Biological activities, therapeutic potential, and pharmacological aspects of blackcurrants (Ribes nigrum L): A comprehensive review.

Blackcurrant possesses various health-endorsing attributes owing to its polyphenol profile. Recent studies have demonstrated its therapeutic potential against various health disorders. Various bioactives present in blackcurrants have different functional and pharmacological aspects including anti-inflammatory, antioxidant, and antimicrobial properties. The most dominant and important bioactive include anthocyanins, flavonols, phenolic acids, and polyunsaturated fatty acids. Food formats derived from blackcurrants comprise pomace, juice, powder, and extracts. All these food formats have industrial, prebiotic, and pharmacological benefits. In the current article, the nutritional composition, industrial applications, and therapeutic potential are discussed in the recent literature. Moreover, novel extraction techniques for the extraction of bioactive compounds present in blackcurrants and their safety concerns have been elaborated.

Small Cell Neuroendocrine Carcinoma of the Vagina: A Rare Presentation.

Primary small cell neuroendocrine carcinoma of the vagina is a very rare disease. We present a case study of a 52-year-old female who presented to the hospital with complaints of urinary dribbling, burning micturition, pain, and per vaginal bleeding for three to four months. A firm globular mass of approximately 5-6 cm was felt in the anterior vaginal wall per speculum examination. Diagnosis of small cell neuroendocrine carcinoma was made with tissue biopsy and immunohistochemistry. Diagnostic imaging (MRI, positron emission tomography (PET)-CT) plays a vital role in reaching the diagnosis and understanding the treatment response. The patient received six cycles of chemotherapy with cisplatin and etoposide and radiotherapy, achieving a complete response, with complete regression of the lesion. The patient had no sign of tumor recurrence and locoregional or distant metastases after six months of follow-up. Nowadays, there is no need for surgery in the treatment of vaginal small cell neuroendocrine carcinoma, rather radiotherapy and chemotherapy are the treatment of choice. We report a case of neuroendocrine cancer of the vagina treated at our institution.

Relationship between the ABO blood group and Rhesus factors with COVID-19 susceptibility.

INTRODUCTION: The molecular research has raised copious hypotheses about different molecular effects on the variable expression of the current virus on the human body. The present prospective study aims to determine clinically as well as statistically, the relation between ABO blood groups and Rhesus (Rh) factor and the severity of the Covid-19 virus. RESEARCH DESIGN AND METHODS: We conducted a prospective, single-centered study at The Combined Military Hospital Lahore, Pakistan. Details of only those patients who exhibit COVID-19 symptoms were included. The odds ratios with a 95% confidence interval and the chi-square test of blood groups and Rhesus factor was also conducted individually with the severity of disease, outcomes, and respiratory symptoms. P-values less than 0.05 was considered significant. RESULTS: The chi-square test and odd ratio yielded no significant results when the covid-19 status was compared with the Rhesus factor (p-value > 0.05). However, the results were found to be significant when associations were run between Covid-19 status and all the blood groups (p-value < 0.05). CONCLUSION: According to the analytical results of the present study, protective nature of all the blood antigens (A, B, AB, none) was observed in patients presenting with Covid-19 symptoms of varying severity.

The Association of Helicobacter pylori With Portal Hypertensive Gastropathy in Patients With and Without Cirrhosis.

INTRODUCTION: Cirrhosis and its associated complication of portal hypertensive gastropathy (PHG), among others, remain a significant cause of death in resource-poor countries with limited capacity for liver transplantation. This research aimed to assess the association of Helicobacter pylori (H. pylori) with portal hypertensive gastropathy and its severity in patients with and without cirrhosis. METHODOLOGY: The study was conducted at a tertiary care hospital in Pakistan from April 2021 to May 2022. Liver cirrhosis was diagnosed by clinical manifestations, ultrasonography, and laboratory investigations. The severity of liver cirrhosis was assessed using the Child-Pugh scoring system. The association of H. pylori with portal hypertensive gastropathy in patients with and without cirrhosis was assessed using the chi-square test. RESULTS: A total of 120 patients participated in the study, of which 40 were without liver cirrhosis, while 80 were with cirrhosis. Among patients with cirrhosis, 24 were in Child-Pugh class A, 26 in class B, and 30 in class C. Of patients with liver cirrhosis who were H. pylori-negative, 37.5% (15/40) had portal hypertensive gastropathy. Of these, 12.5% (5/40) had severe PHG, while 25% (10/40) had mild PHG. Of patients with liver cirrhosis who were H. pylori-positive, 62.5% (25/40) had PHG. Of these, 2.5% (1/40) had severe PHG, while 60% (24/40) had mild PHG. Helicobacter pylori contributed nonsignificantly (p=0.080), showing no association with portal hypertensive gastropathy. CONCLUSION: Helicobacter pylori does not appear to have any significant association to cause or worsen portal hypertensive gastropathy in patients with liver cirrhosis.

SARS-COV-2/COVID-19: scenario, epidemiology, adaptive mutations, and environmental factors.

The coronavirus pandemic of 2019 has already exerted an enormous impact. For over a year, the worldwide pandemic has ravaged the whole globe, with approximately 250 million verified human infection cases and a mortality rate surpassing 4 million. While the genetic makeup of the related pathogen (SARS-CoV-2) was identified, many unknown facets remain a mystery, comprising the virus's origin and evolutionary trend. There were many rumors that SARS-CoV-2 was human-borne and its evolution was predicted many years ago, but scientific investigation proved them wrong and concluded that bats might be the origin of SARS-CoV-2 and pangolins act as intermediary species to transmit the virus from bats to humans. Airborne droplets were found to be the leading cause of human-to-human transmission of this virus, but later studies showed that contaminated surfaces and other environmental factors are also involved in its transmission. The evolution of different SARS-CoV-2 variants worsens the condition and has become a challenge to overcome this pandemic. The emergence of COVID-19 is still a mystery, and scientists are unable to explain the exact origin of SARS-CoV-2. This review sheds light on the possible origin of SARS-CoV-2, its transmission, and the key factors that worsen the situation.

In-situ, Ex-situ, and nano-remediation strategies to treat polluted soil, water, and air - A review.

Nanotechnology, as an emerging science, has taken over all fields of life including industries, health and medicine, environmental issues, agriculture, biotechnology etc. The use of nanostructure molecules has revolutionized all sectors. Environmental pollution is a great concern now a days, in all industrial and developing as well as some developed countries. A number of remedies are in practice to overcome this problem. The application of nanotechnology in the bioremediation of environmental pollutants is a step towards revolution. The use of various types of nanoparticles (TiO2 based NPs, dendrimers, Fe based NPs, Silica and carbon nanomaterials, Graphene based NPs, nanotubes, polymers, micelles, nanomembranes etc.) is in practice to diminish environmental hazards. For this many In-situ (bioventing, bioslurping, biosparging, phytoremediation, permeable reactive barrier etc.) and Ex-situ (biopile, windrows, bioreactors, land farming etc.) methodologies are employed. Improved properties like nanoscale size, less time utilization, high adaptability for In-situ and Ex-situ use, undeniable degree of surface-region to-volume proportion for possible reactivity, and protection from ecological elements make nanoparticles ideal for natural applications. There are distinctive nanomaterials and nanotools accessible to treat the pollutants. Each of these methods and nanotools depends on the properties of foreign substances and the pollution site. The current designed review highlights the techniques used for bioremediation of environmental pollutants as well as use of various nanoparticles along with proposed In-situ and Ex-situ bioremediation techniques.

Helicobacter Pylori Eradication Therapy: Still a Challenge.

Introduction Helicobacter pylori (H. pylori) infection is prevalent worldwide. H. pylori therapies' adverse effects can contribute to noncompliance among patients. This study aimed to assess the association between compliance to H. pylori eradication therapy and adverse effects using various drug regimens. Method We conducted an observational study from September 2017 to February 2020 in two tertiary care hospitals in patients with dyspeptic symptoms. H. Pylori detection was done by histopathological examination of gastric mucosa during upper gastrointestinal endoscopy or stool for H. pylori antigen. Patients with positive results were randomly assigned one of the nine different regimens consisting of a combination of proton pump inhibitors along with at least two antibiotics. The antibiotics used in different combinations were amoxicillin, clarithromycin, metronidazole, doxycycline, levofloxacin, and bismuth sulfate. The treatment groups received standard triple therapy with and without probiotics, sequential, concomitant, levofloxacin-based triple therapy, or sequential and bismuth-based quadruple treatments. All treatments were given for two weeks. At the end of the treatment period, patients were interviewed about completing treatment and any adverse effects they may have experienced during therapy. Data were analyzed using IBM Statistical Package for the Social Sciences (SPSS) Statistics for Windows, Version 22.0 (Armonk, NY: IBM Corp.). Results A total of 250 patients were included in the study (62% males, 38% females) with a mean age of 37 years ± 13 years (range 12-84 years). Most patients completed the treatment regimen (80.4%), and 19.6% did not complete treatment because of adverse effects (p<0.005). The levofloxacin-based, concomitant, and standard triple regimen with probiotic treatments had the highest tolerance (≥85%). Common adverse effects were abdominal and epigastric pain (11%), alteration of taste, and diarrhea (6.5%). Conclusion H. pylori eradication therapy is always a challenge. Patient compliance to the treatment can only be ensured by medicines with fewer adverse effects. In our study, levofloxacin-based triple, concomitant, and standard triple regimens with probiotics are maximally acceptable treatments.

Gastrointestinal and Hepatobiliary Complications of Extensively Drug-Resistant Typhoid at a Tertiary Care Hospital in Pakistan.

INTRODUCTION: Typhoid fever is a major health problem in developing countries. Extensively drug-resistant (XDR) typhoid is an emerging threat to world health. The objectives of this study were to report our blood culture proven patients having XDR typhoid and compare the rate of gastrointestinal (GI) and hepatobiliary manifestations and complications of antimicrobial sensitive and resistant strains. MATERIALS AND METHODS: This prospective observational study was carried out at a tertiary care hospital in Pakistan, from January 2019 till August 2020 on all consecutive blood culture proven patients of Salmonella typhi. A total of 57 cases of Salmonella were identified, of which 10 were nonresistant, seven multi drug-resistant (MDR), 39 extensively drug-resistant (XDR), and one was extended-spectrum beta lactamase (ESBL) positive. Alarmingly, one of the S. typhi isolate in addition to the first line drugs, was also resistant to azithromycin. Patients were treated with antibiotics according to antimicrobial susceptibility of the Salmonella in accordance with the World Health Organization (WHO) and Medical Microbiology and Infectious Diseases Society of Pakistan (MMIDSP) guidelines and GI and hepatobiliary complications were recorded. RESULTS: Overall rate of complications was low. Some 10% (1/10) with nonresistant typhoid, 14% (1/7) with MDR, and 15% (6/39) of our patients with XDR typhoid fever had abdominal tenderness (p=0.95). None of the patients had GI bleeding, abdominal abscess, or peritonitis. Some 20% (2/10) patients with nonresistant typhoid, 29% (2/7) with MDR, and 18% (7/39) with XDR typhoid developed acute hepatitis, with greater than three times elevation of liver transaminases. There was no statistically significant difference in the occurrence of hepatitis between these groups (p=0.98). Interestingly, one of our patients with XDR typhoid also developed cholestatic hepatitis. CONCLUSION: There is no significant difference in GI and hepatobiliary complications amongst antimicrobial sensitive and resistant strains of typhoid. However, emergence of resistant strains calls for focus on prevention and judicious use of antimicrobials.

Induction of Erythrocyte Shrinkage by Omeprazole.

Omeprazole, a proton pump inhibitor blocks the H+/K+-ATPase channels of gastric parietal cells. It is used for the treatment of peptic ulcer. Prolonged use of omeprazole may involve in inducing anemia. The key marker of eryptosis includes membrane blebbing, cell shrinkage and phosphatidylserine (PS) exposure at the cell surface. In current study, the eryptotic, oxidative as well as hemolytic effects of therapeutical doses (0.5, 1 and 1.5 µM) of omeprazole were investigated after exposing erythrocytes for 48 hours. Investigation of eryptosis was done by cell size measurement, PS exposure determination and calcium channel inhibition. As a possible mechanism of omeprazole induced eryptosis, oxidative stress was investigated by determining the catalase, glutathione peroxidase and superoxide dismutase activities. Similarly, necrotic effect of omeprazole on erythrocytes was also evaluated through hemolysis measurement. Results of our study illustrated that 1.5 µM of omeprazole may induce significant decrease in superoxide dismutase, glutathione peroxidase and catalase activities as well as triggered the erythrocytes shrinkage, PS exposure and hemolysis. Role of calcium was also confirmed in inducing erythrocyte shrinkage. It is concluded that the exposure of erythrocytes with 1.5 µM omeprazole may enhance the rate of eryptosis and hemolysis by inducing oxidative stress.

Dubin-Johnson syndrome coexisting with glucose-6-phosphate dehydrogenase deficiency presenting after acute viral hepatitis.

Dubin-Johnson syndrome presents as asymptomatic recurrent hyperbilirubinemia, while Glucose-6-Phosphate-Dehydrgenase-deficiecy as acute haemolytic anaemia. We present a case with coexisting Dubin-Johnson syndrome and Glucose-6-Phosphate Dehydrogenase deficiency unmasked by acute viral hepatitis E.

Features and outcome of AIH patients without elevation of IgG.

BACKGROUND & AIMS: High IgG levels are considered a hallmark of autoimmune hepatitis (AIH). A subgroup of patients with AIH has IgG within the normal range despite evidence of clinical disease activity. The clinical significance of this biomarker has not been explored. METHODS: In a European multicentre study we compared biochemical, clinical and histological features from patients with AIH and normal IgG-values at diagnosis to an age- and sex-matched control group of patients with typical AIH presenting with elevated IgG. Data were assessed at diagnosis, after 12 months of therapy and at last follow-up. RESULTS: Out of 1,318 patients with AIH, 130 (10%) had normal IgG at presentation. Histological and biochemical parameters at diagnosis, as well as treatment response, showed no difference between groups. Stable remission off treatment was achieved more commonly in the normal IgG group than in the typical AIH group (24 vs. 8%; p = 0.0012). Patients of the control group not only had higher IgG levels (29.5 ± 5.8 vs. 12.5 ± 3.2 g/L; p <0.0001), but also a higher IgG/IgA ratio (9.3 ± 6.9 vs. 5.4 ± 2.4; p <0.0001) at diagnosis. The IgG/IgA ratio only declined in patients with typical AIH and was no longer different between groups after 12 months (6.3 ± 4.3 vs. 5.5 ± 2.2; p = 0.1), indicating a selective increase of IgG in typical AIH and its suppression by immunosuppression. Autoantibody titres were higher in the typical AIH group, but not when controlled for IgG levels. CONCLUSIONS: Compared to AIH with typical biochemical features, patients with normal IgG levels at diagnosis (i) show similar biochemical, serological and histological features and comparable treatment response, (ii) appear to lack the selective elevation of serum IgG levels observed in typical active AIH disease, (iii) may represent a subgroup with a higher chance of successful drug withdrawal. LAY SUMMARY: A characteristic feature of autoimmune hepatitis (AIH) is an elevation of immunoglobulin G (IgG), which is therefore used as a major diagnostic criterion, as well as to monitor treatment response. Nevertheless, normal IgG does not preclude the diagnosis of AIH. Therefore, we herein assessed the features of patients with AIH and normal IgG in a large multicentre study. This study demonstrates that about 10% of all patients with AIH have normal IgG; these patients are indistinguishable from other patients with AIH with respect to biochemical markers, liver histology, disease severity and treatment response, but might represent a subgroup with a higher chance of remission after drug withdrawal.

Stimulation of Erythrocyte Membrane Blebbing by Naproxen Sodium.

Naproxen sodium is a nonsteroidal anti-inflammatory drug (NSAID) having antipyretic and analgesic properties, mainly used for the treatment of rheumatoid arthritis and osteoarthritis. Eryptosis is an alternative term used for suicidal erythrocyte death. In the current study, eryptotic effect of naproxen sodium characterized by membrane blebbing was investigated in erythrocytes after 48 hours of treatment with different concentrations (1-25 µM). The experimental work related to investigation of eryptosis was done by cell size measurement and confirmation of calcium role in the induction of membrane blebbing. As a possible mechanism of eryptosis, oxidative stress induced by naproxen sodium was determined by catalase, glutathione peroxidase, and superoxide dismutase activities. Similarly, hemolytic effect of naproxen sodium was also determined by hemolysis measurement. Results of our study illustrated that the therapeutic doses (10-25 µM) of naproxen sodium induce oxidative stress, confirmed by significant decrease in superoxide dismutase, catalase, and glutathione peroxidase activities that lead to the triggering of cell death by eryptosis and hemolysis.

Atorvastatin Induced Erythrocytes Membrane Blebbing.

Atorvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzymeA reductase, is usually used for the treatment of hypercholesterolemia. Besides its pharmacological and side actions, its toxic effects on human nucleus devoid of erythrocytes are still unknown. Eryptosis is an alternative term used for suicidal erythrocyte death. Membrane blebbing is among the common markers of eryptosis. In this study, eryptotic effect of atorvastatin was investigated by exposing the erythrocytes for 48 hours to different concentrations (1-10 µM) of atorvastatin. The experimental work related to investigation of eryptosis was done by cell size measurement and calcium channel inhibition. As a possible mechanism of eryptosis, atorvastatin-induced oxidative stress was evaluated by determining catalase, glutathione peroxidase, and superoxide dismutase activities. Similarly, necrotic effect of atorvastatin was also determined by hemolytic assay. Results of our study illustrated that the tested doses of atorvastatin may induce oxidative stress as observed by significant reduction in superoxide dismutase, glutathione peroxidase, and catalase activities as well as induce eryptosis, featured by erythrocytes membrane blebbing. The study concluded that induction of oxidative stress by atorvastatin may lead to eryptosis.

Diaphragmatic Excursion: Does it Predict Successful Weaning from Mechanical Ventilation?

OBJECTIVE: To measure the diaphragmatic excursion and its outcome on weaning from mechanical ventilation. STUDY DESIGN: Cross-sectional comparative study. PLACE AND DURATION OF STUDY: Medical Intensive Care Unit (ICU), Military Hospital (MH), Rawalpindi, Pakistan, from January to December 2014. METHODOLOGY: Diaphragmatic excursion (DE) in cm was measured through ultrasound by marking liver and spleen displacement in patients who fulfilled the criteria of removal from ventilatory support. The patients were followed up for 48 hours and classified according to the outcome as successful weaning and weaning failure. RESULTS: Out of 100 cases, 76 patients had a successful weaning while 24 had a failed weaning outcome. At a diaphragmatic excursion of 1.2 cm and more, out of 67 cases, 60 had a successful weaning (89.55%) while 7 cases (10.45%) had a weaning failure. At an excursion of less than 1.2 cm, 17 out of 33 cases (51.5%) had successful weaning while 16 (48.48%) had weaning failure. At this cut off point (1.2 cm), the sensitivity and specificity for successful weaning were 78.95% and 70.83%, respectively. The positive and negative likelihood ratio (LR) for these values being 2.70 and 0.29, respectively. The positive predictive value was 82.35% and negative predictive value 60.00%. CONCLUSION: Ultrasonographic measurement of diaphragmatic excursion is a good method for predicting weaning outcome from mechanical ventilation.

Developmental gene regulation by an ancient intercellular communication system in social amoebae.

The social amoebae (Dictyostelia) use quorum sensing-like communication systems to coordinate the periodic transition from uni- to multicellularity. The monophyletic descent of the Dictyostelia provides a unique opportunity to study the origin and adaptive evolution of such intercellular communication systems. We determined that the ability of aggregation-competent cells to respond to the intercellular messenger glorin occurred in the most ancient taxa of the Dictyostelia. We show using Illumina sequencing technology that glorin mediates rapid changes in gene expression at the transition from vegetative growth to aggregation. We conclude that peptide-based communication is the most ancient form of intercellular signaling in the evolution of multicellularity in the social amoebae, but has been repeatedly replaced by other communication systems during the monophyletic evolution of the social amoebae. Glorin communication has parallels with quorum sensing in that the molecule diffuses into the field, stimulates gene expression in receptive cells and coordinates a population-wide response.