Molecular determinants for cold adaptation in an Antarctic Na+/K+-ATPase.

Enzymes from ectotherms living in chronically cold environments have evolved structural innovations to overcome the effects of temperature on catalysis. Cold adaptation of soluble enzymes is driven by changes within their primary structure or the aqueous milieu. For membrane-embedded enzymes, like the Na+/K+-ATPase, the situation is different because changes to the lipid bilayer in which they operate may also be relevant. Although much attention has been focused on thermal adaptation within lipid bilayers, relatively little is known about the contribution of structural changes within membrane-bound enzymes themselves. The identification of specific mutations that confer temperature compensation is complicated by the presence of neutral mutations, which can be more numerous. In the present study, we identified specific amino acids in a Na+/K+-ATPase from an Antarctic octopus that underlie cold resistance. Our approach was to generate chimeras between an Antarctic clone and a temperate ortholog and then study their temperature sensitivities in Xenopus oocytes using an electrophysiological approach. We identified 12 positions in the Antarctic Na+/K+-ATPase that, when transferred to the temperate ortholog, were sufficient to confer cold tolerance. Furthermore, although all 12 Antarctic mutations were required for the full phenotype, a single leucine in the third transmembrane segment (M3) imparted most of it. Mutations that confer cold resistance are mostly in transmembrane segments, at positions that face the lipid bilayer. We propose that the interface between a transmembrane enzyme and the lipid bilayer is a critical determinant of temperature sensitivity and, accordingly, has been a prime evolutionary target for thermal adaptation.

A Survivorship Educational Tool for Latino Adolescent and Young Adult Cancer Survivors.

BACKGROUND: Low receipt of survivorship care by Latino adolescent and young adult (AYA) cancer survivors necessitates development of age-appropriate and culturally tailored interventions aimed at increasing their perceived need for survivorship care. METHOD: This study describes the development and acceptability testing of a culturally tailored intervention, a photonovela, as part of a community-partnered participatory research (CPPR) project. A four-step approach to the photonovela's development was implemented: (a) literature review, (b) RAND-modified Delphi method, (c) photonovela booklet development, and (d) photonovela acceptability testing through focus groups. Using the CPPR approach, community and academic experts and members worked together at all stages of this project to identify educational domains for the photonovela and ensure that community views and scientific knowledge were equally represented. RESULTS: Cancer survivors and their families described the photonovela as entertaining and relatable. Its story positively reflected their own experiences, and they connected strongly with its characters. Acceptability testing of the photonovela played a significant role in its final script and content, and provided additional new insights into understanding survivorship care perspectives for Latino AYA survivors and their families. CONCLUSION: Equal and shared community and academic involvement through CPPR is essential in identifying unique needs and developing culturally acceptable educational interventions for Latino AYA cancer survivors. The photonovela was seen as an important educational resource in enhancing knowledge and increasing perceived need for survivorship care in this population.

Engaging Latino Adolescent and Young Adult (AYA) Cancer Survivors in Their Care: Piloting a Photonovela Intervention.

Latino adolescent and young adult (AYA) cancer survivors represent a growing population given the changing demographics in the USA. They experience significant healthcare disparities and barriers that warrant age-specific and culturally appropriate interventions to improve their clinical and psychosocial outcomes. This single-arm pilot study evaluated a novel intervention - a photonovela - on its ability to educate Latino AYA survivors and their family members and engage them in survivorship care. Ninety-seven participants (Latino AYA survivors and their family members) were recruited for this study. Three surveys assessing survivorship care confidence, cancer stigma, and survivorship care knowledge were administered to families before they received the photonovela, after the intervention, and at a booster phone call session. Mixed effects models were used to evaluate differences in scores at the three time points while accounting for repeated measures and family clustering. Results show that the photonovela was effective in improving survivorship care confidence and knowledge of Latino AYA survivors and their families. This pilot study indicates that the photonovela has potential to be a useful intervention for improving confidence and knowledge regarding the need to seek survivorship care for Latino AYA cancer survivors.

A Case of Langerhans Cell Histiocytosis With Multifocal, Single-System GI Tract Involvement and Literature Review.

Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder, characterized by the pathologic clonal proliferation and accumulation of immature Langerhans cells within organs. Multiple organ systems can be affected, resulting in a spectrum of clinical manifestations. Isolated gastrointestinal involvement in LCH is rare and usually presents in childhood as a multisystem disease and usually has poor outcomes. We describe a 20-year-old Hispanic female with multifocal, single-system gastrointestinal LCH. Initially diagnosed from a CD1a, S100, and CD207 (Langerin) positive appendix tissue after an appendectomy and confirmed multifocal with an endoscopy. She had a full clinical and endoscopic resolution of disease with cytarabine therapy.

Long-term effects of an intensive-practical diabetes education program on HbA1c and self-care.

OBJECTIVE: The purpose of this study was to implement an intensive and practical diabetes education program (DEP) and evaluate its long-term effects and its impact on psychosocial variables. It was hypothesized that the DEP would improve patients' metabolic control (A1c hemoglobin - HbA1c), technical knowledge, self-efficacy and frequency of self-care and decrease barriers and other parameters such as the body mass index (BMI) and LDL cholesterol. These results should be maintained at one-year follow-up. DESIGN AND SETTING: The sample was composed of 40 patients with diabetes type I who attended a diabetes outpatient clinic. A repeated measures design, considering medical and psychosocial variables at six months and one year, was used. RESULTS: Results have statistical and clinical implications. They revealed significant changes that were maintained at one-year follow-up in HbA1c, barriers to self-care, frequency of self-care, knowledge about the disease and perceived self-efficacy. The areas of self-care where the fewest changes took place were diet and exercise, which are highly related to cardiovascular risk factors and are very present in patients with diabetes. Specifically, no changes were observed in BMI or LDL cholesterol. CONCLUSION: The intensive DEP proved to be effective, although specific efforts should be made in certain areas to ensure longer-lasting benefits. Besides, including not only educational but also psychological strategies in patients' education to motivate them to make real lifestyle changes should be a priority in the design of any DEP.

Nicotinamide inhibits the lysosomal cathepsin b-like protease and kills African trypanosomes.

Nicotinamide, a soluble compound of the vitamin B3 group, has antimicrobial activity against several microorganisms ranging from viruses to parasite protozoans. However, the mode of action of this antimicrobial activity is unknown. Here, we investigate the trypanocidal activity of nicotinamide on Trypanosoma brucei, the causative agent of African trypanosomiasis. Incubation of trypanosomes with nicotinamide causes deleterious defects in endocytic traffic, disruption of the lysosome, failure of cytokinesis, and, ultimately, cell death. At the same concentrations there was no effect on a cultured mammalian cell line. The effects on endocytosis and vesicle traffic were visible within 3 h and can be attributed to inhibition of lysosomal cathepsin b-like protease activity. The inhibitory effect of nicotinamide was confirmed by a direct activity assay of recombinant cathepsin b-like protein. Taken together, these data demonstrate that inhibition of the lysosomal protease cathepsin b-like blocks endocytosis, causing cell death. In addition, these results demonstrate for the first time the inhibitory effect of nicotinamide on a protease.

A novel multiplex method for the simultaneous detection and relative quantitation of pollen allergens.

Standardization of pollen protein extracts is essential in order to ensure efficiency and safety in allergy diagnosis and immunotherapy. In this paper, we have optimized a multiplex Western blotting method for the simultaneous detection of four olive pollen allergens (Ole e 1, Ole e 2, Ole e 5, and Ole e 9) on a single blot using a monoclonal antibody from mouse and three polyclonal antibodies raised in rabbit. We utilized unconjugated Fab antibody fragments for blocking rabbit primary antibodies, and fluorescence-based detection. These changes allowed an accurate and reliable comparative quantitation of these allergens among pollen-protein samples from six olive cultivars. In addition, we also tested the IgE-binding capacity of these pollen extracts by reprobing the same blot with a pool of sera from eight patients allergic to olive and detection with enzyme conjugated antibodies. A noticeable variability regarding allergen content and IgE-reactivity was found among the olive cultivars analyzed. Moreover, we could easily confirm the identity of some of the IgE-binding proteins by simply overlapping both fluorescence and chemiluminescence images. This method is versatile since it can be applied to other allergogenic plant species and extended to other allergens.

Evaluation of a Pharmacist-Led Telephonic Medication Therapy Management Program in Rural Arizona: Implications for Community Health Practice.

This study evaluated a pharmacist-led telephonic Medication Therapy Management (MTM) program for rural patients in Arizona with poor access to healthcare services. A pharmacist provided telephonic MTM services to eligible adult patients living in rural Arizona communities with a diagnosis of diabetes and/or hypertension. Data were collected and summarized descriptively for demographic and health conditions, clinical values, and medication-related problems (MRPs) at the initial consultation, and follow-up data collected at 1 and 3 months. A total of 33 patients had baseline and one-month follow-up data, while 15 patients also had three-month follow-up data. At the initial consultation, the following MRPs were identified: medication adherence issues, dose-related concerns, adverse drug events (ADE), high-risk medications, and therapeutic duplications. Recommendations were made for patients to have the influenza, herpes zoster, and pneumonia vaccines; and to initiate a statin, angiotensin converting enzyme inhibitor, angiotensin receptor blocker, beta-blocker, and/or rescue inhaler. In conclusion, this study demonstrated that while pharmacists can identify and make clinical recommendations to patients, the value of these interventions is not fully realized due to recommendations not being implemented and difficulties with patient follow-up, which may have been due to the COVID-19 pandemic. Additional efforts to address these shortcomings are therefore required.

Health-related and cancer risk concerns among siblings of childhood cancer survivors: a report from the Childhood Cancer Survivor Study (CCSS).

OBJECTIVE: To characterize the prevalence and predictors of concerns regarding future health and cancer risk among siblings of childhood cancer survivors. METHODS: This study reports longitudinal data (baseline and follow-up) from 3969 adult siblings (median age = 29 [range 18-56] years) of long-term survivors of childhood cancer (median time since diagnosis 19.6 [9.6-33.8] years). Self-reported future health and cancer risk concerns (concerned vs not concerned) were assessed. Demographics and health data reported by both the siblings and their matched cancer survivors were examined as risk factors for health concerns using multivariable logistic regression. RESULTS: Percentage of siblings reporting future health and cancer risk concerns, respectively, decreased across decade of survivors' diagnosis: 1970s (73.3%; 63.9%), 1980s (67.2%; 62.6%), and 1990s (45.7%; 52.3%). Risk factors associated with future health concerns included sibling chronic health conditions (grade 2 Odds Ratio [OR]=1.57, 95% CI: 1.12-2.20; grades 3-4 OR=1.86, 95% CI: 1.18-2.94; compared to less than grade 2). Risk factors associated with future cancer concerns included sibling chronic health conditions (grade 2 OR=1.43, 95% CI: 1.05-1.94; grades 3-4 OR=1.64, 95% CI: 1.09-2.47; compared to less than grade 2). CONCLUSIONS: Sibling concerns regarding future health and cancer have diminished in recent decades. There are subgroups of siblings that are at-risk for future health and cancer risk concerns. IMPLICATIONS FOR CANCER SURVIVORS: Routine screening of concerns in at-risk siblings of survivors of childhood cancer may benefit the siblings of cancer survivors. These individuals may benefit from early interventions during diagnosis and treatment of their siblings.

Physiological adaptation of an Antarctic Na+/K+-ATPase to the cold.

Because enzymatic activity is strongly suppressed by the cold, polar poikilotherms face significant adaptive challenges. For example, at 0°C the catalytic activity of a typical enzyme from a temperate organism is reduced by more than 90%. Enzymes embedded in the plasma membrane, such as the Na(+)/K(+)-ATPase, may be even more susceptible to the cold because of thermal effects on the lipid bilayer. Accordingly, adaptive changes in response to the cold may include adjustments to the enzyme or the surrounding lipid environment, or synergistic changes to both. To assess the contribution of the enzyme itself, we cloned orthologous Na(+)/K(+)-ATPase α-subunits from an Antarctic (Pareledone sp.; -1.8°C) and a temperate octopus (Octopus bimaculatus; ∼18°C), and compared their turnover rates and temperature sensitivities in a heterologous expression system. The primary sequences of the two pumps were found to be highly similar (97% identity), with most differences being conservative changes involving hydrophobic residues. The physiology of the pumps was studied using an electrophysiological approach in intact Xenopus oocytes. The voltage dependence of the pumps was equivalent. However, at room temperature the maximum turnover rate of the Antarctic pump was found to be 25% higher than that of the temperate pump. In addition, the Antarctic pump exhibited a lower temperature sensitivity, leading to significantly higher relative activity at lower temperatures. Orthologous Na(+)/K(+) pumps were then isolated from two tropical and two Arctic octopus. The temperature sensitivities of these pumps closely matched those of the temperate and Antarctic pumps, respectively. Thus, reduced thermal sensitivity appears to be a common mechanism driving cold adaptation in the Na(+)/K(+)-ATPase.

Improving Cancer Survivorship Care for Latino Adolescent, Young Adult Survivors through Community-Partnered Participatory Research.

Background: Minority adolescent and young adult (AYA) cancer survivors experience disparities in receipt of survivorship care. Objective: This study describes the infrastructure of a community-partnered participatory research (CPPR) project between a community-based organization and a National Cancer Institute (NCI)-designated cancer center to develop culturally-tailored interventions to improve Latino AYA cancer survivor knowledge regarding their need for survivorship care. Methods: Research team participants included the community organization and NCI cancer center directors, a research coordinator, a community liaison, and cross-training program interns. Through use of Jones's theoretical framework, additional stakeholders from academic and community settings were identified and invited to participate in the research team. A process evaluation and qualitative interviews were conducted to assess equal partnership between community and academic stakeholders and determine if the infrastructure followed the five core principles of CPPR. A grounded theory approach was used to analyze qualitative data. Conclusions: CPPR between an NCI-designated cancer center and a community-based organization is a new research model for conducting minority AYA cancer survivor outreach. Open communication was critical in engaging the Latino community to discuss their survivorship needs. Community stakeholders were key to infrastructure success through fostering a cohesive partnership with and acting as the voice of the Latino community. Implementing a cross-training program promoted continued engagement of community members with academic partners. Proper infrastructure development is critical to building successful research partnerships in order to develop culturally-tailored interventions to improve survivorship care knowledge.

Expression of ion transport proteins and routine metabolism in juveniles of tropical gar (Atractosteus tropicus) exposed to ammonia.

Tropical gar (Atractosteus tropicus) thrives in aquatic habitats with high levels of total nitrogen (TAN) and unionized ammonia (NH3). However, the tolerance of TAN and NH3, the excretion mechanisms involved, and the effects of these chemicals on routine metabolism are still unknown. Therefore, our objectives were to assess the acute toxicity of TAN and NH3 in A. tropicus juveniles after a 96-h exposure (LC50-96 h) to NH4Cl and after chronic exposure to two concentrations (15% and 30% of LC50-96 h TAN) for 12 days, as well as to evaluate the transcriptional effects associated with Rhesus proteins (rhag, rhbg, rhcg) and ion transporters (NHE, NKA, NKCC, and CFTR) in gills and skin; and to determine the effects of TAN and NH3 on routine metabolism through oxygen consumption (µM g-1 h-1) and gill ventilation frequency (beats min-1). LC50-96 h values were 100.20 ± 11.21 mg/L for TAN and 3.756 ± 0.259 mg/L for NH3. The genes encoding Rhesus proteins and ion transporters in gills and skin showed a differential expression according to TAN concentrations and exposure time. Oxygen consumption on day 12 showed significant differences between treatments with 15% and 30% TAN. Gill ventilation frequency on day 12 was higher in fish exposed to 30% TAN. In conclusion, A. tropicus juveniles are highly tolerant to TAN, showing upregulation of the genes involved in TAN excretion through gills and skin, which affects routine oxygen consumption and energetic cost. These findings are relevant for understanding adaptations in the physiological response of a tropical ancestral air-breathing fish.

HIV prevalence and correlates of receptive needle sharing among injection drug users in the Mexican-U.s. border city of Tijuana.

Injection drug use is a growing but understudied problem in Tijuana, a city situated on the northwestern Mexico-U.S border. The authors studied factors associated with receptive needle sharing in an effort to inform prevention activities. In 2003, street-recruited injection drug users (IDUs) in Tijuana underwent interviews on injection risk behaviors and rapid HIV antibody tests. Logistic regression was used to identify correlates of receptive needle sharing at the last injection episode. Of 402 IDUs, 87.6% were male; the median age was 34. HIV prevalence was 4.01% (95% CI: 2.29-6.51). One third reported receptive needle sharing at last injection. Factors independently associated with receptive needle sharing were years living in Tijuana (Adjusted Odds Ratio [AdjOR]= 0.97 per year, 95% CI: 0.96-0.99), being bisexual/homosexual (AdjOR=2.12; 95% CI: 1.30 - 3.44), unemployed (AdjOR=2.5; 95% CI: 1.52-4.10), never having an HIV test (AOR: 4.02; 95% CI: 2.44-6.60), having friends who placed importance on avoiding HIV (AdjOR: 0.36; 95% CI: 0.19-0.68) and last injecting in a shooting gallery (AdjOR=1.98; 95% CI: 1.21-3.24). These results underscore the need to increase access to voluntary HIV testing and counseling to IDUs and migrants in Tijuana, as well as expand access to sterile syringes in an effort to avert widespread HIV transmission.

Aislamiento e identificación de microorganismos potencialmente amilolíticos y celulolíticos de suelos de humedales de Bogotá / Isolation and identification of potential amylolytic and cellulolytic microorganisms from soil of Bogota wetlands

RESUMEN Las amilasas y celulasas de origen microbiano se han utilizado desde hace más de tres décadas en la industria. El aislamiento de microorganismos nativos con capacidad amilolítica y celulolítica es el punto de partida para aprovechar la biodiversidad microbiana en la producción de amilasas y celulasas con características específicas que permitan obtener nuevos productos y optimizar procesos industriales donde estas sean aplicables. El objetivo de este trabajo fue aislar, a partir de suelo de cinco humedales en Bogotá, cepas microbianas productoras de enzimas amilolíticas y celulolíticas. Se realizó la medición de halos de hidrólisis en agar almidón y agar carboximetilcelulosa. Se evaluó la actividad enzimática por medio de la producción de azúcares reductores, determinados mediante la técnica del ácido 3,5 dinitrosalicílico. Se seleccionaron cuatro aislamientos amilolíticos diferentes, todos identificados como Bacillus amyloliquefaciens, con actividades entre 480±35 y 752±33 U/mL a 60°C. Cinco aislamientos celulolíticos diferentes fueron seleccionado, dos identificados como Bacillus amyloliquefaciens, dos como Yersinia massiliensis y uno como Stenotrophomonas nitritireducens, con actividades enzimáticas entre 13.82 ± 2.5 y 19.11 ± 2.3 U/mL a 50°C. Estos resultados demuestran que dentro de la biodiversidad de los suelos de humedales de Bogotá existen microrganismos productores de amilasas y celulasas que podrían ser aplicadas en procesos industriales.

ABSTRACT The amylases and cellulases obtained from microorganisms have been used since more than three decades in industry. The isolation of native microbial strains with amylolytic and cellulolytic ability is the starting point to make the best of microbial biodiversity and support the production of amylases and cellulases with novel characteristics to obtain new products and optimize industrial processes where these enzymes can be applied. The objective of this work was to isolate microbial strains with the capacity to produce amylolytic and cellulolytic enzymes from the soil of five wetlands in Bogotá. Hydrolysis halos measurements in starch agar and carboxymethylcellulose agar were performed. The enzymatic activity was determined through the production of reducing sugars which were determined by 3,5-dinitrosalicylic acid method. Four different amylolytic isolations were selected and all of them were identified as Bacillus amyloliquefaciens. The amylolytic activity was between 480 ± 35 and 752±33 U/mL at 60°C. Five different cellulolytic strains were selected and two of them were identified as Bacillus amyloliquefaciens, two as Yersinia massiliensis and one as Stenotrophomonas nitritireducens. Their cellulolytic activities were from 13.82 ± 2.51 to 19.11 ± 2.3 U/mL at 50°C. These results demonstrate that as a part of the Bogota wetlands soil biodiversity there are microorganisms producing amylases and cellulases which might be applied in industrial processes.

Differential expression and sequence polymorphism of the olive pollen allergen Ole e 1 in two Iranian cultivars.

Molecular evidence on the heterogeneity present in the Ole e 1 allergen of the olive pollen is emerging. Such polymorphism is dependent on the cultivar origin of pollen, which also determines wide differences in the expression of this protein. Determination of biochemical and molecular characteristics of Ole e 1 pollen allergen in two Iranian olive cultivars, namely 'Rowghani' and 'Zard' is necessary to assess their allergenicity potential. SDS-PAGE and immunoblotting analysis of pollen extracts showed that both cultivars present high and low expression of Ole e 1, respectively. These protein levels correlated with similarly different levels of transcripts, as determined by RT-PCR. Two-dimensional protein profiles also showed conspicuous differences in the distribution and the level of expression of those spots reacting to an anti-Ole e 1 antibody. Bioinformatic analysis of four Ole e 1 sequences corresponding to 'Rowghani' and two sequences for 'Zard', showed numerous heterogeneities when compared with those Ole e 1 and Ole e 1-like sequences present in databases. Nucleotide substitutions resulted in many cases in changes over the predicted amino acid sequences. A cladistic analysis of the sequences showed Iranian entries in a central position between West-European sequences, and Ole e 1-like sequences from other Oleaceae species. Moreover, amino acid changes affected key epitopes of the protein involved in the recognition of the protein by the human immune system. Putative implications of polymorphism in both the biological role and the allergic reactivity of Ole e 1 are discussed.

Short communication: HIV incidence among vulnerable populations in Honduras: results from an integrated behavioral and biological survey among female sex workers, men who have sex with men, and Garifuna in Honduras, 2006.

Honduras has one of the highest HIV prevalence rates in Central America. Data on HIV incidence are needed to identify groups at greatest need of prevention interventions to inform the national HIV response. We applied a test for recent infection to HIV-positive specimens from a biological and behavioral survey to estimate assay-derived incidence among men who have sex with men (MSM), female sex workers (FSW), and the Garifuna population in Honduras. Assay-derived estimates were compared to the mathematically modeled estimates in the same populations to assess plausibility of the assay-based estimates. Assay-derived incidence was 1.1% (95% CI 0.2-2.0) among MSM, 0.4% (95% CI 0.1-0.8) among the Garifuna, and 0% (95% CI 0-0.01) among FSWs. The modeled incidence estimates were similar at 1.03% among MSM, 0.30% among the Garifuna, and 0.23% among FSWs. HIV incidence based on the assay was highest among MSM in Honduras, lowest among FSWs, and similar to modeled incidence in these groups. Targeted programs on HIV prevention, care, and treatment are urgently needed for the MSM population. Continued support for existing prevention programs for FSWs and Garifuna are recommended.

Characterization of profilin polymorphism in pollen with a focus on multifunctionality.

Profilin, a multigene family involved in actin dynamics, is a multiple partners-interacting protein, as regard of the presence of at least of three binding domains encompassing actin, phosphoinositide lipids, and poly-L-proline interacting patches. In addition, pollen profilins are important allergens in several species like Olea europaea L. (Ole e 2), Betula pendula (Bet v 2), Phleum pratense (Phl p 12), Zea mays (Zea m 12) and Corylus avellana (Cor a 2). In spite of the biological and clinical importance of these molecules, variability in pollen profilin sequences has been poorly pointed out up until now. In this work, a relatively high number of pollen profilin sequences have been cloned, with the aim of carrying out an extensive characterization of their polymorphism among 24 olive cultivars and the above mentioned plant species. Our results indicate a high level of variability in the sequences analyzed. Quantitative intra-specific/varietal polymorphism was higher in comparison to inter-specific/cultivars comparisons. Multi-optional posttranslational modifications, e.g. phosphorylation sites, physicochemical properties, and partners-interacting functional residues have been shown to be affected by profilin polymorphism. As a result of this variability, profilins yielded a clear taxonomic separation between the five plant species. Profilin family multifunctionality might be inferred by natural variation through profilin isovariants generated among olive germplasm, as a result of polymorphism. The high variability might result in both differential profilin properties and differences in the regulation of the interaction with natural partners, affecting the mechanisms underlying the transmission of signals throughout signaling pathways in response to different stress environments. Moreover, elucidating the effect of profilin polymorphism in adaptive responses like actin dynamics, and cellular behavior, represents an exciting research goal for the future.

[Pentosidine: a new biomarker in diabetes mellitus complications]. / Pentosidina: un nuevo biomarcador de las complicaciones en la diabetes mellitus.

Diabetes mellitus causes an increase of morbidity and mortality. Advanced glycosilation end products (AGE) are formed by non-enzymatic glycation between proteins and reducing sugars as glucose. Oxidative reactions (glycoxidations) are essential for the formation of some AGE, for example pentosidine. Increased concentrations of pentosidine can be found in pathological conditions associated with hyperglycaemia and also related to increased oxidative stress. In individuals with diabetes mellitus, pentosidine formation and accumulation is developed at an accelerated rate in cells without insulin control for glucose uptake. Pentosidine has a pivotal role in diabetic complications, probably as a consequence of the diverse properties of this compound, which alters the structure and function of molecules in biological systems. The following review discusses the alterations in the concentration of pentosidine in the body, particularly in relation to changes occurring in diabetes and its complications such as vascular and bone disease, nephropathy, neuropathy and retinopathy. Novel therapeutic approaches which can prevent or ameliorate the toxic effects of AGE in the initiation and progression of diabetic complications are reviewed.

Transmitted drug resistance and type of infection in newly diagnosed HIV-1 individuals in Honduras.

BACKGROUND: Transmitted drug resistance (TDR) reduces the efficacy of antiretroviral treatment and is a public health concern. OBJECTIVES: To gain insight in the epidemiology of TDR in Honduras by evaluating the amount of TDR in a representative sample of newly diagnosed individuals and by determining whether these are recent or established infections. STUDY DESIGN: Two hundred treatment-naïve, newly diagnosed HIV-positive individuals representing different population groups (general population, Garifunas ethnic group, female sex workers and men who have sex with men) and different geographic regions were enrolled during April 2004-April 2007. The HIV-1 pol gene was sequenced to identify drug-resistant mutations and TDR was scored as recommended by the WHO. Specimens were classified as recent or established infections using the BED assay. RESULTS: Among 200 samples analyzed from Honduran patients the prevalence of TDR was 7% (95% CI: 3.9-11.5%), 5% for non-nucleoside reverse transcriptase inhibitors (NNRTIs), 3% for nucleoside reverse transcriptase inhibitors (NRTIs) and 0.5% for protease inhibitors (PIs). Testing of these samples with the BED assay revealed that 12% of the specimens were associated with recent infections. TDR was significantly more common in specimens with recent infection (21%) than established infection (5%) (p=0.016). CONCLUSIONS: The prevalence of TDR in Honduras was moderate (7%). The percentage of specimens who were recently infected was low (12%), suggesting that late HIV diagnosis is common. The TDR prevalence was higher in recent than in established infections, which may indicate that TDR is increasing over time. The higher prevalence of NNRTI and NRTI mutations as compared to PI mutations is probably due to a broader and longer use of these drugs in Honduras.