Comprehensive Linkage and Association Analyses Identify Haplotype, Near to the TNFSF15 Gene, Significantly Associated with Spondyloarthritis

Spondyloarthritis (SpA) is a chronic inflammatory disorder with a strong genetic predisposition dominated by the role of HLA-B27. However, the contribution of other genes to the disease susceptibility has been clearly demonstrated. We previously reported significant evidence of linkage of SpA to chromosome 9q31–34. The current study aimed to characterize this locus, named SPA2. First, we performed a fine linkage mapping of SPA2 (24 cM) with 28 microsatellite markers in 149 multiplex families, which allowed us to reduce the area of investigation to an 18 cM (13 Mb) locus delimited by the markers D9S279 and D9S112. Second, we constructed a linkage disequilibrium (LD) map of this region with 1,536 tag single-nucleotide polymorphisms (SNPs) in 136 families (263 patients). The association was assessed using a transmission disequilibrium test. One tag SNP, rs4979459, yielded a significant P-value (4.9×10⁻⁵). Third, we performed an extension association study with rs4979459 and 30 surrounding SNPs in LD with it, in 287 families (668 patients), and in a sample of 139 cases and 163 controls. Strong association was observed in both familial and case/control datasets for several SNPs. In the replication study, carried with 8 SNPs in an independent sample of 232 cases and 149 controls, one SNP, rs6478105, yielded a nominal P-value<3×10⁻². Pooled case/control study (371 cases and 312 controls) as well as combined analysis of extension and replication data showed very significant association (P<5×10⁻⁴) for 6 of the 8 latter markers (rs7849556, rs10817669, rs10759734, rs6478105, rs10982396, and rs10733612). Finally, haplotype association investigations identified a strongly associated haplotype (P<8.8×10⁻⁵) consisting of these 6 SNPs and located in the direct vicinity of the TNFSF15 gene. In conclusion, we have identified within the SPA2 locus a haplotype strongly associated with predisposition to SpA which is located near to TNFSF15, one of the major candidate genes in this region.     

An Approach to the Stepwise Management of Severe Mitral Regurgitation with Optimal Cardiac Pacemaker Function

Right ventricular apical pacing may cause or worsen mitral regurgitation (MR). Potential mechanisms for this adverse sequelae include intraventricular dyssynchrony, altered papillary muscle function, pacing-induced cardiomyopathy with left ventricular dilation, and annular dilation. In contrast, biventricular (BiV) pacing may improve MR presumably by opposing the negative effects. Whether or not left ventricular lead location is important in treating mitral regurgitation in patients with pacemakers is unknown.We report a case of severe MR and left ventricular (LV) systolic failure in a patient with right ventricular pacing. Multiple potential etiologies for the worsening valve function were noted, and a stepwise iterative optimizing scheme that included basal lateral LV pacing improved mitral valve function and ameliorated heart failure symptoms.     

Exploring Differences in the Content of Job Interviews between Youth with and without a Physical Disability

Objective

Although people with disabilities have great potential to provide advantages to work environments, many encounter barriers in finding employment, especially youth who are looking for their first job. A job interview is an essential component of obtaining employment. The objective of this study is to explore the content of the answers given in job interviews among youth with disabilities compared to typically developing youth.

Methods

A purposive sample of 31 youth (16 with typical development and 15 with disability) completed a mock job interview as part of an employment readiness study. The interview questions focused on skills and experiences, areas for improvement, and actions taken during problem-based scenarios. Transcribed interviews were analyzed using a content analysis of themes that emerged from the interviews.

Results

We found several similarities and differences between youth with disabilities and typically developing youth. Similarities included giving examples from school, emphasizing their “soft skills” (i.e., people and communication skills) and giving examples of relevant experience for the position. Both groups of youth gave similar examples for something they were proud of but fewer youth with disabilities provided examples. Differences in the content of job interview answers between the two groups included youth with disabilities: (1) disclosing their condition; (2) giving fewer examples related to customer service and teamwork skills; (3) experiencing greater challenges in providing feedback to team members and responding to scenario-based problem solving questions; and (4) drawing on examples from past work, volunteer and extra curricular activities.

Conclusions

Clinicians and educators should help youth to understand what their marketable skills are and how to highlight them in an interview. Employers need to understand that the experiences of youth with disabilities may be different than typically developing youth. Our findings also help to inform employment readiness programs by highlighting the areas where youth with disabilities may need extra help as compared to typically developing youth.     

A Comprehensive Approach to Identify Reliable Reference Gene Candidates to Investigate the Link between Alcoholism and Endocrinology in Sprague-Dawley Rats

Gender and hormonal differences are often correlated with alcohol dependence and related complications like addiction and breast cancer. Estrogen (E2) is an important sex hormone because it serves as a key protein involved in organism level signaling pathways. Alcoholism has been reported to affect estrogen receptor signaling; however, identifying the players involved in such multi-faceted syndrome is complex and requires an interdisciplinary approach. In many situations, preliminary investigations included a straight forward, yet informative biotechniques such as gene expression analyses using quantitative real time PCR (qRT-PCR). The validity of qRT-PCR-based conclusions is affected by the choice of reliable internal controls. With this in mind, we compiled a list of 15 commonly used housekeeping genes (HKGs) as potential reference gene candidates in rat biological models. A comprehensive comparison among 5 statistical approaches (geNorm, dCt method, NormFinder, BestKeeper, and RefFinder) was performed to identify the minimal number as well the most stable reference genes required for reliable normalization in experimental rat groups that comprised sham operated (SO), ovariectomized rats in the absence (OVX) or presence of E2 (OVXE2). These rat groups were subdivided into subgroups that received alcohol in liquid diet or isocalroic control liquid diet for 12 weeks. Our results showed that U87, 5S rRNA, GAPDH, and U5a were the most reliable gene candidates for reference genes in heart and brain tissue. However, different gene stability ranking was specific for each tissue input combination. The present preliminary findings highlight the variability in reference gene rankings across different experimental conditions and analytic methods and constitute a fundamental step for gene expression assays.     

Community Landscapes: An Integrative Approach to Determine Overlapping Network Module Hierarchy,Identify Key Nodes and Predict Network Dynamics

Background

Network communities help the functional organization and evolution of complex networks. However, the development of a method, which is both fast and accurate, provides modular overlaps and partitions of a heterogeneous network, has proven to be rather difficult.

Methodology/Principal Findings

Here we introduce the novel concept of ModuLand, an integrative method family determining overlapping network modules as hills of an influence function-based, centrality-type community landscape, and including several widely used modularization methods as special cases. As various adaptations of the method family, we developed several algorithms, which provide an efficient analysis of weighted and directed networks, and (1) determine pervasively overlapping modules with high resolution; (2) uncover a detailed hierarchical network structure allowing an efficient, zoom-in analysis of large networks; (3) allow the determination of key network nodes and (4) help to predict network dynamics.

Conclusions/Significance

The concept opens a wide range of possibilities to develop new approaches and applications including network routing, classification, comparison and prediction.     

Sex Differences in the Association of Adiponectin and Low-Grade Inflammation With Changes in the Body Mass Index From Youth to Middle Age

BackgroundThere are sex differences in low-grade inflammation markers in obesity-related disorders. Little is known, however, about a possible sex-specific association of relative weight change from youth to adulthood with actual low-grade inflammation.ObjectiveThe aim of this study was to identify possible sex differences in adiponectin, interleukin-1β (IL-1β), interleukin-1Ra (IL-1Ra), and high-sensitivity C-reactive protein (hs-CRP) levels with respect to the relative change in body mass index (BMI) from youth to middle age.MethodsThe study population consisted of 403 men and 500 women from 1 Finnish town. Weight, height, and adiponectin, IL-1β, IL-1Ra, and hs-CRP levels were measured in 2003 at a mean age of 46 years. Self-reported weight at the age of 20 years was recorded.ResultsIn women, even after adjustment for BMI in adulthood, a statistically significantly negative linear association was observed between the quartiles of relative change in BMI and adiponectin levels (P < 0.001 for linearity). Significantly positive linear associations were also observed between the change in BMI and IL-1Ra (P = 0.032 for linearity) and hs-CRP (P = 0.029 for linearity) levels. In men, there was no statistically significant association among the quartiles of relative change in BMI and measured inflammatory markers after adjustment for BMI in adulthood.ConclusionsA relative increase in weight may be more harmful in women than in men with respect to adiponectin and inflammatory markers.     

An Automated Approach to Examining Conversational Dynamics between People with Dementia and Their Carers

The progressive neuropathology involved in dementia frequently causes a gradual decline in communication skills. Communication partners who are unaware of the specific communication problems faced by people with dementia (PWD) can inadvertently challenge their conversation partner, leading to distress and a reduced flow of information between speakers. Previous research has produced an extensive literature base recommending strategies to facilitate conversational engagement in dementia. However, empirical evidence for the beneficial effects of these strategies on conversational dynamics is sparse. This study uses a time-efficient computational discourse analysis tool called Discursis to examine the link between specific communication behaviours and content-based conversational engagement in 20 conversations between PWD living in residential aged-care facilities and care staff members. Conversations analysed here were baseline conversations recorded before staff members underwent communication training. Care staff members spontaneously exhibited a wide range of facilitative and non-facilitative communication behaviours, which were coded for analysis of conversation dynamics within these baseline conversations. A hybrid approach combining manual coding and automated Discursis metric analysis provides two sets of novel insights. Firstly, this study revealed nine communication behaviours that, if used by the care staff member in a given turn, significantly increased the appearance of subsequent content-based engagement in the conversation by PWD. Secondly, the current findings reveal alignment between human- and computer-generated labelling of communication behaviour for 8 out of the total 22 behaviours under investigation. The approach demonstrated in this study provides an empirical procedure for the detailed evaluation of content-based conversational engagement associated with specific communication behaviours.     

Quality of Life and Health Perceptions Among Fish-Eating Communities of the Brazilian Amazon: An Ecosystem Approach to Well-Being

Mercury (Hg) contamination in the Brazilian Amazon constitutes a serious environmental and public health issue. This study is part of the CARUSO Project, which uses an ecosystem approach to human health to examine the sources, transmission, and effects of Hg in the Brazilian Amazon, with a view to developing preventive intervention strategy. To date, studies have focused on measures of Hg exposure through fish consumption in relation to health effects; little attention has been given to quality of life (QoL). The objective of this study was to examine the relations between QoL and health perceptions, Hg exposure, sociodemographics, living conditions, and lifestyle in communities along the Tapajós River. A total of 456 adults from 13 villages were interviewed and provided hair samples for Hg analysis. Results showed that perceptions of QoL and health are relatively positive, despite elevated Hg exposure. Logistic regression analyses showed that a positive perception of QoL was associated with the absence of chronic illnesses, not smoking, fruit consumption, residing on the banks of the Tapajós, and living in an in-migrants’ community. The positive perception of health was associated with younger age, the absence of reported symptoms of chronic illnesses, and drinking alcoholic beverages. Cluster analysis revealed that the group that reported the highest QoL had a traditional lifestyle, involving daily fishing and high fish consumption. However, this traditional lifestyle is associated with elevated Hg levels and early reported symptoms potentially linked to Hg exposure. These findings underline the importance of understanding the factors underlying QoL to develop adequate strategies to reduce Hg exposure and promote well-being.     

Modelling the relationship between antibody-dependent enhancement and immunological distance with application to dengue

When antibodies raised in response to a particular pathogen bind with immunologically similar pathogens it may facilitate infection through a phenomenon known as antibody-dependent enhancement (ADE). This process occurs between the four serotypes of dengue virus and, furthermore, secondary infection is a major risk factor in dengue hemorrhagic fever (DHF). Theory has suggested that ADE may be responsible for the large immunological distance between dengue serotypes. We investigate this hypothesis using an epidemic model for dengue in which immunological distance and the strength of immune cross-reaction are expressed separately. Cross-enhancement is considered in three alternative forms acting on susceptibility, transmission and mortality. Previous models have shown that transmission and mortality enhancement can lead to periodicity or chaos. We confirm this result for reasonable levels of susceptibility and transmission enhancement but not for mortality enhancement. We also show that when the two strains have identical basic reproductive numbers no form of enhancement leads to competitive exclusion. When the two strains have different basic reproductive numbers susceptibility or transmission enhancement allow strains with greater immunological similarity to stably coexist but mortality enhancement forces strains to be more distinct. All three forms of enhancement can be associated with DHF and we conclude that mortality enhancement must be dominant if ADE really is responsible for the immunological distance between dengue serotypes.     

An Integrative Approach to the Study of Filamentous Oligomeric Assemblies,with Application to RecA

Oligomeric macromolecules in the cell self-organize into a wide variety of geometrical motifs such as helices, rings or linear filaments. The recombinase proteins involved in homologous recombination present many such assembly motifs. Here, we examine in particular the polymorphic characteristics of RecA, the most studied member of the recombinase family, using an integrative approach that relates local modes of monomer/monomer association to the global architecture of their screw-type organization. In our approach, local modes of association are sampled via docking or Monte Carlo simulations. This enables shedding new light on fiber morphologies that may be adopted by the RecA protein. Two distinct RecA helical morphologies, the so-called “extended” and “compressed” forms, are known to play a role in homologous recombination. We investigate the variability within each form in terms of helical parameters and steric accessibility. We also address possible helical discontinuities in RecA filaments due to multiple monomer-monomer association modes. By relating local interface organization to global filament morphology, the strategies developed here to study RecA self-assembly are particularly well suited to other DNA-binding proteins and to filamentous protein assemblies in general.     

Optimal Cut-Off Points on the Health Anxiety Inventory,Illness Attitude Scales and Whiteley Index to Identify Severe Health Anxiety

Background

Health anxiety can be viewed as a dimensional phenomenon where severe health anxiety in form of DSM-IV hypochondriasis represents a cut-off where the health anxiety becomes clinically significant. Three of the most reliable and used self-report measures of health anxiety are the Health Anxiety Inventory (HAI), the Illness Attitude Scales (IAS) and the Whiteley Index (WI). Identifying the optimal cut-offs for classification of presence of a diagnosis of severe health anxiety on these measures has several advantages in clinical and research settings. The aim of this study was therefore to investigate the HAI, IAS and WI as proximal diagnostic instruments for severe health anxiety defined as DSM-IV hypochondriasis.

Methods

We investigated sensitivity, specificity and predictive value on the HAI, IAS and WI using a total of 347 adult participants of whom 158 had a diagnosis of severe health anxiety, 97 had obsessive-compulsive disorder and 92 were healthy non-clinical controls. Diagnostic assessments were conducted using the Anxiety Disorder Interview Schedule.

Results

Optimal cut-offs for identifying a diagnosis of severe health anxiety was 67 on the HAI, 47 on the IAS, and 5 on the WI. Sensitivity and specificity were high, ranging from 92.6 to 99.4%. Positive and negative predictive values ranged from 91.6 to 99.4% using unadjusted prevalence rates.

Conclusions

The HAI, IAS and WI have very good properties as diagnostic indicators of severe health anxiety and can be used as cost-efficient proximal estimates of the diagnosis.     

Caprylic Triglyceride as a Novel Therapeutic Approach to Effectively Improve the Performance and Attenuate the Symptoms Due to the Motor Neuron Loss in ALS Disease

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and finally death. ALS patients suffer from asthenia and their progressive weakness negatively impacts quality of life, limiting their daily activities. They have impaired energy balance linked to lower activity of mitochondrial electron transport chain enzymes in ALS spinal cord, suggesting that improving mitochondrial function may present a therapeutic approach for ALS. When fed a ketogenic diet, the G93A ALS mouse shows a significant increase in serum ketones as well as a significantly slower progression of weakness and lower mortality rate. In this study, we treated SOD1-G93A mice with caprylic triglyceride, a medium chain triglyceride that is metabolized into ketone bodies and can serve as an alternate energy substrate for neuronal metabolism. Treatment with caprylic triglyceride attenuated progression of weakness and protected spinal cord motor neuron loss in SOD1-G93A transgenic animals, significantly improving their performance even though there was no significant benefit regarding the survival of the ALS transgenic animals. We found that caprylic triglyceride significantly promoted the mitochondrial oxygen consumption rate in vivo. Our results demonstrated that caprylic triglyceride alleviates ALS-type motor impairment through restoration of energy metabolism in SOD1-G93A ALS mice, especially during the overt stage of the disease. These data indicate the feasibility of using caprylic acid as an easily administered treatment with a high impact on the quality of life of ALS patients.     

Sexual Differences in the Behavioral Response of Túngara Frogs, Physalaemus pustulosus, to Cues Associated with Increased Predation Risk

Engaging in mating behaviors usually increases exposure to predators for both males and females. Anti‐predator strategies during reproduction may have important fitness consequences for prey. Previous studies have shown that individuals of several species adjust their reproductive behavior according to their assessment of predation risk, but few studies have explored potential sexual differences in these strategies. In this study, we investigate whether the acoustic cues associated with predatory attacks or those associated with predators themselves affect the mating behavior of female and male túngara frogs, Physalaemus pustulosus. We compared the responses of females approaching a mate and those of calling males when exposed to mating calls associated with sounds representing increased hazard. When presented with mating calls that differed only in whether or not they were followed by a predation‐related sound, females preferentially approached the call without predation‐related sounds. In contrast to females, calling males showed greater vocal response to calls associated with increased risk than to a call by itself. We found significant differences in the responses of females and males to several sounds associated with increased hazard. Females behaved more cautiously than males, suggesting that the sexes balance the risk of predation and the cost of cautious mating strategies differently.     

Modelling the Immune Response to Cancer: An Individual-Based Approach Accounting for the Difference in Movement Between Inactive and Activated T Cells

A growing body of experimental evidence indicates that immune cells move in an unrestricted search pattern if they are in the pre-activated state, whilst they tend to stay within a more restricted area upon activation induced by the presence of tumour antigens. This change in movement is not often considered in the existing mathematical models of the interactions between immune cells and cancer cells. With the aim to fill such a gap in the existing literature, in this work we present a spatially structured individual-based model of tumour–immune competition that takes explicitly into account the difference in movement between inactive and activated immune cells. In our model, a Lévy walk is used to capture the movement of inactive immune cells, whereas Brownian motion is used to describe the movement of antigen-activated immune cells. The effects of activation of immune cells, the proliferation of cancer cells and the immune destruction of cancer cells are also modelled. We illustrate the ability of our model to reproduce qualitatively the spatial trajectories of immune cells observed in experimental data of single-cell tracking. Computational simulations of our model further clarify the conditions for the onset of a successful immune action against cancer cells and may suggest possible targets to improve the efficacy of cancer immunotherapy. Overall, our theoretical work highlights the importance of taking into account spatial interactions when modelling the immune response to cancer cells.     

Predation on the Invasive Copepod,Pseudodiaptomus forbesi,and Native Zooplankton in the Lower Columbia River: An Experimental Approach to Quantify Differences in Prey-Specific Feeding Rates

Invasive planktonic crustaceans have become a prominent feature of aquatic communities worldwide, yet their effects on food webs are not well known. The Asian calanoid copepod, Pseudodiaptomus forbesi, introduced to the Columbia River Estuary approximately 15 years ago, now dominates the late-summer zooplankton community, but its use by native aquatic predators is unknown. We investigated whether three species of planktivorous fishes (chinook salmon, three-spined stickleback, and northern pikeminnow) and one species of mysid exhibited higher feeding rates on native copepods and cladocerans relative to P. forbesi by conducting `single-prey’ feeding experiments and, additionally, examined selectivity for prey types with `two-prey’ feeding experiments. In single-prey experiments individual predator species showed no difference in feeding rates on native cyclopoid copepods (Cyclopidae spp.) relative to invasive P. forbesi, though wild-collected predators exhibited higher feeding rates on cyclopoids when considered in aggregate. In two-prey experiments, chinook salmon and northern pikeminnow both strongly selected native cladocerans (Daphnia retrocurva) over P. forbesi, and moreover, northern pikeminnow selected native Cyclopidae spp. over P. forbesi. On the other hand, in two-prey experiments, chinook salmon, three-spined stickleback and mysids were non- selective with respect to feeding on native cyclopoid copepods versus P. forbesi. Our results indicate that all four native predators in the Columbia River Estuary can consume the invasive copepod, P. forbesi, but that some predators select for native zooplankton over P. forbesi, most likely due to one (or both) of two possible underlying casual mechanisms: 1) differential taxon-specific prey motility and escape responses (calanoids > cyclopoids > daphnids) or 2) the invasive status of the zooplankton prey resulting in naivety, and thus lower feeding rates, of native predators feeding on invasive prey.     

Modelling of the Hydraulic Architecture of Root Systems: An Integrated Approach to Water Absorption--Distribution of Axial and Radial Conductances in Maize

The ‘Hydraulic Tree Model’ of the root system simulateswater uptake through root systems by coupling a root architecturemodel with laws for water flow into and along roots (Doussan,Pagès and Vercambre,Annals of Botany81: 213–223,1998). A detailed picture of water absorption in all roots comprisingthe root system is thus provided. Moreover, the influence ofdifferent distributions of radial and axial hydraulic conductancesin the root system on the patterns of water uptake can be analysed.Use of the model with Varney and Canny's data (1993) for flowalong maize roots demonstrated that a constant conductance inthe root system cannot reproduce the observed water flux profiles.Taking into account the existing data on hydraulic conductancesin maize roots, we fitted the distribution of conductances inthe root system to the observed flux data. The result is that,during root tissue maturation, the radial conductivity decreasesby one order of magnitude while the axial conductance increasesby about three orders of magnitude. Both types of conductanceexhibit abrupt changes in their evolution. Due to the conductancedistribution in the root system, appreciable water potentialgradients may develop in the roots, in both the branch rootsand main axes. An important point is that the conductance distributionin the branch roots described by the model should be relatedto the age of the tissue (and not the distance from the branchroot tip) and is therefore closely related to the developmentprocess. Thus for branch roots, which represent about 90% ofthe calculated total water uptake in 43-d-old maize, water absorptionwill depend on the opening of the metaxylem in the axes, andon the time dependent variation of the conductances in the branchroots.Copyright 1998 Annals of Botany Company Water; absorption; root system; architecture; model; hydraulic conductance;Zea maysL.     

An Approach to Identify SNPs in the Gene Encoding Acetyl-CoA Acetyltransferase-2 (ACAT-2) and Their Proposed Role in Metabolic Processes in Pig

The novel liver protein acetyl-CoA acetyltransferase-2 (ACAT2) is involved in the beta-oxidation and lipid metabolism. Its comprehensive relative expression, in silico non-synonymous single nucleotide polymorphism (nsSNP) analysis, as well as its annotation in terms of metabolic process with another protein from the same family, namely, acetyl-CoA acyltransferase-2 (ACAA2) was performed in Sus scrofa. This investigation was conducted to understand the most important nsSNPs of ACAT2 in terms of their effects on metabolic activities and protein conformation. The two most deleterious mutations at residues 122 (I to V) and 281 (R to H) were found in ACAT2. Validation of expression of genes in the laboratory also supported the idea of differential expression of ACAT2 and ACAA2 conceived through the in silico analysis. Analysis of the relative expression of ACAT2 and ACAA2 in the liver tissue of Jeju native pig showed that the former expressed significantly higher (P<0.05). Overall, the computational prediction supported by wet laboratory analysis suggests that ACAT2 might contribute more to metabolic processes than ACAA2 in swine. Further associations of SNPs in ACAT2 with production traits might guide efforts to improve growth performance in Jeju native pigs.     

Large Thermal Conductivity Differences between the Crystalline and Vitrified States of DMSO with Applications to Cryopreservation

Thermal conductivity of dimethyl-sulfoxide (DMSO) solution is measured in this study using a transient hot wire technique, where DMSO is a key ingredient in many cryoprotective agent (CPA) cocktails. Characterization of thermal properties of cryoprotective agents is essential to the analysis of cryopreservation processes, either when evaluating experimental data or for the design of new protocols. Also presented are reference measurements of thermal conductivity for pure water ice and glycerol. The thermal conductivity measurement setup is integrated into the experimentation stage of a scanning cryomacroscope apparatus, which facilitates the correlation of measured data with visualization of physical events. Thermal conductivity measurements were conducted for a DMSO concentration range of 2M and 10M, in a temperature range of -180°C and 25°C. Vitrified samples showed decreased thermal conductivity with decreasing temperature, while crystalline samples showed increased thermal conductivity with decreasing temperature. These different behaviors result in up to a tenfold difference in thermal conductivity at -180°C. Such dramatic differences can drastically impact heat transfer during cryopreservation and their quantification is therefore critical to cryobiology.     

Differences in the Access to Sterilization between Women Living and Not Living with HIV: Results from the GENIH Study,Brazil

BackgroundIn many countries, young women of reproductive age have been especially affected by the HIV epidemic, which have fostered research to better understand how HIV infection influences and shapes women´s fertility and reproductive and sexual decisions. In Brazil, few studies have focused on the impact of the HIV epidemic on contraceptive choices among women living with HIV (WLHIV).ObjectiveThis study evaluates the impact HIV infection may have in the access to female sterilization in Brazil, using a time-to-event analysis.MethodsA cross-sectional quantitative study (GENIH study) was conducted between February 2013 and April 2014 in the city of São Paulo, comparing two probabilistic samples of 975 WLHIV and 1,003 women not living with HIV (WNLHIV) aged 18 to 49. Sexual and reproductive data was collected retrospectively in order to reconstruct women''s reproductive trajectories. Given the objectives of this study, the analysis was restricted to women with parity one or more and, in case of WLHIV, to those sterilized after HIV diagnosis and not infected through vertical transmission. The final sample analysis included 683 WNLHIV and 690 WLHIV. A series of multivariable-adjusted Cox models estimated the probability of being sterilized after HIV diagnosis, compared with WNLHIV. Models were adjusted for schooling, race/color, and stratified by parity at last delivery (1–2, 3+). Hazard ratios were calculated for female sterilization, and separately for interval and postpartum procedures (performed in conjunction with caesarean section or immediately after vaginal delivery). Additionally, information regarding unmet demand for female sterilization was also explored.FindingsNo statistical difference in the overall risk of sterilization between WLHIV and WNLHIV in the two parity-related groups is observed: HR = 0.88 (0.54–1.43) and 0.94 (0.69–1.29), respectively, among women with 1–2 children and those with three and more. However, significant differences regarding the impact of HIV infection at sterilization are observed depending on the timing and the type of sterilization procedure. The probability of obtaining an interval sterilization is significantly lower for WLHIV compared to those not living with HIV. The reverse occurs regarding postpartum sterilization. Although sterilization is mainly performed in conjunction with caesarean section in Brazil, it is evident that caesarean sections are not the sole factor increasing the risk of sterilization among WLHIV.ConclusionThe results indicate barriers in the access to services offering interval sterilization for WLHIV and certain facilitation in obtaining the procedure in conjunction with caesarean section. Health policy makers at local and national levels should promote institutional changes in order to facilitate access to interval sterilization and to confront the sensitive discussion of WLHIV’s eligibility for postpartum sterilization. It is also urgent to increase access to a wider range of contraceptive methods for WLHIV and promote dual method protection strategies. Moreover, since condom use may decrease in the future in the context of the preventive effect of antiretroviral therapy, promoting dual methods will expand the choices regarding the reproductive rights of women living with HIV.