In the present study, comprehensive stress testing of amlodipine (AM) was carried out according to International Conference on Harmonization (ICH) Q1A(R2) guideline. AM was subjected to acidic, neutral and alkaline hydrolysis, oxidation, photolysis and thermal stress conditions. The drug showed instability in acidic and alkaline conditions, while it remained stable to neutral, oxidative, light and thermal stress. A total of nine degradation products (DPs) were formed from AM, which could be separated by the developed gradient LC method on a C18 column. The products formed under various stress conditions were investigated by LC–MS/MS analysis. The previously developed LC method was suitably modified for LC–MS/MS studies by replacing phosphate buffer with ammonium acetate buffer of the same concentration (pH 5.0). A complete fragmentation pathway of the drug was first established to characterize all the degradation products using LC–MS/MS and multi-stage mass (MSn) fragmentation studies. The obtained mass values were used to study elemental compositions, and the total information helped with the identification of DPs, along with its degradation pathway.

Purpose: This study aimed to evaluate and analyze the feasibility and the oncological and functional outcomes of limb salvage surgery in extremity soft tissue sarcomas (ESTS) and bone tumors invading vessels. Materials and Methods: This single-center retrospective analysis included patients with ESTS encasing or invading major blood vessels that were treated by limb salvage surgery with vascular resection and reconstruction between January 1995 and December 2019. Patients with contiguous involvement of major blood vessels and nerves and patients requiring amputation were excluded from the study. Results: A total of 24 vessels (14 arteries and 10 veins) in 14 patients were reconstructed. Ten (71.4%) patients underwent both arterial and venous reconstruction, and four (28.6%) underwent only arterial reconstruction. Reconstruction was performed with a reversed saphenous vein (RSV) graft in 12 patients and with a synthetic graft (SG) in the other 12 patients. At a median follow-up of 27 months, RSV grafts were patent in 10 of 12 (83.3%) vessels and SGs were patent in 6 of 12 (50.0%) vessels (log-rank test, P=0.083). Out of 14 arteries and 10 veins, 11 arteries and 5 veins were patent, respectively. No patient developed local recurrence, and 2 (14.3%) patients developed distant metastases. Limb salvage rate was 13/14 (92.9%). The mean Musculoskeletal Tumor Society score was 83.3%. The 5- and 10-year overall survival rates were 80% and 50%, respectively. Conclusion Limb salvage surgery in ESTS with vascular resection and reconstruction is feasible and provides favorable oncological and functional outcomes.

Purpose: This study aimed to evaluate and analyze the feasibility and the oncological and functional outcomes of limb salvage surgery in extremity soft tissue sarcomas (ESTS) and bone tumors invading vessels. Materials and Methods: This single-center retrospective analysis included patients with ESTS encasing or invading major blood vessels that were treated by limb salvage surgery with vascular resection and reconstruction between January 1995 and December 2019. Patients with contiguous involvement of major blood vessels and nerves and patients requiring amputation were excluded from the study. Results: A total of 24 vessels (14 arteries and 10 veins) in 14 patients were reconstructed. Ten (71.4%) patients underwent both arterial and venous reconstruction, and four (28.6%) underwent only arterial reconstruction. Reconstruction was performed with a reversed saphenous vein (RSV) graft in 12 patients and with a synthetic graft (SG) in the other 12 patients. At a median follow-up of 27 months, RSV grafts were patent in 10 of 12 (83.3%) vessels and SGs were patent in 6 of 12 (50.0%) vessels (log-rank test, P=0.083). Out of 14 arteries and 10 veins, 11 arteries and 5 veins were patent, respectively. No patient developed local recurrence, and 2 (14.3%) patients developed distant metastases. Limb salvage rate was 13/14 (92.9%). The mean Musculoskeletal Tumor Society score was 83.3%. The 5- and 10-year overall survival rates were 80% and 50%, respectively. Conclusion Limb salvage surgery in ESTS with vascular resection and reconstruction is feasible and provides favorable oncological and functional outcomes.

Antimicrobial Cationic Peptides ; metabolism ; Fermentation ; Food Microbiology ; India ; Lactobacillales ; isolation & purification ; metabolism ; Microbial Sensitivity Tests ; Vegetables ; microbiology

Background/Aims: The mechanism via which supra-esophageal symptoms are generated is unclear. We assessed upper esophageal sphincter (UES) function in novel fashion using functional lumen imaging probe (FLIP) topography. We hypothesize that symptoms related to aspiration of esophageal contents may be associated with a more distensible UES. Methods: FLIP and reflux symptom index score data from patients undergoing diagnostic evaluation for an esophageal complaint over a 10-month period were analyzed retrospectively. UES distensibility on FLIP was studied at 40-70 mL volumes with in-depth analysis at 50 and 60 mL. Symptoms were compared between patients with low, middle, and high UES-distensibility index (UES-DI). Receiveroperating characteristic analysis was performed to determine associations between the UES-DI and individual reflux symptom index symptom item scores. Results: One hundred and eleven subjects were included. Overall, the associations between UES-DI and symptoms that could be related to supra-esophageal aspiration were strongest at the 50 mL FLIP volume. Choking item score was highest in the high UES-DI group (2.8) vs 1.4 (P < 0.001) in the middle UES-DI and 1.1 (P = 0.004) in the low UES-DI groups. Similarly, the cough item score was highest in the high UES-DI group (2.7) vs 1.5 (P = 0.009) and 0.9 (P = 0.002) groups. Conclusion A higher UES-DI measures defective barrier function which could may be the main pathophysiology that generates supra-esophageal symptoms.

Histone modifications have been demonstrated to play a significant role in oral squamous cell carcinoma (OSCC) epigenetic regulation. An in-silico analysis of The Cancer Genome Atlas (TCGA) of various histone acetyl transferases (HATs) and histone deacetylases (HDACs) suggested that HATs do not differ between normal and tumor samples whereas HDAC2 and HDAC1 change maximally and marginally respectively between normal and tumor patients with no change being noted in HDAC6 expression. Hence, this investigation was carried out to validate the expression states of HDAC 1, 2 and 6 mRNAs in buccal mucosa and tongue SCC samples in an Indian cohort. Buccal mucosa and tongue squamous cell carcinoma tissues with intact histopathology were processed for RNA isolation followed by cDNA synthesis which was then subjected to q-PCR for HDACs. The average RNA yield of the tongue tissue sample was ∼2 μg/mg of tissue and the A260/280 ratios were between 2.03 and 2.06. The average RNA yield of buccal mucosa tissue sample was ∼1 μg/mg of tissue and the A260/280 ratio were between 2.00 and 2.08. We have demonstrated that HDAC2 was overexpressed in tongue and buccal mucosa samples. Over-expression of HDAC2 imply potential use of HDACi along with standard chemotherapeutic drug in oral cancer treatment.

Histone modifications have been demonstrated to play a significant role in oral squamous cell carcinoma (OSCC) epigenetic regulation. An in-silico analysis of The Cancer Genome Atlas (TCGA) of various histone acetyl transferases (HATs) and histone deacetylases (HDACs) suggested that HATs do not differ between normal and tumor samples whereas HDAC2 and HDAC1 change maximally and marginally respectively between normal and tumor patients with no change being noted in HDAC6 expression. Hence, this investigation was carried out to validate the expression states of HDAC 1, 2 and 6 mRNAs in buccal mucosa and tongue SCC samples in an Indian cohort. Buccal mucosa and tongue squamous cell carcinoma tissues with intact histopathology were processed for RNA isolation followed by cDNA synthesis which was then subjected to q-PCR for HDACs. The average RNA yield of the tongue tissue sample was ∼2 μg/mg of tissue and the A260/280 ratios were between 2.03 and 2.06. The average RNA yield of buccal mucosa tissue sample was ∼1 μg/mg of tissue and the A260/280 ratio were between 2.00 and 2.08. We have demonstrated that HDAC2 was overexpressed in tongue and buccal mucosa samples. Over-expression of HDAC2 imply potential use of HDACi along with standard chemotherapeutic drug in oral cancer treatment.

Purpose: Prostate cancer (PCa) screening can lead to potential over-diagnosis/over-treatment of indolent cancers. There is a need to optimize practices to better risk-stratify patients. We examined initial longitudinal outcomes of mid-life men with an elevated baseline prostate-specific antigen (PSA) following initiation of a novel screening program within a system-wide network. Materials and Methods: We assessed our primary care network patients ages 40 to 49 years with a PSA measured following implementation of an electronic health record screening algorithm from 2/2/2017–2/21/2018. The multidisciplinary algorithm was developed taking factors including age, race, family history, and PSA into consideration to provide a personalized approach to urology referral to be used with shared decision-making. Outcomes of men with PSA ≥1.5 ng/mL were evaluated through 7/2021. Statistical analyses identified factors associated with PCa detection. Clinically significant PCa (csPCa) was defined as Gleason Grade Group (GGG) ≥2 or GGG1 with PSA ≥10 ng/mL. Results: The study cohort contained 564 patients, with 330 (58.5%) referred to urology for elevated PSA. Forty-nine (8.7%) underwent biopsy; of these, 20 (40.8%) returned with PCa. Eleven (2.0% of total cohort and 55% of PCa diagnoses) had csPCa. Early referral timing (odds ratio [OR], 4.58) and higher PSA (OR, 1.07) were significantly associated with PCa at biopsy on multivariable analysis (both p<0.05), while other risk factors were not. Referred patients had higher mean PSAs (2.97 vs. 1.98, p=0.001). Conclusions Preliminary outcomes following implementation of a multidisciplinary screening algorithm identified PCa in a small, important percentage of men in their forties. These results provide insight into baseline PSA measurement to provide early risk stratification and detection of csPCa in patients with otherwise extended life expectancy. Further follow-up is needed to possibly determine the prognostic significance of such mid-life screening and optimize primary care physician-urologist coordination.

Background: The high prevalence of type 2 diabetes mellitus (T2DM) in the Philippines has burdened the health care system. Therefore, we compared the standard of care Insulin 30/70 + Insulin Glulisine (Arm B) to a traditional insulin regimen NPH Insulin + Regular Insulin (Arm A) to test the concept that both insulin regimens provide comparable effectiveness and safety in real-world practice. Methods : This is a ‘proof-of-concept,’ prospective, randomized, open label pragmatic study of 40 consecutive Filipino T2DM patients from October 2015 to June 2016. The primary endpoint was a reduction in HbA1c at 12 weeks. The secondary endpoints were changes in Fasting Plasma Glucose (FPG), Post Prandial Glucose (PPG), Capillary Blood Sugar (CBS), weight and insulin dose at 12 weeks. ANCOVA and Fisher’s exact tests were used. Results : Patients in treatment arm A showed comparable glycemic control to arm B as measured by reductions in HbA1c (2.89% vs. 2.67%; P = 0.657), FPG (65.94 vs. 46.71 mg/dl; P = 0.57), PPG (76.49 vs. 86.96 mg/dl; P = 0.271) and CBS (115.15 vs. 145.95 mg/dl; P = 0.420). Both treatment arms reported similar weight gain (1.92 vs. 1.22 kg), experienced similar incidence of hypoglycemia (7 vs. 6 patients) and adverse events (AE) (8 vs. 8 patients). Conclusion The traditional combination of NPH Insulin + Regular Insulin offers comparable glycemic control and tolerance as the standard of care without any new safety signals in the Filipino T2DM population. With a lower price, it can be one of the strategies to reduce the fi nancial burden of antidiabetic treatment.
Insulin, Isophane ; Insulin ; Diabetes Mellitus, Type 2