Progressive resistance training improving gait performance and mobility in acute and chronic stroke patients

Stroke, a neurological disorder, leads to long-term disability thereby greatly affecting gait and mobility. The purpose of the current study was to investigate the effects of progressive resistance training in both acute and chronic stroke patients. A quasi interventional study was designed and 46 stroke patients were recruited through convenience sampling technique. Sample size was calculated using epi-tool. Patients who had cognitive problems, balance impairments and contractures were excluded from the study. The study was conducted from January to June 2018, at Rafsan Rehab & Research Centre, Peshawar. Progressive resistance exercises starting at 50 % of one repetition maximum (RM) were performed three days/week and for a total duration of nine weeks. Blind assessor measured readings at baseline and after nine weeks. Gait dynamic index (GDI), Six-Meter Walk Test (SMWT) and Five Times Sit-to-Stand (FTSTS) tools were used to collect the required data. The data was analysed at baseline and after nine weeks on SPSS-20. After nine weeks of intervention significant improvement was recorded in patients on GDI (p<0.001), SMWT score (P<0.001) and FTSTS (p<0.001). Progressive resistance training improves mobility limitations and gait in both acute and chronic stroke patients.måsjekke

Evaluation of gut modulatory and bronchodilator activities of Amaranthus spinosus Linn.

Background The aqueous-methanolic extract of Amaranthus spinosus (A. spinosus Linn.,) whole plant, was studied for its laxative, spasmolytic and bronchodilator activities to validate some of its medicinal uses. Methods The crude extract of A. spinosus was studied in-vivo for bronchodilator and laxative activities and in-vitro using isolated tissue preparations which were mounted in tissue baths assembly containing physiological salt solutions, maintained at 37°C and aerated with carbogen, to assess the spasmolytic effect and to find out the possible underlying mechanisms. Results In the in-vivo experiments in mice, the administration of A. spinosus increased fecal output at doses of 100 and 300 mg/kg showing laxative activity. It also inhibited carbachol-induced bronchospasm in anesthetized rats at 1, 3, 10 and 30 mg/kg indicative of bronchodilator activity. When tested on isolated gut preparations, the plant extract showed a concentration-dependent (0.01-10.0 mg/ml) spasmogenic effect in spontaneously contracting rabbit jejunum and guinea-pig ileum. The spasmogenic effect was partially blocked in tissues pretreated with atropine (0.1 μM). When tested on K+ (80 mM)-induced sustained contractions in isolated rabbit jejunum, the plant extract caused complete relaxation and also produced a shift in the Ca++ concentration-response curves (CRCs) towards right, similar to diltiazem. In rabbit trachea, the plant extract completely inhibited K+ (80 mM) and carbachol (CCh, 1 μM)-induced contractions at 1 mg/ml but pretreatment of tissue with propranolol (1 μM), caused around 10 fold shift in the inhibitory CRCs of the plant extract constructed against CCh-induced contraction. The plant extract (up to 0.3 mg/ml) also increased both force and rate of spontaneous contractions of isolated guinea-pig atria, followed by relaxation at higher concentration (1.0-5.0 mg/ml). The cardio-stimulant effect was abolished in the presence of propranolol, similar to that of isoprenaline. Activity-directed fractionation revealed that the spasmolytic component(s) was separated in the organic fraction, whereas the spasmogenic component was concentrated in the aqueous fraction. Conclusion These results indicate that A. spinosus possesses laxative activity partially mediated through cholinergic action. The spasmolytic effect was mediated through calcium channel blocking (CCB), while bronchodilator activity through a combination of β-adrenergic and CCB pathways, which may explain the traditional uses of A. spinosus in gut and airways disorders

Physical activity, smoking, and genetic predisposition to obesity in people from Pakistan:the PROMIS study

Background: Multiple genetic variants have been reliably associated with obesity-related traits in Europeans, but little is known about their associations and interactions with lifestyle factors in South Asians. Methods: In 16,157 Pakistani adults (8232 controls; 7925 diagnosed with myocardial infarction [MI]) enrolled in the PROMIS Study, we tested whether: a) BMI-associated loci, individually or in aggregate (as a genetic risk score - GRS), are associated with BMI; b) physical activity and smoking modify the association of these loci with BMI. Analyses were adjusted for age, age(2), sex, MI (yes/no), and population substructure. Results: Of 95 SNPs studied here, 73 showed directionally consistent effects on BMI as reported in Europeans. Each additional BMI-raising allele of the GRS was associated with 0.04 (SE = 0.01) kg/m(2) higher BMI (P = 4.5 x 10(-14)). We observed nominal evidence of interactions of CLIP1 rs11583200 (P-interaction = 0.014), CADM2 rs13078960 (P-interaction = 0.037) and GALNT10 rs7715256 (P-interaction = 0.048) with physical activity, and PTBP2 rs11165643 (P-interaction = 0.045), HIP1 rs1167827 (P-interaction = 0.015), C6orf106 rs205262 (P-interaction = 0.032) and GRID1 rs7899106 (P-interaction = 0.043) with smoking on BMI. Conclusions: Most BMI-associated loci have directionally consistent effects on BMI in Pakistanis and Europeans. There were suggestive interactions of established BMI-related SNPs with smoking or physical activity

THE IN VITRO AND EX VIVO EFFECT OF PHYLLANTHUS NIRURI METHANOL EXTRACT ON HEPATIC GLUTATHIONE S-TRANSFERASE ACTIVITY IN STZ-INDUCED DIABETIC SPRAGUE DAWLEY RATS

ABSTRACTObjective: The aim of this study was to investigate the in vitro and ex vivo (acute and sub-chronic doses) effect of Phyllanthus niruri methanol extract (PNME) on the activity of cytosolic glutathione S-transferase (GST) in streptozotocin (STZ)-induced diabetic young female Sprague Dawley (SD) rats.Methods: Young female SD rats were induced type I diabetes mellitus using STZ (60 mg/kg i.v.). The in vitro study was performed on cytosolic fraction of diabetic rat livers using PNME in concentrations of 0.01, 1 and 10 µg/ml. Meanwhile, ex vivo studies were performed on diabetic rats using PNME in doses of 500, 1000, 2000 and 5000 mg/kg p.o. for acute study (1 day) and 100, 500 and 2000 mg/kg/day p.o. for sub-chronic study (14 days). The GST activity in the cytosolic liver fraction was measured using spectrophotometric analysis.Results: The in vitro study showed that, there is no significant effect of the three concentrations of PNME versus control on GST activity in cytosolic fraction of diabetic young female SD rat livers, while for ex vivo study, there is a significant dose independent induction effect on GST enzyme activity at all doses used in acute study. Meanwhile, sub-chronic study showed significant dose-independent induction effect at doses 500 and 2000 mg/kg.Conclusion: This study suggests that Phyllanthus niruri may increase the clearance of drugs that are metabolized by GST enzyme in phase II metabolism when given concomitantly with this plant extract.Key words: Phyllanthus niruri, GST, diabetic rats, cytosolic liver fraction, phase II metabolismÂ

Trans-articular chondrosarcoma grade 2 of proximal phalanx resulting in its fracture along with destruction of middle phalanx of 2nd toe right foot: a case report and review of the literature

Foot is an unusual site for chondrosarcoma and involvement of phalanges is extremely rare. We report a case of grade 2 chondrosarcoma of proximal phalanx resulting in its fracture along with transarticular extension to the middle phalanx of the 2nd toe of right foot in a 62 year old female. The patient presented with 1 and ½ year history of pain and swelling in right 2nd toe. X-ray showed presence of expanding lytic lesion with amorphous calcification along with fracture proximal phalanx. Fine needle aspiration cytology showed some pleomorphs, osteoclasts and some giant cells. We went for amputation of toe without a biopsy. Histopathological examination of specimen showed multiple pleomorphic cells, nuclear atypia, hyperchromasia with some giant cells (grade 2 chondrosarcoma)

In silico design and biological evaluation of a dual specificity kinase inhibitor targeting cell cycle progression and angiogenesis

Methodology: We have utilized a rational in silico-based approach to demonstrate the design and study of a novel compound that acts as a dual inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2) and cyclin-dependent kinase 1 (CDK1). This compound acts by simultaneously inhibiting pro-Angiogenic signal transduction and cell cycle progression in primary endothelial cells. JK-31 displays potent in vitro activity against recombinant VEGFR2 and CDK1/cyclin B proteins comparable to previously characterized inhibitors. Dual inhibition of the vascular endothelial growth factor A (VEGF-A)-mediated signaling response and CDK1-mediated mitotic entry elicits anti-Angiogenic activity both in an endothelial-fibroblast co-culture model and a murine ex vivo model of angiogenesis

A novel training simulator for portable ultrasound identification of incorrect newborn endotracheal tube placement – Observational diagnostic accuracy study protocol

Background: Endotracheal tube (ETT) placement is a critical procedure for newborns that are unable to breathe. Inadvertent esophageal intubation can lead to oxygen deprivation and consequent permanent neurological impairment. Current standard-of-care methods to confirm ETT placement in neonates (auscultation, colorimetric capnography, and chest x-ray) are time consuming or unreliable, especially in the stressful resuscitation environment. Point-of-care ultrasound (POCUS) of the neck has recently emerged as a powerful tool for detecting esophageal ETTs. It is accurate and fast, and is also easy to learn and perform, especially on children.Methods: This will be an observational diagnostic accuracy study consisting of two phases and conducted at the Aga Khan University Hospital in Karachi, Pakistan. In phase 1, neonatal health care providers that currently perform standard-of-care methods for ETT localization, regardless of experience in portable ultrasound, will undergo a two-hour training session. During this session, providers will learn to detect tracheal vs. esophageal ETTs using POCUS. The session will consist of a didactic component, hands-on training with a novel intubation ultrasound simulator, and practice with stable, ventilated newborns. At the end of the session, the providers will undergo an objective structured assessment of technical skills, as well as an evaluation of their ability to differentiate between tracheal and esophageal endotracheal tubes. In phase 2, newborns requiring intubation will be assessed for ETT location via POCUS, at the same time as standard-of-care methods. The initial 2 months of phase 2 will include a quality assurance component to ensure the POCUS accuracy of trained providers. The primary outcome of the study is to determine the accuracy of neck POCUS for ETT location when performed by neonatal providers with focused POCUS training, and the secondary outcome is to determine whether neck POCUS is faster than standard-of-care methods.Discussion: This study represents the first large investigation of the benefits of POCUS for ETT confirmation in the sickest newborns undergoing intubations for respiratory support

Factors associated with low birthweight in term pregnancies: A matched case-control study from rural Pakistan

Low birthweight (LBW) remains a significant public health problem in Pakistan and further understanding of factors associated with LBW is required. We conducted a hospital-based matched case control study to identify risk factors associated with LBW in a rural district of Pakistan. We found that illiteracy (AOR: 2.68; 95% CI: 1.59 - 4.38), nulliparity (AOR: 1.82; 95% CI: 1.26-2.44), having a previous miscarriage/abortion (AOR: 1.22; 95% CI: 1.06-2.35), having \u3c 2 antenatal care (ANC) visits during last pregnancy (AOR: 2.43; 95% CI: 1.34-2.88), seeking ANC in third trimester (AOR: 3.62; 95% CI : 2.14-5.03), non-use of iron folic acid during last pregnancy (AOR: 2.72; 95% CI: 1.75-3.17), having hypertension during last pregnancy (AOR: 1.42; 95% CI: 1.13-2.20), being anemic (AOR: 2.67; 95% CI: 1.65-5.24) and having postpartum weight o

NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap4A) and Down-Regulates Immune Response and Cancer Promotion Genes.

Regulation of gene expression is one of several roles proposed for the stress-induced nucleotide diadenosine tetraphosphate (Ap4A). We have examined this directly by a comparative RNA-Seq analysis of KBM-7 chronic myelogenous leukemia cells and KBM-7 cells in which the NUDT2 Ap4A hydrolase gene had been disrupted (NuKO cells), causing a 175-fold increase in intracellular Ap4A. 6,288 differentially expressed genes were identified with P < 0.05. Of these, 980 were up-regulated and 705 down-regulated in NuKO cells with a fold-change ≥ 2. Ingenuity® Pathway Analysis (IPA®) was used to assign these genes to known canonical pathways and functional networks. Pathways associated with interferon responses, pattern recognition receptors and inflammation scored highly in the down-regulated set of genes while functions associated with MHC class II antigens were prominent among the up-regulated genes, which otherwise showed little organization into major functional gene sets. Tryptophan catabolism was also strongly down-regulated as were numerous genes known to be involved in tumor promotion in other systems, with roles in the epithelial-mesenchymal transition, proliferation, invasion and metastasis. Conversely, some pro-apoptotic genes were up-regulated. Major upstream factors predicted by IPA® for gene down-regulation included NFκB, STAT1/2, IRF3/4 and SP1 but no major factors controlling gene up-regulation were identified. Potential mechanisms for gene regulation mediated by Ap4A and/or NUDT2 disruption include binding of Ap4A to the HINT1 co-repressor, autocrine activation of purinoceptors by Ap4A, chromatin remodeling, effects of NUDT2 loss on transcript stability, and inhibition of ATP-dependent regulatory factors such as protein kinases by Ap4A. Existing evidence favors the last of these as the most probable mechanism. Regardless, our results suggest that the NUDT2 protein could be a novel cancer chemotherapeutic target, with its inhibition potentially exerting strong anti-tumor effects via multiple pathways involving metastasis, invasion, immunosuppression and apoptosis