ANXIETY, DEPRESSION, AND SELF-CARE MANAGEMENT AMONG PATIENTS WITH HYPOTHYROIDISM.

 Objective: The objective of the study was to assess anxiety, depression, and self-care management among patients with hypothyroidism.Methods: A qualitative descriptive study was done among 65 patients who was diagnosed with hypothyroidism, and the data were collected using structured questionnaire to know about self-care management of hypothyroidism and standardized tool (Hamilton rating scale) for assessing anxiety and depression.Results: The result showed that among 65 subjects, 30 (46.2%) had good self-care management, only 1 (1%) had excellent self-care management, 46.1% had severe anxiety, whereas 4.6% subjects had severe depression. There was a positive association between anxiety and depression with self-care management.Conclusion: Hypothyroidism is now becoming more prevalent in the Indian population. From the results of the study, it is obvious that patients with hypothyroidism are at increased risk of anxiety and depression. Self-care management decreases with an increase in anxiety and depression. Hence, proper management is necessary to reduce the deleterious effect of hypothyroidism on physical as well as mental health

Histological heterogeneity of glomerular segmental lesions in focal segmental glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) involves considerable histological heterogeneity in terms of location and quality of the glomerular segmental lesions. The present study investigated the heterogeneity of segmental lesions in each variant of FSGS, determined by the Columbia classification, and its clinical relevance. All glomerular segmental lesions of 80 cases of primary FSGS were evaluated histologically based on location [tip (TIP), perihilar (PH), or not otherwise specified (NOS)], and quality (cellular or fibrous). Among the 1,299 glomeruli of the 80 biopsy specimens, 210 glomeruli (16.2%) had segmental lesions, comprising 57 (27%) cellular TIP, 4 (2%) fibrous TIP, 42 (20%) cellular NOS, 86 (41%) fibrous NOS, and 21 (10%) fibrous PH lesions. Each case was also classified into one of the five histological variants of the Columbia classification: collapsing (COL), TIP, cellular (CEL), PH, or NOS. Overlap of segmental lesions in different location categories was seen in the COL, TIP, and PH variants, and heterogeneity of quality was apparent in the COL and CEL variants. Histological findings of the CEL variant (endocapillary hypercellularity) were observed in nine of the 13 COL variants. Both location and quality correlated with disease duration, degree of proteinuria, and histological severity of global glomerular sclerosis and tubulo-interstitial lesions. These results demonstrated the histological heterogeneity of glomerular segmental lesions in all variants of the Columbia classification, except NOS. However, the fidelity of location and dominance of histological features were generally conserved in the TIP and PH variants. The COL and CEL variants warrant further investigation because of their overlapping histological findings and apparent histological heterogeneity in the glomerular segmental lesions

The degradation of p53 and its major E3 ligase Mdm2 is differentially dependent on the proteasomal ubiquitin receptor S5a.

p53 and its major E3 ligase Mdm2 are both ubiquitinated and targeted to the proteasome for degradation. Despite the importance of this in regulating the p53 pathway, little is known about the mechanisms of proteasomal recognition of ubiquitinated p53 and Mdm2. In this study, we show that knockdown of the proteasomal ubiquitin receptor S5a/PSMD4/Rpn10 inhibits p53 protein degradation and results in the accumulation of ubiquitinated p53. Overexpression of a dominant-negative deletion of S5a lacking its ubiquitin-interacting motifs (UIM)s, but which can be incorporated into the proteasome, also causes the stabilization of p53. Furthermore, small-interferring RNA (siRNA) rescue experiments confirm that the UIMs of S5a are required for the maintenance of low p53 levels. These observations indicate that S5a participates in the recognition of ubiquitinated p53 by the proteasome. In contrast, targeting S5a has no effect on the rate of degradation of Mdm2, indicating that proteasomal recognition of Mdm2 can be mediated by an S5a-independent pathway. S5a knockdown results in an increase in the transcriptional activity of p53. The selective stabilization of p53 and not Mdm2 provides a mechanism for p53 activation. Depletion of S5a causes a p53-dependent decrease in cell proliferation, demonstrating that p53 can have a dominant role in the response to targeting S5a. This study provides evidence for alternative pathways of proteasomal recognition of p53 and Mdm2. Differences in recognition by the proteasome could provide a means to modulate the relative stability of p53 and Mdm2 in response to cellular signals. In addition, they could be exploited for p53-activating therapies. This work shows that the degradation of proteins by the proteasome can be selectively dependent on S5a in human cells, and that this selectivity can extend to an E3 ubiquitin ligase and its substrate

Methamphetamine Increases LPS-Mediated Expression of IL-8, TNF-α and IL-1β in Human Macrophages through Common Signaling Pathways

The use of methamphetamine (MA) has increased in recent years, and is a major health concern throughout the world. The use of MA has been associated with an increased risk of acquiring HIV-1, along with an increased probability of the acquisition of various sexually transmitted infections. In order to determine the potential effects of MA exposure in the context of an infectious agent, U937 macrophages were exposed to various combinations of MA and bacterial lipopolysaccharide (LPS). Treatment with MA alone caused significant increases in the levels of TNF-α, while treatment with both MA and LPS resulted in significant increases in TNF-α, IL-1β and the chemokine IL-8. The increases in cytokine or chemokine levels seen when cells were treated with both LPS and MA were generally greater than those increases observed when cells were treated with only LPS. Treatment with chemical inhibitors demonstrated that the signal transduction pathways including NF-kB, MAPK, and PI3-Akt were involved in mediating the increased inflammatory response. As discussed in the paper, these pathways appear to be utilized by both MA and LPS, in the induction of these inflammatory mediators. Since these pathways are involved in the induction of inflammation in response to other pathogens, this suggests that MA-exacerbated inflammation may be a common feature of infectious disease in MA abusers

Use of Oral Cholera Vaccines in an Outbreak in Vietnam: A Case Control Study

Simple measures such as adequate sanitation and clean water stops the spread of cholera; however, in areas where these are not available, cholera spreads quickly and may lead to death in a few hours if treatment is not initiated immediately. The use of life-saving rehydration therapy is the mainstay in cholera control, however, the rapidity of the disease and the limited access to appropriate healthcare units in far-flung areas together result in an unacceptable number of deaths. The WHO has recommended the use of oral cholera vaccines as a preventive measure against cholera outbreaks since 2001, but this was recently updated so that vaccine use may also be considered once a cholera outbreak has begun. The findings from this study suggest that reactive use of killed oral cholera vaccines provides protection against the disease and may be a potential tool in times of outbreaks. Further studies must be conducted to confirm these findings

Role of Cell-to-Cell Variability in Activating a Positive Feedback Antiviral Response in Human Dendritic Cells

In the first few hours following Newcastle disease viral infection of human monocyte-derived dendritic cells, the induction of IFNB1 is extremely low and the secreted type I interferon response is below the limits of ELISA assay. However, many interferon-induced genes are activated at this time, for example DDX58 (RIGI), which in response to viral RNA induces IFNB1. We investigated whether the early induction of IFNBI in only a small percentage of infected cells leads to low level IFN secretion that then induces IFN-responsive genes in all cells. We developed an agent-based mathematical model to explore the IFNBI and DDX58 temporal dynamics. Simulations showed that a small number of early responder cells provide a mechanism for efficient and controlled activation of the DDX58-IFNBI positive feedback loop. The model predicted distributions of single cell responses that were confirmed by single cell mRNA measurements. The results suggest that large cell-to-cell variation plays an important role in the early innate immune response, and that the variability is essential for the efficient activation of the IFNB1 based feedback loop

Impact of multi-metals (Cd, Pb and Zn) exposure on the physiology of the yeast Pichia kudriavzevii

Metal contamination of the environment is frequently associated to the presence of two or more metals. This work aimed to study the impact of a mixture of metals (Cd, Pb and Zn) on the physiology of the non-conventional yeast Pichia kudriavzevii. The incubation of yeast cells with 5 mg/l Cd, 10 mg/l Pb and 5 mg/l Zn, for 6 h, induced a loss of metabolic activity (assessed by FUN-1 staining) and proliferation capacity (evaluated by a clonogenic assay), with a small loss of membrane integrity (measured by trypan blue exclusion assay). The staining of yeast cells with calcofluor white revealed that no modification of chitin deposition pattern occurred during the exposure to metal mixture. Extending for 24 h, the exposure of yeast cells to metal mixture provoked a loss of membrane integrity, which was accompanied by the leakage of intracellular components. A marked loss of the metabolic activity and the loss of proliferation capacity were also observed. The analysis of the impact of a single metal has shown that, under the conditions studied, Pb was the metal responsible for the toxic effect observed in the metal mixture. Intracellular accumulation of Pb seems to be correlated with the metals toxic effects observed.The authors thank the FCT Strategic Project PEst-OE/EQB/LA0023/2013 and the Project "BioInd-Biotechnology and Bioengineering for improved Industrial and Agro-Food processes" (NORTE-07-0124-FEDER-000028), Co-funded by the Programa Operacional Regional do Norte (ON.2-O Novo Norte), QREN, FEDER. Manuela D. Machado gratefully acknowledges the post-doctoral grant from FCT (SFRH/BPD/72816/2010). Vanessa A. Mesquita gratefully acknowledges the grant from Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES). The authors also thank to Doctor Rosane Freitas Schwan to offer the yeast strain and to Doctor Helena M.V.M. Soares, from the Faculty of Engineering of Porto University, for the use of analytical facilities (AAS with flame atomization and AAS with electrothermal atomization)