Recent studies indicated that intramammary administration of active vitamin D3 hormone (1,25D3) inhibits the inflammatory process associated with mastitis. We hypothesized that attenuation of endoplasmic reticulum (ER) stress by 1,25D3 in mammary epithelial cells (MECs) is an important cellular mechanism contributing to this beneficial effect of intramammary treatment with 1,25D3. To test this hypothesis, the effect of 1,25D3 was studied on induction of ER stress in a transformed human MEC line, MCF-7 cells. Treatment with two different ER stress inducers, thapsigargin (TG) and tunicamycin (TM), caused a dose-dependent induction of ER stress as evident from up-regulation of protein kinase RNA-like ER kinase (PERK), heat shock protein family A (Hsp70) member 5 (HSPA5), activating transcription factor (ATF4), ATF6, DNA damage inducible transcript 3 (DDIT3) and spliced X-box binding protein 1 (sXBP1) and impaired cell viability and decreased expression of vitamin D receptor (VDR) in MCF-7 cells (P less then 0.05). Treatment with 1,25D3 (100 nM) inhibited TG (10 nM)- and TM (1 μg/mL)-induced mRNA and/or protein levels of ATF4, ATF6, DDIT3 and HSPA5 in MCF-7 cells (P less then 0.05). In addition, 1,25D3 (100 nM) antagonized the effect of TG (10 nM) and TM (1 μg/mL) on mRNA and protein levels of VDR and mRNA levels of genes involved in production and degradation of 1,25D3 in MCF-7 cells (P less then 0.05).  https://www.selleckchem.com/products/17-AAG(Geldanamycin).html  Moreover, 1,25D3 (100 nM) inhibited nuclear factor-κB (NF-κB) activation in response to TM (10 nM) and TG (1 μg/mL) in MCF-7 cells. In conclusion, the present findings show that 1,25D3 is effective in attenuating ER stress and the NF-κB-driven inflammatory response in MCF-7 cells. This indicates that attenuation of ER stress by 1,25D3 in MECs may contribute to the recently observed inhibitory effect of intramammary treatment of dairy cows with 1,25D3 on the inflammatory process associated with mastitis.The manila clam Ruditapes philippinarum is widely distributed in the sandy mud sediments of tidal flats and plays a role in seawater purification by filtering suspended organic matter. This study was designed to evaluate differences in seawater purification based on the filtration rate of the manila clam in terms of particulate organic matter (POM) between two tidal flats with different hydrographic regimes. In situ experiments were carried out at Geunso and Sihwa tidal flats, along the west coast of Korea. The amount of POM removed from the water column by the feeding activity of the clam was measured in the field using a closed circulation chamber. The filtration rate of clams for POM at Sihwa tidal flat (2.86 for POC, 2.29 for PON and 5.46 L h-1 gDW-1 for Chl a) was higher than that at Geunso tidal flat (0.61 for POC, 0.89 for PON and 2.54 L h-1 gDW-1 for Chl a) which resulted from differences in the hydrographic regime, including tide characteristics, current speed and submergence time, and food quantity and quality. The current speed was much greater at Geunso tidal flat than at Sihwa tidal flat, but the submergence time by tide was longer at the latter site than the former, resulting in different feeding times for clams. The food quantity in terms of chlorophyll a was higher at Sihwa tidal flat than at Geunso tidal flat, and the food quality based on the C/N ratio of POM was better at the former site than the latter, with values of 12.8 and 15.6, respectively. These findings suggest that hydrographic regime could be important in understanding in situ filtration rates of R. philippinarum.INTRODUCTION Large chain restaurants reduced calories in their newly-introduced menu items from 2012 to 2015. The objective of this study was to provide updated calorie trends through 2018 and examine trends in the macronutrient composition of menu items across this time period. METHODS AND FINDINGS Data were obtained from the MenuStat project and include 66 of the 100 largest revenue generating U.S. chain restaurants (N = 28,238 items) that had data available in all years from 2012 to 2018. Generalized linear models were used to examine per-item calorie and nutrient changes (saturated fat, trans fat, unsaturated fat, sugar, non-sugar carbohydrates, protein, sodium) among (1) items on the menu in all years (common items) and (2) newly introduced items (2013-2018). Overall, there were no significant changes in calories or nutrients among common items from 2012 to 2018. Among all newly introduced items, calories (-120 kcals, -25%, p = 0.01; p-for-trend = 0.02), saturated fat (-3.4g, -41%, p less then 0.01, p-for-trend = 0.06), unsaturated fat (-4.5g, -37%, p = 0.02; p-for-trend = 0.04), non-sugar carbohydrates (-10.3g, -40%, p = 0.02, p-for-trend = 0.69), and protein (-4.3g, -25%, p = 0.04, p-for-trend = 0.02) declined. CONCLUSION Newly introduced menu items in large chain restaurants have continued to decline in calories through 2018, which may help to reduce calorie intake. Other changes in macronutrient content were sporadic and not clearly toward improved dietary quality.BACKGROUND Co-infection with Visceral Leishmaniasis (commonly known as Kala Azar, KA) and Human Immunodeficiency Virus (HIV) is increasingly being diagnosed among patients in Bihar. This qualitative study is the first assessment of self-reported quality of life among patients co-infected with KA-HIV in the Asian context. METHODS We conducted semi-structured, in-depth interviews and adopted an inductive thematic analysis to generate evidence on the quality of life of patients co-infected with KA and HIV. Patients were purposively sampled until saturation was attained. RESULTS We found that patients highly valued income or livelihood potential and health as indicators of a good quality life, and routinely went into debt accessing care in the private setup. This was due to perceptions of poor quality of care in the government setup and a lack of knowledge regarding available government services at the district level. KA symptoms were often misdiagnosed in the private sector as seasonal fever, while care providering process.INTRODUCTION Age-related hearing loss (ARHL) is a consequence of aging of the auditory system. The best known mechanism of cell death in ARHL is apoptosis due to increased production of reactive oxygen species. In this context, it is hypothesized that melatonin, owing to its high antioxidant potential and its action in the mitochondria, helps prevent or delay outer hair cell dysfunction (HCD). AIMS To evaluate the effect of melatonin on the prevention of HCD dysfunction in the ARHL process in a susceptible murine C57BL/6J model. METHOD C57BL/6J animals were divided into two groups control (CG) and melatonin (MG). The CG received a saline and ethanol solution and the MG, melatonin (10 mg/kg/day). The solutions were offered daily (50 μl) orally over a 10-month period. Distortion Product Otoacoustic Emissions (DPOAE) measurements were conducted once a month. RESULTS There was a decrease in DPOAE values in both groups over time and a differentiation between them from the 10th month of life onwards. At 10 months, the MG maintained higher DPOAE values than the CG at all frequencies tested.