 patients, 78 responded to the questionnaire by phone or email. The proforma was filled by 41 (52.5%) males and 37 (47.5%) females. Forty-seven (60.2%) of these patients underwent Roux-en-Y gastric bypass and 31 (39.8%) patients underwent sleeve gastrectomy. Out of 78 bariatric patients, 72 (92.3%) were satisfied with their surgery, five patients (6.4%) were neutral in their response and one patient (1.3%) was dissatisfied with the surgery. Most of the patients (26, 33.3%) declared money as the main driving force for traveling, with long waiting times being the close second reason (19, 24.36%) patients. Conclusion At least 2% of worldwide bariatric procedures are provided for medical tourists. Countries such as Mexico, India, Lebanon, and Romania dominate as providers for patients mainly from the USA, UK, and Germany. The lack of affordable bariatric healthcare and long waiting lists are some of the reasons for patients choosing bariatric tourism. The 92.3% satisfaction rate of patients with the surgery and its outcomes is a significant finding, as it suggests that bariatric surgery services provided in Pakistan are meeting or exceeding the expectations of international patients. The exceptionally high level of patient satisfaction speaks to the quality of care provided by the medical institutions in Pakistan. The data and analysis presented in this study shed light on the motivations and experiences of international patients traveling to Pakistan for bariatric surgery. These insights are invaluable for healthcare providers, policymakers, and the medical tourism industry as they seek to enhance the accessibility, affordability, and quality of healthcare services for domestic and international patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Bashir et al.)

Objective: To report clinical and radiological follow-up outcomes of stent-assisted coiling of wide-necked basilar tip aneurysms and to evaluate the safety and efficacy of this treatment choice., Methods: A retrospective review was carried out of 19 patients with wide-necked basilar tip aneurysms in our institution between 2010 and 2020. The rates of perioperative complication, morbidity, mortality, imaging follow-up and re-treatment were analysed., Results: Our technical complication rate was 11% but did not result in treatment failure. The combined procedure related morbidity and mortality rate of the 19 patients who underwent stent assisted coiling was also 11%. 16 of 19 patients had undergone angiographic follow-up with a mean period of 32 months. 81% of patients with angiographic follow-up had a satisfactory occlusion (RROI or II) with 11% requiring re-treatment. Those requiring re-treatment were both treated with laser-cut stents; this is in contrast with no re-treatments required in the patients treated with braided stents., Conclusion: Our report provides acceptable outcomes in wide-necked basilar termination aneurysms which are very challenging to treat. Aneurysms treated with braided stents had better efficacy outcomes than those with laser-cut stents., Advances in Knowledge: Given the emergent and increasing utility of alternative endovascular techniques such as intrasaccular devices and flow diverters, real-world data are lacking on more conventional approaches such stent-assisted coiling, especially so in the posterior circulation. The associated relatively higher aneurysmal haemorrhagic risk in this location warrants further additional safety and efficacy data for this treatment approach, which this paper provides.

FUSCA 3 (FUS3), a seed master regulator, plays critical role in seed dormancy and oil accumulation. However, its downstream regulation mechanisms remain poorly understood. Here, we explored the roles of AINTEGUMENTA-like 6 (AIL6), a seed transcription factor, in these processes. The activation of AIL6 by FUS3 was demonstrated by dual-LUC assay. Seeds of ail6 mutants showed alterations in fatty acid compositions, and both AtAIL6 (AIL6 from Arabidopsis thaliana) and BnaAIL6 (AIL6 from Brassica napus) rescued the phenotype. Over-expression (OE) of AIL6s reversed changes in seed fatty acid composition. Notably, OE lines showed low seed germination rates down to 12% compared to 100% of wild-type Col-0. Transcriptome analysis of the mutant and an OE line indicated widespread expression changes of genes involved in lipid metabolism and phytohormone pathways. In OE mature seeds, GA4 content decreased more than 15-fold, while abscisic acid and indole-3-acetic acid (IAA) contents clearly increased. Exogenous GA3 treatments did not effectively rescue the low germination rate. Nicking seed coats increased germination rates from 25% to nearly 80% while the wild-type rdr6-11 is 100% and 98% respectively, and elongation of storage time also improved seed germination. Furthermore, dormancy imposed by AIL6 was fully released in the della quintuple mutant. Together, our results indicate AIL6 acts as a manager downstream of FUS3 in seed dormancy and lipid metabolism., Competing Interests: Conflict of interest statement. The authors declare that there is no conflict of interest., (© American Society of Plant Biologists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Guidelines recommend respiratory fluoroquinolone monotherapy or β-lactam plus macrolide combination therapy as first-line options for hospitalized adults with mild-to-moderate community-acquired pneumonia (CAP). Efficacy of these regimens has not been adequately evaluated., Methods: A systematic review of randomized controlled trials (RCTs) comparing respiratory fluoroquinolone monotherapy and β-lactam plus macrolide combination therapy in hospitalised adults with CAP was performed. A meta-analysis was performed using a random effects model. The primary outcome was clinical cure rate. Quality of evidence (QoE) was evaluated using GRADE methodology., Results: A total of 4140 participants in 18 RCTs were included. Levofloxacin (11 trials) or moxifloxacin (6 trials) were the predominant respiratory fluoroquinolones evaluated, and the β-lactam plus macrolide group used ceftriaxone plus a macrolide (10 trials), cefuroxime plus azithromycin (5 trials), and amoxicillin/clavulanate plus a macrolide (2 trials). Patients receiving respiratory fluoroquinolone monotherapy had a significantly higher clinical cure rate (86.5% vs. 81.5%; odds ratio [OR] 1.47; 95% confidence interval [95% CI: 1.17-1.83]; P = 0.0008; I 2 = 0%; 17 RCTs; moderate QoE) and microbiological eradication rate (86.0% vs. 81.0%; OR 1.51 [95% CI: 1.00-2.26]; P = 0.05; I 2 = 0%; 15 RCTs; moderate QoE) than patients receiving β-lactam plus macrolide combination therapy. All-cause mortality (7.2% vs. 7.7%; OR 0.88 [95% CI: 0.67-1.17]; I 2 = 0%; low QoE) and adverse events (24.8% vs. 28.1%; OR 0.87 [95% CI: 0.69-1.09]; I 2 = 0%; low QoE] were similar in the two groups., Conclusion: Respiratory fluoroquinolone monotherapy demonstrated an advantage in clinical cure and microbiological eradication; however, it did not impact mortality., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

We explore how Arab adolescents enact critical consciousness to improve their lives and better their community. Eleven first- and second-generation Arab adolescents participated in a Photovoice study and were asked to reflect on and take photos that represented their well-being, daily life, and sense of belonging and community. The participants discussed their photos over multiple group reflection sessions. Thematic analysis highlights how Arab adolescents make positive change in their community, aided by their connections to community, their awareness of structural challenges they and their communities face, and their sense of agency to make positive change. We contribute to the literature by offering a window into the lived experiences of critical consciousness among Arab adolescents, an underrepresented group in the critical consciousness literature. We also add to the growing body of evidence that highlights the importance of "everyday activism" when considering social change actions., (© 2023 Wiley Periodicals LLC.)

Objective: The aim of the work described here was to measure the characteristics of viscoelasticity and fluidity in a mouse model of hepatic steatosis and inflammation using a nano-indentation test and the Kelvin-Voigt fractional derivative (KVFD) model and to explore the viscoelasticity and fluidity characteristics in mice with different degrees of hepatic steatosis with inflammation., Methods: Twenty-five ApoE mice were randomly divided into an experimental high-fat diet group (n = 15) and an ordinary-food control group (n = 10), then subdivided into four subgroups based on pathological degree of hepatic steatosis: S0 (normal), S1 (mild), S2 (moderate) and S3 (severe). The 25 liver specimens from these mice were evaluated by a slope-keeping relaxation nano-indentation test., Results: Elasticity (E 0 ) was significantly higher in the S3 group than in the S1 and S2 groups, while fluidity (α) and viscosity (τ) were significantly lower in S3 than in S1 and S2 (all p values < 0.05). The following cutoff values for the diagnosis of hepatic steatosis >33% with inflammation were also determined: E 0 > 85.01 Pa (area under the curve [AUC]: 0.917, 95% confidence interval [CI]: 0.735-0.989), α ≤ 0.38 (AUC: 0.885, 95% CI: 0.695-0.977),\ and τ ≤ 3.92 (AUC: 0.813, 95% CI: 0.607-0.939)., Conclusion: Increases in the degree of hepatic steatosis with inflammation in mice paralleled gradual increases in the stiffness of the liver and gradual decreases in the fluidity and viscosity of the liver., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Introduction: Acute necrotizing pancreatitis (ANP) complicates up to 15% of acute pancreatitis cases. ANP has historically been associated with a significant risk for readmission, but there are currently no studies exploring factors that associate with risk for unplanned, early (<30-day) readmissions in this patient population., Methods: We performed a retrospective review of all consecutive patients presenting to hospitals in the Indiana University (IU) Health system with pancreatic necrosis between December 2016 and June 2020. Patients younger than 18 years of age, without confirmed pancreatic necrosis and those that suffered in-hospital mortality were excluded. Logistic regression was performed to identify potential predictors of early readmission in this group of patients., Results: One hundred and sixty-two patients met study criteria. 27.7% of the cohort was readmitted within 30-days of index discharge. The median time to readmission was 10 days (IQR 5-17 days). The most frequent reason for readmission was abdominal pain (75.6%), followed by nausea and vomiting in (35.6%). Discharge to home was associated with 93% lower odds of readmission. We found no additional clinical factors that predicted early readmission., Conclusion: Patients with ANP have a significant risk for early (<30 days) readmission. Direct discharge to home, rather than short or long-term rehabilitation facilities, is associated with lower odds of early readmission. Analysis was otherwise negative for independent, clinical predictors of early unplanned readmissions in ANP., 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., (Published by Elsevier B.V.)

The invested effort and collaboration of clinicians and medical device companies to improve occlusion rates and clinical outcomes for patients with intracranial aneurysms treated via less invasive endovascular means led to the development of the concept of intrasaccular devices. Intrasaccular devices were introduced to offer simple treatment options, offering easier navigation through difficult anatomy, simpler and quicker deployment into large and wide-neck aneurysms. Additionally, they offer easier sizing, whilst offering a wide range of options suitable for aneurysms of different sizes. The concept of most intrasaccular devices is to occupy the aneurysm neck, however offering better stability than simple coiling, therefore increasing the chance of long-term aneurysm occlusion. This is achieved without a sizable metal content within the parent vessel, contrary to flow diverters, theoretically reducing the risk of thromboembolic events. This review aims to discuss the history and latest developments of intrasaccular intracranial devices, which offer an exciting and potentially successful option for treatment of complex intracranial aneurysms.

Hydroxysteroid dehydrogenase (HSDs) is an oil-body sterol protein (steroleosin) with an NADP(H) binding domain that belongs to the short-chain dehydrogenase/reductase (SDR) superfamily. There are numerous studies on the characterization of HSDs in plants. However, thus far, the evolutionary differentiation and divergence analysis of these genes remain to be explored. The current study used an integrated method to elucidate the sequential evolution of HSDs in 64 sequenced plant genomes. Analyses were conducted on their origins, distribution, duplication, evolutionary paths, domain functions, motif composition, properties, and cis-elements. Results indicate that except for algae, HSD1 was widely distributed in plant species ranging from lower to higher plants, while HSD5 was restricted to terrestrial plants, and HSD2 was identified in fewer monocots and several dicot plants. Phylogenetic analysis of HSD proteins revealed that monocotyledonous HSD1 in moss and ferns appeared closest to the outgroup, V. carteri HSD-like, M. musculus HSD1, and H. sapiens HSD1. These data support the hypothesis that HSD1 originated in bryophytes and then in non-vascular and vascular plants, followed by HSD5 only in land plants. Gene structure analysis suggests that HSDs in plant species came up with a fixed number of six exons, and the intron phase was primarily 0, 1, 0, 0, and 0. Similarly, duplication analysis revealed that segmental duplications were the main reason for HSDs in plant species. Physicochemical properties suggest that dicotyledonous HSD1s and HSD5s were mainly acidic. The monocotyledonous HSD1s and HSD2s and the dicotyledonous HSD2s, HSD3s, HSD4s, and HSD6s were mainly basic, implying that HSDs in plants may have a variety of functions. Cis -regulatory elements and expression analysis revealed that HSDs in plants might have roles in several abiotic stresses. Due to the high expression of HSD1s and HSD5s in seeds, these HSDs in plants may have roles in fatty acid accumulation and degradation., 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 © 2023 Saleem, Aziz, Ali, Liu, Alwutayd, Alshegaihi, Niedbała, Elkelish and Zhang.)

Inflammatory conditions play part in the progression of malignancies, and markers signifying growth of these factors can indicate prognosis. Neutrophil-to-lymphocyte (NLR) is used as a marker of subclinical inflammation that may become an integral part of workup to indicate prognosis and associated pathology. This study aims to explore the association of NLR ratio with clinical characteristics, radiological assessment and staging, histopathology, and disease outcomes of breast cancer. A retrospective cohort study was conducted in a tertiary care center to include breast cancer patients that were diagnosed between January 2001 and December 2020. Data including tumor size, lymph nodes, metastasis, histological grading, ER/PR/HER2-neu status, molecular subtypes, clinical staging); nodal findings (sentinel and axillary); pathology from frozen section; and disease outcomes were assessed. Multivariable regression and Kaplan-Meier survival curves were employed to indicate the association of NLR with breast cancer features and disease-free survival. A total of 2050 patients had a median age of 50 years, median NLR levels of 2.14, most common pathology ductal followed by lobular, and most common site of metastasis being lungs followed by bones. Disease-free rate was 7.6%, and a recurrence rate of 1.8%, while 1.6% deaths were reported. NLR was found associated with age, treatment outcomes, tumor size, lymph nodes, metastasis and clinical staging. Other positive correlations were with Ki67 proliferation index, molecular subtypes, and tumor size on frozen section (at transverse and craniocaudal dimensions). Negative correlations were seen with estrogen and progesterone receptors. However, NLR was not found predictable of disease-free survival (P = .160). Significant predictors of disease-free survival were histological grading, ER, PR status, molecular subtype, and Ki67 proliferation index. NLR being a readily available marker has shown novel findings in its association with tumor staging, disease outcomes and characteristics of breast malignancy., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Speech enhancement (SE) reduces background noise signals in target speech and is applied at the front end in various real-world applications, including robust ASRs and real-time processing in mobile phone communications. SE systems are commonly integrated into mobile phones to increase quality and intelligibility. As a result, a low-latency system is required to operate in real-world applications. On the other hand, these systems need efficient optimization. This research focuses on the single-microphone SE operating in real-time systems with better optimization. We propose a causal data-driven model that uses attention encoder-decoder long short-term memory (LSTM) to estimate the time-frequency mask from a noisy speech in order to make a clean speech for real-time applications that need low-latency causal processing. The encoder-decoder LSTM and a causal attention mechanism are used in the proposed model. Furthermore, a dynamical-weighted (DW) loss function is proposed to improve model learning by varying the weight loss values. Experiments demonstrated that the proposed model consistently improves voice quality, intelligibility, and noise suppression. In the causal processing mode, the LSTM-based estimated suppression time-frequency mask outperforms the baseline model for unseen noise types. The proposed SE improved the STOI by 2.64% (baseline LSTM-IRM), 6.6% (LSTM-KF), 4.18% (DeepXi-KF), and 3.58% (DeepResGRU-KF). In addition, we examine word error rates (WERs) using Google's Automatic Speech Recognition (ASR). The ASR results show that error rates decreased from 46.33% (noisy signals) to 13.11% (proposed) 15.73% (LSTM), and 14.97% (LSTM-KF)., Competing Interests: Enter: The authors have declared that no competing interests exist., (Copyright: © 2023 Peracha et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The complete impact of COVID-19 infection continues to develop since the onset of the COVID-19 pandemic. COVID-19 cholangiopathy has been recently described in a subset of patients who recovered from severe COVID-19 infection. The most common phenotype of patients suffering from COVID-19 cholangiopathy had severe infection requiring a stay in the intensive care unit, mechanical ventilation and vasopressor medications. Patients with COVID-cholangiopathy present with severe and prolonged cholestatic liver injury. In cases where biliary cast formation is identified, we defined the entity as "COVID-19 cast-forming cholangiopathy". This subset of COVID-19 cholangiopathy is not well understood and there are no standardized diagnosis or management to this date. The reported clinical outcomes are variable, from resolution of symptoms and liver test abnormalities to liver transplant and death. In this commentary, we discuss the proposed pathophysiology, diagnosis, management, and prognosis of this disease., Competing Interests: Yara Sarkis and Nasir Saleem are co-primary authors. Dr Mark Gromski is a consultant for Boston Scientific, received research support from Olympus and Cook Medical, outside the submitted work; None of the authors disclose a conflict of interest relative to this work., (© 2023 Sarkis et al.)

An incredible eradication of thermal indulgence is required to enhance the flow and heat transfer enhancement in micro/nanofluidic devices. In addition, the rapid transport and instantaneous mixing of colloidal suspensions of metallic particles at nanoscale are exceptionally crucial at ascendency of inertial and surface forces. To address these challenges, the present work is intended to investigate the role of trimetallic nanofluid comprising of three kinds of nano-sized granules (titanium oxide, Silica and Aluminium dioxide) with pure blood through a heated micropump in the presence of inclined magnetic field and axially implemented electric field. To ensure rapid mixing in unidirectional flow, the pump internal surface is lined-up with mimetic motile cilia with slip boundary. The embedded cilia whip in pattern due to dynein molecular motion controlled by time and produce a set of metachronal waves along the pump wall. The shooting technique is executed to compute the numerical solution. In a comparative glance it is revealed that the trimetallic nanofluid exhibits 10% higher heat transfer efficiency as compared to bi-hybrid and mono nanofluids. Moreover, the involvement of electroosmosis results in almost 17% decrease in the heat transfer rate if it values jumps from 1 to 5. The fluid temperature in case of trimetallic nanofluid is higher and thus keeps the heat transfer entropy and the total entropy lower. Furthermore, involvement of thermal radiated and momentum slip significantly contribute in reducing heat losses., (© 2023. The Author(s).)

Background: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality. Corticosteroids may be a beneficial adjunct in the treatment of bacterial pneumonia., Research Question: Is there any benefit of corticosteroid therapy in the management of bacterial CAP among patients requiring hospitalization?, Study Design and Methods: PubMed, Cochrane Library, and Embase were searched to identify randomized controlled trials assessing the use of systemic corticosteroids compared with standard care in the management of CAP. A systematic review, meta-analysis, and Trial Sequential Analysis (TSA) were performed. The primary outcome was all-cause mortality. Secondary outcomes included ICU admission, mechanical ventilation, treatment failure, readmission, and adverse events. Data are presented as risk ratio (RR) with 95% CI, P value, heterogeneity (I 2 ), and TSA-adjusted CIs., Results: Sixteen trials met the eligibility criteria. All-cause mortality (16 studies [3,842 patients]; RR, 0.85 [95% CI, 0.67-1.07]; P = .17; I 2  = 14%; TSA-adjusted CI, 0.61-1.09), ICU admission (six studies [2,619 patients]; RR, 0.66 [95% CI, 0.45-0.97]; P = .04; I 2  = 0%; TSA-adjusted CI, 0.37-1.12), treatment failure (six studies [2,093 patients]; RR, 0.78 [95% CI, 0.37-1.67]; P = .52; I 2  = 68%; TSA-adjusted CI, 0.02-25.5), and the incidence of adverse events (six studies [2,487 patients]; RR, 1.10 [95% CI, 0.97-1.25]; P = .14; I 2  = 53%; TSA-adjusted CI, 0.82-2.41) were similar between patients receiving corticosteroids and patients assigned to the control group. The need for mechanical ventilation (eight studies [1,457 patients]; RR, 0.51 [95% CI, 0.33-0.77]; P = .001; I 2  = 0%; TSA-adjusted CI, 0.20-0.85) was lower among patients receiving corticosteroids compared with those receiving standard care. However, corticosteroid use may be associated with higher rates of hospital readmission (five studies [2,853 patients]; RR, 1.20 [95% CI, 1.05-1.38]; P = .008; I 2  = 0%; TSA-adjusted CI, 0.89-1.98)., Interpretation: Corticosteroid therapy is associated with a lower incidence of progression to requiring mechanical ventilation among patients hospitalized with CAP. No association was found between corticosteroid therapy and mortality, treatment failure, or adverse events., Trial Registry: PROSPERO; No.: CRD42021279359; URL: https://www.crd.york.ac.uk/prospero/., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Doxycycline has been recommended as a treatment option for non-severe community-acquired pneumonia (CAP) in adults. We sought to review the evidence for the efficacy of doxycycline in adult patients with mild-to-moderate CAP., Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) of doxycycline versus comparator to assess the clinical efficacy. The primary outcome was the clinical cure rate. Random effects model meta-analyses were used to generate pooled odds ratio (OR) and evaluate heterogeneity (I2). Risk of bias (RoB) and quality of evidence (QoE) were evaluated using the Cochrane Risk of Bias 2.0 tool and GRADE methods, respectively., Results: We included 6 RCTs with 834 clinically evaluable patients. The trials were performed between 1984 and 2004. Comparators were 3 macrolides (roxithromycin, spiramycin, and erythromycin) and 3 fluoroquinolones (ofloxacin, fleroxacin, and levofloxacin). Four trials had an overall high RoB. The clinical cure rate was similar between the doxycycline and comparator groups (87.2% [381/437] vs 82.6% [328/397]; OR 1.29 [95% confidence interval {CI}: .73-2.28]; I2 = 30%; low QoE). Subgroup analysis of two studies with a low RoB showed significantly higher clinical cure rates in the doxycyline group (87.1% [196/225] vs 77.8% [165/212]; OR 1.92 [95% CI: 1.15-3.21]; P = .01; I2 = 0%). Adverse event rates were comparable between the doxycycline and comparator groups., Conclusions: The efficacy of doxycycline was comparable to macrolides or fluoroquinolones in mild-to-moderate CAP and thus represents a viable treatment option. Considering the lack of recent trials, it warrants large-scale clinical trials., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

For prevention against SARS-CoV-2, various vaccines have been approved globally including Pfizer, Sinopharam, Moderna, Johnson & Johnson etc which have proved quite effective. To evaluate the immunization and safety of Sinopharm vaccine in cancer patients. A prospective study was conducted in the Oncology Department of Nishtar Medical Hospital, Multan from March 2021- September 2021. A total of 150 cancer patients undergoing treatment were included in the study. All the patients were administered 0.5 ml Sinopharm vaccine with 28 day difference between the two doses. A two-month follow-up was done to test the immunization using ELISA kits. Among all the patients, 16 patients (10.7%) had a history of COVID-19 before the administration of the vaccine. At the time of vaccination, 23.3% of patients were seropositive. After the vaccination, 130 patients (86.7%) developed immunity against the infection. 30.6% of participants developed a fever and 20.9% had fatigue. Other side effects were also observed including pain, redness, swelling, itching, chills, anorexia, nausea, vomiting, myalgia and diarrhea. Sinopharm vaccine is effective and safe for patients with malignancies especially in patients receiving radiaton therapy but still recommended for older patients and patients receiving chemotherapy.

Background: Age-related complex medical conditions have been commonly reported among adolescents and young adults with advanced life-limiting illness. There is increasing interest in exploring their palliative care needs and end-of-life experiences., Aim: This scoping review aimed to explore the available literature about providing palliative and end-of-life care to adolescents and young adults with advanced life-limiting illnesses., Design: Scoping review. This review was registered on Open Science Framework (https://doi.org/10.17605/OSF.IO/SPTD7)., Data Sources: Electronic databases (MEDLINEALL, Embase, Emcare, Cochrane Central Register of Controlled Trial CENTRAL, Scopus, PsycINFO, Cochrane Database of Systematic Reviews), Google Scholar and reference lists were searched up to October 2021. We included studies reporting on adolescents and/or young adults with advanced life-limiting illnesses. There were no limitations concerning location, type of illness or study design., Results: We identified 51 studies published between 2002 and 2021. Most studies were published in the United States ( n  = 34, 67%), and nine studies (18%) reported exclusively on patients with non-malignant illnesses. Two thirds of the identified studies were case reports and retrospective chart reviews ( n  = 33). Three main topics were identified: Physical symptom burden ( n  = 26, 51%), Psychological and social needs ( n  = 33, 65%), and end-of-life care ( n  = 30, 59%). Twenty-six studies (51%) were focused only on one topic, and the age range used to identify adolescents and young adults varied based on the study location., Conclusion: The findings of this review shed light on the different palliative care experiences and knowledge gaps related to adolescents and young adults as an underserved and vulnerable patient population. Further research needs to be dedicated toward palliative care programs tailored for adolescents and young adults.

Background Acute appendicitis remains the most common cause of lower abdominal pain leading to emergency visits. Even though the standard treatment of acute appendicitis remains appendectomy, in recent times, multiple randomized control trials and meta-analyses have deduced conservative treatment as a successful alternative treatment. During the coronavirus disease (COVID) pandemic, with a shortage of staff and resources, treatment with conservative management of uncomplicated acute appendicitis became very beneficial under certain circumstances and conditions. This study aimed to assess whether it is effective to manage patients with uncomplicated acute appendicitis with antibiotic therapy. Methodology This was a single hospital based retrospective, cross-sectional study from Jan 2015 to May 2020. Patients with clinical and radiological features of uncomplicated acute appendicitis with Alvarado's score >6 were included in the study. Patients were kept on antibiotics, intravenous fluids, and analgesia as part of a conservative regime. Those who failed to respond to conservative therapy were managed surgically. The follow-up period was six months. Results One hundred eighty-two cases of uncomplicated acute appendicitis were included and managed conservatively, of which 52.2% were males while 47.8% were females. The median age of the patients was 26 years. Conservative treatment was successful in 26.2% of the patients, with a recurrence of 5.5% in the six-month follow-up period. The mean number of days of hospital stay was three days in patients treated with conservative or surgical treatment. Conclusion Conservative management is gaining popularity, and many centers are inclined towards non-operative management; however, appendectomy remains the gold standard treatment for appendicitis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Akbar et al.)

BACKGROUND Renal transplant recipients are susceptible to increased mortality with COVID-19 infection. There is insufficient data regarding risk factors for COVID-19 disease acquisition. We aimed to identify them here. MATERIAL AND METHODS We enrolled Pakistani renal transplant recipients from February 10, 2020, to March 18, 2021, and actively tracked their baseline health status, transplant characteristics, comorbidities, immunosuppressive therapies, and post-transplant follow-ups until September 2021. Furthermore, we formulated 2 questionnaires for their compliance assessment with COVID-19-preventive measures. We also identified COVID-19 disease acquisition, symptomatology, and management. RESULTS Among the 50 enrolled patients, 14 (28%) patients developed COVID-19, which is higher than the incidence observed in general Pakistani population (0.55%). Their mean age was 35.38 years ±11.69 SD years, and 82% of patients were males. The following factors were independently associated with COVID-19 disease: female gender (P value: 0.042), diabetes mellitus (P value: 0.002), anti-thymocyte globulin (ATG) induction (P value: 0.006), in-person follow-ups (P value: 0.000), prolonged immediate and late post-transplant hospital stays (P value: 0.019 and 0.000, respectively), raised post-transplant serum creatinine (P value: 0.019), and COVID-19 protective measures non-compliance (P value: 0.000). Out of 14 infected recipients, 92.85% required symptomatic management and overall mortality was 0%. CONCLUSIONS Female gender, diabetes mellitus, ATG induction, in-person follow-ups, prolonged hospital stays, raised post-transplant serum creatinine, and COVID-19-protective measures non-compliance were associated with the higher acquisition of SARS-CoV-2 infection. By taking concrete measures against these risk factors, we can continue renal transplants, as overall mortality was lower than in the general Pakistani population (2%).

Salt stress obstructs plant's growth by affecting metabolic processes, ion homeostasis and over-production of reactive oxygen species. In this regard silicon (Si) has been known to augment a plant's antioxidant defense system to combat adverse effects of salinity stress. In order to quantify the Si-mediated salinity tolerance, we studied the role of Si (200 ppm) applied through rooting media on antioxidant battery system of barley genotypes; B-10008 (salt-tolerant) and B-14011 (salt-sensitive) subjected to salt stress (200 mM NaCl). A significant decline in the accumulation of shoot (35-74%) and root (30-85%) biomass was observed under salinity stress, while Si application through rooting media enhancing biomass accumulation of shoots (33-49%) and root (32-37%) under salinity stress. The over-accumulation reactive oxygen species i.e., hydrogen peroxide (H 2 O 2 ) is an inevitable process resulting into lipid peroxidation, which was evident by enhanced malondialdehyde levels (13-67%) under salinity stress. These events activated a defense system, which was marked by higher levels of total soluble proteins and uplifted activities of antioxidants enzymatic (SOD, POD, CAT, GR and APX) and non-enzymatic (α-tocopherol, total phenolics, AsA, total glutathione, GSH, GSSG and proline) in roots and leaves under salinity stress. The Si application through rooting media further strengthened the salt stressed barley plant's defense system by up-regulating the activities of enzymatic and non-enzymatic antioxidant in order to mitigate excessive H 2 O 2 efficiently. The results revealed that although salt-tolerant genotype (B-10008) was best adopted to tolerate salt stress, comparably the response of salt-sensitive genotype (B-14011) was more prominent (accumulation of antioxidant) after application of Si through rooting media under salinity stress.

This study aimed to determine the percentage of anti-phospholipase A2 receptor (PLA2R) autoantibody positivity in a cross-section of 74 Pakistani patients with biopsy-proven idiopathic membranous nephropathy. It was an observational study conducted from December 2018 to June 2019. Seventy-four (n=74) consecutive biopsy-proven cases of membranous nephropathy, aged between 12-60 years, were included. Out of them, 63.5% (n=47) were males and 36.5% (n=27) were females. The mean age was 40.2±16.7 years. Anti-PLA2R antibodies were positive in 35 (47.3%) patients, negative in 38 (51.4%) patients, and borderline positive in 1(1.35%) patient. A significant difference (p ≤ 0.05) was noted among different levels of antibodies in both genders. Anti-PLA2R antibodies were detected in approximately half of the diagnosed idiopathic membranous nephropathy cases. However, this percentage was much lower than the studies conducted on other populations around the globe, indicating a possible pathogenic role of other antigens in our population. Key Words: Membranous nephropathy, Phospholipase A2 receptors, Renal biopsy.

Background: Bactericidal antibiotics are generally assumed to be superior to bacteriostatic antibiotics as first-line treatment for pneumonia., Objectives: We performed a systematic review, meta-analysis, and trial sequential analysis (TSA) of randomized controlled trials (RCTs) of bactericidal versus bacteriostatic antibiotics to ascertain clinical superiority. Clinical cure rate was the primary outcome. Secondary outcomes included all-cause mortality, microbiological eradication, treatment failure, and relapse rates., Data Sources: PubMed, Cochrane Library, Embase, and MedRxiv STUDY ELIGIBILITY CRITERIA: Randomized control trials., Particiapants: Adult patients with bacterial pneumonia treated with antibiotics in the community or in-hospital., Interventions: Bacteriostatic versus bactericidal antibiotics., Assessment of Risk of Bias: The Cochrane Collaboration assessing risk of bias 2 tool., Methods of Data Synthesis: Data on dichotomous outcomes are presented as risk ratio (RR). A random-effects model with the generic Mantel-Haenszel method was used for integrating RRs for generalizability of findings. The I 2 method was used to assess the magnitude of variation secondary to heterogeneity., Results: Forty-three RCTs involving 10 752 patients met the eligibility criteria. The clinical cure rate (42 studies, 10 312 patients; RR: 1.02; 95% CI, 0.99-1.05; I 2 : 37%; TSA-adjusted CI, 0.99-1.05), all-cause mortality (25 studies, 8302 patients; RR: 1.07; 95% CI, 0.81-1.42; I 2 : 57%), microbiological eradication (24 studies, 2776 patients; RR: 1.00; 95% CI, 0.97-1.03; I 2 : 0%), treatment failure (31 studies, 7296 patients; RR: 0.96; 95% CI, 0.83-1.11; I 2 : 42%), and relapse rate (5 studies, 1111 patients; RR: 1.15; 95% CI, 0.50-2.63; I 2 : 0%) were similar between bactericidal and bacteriostatic antibiotic treatments., Conclusions: Bactericidal agents are not associated with any statistical difference in clinical cure rates, mortality, microbiological eradication, treatment failure, or relapse rates compared with bacteriostatic antibiotics in the treatment of pneumonia., (Copyright © 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Tomato is an important part of daily food, rich source of multitude nutrients, suitable candidate for bio-pharmaceutical production due to berry size and has numerous health benefits. Transcriptional regulation of metalloregulatory heat shock protein-70 family plays pivotal role in plants tolerance against abiotic stress factors including salinity, heat, cold, drought and trace metal elements such as cadmium (Cd2+)., Methods: Here, we provide comprehensive report on in-silico identification of SlHsp70 family genes in tomato ( Solanum lycopersicum ) and their expression in tomato via qPCR analysis under broad range of trace metal elements., Results: In-silico analysis revealed 23 SlHsp70 family genes in tomato, phylogenetically divided into four groups I-IV and displayed expression in all tissues. Gene Ontology (GO) analysis revealed that SlHSP70 proteins were membrane localized which were involved in metal ions translocation and oxidoreductase activity to counter hyper-accumlation of reactive oxygen species (ROS)., Conclusions: Cd2+ is a widespread heavy metal soil contaminent which is continously polluting fertile soils, a knotty issue which has serious implications over photosynthesis, nitrogen assimilation, minerals and water absorption by plants. Plants exposure to Cd2+ and subsequent qRT-PCR analysis revealed increased expression of SlHsp70-11 in tomato roots, which can be employed in breeding low Cd2+ enriched tomato varieties., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

Purpose: Dural arteriovenous fistulas (dAVF) account for approximately 10-15% of all intracranial arteriovenous abnormalities. dAVFs carry a significant risk of mortality, particularly in cases of acute hemorrhage, of up to 10%. A small proportion of these dAVFs are found in the anterior cranial fossa (ACF), of which the rate of hemorrhage can be as high as up to 91%. The Scepter Mini (SM) is the smallest dual-lumen micro-balloon (MB) available for neurointerventional practice. It consists of a 2.8 French outer diameter, with a 2.2 mm × 9 mm semi-compliant balloon providing a working length of 165 cm. The SM is navigated with a 0.008-inch wire making it a particularly attractive tool accessible to the pedicles normally reached with liquid embolization micro-catheters., Methods: Five consecutive patients over a 1-year period between 2020 and 2021 were evaluated and treated for ACF dAVF using a liquid embolization approach using the SM balloon. All patients were treated using ethylene-vinyl alcohol copolymer (EVOH), of which Squid 18 and/or Squid 12 were the chosen viscosities. Control angiograms were performed for all patients post-embolization., Results: All patients demonstrated complete occlusion of the ACF dAVF on immediate post-treatment angiography. No immediate complications were encountered; particularly, there were no reports of visual field deficit in any of the patients., Conclusion: The MB is a valuable adjunctive tool that can enhance the safety and efficacy of trans-ophthalmic embolization of ACF dAVFs, providing additional protection to the retinal and posterior ciliary arteries against unwanted reflux of liquid embolic agent., (© 2022. Crown.)

Human Leukocyte Antigens (HLA) matching at the serological level used to serve as the measure of histocompatibility between organ donors and recipients. With advancements in HLA typing methods more precise HLA mismatch assessment tools were developed to measure dissimilarities at the molecular level, collectively referred to as Molecular Mismatch load analysis tools. Currently, several software are aimed at deciphering the dissimilarities using somewhat different immunologic rationales. Our goal, in this review is to provide a basic overview of the different computational approaches, provide clinical cases to contextualize concerns regarding the lack of assessment of immunogenicity, and present our personal view regarding the gaps and the needs of our field., 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 © 2022 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Drought is a major environmental threat that affects plant growth and productivity. Strategies to mitigate the detrimental impacts of drought stress on plants are under scrutiny. Nanotechnology is considered an effective tool in resolving a wide range of environmental issues by offering novel and pragmatic solutions. A pot experiment was performed to determine the efficacy of zinc oxide nanoparticles (ZnO NPs) as a foliar application (25 mg L -1 and 100 mg L -1 ) on the growth performance of cucumber subjected to drought stress. Applied ZnO NPs under normal conditions resulted in significant growth and biomass enhancement while reducing drought-induced decline. Photosynthetic pigments, photosynthesis, and PSII activity enhanced due to ZnO NPs application, attaining maximal values at 100 mg L -1 of ZnO NPs. Drought stress restricted growth and biomass buildup in cucumber seedlings by stimulating oxidative stress, which was manifested to excessive buildup of reactive oxygen species (ROS) and peroxidation, thereby decreasing membrane functioning. Plants exposed to ZnO NPs exhibited a reduction in ROS accumulation and lipid peroxidation. The substantial reduction in oxidative damage was manifested with the enhancement of enzymatic and non-enzymatic antioxidant components. The phenol and mineral contents were reduced due to drought stress. In addition, the content of proline, glycine betaine, free amino acids, and sugars increased due to ZnO NPs under normal and drought conditions. Furthermore, the drought-induced decline in the content of phenol and mineral nutrients was mitigated by ZnO NPs foliar application. These findings reveal that exogenous ZnO NPs application may be a pragmatic option in dealing with the drought stress of cucumber seedlings., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To determine if local flap coverage is functionally compatible of digital defects., Study Design: Observational study., Place and Duration of Study: Department of Plastic and Reconstructive Surgery, Fauji Foundation Hospital, Rawalpindi, from January 2017 to June 2019., Methodology: Patients with small and medium skin defects on digits were included. Data was collected for both independent and dependent variables, emphasising on functional outcome based on five parameters (adequate coverage of the defect, functional length of the digit, painless scar, finger-tip sensation, and inter-phalangeal joint motion). Follow-up was done for six months., Results: Total number of patients included in the study was 96, with 45 male and 51 female patients. Mean age of study participants was 26.6 ± 16.9 years. Small to medium size defects were included in the study for coverage by local flaps like cross figure, lateral proximal phalanx, flag, thenar, homo-digital flaps etc. Results were studied in terms of functional outcomes. All the five parameters were achieved in 84 (87.5%) patients. Complications were observed in 10 (10.4%) patients. The most frequent complication was wound infection, which was observed in 2 (2.1%) patients., Conclusion: Local flaps for finger defects are a very effective way of providing durable soft tissue coverage. Key Words: Digital defects, Digital reconstruction, Local flaps for digits, Hand injuries.

Objective: To determine the effects of Pilates exercises on pain, knee range of motion and functional disability in women with knee osteoarthritis., Methods: The double-blind randomised controlled trial was conducted at the National Orthopaedic Hospital, Bahawalpur, Pakistan, from April to September 2018, and comprised female patients with knee osteoarthritis. The subjects were selected and randomised into control group A receiving isometrics and intervention group B receiving Pilates exercises. Both groups received one-hour sessions 3 times per week for 8 weeks. The groups were assessed at baseline and at the end of the 8th week using numeric pain rating scale and Western Ontario and McMaster Universities osteoarthritis index for pain and functionality level respectively. Data was analysed using SPSS 23., Results: Of 44 patients, there were 22(50%) in each of the two groups. Mean age of group B was 57.60±6.34 years, and it was 55.65±7.28 in group B. Mean body mass index of group B was 25.812±4.16, and it was 26.93±4.4 in group A. The study was completed by 40(91%) patients; 20(50%) in each of the two groups. Both groups showed significant improvement for pain, range of motion and physical function post-intervention (p<0.05). Group B showed significantly more improvement in terms of pain and physical function compared to group A (p<0.05)., Conclusions: Pilates exercises were found to be more effective in the treatment of patients with knee osteoarthritis., Trial Registration Number: Chi CTR 2000030486.

Background: Head circumference (HC) measurement is a significant measure of brain volume. It is also considered a powerful predictor in the evaluation of developmental and neurological disorders in children. This study aims to develop smoothed reference curves for HC of the Pakistani children of age 6 to 18 years., Methods: A cross-sectional dataset, consisting of 9194 school-going children of age 6-18 years, were obtained using a multi-ethnic anthropometric survey. For the measurement of HC (cm), the standard procedure was adopted. For both sexes, the smoothed centile curves of HC were developed by using the lambda-mu-sigma (LMS) statistical approach. Moreover, we compared our 50th percentile curves to those produced for few other countries., Results: The centiles curves of both sexes indicated that the HC increased with age. Until the age of 10 years, the boys had larger HC percentiles than those of the girls. From the age of 11 years, upper percentiles (90th, 95th and 97th) of the girls were higher than those of the boys. The comparison of our 50th percentile data for the HC with the data from the United States (US) and Turkish children revealed that the Pakistani children of both genders had smaller head sizes in all ages when compared to those reported for the latter stated countries., Conclusions: Our results show the larger disparity of HC percentiles in different countries. This comprehensive study suggests that the references from the US Centers for Disease Control and Prevention data and other populations are not suitable for Pakistani children. Therefore, each country is required to create its own HC reference curves, separately.

Results: A total of 264 obese and 133 normal BMI women (controls) of age range 20-50 years were selected. Obese women had significantly lower vitamin D compared to control women ( P < 0.05). Among euglycemic (fasting glucose < 100 mg/dl) obese women ( n = 221), 90 (40.7%) were vitamin D deficient. Serum PTH and calcium levels were negatively correlated, though nonsignificantly with vitamin D ( r = -0.172, P = 0.090, and r = -0.051, P = 0.557, respectively). The mean age, BMI, waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), fasting glucose, fasting insulin, PTH, and calcium were not significantly different in vitamin D-deficient as compared to nondeficient obese women. IR was detected in 109 (49.3%) obese women. Mean HOMA-IR in vitamin D-deficient women was significantly higher than that in the nondeficient obese women (3.03 ± 1.64 vs. 2.40 ± 1.02; P = 0.041), but the percentage of women with IR was comparable in both groups (51.1% vs. 45.8%; P = 0.745). Univariate analysis revealed that HOMA-IR was negatively correlated with vitamin D and positively with BMI and PTH. A multivariate regression analysis, stepwise method revealed that BMI and PTH were independent determinants of HOMA-IR instead of vitamin D., Conclusion: More than 40% of obese women were vitamin D deficient. Among euglycemic obese women, 49% were insulin resistant. Prevalence of insulin resistance, though negatively correlated with vitamin D, could be better explained by BMI and PTH levels., Competing Interests: The authors have no competing financial interest., (Copyright © 2021 Nazish Saleem et al.)

Objective: The objective of this study was to evaluate feasibility of supplementing emergency department (ED) concussion discharge instructions for adolescents and parents with a newly created educational comic and a publicly available comic-based video at an outpatient sports neurology clinic., Methods: We created a gender-neutral, 2-page comic to augment text-only ED concussion discharge instructions. A sample of patients evaluated at a sports neurology clinic and their parents/guardians participated. Patients and their parents were randomized to view either the comic only or both the comic and publicly available comic-based video. Patients and parents completed preintervention and postintervention surveys to assess likeability and concussion knowledge including concussion definition, symptoms, return-to-ED criteria, and resuming normal activity. Data were analyzed using descriptive and comparative statistics., Results: A total of 57 patients (47.4% female; mean age, 15 years) and 37 guardians were enrolled. Most (73%) concussions were sports related, with the majority having sought care within 24 hours in an ED (80%). Over half (51%) had experienced 2 or more prior concussions. Overall, 31 adolescents and 20 guardians viewed both comic and video, whereas 26 adolescents and 17 guardians viewed the comic only. Both comic and video were favorably reviewed, but a higher proportion of respondents rated the video more positively than the comic for likability (P < 0.01), comprehensibility (P < 0.05), and increasing understanding (P < 0.05). Patients' knowledge of some concussion symptoms emphasized in the comic increased after reading (emotional changes, P = 0.02; vomiting, P = 0.04)., Conclusions: Patients showed increased concussion knowledge using the favorably endorsed comic-based discharge instructions. Using comic-based supplemental discharge tools may optimize concussion education for adolescents., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: Empiric esophageal dilation is frequently performed for non-obstructive dysphagia. Studies evaluating its efficacy have reported conflicting results. In this meta-analysis, we have evaluated the efficacy of esophageal dilation in the management of non-obstructive dysphagia., Methods: We reviewed several databases from inception to 26 May 2021 to identify randomized controlled trials (RCTs) and observational studies that evaluated the role of empiric esophageal dilation for non-obstructive dysphagia. Our outcomes of interest were clinical success (improvement in dysphagia after dilation) and difference in post-operative dysphagia score between groups. For categorical variables, we calculated pooled odds ratios (OR) with 95% confidence intervals (CI); for continuous variables, we calculated standardized mean difference (SMD) with 95% CI. Data were analyzed using a random effects model. We used GRADE framework to ascertain the quality of evidence., Results: We included 4 studies (3 RCTs and one observational) with 243 patients; there were 133 treated with empiric dilation and 110 controls. We found no significant difference in clinical success (OR (95% CI) 1.91 (0.89, 4.08)) or post-procedure dysphagia score between groups (SMD (95% CI) 0.38 (-0.37, 1.14)). Our findings remained consistent on subgroup analysis including RCTs only. Quality of evidence ranged from low to very low based on GRADE framework., Conclusions: Our meta-analysis does not support the use of empiric esophageal dilation in patients with non-obstructive dysphagia. More studies are required to confirm these findings.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies, particularly those preventing interaction between the viral spike receptor-binding domain and the host angiotensin-converting enzyme 2 receptor, may prevent viral entry into host cells and disease progression., Methods: We performed a systematic review, meta-analysis, trial sequential analysis (TSA), and meta-regression of RCTs to evaluate the benefit of convalescent plasma for COVID-19. The primary outcome was 28-30 day mortality. Secondary outcomes included need for mechanical ventilation and ICU admission. Data sources were PubMed, Embase, MedRxiv, and the Cochrane library on July 2, 2021., Results: We identified 17 RCTs that recruited 15 587 patients with 8027 (51.5%) allocated to receive convalescent plasma. Convalescent plasma use was not associated with a mortality benefit (24.7% vs 25.5%; odds ratio [OR]=0.94 [0.85-1.04]; P=0.23; I 2 =4%; TSA adjusted confidence interval [CI], 0.84-1.05), or reduction in need for mechanical ventilation (15.7% vs 15.4%; OR=1.01 [0.92-1.11]; P=0.82; I 2 =0%; TSA adjusted CI, 0.91-1.13), or ICU admission (22.4% vs 16.7%; OR=0.80 [0.21-3.09]; P=0.75; I 2 =63%; TSA adjusted CI, 0.0-196.05). Meta-regression did not reveal association with titre of convalescent plasma, timing of administration, or risk of death and treatment effect (P>0.05). Risk of bias was high in most studies., Conclusions: In patients with COVID-19, there was no clear mortality benefit associated with convalescent plasma treatment. In patients with mild disease, convalescent plasma did not prevent either the need for mechanical ventilation or ICU admission., Clinical Trial Registration: CRD42021234201 (PROSPERO)., (Copyright © 2021 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

In cardiac muscle cells adrenergic agonists stimulate the generation of reactive oxygen species, followed by redox signaling. We postulated that the antagonists would attenuate such reactive oxygen species generation by the agonists. H9c2 cardiac myoblasts, neonatal rat cardiac myocytes, and HEK293 cells expressing β 1 /β 2 adrenoceptors were stimulated with several agonists and antagonists. All the agonists and antagonists independently generated reactive oxygen species; but its generation was minimum whenever an agonists was added together with an antagonist. We monitored the Ca++ signaling in the treated cells and obtained similar results. In all treatment sets, superoxide and H 2 O 2 were generated in the mitochondria and the cytosol respectively. NOX2 inhibitor gp91ds-tat blocked reactive oxygen species generation by both the agonists and the antagonists. The level of p47phox subunit of NOX2 rapidly increased upon treatment, and it translocated to the plasma membrane, confirming NOX2 activation. Inhibitor studies showed that the activation of NOX2 involves ERK, PI3K, and tyrosine kinases. Recombinant promoter-reporter assays showed that reactive oxygen species generated by both the agonists and antagonists modulated downstream gene expression. Mice injected with the β-adrenergic agonist isoproterenol and fed with the antagonist metoprolol showed a robust induction of p47phox in the heart. We conclude that both the agonism and antagonism of adrenoceptors initiate redox signaling but when added together, they mutually counteract each other's effects. Our study thus highlights the importance of reactive oxygen species in adrenoceptor agonism and antagonism with relevance to the therapeutic use of the β blockers., (Copyright © 2021. Published by Elsevier B.V.)