Mutational spectrum of CFTR in cystic fibrosis patients with gastrointestinal and hepatobiliary manifestations.

BACKGROUND: Cystic fibrosis (CF) is a rare and debilitating autosomal recessive disorder. It hampers the normal function of various organs and causes severe damage to the lungs, and digestive system leading to recurring pneumonia. Cf also affects reproductive health eventually may cause infertility. The disease manifests due to genetic aberrations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This study aimed to screen for CFTR gene variants in Pakistani CF patients representing variable phenotypes. METHODS: Clinical exome and Sanger sequencing were performed after clinical characterization of 25 suspected cases of CF (CF1-CF25). ACMG guidelines were followed to interpret the clinical significance of the identified variants. RESULTS: Clinical investigations revealed common phenotypes such as pancreatic insufficiency, chest infections, chronic liver and lung diseases. Some patients also displayed symptoms like gastroesophageal reflux disease (GERD), neonatal cholestasis, acrodermatitis, diabetes mellitus, and abnormal malabsorptive stools. Genetic analysis of the 25 CF patients identified deleterious variants in the CFTR gene. Notably, 12% of patients showed compound heterozygous variants, while 88% had homozygous variants. The most prevalent variant was p. (Met1Thr or Met1?) at 24%, previously not reported in the Pakistani population. The second most common variant was p. (Phe508del) at 16%. Other variants, including p. (Leu218*), p. (Tyr569Asp), p. (Glu585Ter), and p. (Arg1162*) were also identified in the present study. Genetic analysis of one of the present patients showed a pathogenic variant in G6PD in addition to CFTR. CONCLUSION: The study reports novel and reported variants in the CFTR gene in CF patients in Pakistani population having distinct phenotypes. It also emphasizes screening suspected Pakistani CF patients for the p. (Met1Thr) variant because of its increased observance and prevalence in the study. Moreover, the findings also signify searching for additional pathogenic variants in the genome of CF patients, which may modify the phenotypes. The findings contribute valuable information for the diagnosis, genetic counseling, and potential therapeutic strategies for CF patients in Pakistan.

Clinical exome sequencing reveals a novel pathogenic variant in KIF12 underlying cholestasis with highly variable phenotypes.

Four affected individuals from a large consanguineous family were diagnosed with variable phenotypes of cholestasis based on their clinical laboratory and biopsy findings. Cholestasis is a condition when there is not enough bile flow between liver and small intestine. Two of the affected individuals (IV-1, IV-4) died of cholestatic liver at an early age, while the other two patients are alive with chronic liver disease. Clinical exome and Sanger sequencing identified a novel homozygous pathogenic variant (c.482-7_500del) in the patients.

Effectiveness Of Neuro Mobilisation On Pain, Range Of Motion, Muscle Endurance And Disability In Cervical Radiculopathy: A Systematic Review.

Objective: To assess the effects of the neural mobilisation technique on mobility, pain and disability in cervical radiculopathy patients, and to assess the functional activity level. METHODS: The systematic review was conducted from January 5 to July 5, 2022, and comprised search on Medline, PEDro, Cochrane Library and Embase databases for randomised controlled trials involving patients diagnosed with cervical radiculopathy that were published in the preceding 10 years in the English language. The search terms were divided into four classes by using the guideline for systematic reviews of trials of interventions in the Cochrane neck and back groups and related spinal disorders. Data wasretrieved afterthe studies were subjected to quality assessment and risk of biasness. RESULTS: Of the 1563 studies initially found, 8 (0.51%)were reviewed.Nomatter the approach ordosage used,manual therapy was successful in treating cervical radiculopathy symptomsin all investigations. Conclusion: A multimodal strategy incorporating neural mobilisation appears to be the most successful short-term technique.

A new approach to sustainable logistic processes with q-rung orthopair fuzzy soft information aggregation.

In recent years, as corporate consciousness of environmental preservation and sustainable growth has increased, the importance of sustainability marketing in the logistic process has grown. Both academics and business have increased their focus on sustainable logistics procedures. As the body of literature expands, expanding the field's knowledge requires establishing new avenues by analyzing past research critically and identifying future prospects. The concept of "q-rung orthopair fuzzy soft set" (q-ROFSS) is a new hybrid model of a q-rung orthopair fuzzy set (q-ROFS) and soft set (SS). A q-ROFSS is a novel approach to address uncertain information in terms of generalized membership grades in a broader space. The basic alluring characteristic of q-ROFS is that they provide a broader space for membership and non-membership grades whereas SS is a robust approach to address uncertain information. These models play a vital role in various fields such as decision analysis, information analysis, computational intelligence, and artificial intelligence. The main objective of this article is to construct new aggregation operators (AOs) named "q-rung orthopair fuzzy soft prioritized weighted averaging" (q-ROFSPWA) operator and "q-rung orthopair fuzzy soft prioritized weighted geometric" (q-ROFSPWG) operator for the fusion of a group of q-rung orthopair fuzzy soft numbers and to tackle complexities and difficulties in existing operators. These AOs provide more effective information fusion tools for uncertain multi-attribute decision-making problems. Additionally, it was shown that the proposed AOs have a higher power of discriminating and are less sensitive to noise when it comes to evaluating the performances of sustainable logistic providers.

Nutritional probing and storage stability of papaya jam supplemented with date pit powder.

Jam Quality is a factor robustly influenced by storage conditions. The current research aimed to develop papaya jam with improved nutritional attributes, rheological profile, and shelf-life utilizing date pit powder as a functional ingredient. The effect of date pit powder on the formulated product's physicochemical, microbial, and organoleptic properties was analyzed. Results revealed that overall mineral profile (0.35-1.11%), crude fiber (0.56-2.01%), pH (3.51-3.70%), and antioxidant properties (22.97-30.67%) were significantly increased while water activity reduced (0.77-0.73). Moreover, date pit powder improved the color scores like a*(10.10-10.67), b* (8.13-8.78), L* (25.56-28.09), and textural attributes (Cohesiveness: 0.83-0.90; Firmness: 6.82-6.93) of functional papaya jam. Microbial count reduced from 3.60 × 105-3.06 × 105 cfu/ml by adding date pit powder and staying within the acceptable limit (4.13 × 105-3.60 × 105 cfu/ml) during 2-month storage at refrigeration. Organoleptic evaluation depicted that samples treated with date pit powder scored better than the control, and a sample with 75% pectin replacement was considered best.

Primary Antibiotic Resistance And Effectiveness Of Clarithromycin Vs Metronidazole Based Therapy For Helicobacter Pylori Infection In Children.

BACKGROUND: NASPGHAN guidelines recommend regional antibiotic susceptibility profiling for H. pylori eradication treatment. Profiling local antibiotic resistance patterns is mandatory for successful H. pylori eradication in children. The aim of our study was to determine primary resistance to Clarithromycin and Metronidazole, most commonly used in the eradication regimens in children presenting with symptomatic H. pylori infection. This study was conducted at Children Hospital PIMS Islamabad from June 2020 to August 2021. METHODS: The children of either gender age 2-14 years having symptomatic H. pylori infection (hematemesis, chronic abdominal pain) underwent stool for H. pylori Antigen. Children requiring urgent diagnostic endoscopy underwent rapid urease tests. Biopsies were taken from children having positive stool H. pylori Ag and rapid urease test for histological examination. The biopsy specimens were cultured and subsequently tested for antibiotic sensitivity. RESULTS: Out of 54 children having H. pylori infection 40/54 (74.074%) children had strains susceptible to antimicrobials and 14/54 (25.92%) were having resistance to antimicrobials. According to the pattern of antimicrobial sensitivity, they were further grouped into three (a) Clarithromycin and Metronidazole sensitive group (18/40, 45%) (b) Clarithromycin sensitive and Metronidazole resistant group (12/40, 30%) (c) Metronidazole sensitive group (10/40 25%). CONCLUSIONS: Clarithromycin and Metronidazole cannot be used as1stline treatment for H. pylori eradication in children and can only be used with known antimicrobial susceptibility.

Naproxen sodium nanoparticles are less toxic and gastroprotective agents than the conventional NSAID drug naproxen sodium in Balb/c mice.

Use of non-steroidal anti-inflammatory drugs (NSAIDs) is one of the leading causes of gastric ulcers. Excellent therapeutic properties have made the use of NSAIDs widespread. Nano-drug delivery to reduce systemic toxicity through modulating drug pharmacokinetics may be a better choice. Presently, we investigated if naproxen nanoformulation (PVA capped NPRS-MgO NPs) is less toxic to be used as an alternative drug. Groups of mice were assigned to control, NPRS-treated, CNF-treated, UNF-treated, and MgO NPs-treated groups. Analyses included gross examination of gastric mucosa, calculation of ulcer and inhibition indices, determination of tissue levels of reactive oxygen species (ROS), malondialdehyde (MDA), catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), and reduced glutathione (GSH), histological and immunohistochemical assessment of i-NOS, COX-2, and caspase-3 of stomach mucosa, q-PCR for the detection of mRNA expression of IL-1ß, IL-6, and TNF-α. Results were compared statistically at P < 0.05. Compared to NPRS-treated mice which developed multiple ulcers, had elevated MDA and ROS levels, and deceased CAT, POD, SOD, and GSH levels, significantly increased expression of IL-1ß, IL-6, and TNF-α mRNA, damaged surface epithelium with disrupted glandular architecture and leucocyte infiltration of lamina propria with a marked increase in mucosal COX-2, i-NOS, and caspase-3 expression, oral administration of coated and uncoated naproxen nanoformulations prevented the gross mucosal damage by a restoration of all biochemical, histological, and immunohistochemical alterations to near control levels. The present study demonstrates that naproxen sodium nanoformulation has a gastroprotective action and in the clinical setting can be a better alternative to conventional naproxen.

Comparing the effects of muscle energy technique and mulligan mobilization with movements on pain, range of motion, and disability in adhesive capsulitis.

OBJECTIVES: To compare the effect of muscle energy technique and Mulligan mobilisation with movement on pain, range of motion and disability in patients of adhesive capsulitis. METHODS: The single-blind, randomised controlled study was conducted at the Physiotherapy Department of Mayo Hospital, Lahore, Pakistan, from July to December, 2018, and comprised patients of either gender aged 30-70 years with adhesive capsulitis stage 2. The subjects were randomised using the lottery method into Mulligan mobilisation with movement group A, and the muscle energy technique grouo B. Conventional treatment, including hot packs and exercises like pulley rope exercise, wall climbing, and shoulder wheel, were part of both the groups. Each technique was applied five times per set, 2 sets per session 3 days a week for three weeks. Baseline and post-intervention readings were recorded for pain, range of motion and disability Using numeric pain rating scale, goniometer, and shoulder pain and disability index. Data was analysed using SPSS 23. RESULTS: Of the 70 individuals assessed, 64(91.4%) were included; 32(50%) in each of the two groups. The mean age in group A was 49.93±6.69 years, while in group B it was 49.17±8.92 years. Group A showed significantly better results compared to group B (p<0.05). CONCLUSIONS: Muscle energy technique and Mulligan mobilisation with movement were both found to be effective, but the latter was significantly better compared to the former. CLINICAL TRIAL NUMBER: IRCT20200611047734N2 (https://www.irct.ir/trial/48851).