Decoding the effect of photoperiodic cues in transducing kisspeptin-melatonin circuit during the pubertal onset in common carp.

This study unravels the intricate interplay between photoperiod, melatonin, and kisspeptin to orchestrate the pubertal onset of Common carp. Female fingerlings exposed to long days (LD) exhibited a hormonal crescendo, with upregulated hypothalamic-pituitary-ovarian (HPO) axis genes (kiss1, kiss1r, kiss2, gnrh2, gnrh3) and their downstream targets (lhr, fshr, ar1, esr1). However, the expression of the melatonin receptor (mtnr1a) diminished in LD, suggesting a potential inhibitory role. This hormonal symphony was further amplified by increased activity of key transcriptional regulators (gata1, gata2, cdx1, sp1, n-myc, hoxc8, plc, tac3, tacr3) and decreased expression of delayed puberty genes (mkrn1, dlk1). In contrast, short days (SD) muted this hormonal chorus, with decreased gnrh gene and regulator expression, elevated mtnr1a, and suppressed gonadal development. In in-vitro, estradiol mimicked the LD effect, boosting gnrh and regulator genes while dampening mtnr1a and melatonin-responsive genes. Conversely, melatonin acted as a conductor, downregulating gnrh and regulator genes and amplifying mtnr1a. Our findings illuminate the crucial roles of melatonin and kisspeptin as opposing forces in regulating pubertal timing. LD-induced melatonin suppression allows the kisspeptin symphony to flourish, triggering GnRH release and, ultimately, gonadal maturation. This delicate dance between photoperiod, melatonin, and kisspeptin orchestrates common carp's transition from juvenile to reproductive life.

Appendectomy and asthma: a search for an association in older subjects.

INTRODUCTION: Several risk factors found to be associated with postoperative complications and cancer surgery, which carry a significant morbidity risk to cancer patients. Therefore, prehabilitation is necessary to improve the functional capability and nutritional status of a patient prior to surgery, so that the patient can withstand any postoperative activity and associated deterioration. Thus, this study aims to assess the effectiveness of prehabilitation interventions on the functional status of patients with gastric and oesophageal cancer who underwent esophagectomy and gastrectomy. MATERIAL AND METHODS: An interventional study was carried out among oesophageal and gastric cancer patients who had undergone surgery at the National Cancer Institute of Malaysia. The prehabilitation process took a maximum of two weeks, depending on the patient's optimisation before surgery. The prehabilitation is based on functional capacity (ECOG performance status), muscle function (handgrip strength), cardio-respiratory function (peak flow meter) and nutritional status (calorie and protein). Postoperative outcomes are measured based on the length of hospital stay, complications, and Clavien-Dindo Classification. RESULTS: Thirty-one patients were recruited to undergo a prehabilitation intervention prior to gastrectomy (n=21) and esophagectomy (n=10). Demographically, most of the cancer patients were males (67.7%) with an ideal mean of BMI (23.5±6.0). Physically, the majority of them had physical class (ASA grade) Grade 2 (67.7%), ECOG performance status of 1 (61.3%) and SGA grade B (51.6%). The functional capacity and nutritional status showed a significant improvement after one week of prehabilitation interventions: peak expiratory flow meter (p<0.001), handgrip (p<0.001), ECOG performance (p<0.001), walking distance (p<0.001), incentive spirometry (p<0.001), total body calorie (p<0.001) and total body protein (p=0.004). However, those patients who required two weeks of prehabilitation for optimization showed only significant improvement in peak expiratory flow meter (p<0.001), handgrip (p<0.001), and incentive spirometry (p<0.001). Prehabilitation is significantly associated postoperatively with the length of hospital stay (p=0.028), complications (p=0.011) and Clavien-Dindo Classification (p=0.029). CONCLUSION: Prehabilitation interventions significantly increase the functional capacity and nutritional status of cancer patients preoperatively; concurrently reducing hospital stays and complications postoperatively. However, certain cancer patients might require over two weeks of prehabilitation to improve the patient's functional capacity and reduce complications postoperatively.

A metagenomic-based study of two sites from the Barbadian reef system.

We study the microbiome of sea water collected from two locations of the Barbadian coral reefs. The two sites differ in several environmental and ecological variables including their endogenous benthic community and their proximity to urban development and runoffs from inland watersheds. The composition of the microbial communities was estimated using whole genome DNA shotgun sequencing with adjuvant measurements of chemical and environmental qualities. Although both sites exhibit a similar degree of richness, the less urbanized site (Maycocks reef at Hangman's Bay) has a strong concentration of phototrophs whereas the more urbanized location (Bellairs reef at Folkstone) is enriched for copiotrophs, macroalgal symbionts and marine-related disease-bearing organisms from taxa scattered across the tree of life. Our results are concordant with previous profiles of warm ocean surface waters, suggesting our approach captures the state of each coral reef site, setting the stage for longitudinal studies of marine microbiome dynamics in Barbados. Supplementary Information: The online version contains supplementary material available at 10.1007/s00338-022-02330-y.

Suppression of decoherence tied to electron-phonon coupling in telecom-compatible quantum dots: low-threshold reappearance regime for quantum state inversion.

We demonstrate suppression of dephasing tied to deformation potential coupling of confined electrons to longitudinal acoustic (LA) phonons in optical control experiments on large semiconductor quantum dots (QDs) with emission compatible with the low-dispersion telecommunications band at 1.3 µm. By exploiting the sensitivity of the electron-phonon spectral density to the size and shape of the QD, we demonstrate a fourfold reduction in the threshold pulse area required to enter the decoupled regime for exciton inversion using adiabatic rapid passage (ARP). Our calculations of the quantum state dynamics indicate that the symmetry of the QD wave function provides an additional means to engineer the electron-phonon interaction. Our findings will support the development of solid-state quantum emitters in future distributed quantum networks using semiconductor QDs.

ß-cell replenishment: Possible curative approaches for diabetes mellitus.

AIMS: Diabetes mellitus (DM) is a disorder of heterogeneous etiology marked by persistent hyperglycemia. Exogenous insulin is the only treatment for type 1 diabetes (T1D). Islet transplantation is a potential long cure for T1D but is disapproved due to the possibility of immune rejection in the later stage. The approaches used for treating type 2 diabetes (T2D) include diet restrictions, weight management and pharmacological interventions. These procedures have not been able to boost the quality of life for diabetic patients owing to the complexity of the disorder. DATA SYNTHESIS: Hence, research has embarked on permanent ways of managing, or even curing the disease. One of the possible approaches to restore the pancreas with new glucose-responsive ß-cells is by their regeneration. Regeneration of ß-cells include islet neogenesis, dedifferentiation, and trans-differentiation of the already differentiated cells. CONCLUSIONS: This review briefly describes the islet development, functions of ß-cells, mechanism and factors involved in ß-cell death. It further elaborates on the potential of the existing and possible therapeutic modalities involved in the in-vivo replenishment of ß-cells with a focus on exercise, diet, hormones, small molecules, and phytochemicals.

Genetic variants of resistin and its plasma levels: Association with obesity and dyslipidemia related to type 2 diabetes susceptibility.

Resistin, an adipokine, is involved in obesity and Type 2 Diabetes (T2D). The current study evaluates the association between RETN polymorphisms (-638 G/A, -420C/G & -358 G/A) and the risk towards T2D. Controls and T2D patients were enrolled from Gujarat, India. Polymorphisms of RETN were genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism. For the genotype-phenotype correlation analysis Fasting Blood Glucose (FBG), Body Mass Index (BMI) and plasma lipid profile were used. Plasma levels of resistin were assayed by ELISA. Our study suggests an association of RETN -420C/G polymorphism with T2D risk. The CC genotype of RETN -420C/G polymorphism was found to be associated with FBG, BMI, and total cholesterol. Plasma resistin levels were found to be significantly increased in diabetic patients as compared to controls. Our findings suggest -420C/G polymorphism of RETN as an important factor which could pose a powerful risk towards T2D susceptibility.

Circulatory Omentin-1 levels but not genetic variants influence the pathophysiology of Type 2 diabetes.

OBJECTIVE: Omentin-1, an anti-inflammatory protein, is secreted by the visceral adipose tissue. Altered levels of Omentin-1 are associated with obesity and Type 2 Diabetes (T2D). Although Omentin-1 is implicated in the insulin signaling pathway, the relationship between the genetic variants of Omentin-1 and T2D is not yet explored. The current study evaluates the association of Omentin-1 polymorphisms (rs2274907 A/T and rs1333062 G/T), its transcript and protein levels, and genotype-phenotype correlation with metabolic parameters and T2D susceptibility. METHODS: Plasma and Peripheral Blood Mononuclear Cells (PBMCs) were separated from venous blood taken from 250 controls and 250 T2D patients recruited from Gujarat, India. Genomic DNA was isolated from PBMCs and genotyping of Omentin-1 variants was performed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). RNA was isolated from Visceral Adipose Tissue (VAT) samples of 12 controls and 10 patients, and transcript levels of Omentin-1 were assessed by qPCR. Plasma Omentin-1 levels were estimated by ELISA. Fasting Blood Glucose, Body Mass Index (BMI) and plasma lipid profile were considered for the genotype-phenotype correlation analysis. RESULTS: Our study revealed no association of Omentin-1 genetic variants with T2D risk (p > 0.05). However, the AT genotype of Omentin-1 rs2274907 A/T polymorphism was associated with increased BMI (p = 0.0247). Plasma Omentin-1 levels were significantly decreased (p < 0.0001) however, increased VAT Omentin-1 transcript levels (p = 0.0127) were observed in T2D patients. CONCLUSION: Our findings suggest that decreased circulatory Omentin-1 levels could pose a risk towards T2D susceptibility.

Cardiovascular disease management in people with diabetes outside North America and Western Europe in 2006 and 2015.

AIM: Optimal treatment of cardiovascular disease is essential to decrease mortality among people with diabetes, but information is limited on how actual treatment relates to guidelines. We analysed changes in therapeutic approaches to anti-hypertensive and lipid-lowering medications in people with Type 2 diabetes from 2006 and 2015. METHODS: Summary data from clinical services in seven countries outside North America and Western Europe were collected for 39 684 people. Each site summarized individual-level data from outpatient medical records for 2006 and 2015. Data included: demographic information, blood pressure (BP), total cholesterol levels and percentage of people taking statins, anti-hypertensive medication (angiotensin-converting enzyme inhibitors, calcium channel blockers, angiotensin II receptor blockers, thiazide diuretics) and antiplatelet drugs. RESULTS: From 2006 to 2015, mean cholesterol levels decreased in six of eight sites (range: -0.5 to -0.2), whereas the proportion with BP levels > 140/90 mmHg increased in seven of eight sites. Decreases in cholesterol paralleled increases in statin use (range: 3.1 to 47.0 percentage points). Overall, utilization of anti-hypertensive medication did not change. However, there was an increase in the use of angiotensin II receptor blockers and a decrease in angiotensin-converting enzyme inhibitors. The percentage of individuals receiving calcium channel blockers and aspirin remained unchanged. CONCLUSIONS: Our findings indicate that control of cholesterol levels improved and coincided with increased use of statins. The percentage of people with BP > 140/90 mmHg was higher in 2015 than in 2006. Hypertension treatment shifted from using angiotensin-converting enzyme inhibitors to angiotensin II receptor blockers. Despite the potentially greater tolerability of angiotensin II receptor blockers, there was no associated improvement in BP levels.

Revascularization in Immature and Mature Teeth with Necrotic Pulp: A Clinical Study.

AIM: The aim of this in vivo study was to evaluate the revascularization procedure both in immature and mature teeth with necrotic pulp and open apices, disinfected with triple antibiotic paste followed by inducing blood clot in the root canal. MATERIALS AND METHODS: Fifteen patients were selected who presented with immature and mature permanent teeth with pulpal necrosis and open apices. In the first visit, the root canal was accessed with LA and rubber dam isolation; then the canal was disinfected using triple antibiotic paste containing ciprofloxacin, metronidazole, and clindamycin in the ratio of 1:1:1 and closed with IRM. In the second visit, after administering local anesthesia and isolating with a rubber dam, the triple antibiotic paste was washed out by saline irrigation, and apical papilla beyond the confines of the root canal was stimulated with sterile H file to produce a blood clot. Finally, the access was closed using a double seal with mineral trioxide aggregate (MTA) placed apical to cementoenamel junction and resin bonded cement over the MTA. Radiographic examination and pulp sensibility test was done during the follow-up period of 2,4,6,8 and 10 months. RESULT: After 10 months follow-up, 10 out of 13 patients showed root development and apical closure. The eight patients out of 13 showed root development, apical closure and lateral thickening of radicular dentin and 2 out of 13 patients showed a positive response to electric sensibility test. CONCLUSION: Within the limitation of this study, it can be concluded that there is evidence of root development, increase in lateral wall thickness, apical closure and positive response to pulp sensibility test in both mature and immature teeth with necrotic pulp. CLINICAL SIGNIFICANCE: The conventional approach for management of teeth with necrotic pulp and the open apex is altered with the possibility of tissue regeneration within the pulp space and continued root development through revascularization procedures. It also re-establishes the vitality in a previously nonvital and necrosed tooth.

Impact of lifestyle intervention in primary prevention of Type 2 diabetes did not differ by baseline age and BMI among Asian-Indian people with impaired glucose tolerance.

AIM: To investigate whether the effectiveness of lifestyle interventions on the incidence of diabetes was influenced by the baseline age and BMI of the Asian-Indian participants with prediabetes. METHODS: Pooled data, obtained from two of our Indian Diabetes Prevention Programmes (2006, n=236 and 2013, n=473; total N=709) which had similar baseline characteristics and intervention principles, were analysed. For the present secondary analysis we dichotomously categorized the participants' baseline age (<45 and ≥45 years) and BMI (<25.0 and ≥ 25.0 kg/m2 ). Glycaemic status was ascertained at 6-monthly intervals by oral glucose tolerance tests. The incidence rates of diabetes and relative risk reduction in both the intervention and the control group were calculated for categories of baseline age and BMI. Interactions between the intervention and baseline age and BMI on diabetes risk were also analysed. RESULTS: Incident diabetes was diagnosed in 227 of the total 709 participants (32.0%) [control group 139 participants (38.8%) vs intervention group 88 participants (24.2%)] during the median follow-up period of 2 years. The overall relative risk reduction was 35.4% (95% CI 19.3-48.3). Lifestyle intervention was equally effective in both age groups [relative risk reduction in those aged <45 years: 43.7% (95% CI 19.8-60.5) and in those aged ≥ 45 years: 28.9% (95% CI 5.3-46.6) P for interaction = 0.52] and in categories of BMI [BMI <25 kg/m2 : 36.1% (95% CI 9.5-54.9); and BMI ≥ 25 kg/m2 : 34.8% (95% CI 12.9-51.2); P for interaction = 0.95]. CONCLUSIONS: In Asian-Indian individuals with prediabetes, the effectiveness of lifestyle intervention was not modified by baseline age and BMI.

Rates and predictors of hypoglycaemia in 27 585 people from 24 countries with insulin-treated type 1 and type 2 diabetes: the global HAT study.

AIMS: To determine the global extent of hypoglycaemia experienced by patients with diabetes using insulin, as there is a lack of data on the prevalence of hypoglycaemia in developed and developing countries. METHODS: This non-interventional, multicentre, 6-month retrospective and 4-week prospective study using self-assessment questionnaire and patient diaries included 27 585 patients, aged ≥18 years, with type 1 diabetes (T1D; n = 8022) or type 2 diabetes (T2D; n = 19 563) treated with insulin for >12 months, at 2004 sites in 24 countries worldwide. The primary endpoint was the proportion of patients experiencing at least one hypoglycaemic event during the observational period. RESULTS: During the prospective period, 83.0% of patients with T1D and 46.5% of patients with T2D reported hypoglycaemia. Rates of any, nocturnal and severe hypoglycaemia were 73.3 [95% confidence interval (CI) 72.6-74.0], 11.3 (95% CI 11.0-11.6) and 4.9 (95% CI 4.7-5.1) events/patient-year for T1D and 19.3 (95% CI 19.1-19.6), 3.7 (95% CI 3.6-3.8) and 2.5 events/patient-year (95% CI 2.4-2.5) for T2D, respectively. The highest rates of any hypoglycaemia were observed in Latin America for T1D and Russia for T2D. Glycated haemoglobin level was not a significant predictor of hypoglycaemia. CONCLUSIONS: We report hypoglycaemia rates in a global population, including those in countries without previous data. Overall hypoglycaemia rates were high, with large variations between geographical regions. Further investigation into these differences may help to optimize therapy and reduce the risk of hypoglycaemia.

Identification of a hypoxia-regulated miRNA signature in bladder cancer and a role for miR-145 in hypoxia-dependent apoptosis.

BACKGROUND: Hypoxia leads to the stabilisation of the hypoxia-inducible factor (HIF) transcription factor that drives the expression of target genes including microRNAs (miRNAs). MicroRNAs are known to regulate many genes involved in tumourigenesis. The aim of this study was to identify hypoxia-regulated miRNAs (HRMs) in bladder cancer and investigate their functional significance. METHODS: Bladder cancer cell lines were exposed to normoxic and hypoxic conditions and interrogated for the expression of 384 miRNAs by qPCR. Functional studies were carried out using siRNA-mediated gene knockdown and chromatin immunoprecipitations. Apoptosis was quantified by annexin V staining and flow cytometry. RESULTS: The HRM signature for NMI bladder cancer lines includes miR-210, miR-193b, miR-145, miR-125-3p, miR-708 and miR-517a. The most hypoxia-upregulated miRNA was miR-145. The miR-145 was a direct target of HIF-1α and two hypoxia response elements were identified within the promoter region of the gene. Finally, the hypoxic upregulation of miR-145 contributed to increased apoptosis in RT4 cells. CONCLUSIONS: We have demonstrated the hypoxic regulation of a number of miRNAs in bladder cancer. We have shown that miR-145 is a novel, robust and direct HIF target gene that in turn leads to increased cell death in NMI bladder cancer cell lines.

Geographic differences in the associations between impaired glucose regulation and cardiovascular risk factors among young adults.

AIMS: To assess geographic differences in the association between BMI, blood pressure and lipid levels with impaired glucose regulation among young adults from various geographical regions. METHODS: This was a cross-sectional study including data from 6987 participants aged ≤ 30 years from India, Singapore, Australia, Greenland, Kenya and Tanzania. Impaired glucose regulation was determined by the 75-g oral glucose tolerance test. For each geographical region, BMI, blood pressure and lipids were examined and compared between participants with normal glucose tolerance and those with impaired glucose regulation. Multiple logistic regression models were used to assess the association between risk factors and impaired glucose regulation. RESULTS: Indian and East African people had a higher prevalence of impaired glucose regulation compared with participants from other regions, despite their lower BMI. Compared with the other regions, blood pressure was lower among Indian and Singaporean people but higher in those from Greenland. Greenlanders had the highest, while Indian and East-African people, had the lowest level of HDL cholesterol. BMI was positively associated with impaired glucose regulation in all regions, and there were no statistically significant geographic differences. In the Indian, Singaporean and Australian participants, there was a positive association between blood pressure and impaired glucose regulation. Triglycerides were positively associated with and HDL cholesterol had no association with impaired glucose regulation in all geographical regions. CONCLUSIONS: Higher BMI and triglyceride levels were positively associated with prevalent impaired glucose regulation in all geographical regions. There were geographic differences in the association between impaired glucose regulation and blood pressure and lipids, probably reflecting environmental and genetic factors.

Projected and Observed Aridity and Climate Change in the East Coast of South India under RCP 4.5.

In the purview of global warming, the present study attempts to project changes in climate and quantify the changes in aridity of two coastal districts in south India under the RCP 4.5 trajectory. Projected climate change output generated by RegCM 4.4 model, pertaining to 14 grid points located within the study area, was analyzed and processed for this purpose. The meteorological parameters temperature and precipitations were used to create De Martonne Aridity Index, to assess the spatial distribution of aridity. The original index values ranged from 13.7 to 16.4 mm/°C, characterizing this area as a semidry climate. The outcome from the changed scenario analysis under RCP 4.5 showed that, during the end of the 21st century, the aridity may be increased more as the index values tend to reduce. The increasing trend in the drying phenomenon may be attributed to the rising of mean annual temperatures.

Flavonoid rich extract of Murraya Koenigii alleviates in-vitro LDL oxidation and oxidized LDL induced apoptosis in raw 264.7 Murine macrophage cells.

Several lines of evidences have established a lineage between Oxidised LDL (Ox-LDL) to apoptosis of macrophages in which the high level of intracellular cholesterol play a crucial role. This study assesses the potency of Murraya koenigii (MK) leaf extract in alleviating LDL oxidation and Ox-LDL induced lipotoxicity in murine macrophage (RAW 264.7) cells. Results indicated that presence of MK extract prevented oxidation of LDL as evidenced by its oxidation kinetics and formation of LDL oxidation products. Also, MK extract accounted for improvement in cell viability and mitochondrial membrane potential of Ox-LDL treated cells. The Ox-LDL induced increment in intracellular oxidative stress, nuclear condensation and apoptosis was effectively prevented by MK extract possibly due to their established anti-oxidant and free radical scavenging potentials which may be attributed to the presence of flavonoids present in the extract. Prevention of oxidative modification of LDL, free radical induced damage and Ox-LDL induced death of RAW 264.7 cells provide preliminary evidences of its anti-atherosclerotic potential and warrants further elucidation and validation for its use in-vivo and may be useful as a functional food supplement and an alternative medicine to prevent LDL oxidation and oxidized LDL induced toxicity.

Hypertriglyceridaemic waist phenotype as a simple predictive marker of incident diabetes in Asian-Indian men with prediabetes.

AIM: To determine prospectively the association of baseline hypertriglyceridaemic waist phenotype with incident diabetes in Asian-Indian men with impaired glucose tolerance. METHODS: In a randomized 2-year diabetes prevention trial in 517 men with impaired glucose tolerance, 123 (23.8%) developed diabetes. Baseline anthropometric, metabolic and clinical variables were estimated. Associations of hypertriglyceridaemic waist phenotype (waist circumference ≥ 90cm and a serum triglyceride level of ≥ 1.7 mmol/l) with insulin resistance and incident diabetes were assessed using multiple linear regression and Cox's proportional hazard models, respectively. RESULTS: Men with an isolated enlarged waistline and hypertriglyceridaemic waist phenotype had significantly higher BMI and percentage of total body fat compared with the group with normal waistline and triglyceride levels and the group with isolated hypertriglyceridaemia. The men with hypertriglyceridaemic waist phenotype had higher insulin resistance (mean ± sd homeostasis model assessment of insulin resistance value: 3.6 ± 1.5) compared with those in the isolated enlarged waistline, the isolated hypertriglyceridaemia or the normal waistline and triglyceride level groups (3.1 ± 1.4, 2.7 ± 1.0 and 2.5 ± 1.1, respectively, all P < 0.05 compared with hypertriglyceridaemic waist phenotype). Multiple linear regression analyses showed that hypertriglyceridaemic waist phenotype was significantly associated with insulin resistance after adjusting for age, BMI, family history, percentage of total body fat, smoking, alcohol intake, 2-h plasma glucose and HDL cholesterol level. Hypertriglyceridaemic waist phenotype was independently associated with incident diabetes after adjusting for the above confounders and gamma-glutamyl transferase (hazard ratio 1.49, 95% CI 1.01-2.21; P = 0.047). The association of hypertriglyceridaemic waist phenotype with incident diabetes was abolished when insulin resistance was introduced into the model (hazard ratio 1.39, 95% CI 0.092-2.10; P=0.12). CONCLUSIONS: Hypertriglyceridaemic waist phenotype is a simple clinical proxy measurement for insulin resistance and is strongly associated with incident diabetes in Asian-Indian men with impaired glucose tolerance.

Understanding the safety of the new ultra long acting basal insulin.

Hypoglycaemia is a key safety concern in diabetes management. It is potentially dangerous and the fear of hypoglycaemia may lead to sub-optimal dosing and inadequate glycaemic control. On the other hand, hypoglycaemia may generate adverse effects and disease complications, will compromise the quality of life and will substantially increase the economic burden of treatment budged. Today, treat to target clinical trial designs are mandate for clinical development of any newer anti-diabetic medication. While similar glycaemic targets are expected to be achieved by test and comparator, the newer molecules are definitely expected to show advantage over standard comparator in terms of reduction in frequency and severity of hypoglycaemia. An ultra-long acting basal analogue insulin degludec (IDeg), has been recently approved for the treatment of type 2 and type 1 diabetes mellitus (T2DM and T1DM). The pooled patient-level data for self-reported hypoglycaemia from seven phase 3a trials with IDeg has shown significantly lower episodes of nocturnal confirmed and numerical low overall confirmed hypoglycaemia with IDeg, compared to Insulin glargine (IGlar), which was more pronounced during maintenance phase of treatment in all populations. The most plausible explanation being that, the flat peakless profile of IDeg with least glycaemic variability leads to less hypoglycaemia and adds to the safety profile of this ultra-long acting insulin. The real life practice will further validate the findings of clinical trials.

An appraisal of physico-chemical and microbiological characteristics of Nanmangalam Reserve Forest soil.

A detailed evaluation was performed on the soils of Nanmangalam Reserve Forest (NRF) in order to understand its physico-chemical, microbiological and enzymatic characteristics. The results of analysis showed that soil pH was directly proportional to the soil depth and the soil moisture content was irreversibly related to varying soil depth. Soil organic carbon was positively correlated with (p < 0.01) with total nitrogen, total bacterial count, cellulytic microbes, nitrogen-fixing bacteria, microbial biomass carbon, dehydrogenase activity and soil respiration. During summer, microbial population in the organic layer was more diverse than in the deepest layer. Analysis showed that NRF had low organic carbon content (less than 1%), microbial biomass, nutrient and functional microbes. The overall results of the analysis reinstate that Nanmangalam forest soil is undergoing degradation.

Hypoxia regulates FGFR3 expression via HIF-1α and miR-100 and contributes to cell survival in non-muscle invasive bladder cancer.

BACKGROUND: Non-muscle invasive (NMI) bladder cancer is characterised by increased expression and activating mutations of FGFR3. We have previously investigated the role of microRNAs in bladder cancer and have shown that FGFR3 is a target of miR-100. In this study, we investigated the effects of hypoxia on miR-100 and FGFR3 expression, and the link between miR-100 and FGFR3 in hypoxia. METHODS: Bladder cancer cell lines were exposed to normoxic or hypoxic conditions and examined for the expression of FGFR3 by quantitative PCR (qPCR) and western blotting, and miR-100 by qPCR. The effect of FGFR3 and miR-100 on cell viability in two-dimensional (2-D) and three-dimensional (3-D) was examined by transfecting siRNA or mimic-100, respectively. RESULTS: In NMI bladder cancer cell lines, FGFR3 expression was induced by hypoxia in a transcriptional and HIF-1α-dependent manner. Increased FGFR3 was also in part dependent on miR-100 levels, which decreased in hypoxia. Knockdown of FGFR3 led to a decrease in phosphorylation of the downstream kinases mitogen-activated protein kinase (MAPK) and protein kinase B (PKB), which was more pronounced under hypoxic conditions. Furthermore, transfection of mimic-100 also decreased phosphorylation of MAPK and PKB. Finally, knocking down FGFR3 profoundly decreased 2-D and 3-D cell growth, whereas introduction of mimic-100 decreased 3-D growth of cells. CONCLUSION: Hypoxia, in part via suppression of miR-100, induces FGFR3 expression in bladder cancer, both of which have an important role in maintaining cell viability under conditions of stress.

Vitiligo: interplay between oxidative stress and immune system.

Vitiligo is a multifactorial polygenic disorder with a complex pathogenesis, linked with both genetic and non-genetic factors. The precise modus operandi for vitiligo pathogenesis has remained elusive. Theories regarding loss of melanocytes are based on autoimmune, cytotoxic, oxidant-antioxidant and neural mechanisms. Reactive oxygen species (ROS) in excess have been documented in active vitiligo skin. Numerous proteins in addition to tyrosinase are affected. It is possible that oxidative stress is one among the main principal causes of vitiligo. However, there also exists ample evidence for altered immunological processes in vitiligo, particularly in chronic and progressive conditions. Both innate and adaptive arms of the immune system appear to be involved as a primary event or as a secondary promotive consequence. There is speculation on the interplay, if any, between ROS and the immune system in the pathogenesis of vitiligo. The article focuses on the scientific evidences linking oxidative stress and immune system to vitiligo pathogenesis giving credence to a convergent terminal pathway of oxidative stress-autoimmunity-mediated melanocyte loss.