CHOP‐mediated hepcidin suppression modulates hepatic iron load

The liver is the central regulator of iron metabolism and accordingly, chronic liver diseases often lead to systemic iron overload due to diminished expression of the iron‐regulatory hormone hepcidin. To study the largely unknown regulation of iron metabolism in the context of hepatic disease, we used two established models of chronic liver injury, ie repeated carbon tetrachloride (CCl₄) or thioacetamide (TAA) injections. To determine the impact of CCAAT/enhancer‐binding protein (C/EBP)‐homologous protein (CHOP) on hepcidin production, the effect of a single TAA injection was determined in wild‐type and CHOP knockout mice. Furthermore, CHOP and hepcidin expression was assessed in control subjects and patients with alcoholic liver disease. Both chronic injury models developed a distinct iron overload in macrophages. TAA‐, but not CCl₄‐ injected mice displayed additional iron accumulation in hepatocytes, resulting in a significant hepatic and systemic iron overload which was due to suppressed hepcidin levels. C/EBPα signalling, a known hepcidin inducer, was markedly inhibited in TAA mice, due to lower C/EBPα levels and overexpression of CHOP, a C/EBPα inhibitor. A single TAA injection resulted in a long‐lasting (> 6 days) suppression of hepcidin levels and CHOP knockouts (compared to wild‐types) displayed significantly attenuated hepcidin down‐regulation in response to acute TAA administration. CHOP mRNA levels increased 5‐fold in alcoholic liver disease patients versus controls (p < 0.005) and negatively correlated with hepcidin expression. Our results establish CHOP as an important regulator of hepatic hepcidin expression in chronic liver disease. The differences in iron metabolism between the two widely used fibrosis models likely reflect the differential regulation of hepcidin expression in human liver disease. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Fecal Bacteriotherapy for Clostridium difficile Infections — Its Time Has Come

Clostridium difficile treatment failures and recurrences occur at rates of 22.3% and 22.1%, respectively. For patients who have refractory/recurrent disease, there are limited treatment options. The use of a fecal suspension from a healthy donor instilled via a nasogastric tube, during colonoscopy, or by enema in a patient with recurrent or refractory C. difficile infection has shown a response rate of 75 to 100% with minimal adverse effects. There are multiple published case series that provide variations in administration procedures. The main barrier is the need for institutions and clinics to develop protocols to ensure this treatment modality is available to patients with this debilitating and potentially fatal disease.     

Exposure to domestic violence and the risk of developing depression within 6 months postpartum in Bangladesh

Purpose

Domestic violence (DV) by husbands or in-laws is a recognized problem in many countries and is associated with a wide range of adverse mental health outcomes. However, detailed knowledge on the relationship between DV experience and postpartum depression (PPD) is essential to design appropriate interventions. Therefore, this study assesses the relationship between maternal experience of DV perpetrated by husbands or in-laws and PPD in Bangladesh.

Methods

A cross-sectional survey was conducted from October to December 2019 among 497 mothers within the first 6 months postpartum who attended a health center in Rajshahi City Corporation, Bangladesh. Multivariable logistic regressions were performed to identify the associations after controlling for potential confounders.

Results

The prevalence of PPD in this sample was 34% within the first 6 months after birth; 58.6% of mothers reported having experienced any form of DV in their lifetime. Maternal experience of any form of DV (Adjusted Odds Ratio [AOR] = 1.87; 95% confidence interval [CI] = 1.19–2.93) was associated with PPD, as were experiences of any physical DV (AOR = 2.25; 95% CI = 1.40–3.59), emotional DV (AOR = 2.07; 95% CI = 1.34–3.19), and controlling behavior (AOR = 1.69; 95% CI = 1.08–2.66). Additionally, the likelihood of PPD significantly increased among women who experienced more forms of DV.

Conclusion

DV perpetrated by husband and/or in-laws is highly prevalent and significantly associated with PPD in Bangladesh. Strategies in developing interventions for improving maternal mental health should consider DV perpetrated by either husband or in-laws.

     

The Misuse of Prescribed Drugs During the Syrian Crisis: a Cross-sectional Study

International Journal of Mental Health and Addiction -     

Sleep and neighborhood socioeconomic status: a micro longitudinal study of chronic low-back pain and pain-free individuals

Journal of Behavioral Medicine - Individuals with chronic low back pain (cLBP) frequently report sleep disturbances. Living in a neighborhood characterized by low-socioeconomic status (SES) is...     

Extended-Spectrum β-Lactamases (ESBLs): Characterization,Epidemiology and Detection

β-lactamases of Enterobacteriaceae are the most important mechanism of resistance against β-lactam drugs. Two types of β-lactamases can confer resistance against 3rd generation cephalosporins. Chromosomally mediated β-lactamases are inducible and are not inhibited by clavulanic acid. Resistance due to these enzymes is non-transferable. The 2nd type of enzyme is plasmid-mediated β-lactamases, which are inhibited by clavulanic acid. These enzymes are more important clinically as these can be transferred between various species of Enterobacteria ceae. These enzymes are called extended-spectrum β-lactamases (ESBLs). ESBL-producing Enterobacteriaceae have been responsible for numerous outbreaks of infection throughout the world and pose challenging infection control issues. Antibacterial choice is often complicated by multi-resistance. ESBLs can confer resistance against all β-lactam drugs except carbapenems and cephamycins. Nursing home patients may be an important reservoir of ESBL-containing multiple antibiotic-resistant organisms. Use of broad-spectrum oral antibiotics and probably poor infection control practices may facilitate spread of this plasmid-mediated resistance. In addition to known populations at risk, ambulatory patients with chronic conditions represent another patient population that may harbor ESBL-producing organisms. Various methods can be used for detection of ESBLs in the laboratory. These tests include double disc diffusion test, Vitek ESBL test, E Tests, MIC Determination, genetic method, and isoelectric focusing (IEF).     

Unveiling the optical parameters of vanadium dioxide in the phase transition region: a hybrid modeling approach

The phase change behavior of vanadium dioxide (VO₂) has been widely explored in a variety of optical and photonic applications. Commonly, its optical parameters have been studied in two extreme regimes: hot (metallic) and cold (insulating) states. However, in the transition temperatures, VO₂ acts like an inherent metamaterial with mixed metallic-insulating character. In this range, the portions of metallic and insulating inclusions are tuned by temperature, and therefore a gradual change of optical parameters can be achieved. In this paper, a universal hybrid modeling approach is developed to model VO₂ in the intermediate region. For this aim, the measured reflectivity data, is analyzed and matched through the transfer matrix method (TMM) simulations where an effective medium theory (EMT) is employed. Based on the findings of this approach, not only the relative portions of inclusions are tailored but also their grain shapes are significantly altered in the transition range. Finally, the modeling approach is testified by experimental findings through dynamic device applications operating at short and mid infrared wavelengths. In addition, the hysteretic behaviors on electrical, optical, and structural parameters of the VO₂ film along the heating and cooling cycles are demonstrated by the experiments and scrutinized by the simulations.

A universal hybrid modeling approach is developed to model VO₂ in transition, revealing dynamic behavior of metallic inclusions and grain shapes.     

Characterization of fibrillar collagen isoforms in infarcted mouse hearts using second harmonic generation imaging

We utilized collagen specific second harmonic generation (SHG) signatures coupled with correlative immunofluorescence imaging techniques to characterize collagen structural isoforms (type I and type III) in a murine model of myocardial infarction (MI). Tissue samples were imaged over a four week period using SHG, transmitted light microscopy and immunofluorescence imaging using fluorescently-labeled collagen antibodies. The post-mortem cardiac tissue imaging using SHG demonstrated a progressive increase in collagen deposition in the left ventricle (LV) post-MI. We were able to monitor structural morphology and LV remodeling parameters in terms of extent of LV dilation, stiffness and fiber dimensions in the infarcted myocardium.