REAL-world evidence of risk factors and comorbidities in YOUNG Indian adults with type 2 diabetes mellitus: A REAL YOUNG (diabetes) study.

OBJECTIVE: To assess the clinical characteristics, risk factors, and comorbidities associated with type 2 diabetes mellitus (T2DM) in young adult patients. METHODS: This is a retrospective, multicentric real-world study that included young adults (18-45 years) with T2DM. Primary information including demographics, medical and family history, biochemical measures (pre-and post-prandial blood glucose levels, glycosylated hemoglobin [HbA1c] and blood pressure, and lipid parameters) smoking and drinking habits were collected retrospectively from the medical records of the respective hospitals/clinics. Data were analyzed using descriptive and appropriate comparative statistics. RESULTS: A total of 22,921 patients from 623 sites were included. The median age was 37.0 years and the majority were men (61.6%). The proportion of patients from the age group >35-≤45 years was 62.7%. Among all patients, 46.9% had only T2DM; however, 53.1% of patients had T2DM with other comorbidities (T2DM with hypertension, dyslipidemia, and both). The majority of patients had elevated body mass index (BMI) (overweight, 46.6%; and obese, 22.9%). Family history of T2DM (68.1%) was most common in overall population. Sedentary lifestyle (63.1%), alcohol consumption (38.9%), and regular smoking (23.1%) were the most common associations in patients with T2DM with dyslipidemia and hypertension. Uncontrolled HbA1c level (≥7%) were observed in 79.2% of patients. The level of HbA1c was significantly increased with the duration of T2DM and sedentary lifestyle (p < 0.001). CONCLUSION: Higher BMI, family history of T2DM, sedentary lifestyle, alcohol consumption, and smoking were the most common risk facors, while hypertension and dyslipidemia were the most prevalent comorbidities associated with T2DM in young Indian adults.

Molecular characterization of endangered endemic plant Aloe pseudorubroviolacea using chloroplast matK and plastid rbcL gene.

An endangered and rare species Aloe pseudorubroviolacea from the plant family Asphodelaceae which is presently recorded as endangered in Saudi Arabia collected from Al-Baha region of Saudi Arabia its GPS Latitude and Longitude coordinates 19.8345, 41.5481. The chloroplast matK and rbcL gene was considered in this study based on molecular identification the size is about 571 and 664 bp respectively. From the sequence analysis the gene matK and rbcL confirm that this species is very much closely related with A. rubroviolacea and also inter related with the species Astroloba rubriflora, Chrysopogon gryllus, Chortolirion angolense shows about 98.7% sequence homology. The partial matK and rbcL gene sequence discriminate Aloe pseudorubroviolacea from the closely related plant species, A. rubroviolacea. The gene sequence of rbcL discriminates the species from Chrysopogon gryllus and Chortolirion angolense, demonstrates the nucleotide variations in 3 different sites (623C/T; 653C/T; 700C/A). This study showed that matK and rbcL sequence region of chloroplast gene used to authenticate the samples of A. pseudorubroviolacea and which provide to help in correct identification and conservation process of this medicinally valuable endangered plant species.

Identification of potential drug targets in human pathogen Bacillus cereus and insight for finding inhibitor through subtractive proteome and molecular docking studies.

Bacillus cereus is a gram-positive, anaerobic, spore-forming bacterium related to food poisoning in humans. Vomit and diarrhea are the symptoms of foodborne B. cereus infection caused by emetic toxins and three enterotoxins, respectively. This bacterium is broadly present in soil and foods such as vegetables, spices, milk, and meat. The antibiotics impenem, vancomycin, chloramphenicol, gentamicin, and ciprofloxacin are used for all susceptible strains of B. cereus. But these antibiotics cause side effects in the host due to the drug-host interaction; because the targeted proteins by the drugs are not pathogen specific proteins, they are similar to human proteins also. To overcome this problem, this study focused on identifying putative drug targets in the pathogen B. cereus and finding new drugs to inhibit the function of the pathogen. The identification of drug targets is a pipeline process, starting with the identification of targets non-homologous to human and gutmicrobiota proteins, finding essential proteins, finding other proteins that highly interact with these essential proteins that are also highly important for protein network stability, finding cytoplasmic proteins with a clear pathway and known molecular function, and finding non-druggable proteins. Through this process, two novel drug targets were identified in B. cereus. Among the various antibiotics, Gentamicin had showed good binding affinity with the identified novel targets through molecular modeling and docking studies using Prime and GLIDE module of Schrödinger. Hence, this study suggest that the identified novel drug targets may very useful in drug therapeutic field for finding inhibitors which are similar to Gentamicin and designing new formulation of drug molecules to control the function of the foodborne illness causing pathogen B. cereus.

Molecular perspective and anticancer activity of medicinal plants.

To evaluate phytochemical constituents from the methanolic extracts of medicinal plants Aloe castellorum and Aloe pseudorubroviolacea. The cytotoxic activity of Aloe castellorum and Aloe pseudorubroviolacea leaf extracts against Human colon cancer cell line (HCT-116) was also assessed. The two medicinal plant extracts having significant cytotoxic activity, meanwhile the methanolic extract of Aloe castellorum shows higher cytotoxic activity than Aloe pseudorubroviolacea extract. The Aloe castellorum shows remarkable activity against respective cell line than control. The characteristic chemical constituents of Aloe castellorum and Aloe pseudorubroviolacea leaf extracts were recognized from Gas chromatography and Mass spectrometry (GC-MS) technique. The molecular docking studies also support the cytotoxic activity.

Physico-chemical studies on binary aqueous solutions of Anti-Viral Influenza drugs.

The ultrasonic velocity, density, viscosity and absorption have been measured for solution of Influenza Anti-Viral drugs (Amantadine and Oseltamivir) are presented at room temperature 303K. By taking measurements of Anti Influenza Viral drugs at 0.2, 0.4 and 0.6% concentrations of each solution. The aim of the study is to increase the solubility, stability, sweetness of drugs by the formation of complexation. The ultrasonic velocity, density and viscosity have been measured at 2MHz for the aqueous solutions of (i) Influenza Anti-Viral Drugs + HPMC (Hydroxy Propyl Methyl Cellulose), Lactose and CaCl2 (Calcium Chloride at different concentrations at a temperature 303K.The acoustical parameters such as adiabatic compressibility (ß), intermolecular free length (Lf), internal pressure (πi), Rao's constant (R), relaxation time (τ), acoustical impedance (Za), absorption coefficient (α/f2), free volume (Vf), cohesive energy and solvation number (Sn) have been computed. These properties are attributed to solute-solvent interactions through hydrogen bonding, segment-segment interaction, molecular association, polymer-solvent interaction, polymer-polymer interaction and etc. The total absorption can be considered as the sum of contributions from solute-solvent interactions. These results are further supported by FTIR studies.

Teneligliptin in management of type 2 diabetes mellitus.

Teneligliptin is a recently developed oral dipeptidyl peptidase 4 inhibitor indicated for the management of type 2 diabetes mellitus (T2DM) in adults along with diet and exercise. Teneligliptin has been recently available in Japan (Teneria(®)), Argentina (Teneglucon(®)), and India (Tenepure; Teneza) at relatively affordable price. This is a positive step toward the management of T2DM in developing countries, where the cost of medicine is out-of-pocket expenditure and is a limiting factor for health care. This review evaluates the efficacy and safety of teneligliptin in the management of T2DM. Teneligliptin has been systematically evaluated in T2DM as monotherapy with diet and exercise and in combination with metformin, glimepiride, pioglitazone, and insulin in short-term (12 weeks) and long-term (52 weeks) studies. These studies have reported a reduction in HbA1c of 0.8%-0.9% within 12 weeks of therapy. Two 52-week studies reported sustained improvement in glycemic control with teneligliptin. Teneligliptin has been found to be well tolerated, and the safety profile is similar to other dipeptidyl peptidase 4 inhibitors. Hypoglycemia and constipation are the main adverse events. Teneligliptin can be administered safely to patients with mild, moderate, or severe renal impairment or end-stage renal disease without dose adjustment. Similarly, it can be used in patients with mild-to-moderate hepatic impairment. Teneligliptin is effective and well tolerated and may have an important role in the management of T2DM.

Simpson's paradox - aggregating and partitioning populations in health disparities of lung cancer patients.

It is well known that non-small cell lung cancer (NSCLC) is a heterogeneous group of diseases. Previous studies have demonstrated genetic variation among different ethnic groups in the epidermal growth factor receptor (EGFR) in NSCLC. Research by our group and others has recently shown a lower frequency of EGFR mutations in African Americans with NSCLC, as compared to their White counterparts. In this study, we use our original study data of EGFR pathway genetics in African American NSCLC as an example to illustrate that univariate analyses based on aggregation versus partition of data leads to contradictory results, in order to emphasize the importance of controlling statistical confounding. We further investigate analytic approaches in logistic regression for data with separation, as is the case in our example data set, and apply appropriate methods to identify predictors of EGFR mutation. Our simulation shows that with separated or nearly separated data, penalized maximum likelihood (PML) produces estimates with smallest bias and approximately maintains the nominal value with statistical power equal to or better than that from maximum likelihood and exact conditional likelihood methods. Application of the PML method in our example data set shows that race and EGFR-FISH are independently significant predictors of EGFR mutation.

Biosynthesis of luminescent quantum dots in an earthworm.

The synthesis of designer solid-state materials by living organisms is an emerging field in bio-nanotechnology. Key examples include the use of engineered viruses as templates for cobalt oxide (Co(3)O(4)) particles, superparamagnetic cobalt-platinum alloy nanowires and gold-cobalt oxide nanowires for photovoltaic and battery-related applications. Here, we show that the earthworm's metal detoxification pathway can be exploited to produce luminescent, water-soluble semiconductor cadmium telluride (CdTe) quantum dots that emit in the green region of the visible spectrum when excited in the ultraviolet region. Standard wild-type Lumbricus rubellus earthworms were exposed to soil spiked with CdCl(2) and Na(2)TeO(3) salts for 11 days. Luminescent quantum dots were isolated from chloragogenous tissues surrounding the gut of the worm, and were successfully used in live-cell imaging. The addition of polyethylene glycol on the surface of the quantum dots allowed for non-targeted, fluid-phase uptake by macrophage cells.

Everolimus in metastatic renal cell carcinoma patients intolerant to previous VEGFr-TKI therapy: a RECORD-1 subgroup analysis.

BACKGROUND: A relevant percentage of patients with metastatic renal cell carcinoma develop intolerance to vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFr-TKIs) and require careful selection of subsequent treatment. This retrospective analysis evaluated the safety and efficacy of everolimus in patients enrolled in the phase-III RECORD-1 trial who discontinued previous VEGFr-TKI therapy because of toxicity. METHODS: Patients with an adverse event (AE) as their primary reason for discontinuation of previous VEGFr-TKI therapy were included. Median progression-free survival (PFS) for VEGFr-TKI-intolerant patients in each arm was estimated using the Kaplan-Meier method, and effect on PFS (hazard ratio (HR)) was calculated using the Cox proportional hazard model. RESULTS: In VEGFr-TKI-intolerant patients (n=58, 14%), median PFS was 5.4 months with everolimus and 1.9 months with placebo (HR: 0.32; P=0.004). In sunitinib-intolerant patients (n=26), median PFS was 5.1 months with everolimus and 2.8 months with placebo (HR: 0.28; P=0.033). Grade 3/4 AEs reported with everolimus in VEGFr-TKI-intolerant patients included infections (16%), fatigue (7%) and stomatitis (4%). The toxicity profile of everolimus was similar in the VEGFr-TKI-intolerant and overall study populations. CONCLUSION: Everolimus is well tolerated and efficacious with no increased toxicity in patients intolerant to VEGFr-TKI therapy.

Everolimus in metastatic renal cell carcinoma: Subgroup analysis of patients with 1 or 2 previous vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapies enrolled in the phase III RECORD-1 study.

INTRODUCTION: In the phase III RECORD-1 trial (ClinicalTrials.gov: NCT00410124), patients with metastatic renal cell carcinoma (mRCC) who progressed on previous vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFr-TKI) therapy were randomised 2:1 to everolimus 10mg once daily (n=277) or placebo (n=139). Median progression-free survival (PFS) was 4.9months with everolimus and 1.9months with placebo (hazard ratio [HR], 0.33; P<.001). This preplanned, prospective sub-analysis evaluated PFS benefit of everolimus versus placebo in patients who had previously received 1 or 2 VEGFr-TKIs. PATIENTS AND METHODS: Median PFS was estimated using the Kaplan-Meier method, and Cox proportional hazards model was used to analyse differences in PFS. RESULTS: All patients (100%) received ⩾1 previous VEGFr-TKI; 26% of patients received 2 previous VEGFr-TKIs. Among patients who received 1 previous VEGFr-TKI, median PFS was 5.4months with everolimus and 1.9months with placebo (HR, 0.32; 95%confidence interval [CI], 0.24-0.43; P<.001). Among patients who received 2 previous VEGFr-TKIs, median PFS was 4.0months with everolimus and 1.8months with placebo (HR, 0.32; 95%CI, 0.19-0.54; P<.001). The everolimus safety profile was similar for both groups. CONCLUSIONS: Everolimus was associated with prolonged PFS relative to placebo in patients who received 1 or 2 previous VEGFr-TKIs. Patients who received only 1 previous VEGFr-TKI had apparently longer PFS with everolimus in reference to those who received 2 previous VEGFr-TKIs. These results support the use of everolimus as the standard of care in patients who fail initial VEGFr-TKI therapy.

Optimization of Antimicrobial Production by a Marine Actinomycete Streptomyces afghaniensis VPTS3-1 Isolated from Palk Strait, East Coast of India.

Totally 25 marine soil samples were collected from the region of Palk Strait of Bay of Bengal, Tamil Nadu, and were subjected to the isolation of actinomycetes. Sixty-eight morphologically distinct isolates were obtained and 37% (25) of them had antimicrobial activity. The potential producer was named as Streptomyces sp. VPTS3-1 and the phylogenetic evaluation on the basis of 16S rDNA sequence further categorized the organism as Streptomyces afghaniensis VPTS3-1. Further, the antimicrobial compound was extracted from the isolate using various solvents and the antimicrobial efficacies were tested against bacterial and fungal pathogens. In addition, in vitro optimization of parameters for the antimicrobial compound production revealed that the suitable pH as 7-8, the period of incubation as 9 days, temperature (30°C), salinity (2%), and starch and KNO3 as the suitable carbon and nitrogen sources respectively in starch-casein medium.

Periodontal therapy reduces the severity of active rheumatoid arthritis in patients treated with or without tumor necrosis factor inhibitors.

BACKGROUND: Rheumatoid arthritis (RA) and periodontitis are common chronic inflammatory conditions. Recent studies showed a beneficial effect of periodontal treatment on the severity of active RA. This study was undertaken to further examine the effect of non-surgical periodontal treatment on the signs and symptoms of RA in patients treated with or without anti-tumor necrosis factor-alpha (anti-TNF-alpha) medications. The effect of anti-TNF-alpha therapy on periodontitis also was assessed. METHODS: Forty participants diagnosed with moderate/severe RA (under treatment for RA) and severe periodontitis were randomly assigned to receive initial non-surgical periodontal therapy with scaling/root planing and oral hygiene instructions (n = 20) or no periodontal therapy (n = 20). To control RA, all participants had been using disease-modifying anti-rheumatic drugs, and 20 had also been using anti-TNF-alpha before randomization. Probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), gingival index (GI), plaque index (PI), RA disease activity score 28 (DAS28), and erythrocyte sedimentation rate (ESR) were measured at baseline and 6 weeks later. Linear mixed models were used to identify significant differences between subjects who received periodontal treatment and those who did not. RESULTS: Patients receiving periodontal treatment showed a significant decrease in the mean DAS28, ESR (P <0.001), and serum TNF-alpha (P <0.05). There was no statistically significant decrease in these parameters in patients not receiving periodontal treatment. Anti-TNF-alpha therapy resulted in a significant improvement in CAL, PD, BOP, and GI. CONCLUSIONS: Non-surgical periodontal therapy had a beneficial effect on the signs and symptoms of RA, regardless of the medications used to treat this condition. Anti-TNF-alpha therapy without periodontal treatment had no significant effect on the periodontal condition.

Glycemic level at the first visit and prediction of GDM.

OBJECTIVE: To evaluate the glycemic level at the first visit that is likely to predict gestational diabetes mellitus (GDM). METHODS: Consecutive pregnant women underwent a 75g oral glucose tolerance Test (OGTT) recommended by WHO and diagnosed GDM if 2hr post plasma glucose (PG) value > or = 140 mg/dl. Women with normal OGTT results at the first visit were screened again with an OGTT at the subsequent visits. RESULTS: A total of 4151 pregnant women from different trimesters underwent OGTT. Of them 739 women (17.8%) had GDM. Among the GDM women, 528 (71.4%) were detected at the first visit. On screening during subsequent visits, GDM was diagnosed in the remaining 211(28.6%) women who had normal OGTT in the first visit. We performed the analysis taking the glycemic level in the first visit of 211 pregnant women who manifested GDM in the subsequent visit. During normal pregnancy, 2hr PG level is < 120 mg/dl. Taking this value into consideration among the 211 women who turned to have GDM in the subsequent visits 119 women (56.4%) had 2hrPG > or = 120 mg/dl and the remaining 92(43.6%) had 2hrPG < 120 mg/dl. CONCLUSION: Pregnant women irrespective of 2 hr PG > or = or < 120 mg/dl at initial visit progressed to GDM in the subsequent visit. No glycemic level in the early weeks of pregnancy predicts GDM and at the same time at no statistically significant glycemic cut-off level could we say that a woman will not develop GDM. Hence rescreening in the subsequent trimester or visits is essential.

Retrieval of an IV catheter fragment from the pulmonary artery 11 years after embolization.

The use of a peripherally inserted central catheter (PICC) is occasionally complicated by intravascular fracture and central embolization of the catheter fragment. We present a patient in whom a PICC fragment was retrieved from the pulmonary artery 11 years after embolization following its incidental detection. Despite a history of IV drug abuse and mitral regurgitation, this patient remained asymptomatic and without complications. The catheter fragment was retrieved since the patient was believed to be at risk for endocarditis. This may be the longest duration reported of an embolized catheter fragment that was successfully removed. As the natural history of asymptomatic-retained central venous foreign bodies remains unclear, the decision to remove them should be individualized. In selected cases, these foreign bodies may be retrieved without complications even several years after embolization.