Doctors' Perception Regarding Bariatric Surgery and Major Barriers in Referral of Morbidly Obese Patients for Surgery in Khyber Pakhtunkhwa.

INTRODUCTION: Obesity is on the rise worldwide and has emerged as a global health concern. It has presented itself as the leading cause of morbidity, disability, and healthcare utilization. Bariatric surgery is a viable treatment option that offers sustained weight loss and improvement in comorbidities. The aim of this study is to determine the perception of doctors regarding bariatric surgery and the major barriers to the referral of morbidly obese for surgery. METHOD: This study is a cross-sectional descriptive study conducted from November 1, 2022, to December 31, 2022. It involved prospective data collection through online questionnaires filled by doctors practicing in Peshawar. The sampling technique was non-probability convenience-based sampling. The sample size was 152. Doctors from all age groups and both genders were included in our study. Non-consenting doctors and those who were practicing bariatric surgery were excluded. Data were analyzed using a statistical package for social sciences (SPSS) version 25.0 (IBM Inc., Armonk, NY). Categorical variables have been presented as frequencies and percentages. Numerical variables have been presented as mean ± SD. RESULTS: A total of 152 doctors participated in our research study; 92 were physicians and 60 were surgeons. The majority of our study participants' patient load per week was >75. Around 47% believed bariatric surgery was a valuable tool in the treatment of morbid obesity. The most commonly reported barrier to referral was surgical complications or side effects (28.9%). CONCLUSION: The study concluded that the awareness regarding bariatric and metabolic surgery remains flimsy among the doctor community. Most of the physicians were unaware of the benefits of the surgical management of obesity. They also had doubts regarding the safety of the procedure. We need proper utilization of awareness strategies to overcome these barriers.

Effect of eCG dose on ovarian haemodynamics, hormonal profiles and prolificacy rate when oestrus was induced during low-breeding season in Beetal goats.

The objectives of the experiment were to determine the effect of two doses of equine chorionic gonadotropin (eCG) in a standard synchronization protocol based on a short-term progesterone (P4 ) priming on ovarian structures and haemodynamics, concentrations of steroid hormones and prolificacy rate when oestrus was induced during low-breeding season (LBS) in Beetal dairy goats. We hypothesized that inclusion of eCG in a short-term P4 priming-based synchronization protocol would increase the blood perfusion to ovarian structures leading to enhance oestrous and ovulatory responses and prolificacy rate in goats. Forty-two multiparous acyclic goats were blocked by body condition and, within block, assigned randomly to receive saline as control (CON), low eCG (L-eCG; 300 IU) or high eCG (H-eCG; 600 IU) dose. Initially, a controlled internal drug release (CIDR) device was placed in the anterior vagina on d -8, followed by removal of CIDR on d -3, concurrent with the administration of PGF2α and eCG according to their respective treatments. Goats were monitored for oestrous response. B-mode and Doppler ultrasonography was performed with 12-h interval, starting from day -3 until natural breeding (day 0), and then on days 5, 10, 15 and 20 post-breeding to monitor follicular and luteal dynamics and blood flow, respectively. Blood was sampled at 0, 12, 24, 36 and 60 h after CIDR removal to quantify plasma concentrations of estradiol-17ß (E2 ), whereas plasma concentrations of P4 were assayed at days 5, 10, 15 and 20 after breeding. Pregnancy and prolificacy rates were determined at day 30 and 150 after breeding, respectively. Data were analysed with mixed-effects models, and orthogonal contrasts were used to evaluate the effect of treatment [Con vs. (½ L-eCG + ½ H-eCG)] and dose of eCG (L-eCG vs. H-eCG). Data are presented in sequence as CON, L-eCG, H-eCG (LSM ± SEM). The oestrous intensity score (152.9 vs. 182.7 vs. 186.5 ± 15.1; p = .02) was greater in eCG-treated goats as compared to CON. Administration of eCG reduced the intervals to standing oestrus (66.2 vs. 41.8 vs. 48.9 h ± 5.5; p = .05), breeding (70.2 vs. 44.4 vs. 45.4 h ± 4.5; p = .03) and ovulation (84.5 vs. 61.2 vs. 63.4 h ± 6.2; p = .05) compared with CON goats. The mean growth rate of pre-ovulatory follicle was greater (1.11 vs. 1.49 vs. 1.45 mm ± 0.08; p = .01) in eCG-treated goats resulting in an increased diameter of pre-ovulatory follicle (6.27 vs. 7.20 vs. 7.31 mm ± 0.07; p < .01) and corpora lutea (6.75 vs. 8.26 vs. 8.07 mm ± 0.42; p = .04) than CON. The mean follicular blood flow did not differ among treatments; however, the mean luteal blood flow was greater in L-eCG-treated goats (0.81 vs. 1.61 vs. 1.07 cm2 ± 0.12; p = .001). The mean concentrations of E2 (4.03 vs. 5.21 vs. 4.78 pg/ml ± 0.42; p = .04) and P4 (4.85 vs. 6.39 vs. 6.22 ng/ml ± 0.34; p = .04) were greater in eCG-treated goats. The twinning rate did not differ between treatments; nevertheless, prolificacy rate was greater (p = .04) in L-eCG-treated goats. Collectively, our data suggest that the administration of eCG improves the induction of oestrous and ovarian dynamics. Administration of L-eCG enhances prolificacy rate, therefore, a low dose of eCG might be practically beneficial to improve reproduction during LBS in acyclic Beetal dairy goats.

Study on Various Luteal Characteristics Using Doppler Ultrasonography for Early Pregnancy Diagnosis in Nili-Ravi Buffaloes.

The objective of current study was to assess the trend in various luteal characteristics viz luteal size (LS), plasma progesterone (P4) concentration, and luteal blood flow (LBF) using color Doppler imaging (CDI) and power Doppler imaging (PDI) modes in pregnant and nonpregnant Nili-Ravi buffaloes. Lactating, cyclic, and healthy Nili-Ravi buffaloes (n = 09) without any reproductive abnormality were selected in present study. Buffaloes were synchronized using Ov-Synch, and fixed-time artificially insemination was performed (day = 0). Pregnancy was diagnosed on 30-day post-AI using B-mode ultrasonography based on presence or absence of embryonic heartbeat. Ovaries of all animals were scanned from day 5 till 21 post-AI using both B-mode and Doppler ultrasonography to measure LS and LBF. After each ovarian ultrasound examination, blood samples were collected via jugular venipuncture to determine plasma P4 concentration. According to results, LBF using CDI and PDI was significantly higher (P ≤ 0.05) in pregnant buffaloes on days 13 and 15 post-AI, respectively. The mean LS and plasma P4 concentration did not differ (P ≥ 0.05) between pregnant and nonpregnant animals until day 15 post-AI. However, a significant difference (P ≤ 0.05) was noticed for both on day 17 and onwards. It is concluded that LBF is a more sensitive luteal character as compared to LS and P4 for earlier pregnancy diagnosis in Nili-Ravi buffaloes when ascertained through CDI.

HnRNP F and hnRNP H1 regulate mRNA stability of amyloid precursor protein.

Amyloid precursor protein (APP) is a transmembrane protein that plays a crucial role in the production of amyloid-ß peptides. Any disruption in APP protein production, its mRNA decay rate or processing may result in abnormal production of amyloid-ß peptides and subsequent development of protein aggregation diseases. Therefore, the equilibrium is crucial for neuronal function. An association study of heterogeneous nuclear ribonucleoprotein (hnRNP)-F and hnRNP H1 with APP was carried out in Neuro-2a (N2a) cells. In the present study, we found that hnRNP F and hnRNP H1 were significantly upregulated in the hippocampus of APP/PS1 mice. The changes in APP expression were positively associated with hnRNP F and hnRNP H1 when hnRNP F and hnRNP H1 were depleted or increased in N2a cells. Importantly, cross-linked RNA immunoprecipitation demonstrated binding affinities of hnRNP F and hnRNP H1 for App mRNA. Mechanistically, mRNA stability assay revealed that overexpression of hnRNP F or hnRNP H1 increases the APP level by stabilizing App mRNA half-life, implying that levels of hnRNP F and hnRNP H1 can change the production of APP. Further understanding of the regulatory mechanism of APP expression in association with hnRNP F and hnRNP H1 would provide insights into the mechanism underlying the maintenance of brain health and cognition. This study provides a theoretical basis for the development of hnRNP-stabilizing compounds to regulate APP.

Early prediction keys for COVID-19 cases progression: A meta-analysis.

BACKGROUNDː: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), within few months of being declared as a global pandemic by WHO, the number of confirmed cases has been over 75 million and over 1.6 million deaths since the start of the Pandemic and still counting, there is no consensus on factors that predict COVID-19 case progression despite the diversity of studies that reported sporadic laboratory predictive values predicting severe progression. We review different biomarkers to systematically analyzed these values to evaluate whether are they are correlated with the severity of COVID-19 disease and so their ability to be a predictor for progression. METHODS: The current meta-analysis was carried out to identify relevant articles using eight different databases regarding the values of biomarkers and risk factors of significance that predict progression of mild or moderate cases into severe and critical cases. We defined the eligibility criteria using a PICO model. RESULTS: Twenty-two relevant articles were selected for meta-analysis the following biomarkers C-reactive protein, interleukin-6, LDH, neutrophil, %PD-1 expression, D-dimer, creatinine, AST and Cortisol all recorded high cut-off values linked to severe and critical cases while low lymphocyte count, and low Albumin level were recorded. Also, we meta- analyzed age and comorbidities as a risk factors of progression as hypertension, Diabetes and chronic obstructive lung diseases which significantly correlated with cases progression (p < 0.05). CONCLUSIONS: ː The current meta-analysis is the first step for analysing and getting cut-off references values of significance for prediction COVID-19 case progression. More studies are needed on patients infected with SARS-CoV-2 and on a larger scale to establish clearer threshold values that predict progression from mild to severe cases. In addition, more biomarkers testing also help in building a scoring system for the prediction and guiding for proper timely treatment.

Novel mutations in the PITX2 gene in Pakistani and Mexican families with Axenfeld-Rieger syndrome.

PURPOSE: Axenfeld-Rieger syndrome (ARS) is a rare autosomal dominant disorder that affects the anterior segment of the eye. The aim of this study was to examine the PITX2 gene to identify possible novel mutations in Pakistani and Mexican families affected by the ARS phenotype. METHODS: Three unrelated probands with a diagnosis of ARS were recruited for this study. Genomic DNA was isolated from the peripheral blood of the probands and their family members. Polymerase chain reaction and Sanger sequencing were used for the analysis of coding exons and the flanking intronic regions of the PITX2 gene. Bioinformatics tools and database (VarSome, Provean, and MutationTaster, SIFT, PolyPhen-2, and HOPE) were evaluated to explore missense variants. RESULTS: We identified novel heterozygous variations in the PITX2 gene that segregated with the ARS phenotype within the families. The variant NM_153426.2(PITX2):c.226G > T or p.(Ala76Ser) and the mutation NM_153426.2(PITX2):c.455G > A or p.(Cys152Tyr) were identified in two Pakistani pedigrees, and the mutation NM_153426.2(PITX2):c.242_265del or p.(Lys81_Gln88del), segregated in a Mexican family. CONCLUSION: Our study extends the spectrum of PITX2 mutations in individuals with ARS, enabling an improved diagnosis of this rare but serious syndrome.

Correlation of Homocysteine Level and Age in Patients with Ischemic Stroke.

Introduction Hyperhomocysteinemia is associated with atherosclerosis, as it can be seen in inborn errors of methionine metabolism. Likewise, many studies have also reported more modest increases in serum homocysteine levels in other atherosclerotic disorders like cardiovascular disease and all types of stroke with a positive correlation with age. But overall literature is controversial. Therefore, this study is being conducted to further investigate the relationship between homocysteine ​​levels and age in patients, especially those with ischemic stroke. Material and methods This cross-sectional study is conducted at a major hospital in Karachi in which all patients with ischemic stroke, diagnosed within 24 hours on CT, and age 40-75 years of both genders were enrolled for six months. Other demographics were also noted like gender, smoking status, and comorbidities (diabetes mellitus [DM], hypertension [HTN]). The homocysteine level was also checked by collecting non-fasting blood. Vitamin B12 level was not checked. The age, weight, height, body mass index (BMI), and homocysteine level's means and standard deviations and the gender, DM, hypertension, and smoking status frequencies and percentages were calculated. The correlation coefficient of homocysteine level and age was also calculated. Stratification was done to see the effects of gender, BMI, DM, and HTN on homocysteine levels by applying the chi-square test. Results The mean age of the patients was 55.60 ± 11.45 years. Gender distribution showed that 111 (62.40%) patients were male, and 67 (37.60%) patients were female. Diabetic, hypertensive, and smoking status of the patients was 58 (32.60%), 96 (53.90%), and 53 (29.80%), respectively. The mean homocysteine level was 14.61, with a standard deviation of 1.47. Pearson's correlation test showed that there is no statistically significant correlation between homocysteine levels and age. But a significant linear relationship was found of homocysteine levels with DM and HTN.  Conclusion Further investigation of the relationship of homocysteine ​​levels with age, diabetes mellitus, and hypertension, and the role of homocysteine as a risk factor for ischemic stroke should be carried out on a larger scale to prove its accuracy. The benefits of screening for homocysteine ​​levels also need to be studied in the elderly, especially those with diabetes mellitus and hypertension, which can lead to timely prevention of strokes and ischemic heart disease with vitamin B supplements, and other appropriate interventions.

Identification of novel CYP1B1 gene mutations in patients with primary congenital and primary open-angle glaucoma.

BACKGROUND: CYP1B1 is the most commonly mutated gene in primary congenital glaucoma (PCG), and mutations have also been identified in primary open-angle glaucoma (POAG). This study was undertaken to describe mutations in CYP1B1 in patients and families with PCG and POAG from Pakistan. DESIGN: Case-control series. PARTICIPANTS: Forty families, 190 sporadic POAG cases and 140 controls from Pakistan. METHODS: Patients and healthy individuals of one consanguineous Pakistani family were genotyped with high-resolution single nucleotide polymorphism microarrays. Homozygosity mapping was performed using HomozygosityMapper. Direct sequencing of CYP1B1 gene was performed in probands of the families, sporadic POAG cases and control individuals. MAIN OUTCOME MEASURES: Mutations in the CYP1B1 gene in PCG and POAG patients. RESULTS: Homozygosity mapping in a consanguineous Pakistani family revealed one 11-Mb homozygous region encompassing the CYP1B1 gene. A homozygous CYP1B1 missense mutation (p.Arg390His) was identified in this family. Sequence analysis of CYP1B1 in 39 additional families revealed one known and three novel homozygous mutations in PCG (p.Ala288Pro, p.Asp242Ala, p.Arg355* and p.Arg290Profs*37). In POAG, one novel heterozygous missense mutation (p.Asp316Val) was identified in one family and a previously reported mutation (p.Glu229Lys) was identified in three families. Analysis of CYP1B1 in a panel of 190 sporadic POAG patients revealed three novel heterozygous variants (p.Thr234Lys, p.Ala287Pro and p.Gln362*) and three previously reported heterozygous variants (p.Gly61Glu, p.Glu229Lys and p.Arg368His). The p.Glu229Lys variant was significantly associated with POAG (P = 0.03; odds ratio 2.49). CONCLUSIONS: This study confirms that CYP1B1 mutations are associated with POAG and PCG in the Pakistani population.

Lipid stability and antioxidant profile of microsomal fraction of broiler meat enriched with α-lipoic acid and α-tocopherol acetate.

The importance of the linkage between nutrition and health is a hot issue. Like other food-related sectors, the meat industry is undergoing foremost transformations, driven among other things by changes in consumer requirements. The present study was designed to evaluate the lipid stability and antioxidative potential of leg and breast microsomal fraction of broiler meat fed on ALA and ATA. For the first 3 weeks of growth, broilers were fed on feed supplemented with ATA (200 mg/kg of feed) and during the last 3 weeks broilers were fed on feed supplemented with ALA (25, 75, 150 mg/kg of feed) and a constant level of ATA (200 mg/kg of feed). The body weight of the carcass was measured after every week of growth until 6 weeks. Positive correlation between the antioxidant activity and the TPC was observed. Higher values of TBARS were detected in leg muscles than in breast muscles. HPLC data revealed ALA and ATA contents were higher in T(4) (leg, 5.55 ± 0.19 and 3.87 ± 0.15 µg/mg of protein; breast, 5.63 ± 0.20 and 2.03 ± 0.10 µg/mg of protein, respectively) and lowest in T(5) (ALA, leg, 1.40 ± 0.06 µg/mg of protein; breast, 1.54 ± 0.05 µg/mg of protein; ATA, leg, 1.25 ± 0.06 µg/mg of protein; breast, 0.63 ± 0.008 µg/mg of protein), in which the only oxidized oil was used. Oxidized oil in feed reduced weight gain and increased TBARS, whereas TPC, DPPH, ALA, and ATA values decreased in both leg and breast meat.

A new HPLC method for the simultaneous determination of ascorbic acid and aminothiols in human plasma and erythrocytes using electrochemical detection.

A new, simple, economical and validated high-performance liquid chromatography linked with electrochemical detector (HPLC-ECD) method has been developed and optimized for different experimental parameters to analyze the most common monothiols and disulfide (cystine, cysteine, homocysteine, methionine, reduced (GSH) and oxidized glutathione (GSSG)) and ascorbic acid present in human plasma and erythrocytes using dopamine as internal standard (IS). Complete separation of all the targets analytes and IS at 35°C on Discovery HS C18 RP column (250 mm × 4.6mm, 5 µm) was achieved using 0.05% TFA:methanol (97:3, v/v) as a mobile phase pumped at the rate of 0.6 ml min(-1) using electrochemical detector in DC mode at the detector potential of 900 mV. The limits of detection (3 S/N) and limits of quantification (10 S/N) of the studied compounds were evaluated using dilution method. The proposed method was validated according to standard guidelines and optimization of various experimental parameters and chromatographic conditions was carried out. The optimized and validated HPLC-ECD method was successfully applied for the determination of the abovementioned compounds in human plasma and erythrocytes. The method will be quite suitable for the determination of plasma and erythrocyte profile of ascorbic acid and aminothiols in oxidative stress and other basic research studies.