Impact of Limosilactobacillus fermentum probiotic treatment on gut microbiota composition in sahiwal calves with rotavirus diarrhea: A 16S metagenomic analysis study".

BACKGROUND: Diarrhea poses a major threat to bovine calves leading to mortality and economic losses. Among the causes of calf diarrhea, bovine rotavirus is a major etiological agent and may result in dysbiosis of gut microbiota. The current study was designed to investigate the effect of probiotic Limosilactobacillus fermentum (Accession No.OR504458) on the microbial composition of rotavirus-infected calves using 16S metagenomic analysis technique. Screening of rotavirus infection in calves below one month of age was done through clinical signs and Reverse Transcriptase PCR. The healthy calves (n = 10) were taken as control while the infected calves (n = 10) before treatment was designated as diarrheal group were treated with Probiotic for 5 days. All the calves were screened for the presence of rotavirus infection on each day and fecal scoring was done to assess the fecal consistency. Infected calves after treatment were designated as recovered group. Fecal samples from healthy, recovered and diarrheal (infected calves before sampling) were processed for DNA extraction while four samples from each group were processed for 16S metagenomic analysis using Illumina sequencing technique and analyzed via QIIME 2. RESULTS: The results show that Firmicutes were more abundant in the healthy and recovered group than in the diarrheal group. At the same time Proteobacteria was higher in abundance in the diarrheal group. Order Oscillospirales dominated healthy and recovered calves and Enterobacterials dominated the diarrheal group. Alpha diversity indices show that diversity indices based on richness were higher in the healthy group and lower in the diarrheal group while a mixed pattern of clustering between diarrheal and recovered groups samples in PCA plots based on beta diversity indices was observed. CONCLUSION: It is concluded that probiotic Limosilactobacillus Fermentum N-30 ameliorate the dysbiosis caused by rotavirus diarrhea and may be used to prevent diarrhea in pre-weaned calves after further exploration.

Prevalence and Risk Factors of Anemia in Inflammatory Bowel Diseases: A Case-Control Study.

Introduction Inflammatory bowel diseases (IBDs) including Crohn's disease and ulcerative colitis may induce anemia, ranging from 25% to 75% depending on the study population and diagnostic criteria. It might negatively impact their health and quality of life. Objectives The aim of this work is to study the effectiveness and safety of treatments for anemia in patients with IBD. Methodology This case-control study compared patients with IBD who have anemia (cases; n=60) with patients who have IBD but do not have anemia (controls; n=60) from June 2019 to August 2021 in Hayatabad Medical Complex, Peshawar, Pakistan. Data were collected through interviews, from patients` medical records, and from lab test reports. Statistical analysis was performed using SPSS, Version 23.0 (IBM Corp., Armonk, NY). Results Cases had a greater mean age (45.2 years) than controls (42.8 years). Cases included 60% females and controls 45%. Also, cases earned less (p = 0.019). Anemic patients (group 1) had lower mean hemoglobin (10.2 g/dL) and iron than non-anemic controls (group 2) (p = 0.042 and 0.009, respectively). Anemia increased Crohn's Disease Activity Index and Mayo Score. Group 1 has iron deficiency anemia, whereas group 2 has chronic disease. Group 1 reacts rapidly, but gastrointestinal side effects, allergies, and iron overload are more prevalent. Conclusion IBD patients exhibited low hemoglobin and iron, suggesting anemia. Anemia increased disease activity, but not statistically. IBD patients need iron and anemia treatment. Comparing groups demonstrates differences in anemia types, iron replacement history, treatment response, and bad effects, proposing targeted iron supplementation for deficiency anemia and managing chronic illness factors for chronic disease anemia. IBD anemia treatment involves individualization.

Saddle pulmonary embolism in the setting of COVID-19 infection: A systematic review of case reports and case series.

Saddle pulmonary embolism (SPE) is a rare type of pulmonary embolism that can lead to hemodynamic compromise causing sudden deaths. Due to a dearth of large prospective studies in this area, little is known regarding the epidemiology, and prognosis and factors affecting the latter for COVID-19-associated SPE. We aimed to describe COVID-19-associated SPE and quantify and compare mortality and factors affecting mortality among the cases. We included a total of 25 publications with a total of 35 cases. The average age was 45 ± 16.3 years with 11 females and 24 males. Dyspnoea (82.5%), orthopnoea (43.5%), and cough (43.5%) were the most common symptoms, and obstructive shock was present in five (21.7%) patients. The average reported oxygen (O2) saturation was 85.8% ± 11.9 mm Hg. Hypertension (26.1%), diabetes (21.7%), and deep vein thrombosis (21.7%) were the most commonly reported comorbidities. Right heart strain was recognized in seven (30%) patients on electroencephalogram (S1QIIITIII) and 12 (52.2%) patients on echocardiogram. Anticoagulation, thrombolysis, and percutaneous intervention were tried in 21 (91.3%), 13 (56.5%), and 6 (26.1%) cases, respectively. Despite the aggressive management, 2 of 25 (8.7%) patients died in our smaller case report cohort. We conclude that despite aggressive management modalities, the mortality of SPE remains high in COVID-19.

Prevalence of post-vaccine side effects among COVID-19 immunized community of Southern Pakistan.

BACKGROUND: The response to the vaccine may vary among individuals. Hence, it is important to know how often individuals experience side effects after immunization against COVID-19. OBJECTIVE: This study aimed to assess the incidence of side effects following COVID-19 vaccination across different vaccine recipients in Southern Pakistan and identify the potential factors associated with these side effects in the population. METHODS: The survey was conducted across Pakistan through Google-forms Links from August to October 2021. The questionnaire included demographic information and COVID-19 vaccine information. Chi-square (x2) was performed for comparative analysis to check the significance level with P <0.05. The final analysis included 507 participants who had received COVID-19 vaccines. RESULTS: Of the total 507 COVID-19 vaccines recipients, 24.9% received CoronaVac, 36.5% received BBIBP-CorV, 14.2% received BNT162b2, 13.8% received AZD1222, and 10.7% received mRNA-1273. The most prominent side effects after the first dose were fever, weakness, lethargy, and pain at the site of injection. Moreover, the most commonly reported side effects after the second dose were pain at the injection site, headache, body ache, lethargy, fever, chills, flu-like symptoms, and diarrhea. CONCLUSION: Our results suggested that the side effects due to COVID-19 vaccination can vary between the first and second doses and type of COVID-19 vaccine. Our findings suggest continuing monitoring of vaccine safety and the importance of individualized risk-benefit assessment for COVID-19 immunization.

Study of MDM2 as Prognostic Biomarker in Brain-LGG Cancer and Bioactive Phytochemicals Inhibit the p53-MDM2 Pathway: A Computational Drug Development Approach.

An evaluation of the expression and predictive significance of the MDM2 gene in brain lower-grade glioma (LGG) cancer was carried out using onco-informatics pipelines. Several transcriptome servers were used to measure the differential expression of the targeted MDM2 gene and search mutations and copy number variations. GENT2, Gene Expression Profiling Interactive Analysis, Onco-Lnc, and PrognoScan were used to figure out the survival rate of LGG cancer patients. The protein-protein interaction networks between MDM2 gene and its co-expressed genes were constructed by Gene-MANIA tool. Identified bioactive phytochemicals were evaluated through molecular docking using Schrödinger Suite Software, with the MDM2 (PDB ID: 1RV1) target. Protein-ligand interactions were observed with key residues of the macromolecular target. A molecular dynamics simulation of the novel bioactive compounds with the targeted protein was performed. Phytochemicals targeting MDM2 protein, such as Taxifolin and (-)-Epicatechin, have been shown with more highly stable results as compared to the control drug, and hence, concluded that phytochemicals with bioactive potential might be alternative therapeutic options for the management of LGG patients. Our once informatics-based designed pipeline has indicated that the MDM2 gene may have been a predictive biomarker for LGG cancer and selected phytochemicals possessed outstanding interaction results within the macromolecular target's active site after utilizing in silico approaches. In vitro and in vivo experiments are recommended to confirm these outcomes.

Nanotechnology in interventional cardiology: A state-of-the-art review.

Despite the contemporary techniques and devices available for invasive cardiology procedures, the current diagnostic, and interventional modalities have many shortcomings. As a contemporary cross-disciplinary technique, nanotechnology has demonstrated great potential in interventional cardiology practice. It has a pivotal role in detecting sensitive cardiac biomarkers, nanoparticle-enhanced gadolinium (Gd) contrast to enhance the detection of atherosclerotic cardiovascular disease (ASCVD), and multimodal imaging like including optical coherence tomography (OCT)/infrared luminescence (IR) for coronary plaque characterization. Furthermore, in invasive cardiology, the potential benefit is in miniaturized cardiac implantable electronic devices (CIEDs), including leadless pacemakers and piezoelectric nanogenerators to self-power symbiotic cardiac devices. Nanoparticles are ideal for therapeutic drug delivery systems for atherosclerotic plaque regression, regeneration of fibrotic cardiomyocytes, and disruption of bacterial biofilm to enhance and prolong the effects of antimicrobial agents in infective endocarditis (IE). In summary, nanotechnology-assisted therapies can overtake conventional invasive cardiology and expand the horizon of microtechnology in the diagnosis and treatment of CAD in the foreseeable future.

Human monkeypox virus: An updated review.

The human monkeypox is an emerging zoonotic orthopoxvirus with a clinical presentation similar to that of smallpox. It is difficult to differentiate monkeypox from other orthopedic infections, and laboratory diagnosis is the primary component of disease identification and monitoring. However, current diagnostics are time-consuming, and new tests are needed for rapid and precise diagnosis. Most cases have been reported in Central Africa; however, an increasing number of cases have been reported in Europe, the United States of America (USA), Australia, and the United Arab Emirates. Although investigation of the current global outbreak is still ongoing, viral transmission seems to have occurred during crowded events in Spain and Belgium. New therapeutics and vaccines are being deployed for the treatment and prevention of monkeypox, and more research on the epidemiology, biology, and ecology of the virus in endemic areas is required to understand and prevent further global outbreaks.

Formulation of Modified-Release Bilayer Tablets of Atorvastatin and Ezetimibe: An In-Vitro and In-Vivo Analysis.

The objective of this work was to formulate co-loaded bilayer tablets containing ezetimibe (EZB) and atorvastatin (ATC). ATC loaded in the immediate-release (IR) layer is an HMG CoA reductase inhibitor, while EZB, added in the sustained-release (SR) layer, is a lipid-lowering agent. This study was conducted to evaluate the effects of polymer on the formulation and characterization of bilayer tablets, as well as the therapeutic impact of the concurrent use of both drugs having a sequential release pattern. To obtain the optimized results, four different formulations with variable compositions were developed and evaluated for different parameters. The drug release studies were carried out using a type II dissolution apparatus, using phosphate buffer solution (PBS) of 1.2 pH for IR of EZB for an initial 2 h, followed by 24 h studies for ATC in PBS 6.8 pH. The IR layer showed rapid drug release (96%) in 2 h, while 80% of the ATC was released in 24 h from the SR layer. Locally obtained, 6-week-old female albino rats were selected for in vivo studies. Both preventive and curative models were applied to check the effects of the drug combination on the lipid profile, atherosclerosis and physiology of different organs. Studies have shown that the administration of both drugs with different release patterns has a better therapeutic effect (p < 0.05), both in preventing and in curing hyperlipidemia. Conclusively, through the sequential release of ATC and EZB, a better therapeutic response could be obtained.

A Novel Method of Quantifying the Choriocapillaris in Normal and Post-inflammatory Eyes.

OBJECTIVE: To assess the reliability and validity of gray level co-occurrence matrices (GLCM) in the quantification of choriocapillaris and describe GLCM features in normal and eyes with resolved acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and serpiginous choroiditis (SC). METHODS: In this, multicenter, reliability, validity and comparative study; OCTA was performed on eyes with resolved APMPPE and SC and normal individuals. CC texture classification, low flow area measurements and GLCM feature extraction were performed. RESULTS: A total of 13 normal, 8 APMPPE and 15 SC eyes were analyzed. All GLCM parameters demonstrated an excellent reliability. GLCM parameters were differently distributed across the three groups. Decision-tree based on the random forest predictive model provided an overall accuracy of 86% in classifying the three groups using GLCM features. CONCLUSION: These data demonstrated an excellent reliability and validity of GLCM features in quantifying the choriocapillaris in healthy and diseased eyes.

Intradermal application of tranexamic acid (TA) as treatment of melasma in the out-patients department of a public sector hospital: A pilot study.

The effect of intradermal TA on melasma was evaluated as a possible treatment modality on all of the 11 patients (fitting the inclusion criteria) presenting in the out-patient department of the Benazir Bhutto Hospital, Rawalpindi during Sep 2019 to Mar 2020. Their pre- and post-interventional results were evaluated after being injected with 4 mg/ml of TA on the lesions once weekly for 6 weeks, using Wilcoxon signed rank test in SPSS v 24. The average duration of melasma in our patients was 25.3±7.6 in months. The mean modified MASI score rating was 12.2 (2.3) and 5.1 (1.4) before and after intervention with intradermal TA respectively. The largest difference obtained in the mMASI scores of the patients was 10.8. TA has a distinctive effect as a treatment modality for melasma, as it is easily employable with very few side effects.

Effect of physical activity and vitamin D compared with vitamin D alone on muscle strength, back flexibility and aerobic activity in patients with chronic kidney disease: A comparative study from Pakistan.

BACKGROUND AND OBJECTIVES: To compare the differences in musculoskeletal health with vitamin D alone in comparison with vitamin D with physical activity (PA) among chronic kidney disease (CKD) patients. METHODS AND STUDY DESIGN: An open labeled, randomized, controlled trial was conducted at two tertiary care centers in Pakistan. Patients with CKD stage 2-4 and vitamin D deficiency (<20 ng/mL) were recruited in the trial. Both the arms were given oral vitamin D (cholecalciferol) drops (4000 IU) once daily for three months. One arm received only vitamin D (VD arm), while the second arm received vitamin D along with PA (VDPA arm). RESULTS: Of the 1,235 CKD stage 2-4 subjects contacted, forty-six subjects were enrolled. Eighteen were assigned to VD arm and twenty-eight were assigned to VDPA arm. Between groups comparison shows that bicep strength increases from 15 to 17 kg. Likewise, back flexibility and aerobic fitness also increased among those who receive vitamin D and physical activity, however these differences were not statistically significant (p>0.05). Sensitivity analysis within group comparison shows rise of bicep strength from 13.8 kg to 15.2 kg in the VD alone arm (p=0.05); however, in the VDPA arm, there is a greater difference of 14.3 kg to 17.2 kg (p<0.001). CONCLUSIONS: Targeted PA among CKD patients has potential to improve bicep strength and back flexibility. However, as the sample size was small, further studies would be required to suggest whether a PA should be included as part of the treatment regimen.

Inpatient Case-mix Cost Vs Average Cost for Health Care Services in King Fahd Central Hospital, Saudi Arabia: A Comparative Study.

Health care systems aim to deliver high-quality medical care while considering efficient resource usage and cost-effective forms of interventions. Such purposes require scientific tools or mechanisms which aid in cost assessment before the efforts of cost reduction are considered. Diagnosis-related groups based costing methodology (Case-mix) is considered one of the preferred costing approaches in the health care sector. King Fahd Central hospital Jazan, the only tertiary hospital in the Jazan region, was selected for case-mix system-based patient-level costing of health services. The study's objective was to estimate the cost per Diagnosis-Related Group (DRG) per inpatient admission and compare it with the already established average cost of health care services for inpatients. We applied a cross-sectional retrospective approach to categorize the inpatients based on their diagnosis and procedures and then estimate the actual cost of health care services provided to inpatients during 2018 and compared it with the average cost of the health services. There was a considerable difference between DRG-based costing (SAR 269,663,897) and average costing (SAR 247,035,938). The Diagnosis Related Group costing was found to be more reliable and representative of the services provided to the patients and is recommended to be used for reimbursement purposes.

Examining the Correlation of Google Influenza Trend with Hospital Data: Retrospective Study.

INTRODUCTION: Many studies have explored social media and users search activities such as Google Trends to predict and detect influenza activities. Studies that examined Google Trends correlation with the actual hospital influenza cases were conducted in non-tropical regions that have clearly defined seasons. Tropical areas are known for having less-defined seasonality and the extent of Google Trends concordance with actual influenza cases is unknown for these areas. The goal of this study is to compare Google Trends with hospital cases in tropical regions. METHODS: We analyzed 48,263 influenza cases in the time period of 2010 to 2019. The cases were retrieved from central hospital medical records in tropical regions using the corresponding codes for influenza ICD-10 AM. Cases from the medical records were compared with Google Trends to determine trends, seasonality, and correlation. RESULTS: Graphically, there were some similar areas of the trend, but cross-correlation analysis did not show any significant correlation between hospital and Google Trends with a maximum correlation rate of 0.300. Seasonality analysis showed a clear pattern that peaked around November in Google Trends while hospital data showed less defined seasonality with a smaller peak occurring at the end of December and beginning of January. CONCLUSION: Based on the results, there is a weak correlation between Google Trends and hospital data. More innovative methods are emerging to predict influenza activity using social media and user search data and further study is needed to examine the concurrent trends derived using these methods across regions that have different humidity levels and temperatures.

Association Of Clinical Diagnosis With Histopathology In Various Skin Diseases.

BACKGROUND: Dermatological diagnosis are mainly clinical; however, skin biopsies are frequently done to support clinical diagnosis when in doubt. Aim of this study is to relate the clinical diagnosis of various dermatological conditions with histopathological diagnosis. METHODS: In this descriptive prospective study, 223 patients were enrolled from dermatology OPD at Benazir Bhutto Hospital through non-probability consecutive sampling. Patients were diagnosed clinically and skin biopsies of all patients were taken after informed consent and clinical data was sent to a histopathologist. RESULTS: Patients between ages of 2-85 years were evaluated. Mean age was 39.65±19.43 years. Out of total 223 patients 112 were males and 111 were females. Clinical diagnosis was same as histopathological diagnosis in 180 (80.7%). Out of 80.7% cases, most common disorder was Eczema, 18 cases (10%). The diseases lying in the inflammatory dermatosis group have highest sensitivity, specificity, PPV and NPV, i.e., 91.2%, 90.8%, 84.1% and 86.8% respectively. The discordance between clinical and histological diagnosis was highest in infectious disease group. The concordance between clinical and histological diagnosis in infectious diseases was just 28%. CONCLUSIONS: Documenting a histological diagnosis is essential in dermatology as most of the dermatosis have mimicking clinical presentation. The inflammatory lesions have superior clinical and histopathological correlation as compared to infectious diseases and therefore dermatologists should try to biopsy infective dermatosis more often rather than relying on clinical judgment solely.

Development of unit cost for the health services offered at King FAHD Central hospital Jazan, Saudi Arabia.

BACKGROUND: Efficiency remains one of the most important drivers of decision making in health care system. Fund allocators need to receive structured information about the cost healthcare services from hospitals for better decisions related to resource allocation and budgeting. The objective of the study was to estimate the unit cost for health services offered to inpatients in King Fahd Central hospital (KFCH) Jazan during the financial year 2018. METHODS: We applied a retrospective approach using a top-down costing method to estimate the cost of health care services. Clinical and Administrative departments divided into cost centres, and the unit cost was calculated by dividing the total cost of final care cost centres into the total number of patients discharged in one year. The average cost of inpatient services was calculated based on the average cost of each ward and the number of patients treated. RESULTS: The average cost per patient stayed in KFCH was SAR 19,034, with the highest cost of SAR 108,561 for patients in the Orthopedic ward. The average cost of the patient in the Surgery ward, Plastic surgery, Neurosurgery, Medical ward, Pediatric ward and Gynecology ward was SAR 33,033, SAR 29,425, SAR 23,444, SAR 20,450, SAR 9579 and SAR 8636 respectively. CONCLUSION: This study provides necessary information about the cost of health care services in a tertiary care setting. This information can be used as a primary tool and reference for further studies in other regions of the country. Hence, this data can help to provide a better understanding of tertiary hospital costing in the region to achieve the privatization objective.

Identification of novel vaccine candidates against carbapenem resistant Klebsiella pneumoniae: A systematic reverse proteomic approach.

Klebsiella pneumoniae is declared as antibiotic resistant by WHO, with the critical urgency of developing novel antimicrobial therapeutics as drug resistance is the second most dangerous threat after terrorism. Besides many attempts still, there is no effective vaccine available against K. pneumoniae. By utilizing all the available proteomic data we prioritized the novel proteins ideal for vaccine development using bioinformatics tools and techniques. Among the huge data, eight proteins passed all the barriers and were considered ideal candidates for vaccine development. These include: copper silver efflux system outer membrane protein (CusC), outer membrane porin protein (OmpN), Fe++ enterobactin transporter substrate binding protein (fepB), zinc transporter substrate binding protein (ZnuA), ribonuclease HI, tellurite resistant methyltransferase (the B), and two uncharacterized hypothetical proteins (WP_002918223 and WP_002892366). These proteins were also subjected to epitope analysis and were found best for developing subunit vaccine against K. pneumoniae. The study shows that the potential vaccine targets are sufficiently efficient being virulent, of outer membranous origin and can be proposed for the DNA third-generation vaccines development that would help to cope up infections caused by multidrug-resistant K. pneumoniae.

Interaction of human dynein light chain 1 (DYNLL1) with enterochelin esterase (Salmonella typhimurium) and protective antigen (Bacillus anthraci) might be the potential cause of human infection.

The cytoplasmic dynein light chain 1 (DYNLL1) is an important constituent of motor proteins complex. In human it is encoded by DYNLL1 gene. It is involved in cargo transport functions and interacts with many viral proteins with the help of short linear consensus motif sequence (K/R) XTQT. Viral proteins bind to DYNLL1 through its consensus short linear motif (SLiM) sequence to reach the target site in the cell and cause different infections in the host. It is still unknown if bacterial proteins also contain the same conserved SLiMs sequence through which they bind to this motor protein and cause infections. So, it is important to investigate the role of DYNLL1 in human bacterial infections. The interaction partner proteins of DYNLL1 against conserved viral motif sequences were predicted through PDBSum. Pairwise sequence alignment, between viral motif sequence and that of predicted proteins, was performed to identify conserved region in predicted interaction partners. Docking between the DYNLL1 and new pathogenic interaction partners was performed, by using PatchDock, to explore the protein-protein binding quality. Interactions of docked complexes were visualized by DimPlot. Three pathogenic bacterial proteins i.e., enterochelin esterase (3MGA), protective antigen (3J9C) and putative lipoprotein (4KT3) were selected as candidate interaction partners of DYNLL1. The putative lipoprotein (4KT3) showed low quality binding with DYNLL1. So, enterochelin esterase (3MGA) and protective antigen (3J9C) were speculated to be involved in human bacterial infections by using DYNLL1 to reach their target sites.

Physical and chemical mutagens improved Sporotrichum thermophile, strain ST20 for enhanced Phytase activity.

OBJECTIVE: Phosphorous is an essential micronutrient of plants and involved in critical biological functions. In nature, phosphorous is mostly present in immobilized inorganic mineral and in the fixed organic form including phytic acid and phosphoesteric compounds. However, the bioavailability of bound phosphorous could be enhanced by the use of phosphate solubilizing microorganisms such as bacteria and fungi. The phytases are widespread in an environment and have been isolated from different sources comprising bacteria and fungi. METHODOLOGY: In current studies, we show the successful use of gamma rays and EMS (Ethyl Methane Sulphonate) mutagenesis for enhanced activity of phytases in a fungal strain Sporotrichum thermophile. RESULTS: We report an improved strain ST2 that could produce a clear halo zone around the colony, up to 24 mm. The maximum enzymatic activity was found of 382 U/mL on pH 5.5. However, the phytase activity was improved to 387 U/ml at 45 °C. We also report that the mutants produced through EMS showed the greater potential for phytase production. CONCLUSION: The current study highlights the potential of EMS mutagenesis for strain improvement over physical mutagens.

Molecular analysis of V617F mutation in Janus kinase 2 gene of breast cancer patients.

BACKGROUND: Breast cancer is a multifactorial disease with the highest frequency in females. Genetic and environmental factors can cause mutation in several genes like tyrosine kinase, JAK2 gene which may initiate cancer. Molecular analysis of mutations in the JAK2 gene along with determination of environmental, clinical and haematological risk factors associated with breast cancer patients is need of hour to improve patient's healthcare. Somatic JAK2 valine-to-phenylalanine (617 codon) mutation is one of the widely prevalent mutations. METHODS: Blood was collected from seventy breast cancer patients after their consent. The questionnaire included risk factors, age group, locality, number of children, tumor type, family history, time of initial diagnosis, no of cycles/month, water conditions and exposure to radiations. Molecular analysis were carried out from genomic DNA using Sanger sequencing and allele-specific PCR to check the V617F point mutation. RESULTS: The breast cancer risk factors includes unfiltered water (68.57%), urban (58.57%), menopause (55.71%), family history of cancer (18.57%), tumor grades (II, 37.14% and III, 35.71%), consanguineous marriages (44.28%) and having more than 3-4 children (45.71%). Prevalence of breast cancer was higher after the age of 35 and maximum at 35-50. In allele-specific PCR of 70 patients, 25 patients were wild type (229 bp), 25 patients were with partially deleted gene (200 bp), and 20 patient had shown no or less than 40 bp size fragments. In Sanger's sequencing of 70 BC cases, 18% were found to be positive for V617F point mutation, including 6 homozygous (T/T) and 7 heterozygous (G/T) mutations at nucleotide position 1849 in exon 14 of the JAK2 gene. CONCLUSIONS: Environmental and clinical risk factors were associated with breast cancer which can be overcome by improving awareness of associated risks, health facilities and reducing stress.

Implications of advanced oxidation protein products (AOPPs), advanced glycation end products (AGEs) and other biomarkers in the development of cardiovascular diseases.

OBJECTIVE: To study the putative effects of Advanced Oxidation Protein Products (AOPPs) and Advanced Glycation End Products (AGEs) in the development and progression of cardiovascular disease (CVD). METHODOLOGY: AGEs, AOPPs, e-NOS, lipid profile, circulating stress and inflammatory biomarkers were evaluated among fifty cardiovascular patients and fifty controls. Independent student's t-test was done for statistical analysis. RESULTS: The malondialdehyde mean level in CVD patients (5.45 nmol/ml) was significantly higher than control (1.36 nmol/ml) (p value = 0.018). Nitric oxide in CVD patients (55.72 ng/ml) was remarkably increased as compared to normal subjects (19.19 ng/ml). A significant change in the mean serum level of AGEs in CVD patients (2.74 ng/ml) and normal individuals (0.85 ng/ml) was recorded (p value = 0.000). The AOPPs also showed significant increased levels in CVD group (132.07 ng/ml) in comparison with normal subjects (83.05 ng/ml) (p value = 0.011). The mean eNOS serum level in CVD group (15.50 U/L) was higher than control group (11.28 U/L) (p value = 0.004). Cardiovascular disease patients, in comparison with healthy controls, showed increased level of total cholesterol (5.48 mmol/L vs 4.45 mmol/L), triglycerides (2.59 mmol/L vs 1.24 mmol/L), and low density lipoprotein (2.47 mmol/L vs 2.31 mmol/L) along with decrease in high density lipoprotein (1.39 mmol/L vs 1.74 mmol/L). The mean MMP-11 serum levels in CVD group (98.69 ng/ml) was almost double of control group (45.60 ng/ml) (p value = 0.017). The mean serum level of TNF-α and IL1-α were 32.16 pg/ml and 6.64 pg/ml in CVD patient. The significant decreasing trend of SOD (p value = 0.041), CAT (p value = 0.018), GSH (p value = 0.036) and GRx (p value = 0.029) but increasing drift of GPx (0.023) level was observed in CVD patients. CONCLUSION: This study provides strong evidence that CVD patients presented with elevated oxidative stress, enhanced inflammation and lipid profile in their serum. Therefore, the study strongly approves that AGEs, AOPPs, inflammatory and lipoxidative biomarkers hold predictive potential in causing and aggravating the disease, thus by controlling these factors CVD progression can be inhibited.