Enlarging right thigh mass

Skeletal Radiology -     

Human pancreatic secretory trypsin inhibitor stabilizes intestinal mucosa against noxious agents

Pancreatic secretory trypsin inhibitor (PSTI) is a serine protease inhibitor, expressed in gut mucosa, whose function is unclear. We, therefore, examined the effects of PSTI on gut stability and repair. Transgenic mice overexpressing human PSTI within the jejunum (FABPi(-1178 to +28) hPSTI construct) showed no change in baseline morphology or morphometry but reduced indomethacin-induced injury in overexpressing hPSTI region by 42% (P < 0.01). Systemic recombinant hPSTI did not affect baseline morphology or morphometry but truncated injurious effects in prevention and recovery rat models of dextran-sodium-sulfate-induced colitis. In vitro studies showed PSTI stimulated cell migration but not proliferation of human colonic carcinoma HT29 or immortalized mouse colonic YAMC cells. PSTI also induced changes in vectorial ion transport (short-circuit current) when added to basolateral but not apical surfaces of polarized monolayers of Colony-29 cells. Restitution and vectorial ion transport effects of PSTI were dependent on the presence of a functioning epidermal growth factor (EGF) receptor because cells with a disrupted (EGFR(-/-) immortalized cells) or neutralized (EGFR blocking antibodies or tyrosine kinase inhibitor) receptor prevented these effects. PSTI also reduced the cytokine release of lipopolysaccharide-stimulated dendritic cells. We conclude that administration of PSTI may provide a novel method of stabilizing intestinal mucosa against noxious agents and stimulating repair after injury.     

A comprehensive review on Brigatinib – A wonder drug for targeted cancer therapy in non-small cell lung cancer

The mortality rate in patients suffering from non-small cell lung cancer (NSCLC) is quite high. This type of cancer mainly occurs due to rearrangements in the anaplastic lymphoma kinase (ALK) gene which leads to form an oncogene of fused gene NPM-ALK. Brigatinib is recently approved by FDA in April 2017 as a potent tyrosine kinase inhibitor (TKI) for the NSCLC therapy. In the present scenario, it is no less than a wonder drug because it is indicated for the treatment of advanced stages of metastatic ALK positive NSCLC, a fatal disease to overcome the resistance of various other ALK inhibitors such as crizotinib, ceritinib and alectinib. In addition to ALK, it is also active against multiple types of kinases such as ROS1, Insulin like growth factor-1Receptor and EGFR. It can be synthesized by using N-[2-methoxy-4-[4-(dimethylamino) piperidin-1-yl] aniline] guanidine and 2,4,5-trichloropyrimidine respectively in two different ways. Its structure consists of mainly dimethylphosphine oxide group which is responsible for its pharmacological activity. It is active against various cell lines such as HCC78, H2228, H23, H358, H838, U937, HepG2 and Karpas- 299. Results of ALTA (ALK in Lung Cancer Trial of AP26113) phase ½ trial shows that 90?mg of brigatinib for 7?days and then 180?mg for next days is effective in the treatment of NSCLC. Brigatinib has been shown to have favorable risk benefit profile and is a safer drug than the available cytotoxic chemotherapeutic agents. In comparison to other FDA approved drugs for the same condition, it causes fewer minor adverse reactions which can be easily managed either by changing the dose or by providing good supportive care. This article is intended to provide readers with an overview of chemistry, pharmacokinetic, pharmacodynamic and safety profile of brigatinib, which addresses an unmet medical need.     

Seasonal variation in the association between household food insecurity and child undernutrition in Bangladesh: Mediating role of child dietary diversity

Household food insecurity (HFI) and child dietary diversity (CDD) are variable across seasons. We examined seasonal variation in HFI and child undernutrition association and tested how CDD mediates this association. We analyzed data for 26,353 children aged 6–59 months drawn from nationally representative cross-sectional Food Security and Nutrition Surveillance Project data collected during 2012–2014 in Bangladesh across three seasons annually: Post-Aman harvest (January–April); Monsoon (May–August); and Post-Aus harvest (September–December). Multivariable logistic regression analysis adjusted for individual, maternal, household and geographical characteristics reveals that children of food-insecure households were more likely than food-secure households to be stunted (adjusted odds ratio, AOR: 1.12; 95% confidence interval, CI: 1.02–1.23; p < 0.05), wasted (AOR: 1.21; 95% CI: 1.05–1.39; p < 0.01) and underweight (AOR: 1.16; 95% CI: 1.04–1.3; p < 0.01). CDD mediated 6.1% of the total effect of HFI on underweight. These findings varied across seasons. HFI was associated with greater odds of underweight during Monsoon (AOR: 1.32; 95% CI: 1.08–1.62; p < 0.01) and Post-Aus (AOR: 1.21; 95% CI: 1.06–1.37; p < 0.01) while wasting during Post-Aus (AOR: 1.65; 95% CI: 1.35–2.01; p < 0.001). CDD largely mediated the total effect of HFI on underweight during the Post-Aman in 2012–2014 (23.2%). CDD largely mediated the total effect of HFI on wasting (39.7%) during Post-Aman season in 2014 and on underweight (13.7%) during the same season in 2012. These findings demonstrate that HFI is seasonally associated with child undernutrition and mediated by CDD as well in Bangladesh and seasonality and diversity should be considered while designing appropriate population-level food-based interventions to resolve child undernutrition.     

Use of designing for behaviour change framework in identifying and addressing barriers to and enablers of animal source feeding to children ages 8–23 months in Bandarban Hill District in Bangladesh: Implications for a nutrition-sensitive agriculture programme

Inadequate diet quality is a cause of undernutrition among children 6–23 months of age in Bangladesh, particularly in remote and isolated areas such as Bandarban District. Feeding animal source foods can help to combat stunting and wasting problems among children, but it may not be accessible or acceptable. A barrier analysis using the Designing for Behavior Change Framework was conducted in Bandarban district with participants from 4 ethnic groups, to explore potential barriers and key motivators by examining 12 behavioural determinants of consumption of animal-source food in complementary feeding for children 8–23 months. Data were collected from 45 mothers of children 8–23 months, who provided animal-source foods to their children (doers), and from 45 mothers who did not (non-doers), for a total of 90 interviews. Nine determinants were statistically significantly different between doers and non-doers as follows: self-efficacy, positive consequences, negative consequences, social norms, access, reminders, perceived risk, perceived severity and perceived action efficacy. Nearby access to purchase animal-source foods, rearing poultry or livestock at home and the support of household and community members are enablers to feeding animal-source food. In contrast, these same factors are barriers for non-doers. The lack of money to spend on animal-source foods is also a barrier. An integrated nutrition-sensitive and gender-transformative animal-based food production, and inclusive market programme could increase access to meat and eggs at the household level, increase opportunities to earn income and support gender-equitable household workloads and decision-making for optimal child feeding.     

Cancer-Related Fatigue After Esophageal Cancer Surgery: Impact of Postoperative Complications

Annals of Surgical Oncology - The impact of postoperative complications on cancer-related fatigue is unknown. This nationwide prospective cohort study aimed to assess the trajectory of...     

Synthesis,biological activities,and pharmacokinetics studies of a mutual prodrug of aceclofenac and paracetamol

An ester-based mutual prodrug (aceclofenac–paracetamol; AC-PR) was synthesized (one-pot method) with an aim of improving the therapeutic index through prevention of gastrointestinal irritation and bleeding that is associated with aceclofenac. The release of aceclofenac and paracetamol from the ester prodrug (AC-PR) was studied by reverse phase HPLC in hydrochloric acid buffer (pH 1.2), phosphate buffer (pH 7.4), 80 % v/v human plasma, 10 % w/v rat intestinal homogenate and 10 % w/v rat liver homogenate (pH 7.4). The prodrug showed negligible hydrolysis at pH 1.2 as compared to pH 7.4, suggesting that very less of the prodrug would hydrolyze in stomach, but would release the parent drugs at pH 7.4 in adequate amounts. The prodrug showed enhanced anti-inflammatory activity and significant protection against acetic acid-induced writhings (analgesic activity) as compared to that of aceclofenac. Further, the prodrug produced reduced number of ulcers as compared to that of the parent drug. These results suggest that the synthesized mutual prodrug (AC-PR) is better in terms of activity and GIT toxicity than the parent drug.     

Treatment of renal stones with flexible ureteroscopy in preschool age children

The aim of the study is to evaluate the efficacy and safety of retrograde intrarenal surgery (RIRS) to treat renal stones in preschool age (<7 years) children. From September 2005 to May 2013, a total of 65 children (31 boys and 34 girls) with 72 renal stones were treated using RIRS. Patients were considered stone-free when the absence of residual fragments was observed on imaging studies. In the presence of residual calculi >4 mm, a second-stage RIRS was performed. The pre-operative, operative and post-operative data of the patients were retrospectively analyzed. A total of 65 patients with a mean age of 4.31 ± 1.99 years (6 months–7 years) were included in the present study. The mean stone size was 14.66 ± 6.12 mm (7–30 mm). The mean operative time was 46.47 ± 18.27 min. In 5 (7.69 %) patients, the initial procedure failed to reach the renal collecting system and ended with the insertion of a pigtail stent. The stone-free rates were 83.07 and 92.3 % after the first and second procedures, respectively. Complications were observed in 18 (27.7 %) patients and classified according to the Clavien system. Post-operative hematuria (Clavien I) occurred in 6 (9.2 %) patients, post-operative urinary tract infection with fever (Clavien II) was observed in 10 (15.4 %) patients, and ureteral wall injury (Clavien III) was noted in 2 (3 %) patients. RIRS is an effective and safe procedure that can be used to manage renal stones in preschool age children.     

Determination of Non-Recrystallization Temperature for Niobium Microalloyed Steel

In the present investigation, the non-recrystallization temperature (T_NR) of niobium-microalloyed steel is determined to plan rolling schedules for obtaining the desired properties of steel. The value of T_NR is based on both alloying elements and deformation parameters. In the literature, T_NR equations have been developed and utilized. However, each equation has certain limitations which constrain its applicability. This study was completed using laboratory-grade low-carbon Nb-microalloyed steels designed to meet the API X-70 specification. Nb- microalloyed steel is processed by the melting and casting process, and the composition is found by optical emission spectroscopy (OES). Multiple-hit deformation tests were carried out on a Gleeble^® 3500 system in the standard pocket-jaw configuration to determine T_NR. Cuboidal specimens (10 (L) × 20 (W) × 20 (T) mm³) were taken for compression test (multiple-hit deformation tests) in gleeble. Microstructure evolutions were carried out by using OM (optical microscopy) and SEM (scanning electron microscopy). The value of T_NR determined for 0.1 wt.% niobium bearing microalloyed steel is ~ 951 °C. Nb- microalloyed steel rolled at T_NR produce partially recrystallized grain with ferrite nucleation. Hence, to verify the TNR value, a rolling process is applied with the finishing rolling temperature near TNR (~951 °C). The microstructure is also revealed in the pancake shape, which confirms T_NR.