Congenital septal defects in Karachi, Pakistan: an update of mutational screening by high-resolution melting (HRM) analysis of MTHFR C677T.

BACKGROUND: Congenital heart defects (CHDs) are the heart structural malformations present at birth. Septal defects account for 40% of CHD, including atrial, ventricular and atrioventricular septal defects. In Pakistan, the prevalence of CHD is 3.4 in 1000, and a study estimated that 60,000 babies are born with CHD annually. Methylenetetrahydrofolate reductase (MTHFR), a chief enzyme, involved in the folate metabolism. The missense mutation, C677T (rs1801133), exists in MTHFR gene, results in a MTHFR thermolabile variant having low enzymatic activity. The study is aim to identify the MTHFR C677T variant association with septal defects. METHODS: Samples of 194 CHD patients (age [Formula: see text]= 5.8 ± 5.1) and 50 normal echo controls (age [Formula: see text]= 6.0 ± 4.9), confirmed by pediatric consultant, were collected. Extracted DNA, quantified by agarose gel electrophoresis and nanodrop, was screened for SNP by high-resolution melting (HRM). Further, HRM results were confirmed using restriction analysis and sequencing. HRM was simply and precisely genotyped the samples within 3 h at low cost. RESULTS: Genotypic data suggested that heterozygous mutant (CT) was frequent in congenital septal defect patients (0.26) which was higher than controls (0.143), p > 0.05. Mutant (TT) genotype was not found in this study. CONCLUSIONS: rs1801133 has lack of significant association with congenital septal defects. The absence of TT genotype in this study suggesting the role of natural selection in targeted population. HRM is an easy, fast and next generation of PCR, which may be used for applied genomics.

ß-Aminoisobutyric acid supplementation attenuated salt-sensitive hypertension in Dahl salt-sensitive rats through prevention of insufficient fumarase.

The human Dietary Approaches to Stop Hypertension-Sodium Trial has shown that ß-aminoisobutyric acid (BAIBA) may prevent the development of salt-sensitive hypertension (SSHT). However, the specific antihypertensive mechanism remains unclear in the renal tissues of salt-sensitive (SS) rats. In this study, BAIBA (100 mg/kg/day) significantly attenuated SSHT via increased nitric oxide (NO) content in the renal medulla, and it induced a significant increase in NO synthesis substrates (L-arginine and malic acid) in the renal medulla. BAIBA enhanced the activity levels of total NO synthase (NOS), inducible NOS, and constitutive NOS. BAIBA resulted in increased fumarase activity and decreased fumaric acid content in the renal medulla. The high-salt diet (HSD) decreased fumarase expression in the renal cortex, and BAIBA increased fumarase expression in the renal medulla and renal cortex. Furthermore, in the renal medulla, BAIBA increased the levels of ATP, ADP, AMP, and ADP/ATP ratio, thus further activating AMPK phosphorylation. BAIBA prevented the decrease in renal medullary antioxidative defenses induced by the HSD. In conclusion, BAIBA's antihypertensive effect was underlined by the phosphorylation of AMPK, the prevention of fumarase's activity reduction caused by the HSD, and the enhancement of NO content, which in concert attenuated SSHT in SS rats.

Comparison of High CPAP versus NIPPV in Preterm Neonates: A Retrospective Cohort Study.

OBJECTIVE: The aim of this study was to compare outcomes following receipt of high continuous positive airway pressure (CPAP) versus nasal intermittent positive pressure ventilation (NIPPV) in extremely preterm neonates. STUDY DESIGN: We retrospectively compared outcomes of preterm neonates (22-28 weeks' gestation) following their first episode of either high CPAP (≥ 9 cm H2O) or NIPPV. Primary outcome was failure of high CPAP or NIPPV within 7 days, as determined by either need for intubation or use of an alternate noninvasive mode. RESULTS: During the 3-year study period, 53 infants received high CPAP, while 119 patients received NIPPV. There were no differences in the primary outcome (adjusted odds ratio 1.21; 95% confidence interval 0.49-3.01). The use of alternate mode of noninvasive support was higher with the use of high CPAP but no other outcome differences were noted. CONCLUSION: Based on this cohort, there was no difference in incidence of failure between high CPAP and NIPPV, although infants receiving high CPAP were more likely to require an alternate mode of noninvasive support. KEY POINTS: · Use of high CPAP pressures (defined as ≥9 cm H2O) is gradually increasing during care of preterm neonates.. · Limited data exists regarding its efficacy and safety.. · This study compares high CPAP with NIPPV, and demonstrates comparable short-term clinical outcomes..

Momordica charantia Extract Confers Protection Against Hypertension in Dahl Salt-Sensitive Rats.

Hypertension is one of the main factors of cardiovascular disease worldwide and is strongly related to the overall mortality. High salt intake is a major risk factors for hypertension. Identifying functional foods that can help prevent mechanistic abnormalities mediating salt-induced hypertension is an issue of considerable nutraceutical and scientific interest. Dietary Momordica charantia may be an alternative approach to avoid salt-induced hypertension. Dahl salt-sensitive (DSS) rats were used to determine whether Momordica charantia water extracts (ME) exerts anti-hypertensive effects in the present study. ME gavage could significantly prevented the increase of blood pressure, blood urea nitrogen, creatinine, and urine protein-to-creatinine ratio of DSS rats. Metabolomics analysis indicated that high-salt diet induced abnormal amino acid metabolism was related to nitric oxide (NO) deficiency, but ME gavage could upregulate the activities of nitric oxide synthase, aspartate aminotransferase, argininosuccinate lyase, argininosuccinate synthase and restore endogenous synthesis of arginine and NO. Meanwhile, renal function was improved after ME gavage. Citrulline, as one of the important component in ME, could attenuate salt-induced hypertension by increasing endogenous synthesis of arginine and NO. Antioxidants in ME, such as phenolic compound, may avoid high-salt induced oxidative stress in DSS rats, which may be another mechanism by which ME prevented blood pressure increase. Thus, the present study indicated that feeding Momordica charantia could avoid high-salt-induced hypertension in DSS rats.

Direct detection of Strongyloides infection via molecular and antigen detection methods.

Laboratory diagnosis of Strongyloides infections can be grouped into direct and indirect detection methods, and a combination of the two methods is often needed to reach an accurate and timely diagnosis. This review focuses on non-conventional direct detection via molecular and antigen detection assays. Conventional PCR is the most commonly used molecular diagnostic for Strongyloides. Real-time PCR is accurate and highly sensitive for quantitative and qualitative analysis. Meanwhile, PCR-RFLP can efficiently distinguish human and dog isolates of S. stercoralis, S. fuelleborni (from monkey), and S. ratti (from rodent). Loop-mediated isothermal amplification (LAMP) amplifies DNA isothermally with high specificity, efficiency, and rapidity, and has potential for point-of-care (POC) translation. As for antigen detection assay, coproantigen detection ELISAs for strongyloidiasis traditionally relied on raising rabbit polyclonal antibodies against the parasite antigens for use as capture or detection reagents. Subsequently, hybridoma technology using animals has enabled the discovery of monoclonal antibodies specific to Strongyloides antigens and was utilised to develop antigen detection assays. In recent times, phage display technology has facilitated the discovery of scFv antibody against Strongyloides protein that can accelerate the development of such assays. Improvements in both direct detection methods are being made. Strongyloides molecular diagnostics is moving from the detection of a single infection to the simultaneous detection of soil-transmitted helminths. Meanwhile, antigen detection assays can also be multiplexed and aptamers can be used as antigen binders. In the near future, these two direct detection methods may be more widely used as diagnostic tools for strongyloidiasis.

Diagnostic accuracy of NMP 22 and urine cytology for detection of transitional cell carcinoma urinary bladder taking cystoscopy as gold standard.

OBJECTIVE: To determine diagnostic accuracy of NMP 22 and urine cytology in the detection of transitional cell carcinoma (TCC) urinary bladder taking cystoscopy as a gold standard in patients having provisional diagnosis of bladder cancer (BC). METHODS: This cross sectional validational study enrolled 380 patients fulfilling selection criteria and was conducted at Armed Forces Institute of Urology (AFIU) Rawalpindi, Pakistan form July 2018 to July 2019. The urine sample collected underwent NMP22 and cytological analysis followed by rigid cystoscopy. Reports of all three tests divided patients into positive or negative for malignancy as per defined criteria. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of NMP 22, urine cytology and their combination was determined. Receiver operating characteristic (ROC) curve analysis performed and area under the curve (AUC) compared among these tests. RESULTS: The average age of patients was 53.08 ± 12.41 years having male to female ratio 3.75:1(300 males and 80 females). NMP 22 had better sensitivity and comparable specificity to cytology (81.9 & 81.2% vs 54 & 93.9%). Combination of NMP 22 / cytology outperformed both in terms of sensitivity (91.63 vs 81.83 vs 53.96), NPV (87.59 vs 77.46 vs 61.02) and diagnostic accuracy (85.26 vs 81.58 vs 71.32) but at the cost of specificity (76.97 vs 81.21 vs 93.94) and PPV (83.83 vs 85.02 vs 92.06). ROC curve revealed statistically significant higher AUC (0.843 vs .815 vs .73) for combination as compared to NMP 22 and Cytology (p < 0.001). CONCLUSION: NMP22 is a quick, point of care test having higher sensitivity, NPV and accuracy but similar specificity and PPV to urine cytology for detection of TCC urinary bladder. Combination outperformed both in terms of sensitivity while having modest specificity.

Curcumin attenuates insulin resistance and hepatic lipid accumulation in a rat model of intra-uterine growth restriction through insulin signalling pathway and sterol regulatory element binding proteins.

The objective of the present study was to investigate the effect of curcumin on insulin resistance (IR) and hepatic lipid accumulation in intra-uterine growth restriction (IUGR). Rats with a normal birth weight (NBW) or IUGR were fed basic diets (NBW and IUGR groups) or basic diets supplemented with curcumin (NBW-C and IUGR-C groups) from 6 to 12 weeks. Rats in the IUGR group showed higher levels of glucose and homeostasis model assessment for insulin resistance index (HOMA-IR) (P < 0·05) than in the NBW group. The livers of IUGR rats exhibited higher (P < 0·05) concentration of TAG and lower (P < 0·05) activities of lipolysis enzymes compared with the normal rats. In response to dietary curcumin supplementation, concentrations of serum insulin, glucose and HOMA-IR, pyruvate, TAG, total cholesterol and NEFA in the liver were decreased (P < 0·05). The concentrations of glycogen and activities of lipolysis enzymes in the liver were increased (P < 0·05) in the IUGR-C group compared with the IUGR group. These results were associated with lower (P < 0·05) phosphorylated insulin receptor substrate 1, protein kinase B or Akt, glycogen synthase kinase 3ß and expressions of sterol regulatory element binding protein 1 and fatty acid synthase (FASN); decreased expressions for Cd36, sterol regulatory element binding protein 1c (Srebf1) and Fasn; increased (P < 0·05) expression of PPARα; and expressions for Ppara and hormone-sensitive lipase in the liver of IUGR-C rats than the IUGR rats. Maternal malnutrition caused IR and lipid accumulation in the liver. Curcumin supplementation prevented IR by regulating insulin signalling pathways and attenuated hepatic lipid accumulation.

Seroprevalence of Human Cytomegalovirus in Pregnant Women in the Asir Region, Kingdom of Saudi Arabia.

BACKGROUND: Human cytomegalovirus (HCMV) infection spreads easily by interpersonal contact. OBJECTIVE: This study determined the prevalence of seropositivity of cytomegalovirus immunoglobulin G (IgG) in the Asir Region, Kingdom of Saudi Arabia. METHODS: The study evaluated the seropositivity for cytomegalovirus-specific IgG in 460 females. Collected samples were processed and tested using enzyme-linked immunosorbent assay and specific HCMV IgG. RESULTS: The study showed that all the respondents aged 15-20 years were seropositive for the HCMV. HCMV seropositive status was recorded in 99.2% of the older patients (>40 years of age). In the remaining age groups, the rate of seropositivity ranged from 95.7 (age range 20-25 years) to 98.9% (age range 30 years). CONCLUSIONS: In all age groups of females tested, the prevalence of seropositive for HCMV was high, i.e., in the range of 95.7-100%.

Pesticide Residues Identification by Optical Spectrum in the Time-Sequence of Enzyme Inhibitors Performed on Microfluidic Paper-Based Analytical Devices (µPADs).

Pesticides vary in the level of poisonousness, while a conventional rapid test card only provides a general "absence or not" solution, which cannot identify the various genera of pesticides. In order to solve this problem, we proposed a seven-layer paper-based microfluidic chip, integrating the enzyme acetylcholinesterase (AChE) and chromogenic reaction. It enables on-chip pesticide identification via a reflected light intensity spectrum in time-sequence according to the different reaction efficiencies of pesticide molecules and assures the optimum temperature for enzyme activity. After pretreatment of figures of reflected light intensity during the 15 min period, the figures mainly focused on the reflected light variations aroused by the enzyme inhibition assay, and thus, the linear discriminant analysis showed satisfying discrimination of imidacloprid (Y = -1.6525X - 139.7500), phorate (Y = -3.9689X - 483.0526), and avermectin (Y = -2.3617X - 28.3082). The correlation coefficients for these linearity curves were 0.9635, 0.8093, and 0.9094, respectively, with a 95% limit of agreement. Then, the avermectin class chemicals and real-world samples (i.e., lettuce and rice) were tested, which all showed feasible graphic results to distinguish all the chemicals. Therefore, it is feasible to distinguish the three tested kinds of pesticides by the changes in the reflected light spectrum in each min (15 min) via the proposed chip with a high level of automation and integration.

Dietary enzymatically treated Artemisia annua L. improves meat quality, antioxidant capacity and energy status of breast muscle in heat-stressed broilers.

BACKGROUND: Heat stress (HS) is detrimental to animal-origin food production. Artemisia annua L., a natural source of phenolic compounds and flavonoids, exhibits antioxidant properties. This study was conducted to evaluate the effects of dietary enzymatically treated Artemisia annua L. (EA) supplementation on meat quality, antioxidant capacity, and energy status of breast muscle in heat-stressed broilers. RESULTS: The inclusion of EA increased the redness, reduced drip loss, decreased reactive oxygen metabolites and thiobarbituric acid-reactive substances, increased antioxidant enzyme activities, and reduced the ferric reducing antioxidant power and free-radical scavenging abilities of breast muscle in heat-treated broilers. Dietary EA supplementation increased adenosine phosphate concentrations and energy charge, and decreased the mRNA expression levels of heat-shock protein 70 and 90, but increased the mRNA expression levels of avian uncoupling protein, peroxisome proliferator-activated receptor-γ coactivator-1α, and sirtuin 1 in the breast muscle of broilers exposed to HS. CONCLUSION: Dietary EA supplementation improved meat quality, antioxidant capacity, and energy status in breast muscle of heat-stressed broilers, which might be associated with altering pertinent mRNA expression; EA could therefore be used as a promising feed additive to mitigate HS in the poultry industry. This study recommended 1.00-1.25 g/kg EA in broiler diet. © 2018 Society of Chemical Industry.

Outbreak investigation report of dengue fever during June-November 2014: A case study of district Swat, Pakistan.

OBJECTIVE: To determine the frequency distribution of dengue fever during the 2014 outbreak in a district in northern Pakistan. METHODS: This cross-sectional study was conducted between June and November, 2014, at Saidu Sharif Teaching Hospital, Swat, Pakistan, where patients were screened for dengue virus non-structural protein using Dengue Duo strips from Standard Diagnostics (SD). Data was obtained from patient's record, filled forms and through questionnaire. RESULTS: Of the total 812 patients, 290(35.71%) tested positive for dengue virus non-structural protein, of whom 175(60.34%) were males and 115(39.66%) were females. Overall, 146(50.34%), cases were recorded in the 16-30 age group, while 7(2.41%) were reported in those aged >60 years. The highest numbers of cases were recorded from Faizabad 84(28.96%), whereas the lowest numbers of cases 42(14.48%) were reported from Sethi Amankot. CONCLUSIONS: Dengue virus affected male individuals more compared to female. The affected areas had poor drainage and water storage system.

Protective effects of leucine on redox status and mitochondrial-related gene abundance in the jejunum of intrauterine growth-retarded piglets during early weaning period.

The aim of this study was to investigate the effects of dietary supplementation with 0.35% l-leucine on redox status and gene abundance relating to mitochondrial biogenesis and function in the jejunum of intrauterine growth-retarded (IUGR) piglets during early weaning period. According to a 2 × 2 factorial arrangement, 16 IUGR and 16 normal body weight (NBW) piglets were fed a basal diet without l-leucine supplementation or a basal diet plus 0.35% l-leucine supplementation from the age of 14 to 35 d. The results showed that compared with NBW piglets, IUGR piglets had a lower (p < 0.05) jejunal DNA concentration, a reduced (p < 0.05) manganese superoxide dismutase (MnSOD) and total antioxidant capability (T-AOC) activities and mitochondrial DNA content in the jejunum. Leucine supplementation increased (p < 0.05) MnSOD and T-AOC activities and decreased (p < 0.05) the malondialdehyde content in the jejunum of IUGR piglets. The mRNA gene abundance of nuclear respiratory factor-1 (NRF1), mitochondrial transcription factor A (TFAM), ATP synthase (ATPs), cytochrome c oxidase V (CcOX V), cytochrome c and glucokinase in the jejunum of IUGR piglets was reduced (p < 0.05) compared with NBW piglets. However, NRF1, peroxisome proliferation-activated receptor gamma coactivator-1 alpha, TFAM, ATPs and CcOX I mRNA gene abundance in the jejunum of IUGR piglets were increased (p < 0.05) by diets supplemented with leucine. These data indicate that leucine supplementation has therapeutic potential for attenuating intestinal oxidative stress and mitochondrial dysfunction in IUGR piglets during the early period of life via increasing enzyme activities and up-regulating mRNA gene abundance.

MEDICAL EXPULSIVE TREATMENT OF DISTAL URETERAL STONE USING TAMSULOSIN.

BACKGROUND: Many minimally invasive interventional techniques as well as expectant treatment exist for the management of lower ureteric calculi. This study was conducted to evaluate th efficacy of tamsulosin as an expulsive pharmacologic therapy for the treatment of distal uretern stone. METHODS: This randomized control trial included 100 patients over 18 years of age wit stone Size > or = mm in distal 1/3 of ureter. Patients were randomly assigned into two groups (A & B Group A Patients were given Capsule Tamsulosin 0.4 mg, 1 daily up to 4 weeks while group B patients were given placebo, 1 Capsule daily up to 4 weeks. The primary endpoint was expulsio rate. A written informed consent was taken from all the patients. Expulsion time, need for analgesics, need for hospitalization and drug side effects were secondary endpoints. RESULTS: A total of 49 patients in group A and 48 patients in group B reported back, therefore 97 out of 10 patients were evaluated. Mean age of the patients was 36.34 years (range 18-57 years). Mea stone size was 5.78 mm (range 4-8 mm) in greatest dimension. A stone expulsion rate of 85.71C (42 patients) was noted in group A and 54.20% (26 patients) in group B. Group A revealed statistically significant advantage in term of stone expulsion rate (p=0.032). Considering expulsio time in days group A showed statistically significant advantage (p=0.015). Regarding age, se) stone size and stone lateralization (right/left), there was no significant difference between th group A and B. No drug side effects were noted in both the groups. CONCLUSION: By usin tamsulosin a higher stone expulsion rates can be achieved in a shorter time. More randomize control trials are required to establish tamsulosin as a standard medical expulsive treatment fc

Examining sea levels forecasting using autoregressive and prophet models.

Global climate change in recent years has resulted in significant changes in sea levels at both global and local scales. Various oceanic and climatic factors play direct and indirect roles in influencing sea level changes, such as temperature, ocean heat, and Greenhouse gases (GHG) emissions. This study examined time series analysis models, specifically Autoregressive Moving Average (ARIMA) and Facebook's prophet, in forecasting the Global Mean Sea Level (GMSL). Additionally, Vector Autoregressive (VAR) model was utilized to investigate the influence of selected oceanic and climatic factors contributing to sea level rise, including ocean heat, air temperature, and GHG emissions. Moreover, the models were applied to regional sea level data from the Arabian Gulf, which experienced higher fluctuations compared to GMSL. Results showed the capability of autoregressive models in long-term forecasting, while the Prophet model excelled in capturing trends and patterns in the time series over extended periods of time.

Prevalence and Risk Factors of Pressure Ulcers in Bedbound Diabetic vs. Non-diabetic Patients in a Lower-Middle-Income Country.

Introduction Pressure ulcers, also known as bedsores, are a significant concern for bedridden individuals, presenting both physical and socioeconomic challenges. Factors such as prolonged immobility, chronic medical conditions, and poor nutrition contribute to their development. Despite extensive research in some regions, studies comparing diabetic and non-diabetic populations remain limited, particularly in low-income settings. This study aimed to investigate the risk factors and frequency of pressure ulcers among bedridden patients, addressing this gap in understanding and guiding targeted interventions. Materials and methods A cross-sectional study was conducted across four government hospitals in Peshawar, Pakistan. A total of 388 bedridden patients with pressure ulcers were included, and data were collected through a questionnaire. The questionnaire covered demographics, comorbidities, duration of bedbound status, BMI, and caregivers' awareness of pressure ulcer care. Data analysis was performed using SPSS version 22.0 (Armonk, NY: IBM Corp.), with qualitative data presented as frequencies and percentages and quantitative data as mean and standard deviation. Chi-square tests were utilized for significance, with p<0.05 considered significant. Results Of the 388 patients analyzed, 230 (59.3%) were diabetic, highlighting the prevalence of diabetes among pressure ulcer cases. The majority of diabetic patients with ulcers were over 41 years old, and 293 (75.5%) had comorbidities. Surgical intervention was the primary cause of ulcers in 213 (54.8%) cases, followed by stroke in 77 (19.8%) cases. Notably, 252 (65%) of caregivers exhibited inadequate knowledge regarding ulcer care. Stage II ulcers were prevalent in both diabetic and non-diabetic cohorts. Conclusions Pressure ulcers are poorly controlled complications observed in bedridden individuals, highlighting a critical need for comprehensive preventive measures and caregiver education to alleviate the burden of pressure ulcers, especially in diabetic patients. Factors such as prolonged immobility, surgical interventions, and insufficient caregiver knowledge contribute to the development of pressure ulcers. Understanding these complexities is essential for implementing effective care approaches and mitigating the impact of pressure ulcers.

Effects of feeding fermented Ginkgo biloba leaves on small intestinal morphology, absorption, and immunomodulation of early lipopolysaccharide-challenged chicks.

Aspergillus niger-fermented-Ginkgo biloba leaves (FG) and the comparative effect with nonfermented (NF)-Ginkgo leaves were investigated on morphology, absorption, and immunity of small intestine after lipopolysaccharide (LPS)-challenge in chicks at an early age. Broiler chicks (180 d of age) were divided into 3 treatment groups and were fed 1 of 3 diets: basal diet or basal diet supplemented with 0.5% NF or FG (control, NF, and FG group, respectively). Half of the birds from each treatment group were injected intraperitoneally with LPS (500 µg/kg of BW) or 0.9% NaCl solution (the sham control groups) at 10, 12, 15, 17, 19, and 21 d of age. The results indicated that when LPS-challenged birds were pretreated with FG, the decrease of ADG, ADFI, duodenal and jejunal relative weights, villus height, crypt depth, alkaline phosphatase activity, and plasma d-xylose were dramatically attenuated (P < 0.05 or P < 0.01). Meanwhile, a significant decrease (P < 0.05 or P < 0.01) of duodenal and jejunal interferon-γ, interleukin (IL)-4, IL-13, IL-18, inducible nitric oxide synthase, and duodenal sodium glucose co-transporter 1 mRNA expressional levels were found in LPS-challenged birds pretreated with FG. In conclusion, FG-supplemented diets minimized the deleterious effects of LPS and improved intestinal development, absorption, and immunity in immune-stressed chickens.

Customer churn prediction using composite deep learning technique.

Customer churn, a phenomenon that causes large financial losses when customers leave a business, makes it difficult for modern organizations to retain customers. When dissatisfied customers find their present company's services inadequate, they frequently migrate to another service provider. Machine learning and deep learning (ML/DL) approaches have already been used to successfully identify customer churn. In some circumstances, however, ML/DL-based algorithms lacks in delivering promising results for detecting client churn. Previous research on estimating customer churn revealed unexpected forecasts when utilizing machine learning classifiers and traditional feature encoding methodologies. Deep neural networks were also used in these efforts to extract features without taking into account the sequence information. In view of these issues, the current study provides an effective method for predicting customer churn based on a hybrid deep learning model termed BiLSTM-CNN. The goal is to effectively estimate customer churn using benchmark data and increase the churn prediction process's accuracy. The experimental results show that when trained, tested, and validated on the benchmark dataset, the proposed BiLSTM-CNN model attained a remarkable accuracy of 81%.

Dietary L-arginine supplementation improves the intestinal development through increasing mucosal Akt and mammalian target of rapamycin signals in intra-uterine growth retarded piglets.

Intra-uterine growth retardation (IUGR) impairs postnatal growth and development of the small intestine (SI) in neonatal pigs and infants. L-Arginine (Arg), a critical amino acid involved in promoting growth and metabolism in young mammals, is more deficient in IUGR fetuses. However, little is known whether dietary Arg supplementation would accelerate the impaired development of the SI induced by IUGR in piglets. In the present study, a total of six litters of newborn piglets were used. In each litter, one normal and two IUGR littermates were obtained. Piglets were fed milk-based diets supplemented with 0 (Normal), 0 (IUGR) and 0·60% Arg (IUGR+Arg) from 7 to 14 d of age, respectively. Compared with Normal piglets at 14 d of age, IUGR decreased (P < 0·05) the growth performance, entire SI weight, and villus height in the jejunum and ileum. IUGR piglets had lower (P < 0·05) mucosal concentrations of Arg, insulin, insulin growth factor 1, as well as phosphorylated Akt, mammalian target of rapamycin (mTOR) and p70 S6 kinase but higher (P < 0·05) enterocyte apoptosis index (AI). After Arg treatment in IUGR piglets, the growth performance, weight of entire SI and mucosa, and villus height in the jejunum and ileum were increased (P < 0·05). Diet supplemented with Arg also increased (P < 0·05) the levels of Arg, insulin, phosphorylated Akt and mTOR in SI mucosa of IUGR piglets, and decreased (P < 0·05) the AI and caspase-3 activity. In conclusion, Arg has a beneficiary effect in improving the impaired SI development in IUGR piglets via regulating cell apoptosis and activating Akt and mTOR signals in SI mucosa.

Ureterovaginal fistula--etiological factors and outcome.

OBJECTIVE: To assess the etiological factors and the outcome of ureterovaginal fistula in an urban setting. METHODS: The observational study was conducted at the Armed Forces Institute of Urology, Military Hospital, Rawalpindi, from January 2009 to January 2011. All the patients of uretero-vaginal fistula at the centre were included on the basis of non-probability purposive sampling. The etiology, clinical presentation and the investigative procedures were recorded. The operative modality contemplated was noted and post-operative results were evaluated. The data was entered in a structured proforma and analysed for descriptive statistics using SPSS version 14.0. RESULTS: Seventeen cases of ureterovaginal fistula were recorded. Amongst these 10 (58.8%) were post-hysterectomy, while 7 (41.1%) cases post-caesarean section. The emergency procedures performed by the residents/junior registrars contributed 12 (70.2%) of the cases. All these patients were treated surgically; 14 (82.3%) were managed with ureteroneocystostomy, 2 (11.7%) required Boari Flap reconstruction, and in psoas hitch was performed in 1 (5.8%) case. The time of intervention was 4 - 12 weeks (9.76 +/- 2.223). Post-operatively, only 1 (5.8%) case had superficial wound infection and 1 (5.8%) urinary tract infection. All the patients remained dry with a follow-up period of 3 - 24 months (mean 12.24 +/- 6.879). CONCLUSION: Ureterovaginal fistula is one of the complications of emergency procedures, especially in the hands of inexperienced surgeons. Prompt diagnosis and surgical intervention produce excellent results. Intervention can be done safely as early as 4 weeks after the initiation of the condition.

Structural and dynamic investigation of non-synonymous variations in Renin-AGT complex revealed altered binding via hydrogen-bonding network reprogramming to accelerate the hypertension pathway.

Hypertension is one of the major issues worldwide and one of the main factors involved in heart and kidney failure. Angiotensinogen and renin are key components of the renin-angiotensin-aldosterone system, which plays an indispensable role in hypertension. The aim of this study was to find out the non-synonymous mutations and structure-based mutation-function correlation in the renin-AGT complex and reveal the most deleterious mutations to accelerated hypertension. In the current study, we employed computational modeling and molecular simulation approaches to demonstrate the impact of specific mutations in the REN-AGT interface in hypertension. Computational algorithms, that is, PhD-SNP, PolyPhen-1, MAPP, Sorting Intolerant from Tolerant, Screening of non-acceptable polymorphism, PredictSNP, PolyPhen-2, and Protein Analysis Through Evolutionary Relationships predicted 20 mutations as deleterious in AGT while only five mutations were confirmed as deleterious in the renin protein. Investigation of the bonding analysis revealed that two mutations S107L and V193F in renin altered the hydrogen-bonding paradigm at the interface site. Furthermore, exploration of structural-dynamic behaviors demonstrated by that these mutations also increases the structural stability to regulate the expression of disease pathway. The flexibility index of each residues and structural compactness analysis further validated the findings by portraying the difference in the dynamic behavior in contrast to the wild type. Binding energy calculations based on molecular mechanics/generalized Born surface area methods were used which further established the binding differences between the wild type, S107L, and V193F mutant variants. The total binding energy for wild type, S107L, and V193F was reported to be -27.79, -47.72, and -38.25, respectively. In conclusion, these two mutations increase the binding free energy alongside the docking score to enhance the binding between renin and AGT to overexpress this pathway in a hypertension disease condition. Patients with these mutations may be screened for potential therapeutic intervention.