α-Cleavage of 2,2-Diazido-2,3-dihydroinden-1-one in Solution and Cryogenic Matrices.

The Norrish type I (α-cleavage) reaction is an excellent photochemical method for radical-pair formation in solution. However, in cryogenic matrices, the starting material typically re-forms before the radical pair diffuses apart. This study focused on N2 extrusion from an azido alkyl radical to prevent radical-pair recombination. Irradiation of 2,2-diazido-2,3-dihydroinden-1-one (1) in methanol mainly yielded methyl 2-cyanomethylbenzoate (2) and 2-cyanomethylbenzoic acid (3) via α-cleavage. Laser flash photolysis of 1 in argon-saturated acetonitrile resulted in α-cleavage to form triplet biradical 31Br1 (λmax ∼ 410 nm, τ ∼ 400 ns). In contrast, upon irradiation in glassy 2-methyltetrahydrofuran matrices, triplet alkylnitrene 31N was directly detected using electron spin resonance (D/hc = 1.5646 cm-1, E/hc = 0.00161 cm-1) and absorption spectroscopy (λmax = 276 and 341 nm). Irradiation of 1 in argon matrices generated 31N, benzoyl azide 4, singlet benzoylnitrene 14N, and isocyanide 5, as revealed by IR spectroscopy. The experimental results supported by density functional theory calculations [B3PW91/6-311++G(d,p)] suggest that irradiation of 1 in matrices results in α-cleavage to form biradical 31Br1, which extrudes N2 to yield 31Br2. Rearrangement of 31Br2 into 31N competes with cleavage of a N3 radical to form radical 1Ra3. The N3/1Ra3 radical pair combines to form 4, which upon irradiation yields 14N and 5.

Morbidity and Mortality Following Surgery for Pancreatic Cancer in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Measuring postoperative outcomes after complex cancer operations such as pancreatectomy is vital to improve cancer surgery in low- and middle-income countries (LMICs); however, such data is often limited. This study aimed to review existing research and obtain baseline estimates for postoperative mortality and morbidity after pancreatic cancer surgery in LMICs. METHODS: PubMed, Embase, Web of Science Core Collection, and Global Index Medicus were systematically searched for original articles published between January 2005 and May 2022. LMICs based studies reporting postoperative mortality, morbidity, and/or length of stay of patients with primary pancreatic tumors undergoing pancreaticoduodenectomy and/or distal pancreatectomy were included. RESULTS: Of 18 344 unique titles and abstracts retrieved, 114 studies met the inclusion criteria. Of these, 51 "good" quality studies comprising 7528 patients were included in the meta-analyses. Pooled estimates for pancreatic fistula were 16.6% (95% CI 14.0-19.7, p < 0.001); 16.0% (95% CI 11.1-22.5, p < 0.001) for Clavien-Dindo grade 3 and 4 complications; 13.4% (95% CI 9.8-17.9, p < 0.001) for wound infection; and 4.4% (95% CI 3.3-5.7, p < 0.001) for postoperative mortality. CONCLUSION: This is the first systematic review and meta-analysis examining surgical complications after pancreatic surgery in LMICs. We highlight a lack of data and the need to further evaluate surgical outcomes in LMICs.

The environment under the knife: A review of current Eco-surgical strategies and recommendations for Pakistan.

The healthcare sector at its core is based on the fundamentals belief to do no harm and bring about betterment in the lives of the people. Paradoxically, hospitals are one of the leading contributors to pollution, greenhouse gas (GHG) emissions and toxic waste material worldwide. Surgical care delivery is quite resource intensive, consuming significant amount of energy and equipment as well as producing large quantities of waste. With climate change being a global priority, it is crucial that hospitals re-evaluate the environmental impact of such practices. The current review was planned to identify areas of improvement in surgical care in terms of sustainability, as well as describe efficient and innovative strategies for hospitals in Pakistan to lessen their impact on the environment. The implementation of the 5 R's strategy for surgical care (Reduce, Reuse, Recycle, Rethink and Research) as well as general measures to improve energy efficiency, waste management and inter-sectoral collaboration will provide significant benefits to the environment and advance efforts to creating a more sustainable future for surgical healthcare in Pakistan.

COVID-19 and fertility-at the crossroads of autoimmunity and thrombosis.

The SARS-CoV-2 virus is known to mediate attack via ACE-2 Receptor, thus having adverse effects on cardiovascular, respiratory, digestive and reproductive systems, the latter being an area of emerging concern, due to the associated impact on fertility, with potential for an outsized effect on population distribution and socioeconomic road map in subsequent years. This narrative review aims to put forth the current evidence of effect of SARS-CoV-2 on human fertility from a multipronged immunologic, haematologic, and gynaecologic perspective; highlighting the areas of contradiction and potential future measures. A literature search was conducted through the MEDLINE and SCOPUS databases to identify articles on the subject in English. Relevant information was extracted from around 300 articles for this review. The existing data give non-conclusive evidence about the impact of SARS-CoV-2 infection on fertility; however, a greater impact on male fertility as compared to females merits further exploration. However, reproduction and fertility is a key concern and considering the pandemic is prolonged, natural conception or ART require extra precautions.

COVID-19, hydroxychloroquine and sudden cardiac death: implications for clinical practice in patients with rheumatic diseases.

Sudden cardiac death is commonly seen due to arrhythmias, which is a common cardiac manifestation seen in COVID-19 patients, especially those with underlying cardiovascular disease (CVD). Administration of hydroxychloroquine (HCQ) as a potential treatment option during SARS-CoV-2, initially gained popularity, but later, its safe usage became questionable due to its cardiovascular safety, largely stemming from instances of cardiac arrhythmias in COVID-19. Moreover, in the setting of rheumatic diseases, in which patients are usually on HCQ for their primary disease, there is a need to scale the merits and demerits of HCQ usage for the treatment of COVID-19. In this narrative review, we aim to address the association between usage of HCQ and sudden cardiac death in COVID-19 patients. MEDLINE, EMBASE, ClinicalTrials.gov and SCOPUS databases were used to review articles in English ranging from case reports, case series, letter to editors, systematic reviews, narrative reviews, observational studies and randomized control trials. HCQ is a potential cause of sudden cardiac death in COVID-19 patients. As opposed to the reduction in CVD with HCQ in treatment of systemic lupus erythematous, rheumatoid arthritis, and other rheumatic diseases, safe usage of HCQ in COVID-19 patients is unclear; whereby, it is observed to result in QTc prolongation and Torsades de pointes even in patients with no underlying cardiovascular comorbidity. This is occasionally associated with sudden cardiac death or cardiac arrest; hence, its clinical efficacy needs further investigation by large-scale clinical trials.

Plagiarism in Non-Anglophone Countries: a Cross-sectional Survey of Researchers and Journal Editors.

BACKGROUND: Plagiarism is one of the most common violation of publication ethics, and it still remains an area with several misconceptions and uncertainties. METHODS: This online cross-sectional survey was conducted to analyze plagiarism perceptions among researchers and journal editors, particularly from non-Anglophone countries. RESULTS: Among 211 respondents (mean age 40 years; M:F, 0.85:1), 26 were scholarly journal editors and 70 were reviewers with a large representation from India (50, 24%), Turkey (28, 13%), Kazakhstan (25, 12%) and Ukraine (24, 11%). Rigid and outdated pre- and post-graduate education was considered as the origin of plagiarism by 63% of respondents. Paraphragiarism was the most commonly encountered type of plagiarism (145, 69%). Students (150, 71%), non-Anglophone researchers with poor English writing skills (117, 55%), and agents of commercial editing agencies (126, 60%) were thought to be prone to plagiarize. There was a significant disagreement on the legitimacy of text copying in scholarly articles, permitted plagiarism limit, and plagiarized text in methods section. More than half (165, 78%) recommended specifically designed courses for plagiarism detection and prevention, and 94.7% (200) thought that social media platforms may be deployed to educate and notify about plagiarism. CONCLUSION: Great variation exists in the understanding of plagiarism, potentially contributing to unethical publications and even retractions. Bridging the knowledge gap by arranging topical education and widely employing advanced anti-plagiarism software address this unmet need.

Surgical Education and Training during the COVID-19 Pandemic: Strategies and Solutions for Pakistan.

The coronovirus disease-2019 pandemic has severely impacted surgical education and training in Pakistan and worldwide, causing problems, such as risk of infection, limited hands-on training, examination delays, and trainee redeployment to non-surgical specialties. The current review was planned to describe innovative strategies adopted by surgical training programmes worldwide in order to suggest comprehensive recommendations at the level of the College of Physicians and Surgeons Pakistan and individual institutions to counter the challenges presented by the pandemic in Pakistan. The innovative use of technology, including open-access online educational portals, virtual educational activities and simulation-based learning, can help reform education delivery during the pandemic. Hospitals' implementation of "shift schedules" for rotations helps continue training while minimising risks. Moreover, examination boards and residency programmes must appropriately tailor their eligibility criteria and assessment processes to the current situation. Lastly, it is vital to safeguard trainees' mental wellness during the pandemic and after by ensuring readily available professional psychological support when needed.

Case report: severe hypertrophic cardiomyopathy in a female neonate caused by de novo variant in NDUFB11.

Background: Hypertrophic cardiomyopathy in the neonate has a diverse genetic background, and non-sarcomeric variants may not be identified on commercial genetic testing panels. NDUFB11 is an X-linked mitochondrial Complex I protein and is known to cause histiocytoid cardiomyopathy but has not been described in female infants with hypertrophic cardiomyopathy. We present this first reported case of obstructive hypertrophic cardiomyopathy in a female neonate secondary to a pathogenic variant in NDUFB11. Case summary: A term female neonate presented following a prenatal diagnosis of biventricular hypertrophy and growth restriction. She developed lactic acidosis after birth and whole-genome sequencing identified a de novo variant in the mitochondrial Complex I gene, NDUFB11 (c.391G>A, p.Glu131Lys). There was progression of left ventricular hypertrophy and obstruction, with rapid development of heart failure symptoms. She was unresponsive to beta-blocker medical therapy and was not suitable for advanced mechanical support. There was subsequent clinical deterioration resulting in death by 3 months of age. Discussion: Hemizygous variants in NDUFB11 have been associated with hypertrophic cardiomyopathy in male infants previously, and skewed X-linked inactivation likely resulted in the presentation described here in a female infant. This variant was not identifiable by commercial cardiomyopathy panels. We highlight the importance of rapid whole-genome sequencing in cases of infantile hypertrophic cardiomyopathy and the importance of genetic diagnosis in guiding prognosis and care for these individuals.

Cohort study investigating evolution and factors associated with dyspnoea after anatomic lung resection.

Background: Dyspnoea is common following surgical resection for non-small cell lung cancer (NSCLC). The effects range from reduced quality of life to impact on adjuvant therapy outcomes. Currently, dyspnoea beyond the immediate postoperative phase and risk factors are not well characterised. We hope to assess the evolution of patient-reported dyspnoea after anatomic lung resection and associated factors. Methods: Single-centre cohort study with analysis on data collected longitudinally of 131 patients undergoing anatomic lung resections for NSCLC between September 2014 and December 2018. The European Organization for Research and Treatment Lung Cancer-specific Quality of Life Questionnaire Dyspnoea Scale was used to measure dyspnoea before and after surgery. Multivariable regression analysis was used to identify factors associated with clinically meaningful perioperative changes in dyspnoea at 6-12 months. Results: Mean Dyspnoea Scale scores preoperatively and 6-12 months after resection were 12.6 (standard deviation 17.4) and 17.9 (standard deviation 20.5), respectively. Of all patients 31% experienced a clinically meaningful increase in dyspnoea, defined as >10 points between Dyspnoea Scale scores preoperatively and at 6-12 months. Comparatively, 71% of patients without preoperative symptoms of dyspnoea developed a clinically meaningful increase of dyspnoea postoperatively. After adjusting the analysis for baseline factors and preoperative Dyspnoea Scale score, female sex remained the only patient factor associated with increased postoperative dyspnoea at 6-12 months after surgery (P=0.046). A total of 34% of patients reported increased dyspnoea after lobectomies and 9% after segmentectomies (P=0.014). Segmentectomy (as opposed to larger resections) was the only surgical factor associated with lower risk of increased dyspnoea (P=0.057). Conclusions: A clinically meaningful increase in dyspnoea is frequent after lung resection. Postoperative evolution of dyspnoea is non-predictable using objective baseline factors highlighting the importance of patient reported symptoms and involvement in clinical consultation.

Increased minute ventilation-to-carbon dioxide slope during cardiopulmonary exercise test is associated with poor postoperative outcome following lung cancer resection.

OBJECTIVES: Ventilatory efficiency [minute ventilation-to-carbon dioxide output slope (VE/VCO2 slope)] can be measured at sub-maximal workload during cardiopulmonary exercise test. The aim of this study is to assess the association between VE/VCO2 slope and outcome after lung cancer resections. METHODS: Retrospective, single-centre analysis on all patients undergoing lung resection for cancer (April 2014-August 2022) and with a preoperative cardiopulmonary exercise test. VE/VCO2 slope >40 was chosen as high-risk threshold. Logistic regression analysis was used to test the association of VE/VCO2 slope and several patient- and surgery-related factors with 90-day mortality. RESULTS: A total of 552 patients were included (374 lobectomies, 81 segmentectomies, 55 pneumonectomies and 42 wedge resections). Seventy-four percent were minimally invasive procedures. Cardiopulmonary morbidity was 32%, in-hospital/30-day mortality 6.9% and 90-day mortality 8.9%. A total of 137 patients (25%) had a slope of >40. These patients were older (72 vs 70 years, P = 0.012), had more frequently coronary artery disease (17% vs 10%, P = 0.028), lower carbon monoxide lung diffusion capacity (57% vs 68%, P < 0.001), lower body mass index (25.4 vs 27.0 kg/m2, P = 0.001) and lower peak VO2 (14.9 vs 17.0 ml/kg/min, P < 0.001) than those with a lower slope. The cardiopulmonary morbidity among patients with a slope of >40 was 40% vs 29% in those with lower slope (P = 0.019). Ninety-day mortality was 15% vs 6.7% (P = 0.002). The 90-day mortality of elderly patients with slope >40 was 21% vs 7.8% (P = 0.001). After adjusting for peak VO2 value, extent of operation and other patient-related variables in a logistic regression analysis, VE/VCO2 slope retained a significant association with 90-day mortality. CONCLUSIONS: VE/VCO2 slope was strongly associated with morbidity and mortality following lung resection and should be included in the functional algorithm to assess fitness for surgery.

Self-reported dyspnoea and shortness of breathing deterioration in long-term survivors after segmentectomy or lobectomy for early-stage lung cancer.

OBJECTIVES: The aim of this study was to assess the self-reported current dyspnoea and perioperative changes of dyspnoea in long-term survivors after minimally invasive segmentectomy or lobectomy for early-stage lung cancer. METHODS: Cross-sectional telephonic survey of patients alive and disease-free as of March 2023, with pathologic stage IA1-2, non-small-cell lung cancer, assessed 1-5 years after minimally invasive segmentectomy or lobectomy (performed from January 2018 to January 2022). Current dyspnoea level: Baseline Dyspnoea Index score <10. Perioperative changes of dyspnoea were assessed using the Transition Dyspnoea Index. A negative Transition Dyspnoea Index focal score indicates perioperative deterioration in dyspnoea. Mixed effect models were used to examine demographic, medical and health-related correlates of current dyspnoea and changes in dyspnoea level. RESULTS: A total of 152 of 236 eligible patients consented or were available to respond to the telephonic interview(67% response rate): 90 lobectomies and 62 segmentectomies. The Baseline Dyspnoea Index score was lower (greater dyspnoea) in lobectomy patients (median 7, interquartile range 6-10) compared to segmentectomy (median 9, interquartile range 6-11), P = 0.034. 70% of lobectomy patients declared to have a current dyspnoea vs 53% after segmentectomy, P = 0.035. 82% of patients after lobectomy reported a perioperative deterioration in their dyspnoea compared to 57% after segmentectomy, P = 0.002. Mixed effect logistic regression analysis adjusting for patient-related factors and time elapsed from operation showed that segmentectomy was associated with a reduced risk of perioperative dyspnoea deterioration (as opposed to lobectomy) (Odds ratio (OR) 0.31, P = 0.004). CONCLUSIONS: Our findings may be valuable to inform the shared decision-making process by complementing objective data on perioperative changes of pulmonary function.

Necrotizing Infection of the Breast: A Case Report on a Rare Presentation of Breast Carcinoma.

Necrotizing infection (NI) of the breast associated with underlying malignancy is a rare phenomenon characterized by necrosis of breast parenchyma, causing a delay in diagnosis and even leading to sepsis. We present a case of a 42-year-old female with NI of the right breast while on homeopathic treatment for a right breast lump for six months. Tissue culture showed a polymicrobial infection and histopathology established the diagnosis of breast carcinoma. After treating the NI, her breast cancer was managed as per standard guidelines.

A Comprehensive Assessment of Blood Transfusions in Elective Thyroidectomy Based on 180,483 Patients.

OBJECTIVES: To assess the incidence, risk factors, and complications of blood transfusions (BTs) in elective thyroidectomy patients. METHODS: A retrospective cohort study was conducted using the American College of Surgeons National Surgical Quality Improvement Program. Adult patients who underwent elective thyroidectomy from 2005 to 2019 were divided into two cohorts based on whether they received BT or not. Multivariable binary logistic regression models were used to identify risk factors of BT and its impact on postoperative complications. RESULTS: Of 180,483 patients, 0.13% received BT. Risk factors for BT included underweight body mass index (BMI) (adjusted odds ratio [OR] 3.179, 95% confidence interval [CI] 1.444-6.996), bleeding disorders (OR 2.121, 95% CI 1.149-3.913), anemia (OR 4.730, 95% CI 3.472-6.445), preoperative transfusion (OR 7.230, 95% CI 1.454-35.946), American Society of Anesthesiology physical statuses 3-5 (OR 3.103, 95% CI 2.143-4.492), operative time >150 min (OR 4.390, 95% CI 1.996-9.654), and inpatient thyroidectomy (OR 5.791, 95% CI 3.816-8.787). In addition, transfusion was independently associated with any postoperative complication, non-infectious, cardiac, pulmonary, renal, vascular, or infectious complications, surgical site infection, sepsis, septic shock, wound disruption, pneumonia, unplanned reoperation, prolonged length of stay, and mortality. CONCLUSION: Recognition of risk factors of BT is imperative to identify at-risk patients and reduce transfusions by controlling modifiable risk factors such as anemia, operative time, and BMI. In cases where transfusions are still indicated, surgeons should optimize care to prevent or adequately manage transfusion-associated complications. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:2078-2084, 2022.

Application in medicine: Has artificial intelligence stood the test of time.

ABSTRACT: Artificial intelligence (AI) has proven time and time again to be a game-changer innovation in every walk of life, including medicine. Introduced by Dr. Gunn in 1976 to accurately diagnose acute abdominal pain and list potential differentials, AI has since come a long way. In particular, AI has been aiding in radiological diagnoses with good sensitivity and specificity by using machine learning algorithms. With the coronavirus disease 2019 pandemic, AI has proven to be more than just a tool to facilitate healthcare workers in decision making and limiting physician-patient contact during the pandemic. It has guided governments and key policymakers in formulating and implementing laws, such as lockdowns and travel restrictions, to curb the spread of this viral disease. This has been made possible by the use of social media to map severe acute respiratory syndrome coronavirus 2 hotspots, laying the basis of the "smart lockdown" strategy that has been adopted globally. However, these benefits might be accompanied with concerns regarding privacy and unconsented surveillance, necessitating authorities to develop sincere and ethical government-public relations.

SARS-CoV-2: Has artificial intelligence stood the test of time.

ABSTRACT: Artificial intelligence (AI) has proven time and time again to be a game-changer innovation in every walk of life, including medicine. Introduced by Dr. Gunn in 1976 to accurately diagnose acute abdominal pain and list potential differentials, AI has since come a long way. In particular, AI has been aiding in radiological diagnoses with good sensitivity and specificity by using machine learning algorithms. With the coronavirus disease 2019 pandemic, AI has proven to be more than just a tool to facilitate healthcare workers in decision making and limiting physician-patient contact during the pandemic. It has guided governments and key policymakers in formulating and implementing laws, such as lockdowns and travel restrictions, to curb the spread of this viral disease. This has been made possible by the use of social media to map severe acute respiratory syndrome coronavirus 2 hotspots, laying the basis of the "smart lockdown" strategy that has been adopted globally. However, these benefits might be accompanied with concerns regarding privacy and unconsented surveillance, necessitating authorities to develop sincere and ethical government-public relations.

Heterologous expression, molecular studies and biochemical characterization of a novel alkaline esterase gene from Bacillus thuringiensis for detergent industry.

Present study was aimed to clone and express the esterase encoding gene from Bacillus thuringiensis in E. coli BL21. Purification of recombinant esterase enzyme was achieved up to 48.6 purification folds by ion exchange chromatography with specific activity of 126.36 U mg-1. Molecular weight of esterase enzyme was 29 kDa as measured by SDS-PAGE. Purified esterase enzyme showed stability up to 90% at 90 °C and remained stable in a wide pH range (8-11). Molecular docking strengthens the experimental results by showing the higher binding energy with p-NP-butyrate. Enzyme activity was found to be reduced by EDTA but enhanced in the presence of other metal ions. Enzyme activity was reduced with 1% SDS, PMSF, and urea but organic solvents did not show considerable impact on it even at higher concentrations. Purified recombinant esterase was also found to be compatible with commercial laundry detergents and showed very good stability (up to 90%). All these properties proved the esterase enzyme from B. thuringensis a significant addition in detergent industry.