Thyroid profile in newly diagnosed male HIV patients: a study from North Western part of India

Background: The aim of this study was to determine proportion of newly diagnosed male HIV cases with thyroid dysfunction at different levels of CD4 counts.Methods: 195 newly diagnosed male HIV patients attending medical OPD, ART centre and medical wards of SMS Medical College and Hospital, during a period of May 2012 to April 2013 were enrolled in the study. These patients were divided in three groups on the basis of CD4 cell counts. Group A: CD4 counts 500/mm3.Results: We concluded a negative correlation between the CD4 counts and serum TSH level (r = -0.382) which was significant (p-value <0.05). Overall 32 (16.41%) patients had increased TSH, 4 (2.05%) patients had decreased and 159 (81.53%) patients had normal TSH level. Plasma TSH values in group A were higher than group B and C and they were highly significant (p<.001). Mean plasma TSH values in patients of group A, B and C was 4.56±3.60 µIU/mL (range: 1.10-17.74), 2.20±1.02 µIU/mL (range:0.24-4.22) and 2.23±1.06 µIU/mL (range:0.28-4.25) respectively. (Reference normal value = 0.4-4.0 µIU/mL). There was significantly positive correlation (p-value < 0.01) found between the CD4 counts and serum free T4 levels (r = +0.378).Conclusions: This study has demonstrated a high prevalence of thyroid dysfunction in HIV infected patients of this part of country. High prevalence of thyroid dysfunction may contribute to the morbidity of the patients and have a bearing on quality of life of the HIV infected patients. Severity of hypothyroidism was correlated with decreasing CD4 cell count

Experiences in the Integration of Design Across the Mechanical Engineering Curriculum

The Faculty of the School of Mechanical Engineering at Purdue University have effected a major change in the Purdue Mechanical Engineering program by integrating design throughout the curriculum. In doing so, a significant level of faculty interaction has been achieved as well. The goals of the curriculum revision are: (1) to improve student skills in how to solve open-ended design problems, (2) to reduce the core of the curriculum to allow flexibility in course selection, and allow time for solving design problems, (3) to improve student skills in team work and communications, and (4) to improve student skills in using computers as tools for solving engineering problems. Reduction of the core allowed the addition of a sophomore cornerstone design course. This cornerstone course teaches students how to solve open-ended problems, bridging the gap between solution strategies that are effective for the science and mathematics courses, and those needed to solve open-ended engineering problems. The design fundamentals taught in the cornerstone course are applied in the core courses, such as heat transfer, thermodynamics, instrumentation, and machine design. The senior design experience comes primarily from a design elective and the capstone design course. This paper presents an overview of the curriculum revision process, and the changes which resulted from it. It also discusses the issues associated with infusing design projects into core courses which have traditionally focused on teaching engineering science fundamentals. Plans for the future evolution of the curriculum are also discussed

Biofabrication of the osteochondral unit and its applications: Current and future directions for 3D bioprinting

Multiple prevalent diseases, such as osteoarthritis (OA), for which there is no cure or full understanding, affect the osteochondral unit; a complex interface tissue whose architecture, mechanical nature and physiological characteristics are still yet to be successfully reproduced in vitro. Although there have been multiple tissue engineering-based approaches to recapitulate the three dimensional (3D) structural complexity of the osteochondral unit, there are various aspects that still need to be improved. This review presents the different pre-requisites necessary to develop a human osteochondral unit construct and focuses on 3D bioprinting as a promising manufacturing technique. Examples of 3D bioprinted osteochondral tissues are reviewed, focusing on the most used bioinks, chosen cell types and growth factors. Further information regarding the applications of these 3D bioprinted tissues in the fields of disease modelling, drug testing and implantation is presented. Finally, special attention is given to the limitations that currently hold back these 3D bioprinted tissues from being used as models to investigate diseases such as OA. Information regarding improvements needed in bioink development, bioreactor use, vascularisation and inclusion of additional tissues to further complete an OA disease model, are presented. Overall, this review gives an overview of the evolution in 3D bioprinting of the osteochondral unit and its applications, as well as further illustrating limitations and improvements that could be performed explicitly for disease modelling

Infection with soil-transmitted helminths and their impact on coinfections

The most important soil-transmitted helminths (STHs) affecting humans are roundworms, whipworms, and hookworms, with a large proportion of the world’s population infected with one or more of these intestinal parasites. On top of that, concurrent infections with several viruses, bacteria, protozoa, and other helminths such as trematodes are common in STH-endemic areas. STHs are potent immunomodulators, but knowledge about the effects of STH infection on the direction and extent of coinfections with other pathogens and vice versa is incomplete. By focusing on Kenya, a country where STH infections in humans are widespread, we provide an exemplary overview of the current prevalence of STH and co-occurring infections (e.g. with Human Immunodeficiency Virus, Plasmodium falciparum, Giardia duodenalis and Schistosoma mansoni). Using human data and complemented by experimental studies, we outline the immunomechanistic interactions of coinfections in both acutely STH transmigrated and chronically infected tissues, also highlighting their systemic nature. Depending on the coinfecting pathogen and immunological readout, STH infection may restrain, support, or even override the immune response to another pathogen. Furthermore, the timing of the particular infection and host susceptibility are decisive for the immunopathological consequences. Some examples demonstrated positive outcomes of STH coinfections, where the systemic effects of these helminths mitigate the damage caused by other pathogens. Nevertheless, the data available to date are rather unbalanced, as only a few studies have considered the effects of coinfection on the worm’s life cycle and associated host immunity. These interactions are complex and depend largely on the context and biology of the coinfection, which can act in either direction, both to the benefit and detriment of the infected host

Association of angiotensin-converting enzyme, methylene tetrahydrofolate reductase and paraoxonase gene polymorphism and coronary artery disease in an Indian population

Background: Coronary artery disease (CAD) and cancer remain the leading causes of death in most developed countries. Elucidating the genetic components that contribute to their pathogenesis is challenging. In this case-control association study, we examine the association of single nucleotide polymorphisms (SNPs) in paraoxonase 573 A/G genes, methylene tetrahydrofolate reductase (MTHFR) 677 C/T and angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with CAD independently, as well as synergistically, in a north Indian population. Methods and results: Patients with at least 50% stenosis of at least one major coronary artery were classified as cases. The controls had no myocardial infarction. Polymerase chain reactions (PCR) followed by restriction fragment length polymorphism (RFLP) analyses were carried out to determine the SNPs. No significant association of the polymorphisms of the ACE or MTHFR genes with the risk of CAD was observed. However, the allele frequencies of the 573 A/G polymorphism of the paraoxonase gene differed significantly among cases and controls before and after controlling for confounding factors. The frequencies of AG vs AA genotypes and GG+AG vs AA genotypes also differed significantly in the two groups (p = 0.0002). The interaction of paraoxanase with both MTHFR and ACE independently showed significant positive associations Conclusions: The identification of &#8216;at risk&#8217; individuals by genetic mapping of susceptible genes for effective control of other host factors will be a very effective and practical approach for prevention, as well as the development of improved therapy for patients. (Cardiol J 2011; 18, 4: 385&#8211;394

Recent Developments and Characterization Techniques in 3D printing of Corneal Stroma Tissue

Corneal stroma has a significant function in normal visual function. The corneal stroma is vulnerable because of being the thickest part of the cornea, as it can be affected easily by infections or injuries. Any problems on corneal stroma can result in blindness. Donor shortage for corneal transplantation is one of the main issues in corneal transplantation. To address this issue, the corneal tissue engineering focuses on replacing injured tissues and repairing normal functions. Currently, there are no available, engineered corneal tissues for widely accepted routine clinical treatment, but new emerging 3D printing applications are being recognized as a promising option. Recent in vitro researches revealed that the biocompatibility and regeneration possessions of 3D-printed hydrogels outperformed conventional tissue engineering approaches. The goal of this review is to highlight the current developments in the characterization of 3D cell-free and bioprinted hydrogels

Parasitic nematodes exert antimicrobial activity and benefit from microbiota-driven support for host immune regulation

Intestinal parasitic nematodes live in intimate contact with the host microbiota. Changes in the microbiome composition during nematode infection affect immune control of the parasites and shifts in the abundance of bacterial groups have been linked to the immunoregulatory potential of nematodes. Here we asked if the small intestinal parasite Heligmosomoides polygyrus produces factors with antimicrobial activity, senses its microbial environment and if the anti-nematode immune and regulatory responses are altered in mice devoid of gut microbes. We found that H. polygyrus excretory/secretory products exhibited antimicrobial activity against gram(+/-) bacteria. Parasites from germ-free mice displayed alterations in gene expression, comprising factors with putative antimicrobial functions such as chitinase and lysozyme. Infected germ-free mice developed increased small intestinal Th2 responses coinciding with a reduction in local Foxp3(+)RORγt(+) regulatory T cells and decreased parasite fecundity. Our data suggest that nematodes sense their microbial surrounding and have evolved factors that limit the outgrowth of certain microbes. Moreover, the parasites benefit from microbiota-driven immune regulatory circuits, as an increased ratio of intestinal Th2 effector to regulatory T cells coincides with reduced parasite fitness in germ-free mice

Biowaiver monographs for immediate release solid oral dosage forms: prednisolone.

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing prednisolone are reviewed. Data on its solubility, oral absorption, and permeability are not totally conclusive, but strongly suggest a BCS Class 1 classification. Prednisolone's therapeutic indications and therapeutic index, pharmacokinetics, and the possibility of excipient interactions were also taken into consideration. Available evidence indicates that a biowaiver for IR solid oral dosage forms formulated with the excipients tabulated in this article would be unlikely to expose patients to undue risks

Biowaiver monographs for immediate release solid oral dosage forms: acetaminophen (paracetamol).

Literature data are reviewed on the properties of acetaminophen (paracetamol) related to the biopharmaceutics classification system (BCS). According to the current BCS criteria, acetaminophen is BCS Class III compound. Differences in composition seldom, if ever, have an effect on the extent of absorption. However, some studies show differences in rate of absorption between brands and formulations. In particular, sodium bicarbonate, present in some drug products, was reported to give an increase in the rate of absorption, probably caused by an effect on gastric emptying. In view of Marketing Authorizations (MAs) given in a number of countries to acetaminophen drug products with rapid onset of action, it is concluded that differences in rate of absorption were considered therapeutically not relevant by the Health Authorities. Moreover, in view of its therapeutic use, its wide therapeutic index and its uncomplicated pharmacokinetic properties, in vitro dissolution data collected according to the relevant Guidances can be safely used for declaring bioequivalence (BE) of two acetaminophen formulations. Therefore, accepting a biowaiver for immediate release (IR) acetaminophen solid oral drug products is considered scientifically justified, if the test product contains only those excipients reported in this paper in their usual amounts and the test product is rapidly dissolving, as well as the test product fulfils the criterion of similarity of dissolution profiles to the reference product