Misoprostol for non-alcoholic steatohepatitis: a randomised control trial.

INTRODUCTION: The management of non-alcoholic steatohepatitis (NASH) is an unmet clinical need. Misoprostol, a structural analogue of naturally occurring prostaglandin E1, has been reported to decrease proinflammatory cytokine production and may have a potential role in treating NASH. We aimed to evaluate the efficacy and safety of misoprostol in treating patients with NASH. METHODS: In this phase 2, double-blind, randomised, placebo-controlled trial, patients with NASH were randomly assigned in a 1:1 ratio to receive 200 µg of misoprostol or placebo thrice daily for 2 months. The primary endpoint was an improvement in liver function tests (LFTs), interleukin-6 (IL-6) and endotoxin levels. The secondary endpoint was improvement in insulin resistance, dyslipidaemia, hepatic fibrosis and hepatic steatosis. RESULTS: A total of 50 patients underwent randomisation, of whom 44 (88%) were males. The age range was 25-64 years (mean±SE of mean (SEM) 38.1±1.4). 19 (38%) patients had concomitant type 2 diabetes mellitus. 32 (64%) patients were either overweight or obese. At the end of 2 months' treatment, a reduction in total leucocyte count (TLC) (p=0.005), alanine aminotransferase (ALT) (p<0.001), aspartate aminotransferase (AST) (p=0.002) and controlled attenuation parameter (CAP) (p=0.003) was observed in the misoprostol group, whereas placebo ensued a decline in ALT (p<0.001), AST (p=0.018), gamma-glutamyl transferase (GGT) (p=0.003), CAP (p=0.010) and triglycerides (p=0.048). There was no diminution in insulin resistance, hepatic fibrosis (elastography) and dyslipidaemia in both groups. However, misoprostol resulted in a significant reduction in CAP as compared with the placebo group (p=0.039). Moreover, in the misoprostol group, pretreatment and post-treatment IL-6 and endotoxin levels remained stable, while in the placebo group, an increase in the IL-6 levels was noted (p=0.049). Six (12%) patients had at least one adverse event in the misoprostol group, as did five (10%) in the placebo group. The most common adverse event in the misoprostol group was diarrhoea. No life-threatening events or treatment-related deaths occurred in each group. CONCLUSION: Improvement in the biochemical profile was seen in both misoprostol and placebo groups without any statistically significant difference. However, there was more improvement in steatosis, as depicted by CAP, in the misoprostol group and worsening of IL-6 levels in the placebo group. TRIAL REGISTRATION NUMBER: NCT05804305.

NCPbook: A comprehensive database of noncanonical peptides.

Noncanonical peptides (NCPs) are a class of peptides generated from regions previously thought of as noncoding, such as introns, 5' UTRs, 3' UTRs, and intergenic regions. In recent years, the significance and diverse functions of NCPs have come to light, yet a systematic and comprehensive NCP database remains absent. Here, we developed NCPbook (https://ncp.wiki/ncpbook/), a database of evidence-supported NCPs, which aims to provide a resource for efficient exploration, analysis, and manipulation of NCPs. NCPbook incorporates data from diverse public databases and scientific literature. The current version of NCPbook includes 180,676 NCPs across 29 different species, evidenced by MS, ribosome profiling, or molecular experiments. These NCPs are distributed across kingdoms, comprising 123,408 from 14 plant species, 56,999 from 7 animal species, and 269 from 8 microbial species. Furthermore, NCPbook encompasses 9,166 functionally characterized NCPs playing important roles in immunity, stress resistance, growth, and development. Equipped with a user-friendly interface, NCPbook allows users to search, browse, visualize, and retrieve data, making it an indispensable platform for researching NCPs in various plant, animal, and microbial species.

Association Between Raja Isteri Pengiran Anak Saleha Appendicitis (RIPASA) Scoring and Pathological Severity of Acute Appendicitis: A Cross-Sectional Study.

Background and objectives Appendicitis is a frequent cause of abdominal pain. Because of the limited availability of imaging services in many medical centers and an urge to reduce the substantial number of unnecessary appendectomies, several clinical diagnostic tools have been constructed. A novel diagnostic tool, referred to as the Raja Isteri Pengiran Anak Saleha Appendicitis (RIPASA) score, has been created to assist in identifying acute appendicitis (AA) in Asian nations. The study aimed to assess the correlation between RIPASA scores and the severity of appendicitis as determined by pathological examination. Materials and methods The study was a prospective observational investigation undertaken in the Department of General Surgery at Muslim education society (MES) Medical College Perinthalmanna over 12 months. The study included all patients who had been diagnosed with AA and underwent appendectomy, provided they satisfied both the inclusion and exclusion criteria. An analysis was conducted on a convenience sample of 225 individuals using a prestructured proforma. The RIPASA scores were estimated before their surgery, taking into account their age, gender, symptoms, physical examination findings, and laboratory findings. These scores were subsequently contrasted with the histopathological results obtained after the appendectomy. The individuals were categorized into three groups according to their RIPASA scores. The lower-score category, scores between 4 and 7. The intermediate-score category consists of scores ranging from 7.5 to 11.5, while the higher-score category includes scores of 12 and above. These scores are correlated with the histopathology report (HPR) to determine the presence of appendicitis, perforated appendix, appendicular abscess, or the absence of pathology observed. Results The study population comprised of 137 (60.9%) males and 88 (39.1%) females. Among these, 177 individuals (78.7%) were younger than 40 years, while 48 individuals (21.3%) were older than 40 years. Out of 225 cases, 146 cases were AA (64.9%), 27 (12%) appendicular abscess cases, and 41 (18.2%) appendicular perforation cases. The normal appendix was noted in 11 out of 225 cases in the low-score group. The association between the histopathological report and RIPASA score was found to be statistically highly significant (p=0.000). In the low-score group, there were 14 cases of appendicitis (53.8%), one case of appendicular abscess (3.8%), a total of 11 cases without pathology observed (42.3%), and no reported instances of appendicular perforation. In the intermediate-score category, there were 121 cases of appendicitis (89.6%), 12 cases of appendicular abscess (8.9%), 2 cases of appendicular perforation (1.5%), and no reported cases in the non-pathology category. Among the high-score category, there were 11 cases of appendicitis (17.2%), 14 cases of appendicular abscess (21.9%), 39 cases of appendicular perforation (60.9%), and no reported instances of negative appendectomy. Conclusion The study has shown that the RIPASA scoring system had a high diagnostic efficacy in identifying AA. This scoring system is an effective, dependable, cost-effective, noninvasive, reproducible, and safe diagnostic technique that does not require additional expenses or concerns.

Clinical, Histopathological, and Radiological Profile of Patients Presenting With Thyroid Malignancies Among the Kerala Population.

BACKGROUND AND OBJECTIVE: Thyroid cancer, though relatively uncommon among all cancer types, stands as the primary form of endocrine tumor. Over the last 20 years, there has been a significant uptick in its occurrence. Papillary thyroid carcinoma (PTC), which is well-differentiated, emerges as the dominant subtype, in regions where iodine levels are deemed adequate. The study aimed to study the clinicopathological profile of patients diagnosed with thyroid malignancies at the Muslim Educational Society (MES) Medical College Perinthalmanna. MATERIALS AND METHODS: This is a retrospective study undertaken at the MES Medical College by the Department of General Surgery and Endocrine Surgery. The study focuses on patients who have been diagnosed with thyroid cancer through a biopsy. Case sheets of all those patients diagnosed with thyroid malignancy were referred from the Medical Records Library to collect the relevant medical and sociodemographic data. This data was entered in the proforma, which was transferred to the Excel sheet and processed in IBM SPSS Statistics for Windows, Version 20 (Released 2011; IBM Corp., Armonk, New York, United States). RESULTS: The study included predominantly middle-aged individuals (40-60 years), with 22 (55%) falling within this age range, followed by 14 (35%) aged between 20 and 40 years, and only four (10%) above 60 years. Female patients constituted 82.5% of the study group. Most cases presented with swelling lasting less than six months 23 (57.5%), while only four (10%) had swelling lasting more than five years. Compression symptoms were rare, with only three (7.5%) experiencing dysphagia or dyspnea. Pain was reported in two (5%) of the cases. Hypothyroidism, toxic manifestations, or hoarseness were observed in one (2.5%) of the patients. Regarding swelling characteristics, most were greater than 4 cm in size (29, 72%) and firm in consistency (25, 62.5%). Nodular surfaces were present in 19 (47.5%) of the cases, while 38 (95%) of the swellings were mobile. Palpable lymph nodes were noted in 13 (32.5%) of cases. Radiologically, hypoechoic lesions were observed in 26 (65%) of cases, with microcalcification in 29 (72.5%) and peripheral vascularity in 31 (77.5%). Papillary carcinoma was the most common histological type (34, 85%), with medullary and follicular carcinomas accounting for five (12.5%) and one (2.5%), respectively. An association was found between the duration of swelling and histological type (p = 0.05) and between the mobility of swelling and histological type (p < 0.05). However, no significant associations were observed between imaging findings and histological type (p > 0.05). The gender distribution did not show a statistically significant association with histological type. CONCLUSION: The findings of the study revealed a statistically insignificant association between age, gender, clinical features, and the histological type of thyroid malignancy. Additionally, there was no statistically significant association between the histological type of thyroid malignancy and the size or type of surface or consistency of thyroid swelling or ultrasonographic findings of the swelling like echogenicity, microcalcification, increased peripheral vascularity, or loss of peripheral halo.

Fabrication of curcumin-loaded oleogels using camellia oil bodies and gum arabic/chitosan coatings for controlled release applications.

This study has explored the potential of plant-derived oil bodies (OBs)-based oleogels as novel drug delivery systems for in vitro release under simulated physiological conditions. To obtain stable OBs-based oleogels, gum arabic (GA) and chitosan (CH) were coated onto the curcumin-loaded OBs using an electrostatic deposition technique, followed by 2,3,4-trihydroxybenzaldehyde (TB) induced Schiff-base cross-linking. Microstructural analyses indicated successful encapsulation of curcumin into the hydrophobic domain of the OBs through a pH-driven method combined with ultrasound treatment. The curcumin encapsulation efficiency of OBs increased up to 83.65 % and 92.18 % when GA and GA-CH coatings were applied, respectively, compared to uncoated OBs (63.47 %). In addition, GA-CH coatings retained the structural integrity of oleogel droplets with superior oil-holding capacity (99.07 %), while TB addition induced interconnected 3D-network structures with excellent gel strength (≥4.8 × 105 Pa) and thermal stability (≥80 °C). GA-CH coated oleogels appeared to provide the best protection for loaded bioactive against UV irradiation and high temperature-induced degradation during long-term storage. The combination of biopolymer coatings and TB-induced Schiff-base cross-linking synergistically hindered the simulated gastric degradability of oleogels, releasing only 23.35 %, 12.46 % and 7.19 % of curcumin by GA, GA-CH and GA-CH-TB stabilized oleogels, respectively, while also resulting in sustained release effects during intestinal conditions.

Outcomes of patients with elevated pulmonary artery systolic pressure on echocardiography due to chronic lung diseases.

BACKGROUND: Pulmonary hypertension is associated with increased mortality, and lung diseases are the second most common cause of pulmonary hypertension. We aimed to evaluate the prognostic value of echocardiography in low-middle income countries where right heart catheterization is difficult to perform. METHODS: This retrospective chart review study included adult patients hospitalized from June 2012 to May 2021, with a pulmonary artery systolic pressure (PASP) of ≥35 mmHg on echocardiography. The control arm consisted of patients with similar lung diseases who did not have an elevated PASP. RESULTS: The study and control arm consisted of 128 patients each, with both groups having similar lung diseases. Obesity hypoventilation syndrome was the most common etiology of elevated PASP (28.1 %), followed by pulmonary embolism (20.3 %). The overall 1-year mortality of the study cohort, after diagnosis of elevated PASP, was 20.3 %. The control cohort with normal PASP had a 1-year mortality of 4.7 %. In the study cohort, patients with bronchiectasis had the highest cause-specific 1-year mortality (45.5 %). In the normal PASP cohort, the highest cause-specific 1-year mortality was observed in patients with interstitial lung disease (13.0 %). One-year hospital readmission was observed in 46.9 % and 33.6 % of patients in the study and control arms, respectively. On multivariate analysis, increased odds of 1-year mortality were observed in patients with elevated PASP, patients with 1-year hospital readmission, and in patients with interstitial lung disease or bronchiectasis. CONCLUSION: Elevated PASP on echocardiography may be a prognostic factor for mortality in patients with chronic lung diseases.

Laparoscopic Versus Open Inguinal Hernia Repair: A Comparative Study.

BACKGROUND: Inguinal hernia is a common surgical problem around the world. The two types of groin hernias are femoral hernias and direct and indirect inguinal hernias. The incidence rate is higher among males. This investigation intends to differentiate between open and laparoscopic methods of inguinal hernia surgery with respect to operative time, seroma formation, duration of hospitalization, and return to normal activity. MATERIALS AND METHODS: This prospective observational study included 84 patients with unilateral, bilateral, direct, and indirect inguinal hernias, but excluded those who were unwilling to have surgery, were under 12, had comorbidities, or had complete and recurrent hernias. In the end, 42 underwent open, and 42 underwent laparoscopic repair. Visual analog scales were used for pain assessments. Chi-square and unpaired student T-tests were employed (p<0.05). RESULTS: Among the 84 individuals analyzed, 79 (94.04%) were male patients, with the majority of them falling between the ages of 41 and 55. In contrast to the open group of patients, the laparoscopic group experienced a significant increase in operative time with a highly significant statistical difference (p<0.0001), and the laparoscopic group experienced a significant decrease in post-operative pain score with an insignificant p-value. A significant statistical difference (p<0.005) was estimated among the laparoscopic and open groups of patients in terms of post-operative hospitalization. Returning to normal activities was significantly different for laparoscopic patients relative to the open group (p-value<0.001). With a high level of significance of p<0.001, laparoscopic hernia repair required less time to recover before returning to normal activities than open hernia repair (p<0.005). CONCLUSION: In terms of decreased post-operative discomfort, shorter hospitalization, and an earlier return to activities, laparoscopic hernia repair has been found to be superior to open hernia repair, which is also known as Lichtenstein surgery. However, there was no discernible difference among the two groups with regard to post-operative problems, including seroma development and wound infections. To assess chronic discomfort and recurrence rates after laparoscopic hernia surgery, additional studies and extended follow-up are required.

Orthopaedic Surgery Complications at a Tertiary Care Hospital in a Low- and Middle-Income Country: A National Surgical Quality Improvement Project Analysis.

BACKGROUND: Through a comparison of orthopaedic surgical procedures performed at a tertiary care hospital in Pakistan with other participating hospitals of National Surgical Quality Improvement Project (NSQIP), we aim to identify the areas of orthopaedic surgical care at our center that need improvement and also those which are at par with international standards. METHODS: The study analyses orthopaedic surgeries at a tertiary care hospital in Pakistan using NSQIP registry to compare complication rates with other American College of Surgeons-NSQIP participant hospitals. Two reviewers collect data in different days every 8 days to reduce bias, and the results are reported in odds ratios using quarterly reports. This study included 584 eligible orthopaedic cases performed in 2021. Yearly institutional reports with odds ratios were also used to identify areas needing improvement and to implement changes to improve orthopaedic surgical outcomes at said institute. RESULTS: The quarterly reports suggest a relatively higher OR for certain indicators such as cardiac events, surgical site infection, mortality, and morbidity throughout. The renal failure rate was very high in the third and fourth quarters with odds ratios of 4.57 and 10.31, respectively. However, the official NSQIP annual institutional report for 2021 identified sepsis, surgical site infections, and cardiac complications as areas 'needing improvement'. It also indicated that the hospital performed exemplarily when it came to venous thromboembolism (VTE). As for the rest of the indicators, the hospital fell in the 'as expected' category of the NSQIP standards. CONCLUSION: This initial report helps the hospital's orthopaedic department in recognizing areas for improvement and making system-level changes to improve patient outcomes. The implementation of these interventions has yielded favorable outcomes, as evidenced by the findings in the NSQIP yearly report for 2022. Reinforcements and measures are needed to be taken to reduce the adverse events even further and to improve the patient outcomes and quality.

Assessment of Acceptability of Pre-exposure Prophylaxis for HIV Prevention Among Men Who Sex with Men and Transgender Community in Pakistan.

OBJECTIVE: To assess the level of acceptability of oral pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) and transwomen (TW) in Pakistan. STUDY DESIGN: Cross-sectional study. Place and Duration of the Study: Online study portal from September to November 2021. METHODOLOGY: The study participants were recruited through snowball sampling. Consenting individuals who were >13 years and were identified as MSM or TW were included in the study. Data were analysed using SPSS version 25. Frequencies, percentages and correlation coefficients were computed. RESULTS: A total of 347 participants were recruited. The mean age of all participants was 29.8 ± 6.7 years. Fifty-eight (19.7%) of the participants had chemsex with amphetamine-type stimulants (ATS) at least once in preceding six months of the study, and 58 (19.7%) had a sexually transmitted infection (STI) in preceding six months whereas 10 (3.4%) participants had used drugs via injection. Two hundred and thirty-eight (72%) of the participants were aware of PrEP, 30 (11.7%) had used PrEP in the past, and 3.88% were currently using PrEP. The willingness to use PrEP, free of cost, was shown by 300 participants (86.45%) and by 180 (54.5%), if available at a low cost. CONCLUSION: There was a high prevalence of risk factors posing them at considerable risk of human immunodeficiency virus (HIV). The majority was aware of PrEP for HIV prevention. The willingness to use PrEP was high when PrEP was offered free of cost but dropped down when participants were asked to pay for PrEP. Based on this finding, PrEP should be available free of cost at the community preferred outlets. KEY WORDS: Gay, Men who have sex with men, HIV, Pre-exposure prophylaxis Pakistan, Transwomen, Chemsex, People living with HIV.

Predicting the effects of rare genetic variants on oncogenic signaling pathways: A computational analysis of HRAS protein function.

The HRAS gene plays a crucial role in regulating essential cellular processes for life, and this gene's misregulation is linked to the development of various types of cancers. Nonsynonymous single nucleotide polymorphisms (nsSNPs) within the coding region of HRAS can cause detrimental mutations that disrupt wild-type protein function. In the current investigation, we have employed in-silico methodologies to anticipate the consequences of infrequent genetic variations on the functional properties of the HRAS protein. We have discovered a total of 50 nsSNPs, of which 23 were located in the exon region of the HRAS gene and denoting that they were expected to cause harm or be deleterious. Out of these 23, 10 nsSNPs ([G60V], [G60D], [R123P], [D38H], [I46T], [G115R], [R123G], [P11OL], [A59L], and [G13R]) were identified as having the most delterious effect based on results of SIFT analysis and PolyPhen2 scores ranging from 0.53 to 69. The DDG values -3.21 kcal/mol to 0.87 kcal/mol represent the free energy change associated with protein stability upon mutation. Interestingly, we identified that the three mutations (Y4C, T58I, and Y12E) were found to improve the structural stability of the protein. We performed molecular dynamics (MD) simulations to investigate the structural and dynamic effects of HRAS mutations. Our results showed that the stable model of HRAS had a significantly lower energy value of -18756 kj/mol compared to the initial model of -108915 kj/mol. The RMSD value for the wild-type complex was 4.40 Å, and the binding energies for the G60V, G60D, and D38H mutants were -107.09 kcal/mol, -109.42 kcal/mol, and -107.18 kcal/mol, respectively as compared to wild-type HRAS protein had -105.85 kcal/mol. The result of our investigation presents convincing corroboration for the potential functional significance of nsSNPs in augmenting HRAS expression and adding to the activation of malignant oncogenic signalling pathways.

Thoracoscopic vs open repair of congenital diaphragmatic hernia after extracorporeal membrane oxygenation: a comparison of intra-operative data.

PURPOSE: ECMO is an escalation treatment for hypoxic respiratory failure in patients with CDH. Open repair has been advocated after ECMO indicating that physiological changes associated to thoracoscopic repair were not well tolerated. METHODS: We have performed a retrospective review of all patients who underwent ECMO prior CDH repair over a 7 year period (2015-2021). Outcome measures were intra-operative Ph, PCO2, PO2 and FiO2 at 30 min, 1 h 30 min, and 2 h 30 min of surgery, operative time and recurrence rate. Data are shown in median (range). RESULTS: Eleven patients required ECMO prior CDH repair. Six of eleven (55%) were done thoracoscopically (Group A) and five of eleven (45%) via laparotomy (Group B). Two of six (33%) patients (Group A) were converted to a laparotomy, one of six (16%) patient developed a recurrence, and there was no recurrence in Group B. Two of five (40%) patients died within the first 60 days of life, whilst there was no death in Group A. Intra-operative values are shown below. CONCLUSION: Whilst this is a preliminary report of a limited number of patients, there is no obvious difference of intra-operative blood gas parameters during surgical repair in patients after ECMO. Thoracoscopic CDH repair may be considered in patients after ECMO.

Ginsenoside Rb1, a principal effective ingredient of Panax notoginseng, produces pain antihypersensitivity by spinal microglial dynorphin A expression.

Panax notoginseng (Chinese ginseng, Sanqi), one of the major ginseng species, has been traditionally used to alleviate different types of chronic pain. The raw P. notoginseng powder is commonly available in China as a non-prescription drug to treat various aliments including arthritic pain. However, strong scientific evidence is needed to illustrate its pain antihypersensitive effects, effective ingredients and mechanism of action. The oral P. notoginseng powder dose-dependently alleviated formalin-induced tonic hyperalgesia, and its total ginsenosides remarkably inhibited neuropathic pain hypersensitivity. Ginsenoside Rb1, the most abundant ginsenoside of P. notoginseng, dose-dependently produced neuropathic pain antihypersensitivity. Conversely, ginsenosides Rg1, Re and notoginseng R1, the other major saponins from P. notoginseng, failed to inhibit formalin-induced tonic pain or mechanical allodynia in neuropathic pain. Ginsenoside Rb1 metabolites ginsenosides Rg3, Compound-K and protopanaxadiol also had similar antineuropathic pain efficacy to ginsenoside Rb1. Additionally, intrathecal ginsenoside Rb1 specifically stimulated dynorphin A expression which was colocalized with microglia but not neurons or astrocytes in the spinal dorsal horn and primary cultured cells. Pretreatment with microglial metabolic inhibitor minocycline, dynorphin A antiserum and specific κ-opioid receptor antagonist GNTI completely blocked Rb1-induced mechanical antiallodynia in neuropathic pain. Furthermore, the specific glucocorticoid receptor (GR) antagonist Dex-21-mesylate (but not GPR30 estrogen receptor antagonist G15) also entirely attenuated ginsenoside Rb1-related antineuropathic pain effects. All these results, for the first time, show that P. notoginseng alleviates neuropathic pain and ginsenoside Rb1 is its principal effective ingredient. Furthermore, ginsenoside Rb1 inhibits neuropathic pain by stimulation of spinal microglial dynorphin A expression following GR activation.

Reverse Takotsubo cardiomyopathy associated with tonic clonic seizure: a rare form of Takotsubo cardiomyopathy.

A woman in her 30s presented with generalised tonic clonic seizure secondary to known pilocytic astrocytoma. This seizure activity resolved spontaneously after 5 min. On clinical assessment, she was neurologically stable and further neurological investigations did not reveal progression of previously recognised pilocytic astrocytoma. Incidentally, she was found to have an elevated troponin, which significantly increased on serial assessment. ECG was unremarkable and echocardiography revealed regional wall motion abnormalities involving basal segments of the left ventricle with apical sparing. She underwent cardiac MRI, which confirmed the presence of regional wall motion abnormalities seen on echocardiography; however, there was no evidence of myocardial oedema or late gadolinium enhancement. Subsequently, she had an invasive coronary angiogram with intravascular ultrasound which ruled out acute coronary plaque event and coronary dissection. In view of the above, a diagnosis of reverse Takotsubo cardiomyopathy was made. This is a relatively rare entity characterised by the presence of akinesia/hypokinesia in the basal segments with preserved apical contractility; often seen in younger patients.

Co-relation of Monocyte Count in High vs. Low Thrombus Burden ST-Segment Elevated Myocardial Infarction (STEMI) Patients Undergoing Primary Percutaneous Coronary Intervention.

Introduction Primary percutaneous coronary intervention (PPCI) in ST-elevation myocardial infarction (STEMI) patients can lead to poor outcomes. Intra-coronary thrombus development due to atherosclerotic plaque rupture and coronary blood flow blockage causes STEMI. Intracranial thrombosis in STEMI patients is fatal. It was our goal to establish how often patients with STEMI underwent PPCI with a high thrombus burden versus a low thrombus burden and to compare the mean monocyte count between the two groups. Material and methods This cross-sectional study was conducted at KRL Hospital Islamabad from October 2021 to March 2022. At a 95% level of confidence, a 5% margin of error, and keeping a population size of 330, a sample size of 178 was obtained using the Raosoft sample size calculator (Raosoft, Inc., Seattle, WA). The non-probability consecutive sampling method was used. All patients with STEMI undergoing PPCI, aged between 18 and 80 years, and presenting within 24 hours of symptoms were included in our study. Pre-PPCI pharmacological treatment given within three hours of the onset of a heart attack to stabilize patients with myocardial infarction included aspirin, clopidogrel, and an intravenous bolus of 70 U/kg of body weight of un-fractionated heparin. The collected data were analyzed using SPSS version 26.0 (IBM Corp., Armonk, NY). Fisher's exact test was employed, and a p-value of less than 0.05 was deemed statistically significant. The odds ratio and confidence interval were also calculated. Results A total of 178 participants were included in the research, out of which males were predominant with more than half of the study population. The mean age in patients having a low thrombus burden was 37.75 ± 6.39 years and that of patients with a high thrombus burden was mean 56.04 ± 7.98 years. In high thrombus burden patients, diabetes mellitus was found in 98.3%, hypertension in 120 patients (100%), obesity in (60%), and tobacco consumption in 120 patients (100%). The mean monocyte count in high burden patients was 70.27 ± 3.24, whereas it was 61.89 ± 5.71 in low burden patients. Only five patients had a Thrombolysis In Myocardial Infarction (TIMI) score of 5 while 34.8% of patients arrived in three to six hours and 12.9% arrived in less than three hours. Patients with a high monocyte count have 1.3 times more chances of developing the disease when the monocyte count was high (OR = 1.318, 95% CI = 1.140-1.524). Conclusion Patients with STEMI undergoing PPCI had a higher monocyte count upon admission, which was an independent clinical predictor of a high thrombus burden. Our findings suggest that admission monocyte count may be available for early risk stratification of high-thrombus burden in acute STEMI patients and might allow the optimization of anti-thrombotic therapy to improve the outcomes of PPCI.

Comparison of the Efficacy of Tap Water Iontophoresis Versus Aluminum Chloride Hexahydrate in the Treatment of Palmoplantar Hyperhidrosis.

OBJECTIVE: To compare the efficacy of tap water iontophoresis (TWI) versus aluminum chloride (AC) hexahydrate in the treatment of palmoplantar hyperhidrosis. METHODS: The study was a randomized control trial performed at the dermatology department of Pakistan Navy Station (PNS) Shifa Hospital, Karachi from March 2022 to September 2022. A total of 70 palmoplantar hyperhidrosis patients were included in the study after getting approval from the ethical committee. Patients were divided into two groups. Group A patients were treated with TWI three times a week for four weeks. Group B patients were treated with a 20% AC topical solution applied at night to the affected areas for four weeks. The Hyperhidrosis Disease Severity Scale (HDSS) score for both groups was calculated at baseline, one, two, three, and four weeks. The final response was labeled at four weeks by comparing mean HDSS reduction in both groups. SPSS version 28 (IBM Corp., Armonk, NY) was used for data analysis. RESULTS: Mean HDSS was compared for both groups at the end of the study, which showed a significant reduction in the mean score from 3.40 ± 0.65 to 1.48 ± 0.78 in group A, as compared to a decline in scores in group B from 3.28 ± 0.67 to 2.14 ± 0.94 (p = 0.002). In group A, zero, one, two, and three points HDSS improvement was 2.9%, 25.7%, 48.6%, and 22.9%, respectively. Whereas in group B, it was 34.3%, 22.9%, 34.3%, and 8.6%, respectively (p = 0.001). CONCLUSION: As compared to AC topical solution, TWI is an effective, safe, and inexpensive management option for palmoplantar hyperhidrosis. It causes more improvement in HDSS scores and has lesser side effects.

Fatty acid exporter 1 enhances seed oil content in Brassica napus.

Fatty acid exporter 1 (FAX1) is an initial transporter for fatty acid (FA), in charge of transporting FA from the inside of the plastid to the outside. Brassica napus (B. napus) has nineteen members in the FAX family, of which there are six FAX1 homologous genes. Here, we generated the BnaFAX1 CRISPR mutants (BnaA09.FAX1 and BnaC08.FAX1 were both edited) and overexpression (OE) plants of BnaA09.FAX1 in B. napus. The results showed that the FA content was increased by 0.6-0.9% in OE plant leaves, and the seed oil content was increased by 1.4-1.7% in OE lines, compared to WT. Meanwhile, the content of triacylglycerol, diacylglycerol, and phosphatidylcholine was significantly increased in OE seeds. Moreover, seedling biomass and plant height of OE plants were increased compared to WT plants. However, the traits above had no significant difference between the mutants and WT. These results suggest that BnaA09.FAX1 plays a role in improving seed oil accumulation and plant growth, while the function of BnaFAX1 may be compensated by other homologous genes of BnaFAX1 and other BnaFAX genes in the mutants. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01346-0.

Phytochemical profile and antiproliferative activities of acetone extracts of Asplenium polypodioides Blume. and A. dalhousiae Hook. in MDA-MB-231 breast cancer cells.

The plants extracts are widely used in traditional medicines and hence considered a potential source for drug discovery. In this study, we assessed the phytochemical composition of Asplenium dalhousiae and Asplenium polypodioides in acetone extracts and checked its antiproliferative potential in MDA-MB-231 cells. We found that both plants are rich in phenolic and flavonoid compounds and are efficient in antioxidant activities. The total phenolic compounds in A. dalhousiae were 44.15 ± 1.38 µg/mg whereas in A. polypodioides were 27.73 ± 1.35 µg/mg. Total flavonoids in A. dalhousiae were 105.39 ± 2.92 µg/mg whereas in A. polypodioides were 101.56 ± 1.75 µg/mg. The ferric reducing power assay indicates 66.38 ± 2.6% reduction by A. dalhousiae whereas 78.43 ± 0.47% reduction by A. polypodioides. Similarly, the total antioxidant capacity of A. dalhousiae was found to be 59.95 ± 1.13 whereas for A. polypodioides the recorded value was 33.03 ± 1.67%. Using GCMS analysis, we identified 25 compounds in A. dalhousiae whereas 26 in A. polypodioides. Four of these compounds are common in both plants. The morphological study and MTT assay revealed that both plants have antiproliferative potential as both plants exerted significant effects on the shape of the MDA-MB-231 cells and inhibited cellular proliferation in time and dose dependent manner. We conclude that both Asplenium plants have potential anticancer compounds.

Proteome-wide identification of S-sulphenylated cysteines in Brassica napus.

Deregulation of reduction-oxidation (redox) metabolism under environmental stresses results in enhanced production of intracellular reactive oxygen species (ROS), which ultimately leads to post-translational modifications (PTMs) of responsive proteins. Redox PTMs play an important role in regulation of protein function and cellular signalling. By means of large-scale redox proteomics, we studied reversible cysteine modification during the response to short-term salt stress in Brassica napus (B. napus). We applied an iodoacetyl tandem mass tags (iodoTMT)-based proteomic approach to analyse the redox proteome of B. napus seedlings under control and salt-stressed conditions. We identified 1,821 sulphenylated sites in 912 proteins from all samples. A great number of sulphenylated proteins were predicted to localize to chloroplasts and cytoplasm and GO enrichment analysis of differentially sulphenylated proteins revealed that metabolic processes such as photosynthesis and glycolysis are enriched and enzymes are overrepresented. Redox-sensitive sites in two enzymes were validated in vitro on recombinant proteins and they might affect the enzyme activity. This targeted approach contributes to the identification of the sulphenylated sites and proteins in B. napus subjected to salt stress and our study will improve our understanding of the molecular mechanisms underlying the redox regulation in response to salt stress.

Cyclam-Modified Polyethyleneimine for Simultaneous TGFß siRNA Delivery and CXCR4 Inhibition for the Treatment of CCl4-Induced Liver Fibrosis.

BACKGROUND: Liver fibrosis is a chronic liver disease with excessive production of extracellular matrix proteins, leading to cirrhosis, hepatocellular carcinoma, and death. PURPOSE: This study aimed at the development of a novel derivative of polyethyleneimine (PEI) that can effectively deliver transforming growth factor ß (TGFß) siRNA and inhibit chemokine receptor 4 (CXCR4) for TGFß silencing and CXCR4 Inhibition, respectively, to treat CCl4-induced liver fibrosis in a mouse model. METHODS: Cyclam-modified PEI (PEI-Cyclam) was synthesized by incorporating cyclam moiety into PEI by nucleophilic substitution reaction. Gel electrophoresis confirmed the PEI-Cyclam polyplex formation and stability against RNAase and serum degradation. Transmission electron microscopy and zeta sizer were employed for the morphology, particle size, and zeta potential, respectively. The gene silencing and CXCR4 targeting abilities of PEI-Cyclam polyplex were evaluated by luciferase and CXCR4 redistribution assays, respectively. The histological and immunohistochemical staining determined the anti-fibrotic activity of PEI-Cyclam polyplex. The TGFß silencing of PEI-Cyclam polyplex was authenticated by Western blotting. RESULTS: The 1H NMR of PEI-Cyclam exhibited successful incorporation of cyclam content onto PEI. The PEI-Cyclam polyplex displayed spherical morphology, positive surface charge, and stability against RNAse and serum degradation. Cyclam modification decreased the cytotoxicity and demonstrated CXCR4 antagonistic and luciferase gene silencing efficiency. PEI-Cyclam/siTGFß polyplexes decreased inflammation, collagen deposition, apoptosis, and cell proliferation, thus ameliorating liver fibrosis. Also, PEI-Cyclam/siTGFß polyplex significantly downregulated α-smooth muscle actin, TGFß, and collagen type III. CONCLUSION: Our findings validate the feasibility of using PEI-Cyclam as a siRNA delivery vector for simultaneous TGFß siRNA delivery and CXCR4 inhibition for the combined anti-fibrotic effects in a setting of CCl4-induced liver fibrosis.

Discordant Pathological and Endoscopic Diagnosis: Consider Floaters.

A tissue floater or extraneous cross-contamination tissue on a microscopic slide is rare; however, it is a potential cause of diagnostic error. Occasionally, on collecting and processing of specimens, cross-contamination of tissue occurs leading to pathologic findings that are inconsistent with endoscopic findings. If the extraneous tissue is neoplastic, it can lead to a false-positive diagnosis. We present a case of discordant pathological and endoscopic diagnosis of invasive squamous carcinoma of the esophagus.