Acephalic Acardiac Fetus

Acardia (Twin Reversed Arterial Perfusion Sequence) is a rare and one of the most bizarre congenital malformations occurring in multiple pregnancies. It affects 1 in 35,000 pregnancies. Usually one twin shows absence of heart and other is structurally normal. The acardiac twin presents with many bizarre anomalies such as lack of head, thorax and upper extremities. We report a case of autopsy study of acardiac twin with severe malformations. The case has been presented for its rarity

Health information-seeking behavior among hypothyroid patients at Saveetha Medical College and Hospital

BACKGROUND: Hypothyroidism causes considerable morbidity. Low knowledge coupled with inadequate health literacy may lead to poor prevention and management. This study aimed to assess health information-seeking behavior and hypothyroid knowledge among South Indian hypothyroid patients.METHODS: This cross-sectional study was conducted in October 2013 in Saveetha Medical College, Chennai, India. Hundred clinically diagnosed hypothyroid patients >18 years were interviewed in a hospital using a 57-item questionnaire to gather information on their socio-demographics, self-reported disease history, hypothyroid-related knowledge, health information sources, health literacy and health information-seeking behavior. Hypothyroidism was assessed by free T3 and T4 levels.RESULTS: Mean age of participants was 38 years (SD=12) with median age of 39.5 years, majority of the participants being females (77%) and living in urban setting (52%). Mean free T3 level was 0.0137ng/dl (SD= 0.003) and mean free T4 was 0.7ng/dl (SD= 0.06). Ninety three percent of the participants received initial hypothyroidism education from their physicians at the time of diagnosis. Half of the participants had incorrect hypothyroidism-related knowledge; similar between both genders. Participants with inadequate health literacy had poor knowledge about the hypothyroidism. Hypothyroidism-related health information was sought almost exclusively from health professionals, predominantly regarding treatment, linked to their faith in qualified medical assistance. Economic status primarily determined healthcare-seeking behavior. Marital status, education level, annual household income and health literacy were significantly associated with knowledge.CONCLUSION: Participants having higher educational qualification, higher annual household income and adequate health literacy had considerable knowledge about hypothyroidism. Developing multi-factorial and tailored health education for patients with marginal or inadequate health literacy is needed. Exploring healthcare institutions as a medium for delivery of such education should be explored.KEYWORDS: Hypothyroidism, Health Information-seeking Behavior, Knowledge, Health Literac

Accuracy of physical examination in the diagnosis of hypothyroidism: a cross-sectional, double-blind study

Background: Hypothyroidism is a common, potentially treatable endocrine disorder. Since hypothyroidism is not always associated with the signs and symptoms typically attributed to it, the diagnosis is often missed. Conversely, patients with typical signs and symptoms may not have the disease when laboratory tests are performed. Aims: We aimed to determine the accuracy of physical examination in the diagnosis of hypothyroidism. Setting and design: Prospective, hospital-based, cross-sectional diagnostic study. Material and Methods: Consecutive outpatients from the medicine department were screened and an independent comparison of physical signs (coarse skin, puffy face, slow movements, bradycardia, pretibial oedema and ankle reflex) against thyroid hormone assay (TSH and FT4) was performed. Statistical analysis: Diagnostic accuracy was measured as sensitivity, specificity, positive likelihood ratios, negative likelihood ratios and positive and negative predictive values. Results: Of the 1450 patients screened, 130 patients (102 women and 28 men) underwent both clinical examination and thyroid function tests. Twenty-three patients (18%) were diagnosed to have hypothyroidism by thyroid hormone assays. No single sign could easily discriminate a euthyroid from a hypothyroid patient (range of positive likelihood ratio (LR+) 1.0 to 3.88; range of negative likelihood ratio (LR-): 0.42 to 1.0). No physical sign generated a likelihood ratio large enough to increase the post-test probability significantly. The combination of signs that had the highest likelihood ratios (coarse skin, bradycardia and delayed ankle reflex) was associated with modest accuracy (LR+ 3.75; LR- 0.48). Conclusion: Clinicians cannot rely exclusively on physical examination to confirm or rule out hypothyroidism. Patients with suspected hypothyroidism require a diagnostic workup that includes thyroid hormone assays

Regulatory de novo mutations underlying intellectual disability

The genetic aetiology of a major fraction of patients with intellectual disability (ID) remains unknown. De novo mutations (DNMs) in protein-coding genes explain up to 40% of cases, but the potential role of regulatory DNMs is still poorly understood. We sequenced 63 whole genomes from 21 ID probands and their unaffected parents. In addition, we analysed 30 previously sequenced genomes from exome-negative ID probands. We found that regulatory DNMs were selectively enriched in fetal brain-specific enhancers as compared with adult brain enhancers. DNM-containing enhancers were associated with genes that show preferential expression in the prefrontal cortex. Furthermore, we identified recurrently mutated enhancer clusters that regulate genes involved in nervous system development (CSMD1, OLFM1, and POU3F3). Most of the DNMs from ID probands showed allele-specific enhancer activity when tested using luciferase assay. Using CRISPR-mediated mutation and editing of epigenomic marks, we show that DNMs at regulatory elements affect the expression of putative target genes. Our results, therefore, provide new evidence to indicate that DNMs in fetal brain-specific enhancers play an essential role in the aetiology of ID

Angiotensin II, via angiotensin receptor type 1/nuclear factor-κB activation, causes a synergistic effect on interleukin-1-β-induced inflammatory responses in cultured mesangial cells

Introduction: The nuclear factor-κB (NF-κB) is an important regulator of the inflammatory response. Angiotensin II (Ang II) activates the NF-κB pathway linked to renal inflammation. Although both AT1 and AT2 receptors are involved in Ang II-mediated NF-κB activation, the biological processes mediated by each receptor are not fully characterized. Interleukin-1β (IL-1β) is an important macrophage-derived cytokine that regulates immune and inflammatory processes, activating intracellular pathways shared with Ang II, including the NF-κB. Materials and methods: In vitro studies were done in primary cultured rat mesangial cells. NF-κB pathway was evaluated by phosphorylated levels of p65/IκB and DNA binding activity. The Ang II receptor subtype was determined by pretreatment with AT1 and AT2 antagonists. Results: In mesangial cells the simultaneous presence of Ang II and IL-1β caused a synergistic activation of the NF-κB pathway and a marked upregulation of proinflammatory factors under NF-κB control, including monocyte chemoattractant protein-1. The AT1, but not AT2, antagonist abolished the synergistic effect on NF-κB activation and proinflammatory genes caused by coincubation of Ang II and IL-1β. Conclusions: These data indicates that Ang II, via AT1/NF-κB pathway activation, cooperates with IL-β to increase the inflammatory response in mesangial cellsThis work was supported by grants from the Instituto de Salud Carlos III (ISCIIIRETIC REDinREN RD06/0016, RD12/0021, PI11/01854), Comunidad de Madrid (Fibroteam S2010/BMD- 2321, S2010/BMD-2378), and Research Institute Queen Sophia (IRSIN). Programa Intensificación Actividad Investigadora (ISCIII/Agencia Laín-Entralgo/CM) to AO. MA and ESL are supported by a ‘Sara Borrell’ postdoctoral contract from Instituto de Salud Carlos III (CD10/00347 and CD09/00066, respectively

Scalar-field Pressure in Induced Gravity with Higgs Potential and Dark Matter

A model of induced gravity with a Higgs potential is investigated in detail in view of the pressure components related to the scalar-field excitations. The physical consequences emerging as an artifact due to the presence of these pressure terms are analysed in terms of the constraints parting from energy density, solar-relativistic effects and galactic dynamics along with the dark matter halos.Comment: 26 pages, 3 figures, Minor revision, Published in JHE

Detection of regulator genes and eQTLs in gene networks

Genetic differences between individuals associated to quantitative phenotypic traits, including disease states, are usually found in non-coding genomic regions. These genetic variants are often also associated to differences in expression levels of nearby genes (they are "expression quantitative trait loci" or eQTLs for short) and presumably play a gene regulatory role, affecting the status of molecular networks of interacting genes, proteins and metabolites. Computational systems biology approaches to reconstruct causal gene networks from large-scale omics data have therefore become essential to understand the structure of networks controlled by eQTLs together with other regulatory genes, and to generate detailed hypotheses about the molecular mechanisms that lead from genotype to phenotype. Here we review the main analytical methods and softwares to identify eQTLs and their associated genes, to reconstruct co-expression networks and modules, to reconstruct causal Bayesian gene and module networks, and to validate predicted networks in silico.Comment: minor revision with typos corrected; review article; 24 pages, 2 figure

Comparison of pulmonary and extrapulmonary tuberculosis in Nepal- a hospital-based retrospective study

<p>Abstract</p> <p>Background</p> <p>Studies from developed countries have reported on host-related risk factors for extra-pulmonary tuberculosis (EPTB). However, similar studies from high-burden countries like Nepal are lacking. Therefore, we carried out this study to compare demographic, life-style and clinical characteristics between EPTB and PTB patients.</p> <p>Methods</p> <p>A retrospective analysis was carried out on 474 Tuberculosis (TB) patients diagnosed in a tertiary care hospital in western Nepal. Characteristics of demography, life-style and clinical features were obtained from medical case records. Risk factors for being an EPTB patient relative to a PTB patient were identified using logistic regression analysis.</p> <p>Results</p> <p>The age distribution of the TB patients had a bimodal distribution. The male to female ratio for PTB was 2.29. EPTB was more common at younger ages (< 25 years) and in females. Common sites for EPTB were lymph nodes (42.6%) and peritoneum and/or intestines (14.8%). By logistic regression analysis, age less than 25 years (OR 2.11 95% CI 1.12–3.68) and female gender (OR 1.69, 95% CI 1.12–2.56) were associated with EPTB. Smoking, use of immunosuppressive drugs/steroids, diabetes and past history of TB were more likely to be associated with PTB.</p> <p>Conclusion</p> <p>Results suggest that younger age and female gender may be independent risk factors for EPTB in a high-burden country like Nepal. TB control programmes may target young and female populations for EPTB case-finding. Further studies are necessary in other high-burden countries to confirm our findings.</p

How managers can build trust in strategic alliances: a meta-analysis on the central trust-building mechanisms

Trust is an important driver of superior alliance performance. Alliance managers are influential in this regard because trust requires active involvement, commitment and the dedicated support of the key actors involved in the strategic alliance. Despite the importance of trust for explaining alliance performance, little effort has been made to systematically investigate the mechanisms that managers can use to purposefully create trust in strategic alliances. We use Parkhe’s (1998b) theoretical framework to derive nine hypotheses that distinguish between process-based, characteristic-based and institutional-based trust-building mechanisms. Our meta-analysis of 64 empirical studies shows that trust is strongly related to alliance performance. Process-based mechanisms are more important for building trust than characteristic- and institutional-based mechanisms. The effects of prior ties and asset specificity are not as strong as expected and the impact of safeguards on trust is not well understood. Overall, theoretical trust research has outpaced empirical research by far and promising opportunities for future empirical research exist

General Minimal Flavor Violation

A model independent study of the minimal flavor violation (MFV) framework is presented, where the only sources of flavor breaking at low energy are the up and down Yukawa matrices. Two limits are identified for the Yukawa coupling expansion: linear MFV, where it is truncated at the leading terms, and nonlinear MFV, where such a truncation is not possible due to large third generation Yukawa couplings. These are then resummed to all orders using non-linear sigma-model techniques familiar from models of collective breaking. Generically, flavor diagonal CP violating (CPV) sources in the UV can induce O(1) CPV in processes involving third generation quarks. Due to a residual U(2) symmetry, the extra CPV in B_d-\bar B_d mixing is bounded by CPV in B_s-\bar B_s mixing. If operators with right-handed light quarks are subdominant, the extra CPV is equal in the two systems, and is negligible in processes involving only the first two generations. We find large enhancements in the up type sector, both in CPV in D-\bar D mixing and in top flavor violation.Comment: 5 pages and no figure