An Internet survey of risk factors for injury in North American dogs competing in flyball.

A survey was used to investigate injuries in dogs competing in flyball. Complete surveys were obtained from 272 respondents with 589 dogs. In the past year, 23.3% of dogs were injured, with 34.1% injured during their career to date. Common injury sites were paws/digits, back, shoulder, and iliopsoas muscle/groin. Injury in previous years, modified by weight:height ratio, was a significant risk factor for injury. Dogs > 2 y of age had increased risk of injury, as did dogs with best times < 4.0 s. Canadian dogs had increased risk of injury (30.7% injured) compared to United States dogs (20.1% injured). This relationship was modified by participation in other sports, which generally reduced risk of injury in Canadian dogs. Further investigation of risk factors should include differences in training and competition between the United States and Canada, as well as injury prevention strategies.

Un sondage Internet sur les facteurs de risque de blessure chez les chiens nord-américains participant au flyball. Un sondage a été utilisé pour enquêter sur les blessures chez les chiens participant au flyball. Des enquêtes complètes ont été obtenues auprès de 272 répondants avec 589 chiens. Au cours de la dernière année, 23,3 % des chiens ont été blessés, et 34,1 % au cours de leur carrière à ce jour. Les sites de blessure les plus courants étaient les pattes/doigts, le dos, l'épaule et l'aine/muscle psoas iliaque. Les blessures des années précédentes, modifiées par le rapport poids/taille, étaient un facteur de risque important de blessures. Les chiens de plus de 2 ans présentaient un risque accru de blessures, tout comme les chiens avec les meilleurs temps < 4,0 s. Les chiens canadiens présentaient un risque accru de blessures (30,7 % de blessés) par rapport aux chiens américains (20,1 % de blessés). Cette relation était modifiée par la participation à d'autres sports, ce qui réduisait généralement le risque de blessure chez les chiens canadiens. Une enquête plus approfondie sur les facteurs de risque devrait inclure les différences d'entraînement et de compétition entre les États-Unis et le Canada, ainsi que des stratégies de prévention des blessures.(Traduit par Dr Serge Messier).

Ancestral state reconstruction by comparative analysis of a GRN kernel operating in echinoderms.

Diverse sampling of organisms across the five major classes in the phylum Echinodermata is beginning to reveal much about the structure and function of gene regulatory networks (GRNs) in development and evolution. Sea urchins are the most studied clade within this phylum, and recent work suggests there has been dramatic rewiring at the top of the skeletogenic GRN along the lineage leading to extant members of the euechinoid sea urchins. Such rewiring likely accounts for some of the observed developmental differences between the two major subclasses of sea urchins-cidaroids and euechinoids. To address effects of topmost rewiring on downstream GRN events, we cloned four downstream regulatory genes within the skeletogenic GRN and surveyed their spatiotemporal expression patterns in the cidaroid Eucidaris tribuloides. We performed phylogenetic analyses with homologs from other non-vertebrate deuterostomes and characterized their spatiotemporal expression by quantitative polymerase chain reaction (qPCR) and whole-mount in situ hybridization (WMISH). Our data suggest the erg-hex-tgif subcircuit, a putative GRN kernel, exhibits a mesoderm-specific expression pattern early in Eucidaris development that is directly downstream of the initial mesodermal GRN circuitry. Comparative analysis of the expression of this subcircuit in four echinoderm taxa allowed robust ancestral state reconstruction, supporting hypotheses that its ancestral function was to stabilize the mesodermal regulatory state and that it has been co-opted and deployed as a unit in mesodermal subdomains in distantly diverged echinoderms. Importantly, our study supports the notion that GRN kernels exhibit structural and functional modularity, locking down and stabilizing clade-specific, embryonic regulatory states.

Safety and functional outcomes associated with short-term rehabilitation therapy in the post-operative management of tibial plateau leveling osteotomy.

This retrospective cohort study using electronic questionnaires compared the perioperative complication rates of tibial plateau levelling osteotomy (TPLO) surgery and the 8-week, 6-month, and 1-year functional outcomes, between rehabilitation and traditional post-operative management. Dogs were placed into 1 of 2 cohort groups based on attending veterinarian's selected management: i) "traditional" involving restriction to cage rest and leash walking, and ii) "rehabilitation" performed by a certified practitioner. There was no statistically significant difference in complication rates in the perioperative period between the 2 treatment cohorts (P > 0.1). The rehabilitation group was 1.9 times more likely to reach full function at 8 wk (P = 0.045). Conversely, the traditional group was 2.9 times more likely be categorized as having unacceptable function at 8 wk after surgery (P = 0.05). This study suggests that rehabilitation performed by a certified practitioner is safe and may improve short-term outcomes when used in the initial postoperative management for dogs treated with TPLO.

Sécurité et résultats fonctionnels associés à la thérapie de réadaptation à court terme dans la thérapie de la gestion postopératoire de l'ostéotomie de nivellement du plateau tibial. Cette étude rétrospective de cohortes à l'aide de questionnaires a comparé les taux des complications périopératoires de la chirurgie de l'ostéotomie de nivellement du plateau tibial (ONPT) et les résultats fonctionnels à 8 semaines, à 6 mois et à 1 an, entre la réadaptation et la gestion postopératoire traditionnelle. Les chiens ont été placés dans 1 de 2 groupes de cohorte selon la gestion choisie par le vétérinaire traitant : i) la «gestion traditionnelle¼ comportant le repos en cage et la marche en laisse et ii) la «réadaptation¼ effectuée par un praticien certifié. Il n'y avait pas de différence statistique significative pour les taux de complication durant la période périopératoire entre les 2 cohortes de traitement (P > 0,1). Il était 1,9 fois plus probable que le groupe de réadaptation parvienne à une fonction complète à 8 semaines (P = 0,045). Inversement, il était 2,9 fois plus probable que le groupe traditionnel soit classé comme ayant une fonction inacceptable à 8 semaines après la chirurgie (P = 0,05). Cette étude suggère que la réadaptation effectuée par un praticien certifié est sécuritaire et améliore les résultats à court terme lorsqu'elle est utilisée dans la gestion postopératoire des chiens traités à l'aide d'une ONPT.(Traduit par Isabelle Vallières).

Prevalence of dyslipidemia and metabolic syndrome risk factor in overweight and obese children.

OBJECTIVE: To study the prevalence of dyslipidemia and metabolic syndrome risk factors in overweight/ obese children and adolescents. METHODOLOGY: The study included 139 healthy white Argentinean children/adolescents (aged 8-14 years) who were overweight (n = 30) or obese (n = 109), based on BMI z score according to WHO, 2007. Children were referred to the Nutrition Clinic, San Martin University Hospital, Buenos Aires, Argentina for evaluation and treatment. Dyslipidemia was considered when one or more serum lipids (mg/dL) were out of range: total cholesterol ≥ 200, high-density lipoprotein (HDL-C) ≤ 40, triglycerides (TG) > 110, low-density lipoprotein (LDL-C) > 130 or non-HDL-C > 145 and fasting blood glucose (FBG) > 110. Additional metabolic syndrome risk factors included: increased waist circumference (WC, ≥ 90th percentile) and high blood pressure (> 90th percentile). A history of low birth weight (< 2.5 kg) and a family history of: dyslipidemia (FHDL), premature acute myocardial infarction (FHPAMI) and/or type 2 diabetes mellitus (FHT2DM) were also assessed. RESULTS: The prevalence of dyslipidemia among overweight and obese children was 50.4% and its pattern was: hypertriglyceridemia 31.9%, low HDL-C 29.7%, high non-HDL-C 15.8%, hypercholesterolemia 11.9%, and elevated LDL-C 10.7%. The dyslipidemia was more often detected among those with increased WC (55.4%), FHDL (51.1%), and FHT2DM (48%); prevalence was lower in those with FHPAMI (18.7%) and low birth weight (4.3%). Most children presented a variety of metabolic syndrome risk factors; only 25.8% did not have any such alterations identified. BMI z score showed a positive association with TG and negative with HDL-C. Overweight and obesity increased the odds ratios of metabolic syndrome risk factors, hypertriglyceridemia and low HDL-C. CONCLUSIONS: Overweight/obese children were prone to have dyslipidemia and metabolic syndrome. Excess body weight is an important harbinger of health that requires the assessment of multiple parameters to discern further health concerns that may be amenable to specific treatment.

[Guidelines for the prevention, diagnosis and treatment of obesity. Update 2024]. / Guías de práctica clínica para la prevención, el diagnóstico y el tratamiento de la obesidad. Actualización 2024.

This document updates the "Clinical practice guidelines for the prevention, diagnosis and treatment of obesity" issued by the Nutrition Committee of the Argentine Pediatric Society, published in Archivos Argentinos de Pediatría in 2011. Obesity has a multifactorial etiology. It is recommended to diagnose it taking into account anthropometry, personal and family history, and clinical data that indicate complications (sleep apnea, elevated alanine transaminase and/or glycemia, and other components of the metabolic syndrome). It is proposed to know the risks and management of the hospitalized patient with obesity. This document reinforces the role of a healthy lifestyle as the main therapeutic strategy, recognizing the possibility of other treatments with very precise indications (pharmacological and surgical). Considering that obesity is a chronic disease, access to treatment must be guaranteed and patient follow-up must be promoted through the intervention of an interdisciplinary team.

Este documento actualiza las "Guías de práctica clínica para la prevención, el diagnóstico y el tratamiento de la obesidad" realizadas por el Comité de Nutrición de la Sociedad Argentina de Pediatría, publicado en Archivos Argentinos de Pediatría en 2011. La obesidad tiene etiología multifactorial. Se recomienda realizar su diagnóstico considerando antropometría, antecedentes personales y familiares, y datos clínicos que indiquen complicaciones (apnea de sueño, elevación de alanina transaminasa y/o glucemia y otros componentes del síndrome metabólico). En este documento se refuerza el rol del estilo de vida saludable como principal estrategia terapéutica, reconociendo la posibilidad de otros tratamientos con indicaciones muy precisas (farmacológico y quirúrgico). Considerando que la obesidad es una enfermedad crónica, se debe garantizar el acceso al tratamiento y promover el seguimiento de los pacientes mediante la intervención de un equipo interdisciplinario.

Proposed Canadian Consensus Guidelines on Osteoarthritis Treatment Based on OA-COAST Stages 1-4.

The Canadian consensus guidelines on OA treatment were created from a diverse group of experts, with a strong clinical and/or academic background in treating OA in dogs. The document is a summary of the treatment recommendations made by the group, with treatments being divided into either a core or secondary recommendation. Each treatment or modality is then summarized in the context of available research based support and clinical experience, as the treatment of OA continues to be a multimodal and commonly a multidisciplinary as well as individualized approach. The guidelines aim to help clinicians by providing clear and clinically relevant information about treatment options based on COAST defined OA stages 1-4.

Improving employees' views about persons with mental disorders as potential workmates: A 2-year partially controlled study.

For many persons with mental disorders (MDs), having a job is a main life goal and a recovery sign. The possibility for these persons to enter the job market is limited by stigma. This study explored whether the participation of people with MDs in a job-training course would positively influence employees' opinions about workmates with these disorders. The job-training course was run by company trainers in a megastore 3 times over a 2-year period for a total of 18 participants with MDs. In the training store, employees' views regarding persons with MDs were assessed at pre- and postintervention with the use of matched questionnaires. At postintervention, views among the training store's employees were also compared with those of employees from other stores (controls). Compared with paired preintervention assessment, at postintervention, the training store's employees were more optimistic about recovery; more skeptical about unpredictability, dangerousness, and social distance from persons with MDs; more skeptical about difficulties of these persons in that workplace; more willing to have workmates with MDs; and more confident in the acceptance of workers with MDs by colleagues. Compared with controls, at postintervention, the training store's employees had higher levels of acceptance and lower perception of dangerousness and unpredictability, were more confident in the capacities of persons with MDs to acquire organizational skills and in their acceptance by colleagues, and were surer that having coworkers with MDs would improve the company public image. Providing job-training courses to persons with MDs could be helpful to reduce stigma against such persons in ordinary work contexts. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

A Systematic Review of Musculoskeletal Mobilization and Manipulation Techniques Used in Veterinary Medicine.

Mobilization and manipulation techniques are often used in small animal and equine practice; however, questions remain concerning indications, dosing and efficacy. A bibliographic search was performed to identify peer-reviewed publications from 1980 to 2020 that evaluated the clinical effects of musculoskeletal mobilization and manipulation techniques in dogs, cats and horses. The search strategy identified 883 papers for review. Inclusion and exclusion criteria were applied. The clinical indications, dosages, outcome parameters, and reported efficacy within each publication were recorded and categorized for comparison with scientific quality assessed according to a standardized grading system. Fourteen articles were included in this systematic review of which 13 were equine and one was a canine study. Seven of these were cohort studies and seven were randomized controlled clinical trials. The canine study involved carpal immobilization-remobilization and all equine studies focused on the effects of passive mobilization (n = 5) or manipulation (n = 8) of the axial skeleton. Study quality was low (n = 4), moderate (n = 7), and high (n = 3) and included a wide array of outcome parameters with varying levels of efficacy and duration of therapeutic effects, which prevented further meta-analysis. Therefore, it was difficult to draw firm conclusions despite all studies reporting positive effects. Optimal technique indications and dosages need to be determined to improve the standardization of these treatment options.

Acceptability of the Transitional Wearable Companion "+me" in Children With Autism Spectrum Disorder: A Comparative Pilot Study.

+me is an experimental interactive soft toy, looking like a panda, developed for young children. When touched on the paws or head (inputs), the toy can emit attractive responses such as colored lights and amusing sounds (outputs). +me is wirelessly connected to a control tablet through which an adult caregiver can modify its input-output contingencies so as to produce different, rewarding response patterns using the same device. Given these features, we propose +me as a potential novel tool to support the therapy of Autism Spectrum Disorder (ASD). The allure of the device could be exploited to capture the attention and encourage the social interaction of toddlers during play activities with therapists. In this pilot study, +me was tested on two small groups of children aged 30-48 months, one group diagnosed with ASD and the second with Communication Disorder, a condition that often presents-especially at an early age-overlapping symptoms with ASD. The proposed play activities aimed to foster simple imitative behaviors and stimulate the engagement of the children. The results were compared with those of a previous test run on Typically Developed children. Preliminary observations, based on the analysis of video recordings, suggest that, on average, +me is able to encourage a positive engagement and that different groups tend to manifest some different behaviors.

Magnetic chains of Fe3 clusters in the {Fe3YO2} butterfly molecular compound.

The "butterfly" molecule [Fe3Y(µ3-O)2(CCl3COO)8(H2O)(THF)3] (in brief {Fe3YO2}) includes three Fe3+ ions which build a robust Fe3 cluster with a strong intracluster antiferromagnetic exchange and a total spin S = 5/2. It represents the starting magnetic system to study further interactions with magnetic rare earths when Y is replaced with lanthanides. We present heat capacity and equilibrium susceptibility measurements below 2 K, which show that each cluster has a sizeable magnetic anisotropy pointing to the existence of intercluster interactions. However, no phase transition to a long-range magnetically ordered phase is observed down to 20 mK. The intercluster interaction is analysed in the framework of the one-dimensional Blume-Capel model with an antiferromagnetic chain interaction constant J/kB = -40(2) mK between Fe3 cluster spins, and a uniaxial anisotropy with parameter D/kB = -0.56(3) K. This is associated to single chains of Fe3 clusters oriented along the shortest intercluster distances displayed by the crystal structure of {Fe3YO2}. Ac susceptibility measurements reveal that the magnetic relaxation is dominated by a quantum tunnelling process below 0.2 K, and by thermally activated processes above this temperature. The experimental activation energy of this single chain magnet, Ea/kB = 3.4(6) K, can be accounted for by the combination of contributions arising from single-molecule magnetic anisotropy and spin-spin correlations along the chains.

Evolutionary analysis of the cis-regulatory region of the spicule matrix gene SM50 in strongylocentrotid sea urchins.

An evolutionary analysis of transcriptional regulation is essential to understanding the molecular basis of phenotypic diversity. The sea urchin is an ideal system in which to explore the functional consequence of variation in cis-regulatory sequences. We are particularly interested in the evolution of genes involved in the patterning and synthesis of its larval skeleton. This study focuses on the cis-regulatory region of SM50, which has already been characterized to a considerable extent in the purple sea urchin, Strongylocentrotus purpuratus. We have isolated the cis-regulatory region from 15 individuals of S. purpuratus as well as seven closely related species in the family Strongylocentrotidae. We have performed a variety of statistical tests and present evidence that the cis-regulatory elements upstream of the SM50 gene have been subject to positive selection along the lineage leading to S. purpuratus. In addition, we have performed electrophoretic mobility shift assays (EMSAs) and demonstrate that nucleotide substitutions within Element C affect the ability of nuclear proteins to bind to this cis-regulatory element among members of the family Strongylocentrotidae. We speculate that such changes in SM50 and other genes could accumulate to produce altered patterns of gene expression with functional consequences during skeleton formation.

Exploring the sea urchin genome with undergraduates using bioinformatic tools.

It is important to provide undergraduate students with research experiences so that they obtain essential problem-solving skills and come to appreciate the process of science whether or not they pursue graduate study. However, such experiences can be difficult to achieve at a primarily undergraduate institution where time and resources are limited. One strategy is to incorporate research into the laboratory component of courses, with students having input into the specific topic being investigated. In this chapter, we present a series of activities that can be brought together as a semester or year-long project after students select a gene with the potential to be analyzed in a novel species of echinoderm. Students become acquainted with important databases, software programs, and online tools as they clone their gene, confirm its identity through alignment with homologous sequences, and characterize its expression through both qPCR and WMISH. We provide streamlined protocols that allow the work to be accomplished in an efficient manner, and conclude with ideas for assignments that can be completed in parallel to improve students' writing and oral communication skills in preparation for any career.

Acceptability of the Transitional Wearable Companion "+me" in Typical Children: A Pilot Study.

This work presents the results of the first experimentation of +me-the first prototype of Transitional Wearable Companion-run on 15 typically developed (TD) children with ages between 8 and 34 months. +me is an interactive device that looks like a teddy bear that can be worn around the neck, has touch sensors, can emit appealing lights and sounds, and has input-output contingencies that can be regulated with a tablet via Bluetooth. The participants were engaged in social play activities involving both the device and an adult experimenter. +me was designed with the objective of exploiting its intrinsic allure as an attractive toy to stimulate social interactions (e.g., eye contact, turn taking, imitation, social smiles), an aspect potentially helpful in the therapy of Autism Spectrum Disorders (ASD) and other Pervasive Developmental Disorders (PDD). The main purpose of this preliminary study is to evaluate the general acceptability of the toy by TD children, observing the elicited behaviors in preparation for future experiments involving children with ASD and other PDD. First observations, based on video recording and scoring, show that +me stimulates good social engagement in TD children, especially when their age is higher than 24 months.

Action Observation With Dual Task for Improving Cognitive Abilities in Parkinson's Disease: A Pilot Study.

Action observation therapy (AOT) has been recently proposed as a new rehabilitation approach for treatment of motor deficits in Parkinson's disease. To date, this approach has never been used to deal with cognitive deficits (e.g., deficits in working memory, attention), which are impairments that are increasingly recognized in Parkinsonian patients. Typically, patients affected by these dysfunctions have difficulty filtering out irrelevant information and tend to lose track of the task goal. In this paper, we propose that AOT may also be used to improve cognitive abilities of Parkinsonian patients if it is used within a dual task framework. We articulate our hypothesis by pivoting on recent findings and on preliminary results that were obtained through a pilot study that was designed to test the efficacy of a long-term rehabilitation program that, for the first time, uses AOT within a dual task framework for treating cognitive deficits in patients with Parkinson's disease. Ten Parkinson's disease patients underwent a 45-min treatment that consisted in watching a video of an actor performing a daily-life activity and then executing it while performing distractive tasks (AOT with dual task). The treatment was repeated three times per week for a total of 4 weeks. Patients' cognitive/motor features were evaluated through standard tests four times: 1 month before treatment, the first and the last day of treatment and 1 month after treatment. The results show that this approach may provide relevant improvements in cognitive aspects related to working memory (verbal and visuospatial memory) and attention. We discuss these results by pivoting on literature on action observation and recent literature demonstrating that the dual task method can be used to stimulate cognition and concentration. In particular, we propose that using AOT together with a dual task may train the brain systems supporting executive functions through two mechanisms: (i) stimulation of goal setting within the mirror neuron system through action observation and (ii) working memory and persistent goal maintenance through dual task stimuli.

Three-class-resistant human immunodeficiency virus type 1 variant in a drug-naive heterosexual couple.

Combination antiretroviral treatment was initiated in a heterosexual couple newly diagnosed with human immunodeficiency virus type 1 infection. Multiple genotypic drug resistance testing following early rebound of viral load revealed that the same three-class-resistant human immunodeficiency virus type 1 strain had been present in both patients since before initiation of treatment.

Spinal epidural abscess in two calves.

OBJECTIVE: To report clinical signs, diagnostic and surgical or necropsy findings, and outcome in 2 calves with spinal epidural abscess (SEA). STUDY DESIGN: Clinical report. ANIMALS: Calves (n=2). METHODS: Calves had neurologic examination, analysis and antimicrobial culture of cerebrospinal fluid (CSF), vertebral column radiographs, myelography, and in 1 calf, magnetic resonance imaging (MRI). A definitive diagnosis of SEA was confirmed by necropsy in 1 calf and during surgery and histologic examination of vertebral canal tissue in 1 calf. RESULTS: Clinical signs were difficulty in rising, ataxia, fever, apparent spinal pain, hypoesthesia, and paresis/plegia which appeared 15 days before admission. Calf 1 had pelvic limb weakness and difficulty standing and calf 2 had severe ataxia involving both thoracic and pelvic limbs. Extradural spinal cord compression was identified by myelography. SEA suspected in calf 1 with discospondylitis was confirmed at necropsy whereas calf 2 had MRI identification of the lesion and was successfully decompressed by laminectomy and SEA excision. Both calves had peripheral neutrophilia and calf 2 had neutrophilic pleocytosis in CSF. Bacteria were not isolated from CSF, from the surgical site or during necropsy. Calf 2 improved neurologically and had a good long-term outcome. CONCLUSION: Good outcome in a calf with SEA was obtained after adequate surgical decompression and antibiotic administration. CLINICAL RELEVANCE: SEA should be included in the list of possible causes of fever, apparent spinal pain, and signs of myelopathy in calves.

Association between persistent endocrine-disrupting chemicals (PBDEs, OH-PBDEs, PCBs, and PFASs) and biomarkers of inflammation and cellular aging during pregnancy and postpartum.

BACKGROUND: Endocrine-disrupting chemicals (EDCs) can target immune and metabolic pathways. However, few epidemiologic studies have examined the influence of EDCs on measures of inflammation and cellular aging during pregnancy and postpartum. OBJECTIVE: We investigated associations between prenatal exposures to polybrominated diphenyl ethers (PBDEs), hydroxylated PBDE metabolites (OH-PBDEs), polychlorinated biphenyls (PCBs), and per- and polyfluorochemicals (PFASs) with repeated biomarker measurements of inflammation and cellular aging in women during pregnancy and the postpartum period. METHODOLOGY: Overweight or obese pregnant women were recruited from the San Francisco Bay area (n = 103) during their first or second trimester of pregnancy. Blood samples were collected from participants at baseline (median 16 weeks gestation) and at three and nine months postpartum. Serum concentrations of PBDEs, OH-PBDEs, PCBs, and PFASs were measured at baseline. Inflammation biomarkers (interleukin 6 [IL-6], interleukin 10 [IL-10], and tumor necrosis factor [TNF-α]) and leukocyte telomere length (LTL), a biomarker of cellular aging, were measured at all three time points. Associations between serum chemical concentrations and repeated measures of IL-6, IL-10, TNF-α, and LTL were examined using linear mixed models. We also examined the potential for effect modification by time (visit) and obesity. RESULTS: In adjusted models, we observed positive relationships between PBDEs and pro-inflammatory cytokines (IL-6 and TNF-α). A doubling in ∑PBDEs was associated with a 15.26% (95% CI 1.24, 31.22) and 3.74% (95% CI -0.19, 7.82) increase in IL-6 and TNF-α, respectively. Positive associations were also observed for PFASs and IL-6. A two-fold increase in ∑PFASs was associated with a 20.87% (95% CI 3.46, 41.22) increase in IL-6. 5-OHBDE-47 was inversely associated with anti-inflammatory cytokine IL-10. Some EDC-outcome associations, including those of PBDEs with TNF-α, were stronger during pregnancy (compared to three or nine months postpartum) and among obese (compared to overweight) women (p-interaction <0.05). CONCLUSIONS: These findings suggest that exposure to specific EDCs is associated with increased inflammation among women during pregnancy and the postpartum period. Future studies should replicate these findings in additional study populations and examine the implications of these associations for maternal and child health.

Use of peripheral blood DNA for genotype antiretroviral resistance testing in drug-naive HIV-infected subjects.

Parallel analysis of peripheral blood mononuclear cell DNA and plasma RNA from 169 drug-naive human immunodeficiency virus-infected subjects revealed that evaluation of both compartments increases the sensitivity of detection of drug resistance-related mutations, compared with examination of either source alone. Peripheral blood mononuclear cell DNA may play a role in the surveillance of transmitted antiretroviral resistance.

Natural variability in the HR-1 and HR-2 domains of HIV type 1 gp41 from different clades circulating in Italy.

The human immunodeficiency virus type 1 (HIV-1) HR-1 and HR-2 gp41 regions were sequenced in a total of 228 plasma or peripheral blood mononuclear cell samples obtained from an equal number of enfuvirtide-naive subjects for pol genotypic resistance testing in clinical practice. Phylogenetic analysis of the env sequences indicated that 102 belonged to subtype B and 95 to non-B subtypes (31 CRF02_AG, 21 F1, 14 C, 11 A1/A2/A3, 9 CRF01_AE, 9 others) while the remaining 31 were unique recombinant forms. There was considerable variability in the consensus sequence of different clades, particularly in HR-2. The HR-1 amino acid region 36-45, containing all of the enfuvirtide resistance mutations so far characterized, was well conserved except for position 42 where serine and asparagine were unevenly distributed in different subtypes. Enfuvirtide resistance mutations were not present in any sample, reinforcing the expectation that enfuvirtide is effective against many different HIV-1 clades and recombinants. However, some of the mutations outside the amino acid 36-45 region and provisionally suggested to play a role in modulating resistance were detected in a minority of cases. Molecular epidemiological surveys coupled with long-term observation of in vivo response to enfuvirtide and future fusion inhibitors are required to clarify the clinical significance of gp41 natural variability.

Evidence of differential selection of HIV-1 variants carrying drug-resistant mutations in seroconverters.

OBJECTIVES: To estimate the relative efficiency of transmission of different HIV-1 drug-resistance mutations from patients failing treatment, considered as potential transmitters (PTs), to seroconverters (SCs). DESIGN: Ecological cross-sectional study. METHODS: HIV-1 protease and reverse transcriptase (RT) sequence data, obtained from 155 SCs and 2,690 PTs at the Department of Molecular Biology of the University of Siena, Italy, in the period 1997-2004 were used. The efficiency of transmission was studied by odds ratio (OR) analysis and evaluation of 95% confidence intervals (95% CIs). For mutations not detected in viruses from SCs, a binomial probability model was used, assuming P-values <0.05 as indicative of a negative selection at transmission. RESULTS: The overall prevalence of drug mutations associated with nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs) and protease inhibitors (PIs) was 13.2%, 4.6% and 2.0% in SCs, and 69.9%, 27.6% and 33.7% in PTs, respectively. Among RT mutations present both in PTs and SCs, M1841/V and T215F/Y had the lowest relative efficiency of transmission, whereas V1181, Y181C/I and K219E/Q showed the highest relative efficiency. Of the three major protease mutations that could be evaluated by this approach, M46l/L had a lower rate of transmission than 184V and L90M. Among the mutations not detected in viruses from SCs, the RT E44D, V1081, Q151M and Y188C/H/L, and the protease D30N, G48V and V82A/F/S/T substitutions appeared to be negatively selected. CONCLUSIONS: The transmission rate of drug-resistant HIV-1 variants may be differentially affected by the mutational pattern. The binomial model enabled to evaluate the negative selection against specific substitutions. Given the low prevalence of some resistance mutations in SCs, very large data sets are required to evaluate the potential selection of such mutations.