Significance of additives to enhance the acceptance of poison bait in poultry rodents of Haripur, Khyber Pakhtunkhwa, Pakistan.

Rodent infestation on poultry farms incurs heavy economic losses to this industry by causing feed loss and disease introduction. Development and continuous improvement of rodents control techniques are vital to minimize and control the damages caused by rodents. Here, we test the feed preference of rodents for locally available and palatable food grains viz. millet (whole), wheat (cracked) and rice (broken) and taste additives namely whole egg (5%), eggshell (5%), peanut cracked (5%) and yeast (2%) that were offered mixed in millet-wheat (50:50 by wt.) bait. We tested the preferences of different food additives through a process of feed choice mechanism. We applied two different techniques to compare the preference of mixed feed baits, these techniques included no-choice with multiple choice feeding tests and paired choice with multiple choices feeding tests. The results indicated that consumption of bait with added whole egg was significantly higher (p > 0.05). Further test for its effectiveness as a carrier for rodenticides revealed 56%, 82% and 92%, reduction in rodent activities with zinc phosphide (2%), coumatetralyl (0.0375%) and Brodifacoum (0.005%) respectively. Our results point to a need on continuous improvement of feed baits by using different combinations to effectively control the rodent infestation.

Characterization and Evaluation of Silk Sericin-Based Hydrogel: A Promising Biomaterial for Efficient Healing of Acute Wounds.

The present study was aimed to prepare the potent silk sericin-based hydrogels in combination with plant extracts (curcumin and banana peel powder) and silver nanoparticles (AgNPs) to accelerate the acute wound healing process. Experimental excision wounds were created in mice by biopsy puncture, and the wound healing potential of silk sericin (2%)-based hydrogel and its combinations with curcumin (2%), banana peel powder (2%), and AgNPs (2%) was estimated by calculating the percent wound contraction, healing time, histology of skin tissues, and different biochemical tests. The results showed that the mice treated with sericin-based hydrogels showed significantly (P < 0.001) high percent wound contraction as compared to negative control, and wounds were healed in 11 days. The histological evaluation also showed that wounds covered with hydrogels were healed more than the uncovered wounds. Furthermore, the results of biochemical tests revealed that the treatment groups showed a significant (P < 0.001) decrease in the serum level of pro-inflammatory cytokines (IL-6). A significant (P < 0.001) increase in anti-inflammatory cytokines (IL-10) and anti-oxidant enzymes was observed in treatment groups. The highest wound healing potential was observed by sericin-based hydrogel containing banana peel powder, leaving behind the commercially available ointment polyfax (positive control). It can be concluded that the silk sericin-based hydrogels in combination with plant extract and AgNPs can be used as natural biomaterials in wound dressing for the rapid healing of acute wounds.

Nutritional and medicinal plants as potential sources of enzyme inhibitors toward the bioactive functional foods: an updated review.

Enzymes are biologically active complex protein molecules that catalyze most chemical reactions in living organisms, and their inhibitors accelerate biological processes. This review emphasizes medicinal food plants and their isolated chemicals inhibiting clinically important enzymes in common diseases. A mechanistic overview was investigated to explain the mechanism of these food bases enzyme inhibitors. The enzyme inhibition potential of medicinal food plants and their isolated substances was searched in Ovid, PubMed, Science Direct, Scopus, and Google Scholar. Cholinesterase, amylase, glucosidase, xanthine oxidase, tyrosinase, urease, lipoxygenase, and others were inhibited by crude extracts, solvent fractions, or isolated pure chemicals from medicinal food plants. Several natural compounds have shown tyrosinase inhibition potential, including quercetin, glabridin, phloretin-4-O-ß-D-glucopyranoside, lupinalbin, and others. Some of these compounds' inhibitory kinetics and molecular mechanisms are also discussed. Phenolics and flavonoids inhibit enzyme activity best among the secondary metabolites investigated. Several studies showed flavonoids' significant antioxidant and anti-inflammatory activities, highlighting their medicinal potential. Overall, many medicinal food plants, their crude extracts/fractions, and isolated compounds have been studied, and some promising compounds depending on the enzyme have been found. Still, more studies are recommended to derive potential pharmacologically active functional foods.

Green synthesized silver nanoparticles from eucalyptus leaves can enhance shelf life of banana without penetrating in pulp.

Bananas are exposed to serious post-harvest problems resulting in agricultural and economic losses across the world. The severity of problem is linked with the process of rapid ripening and pathogens attack. Such problems have led to economic losses as well as a lower yield of nutritionally rich bananas. The global demand to increase the life span of bananas and their protection from pathogens-borne diseases urged the use of antimicrobial edible coatings of nanoparticles. The present experiment has explored the innovative development of green synthesized nanoparticles from Eucalyptus leaf extract (ELE) to increase the shelf life of bananas up to 32 days from the day of collection. Statistically significant results were recorded (P = 0.05) by applying five different concentrations of silver nanoparticles (AgNPs) in ranges of 0.01-0.05%. Various morphological and physiological parameters such as color, decay, firmness, weight loss, pulp to peel ratio, pH, titrable acidity (TA), phenolic contents, protein estimation, ethylene production, starch content and total soluble sugars were measured in Cavendish banana (Basrai). Bananas treated with 0.01% AgNPs showed maximum control on its ripeness over morphological and physiological changes. The increase in shelf life was in order 0.01%>0.02%>0.03%>0.04%>0.05%> control. Further, AgNPs reduced the process of ripening by controlling ethylene production. The result has also proved the safety of banana consumption by simple removal of banana peel as penetration of AgNPs from the peel to the pulp was not detected. It is recommended to use 0.01% AgNPs to enhance the shelf life of banana without effecting its nutritive value.

Investigating In Situ Expression of c-MYC and Candidate Ubiquitin-Specific Proteases in DLBCL and Assessment for Peptidyl Disruptor Molecule against c-MYC-USP37 Complex.

Diffuse Large B-Cell Lymphoma (DLBCL) is the most common form of non-Hodgkin's lymphoma (NHL). Elevated expression of c-MYC in DLBCL is associated with poor prognosis of the disease. In different cancers, c-MYC has been found regulated by different ubiquitin-specific proteases (USPs), but to date, the role of USPs in c-MYC regulation has not been investigated in DLBCL. In this study, in situ co expression of c-MYC and three candidates USPs, USP28, USP36 and USP37, have been investigated in both the ABC and GCB subtypes of DLBCL. This shows that USP37 expression is positively correlated with the c-MYC expression in the ABC subtype of DLBCL. Structurally, both c-MYC and USP37 has shown large proportion of intrinsically disordered regions, minimizing their chances for full structure crystallization. Peptide array and docking simulations has shown that N-terminal region of c-MYC interacts directly with residues within and in proximity of catalytically active C19 domain of the USP37. Given the structural properties of the interaction sites in the c-MYC-USP37 complex, a peptidyl inhibitor has been designed. Molecular docking has shown that the peptide fits well in the targeted site of c-MYC, masking most of its residues involved in the binding with USP37. The findings could further be exploited to develop therapeutic interventions against the ABC subtype of DLBCL.

Enhanced Expression of RAGE AXIS Is Associated with Severity of COVID-19 in Patients with Comorbidities.

Background: There is a limited understanding of molecular and cellular events that derive disease progression in patients with corona virus disease 2019 (COVID-19). Receptor for advanced glycation end products (RAGE) is hyperactive in development and complications of several diseases by mediating oxidative stress and inflammation in the body. The present study aims to explore activation of RAGE signaling in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with preexisting comorbidities, including hypertension and or diabetes. Methods: A total of 442 subjects with COVID-19, were recruited for the study. The molecular mechanism of Covid-19 was explored in blood cells, using ELISA, RT- PCR and Western blot. Results: Enhanced levels of ligands of RAGE, including AGEs, S100, and high-mobility group box-1 (HMGB-1) were observed in COVID-19 patients with severe diseases; however, their level was significantly higher in COVID-19 patients with comorbidities compared to COVID-19 patients without comorbidities. The expression of RAGE in parallel to ligands accumulation was significantly increased in patients with severe disease and comorbidities compared to COVID-19 patients with severe disease without comorbidities. The expression of downstream effectors of RAGE, including STAT-3 and nuclear factor kappa B (NF-kB), was also enhanced and their activity was increased in COVID-19 patients with comorbidities. Levels of inflammatory and oxidative stress biomarkers were markedly increased in COVID-19 patients with comorbidities. Conclusions: We conclude that upregulated RAGE axis plays critical role, to worsen the severity of the SARS-CoV-2 infection in patients with preexisting comorbidities and partly explain inflammatory and oxidative stress storm in severe COVID-19 patients.

Case report on severe splenic injury following colonoscopy with disproportionately stable presentation: A rural hospital perspective.

INTRODUCTION: Detection of splenic injury following routine colonoscopy is slowly on the rise. Mostly presenting as left upper abdominal or shoulder tip pain along with a sharp fall in haemoglobin level and hemodynamic instability, sometimes the presentation and initial workup may be vague and falsely reassuring. CASE PRESENTATION: This is demonstrated in the case of a 72 year old male who presented with vague but severe left lower abdominal pain following colonoscopy, during which one caecal polyp was removed and no intraoperative complications were reported. On emergency presentation, abdominal examination was not particularly concerning with only mild left lower tenderness and minimal guarding. Vital signs remained largely normal and blood counts were reasonable. Close to being discharged, patient demonstrated brief hypotension post ambulation which was easily reversed with a fluid bolus. Upon surgical review, a high index of suspicion prompted further investigation which revealed an unsuspected complication necessitating urgent laparotomy and splenectomy. DISCUSSION: Splenic injury is slowly becoming an increasingly reported complication following colonoscopy. While many cases present with typical features, others may only display subtle signs of deterioration, and warrant a high degree of suspicion. CONCLUSION: Rural doctors should be aware of and able to recognise this potentially fatal complication to ensure timely successful management.

Multifunctional role of Nobiletin in cancer chemoprevention.

The diversity of highly bioactive and pharmacologically active natural products which recognize essential biological targets having exquisite specificity, constitutes a massive pharmacological database for discovery of valuable drugs. The rapid accumulation of information has revealed chemopreventive role of nobiletin against wide variety of cancers. Recent efforts are now being expanded and new integrative omics technologies have illuminated continuously upgrading list of molecular mechanisms which underlie carcinogenesis and metastasis. In this mini-review, we explore the progress that has been made in the identification of promising molecular targets of nobiletin.

Production of Glucoamylase from Novel Strain of Alternaria Alternata under Solid State Fermentation.

Glucoamylase has an essential role as biocatalyst in various important industries of Pakistan. It is synthesized by using various fungal and bacterial strains, and different ecocultural conditions are applied under solid substrate fermentation method (SSF) to get the highest yield of glucoamylase. Alternaria alternata is an important fungus that can grow on industrial raw material like wheat bran, dried potato powder, tea leaves, rice husk, and sugar cane peel which are used as substrate. Among all, dried potato powder (10g) proved the best fermentation media for growth of fungal strain as well as maximum glucoamylase producer. Moreover, several chemical and physical states were also explored through solid substrate fermentation technique on glucoamylase yield. The highest glucoamylase production was recorded after 72 hours incubation in incubation chamber with 10g raw substrate, 1ml inoculum spore solution, 30°C temperature, and 5 pH. Further, phosphate buffer (5 pH) as moistening agent, 5% starch concentration and media additive as nitrogen (yeast extract), and carbon source (maltose) were screened for maximum glucoamylase titer (17.3 ± 0.05a°U/ml/min) and the highest specific activity (39.2U/mg). These cultural conditions were most appropriate for growth of A. alternata on solid media and production of highest glucoamylase under solid state fermentation procedure that could be utilized for commercial synthesis of glucoamylase.

Frontiers of Ferroptosis in Cancer Treatment.

Recent phenomenal advancements in genomic and proteomic technologies and rapid breakthroughs in the interpretation of large gene expression datasets have enabled scientists to comprehensively characterize the gene signatures involved in ferroptosis. Ferroptosis is an iron-dependent form of non-apoptotic cell death that has gained the worthwhile attention of both basic and clinical researchers. Ferroptosis has dichotomous, context-dependent functions both as a tumor suppressor and promoter of carcinogenesis. Essentially, pharmacological modulation of ferroptosis by its induction as well as its inhibition holds enormous potential to overcome drug resistance and to improve the therapeutic potential of chemotherapeutic drugs in a wide variety of cancers.

Efficacy of linking Breast Awareness Clinics in Gynecology and Obstetrics departments: A pilot project in Zubaida Bani Wing, Fazle-Omar Hospital, Chenab Nagar, Pakistan.

Objectives: Pakistani female population has the highest incidence of Breast cancer among the women belonging to all other Asian countries. This contributed to 28.7% of all new cases of malignancies in 2020 and is also the cause of uppermost cancer mortality in Pakistani females. The number of deaths can be reduced by promoting breast cancer screening, according to recommended programs for high-risk populations. Methods: In order to encourage breast self-examination in women, 12 Breast Cancer Awareness Clinics were set up in Gynecology and Obstetrics outdoor, Zubaida Bani Wing, Fazle Omar Hospital, Chenab Nagar, Pakistan, from September 2019 to February 2020. A total of 238 women with a mean of 29.97±8.9 years were examined and trained to perform the breast self-examination. Results: Around 41% of 222 valid responded women reported that they had knowledge that breast cancer is the major threat to their health in Pakistan. Only 20% were aware of breast cancer screening but poor cognizance about the recommendations for Pakistani women. Knowledge about Breast Self-Examination was recorded in 15 %, whereas only 5.4 % of all the women included in the present study reported to practice it. Moreover, eighty-six percent of the respondents were reported to be hesitant to visit the male doctor. Three cases of most suspected malignancies were referred to specialist consultants and few cases were endorsed for immediate mammograms. Conclusion: Setting up breast awareness and screening clinics at gynecology outdoors with trained female assistants can be effective in promoting Breast Self-Examination and elaborating screening programs countywide to obtain long term benefits in a high-risk population of Pakistan.

An Ignored Contributing Factor of Vitamin-D Deficiency, despite the Strong Association with Breast Carcinoma among Women in Punjab, Pakistan.

Pakistani females are at elevated risk of breast cancer, hence there is a need to explore every possible potential contributing factor. The present study was performed to analyze the perception of women about their Vit-D levels in both urban and rural areas. Women included 154 clinically diagnosed breast cancer patients from different hospitals and 248 randomly selected females as control group were recruited from Punjab, Pakistan. Statistical analysis was done using SPSS to find the association of Vit-D deficiency with breast carcinoma in different age groups. Out of a total of 402 respondent, 51.5% were completely ignorant of their Vit-D level. Pearson's Chi- square test for those who had perception about Vit-D deficiency among the breast cancer patients and control group revealed asymptotic 2-sided significance of 0.004 while among different age groups, 41 to 50 years were most prone to deficiency with P = 0.003. Urban women were found to had 12% greater association of Vit-D deficiency as compared to women living in rural areas. It was concluded that Vit-D deficiency is a highly contributing factor for breast cancer so every female must be aware of the importance of Vit-D and should maintain a sufficient level of this crucially important vitamin.

Anatomical Variations in Pulmonary Fissures on Computed Tomography (CT).

Objective To determine the frequency of anatomical variations in lung fissures using computed tomography (CT) at a tertiary care hospital in Karachi, Pakistan. Methods A cross-sectional study was conducted in the department of Radiology and Imaging Services at Memon Medical Institute Hospital, Karachi, between November 2021 to April 2022. Patients aged between 15 to 92 years with a completed high-resolution CT scan chest were included. Subjects with no significant structural lung disease that could alter the anatomy were analyzed. Baseline data was gathered using a pre-designed questionnaire, and two qualified radiologists assessed the CT chest images. Results A total of 382 subjects participated in this study, out of which 57.1% were males whilst 42.9% were females. The right horizontal fissure was absent in 10 (2.6%) cases. Accessory fissures were seen in 7.33%. The most common fissural variation was azygos fissure (14; 3.7%), followed by superior accessory fissure (six; 1.6%), inferior accessory fissures (four; 1%), and left horizontal fissure (four; 1%). These variations were more common in males. The significant difference was only seen in the superior accessory fissures with respect to gender (P-value<0.05). Conclusion This study showed the presence of accessory fissures in 7.33% of patients, the most common being the azygos fissure, irrespective of gender. The absence of normal right horizontal fissures was observed in 2.6% of cases.

Regulation of cell signaling pathways by Wogonin in different cancers: Mechanistic review.

Natural products have historically been invaluable as a premium source of therapeutic agents. Recent advancements in genomics and structural biology have portrayed a high-resolution landscape of the diversity of proteins targeted by pharmacologically active products from natural sources. Natural product research has generated valuable wealth of information and cutting-edge research-works have leveraged our conceptual knowledge altogether to a new level. Wogonin (5,7-dihydroxy-8-methoxyflavone) is an O-methylated flavone and has attracted noteworthy appreciation because of its ability to pharmacologically target plethora of cell signaling pathways in different cancers. In this mini-review, we have gathered scattered pieces of available scientific evidence to summarize how wogonin pharmaceutically targeted Wnt/?-catenin, JAK/STAT, VEGF/VEGFR and TRAIL-driven apoptotic pathways in wide variety of cancers. We have also critically analyzed how wogonin prevented carcinogenesis and metastasis in tumor-bearing mice. Although researchers have uncovered pleiotropic role of wogonin in the regulation of different oncogenic signaling cascades but there are visible knowledge gaps in our understanding related to regulation of non-coding RNAs by wogonin. Future studies must converge on the unraveling of additional drug targets for wogonin to achieve a fuller and realistic understanding of the chemopreventive properties of wogonin.

Primary Hodgkin's Lymphoma of bone in 7-year-old- an exceptional case report of youngest child in literature.

Hodgkin lymphoma (HL) is mainly considered a nodal disease but extra nodal involvement can also be seen with variable frequency. Solitary bone involvement in HL known as Primary osseous hodgkin lymphoma (POHL) is very rare. It is defined as a lymphoma that is restricted to the bone without any simultaneous organ or lymph node involvement at the time of initial diagnosis. Primary Hodgkin lymphoma of the bone can be very challenging to diagnose because of its rarity especially in children and its variable presentation. Here we report the youngest case of POHL in a girl 7 years of age. She presented with the left leg pain and B-symptoms of fever and weight loss. Initial workup and imaging were suggestive of infection or a bone tumor. Bone biopsy of left hip joint after the multiple courses of antibiotics revealed Reed Sternberg cells in the mixed inflammatory background with CD30 and PAX-5 immunohistochemical positivity confirming classical hodgkin lymphoma, mixed cellularity type. CD99 and CD1a were negative excluding ewing sarcoma and langerhan cell Histiocytosis respectively. Absence of significant lymphadenopathy or visceromegaly on staging computerized tomography (CT) scan confirmed a very rare POHL. She received standard conventional chemotherapy with radiation. Our patient is in remission for five years after treatment.

Differential expression of micro RNA-29 family in non-diabetic adults of diabetic and non-diabetic parents.

OBJECTIVE: MicroRNAs are known to regulate 60% of genes at post translational level. MicroRNAs including Micro RNA-29 family play a vital role in cellular activities and have validate role in numerous metabolic disorders inclusive of diabetes mellitus and its complications. While micro RNA profile changes years before the occurrence of disease. This cross-sectional study was conducted in non-diabetic adults of diabetic and non-diabetic parents to explore the early changes in expression of micro RNA-29 family as it can be served as early biomarker of type 2 diabetes in non-diabetic adults. This study was conducted from January 2019 to January 2021. Micro RNA was extracted from plasma of 50 participants and expression was compared through qPCR. While data was analyzed through SPSS version 21.0. RESULTS: 29a and 29b had lower expression in participants with family history of DM compared to those having no family history of DM (P < 0.0001). While micro RNA 29c was found to be significantly higher in participants with positive family history of type 2 diabetes as compared to those without family history of diabetes (P = 0.001).

Sonographic diagnosis of appendicitis: A pictorial essay and a new diagnostic maneuver.

While many cases of appendicitis are easy to diagnose clinically, a significant number need further workup in the form of imaging. Ultrasound and CT are both used extensively to diagnose or exclude appendicitis, or arrive at an alternate diagnosis. Ultrasound has many advantages but can be a difficult modality to use due to, among other reasons, the anatomical variations in appendicial location. The true retrocolic appendix is particularly difficult to diagnose with ultrasound. This pictorial essay examines the ultrasound features of normal and diseased appendix and proposes a new examining station, the prone view, for visualizing true retrocolic appendicitis.

Cesarean Scar Ectopic Pregnancy: A Diagnostic and Management Challenge.

Cesarean section scar pregnancy is the rarest form of ectopic pregnancy. Cesarean scar ectopic pregnancy poses a diagnostic and management challenge, and if not diagnosed and adequately treated in early pregnancy, it may lead to considerable maternal morbidity or mortality. We describe the presentation, workup including radiology studies, and subsequent management plan of a cesarean scar ectopic pregnancy in a 34-year-old female with a history of four previous cesarean sections. We were successful in treating this rare form of ectopic pregnancy without any maternal morbidity with a combination of medical and surgical management.

Factors Impeding Health-Care Professionals to Effectively Treat Coronavirus Disease 2019 Patients in Pakistan: A Qualitative Investigation.

The coronavirus disease 2019 (COVID-19) pandemic, first reported in late December 2019, is regarded as the most significant public health emergency of the century. According to the World Health Organization (WHO), the current outbreak of COVID-19 has affected millions of people and killed hundreds of thousands in more than 200 countries, including Pakistan. Health-care professionals (HCPs) cannot minimize human interactions or isolate themselves from patients due to their jobs and moral duties. Hence, the outbreak needed HCPs to work in adverse and challenging conditions with possible mental health problems. In light of the stated background, this study aims to explore and understand the factors that impede HCPs to effectively treat COVID-19 patients in Karachi, Pakistan. Based on qualitative methods, a phenomenological approach was considered to record the true experiences of HCPs. Twelve doctors and nurses were recruited from five COVID-19 designated hospitals in Karachi, Sindh Province, using purposive and snowball sampling. Semi-structured in-depth telephone interviews were conducted from April 6 to 14, 2020, and analyzed through thematic analysis. The findings suggest that there were two types of constraints, institutional and personal, which were impeding HCPs to treat COVID-19 patients effectively. Institutional constraints include the poor condition of isolation wards, inadequate availability of personal protective equipment (PPE), excessive and uneven workload, and absence of emotional and psychological support in hospitals. Besides, personal constraints include nervousness due to the novel virus, a constant fear of becoming infected, fear of taking virus to family, extreme isolation and loneliness, and feeling of powerlessness. The study found that HCPs in Pakistan have been dealing with a high risk of infection, causing mental health problems such as stress, anxiety, and depressive symptoms. These mental health problems not only affect attention, understanding, and decision-making capacity of HCPs, which could hinder the fight against COVID-19, but they could also have a continuous effect on their overall well-being on a long-term basis. Therefore, the present study outlines important clinical and policy strategies that are needed to support HCPs as the pandemic continues.

Pharmacological effects of oral vitamin D intake on pulmonary function Test and Interleukin-17 in adult asthmatic patients in Karachi.

Vitamin D is an anti-inflammatory and immuno-modulatory secosteroid. Previous studies showed strong link between childhood and adult onset asthma with vitamin D. Interleukin 17 is an inflammatory cytokine and plays a major role in the worsening of asthma. The aim of this study is to compare the effects of serum vitamin D on serum IL 17 and pulmonary function test (FVC, FEV1, FEV1/FVC) before and after oral vitamin D supplementation. Fifty severe asthmatic patients were selected from out patient department of Chest Medicine Ward, Jinnah post graduate medical center, Karachi. Spirometry was performed by vitalograph compact. Baseline values were as follows: serum vitamin D=13.19±2.37ng/ml, IL-17=20.70±2.13ng/ml, FVC=2.31±0.40L, FEV1=1.40±0.28L,FEV1/FVC=60.15±4.61%. Subjects were given 1000 IU of oral vitamin D capsule per day for six weeks. After this trial all values were found as serum vitamin D=19.03±1.26ng/ml (p<0.001), IL 17=15.40ng/ml (p<0.001), FVC=2.90±0.60 L (p<0.001), FEV1=2.01±0.10L (p<0.001), FEV1/FVC=63.79% ±1.45 (p<0.001). It may be concluded that improvement in serum vitamin D levels improves the status of lung functions, decreases the airway inflammation and hence may decrease the asthma severity.