Development of novel polymer haemoglobin based particles as an antioxidant, antibacterial and an oxygen carrier agents.

This innovative work aims to develop highly biocompatible and degradable nanoparticles by encapsulating haemoglobin (Hb) within poly-ε-caprolactone for novel biomedical applications. We used a modified double emulsion solvent evaporation method to fabricate the particles. A Scanning electron microscope (SEM) characterized them for surface morphology. Fourier Transform Infrared Spectroscopy (FTIR) and Ultraviolet-visible spectroscopies (UV-visible) elucidated preserved chemical and biological structure of encapsulated haemoglobin. The airproof equilibrium apparatus obtained the oxygen-carrying capacity and P50 values. The DPPH assay assessed free radical scavenging potential. The antibacterial properties were observed using four different bacterial strains by disk diffusion method. The MTT assay investigates the cytotoxic effects on mouse fibroblast cultured cell lines (L-929). The MTT assay showed that nanoparticles have no toxicity over large concentrations. The well-preserved structure of Hb within particles, no toxicity, high oxygen affinity, P50 value, and IC50 values open the area of new research, which may be used as artificial oxygen carriers, antioxidant, and antibacterial agents, potential therapeutic agents as well as drug carrier particles to treat the cancerous cells. The novelty of this work is the antioxidant and antibacterial properties of developed nanoparticles are not been reported yet. Results showed that the prepared particles have strong antioxidant and antibacterial potential.

Phytochemical analysis and gastroprotective effect of Stellaria media (L.) Vill. methanolic extract on piroxicam-induced gastric ulcer in Wistar rats.

Stellaria media L. has traditionally been used to treat inflammatory and gastrointestinal ailments. This study aimed to phytochemically characterize the S. media extract and explore its anti-ulcer efficacy against piroxicam-induced stomach lesions in Wistar rats. Phytochemical analysis was performed and antioxidant capacity of extract was determined using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. In vivo, piroxicam (30mg/kg) was administered to induce gastric ulceration. Gastro protective effect of S. media extract was observed at 150, 300 and 450mg/kg, respectively. While omeprazole (20mg/kg) was used as a conventional anti-ulcer drug. After oral treatment for 14 days, stomach acidic secretions, ulcerogenic indices, hematological markers and oxidative stress parameters were assessed along with histological examination. The existence of polyphenol contents in S. media extract was confirmed in correlation to a marked DPPH inhibition (IC50 27.94µg/mL). S. media extract resulted in a dose-dependent elevation in gastric pH while a decrease in acid volume, acidity and ulceration. Also, S. media extract administration restored the impaired hematological markers (RBCs, Hb, WBCs and PLTs) and decreased oxidative stress by reducing oxidants (TOS and MDA) while raising antioxidants (TAC and CAT). Furthermore, gastric histological results corroborated the aforementioned findings. Conclusively, S. media could provide a promising protective effect against drug-induced gastric ulceration.

Development of a Lateral-Flow Immunochromatographic Strip for the Detection of Oxytetracycline Residues in Biological Fluids.

Oxytetracycline (OTC) is extensively used in veterinary medicine and for growth promotion around the globe. The indiscriminate use of OTC in food-producing animals leaves residues in animal products. The presence of these residues in animal products causes economic losses and harmful effects on consumers. Different regulatory bodies set maximum residue limits (MRLs) for different tetracyclines. To avoid harmful effects, there is a need for a simple, fast, and economical method for the screening of animal products. In this study, a fast, economical, and user-friendly lateral-flow immunochromatographic (LFIC) assay based on gold nanoparticles (AuNPs) was developed to detect the presence of OTC residues in biological fluids. AuNPs provided visual results as red lines in 6-15 min. Polyclonal rabbit IgG antibodies were produced using the immunogen of OTC. These antibodies were purified by the combined ammonium sulfate-octanoic acid precipitation method. Antibodies were conjugated to AuNPs as recognition biomolecules. A LFIC strip was optimized using borate buffer spiked with different concentrations of the OTC. The visual limit of detection (LOD) in different biological samples (milk, serum, and urine) was determined using samples spiked with OTC. The LOD was found to be 15 µg/L, which is very low from the MRL (100 µg/L) set by different regulatory authorities. This LFIC strip can be used to detect OTC residues in biological fluids for point-of-care testing (POCT). These strips are easy to use, cost-effective, and portable and provide quick results without the use of laboratory instruments.

The Association Between Deficiency of Vitamin D and Diabetes Mellitus Type 2 (DMT2).

Background  The impact of vitamin D deficiency on the incidence of various diseases and its relationship with the progression of diabetes mellitus type 2 (DMT2) is still controversial. The present study evaluated the incidence of vitamin D deficiency in patients with DMT2. Methodology  A cross-sectional study was conducted in a tertiary care hospital, Sindh, Pakistan from October 2020 to September 2021. A total of 525 patients of DMT2 were recruited. Another 525 patients acted as healthy controls. In patients with DMT2, blood samples were taken in the morning to measure vitamin D levels. All socio-demographic and clinical data were documented in a predefined pro forma. The association between the incidence of DMT2 and hypovitaminosis was explored.  Results The mean age of the patients was 50 ± 5.5 years. There were 100 (54.1%) male and 85 (45.9%) female patients. The mean duration of diabetes of the patients was 6.8 ± 2.4 years. The mean serum 25-hydroxy vitamin D level was 22.3 ±10.4 ng/ml. In the case group, the majority of the patients had vitamin D deficiency i.e. 54.1%, while only 25.9% of controls had hypovitaminosis. Vitamin D deficiency was significantly correlated with the occurrence of DMT2 (p<0.0001).  Conclusion The current study indicates that patients with diabetes mellitus type 2 (DMT2) more frequently suffer from vitamin D deficiency. Those patients with vitamin D deficiency and DMT2 can benefit from vitamin D replenishment. This may help improve glycemic control in these patients. This study served as a catalyst for future studies where the relationship between hypovitaminosis and insulin resistance can be thoroughly explored.

Hepatic manifestations of COVID-19 and effect of remdesivir on liver function in patients with COVID-19 illness.

COVID-19 has emerged as a major global health crisis since the first cases were reported in China in December 2019. Remdesivir is the only broad-spectrum antiviral approved by the US Food and Drug Administration to treat hospitalized patients with COVID-19 infection. Although the adverse effects of remdesivir are largely unknown, data from randomized controlled trials have demonstrated its deleterious effect on the liver. This review briefly addresses the hepatic manifestations of COVID-19 infection and the data regarding the efficacy and adverse effects of remdesivir on liver function when used in patients hospitalized with COVID-19. Through a literature search, we identified five randomized controlled trials, two case reports, and one case series, including a total of 2375 patients. Although mild transaminase elevation has been reported as a feature of COVID-19, there has been a concern of hepatotoxicity associated with the use of remdesivir. Based on the limited available data regarding the adverse effects of remdesivir on hepatic function, it is prudent to exercise caution by evaluating baseline liver function, avoiding the use of potentially hepatotoxic drugs, and closely monitoring liver function when using remdesivir in patients hospitalized with COVID-19.

Multiplex Molecular Stool Testing Rarely Impacts Antimicrobial Treatment Decisions More Than Three Days After Admission.

Background Acute diarrheal illness in the United States is a significant cause of healthcare utilization and hospitalizations. For patients who develop diarrhea while hospitalized, testing for pathogens other than Clostridium difficile (C. difficile) using conventional stool testing is low yield. Newer testing modalities for infectious diarrhea such as the multiplex molecular stool testing provide an improved detection rate and a faster turn-around time compared to conventional stool testing.  Methods We retrospectively examined the use of a multiplex molecular stool test at our institution for all hospital encounters over a two-year period to determine which organisms were identified ≤ 3 days and > 3 days after admission.  Results A total of 2032 patients underwent multiplex molecular stool testing during the study period, with 1698 (83.6%) performed ≤ 3 days and 334 (16.3%) > 3 days after admission. An enteric non-C. difficile pathogen was identified more frequently when patients were tested ≤ 3 days after admission (350, 20.6%) as compared to > 3 days after admission (38, 11.4%, p<0.0001). Excluding coinfections, C. difficile was identified more frequently when patients were tested > 3 days after admission (64, 20.3%) versus another organism (30, 9.0%) (p<0.0001). Of those patients with a non-C. difficile pathogen identified > 3 days after admission, a bacterial pathogen amenable to treatment was only identified in 6% (21) of patients.  Conclusion Multiplex molecular stool testing for patients tested > 3 days after admission is a low yield of information that could guide antimicrobial treatment decisions, and C. difficile testing is more useful in this clinical situation.

Outer Membrane Protein-Coated Nanoparticles as Antibacterial Vaccine Candidates.

Nanoformulations are novel therapeutic strategies as compared to traditional treatments. The development of biomimetic nanoparticles by combining the natural cellular material with synthetic nanoparticles has inspired innovative vaccine strategies for modifying the antibacterial immunity. A lot of work has been done in which synthetic nanoparticles are coated with biomimetic cellular membranes for enhancement of biological functions and treatments. Outer membrane protein of bacteria not only act as adjuvant but also contain a large number of immunogenic antigens that play an important role in motivating the native immunity and stimulating the immune responses of the body. Outer membrane protein coating onto the surfaces of synthetic nanoparticles has synergistic effects to produce antibacterial responses. This article reviews the recent improvements related to the bacterial membrane-coated nanoparticles for antibacterial immunization.

Bed side teaching: Student's perception and its correlation with academic performance.

OBJECTIVE: To determine student's perception of bedside clinical teaching and to correlate it with their performance in assessment. METHODS: This cross-sectional study of correlational survey was conducted at Services Institute of Medical Sciences in September 2019, involving students of final professional year who filled a proforma to rate their bedside teaching experience during clinical rotations using rating scale. Mean scores of items were determined with score < 3 reflecting dis-satisfaction. Mean scores were compared between high and low performing students using student's t test. RESULTS: Total of 160 students participated. Physical environment domain was assigned lowest scores by students (mean 2.94±0.74) followed by teaching task by teachers (3.04±0.72), group dynamics (3.16±0.81) and patient comfort and attitude towards patient (3.87±0.60). Teaching task by teacher had maximum stems with scores < 3 needing significant improvement. Students with low academic performance were more unsatisfied with group dynamics of bedside teaching (p value 0.009), especially lack of equal opportunities of participation for every member (p value <0.000) in clinical rotations. CONCLUSION: Small size group with adequate space for bedside training and faculty training can enhance learning experience of students. Ensuring active participation of each group member during bedside learning can improve academic performance of students.

ST Elevation in a Patient With COVID-19 Infection-Associated Fever: A Case of Brugada Pattern.

Coronavirus disease 2019 (COVID-19) is a global pandemic presenting with various cardiovascular manifestations. Although Brugada pattern ST-segment elevation (STE) is well described in patients admitted with febrile illness, the implication of recognizing this abnormality in patients with COVID-19 is critical in providing appropriate care for the patient and also reducing the exposure of healthcare professionals to the risk of infection. We report a patient with COVID-19 infection presenting with STE due to fever-related unmasking of Brugada pattern, who was managed conservatively.

Primary prophylaxis of hepatic encephalopathy in decompensated cirrhosis: Low dose vs. full dose rifaximin.

OBJECTIVE: To compare efficacy of high vs low dose rifaximin for primary prophylaxis of portosystemic encephalopathy (PSE) in decompensated liver cirrhosis. METHODS: In a quasi-experimental double blind randomized study at Services Institute of Medical Sciences (SIMS), Lahore from August 2017 to August 2018, patients of decompensated cirrhosis with no previous PSE were randomized to receive twice daily rifaximin 200mg in Group-A and 550mg in Group-B. Patients were followed for 6 months for development of PSE. RESULTS: In 75 included patients, mean age was 53.8(±10.7) years and male/female ratio was 0.97/1(37/38). After randomization, 34 (45.3%) patients were included in Group-A and 41 (54.7%) patients in Group-B. During 6 month follow up 24 (32%) patients developed PSE, 12 (35.2%) in Group-A and 12 (29.2%) in Group-B, difference was not significant (p value 0.57). In 6 months, 13 (17.3%) patient died, 6 (17.6%) in Group-A and 7 (17.07%) patients in Group-B, difference not significant (p value 0.94). Patients who died had higher bilirubin (p < 0.00), higher serum creatinine (p 0.05), high CTP score (p 0.04) and worse MELD score (p 0.004). CONCLUSION: Rifaximin is not effective for primary prophylaxis of overt hepatic encephalopathy in decompensated cirrhosis patients.

Prevalence of extensive drug resistance in bacterial isolates harboring blaNDM-1 in Quetta Pakistan.

OBJECTIVE: Extensive drug resistant Gram-negative bacilli, harboring New Delhi metallo-ß-lactamase-1 (bla NDM-1) having the ability to hydrolyze ß-lactams, have become a vital global clinical threat. The present study was, therefore, designed to investigate the prevalence and epidemiology of NDM-1 producers in Quetta, Pakistan. METHODS: This study was carried out in Microbiology Laboratory, Bolan Medical Complex Hospital Quetta, Biotechnology laboratory, BUITEMS Quetta and Hi-tech laboratory, CASVAB, University of Balochistan, Quetta, from March to June 2018, during the hot season. Biochemical and molecular approaches were applied for the identification of bacterial isolates. Minimum Inhibitory Concentrations (MICs) were determined using E-test method. Carbapenemase activity was ascertained by Modified Hodge Test (MHT) and the presence of blaNDM-1 gene was recognized by Polymerase Chain Reaction (PCR). RESULTS: We isolated five bla NDM-1 harboring isolates of three different species namely Morganella morganii (n=2) Enterobacter cloacae (n=2) and Citrobacter freundii (n=1), from 300 pus samples. These isolates were found extensive drug resistant (XDR). Strikingly, two isolates of M. morganii were displaying resistance against 23 antibiotics of sulphonamides, aminoglycosides, polypeptide, monobactams, tetracyclines, quinolones, macrolides, cephalosporins, phosphonic acid and ß-lactams groups, suggesting Pan Drug Resistance (PDR). CONCLUSION: This is the first report on emergence of PDR strain of M. morganii producing NDM-1 in the province of Balochistan, Pakistan. The presence of bla NDM-1 in different bacterial species and their extensive rather pan drug resistance pattern poses a momentous clinical threat.

Effect of adding daclatasvir in sofosbuvir-based therapy in genotype 3 hepatitis C: real-world experience in Pakistan.

OBJECTIVE: To determine real-world effect of adding daclatasvir (DCV) to chronic hepatitis C treatment by comparing sustained viral response of sofosbuvir (SOF)/DCV±ribavirin (RBV) and SOF+RBV combination in patients with genotype 3 hepatitis C. PATIENTS AND METHODS: Patients with chronic hepatitis C, genotype 3, presenting at the DHMC Hepatology Clinic from October 2014 till March 2018 were treated initially with 6 months of SOF/RBV, and once DCV was available, with SOF/DCV±RBV for 3 or 6 months. Negative hepatitis C virus RNA by PCR, sustained viral response 12 weeks after treatment (SVR12), was the primary end point for per-protocol analysis. RESULTS: The mean age of the 440 enrolled patients was 51.04 (±11.9) years, and male to female ratio was 0.97/1 (217/223). Liver cirrhosis was present in 260 (59.1%) patients, and 89 (20.2%) had decompensated liver disease. Treatment-experienced patients were 124 (28.2%). We included 398 (90.4%) patients with completed follow-up in final analysis, excluding either dropped out, failed to complete therapy or died during follow-up. SVR12 was achieved in 366 (91.9%), being significantly lower (P=0.001) in patients with cirrhosis at 89.9% (205/228), and even lower SVR12 (P=0.006) in decompensated cirrhosis at 87.01% (67/77). SVR12 was also inferior (P=0.005) in treatment experienced patients at 85.8% (97/113) than treatment-naive patients at 94.3% (269/285). Among 285 patients treated with SOF/RBV, SVR12 was achieved in 264 (92.6%), which is not significantly different from SVR12 with SOF/DCV±RBV at 90.2% (102/113) (P=0.57). CONCLUSION: In patients with chronic hepatitis C genotype 3, SOF/RBV and SOF/DCV±RBV have similar sustained viral response, and patients with liver cirrhosis and past treatment experience have suboptimal response in Pakistan.

Health Related Quality of Life (HRQOL) and its correlation with academic performance of medical students.

OBJECTIVE: To determine health related quality of life (HRQOL) of medical students and its correlation with their academic performance. METHODS: Cross sectional study at Services Institute of Medical Sciences, included students of 4th and final year MBBS, who filled SF-36 proforma of HRQOL. Scores of 8-domains and of physical component and mental component summary were determined. Marks in all professional examinations were used to stratify students as high performers (≥ 70% marks) and average performing students (< 70%). HRQOL scores was correlated with academic performance using unpaired student's t-test. RESULTS: Among 267 students included, mental health score (56.2±21.3) was lower than physical health component score (69.03±18.5). Role limitation due to emotional health (RE) (44.81), Vitality (VT) (54.19) and general health perception (GH) (58.89) had lower scores among 8-domains of questionnaire. Female students had significantly lower scores in role limitation due to emotional problems (p value <0.04), vitality (<0.05), bodily pain (p value <0.05) and general health perception (p value<0.03) than male students. Physical health and role limitation due to physical health domains were better in high performing students. CONCLUSION: Mental health of medical students is suboptimal, especially among female students. Students with better physical health have better academic performance.

High-grade Burkitt Lymphoma Presenting as a Buttock Mass and Foot Drop.

Burkitt lymphoma (BL), a highly aggressive B-cell non-Hodgkin lymphoma (NHL), usually presents in children and young adults with large extranodal masses involving jaw bones, gastrointestinal tract, and central nervous system. The three main subtypes of BL are endemic, sporadic, and immunodeficiency variant. Extranodal involvement is common in each variant of BL, although muscle tissue involvement is distinctly rare. Mode of spread may be hematogenous or via direct extension of the primary tumor. In this report, we present a case of a 41-year-old male who presented with a palpable mass in the buttock leading to foot drop as the initial manifestation of BL. An exhaustive review of the literature failed to discover any previous reports of BL occurring in this location.

Glomangiosarcoma Involving the Heart with an Unknown Primary Lesion.

Glomus tumors are usually benign tumors of the glomus cells with the immunocytochemical and structural features of smooth muscle cells. The majority of the cases of glomus tumors are benign but, rarely, they demonstrate malignant features both clinically and histologically (also known as glomangiosarcomas). Although glomangiosarcoma involving extracutaneous sites is uncommon, a few cases have been reported. A glomangiosarcoma of the heart is extremely rare due to the rarity of glomus bodies in the myocardium. In this case report, we present the case of a 31-year-old female with glomangiosarcoma involving the heart with an unknown primary lesion.

Clinico-epidemiological Characteristics of Corrosive Ingestion: A Cross-sectional Study at a Tertiary Care Hospital of Multan, South-Punjab Pakistan.

Introduction Corrosive ingestion is a grave public health problem. It is a medical emergency and shows diverse clinical presentations. The ingestion of corrosive substances has devastating effects on upper gastrointestinal and respiratory tracts and the corrosive injury is associated with numerous life-threatening complications. The present study aims to explore the clinico-epidemiological characteristics of patients of corrosive ingestion presenting at a tertiary care hospital of Multan, Pakistan. Method The target study population consists of all the patients with primary diagnosis of corrosive ingestion who presented to the department of thoracic surgery, Nishtar Medical University Hospital Multan, Pakistan, from January 2016 to December 2017. The follow-up cases and the cases with ingestion of substances other than corrosives were not included in the study. All the included cases were evaluated by detailed history, thorough physical examination and the necessary investigations. The post-cor-rosive tissue damage was classified accord-ing to Zargar's classification system. All the demographic data and other variables were measured and recorded using a Performa. The data were analyzed by using computer program SPSS 21 version. Results The total study population was 206 patients. There were 135 females (65.5%) and 71 male patients (34.5%). Age ranged from 2 to 42 years (mean 23.44 ± 7.19). Only seven cases were found in the age group of 2-7 years. The residents of rural areas showed a slightly increased inclination towards corrosive ingestion. One hundred and ten cases were unmarried (53.4%) while 90 patients were married (43.7%). The incidence of corrosive ingestion was much high in illiterate/less educated patients belonging to the groups of lower socio-economic status. One hundred and ninety-seven patients ingested corrosive substances deliberately with the suicidal intention (95.6%). The acid used as bathroom cleaner and the laundry bleaches were the most commonly used corrosive agents. In 166 cases the corrosive materials were already present at home for domestic purposes (80.6%), but 18 subjects particularly purchased these corrosive substances to commit suicide. The quantity of ingested material ranged between 10 ml and 150 ml with a mean of 42.6 ml ± 33.2. The shortest hospital stay was one day, and the longest one was 60 days. Esophagus and oropharyngeal area were the most common site which sustained the corrosive injury, whereas corrosive injury to duodenum was least frequent (34.5 %). Conclusion Corrosive ingestion is a serious medical problem and it requires a multidisciplinary approach and a good coordination between different medical specialists. Underprivileged teenager females of rural areas are more likely to ingest corrosive materials with suicidal intention. In most of the ingestions, household cleaning products are used. Only the patients with severe corrosive injury should be admitted to intensive care units. Enforcing regulations for the manufacturers of household cleaning products can significantly reduce the incidence of this potentially fatal condition.

Dysfunctional Closed Chest Drainage - Common Causative Factors and Recommendations for Prevention.

Introduction Dysfunctional closed chest drainage unit (CDU) dysfunction is a common but serious clinical problem associated with tube thoracostomy and results in a significant rise in morbidity, prolonged hospital stays, and increased economic burden. This observational study examines the proximate factors of closed CDU dysfunction in addition to their relative frequency. Based on our findings, we suggest logical recommendations for preventing the factors that contribute to closed chest drainage unit dysfunction. Method The study target population consists of all those individuals who had experienced tube thoracostomy for any pathology related to the chest cavity treated in the Department of Thoracic Surgery, Nishter Medical University, Multan, Pakistan, from February 2015 to January 2017. The study population was not restricted by age or gender. Of the 727 examined cases, only those patients who had experienced tube thoracostomy and had significant failure in draining the pleural collection were included in the study. Detailed histories were collected, and thorough physical examinations were carried out for each participant. Chest x-rays and, if needed, computed tomography (CT) scans were obtained to properly examine the placement of the chest tubes and detect the causative factor of the closed CDU dysfunction. Results A total of 139 cases were included in the study. The most common cause of closed CDU dysfunction was the use of the wrong CDU connection (n = 24, 17.3%). Other common problems included inadequate prime fluid use, loose connections, kinked tubes, and overly full bottles. Conclusion Closed CDU dysfunction may be prevented by adopting and following proper protocols for tube thoracostomy.

Lactate Dehydrogenase and ß-Glucuronidase as Salivary Biochemical Markers of Periodontitis Among Smokers and Non-Smokers.

OBJECTIVES: This study aimed to establish lactate dehydrogenase (LDH) and ß-glucuronidase as salivary biomarkers of periodontitis among smokers and non-smokers. METHODS: This cross-sectional case-control study was conducted at the Aligarh Muslim University, Aligarh, India, between January and June 2017. A total of 200 participants were divided into four groups based on their periodontal and smoking statuses. Unstimulated mixed saliva samples were collected to estimate LDH and ß-glucuronidase levels. In addition, total protein was estimated using Lowry's method. RESULTS: There was a significant increase in enzyme activity in the periodontitis groups compared to the non-periodontitis groups (P <0.001). However, significantly lower enzyme activity was observed among smokers, irrespective of periodontal status (P <0.001). Nevertheless, a receiver operating characteristic curve analysis indicated the diagnostic potential of both enzymes to be fair-to-excellent. CONCLUSION: Although smoking was found to significantly alter enzyme activity, LDH and ß-glucuronidase were reliable salivary biomarkers of periodontitis among both smokers and non-smokers.

Diode Laser Assisted Excision and Low Level Laser Therapy in the Management of Mucus Extravasation Cysts: A Case Series.

Introduction: Mucus extravasation cyst is a commonly occurring lesion in oral cavity that may result from traumatic severance of a salivary gland duct with subsequent extravasation of mucus into fibrous connective tissue. After a conventional excision or marsupialization, recurrence is not uncommon. Diode laser offers an effective modality for management of such lesions. Case Reports: Four patients were referred with painless fluctuant swellings on labial and buccal mucosa. After recording history and clinical examination, provisional diagnosis of mucocele was made. All the lesions were excised with a diode laser and biopsy was performed. Surgical wounds were treated with low-level laser therapy (LLLT). Results: Uneventful healing was observed in all 4 cases. Significant reduction in postoperative discomfort was recorded after application of LLLT. Histopathological findings were suggestive of mucus extravasation cysts. Conclusion: Diode laser appears to be a good alternative to conventional modalities for the management of mucus extravasation cysts.