25 resultados para CUTANEOUS MANIFESTATIONS


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The foetus is dependent on its mother for passive immunity involving receptor-mediated specific transport of antibodies. IgG antibody is present in highest concentration in serum and is the only antibody type that can cross the placenta efficiently, except for its IgG2 subclass. Most of the pathogenic manifestations affecting the foetus involve capsular antigens and polysaccharides of pathogens and it is known that immune response to these antigens is primed to the predominant production of IgG2 type of antibody. Paradoxically, the IgG2 subclass cannot cross the placenta and neutralize such antigens; therefore, infections related to these antigens may persist and can lead to serious conditions like miscarriage and stillbirth. This article describes in brief the properties of IgG subclasses, intrauterine infections seen during pregnancy and discusses possible IgG-based strategies to manage infections to afford protection to the foetus.

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The term design in this paper particularly refers to the process (verb) and less-to the outcome or product. Design comprises a complex set of activities today involving both man and machine. Sustainability is a fundamental paradigm and carries significance in any process, natural or manmade, and its outcome. In simple terms, sustainability implies a state of sustainable living, viz, health and continuity, nurtured by diversity and evolution (innovations) in an ever-changing world. Design, in a similar line, has been comprehensively investigated and its current manifestations including design-aids (Computer Aided Design) have been evaluated in terms of sustainability. The paper investigates the rationale of sustainability to design as a whole - its purpose, its adoption in the natural world, its relevance to humankind and the technologies involved. Throughout its history, technology has been used to aid design. But in the current context of advanced algorithms and computational capacity, design no longer remains an exclusively animate faculty. Given this scenario, investigating sustainability in the light of advanced design aids such as CAD becomes pertinent. Considering that technology plays a part in design activities, the paper explores where technology must play a part and to what degree amongst the various activities that comprise design. The study includes an examination of the morphology of design and the development of a systems-thinking integrated forecasting model to evaluate the implications of CAD tools in design and sustainability. The results of the study along with a broad range of recommendations have been presented. (c) 2012 Elsevier Ltd. All rights reserved.

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A controlled laboratory experiment was carried out on forty Indian male college students for evaluating the effect of indoor thermal environment on occupants' response and thermal comfort. During experiment, indoor temperature varied from 21 degrees C to 33 degrees C, and the variables like relative humidity, airflow, air temperature and radiant temperature were recorded along with skin (T-sk) and oral temperature (T-core) from the subjects. From T-sk and T-c, body temperature (T-b) was evaluated. Subjective Thermal Sensation Vote (TSV) was recorded using ASHRAE 7-point scale. In PMV model, Fanger's T-sk equation was used to accommodate adaptive response. Stepwise regression analysis result showed T-b was better predictor of TSV than T-sk and T-core. Regional skin temperature response, lower sweat threshold temperature with no dipping sweat and higher cutaneous sweating threshold temperature were observed as thermal adaptive responses. Using PMV model, thermal comfort zone was evaluated as (22.46-25.41) degrees C with neutral temperature of 23.91 degrees C, whereas using TSV response, wider comfort zone was estimated as (23.25-2632) degrees C with neutral temperature at 24.83 degrees C. It was observed that PMV-model overestimated the actual thermal response. Interestingly, these subjects were found to be less sensitive to hot but more sensitive to cold. A new TSV-PPD relation (PPDnew) was obtained with an asymmetric distribution of hot-cold thermal sensation response in Indians. (C) 2013 Elsevier Ltd. All rights reserved.

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A controlled laboratory experiment was carried out on forty Indian male college students for evaluating the effect of indoor thermal environment on occupants' response and thermal comfort. During experiment, indoor temperature varied from 21 degrees C to 33 degrees C, and the variables like relative humidity, airflow, air temperature and radiant temperature were recorded along with subject's physiological parameters (skin (T-sk) and oral temperature (T-c)) and subjective thermal sensation responses (TSV). From T-sk and T-c, body temperature (T-b) was evaluated. Subjective Thermal Sensation Vote (TSV) was recorded using ASHRAE 7-point scale. In PMV model, Fanger's T-sk equation was used to accommodate adaptive response. Step-wise regression analysis result showed T-b was better predictor of TSV than T-sk and T-c. Regional skin temperature response, suppressed sweating without dipping, lower sweating threshold temperature and higher cutaneous threshold for sweating were observed as thermal adaptive responses. These adaptive responses cannot be considered in PMV model. To incorporate subjective adaptive response, mean skin temperature (T-sk) is considered in dry heat loss calculation. Along with these, PMV-model and other two methodologies are adopted to calculate PMV values and results are compared. However, recent literature is limited to measure the sweat rate in Indians and consideration of constant Ersw in PMV model needs to be corrected. Using measured T-sk in PMV model (Method(1)), thermal comfort zone corresponding to 0.5 <= PMV <= 0.5 was evaluated as (22.46-25.41) degrees C with neutral temperature of 23.91 degrees C, similarly while using TSV response, wider comfort zone was estimated as (23.25-26.32) degrees C with neutral temperature at 24.83 degrees C, which was further increased to with TSV-PPDnew, relation. It was observed that PMV-model overestimated the actual thermal response. Interestingly, these subjects were found to be less sensitive to hot but more sensitive to cold. A new TSV-PPD relation (PPDnew) was obtained from the population distribution of TSV response with an asymmetric distribution of hot-cold thermal sensation response from Indians. The calculations of human thermal stress according to steady state energy balance models used on PMV model seem to be inadequate to evaluate human thermal sensation of Indians. Relevance to industry: The purpose of this paper is to estimate thermal comfort zone and optimum temperature for Indians. It also highlights that PMV model seems to be inadequate to evaluate subjective thermal perception in Indians. These results can be used in feedback control of HVAC systems in residential and industrial buildings. (C) 2014 Elsevier B.V. All rights reserved.

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Water-tert-butyl alcohol (TBA) binary mixture exhibits a large number of thermodynamic and dynamic anomalies. These anomalies are observed at surprisingly low TBA mole fraction, with x(TBA) approximate to 0.03-0.07. We demonstrate here that the origin of the anomalies lies in the local structural changes that occur due to self-aggregation of TBA molecules. We observe a percolation transition of the TBA molecules at x(TBA) approximate to 0.05. We note that ``islands'' of TBA clusters form even below this mole fraction, while a large spanning cluster emerges above that mole fraction. At this percolation threshold, we observe a lambda-type divergence in the fluctuation of the size of the largest TBA cluster, reminiscent of a critical point. Alongside, the structure of water is also perturbed, albeit weakly, by the aggregation of TBA molecules. There is a monotonic decrease in the tetrahedral order parameter of water, while the dipole moment correlation shows a weak nonlinearity. Interestingly, water molecules themselves exhibit a reverse percolation transition at higher TBA concentration, x(TBA) approximate to 0.45, where large spanning water clusters now break-up into small clusters. This is accompanied by significant divergence of the fluctuations in the size of largest water cluster. This second transition gives rise to another set of anomalies around. Both the percolation transitions can be regarded as manifestations of Janus effect at small molecular level. (C) 2014 AIP Publishing LLC.

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Epidemiological studies of Staphylococcus aureus have shown a relation between certain clones and the presence of specific virulence genes, but how this translates into virulence-associated functional responses is not fully elucidated. Here we addressed this issue by analyses of community-acquired S. aureus strains characterized with respect to antibiotic resistance, ST types, agr types, and virulence gene profiles. Supernatants containing exotoxins were prepared from overnight bacterial cultures, and tested in proliferation assays using human peripheral blood mononuclear cells (PBMC). The strains displayed stable phenotypic response profiles, defined by either a proliferative or cytotoxic response. Although, virtually all strains elicited superantigen-mediated proliferative responses, the strains with a cytotoxic profile induced proliferation only in cultures with the most diluted supernatants. This indicated that the superantigen-response was masked by a cytotoxic effect which was also confirmed by flow cytometry analysis. The cytotoxic supernatants contained significantly higher levels of alpha-toxin than did the proliferative supernatants. Addition of alpha-toxin to supernatants characterized as proliferative switched the response into cytotoxic profiles. In contrast, no effect of Panton Valentine Leukocidin, delta-toxin or phenol soluble modulin alpha-3 was noted in the proliferative assay. Furthermore, a significant association between agr type and phenotypic profile was found, where agrII and agrIII strains had predominantly a proliferative profile whereas agrI and IV strains had a predominantly cytotoxic profile. The differential response profiles associated with specific S. aureus strains with varying toxin production could possibly have an impact on disease manifestations, and as such may reflect specific pathotypes.

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Methylglyoxal, which is technically known as 2-oxopropanal or pyruvaldehyde, shows typical reactions of carbonyl compounds as it has both an aldehyde and a ketone functional group. It is an extremely cytotoxic physiological metabolite, which is generated by both enzymatic and nonenzymatic reactions. The deleterious nature of the compound is due to its ability to glycate and crosslink macromolecules like protein and DNA, respectively. However, despite having toxic effects on cellular processes, methylglyoxal retains its efficacy as an anticancer drug. Indeed, methylglyoxal is one of the well-known anticancer therapeutic agents used in the treatment. Several studies on methylglyoxal biology revolve around the manifestations of its inhibitory effects and toxicity in microbial growth and diabetic complications, respectively. Here, we have revisited the chronology of methylglyoxal research with emphasis on metabolism of methylglyoxal and implications of methylglyoxal production or detoxification on bacterial pathogenesis and disease progression. (C) 2014 IUBMB Life, 66(10): 667-678, 2014

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Background: Coats plus syndrome is an autosomal recessive, pleiotropic, multisystem disorder characterized by retinal telangiectasia and exudates, intracranial calcification with leukoencephalopathy and brain cysts, osteopenia with predisposition to fractures, bone marrow suppression, gastrointestinal bleeding and portal hypertension. It is caused by compound heterozygous mutations in the CTC1 gene. Case presentation: We encountered a case of an eight-year old boy from an Indian family with manifestations of Coats plus syndrome along with an unusual occurrence of dextrocardia and situs inversus. Targeted resequencing of the CTC1 gene as well as whole exome sequencing (WES) were conducted in this family to identify the causal variations. The identified candidate variations were screened in ethnicity matched healthy controls. The effect of CTC1 variation on telomere length was assessed using Southern blot. A novel homozygous missense mutation c.1451A > C (p.H484P) in exon 9 of the CTC1 gene and a rare 3'UTR known dbSNP variation (c.*556 T > C) in HES7 were identified as the plausible candidates associated with this complex phenotype of Coats plus and dextrocardia. This CTC1 variation was absent in the controls and we also observed a reduced telomere length in the affected individual's DNA, suggesting its likely pathogenic nature. The reported p.H484P mutation is located in the N-terminal 700 amino acid regionthat is important for the binding of CTC1 to ssDNA through its two OB domains. WES data also showed a rare homozygous missense variation in the TEK gene in the affected individual. Both HES7 and TEK are targets of the Notch signaling pathway. Conclusions: This is the first report of a genetically confirmed case of Coats plus syndrome from India. By means of WES, the genetic variations in this family with unique and rare complex phenotype could be traced effectively. We speculate the important role of Notch signaling in this complex phenotypic presentation of Coats plus syndrome and dextrocardia. The present finding will be useful for genetic diagnosis and carrier detection in the family and for other patients with similar disease manifestations.

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In India, the low prevalence of HIV-associated dementia (HAD) in the Human immunodeficiency virus type 1 (HIV-1) subtype C infection is quite paradoxical given the high-rate of macrophage infiltration into the brain. Whether the direct viral burden in individual brain compartments could be associated with the variability of the neurologic manifestations is controversial. To understand this paradox, we examined the proviral DNA load in nine different brain regions and three different peripheral tissues derived from ten human subjects at autopsy. Using a highly sensitive TaqMan probe-based real-time PCR, we determined the proviral load in multiple samples processed in parallel from each site. Unlike previously published reports, the present analysis identified uniform proviral distribution among the brain compartments examined without preferential accumulation of the DNA in any one of them. The overall viral DNA burden in the brain tissues was very low, approximately 1 viral integration per 1000 cells or less. In a subset of the tissue samples tested, the HIV DNA mostly existed in a free unintegrated form. The V3-V5 envelope sequences, demonstrated a brain-specific compartmentalization in four of the ten subjects and a phylogenetic overlap between the neural and non-neural compartments in three other subjects. The envelope sequences phylogenetically belonged to subtype C and the majority of them were R5 tropic. To the best of our knowledge, the present study represents the first analysis of the proviral burden in subtype C postmortem human brain tissues. Future studies should determine the presence of the viral antigens, the viral transcripts, and the proviral DNA, in parallel, in different brain compartments to shed more light on the significance of the viral burden on neurologic consequences of HIV infection.

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The characteristics of neurological, psychiatric, developmental and substance-use disorders in low-and middle-income countries are unique and the burden that they have will be different from country to country. Many of the differences are explained by the wide variation in population demographics and size, poverty, conflict, culture, land area and quality, and genetics. Neurological, psychiatric, developmental and substance-use disorders that result from, or are worsened by, a lack of adequate nutrition and infectious disease still afflict much of sub-Saharan Africa, although disorders related to increasing longevity, such as stroke, are on the rise. In the Middle East and North Africa, major depressive disorders and post-traumatic stress disorder are a primary concern because of the conflict-ridden environment. Consanguinity is a serious concern that leads to the high prevalence of recessive disorders in the Middle East and North Africa and possibly other regions. The burden of these disorders in Latin American and Asian countries largely surrounds stroke and vascular disease, dementia and lifestyle factors that are influenced by genetics. Although much knowledge has been gained over the past 10 years, the epidemiology of the conditions in low-and middle-income countries still needs more research. Prevention and treatments could be better informed with more longitudinal studies of risk factors. Challenges and opportunities for ameliorating nervous-system disorders can benefit from both local and regional research collaborations. The lack of resources and infrastructure for health-care and related research, both in terms of personnel and equipment, along with the stigma associated with the physical or behavioural manifestations of some disorders have hampered progress in understanding the disease burden and improving brain health. Individual countries, and regions within countries, have specific needs in terms of research priorities.