Infantile thiamine deficiency in South and Southeast Asia: An age-old problem needing new solutions

Infantile beriberi, a potentially fatal disorder caused by thiamine deficiency, is often viewed as a disease confined to history in regions of the world with predominant white rice consumption. Recent case reports have, however, highlighted the persistence of thiamine deficiency as a cause of infant mortality in South and Southeast Asia. Low infant thiamine status and incidence of beriberi is attributable to maternal thiamine deficiency and insufficient breast milk thiamine. Poor dietary diversity, food preparation and cooking practices and traditional post-partum food restrictions likely play a role in these high-risk regions. Given the contribution of thiamine deficiency to infant mortality and emerging evidence of long-lasting neurodevelopmental deficits of severe and even subclinical deficiency in early life, public health strategies to prevent thiamine deficiency are urgently needed. However, efforts are hampered by uncertainties surrounding the identification and assessment of thiamine deficiency, due to the broad non-specific clinical manifestations, commonly referred to as thiamine deficiency disorders (TDD), that overlap with other conditions resulting in frequent misdiagnosis and missed treatment opportunities, and secondly the lack of readily available and agreed upon biomarker analysis and cut-off thresholds. This review will discuss the key challenges and limitations in the current understanding of TDD and explore how ongoing initiatives plan to fill persistent knowledge gaps, namely in the development of a standardised case definition to help more accurately diagnose and treat TDD in low-resource settings. Given more attention and ensuring greater recognition of TDD will support the design and implementation of treatment and prevention programmes, and ensure beriberi can truly be considered 'the forgotten disease of Asia'

Synthetic studies with Pinus elliottiis ' rosin derivatives. Oxidation of maleopimaric anhydride methyl ester and trimethyl fumaropimarate

Ozonolysis of maleopimaric anhydride methyl ester in the presence of tetracyanoethylene led to an epoxide and an ozonide. Ozonolysis of the trimethyl fumaropimarate, followed by treatment with Me2S, led to an epoxide, a diene, a keto-acid and an allylic oxidation product. Some of the compounds obtained were active against Staphylococcus aureus, Bacillus subtilis and Micrococcus luteus.111596

Effect of concurrent vitamin A and iodine deficiencies on the thyroid-pituitary axis in rats

OBJECTIVE: Deficiencies of vitamin A and iodine are common in many developing countries. Vitamin A deficiency (VAD) may adversely affect thyroid metabolism. The study aim was to investigate the effects of concurrent vitamin A and iodine deficiencies on the thyroid-pituitary axis in rats. DESIGN: Weanling rats (n = 56) were fed diets deficient in vitamin A (VAD group), iodine (ID group), vitamin A and iodine (VAD + ID group), or sufficient in both vitamin A and iodine (control) for 30 days in a pair-fed design. Serum retinol (SR), thyroid hormones (FT(4), TT(4), FT(3), and TT(3)), serum thyrotropin (TSH), pituitary TSHbeta mRNA expression levels, and thyroid weights were determined at the end of the depletion period. MAIN OUTCOME: Compared to the control and ID groups, SR concentrations were about 35% lower in the VAD and VAD + ID groups (p < 0.001), indicating moderate VA deficiency. Comparing the VAD and control groups, there were no significant differences in TSH, TSHbeta mRNA, thyroid weight, or thyroid hormone levels. Compared to the control group, serum TSH, TSHbeta mRNA, and thyroid weight were higher (p < 0.05), and FT4 and TT4 were lower (p < 0.001), in the VAD + ID and ID groups. Compared to the ID group, TSH, TSHbeta mRNA, and thyroid weight were higher (p < 0.01) and FT(4) and TT(4) were lower (p < 0.001) in the VAD + ID group. There were no significant differences in TT3 or FT3 concentrations among groups. CONCLUSION: Moderate VAD alone has no measurable effect on the pituitary-thyroid axis. Concurrent ID and VAD produce more severe primary hypothyroidism than ID alone

Molecular identification of adenoviruses associated with respiratory infection in Egypt from 2003 to 2010.

BACKGROUND: Human adenoviruses of species B, C, and E (HAdV-B, -C, -E) are frequent causative agents of acute respiratory infections worldwide. As part of a surveillance program aimed at identifying the etiology of influenza-like illness (ILI) in Egypt, we characterized 105 adenovirus isolates from clinical samples collected between 2003 and 2010. METHODS: Identification of the isolates as HAdV was accomplished by an immunofluorescence assay (IFA) and confirmed by a set of species and type specific polymerase chain reactions (PCR). RESULTS: Of the 105 isolates, 42% were identified as belonging to HAdV-B, 60% as HAdV-C, and 1% as HAdV-E. We identified a total of six co-infections by PCR, of which five were HAdV-B/HAdV-C co-infections, and one was a co-infection of two HAdV-C types: HAdV-5/HAdV-6. Molecular typing by PCR enabled the identification of eight genotypes of human adenoviruses; HAdV-3 (n = 22), HAdV-7 (n = 14), HAdV-11 (n = 8), HAdV-1 (n = 22), HAdV-2 (20), HAdV-5 (n = 15), HAdV-6 (n = 3) and HAdV-4 (n = 1). The most abundant species in the characterized collection of isolates was HAdV-C, which is concordant with existing data for worldwide epidemiology of HAdV respiratory infections. CONCLUSIONS: We identified three species, HAdV-B, -C and -E, among patients with ILI over the course of 7 years in Egypt, with at least eight diverse types circulating

An approach for the identification of targets specific to bone metastasis using cancer genes interactome and gene ontology analysis

Metastasis is one of the most enigmatic aspects of cancer pathogenesis and is a major cause of cancer-associated mortality. Secondary bone cancer (SBC) is a complex disease caused by metastasis of tumor cells from their primary site and is characterized by intricate interplay of molecular interactions. Identification of targets for multifactorial diseases such as SBC, the most frequent complication of breast and prostate cancers, is a challenge. Towards achieving our aim of identification of targets specific to SBC, we constructed a 'Cancer Genes Network', a representative protein interactome of cancer genes. Using graph theoretical methods, we obtained a set of key genes that are relevant for generic mechanisms of cancers and have a role in biological essentiality. We also compiled a curated dataset of 391 SBC genes from published literature which serves as a basis of ontological correlates of secondary bone cancer. Building on these results, we implement a strategy based on generic cancer genes, SBC genes and gene ontology enrichment method, to obtain a set of targets that are specific to bone metastasis. Through this study, we present an approach for probing one of the major complications in cancers, namely, metastasis. The results on genes that play generic roles in cancer phenotype, obtained by network analysis of 'Cancer Genes Network', have broader implications in understanding the role of molecular regulators in mechanisms of cancers. Specifically, our study provides a set of potential targets that are of ontological and regulatory relevance to secondary bone cancer.Comment: 54 pages (19 pages main text; 11 Figures; 26 pages of supplementary information). Revised after critical reviews. Accepted for Publication in PLoS ON

Spin Caloritronics

This is a brief overview of the state of the art of spin caloritronics, the science and technology of controlling heat currents by the electron spin degree of freedom (and vice versa).Comment: To be published in "Spin Current", edited by S. Maekawa, E. Saitoh, S. Valenzuela and Y. Kimura, Oxford University Pres

The effect of a manual instrumentation technique on five types of premolar root canal geometry assessed by microcomputed tomography and three-dimensional reconstruction

<p>Abstract</p> <p>Background</p> <p>Together with diagnosis and treatment planning, a good knowledge of the root canal system and its frequent variations is a necessity for successful root canal therapy. The selection of instrumentation techniques for variants in internal anatomy of teeth has significant effects on the shaping ability and cleaning effectiveness. The aim of this study was to reveal the differences made by including variations in the internal anatomy of premolars into the study protocol for investigation of a single instrumentation technique (hand ProTaper instruments) assessed by microcomputed tomography and three-dimensional reconstruction.</p> <p>Methods</p> <p>Five single-root premolars, whose root canal systems were classified into one of five types, were scanned with micro-CT before and after preparation with a hand ProTaper instrument. Instrumentation characteristics were measured quantitatively in 3-D using a customized application framework based on MeVisLab. Numeric values were obtained for canal surface area, volume, volume changes, percentage of untouched surface, dentin wall thickness, and the thickness of dentin removed. Preparation errors were also evaluated using a color-coded reconstruction.</p> <p>Results</p> <p>Canal volumes and surface areas were increased after instrumentation. Prepared canals of all five types were straightened, with transportation toward the inner aspects of S-shaped or multiple curves. However, a ledge was formed at the apical third curve of the type II canal system and a wide range in the percentage of unchanged canal surfaces (27.4-83.0%) was recorded. The dentin walls were more than 0.3 mm thick except in a 1 mm zone from the apical surface and the hazardous area of the type II canal system after preparation with an F3 instrument.</p> <p>Conclusions</p> <p>The 3-D color-coded images showed different morphological changes in the five types of root canal systems shaped with the same hand instrumentation technique. Premolars are among the most complex teeth for root canal treatment and instrumentation techniques for the root canal systems of premolars should be selected individually depending on the 3-D canal configuration of each tooth. Further study is needed to demonstrate the differences made by including variations in the internal anatomy of teeth into the study protocol of clinical RCT for identifying the best preparation technique.</p

Contribution of human hematopoietic stem cells to liver repair

Immune-deficient mouse models of liver damage allow examination of human stem cell migration to sites of damage and subsequent contribution to repair and survival. In our studies, in the absence of a selective advantage, transplanted human stem cells from adult sources did not robustly become hepatocytes, although some level of fusion or hepatic differentiation was documented. However, injected stem cells did home to the injured liver tissue and release paracrine factors that hastened endogenous repair and enhanced survival. There were significantly higher levels of survival in mice with a toxic liver insult that had been transplanted with human stem cells but not in those transplanted with committed progenitors. Transplantation of autologous adult stem cells without conditioning is a relatively safe therapy. Adult stem cells are known to secrete bioactive factors that suppress the local immune system, inhibit fibrosis (scar formation) and apoptosis, enhance angiogenesis, and stimulate recruitment, retention, mitosis, and differentiation of tissue-residing stem cells. These paracrine effects are distinct from the direct differentiation of stem cells to repair tissue. In patients at high risk while waiting for a liver transplant, autologous stem cell therapy could be considered, as it could delay the decline in liver function

Direct knock-on of desolvated ions governs strict ion selectivity in K+ channels

The seeming contradiction that K+ channels conduct K+ ions at maximal throughput rates while not permeating slightly smaller Na+ ions has perplexed scientists for decades. Although numerous models have addressed selective permeation in K+ channels, the combination of conduction efficiency and ion selectivity has not yet been linked through a unified functional model. Here, we investigate the mechanism of ion selectivity through atomistic simulations totalling more than 400 μs in length, which include over 7,000 permeation events. Together with free-energy calculations, our simulations show that both rapid permeation of K+ and ion selectivity are ultimately based on a single principle: the direct knock-on of completely desolvated ions in the channels' selectivity filter. Herein, the strong interactions between multiple 'naked' ions in the four filter binding sites give rise to a natural exclusion of any competing ions. Our results are in excellent agreement with experimental selectivity data, measured ion interaction energies and recent two-dimensional infrared spectra of filter ion configurations

Spontaneous Quaternary and Tertiary T-R Transitions of Human Hemoglobin in Molecular Dynamics Simulation

We present molecular dynamics simulations of unliganded human hemoglobin (Hb) A under physiological conditions, starting from the R, R2, and T state. The simulations were carried out with protonated and deprotonated HC3 histidines His(β)146, and they sum up to a total length of 5.6µs. We observe spontaneous and reproducible T→R quaternary transitions of the Hb tetramer and tertiary transitions of the α and β subunits, as detected from principal component projections, from an RMSD measure, and from rigid body rotation analysis. The simulations reveal a marked asymmetry between the α and β subunits. Using the mutual information as correlation measure, we find that the β subunits are substantially more strongly linked to the quaternary transition than the α subunits. In addition, the tertiary populations of the α and β subunits differ substantially, with the β subunits showing a tendency towards R, and the α subunits showing a tendency towards T. Based on the simulation results, we present a transition pathway for coupled quaternary and tertiary transitions between the R and T conformations of Hb