Paternal Psychosocial Characteristics and Corporal Punishment of their 3-Year Old Children

This study uses data from 2,309 biological fathers who participated in the Fragile Families and Child Wellbeing Study (FFCWS) to examine associations between psychosocial characteristics and levels of corporal punishment (CP) toward their 3-year old children over the past month. Results indicate that 61% of the fathers reported no CP over the past month, 23% reported using CP once or twice, and 16% reported using CP a few times in the past month or more. In multivariate models controlling for important socio-demographic factors as well as characteristics of the child, fathers’ parenting stress, major depression, alcohol use, and drug use were significantly associated with greater use of CP, whereas involvement with the child and generalized anxiety order were not. Girls were less likely to be the recipient of CP than boys, and child externalizing behavior problems but not internalizing behavior problems were associated with more CP.Fragile families, childbearing, nonmarital childbearing, fartherhood, fathers, corporal punishment, behavior problems, stress, depression

Restoring Lost Anti-HER-2 Th1 Immunity in Breast Cancer: A Crucial Role for Th1 Cytokines in Therapy and Prevention

The ErbB/B2 (HER-2/neu) oncogene family plays a critical role in the development and metastatic spread of several tumor types including breast, ovarian and gastric cancer. In breast cancer, HER-2/neu is expressed in early disease development in a large percentage of DCIS lesions and its expression is associated with an increased risk of invasion and recurrence. Targeting HER-2 with antibodies such as trastuzumab or pertuzumab has improved survival, but patients with more extensive disease may develop resistance to therapy. Interestingly, response to HER-2 targeted therapies correlates with presence of immune response genes in the breast. Th1 cell production of the cytokines interferon gamma (IFNγ) and TNFα can enhance MHC class I expression, PD-L1 expression, augment apoptosis and tumor senescence, and enhances growth inhibition of many anti-breast cancer agents, including anti-estrogens and HER-2 targeted therapies. Recently, we have identified that a loss of anti-HER-2 CD4 Th1 in peripheral blood occurs during breast tumorigenesis and is dramatically diminished, even in Stage I breast cancers. The loss of anti-HER-2 Th1 response is specific and not readily reversed by standard therapies. In fact, this loss of anti-HER-2 Th1 response in peripheral blood correlates with lack of complete response to neoadjuvant therapy and diminished disease-free survival. This defect can be restored with HER-2 vaccinations in both DCIS and IBC. Correcting the anti-HER-2 Th1 response may have significant impact in improving response to HER-2 targeted therapies. Development of immune monitoring systems for anti-HER-2 Th1 to identify patients at risk for recurrence could be critical to improving outcomes, since the anti-HER-2 Th1 response can be restored by vaccination. Correction of the cellular immune response against HER-2 may prevent recurrence in high-risk patients with DCIS and IBC at risk of developing new or recurrent breast cancer.Fil: Nocera, Nadia F.. University of Pennsylvania; Estados UnidosFil: Lee, M. Catherine. H. Lee Moffitt Cancer Center; Estados UnidosFil: De La Cruz, Lucy M.. University of Pennsylvania; Estados UnidosFil: Rosemblit, Cinthia. University of Pennsylvania; Estados UnidosFil: Czerniecki, Brian J.. H. Lee Moffitt Cancer Center; Estados Unido

Glutathione is required for growth and cadmium tolerance in the amphibian chytrid fungus, Batrachochytrium dendrobatidis

Batrachochytrium dendrobatidis (Bd) is a lethal amphibian pathogen, partly due to its ability to evade the immune system of susceptible frog species. In many pathogenic fungi, the antioxidant glutathione is a virulence factor that helps neutralize oxidative stressors generated from host immune cells, as well as other environmental stressors such as heavy metals. The role of glutathione in stress tolerance in Bd has not been investigated. Here, we examine the changes in the glutathione pool after stress exposure and quantify the effect of glutathione depletion on cell growth and stress tolerance. Depletion of glutathione repressed growth and release of zoospores, indicating that glutathione is essential for life cycle completion in Bd. Supplementation with 2 mM were strongly inhibitory to Bd cells. While hydrogen peroxide exposure lowered the total cellular glutathione levels by 42 %, glutathione depletion did not increase the sensitivity to hydrogen peroxide. Exposure to cadmium increased total cellular glutathione levels by 93 %. Glutathione-depleted cells were more sensitive to cadmium, and this effect was attenuated by glutathione supplementation, suggesting that glutathione plays an important role in cadmium tolerance. The effects of heat and salt were exacerbated by the addition of exogenous glutathione. The impact of glutathione levels on Bd stress sensitivity may help explain differences in host susceptibility to chytridiomycosis and may provide opportunities for synergistic therapeutic

Antibiotic Treatment Expands the Resistance Reservoir and Ecological Network of the Phage Metagenome

The mammalian gut ecosystem has significant influence on host physiology1–4, but the mechanisms that sustain this complex environment in the face of different stresses remain obscure. Perturbations to this ecosystem, such as through antibiotic treatment or diet, are currently interpreted at the level of bacterial phylogeny5–7. Less is known about the contributions of the abundant population of phage to this ecological network. Here, we explore the phageome as a potential genetic reservoir for bacterial adaptation by sequencing murine fecal phage populations following antibiotic perturbation. We show that antibiotic treatment leads to the enrichment of phage-encoded genes that confer resistance via disparate mechanisms to the administered drug as well as genes that confer resistance to antibiotics unrelated to the administered drug, and we demonstrate experimentally that phage from treated mice afford aerobically cultured naïve microbiota increased resistance. Systems-wide analyses uncover post-treatment phage-encoded processes related to host colonization and growth adaptation, indicating that the phageome broadly enriches for functionally beneficial genes under stress-related conditions. We also show that antibiotic treatment expands the interactions between phage and bacterial species, leading to a more highly connected phage-bacterial network for gene exchange. Our work implicates the phageome in the emergence of multidrug resistance and indicates that the adaptive capacity of the phageome may represent a community-based mechanism for protecting the gut microflora, preserving its functional robustness during antibiotic stress

In the Information Age, Do Dementia Caregivers Get the Information They Need? Semi-Structured Interviews to Determine Informal Caregivers’ Education Needs, Barriers, and Preferences

Most patients with dementia or cognitive impairment receive care from family members, often untrained for this challenging role. Caregivers may not access publicly available caregiving information, and caregiver education programs are not widely implemented clinically. Prior large surveys yielded broad quantitative understanding of caregiver information needs, but do not illuminate the in-depth, rich, and nuanced caregiver perspectives that can be gleaned using qualitative methodology. We aimed to understand perspectives about information sources, barriers and preferences, through semi-structured interviews with 27 caregivers. Content analysis identified important theme

Reciprocal knock-in mice to investigate the functional redundancy of lamin B1 and lamin B2.

Lamins B1 and B2 (B-type lamins) have very similar sequences and are expressed ubiquitously. In addition, both Lmnb1- and Lmnb2-deficient mice die soon after birth with neuronal layering abnormalities in the cerebral cortex, a consequence of defective neuronal migration. The similarities in amino acid sequences, expression patterns, and knockout phenotypes raise the question of whether the two proteins have redundant functions. To investigate this topic, we generated "reciprocal knock-in mice"-mice that make lamin B2 from the Lmnb1 locus (Lmnb1(B2/B2)) and mice that make lamin B1 from the Lmnb2 locus (Lmnb2(B1/B1)). Lmnb1(B2/B2) mice produced increased amounts of lamin B2 but no lamin B1; they died soon after birth with neuronal layering abnormalities in the cerebral cortex. However, the defects in Lmnb1(B2/B2) mice were less severe than those in Lmnb1-knockout mice, indicating that increased amounts of lamin B2 partially ameliorate the abnormalities associated with lamin B1 deficiency. Similarly, increased amounts of lamin B1 in Lmnb2(B1/B1) mice did not prevent the neurodevelopmental defects elicited by lamin B2 deficiency. We conclude that lamins B1 and B2 have unique roles in the developing brain and that increased production of one B-type lamin does not fully complement loss of the other

Essential trauma management training: addressing service delivery needs in active conflict zones in eastern Myanmar

<p>Abstract</p> <p>Introduction</p> <p>Access to governmental and international nongovernmental sources of health care within eastern Myanmar's conflict regions is virtually nonexistent. Historically, under these circumstances effective care for the victims of trauma, particularly landmine injuries, has been severely deficient. Recognizing this, community-based organizations (CBOs) providing health care in these regions sought to scale up the capacity of indigenous health workers to provide trauma care.</p> <p>Case description</p> <p>The Trauma Management Program (TMP) was developed by CBOs in cooperation with a United States-based health care NGO. The goal of the TMP is to improve the capacity of local health workers to deliver effective trauma care. From 2000 to the present, international and local health care educators have conducted regular workshops to train indigenous health workers in the management of landmine injuries, penetrating and blunt trauma, shock, wound and infection care, and orthopedics. Health workers have been regularly resupplied with the surgical instruments, supplies and medications needed to provide the care learnt through TMP training workshops.</p> <p>Discussion and Evaluation</p> <p>Since 2000, approximately 300 health workers have received training through the TMP, as part of a CBO-run health system providing care for approximately 250 000 internally displaced persons (IDPs) and war-affected residents. Based on interviews with health workers, trauma registry inputs and photo/video documentation, protocols and procedures taught during training workshops have been implemented effectively in the field. Between June 2005 and June 2007, more than 200 patients were recorded in the trauma patient registry. The majority were victims of weapons-related trauma.</p> <p>Conclusion</p> <p>This report illustrates a method to increase the capacity of indigenous health workers to manage traumatic injuries. These health workers are able to provide trauma care for otherwise inaccessible populations in remote and conflicted regions. The principles learnt during the implementation of the TMP might be applied in similar settings.</p

Apolipoprotein E mediates evasion from hepatitis C virus−neutralizing antibodies

Background &#38; Aims Efforts to develop an effective vaccine against hepatitis C virus (HCV) have been hindered by the propensity of the virus to evade host immune responses. HCV particles in serum and in cell culture associate with lipoproteins, which contribute to viral entry. Lipoprotein association has also been proposed to mediate viral evasion of the humoral immune response, though the mechanisms are poorly defined. Methods We used small interfering RNAs to reduce levels of apolipoprotein E (apoE) in cell culture−derived HCV−producing Huh7.5-derived hepatoma cells and confirmed its depletion by immunoblot analyses of purified viral particles. Before infection of naïve hepatoma cells, we exposed cell culture−derived HCV strains of different genotypes, subtypes, and variants to serum and polyclonal and monoclonal antibodies isolated from patients with chronic HCV infection. We analyzed the interaction of apoE with viral envelope glycoprotein E2 and HCV virions by immunoprecipitation. Results Through loss-of-function studies on patient-derived HCV variants of several genotypes and subtypes, we found that the HCV particle apoE allows the virus to avoid neutralization by patient-derived antibodies. Functional studies with human monoclonal antiviral antibodies showed that conformational epitopes of envelope glycoprotein E2 domains B and C were exposed after depletion of apoE. The level and conformation of virion-associated apoE affected the ability of the virus to escape neutralization by antibodies. Conclusions In cell-infection studies, we found that HCV-associated apoE helps the virus avoid neutralization by antibodies against HCV isolated from chronically infected patients. This method of immune evasion poses a challenge for the development of HCV vaccines