Biochanin A impedes STAT3 activation by upregulating p38δ MAPK phosphorylation in IL-6-stimulated macrophages

Inflammation Research - IL-6-induced STAT3 activation is associated with various chronic inflammatory diseases. In this study, we investigated the anti-STAT3 mechanism of the dietary polyphenol,...     

Curcumin as a potential therapeutic candidate for Helicobacter pylori associated diseases

Curcumin, a yellow pigment and principal polyphenolic Curcuminoid obtained from the turmeric rhizome Curcuma longa, is commonly used as a food-coloring agent. Studies suggest that curcumin has a wide range of beneficial properties e.g., anti-inflammatory, anti-oxidant, anti-cancer, anti-proliferative, anti-fungal and anti-microbial. These pleiotropic activities prompted several research groups to elucidate the role of curcumin in Helicobacter pylori (H. pylori) infection. This is the first review with this heading where we discussed regarding the role of curcumin as an anti-H. pylori agent along with its potential in other gastrointestinal diseases. Based on several in vitro, early cell culture, animal research and few pre-clinical trials, curcumin projected as a potential therapeutic candidate against H. pylori mediated gastric pathogenesis. This review sheds light on the anti-H. pylori effects of curcumin in different models with meticulous emphasis on its anti-oxidant, anti-inflammatory and anti-carcinogenic effects as well as some critical signaling and effecter molecules. Remarkably, non-toxic molecule curcumin fulfills the characteristics for an ideal chemopreventive agent against H. pylori mediated gastric carcinogenesis but the foremost challenge is to obtain the optimum therapeutic levels of curcumin, due to its low solubility and poor bioavailability. Further, we have discussed about the possibilities for improving its efficacy and bioavailability. Lastly, we concluded with the anticipation that in near future curcumin may be used to develop a therapeutic drug against H. pylori mediated gastric ailments through improved formulation or delivery systems, facilitating its enhanced absorption and cellular uptake.     

First Hour Initiation of Breastfeeding and Exclusive Breastfeeding at Six Weeks: Prevalence and Predictors in a Tertiary Care Setting

Objective

To assess the prevalence of first hour breastfeeding initiation and exclusive breastfeeding at 6 wk and identify its barriers in healthy term babies born in a tertiary hospital setting.

Methods

A prospective observational cohort study was carried out in consecutively selected 400 mothers who delivered (normal, instrumental or cesarean) term healthy babies in a tertiary care hospital setting. All mother-infant dyads were enroled within 48 h of delivery.

Results

Breastfeeding was initiated within first hour in 255 out of 400, i.e., 64 % of babies. Cesarean delivery and male gender were strongest risk factors for delayed initiation of breastfeeding [OR (95 % CI)?=?1.99 (1.14–3.48) and 34.17 (17.10–70.40) respectively]. Among the babies followed up till 6–8 wk, 83 % were exclusively breastfed. Breast milk substitutes were given in 172/400 (43 %) babies on day one, which emerged as an independent predictor of failure to continue exclusive breastfeeding at 6 wk (OR 2.96; 95 % CI 1.09–8.06). Odds of exclusive breastfeeding were two times higher in babies breastfed within first hour (n?=?255/400, 64 %) when compared to babies initiated breastfeeds beyond first hour (n?=?145/400, 36 %) (OR 2.01;05 % CI 1.12–3.61).

Conclusions

Cesarean section and male gender emerged as significant risk factors for delayed initiation (beyond first hour) of breastfeeding in the index study cohort. In addition, use of breast milk substitute emerged as the only predictor for failure to continue exclusive breastfeeding at six weeks in a tertiary care hospital.     

Dsteosynthesis with long volar locking plates for meta- physeal-diaphyseal fractures of the distal radius

Objective：Metaphyseal-diaphyseal fractures of the distal radius are a major treatment dilemma and orthopaedic surgeons have to pay due consideration to restoration of anatomy of distal radius together with rotation of the radial shaft and maintenance of radial bow and interosseous space.We performed this study to evaluate the clinic-radiological outcome of metaphyseal-diaphyseal fractures of the distal radius treated with long volar locking plates.Methods：This prospective study involved 27 patients （22 males and 5 females） with metaphyseal-diaphyseal fracture of the distal radius.Their mean age was （30.12±11.48） years （range 19-52 years） and the follow-up was 26.8 months （range 22-34 months）.All patients underwent open reduction and internal fixation with a long volar locking plate.According to AO/OTA classification,there were 7 type A3,13 type C2 and 7 type C3 fractures.Subjective assessment was done based on the disabilities of the arm,shoulder and hand （DASH） questionnaire.Functional evaluation was done by measuring grip strength and range of motion around the wrist and the radiological determinants included radial angle,radial length,volar angle and ulnar variance.The final assessment was done according to Gartland and Werley scoring system.Results：Postoperative radiological parameters were well maintained throughout the trial,and there was significant improvement in the functional parameters from 6 weeks to final follow-up.The average DASH scores improved from 37.5 at 6 weeks to 4.2 at final follow-up.Final assessment using Gartland and Werley scoring system revealed 66.67%（n=l8） excellent and 33.33% （n=9） good results.There was one case of superficial infection which responded to antibiotics and another carpel tunnel syndrome which was managed conservatively.Conclusion：Volar locking plate fixation for metaphyseal-diaphyseal fractures of distal radius is associated with excellent to good functional outcome,early rehabilitation and minimal complications.     

Design and Development of a Medical Image Databank for Assisting Studies in Radiomics

Journal of Digital Imaging - CompreHensive Digital ArchiVe of Cancer Imaging - Radiation Oncology (CHAVI-RO) is a multi-tier WEB-based medical image databank. It supports archiving de-identified...     

Stroke and the “Stroke Belt” in Dialysis: Contribution of Patient Characteristics to Ischemic Stroke Rate and Its Geographic Variation

Geographic variation in stroke rates is well established in the general population, with higher rates in the South than in other areas of the United States. ESRD is a potent risk factor for stroke, but whether regional variations in stroke risk exist among dialysis patients is unknown. Medicare claims from 2000 to 2005 were used to ascertain ischemic stroke events in a large cohort of 265,685 incident dialysis patients. A Poisson generalized linear mixed model was generated to determine factors associated with stroke and to ascertain state-by-state geographic variability in stroke rates by generating observed-to-expected (O/E) adjusted rate ratios for stroke. Older age, female sex, African American race and Hispanic ethnicity, unemployed status, diabetes, hypertension, history of stroke, and permanent atrial fibrillation were positively associated with ischemic stroke, whereas body mass index >30 kg/m² was inversely associated with stroke (P<0.001 for each). After full multivariable adjustment, the three states with O/E rate ratios >1.0 were all in the South: North Carolina, Mississippi, and Oklahoma. Regional efforts to increase primary prevention in the “stroke belt” or to better educate dialysis patients on the signs of stroke so that they may promptly seek care may improve stroke care and outcomes in dialysis patients.Stroke is a catastrophic health event and a leading cause of disability. It represents a particularly heavy burden for the long-term dialysis population, in whom stroke rates are substantially higher than in the general population.¹ In the general population, there is substantial geographic variability in stroke rates, with the southeastern United States having long been recognized as a “stroke belt” of higher stroke mortality rates.^2–4 However, whether a stroke belt of increased ischemic stroke incidence exists in dialysis patients has not been formally studied.Although one might suspect that the same factors contributing to ischemic stroke risk in the general population also apply to dialysis patients, there are several reasons to posit that this might not be the case. First, unlike the general population, dialysis patients across the United States have consistent access to insurance and frequent contact with health care providers, who routinely measure their BP, irrespective of geographic location. Second, the nature of vascular disease differs between dialysis and nondialysis patients, so different pathophysiologic mechanisms may be operative in the two populations.⁵ Third, dialysis patients fundamentally represent a “survivor cohort” relative to individuals with (predialysis) CKD and its attendant cardiovascular disorders, suggesting that epidemiologic trends evident in one population might not be found in the other.⁶ Accordingly, it is uncertain whether there is substantial geographic variation in stroke risk among dialysis patients and what factors might, in part, explain such a finding.To address this gap in knowledge, we constructed a large cohort of incident dialysis patients to determine whether ischemic stroke rates vary by geography and how differences in stroke rates might be explained by patient characteristics. We reasoned that uncovering the existence of geographic variability in the stroke rates of dialysis patients might provide direction for focused health care efforts in regions at elevated risk, such as screening new dialysis patients for symptoms that might be referable to old strokes, lowering the threshold for investigating cerebrovascular disease, or educating dialysis patients on the importance of seeking immediate care for stroke-type symptoms.     

Unexpected link between iron and drug resistance of Candida spp.: iron depletion enhances membrane fluidity and drug diffusion, leading to drug-susceptible cells

Inthis study, we show that iron depletion in Candida albicans with bathophenanthrolene disulfonic acid and ferrozine as chelators enhanced its sensitivity to several drugs, including the most common antifungal, fluconazole (FLC). Several other species of Candida also displayed increased sensitivity to FLC because of iron restriction. Iron uptake mutations, namely, Deltaftr1 and Deltaftr2, as well as the copper transporter mutation Deltaccc2, which affects high-affinity iron uptake in Candida, produced increased sensitivity to FLC compared to that of the wild type. The effect of iron depletion on drug sensitivity appeared to be independent of the efflux pump proteins Cdr1p and Cdr2p. We found that iron deprivation led to lowering of membrane ergosterol by 15 to 30%. Subsequently, fluorescence polarization measurements also revealed that iron-restricted Candida cells displayed a 29 to 40% increase in membrane fluidity, resulting in enhanced passive diffusion of the drugs. Northern blot assays revealed that the ERG11 gene was considerably down regulated in iron-deprived cells, which might account for the lowered ergosterol content. Our results show a close relationship between cellular iron and drug susceptibilities of C. albicans. Considering that multidrug resistance is a manifestation of multifactorial phenomena, the influence of cellular iron on the drug susceptibilities of Candida suggests iron as yet another novel determinant of multidrug resistance.