Multidrug-Resistant Salmonella enterica Isolated in Paca (Cuniculus paca) Carcasses from the Belen Market, Iquitos, Perú.

The consumption of wildlife meat is traditionally accepted in the Peruvian Amazon; however, little is known about the pathogens present in this type of food. One of the most frequently consumed species is a rodent, the paca (Cuniculus paca) or "majaz" in the Peruvian language. The objective of this study was to determine the presence of Salmonella enterica and its antimicrobial resistance profile in paca carcasses sold in the Belen Market of Iquitos-Peru. An observational, descriptive, cross-sectional study was carried out. Fresh and smoked paca carcasses (72 samples) were evaluated during the low-rain period (July 2019) in the traditional market of Iquitos, in the Amazonian Region. Meat samples were swabbed, and International Standards Organization (ISO) 6579-1: 2017 protocol was followed to Salmonella isolation. Antimicrobial susceptibility analysis was performed by the disk diffusion method. In addition, serotyping was performed by using the Kauffmann-White scheme. A total of 25 strains of S. enterica were isolated in the paca carcasses, mainly in fresh carcasses (48.6%). The serovars isolated were Agona (45.8%), Infantis (41.7%), Wangata (8.3%), and Javiana (4.2%). A considerable number of the isolated strains were multidrug resistant (40%). The highest prevalence of resistance corresponded to trimethoprim-sulfamethoxazole (64%) followed by nitrofurantoin (44%), chloramphenicol (40%), cefotaxime (40%), and nalidixic acid (40%). Ten strains isolated (40%) were identified as producers of extended spectrum beta lactamases, all in S. enterica serovar Infantis. This study describes the presence of Salmonella Infantis with multidrug resistance profiles in wildlife meat carcasses, making the consumption of this type of products a risk factor for the development of foodborne diseases in the Amazon region. Institutional Review Board: Approval Resolution of Thesis Project: N° 024-DACMVZ-DAFCVB-U.CIENTÍFICA-2019.

GPU-accelerated iterative reconstruction for limited-data tomography in CBCT systems.

BACKGROUND: Standard cone-beam computed tomography (CBCT) involves the acquisition of at least 360 projections rotating through 360 degrees. Nevertheless, there are cases in which only a few projections can be taken in a limited angular span, such as during surgery, where rotation of the source-detector pair is limited to less than 180 degrees. Reconstruction of limited data with the conventional method proposed by Feldkamp, Davis and Kress (FDK) results in severe artifacts. Iterative methods may compensate for the lack of data by including additional prior information, although they imply a high computational burden and memory consumption. RESULTS: We present an accelerated implementation of an iterative method for CBCT following the Split Bregman formulation, which reduces computational time through GPU-accelerated kernels. The implementation enables the reconstruction of large volumes (>10243 pixels) using partitioning strategies in forward- and back-projection operations. We evaluated the algorithm on small-animal data for different scenarios with different numbers of projections, angular span, and projection size. Reconstruction time varied linearly with the number of projections and quadratically with projection size but remained almost unchanged with angular span. Forward- and back-projection operations represent 60% of the total computational burden. CONCLUSION: Efficient implementation using parallel processing and large-memory management strategies together with GPU kernels enables the use of advanced reconstruction approaches which are needed in limited-data scenarios. Our GPU implementation showed a significant time reduction (up to 48 ×) compared to a CPU-only implementation, resulting in a total reconstruction time from several hours to few minutes.

Control of dopaminergic neuron survival by the unfolded protein response transcription factor XBP1.

Parkinson disease (PD) is characterized by the selective loss of dopaminergic neurons of the substantia nigra pars compacta (SNpc). Although growing evidence indicates that endoplasmic reticulum (ER) stress is a hallmark of PD, its exact contribution to the disease process is not well understood. Here we report that developmental ablation of X-Box binding protein 1 (XBP1) in the nervous system, a key regulator of the unfolded protein response (UPR), protects dopaminergic neurons against a PD-inducing neurotoxin. This survival effect was associated with a preconditioning condition that resulted from induction of an adaptive ER stress response in dopaminergic neurons of the SNpc, but not in other brain regions. In contrast, silencing XBP1 in adult animals triggered chronic ER stress and dopaminergic neuron degeneration. Supporting this finding, gene therapy to deliver an active form of XBP1 provided neuroprotection and reduced striatal denervation in animals injected with 6-hydroxydopamine. Our results reveal a physiological role of the UPR in the maintenance of protein homeostasis in dopaminergic neurons that may help explain the differential neuronal vulnerability observed in PD.

Impact of HLA selection pressure on HIV fitness at a population level in Mexico and Barbados.

UNLABELLED: Previous studies have demonstrated that effective cytotoxic T lymphocyte (CTL) responses drive the selection of escape mutations that reduce viral replication capacity (VRC). Escape mutations, including those with reduced VRC, can be transmitted and accumulate in a population. Here we compared two antiretroviral therapy (ART)-naive HIV clade B-infected cohorts, in Mexico and Barbados, in which the most protective HLA alleles (HLA-B*27/57/58:01/81:01) are differentially expressed, at 8% and 34%, respectively. Viral loads were significantly higher in Mexico than in Barbados (median, 40,774 versus 14,200; P < 0.0001), and absolute CD4(+) T-cell counts were somewhat lower (median, 380/mm(3) versus 403/mm(3); P = 0.007). We tested the hypothesis that the disparate frequencies of these protective HLA alleles would be associated with a higher VRC at the population level in Mexico. Analysis of VRC in subjects in each cohort, matched for CD4(+) T-cell count, revealed that the VRC was indeed higher in the Mexican cohort (mean, 1.13 versus 1.03; P = 0.0025). Although CD4 counts were matched, viral loads remained significantly higher in the Mexican subjects (P = 0.04). This VRC difference was reflected by a significantly higher frequency in the Barbados cohort of HLA-B*27/57/58:01/81:01-associated Gag escape mutations previously shown to incur a fitness cost on the virus (P = 0.004), a difference between the two cohorts that remained statistically significant even in subjects not expressing these protective alleles (P = 0.01). These data suggest that viral set points and disease progression rates at the population level may be significantly influenced by the prevalence of protective HLA alleles such as HLA-B*27/57/58:01/81:01 and that CD4 count-based guidelines to initiate antiretroviral therapy may need to be modified accordingly, to optimize the effectiveness of treatment-for-prevention strategies and reduce HIV transmission rates to the absolute minimum. IMPORTANCE: Immune control of HIV at an individual level is strongly influenced by the HLA class I genotype. HLA class I molecules mediating effective immune control, such as HLA-B*27 and HLA-B*57, are associated with the selection of escape mutants that reduce viral replicative capacity. The escape mutants selected in infected patients can be transmitted and affect the viral load and CD4 count in the recipient. These findings prompt the hypothesis that the frequency of protective alleles in a population may affect viral set points and rates of disease progression in that population. These studies in Mexico and Barbados, where the prevalence rates of protective HLA alleles are 8% and 34%, respectively, support this hypothesis. These data suggest that antiretroviral therapy (ART) treatment-for-prevention strategies will be less successful in populations such as those in Mexico, where viral loads are higher for a given CD4 count. Consideration may therefore usefully be given to ART initiation at higher absolute CD4 counts in such populations to optimize the impact of ART for prevention.

Targeting the UPR transcription factor XBP1 protects against Huntington's disease through the regulation of FoxO1 and autophagy.

Mutations leading to expansion of a poly-glutamine track in Huntingtin (Htt) cause Huntington's disease (HD). Signs of endoplasmic reticulum (ER) stress have been recently reported in animal models of HD, associated with the activation of the unfolded protein response (UPR). Here we have investigated the functional contribution of ER stress to HD by targeting the expression of two main UPR transcription factors, XBP1 and ATF4 (activating transcription factor 4), in full-length mutant Huntingtin (mHtt) transgenic mice. XBP1-deficient mice were more resistant to developing disease features, associated with improved neuronal survival and motor performance, and a drastic decrease in mHtt levels. The protective effects of XBP1 deficiency were associated with enhanced macroautophagy in both cellular and animal models of HD. In contrast, ATF4 deficiency did not alter mHtt levels. Although, XBP1 mRNA splicing was observed in the striatum of HD transgenic brains, no changes in the levels of classical ER stress markers were detected in symptomatic animals. At the mechanistic level, we observed that XBP1 deficiency led to augmented expression of Forkhead box O1 (FoxO1), a key transcription factor regulating autophagy in neurons. In agreement with this finding, ectopic expression of FoxO1 enhanced autophagy and mHtt clearance in vitro. Our results provide strong evidence supporting an involvement of XBP1 in HD pathogenesis probably due to an ER stress-independent mechanism involving the control of FoxO1 and autophagy levels.

Hereditary haemochromatosis: Prevalence and characterization of the disease in a tertiary hospital in Aragon.

BACKGROUND: The main genetic cause of iron overload is haemochromatosis (HC). In recent years, the study of non-HFE genes (HFE2, HJV, HAMP, TRF2, SLC40A1, and BMP6) has become relevant thanks to next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA) techniques. Our objectives were to estimate the prevalence of both HFE (C282Y/HY63D variants) and non-HFE variants attending a tertiary hospital in Aragón, to predict the effect of the variants on the protein, and to establish a genotype-phenotype correlation evaluating with the clinical context. METHODS: Retrospective descriptive study from 2006 to 2020 of patients attended at genetic consultation in a reference hospital for HC in Aragon. We calculated prevalence of HFE and non-HFE variants. We analysed non-HFE genes (HFE2, HJV, HAMP, TRF2, SLC40A1, and BMP6), used bioinformatics tools, consulted different databases and measured clinical parameters (laboratory and imaging). RESULTS: The prevalence of C282Y homozygous was 5.95% respect the total of cases and 0.025% respect our population. The prevalence of non-HFE HC variants was 1.94% respect the total of cases and 0.008% respect our population. We found 27 variants in non-HFE genes and 4 in HFE gene, of which 6 were classified as variant of uncertain clinical significance (VUS), or likely pathogenic or pathogenic according to the ACMG classification criteria. CONCLUSION: Our prevalence results are as expected, and similar to those obtained by other studies. Although some of the genetic findings explain the clinical symptoms of some of our patients, we remain have a high number of patients without a clear molecular diagnosis.

Effects of antidiabetic drugs on bone metabolism.

Objectives: The prevalence of diabetes mellitus type 2 (DMT2) is increasing exponentially worldwide. DMT2 patients have been found to be at a higher risk for bone fractures than the healthy population. Hence, improving our understanding of the impact of antidiabetic drugs on bone metabolism is crucial. Methods: A descriptive, retrospective study involving 106 patients receiving six groups of antidiabetic drugs: insulin; dipeptidylpeptidase four inhibitors (DPP4i); glucagon-like peptide type 1 receptor agonists (GLP1ra); sulfonylureas; sodium-glucose cotransporter two inhibitors (SGLT2i); and pioglitazone, in which osteocalcin (OC), bone alkaline phosphatase (BAP) and C-terminal telopeptide of collagen type 1 or beta-crosslaps (ß-CTx) were determined. Results: ß-CTx concentrations were higher in the patients treated with pioglitazone, as compared to patients treated with DPP4i (p=0.035), SGLT2i (p=0.020) or GLP1ra (p<0.001). The lowest ß-CTx concentrations were observed in the patients treated with GLP1ra. Conclusions: Bone remodeling is influenced by the type of antidiabetic drug administered to DMT2 patients. In our study, the patients who received pioglitazone showed higher ß-CTx concentrations, as compared to patients treated with other types of antidiabetic drugs. This finding highlights the convenience of avoiding these drugs, especially in postmenopausal women with DMT2. GLP1ra drugs were associated with the lowest ß-CTx concentrations, which suggests that these agents could exert beneficial effects on bone metabolism.

Translating Open-Ended Questions in Cross-Cultural Qualitative Research: A Comprehensive Framework.

INTRODUCTION: Globalization has increased the importance of multicultural research to address health disparities and improve healthcare outcomes for underrepresented communities. The International Nursing Network for HIV Research (The Network) serves as a platform for researchers to collaborate on cross-cultural and cross-national HIV studies. This article discusses the Network's approach to overcoming barriers in multicultural and multinational research in a qualitative context. METHODS: The network created a protocol to guide decision-making throughout the translation process of qualitative data collected from participants in their native languages. The protocol includes aspects of why, when, what, who, how, where, and by what means the translation is completed. RESULTS: The protocol has allowed researchers to enhance the validity, reliability, and cultural sensitivity of translation process, ensuring the clarity and impact of their research findings. DISCUSSION: Rigorous translation practices promote cross-cultural understanding and respect for participants' perspectives, fostering global collaborations and knowledge exchange.

Differential clade-specific HLA-B*3501 association with HIV-1 disease outcome is linked to immunogenicity of a single Gag epitope.

The strongest genetic influence on immune control in HIV-1 infection is the HLA class I genotype. Rapid disease progression in B-clade infection has been linked to HLA-B*35 expression, in particular to the less common HLA-B*3502 and HLA-B*3503 subtypes but also to the most prevalent subtype, HLA-B*3501. In these studies we first demonstrated that whereas HLA-B*3501 is associated with a high viral set point in two further B-clade-infected cohorts, in Japan and Mexico, this association does not hold in two large C-clade-infected African cohorts. We tested the hypothesis that clade-specific differences in HLA associations with disease outcomes may be related to distinct targeting of critical CD8(+) T-cell epitopes. We observed that only one epitope was significantly targeted differentially, namely, the Gag-specific epitope NPPIPVGDIY (NY10, Gag positions 253 to 262) (P = 2 × 10(-5)). In common with two other HLA-B*3501-restricted epitopes, in Gag and Nef, that were not targeted differentially, a response toward NY10 was associated with a significantly lower viral set point. Nonimmunogenicity of NY10 in B-clade-infected subjects derives from the Gag-D260E polymorphism present in ∼90% of B-clade sequences, which critically reduces recognition of the Gag NY10 epitope. These data suggest that in spite of any inherent HLA-linked T-cell receptor repertoire differences that may exist, maximizing the breadth of the Gag-specific CD8(+) T-cell response, by the addition of even a single epitope, may be of overriding importance in achieving immune control of HIV infection. This distinction is of direct relevance to development of vaccines designed to optimize the anti-HIV CD8(+) T-cell response in all individuals, irrespective of HLA type.

Hereditary hemochromatosis: An update vision of the laboratory diagnosis.

Haemochromatosis (HC) is an inherited disorder of iron metabolism. The 85-90% of Hereditary hemochromatosis cases are caused by mutations in HFE gene (HC type 1). The remaining 10-15% of HC cases are caused by mutations in other non-HFE genes (HJV, HAMP, TRF2, SLC40A1, BMP6). The study of patients for the diagnosis of HC has an important laboratory approached: analysis of biochemical parameters and genetic studies. To confirm a case, it is necessary to carry out a genetic study of the C282Y and H63D mutations. The presence of C282Y mutation in homozygosis is compatible with the diagnosis of HC type 1. Due to the incomplete penetrance of this mutation and the variable phenotypic expression, the severe forms of the disease are relatively rare. The study of variants in non-HFE genes allows more detailed study of both non-classic HC cases and those with more severe clinical expression. The genotype characterization of a patient not always justified the phenotype expression of the symptoms in this disease. All laboratory clinicians must consider recommendation provide by the experts in the Materia.

Renal histopathology in critically ill patients with Septic Acute Kidney Injury(S-AKI).

PURPOSE: To describe the kidney histopathology of patients with S-AKI and correlate the histological findings with AKI severity, presence of septic shock, and the degree of multiple organic dysfunction (MOD) using the SOFA score. MATERIALS AND METHODS: This was a prospective, observational, and analytical study of a cohort of critically ill patients with S-AKI who died from sepsis at the "Hospital Español" intensive care unit (ICU). Kidney necropsies were performed within 2 h after death. RESULTS: We considered twenty (20) patients, with all of them exhibiting S-AKI stage 3 at the same time. In renal histopathology analysis, nonspecific tubulointerstitial (TI) lesions were found in almost all patients (95%). The more frequently found nonspecific TI lesions involved leukocyte infiltration (85%). Necrotic TI lesions were found in 6 patients (30%), and necrotic tubular cell casts were the most frequent lesions (50% of patients). It was not possible to demonstrate an association between the presence of necrotic TI lesions and factors such as the APACHE II score, the global SOFA score, ICU stays, AKI length and renal replacement therapy (RRT). CONCLUSIONS: The main histopathological findings in kidney necropsies in patients with S-AKI KDIGO 3, showed nonspecific TI lesions, and TI necrosis was only observed in 30% of the cases; therefore, S-AKI cannot be considered to be synonymous with acute tubular necrosis (ATN).

Progress in Respiratory Gene Therapy.

The prospect of gene therapy for inherited and acquired respiratory disease has energized the research community since the 1980s, with cystic fibrosis, as a monogenic disorder, driving early efforts to develop effective strategies. The fact that there are still no approved gene therapy products for the lung, despite many early phase clinical trials, illustrates the scale of the challenge: In the 1990s, first-generation non-viral and viral vector systems demonstrated proof-of-concept but low efficacy. Since then, there has been steady progress toward improved vectors with the capacity to overcome at least some of the formidable barriers presented by the lung. In addition, the inclusion of features such as codon optimization and promoters providing long-term expression have improved the expression characteristics of therapeutic transgenes. Early approaches were based on gene addition, where a new DNA copy of a gene is introduced to complement a genetic mutation: however, the advent of RNA-based products that can directly express a therapeutic protein or manipulate gene expression, together with the expanding range of tools for gene editing, has stimulated the development of alternative approaches. This review discusses the range of vector systems being evaluated for lung delivery; the variety of cargoes they deliver, including DNA, antisense oligonucleotides, messenger RNA (mRNA), small interfering RNA (siRNA), and peptide nucleic acids; and exemplifies progress in selected respiratory disease indications.

Correction of a chronic pulmonary disease through lentiviral vector-mediated protein expression.

We developed a novel lentiviral vector, pseudotyped with the F and HN proteins from Sendai virus (rSIV.F/HN), that produces long-lasting, high-efficiency transduction of the respiratory epithelium. Here we addressed whether this platform technology can secrete sufficient levels of a therapeutic protein into the lungs to ameliorate a fatal pulmonary disease as an example of its translational capability. Pulmonary alveolar proteinosis (PAP) results from alveolar granulocyte-macrophage colony-stimulating factor (GM-CSF) insufficiency, resulting in abnormal surfactant homeostasis and consequent ventilatory problems. Lungs of GM-CSF knockout mice were transduced with a single dose of rSIV.F/HN-expressing murine GM-CSF (mGM-CSF; 1e5-92e7 transduction units [TU]/mouse); mGM-CSF expression was dose related and persisted for at least 11 months. PAP disease biomarkers were rapidly and persistently corrected, but we noted a narrow toxicity/efficacy window. rSIV.F/HN may be a useful platform technology to deliver therapeutic proteins for lung diseases requiring long-lasting and stable expression of secreted proteins.

Replicative capacity of human immunodeficiency virus type 1 transmitted from mother to child is associated with pediatric disease progression rate.

Human immunodeficiency virus (HIV)-infected infants in the developing world typically progress to AIDS or death within the first 2 years of life. However, a minority progress relatively slowly. This study addresses the potential contribution of viral factors to HIV disease progression in eight infants selected from a well-characterized cohort of C clade HIV-infected infants, monitored prospectively from birth in Durban, South Africa. Three infants were defined as "progressors," and five were defined as "slow progressors." We observed that slow-progressor infants carry HIV isolates with significantly lower replicative capacity compared to virus from progressors. Furthermore, our data suggest a link between the attenuated viral phenotype and HLA-B* 57/5801 epitope-specific Gag mutational patterns of the transmitted virus and not to coreceptor usage or to the presence of Nef deletions or insertions. These data underline the importance of virus-host interactions and highlight the contribution of viral attenuation through Gag-specific CD8(+) T-cell escape mutations, among other factors, in the control of pediatric HIV infection.

Optimization of a calibration phantom for quantitative radiography.

OBJECTIVE: Dual energy radiography (DER) makes it possible to obtain separate images for soft-tissue and bony structures (tissue maps) based on the acquisition of two radiographs at different source peak-kilovoltage values. Current DER studies are based on the weighted subtraction method, which requires either manual tuning or the use of precomputed tables, or on decomposition methods, which make use of a calibration to model soft-tissue and bone components. In this study, we examined in depth the optimum method to perform this calibration. METHODS: We used simulations to optimize the calibration protocol and evaluated the effect of the material and size of a calibration phantom composed of two wedges and its positioning in the system. Evaluated materials were water, PMMA and A-150 as soft-tissue equivalent, and Teflon, B-100 and aluminum as bone equivalent, with sizes from 5 to 30 cm. Each material combination was compared with an ideal phantom composed of soft tissue and bone. Our simulation results enabled us to propose four designs that were tested with the NOVA FA X-ray system with a realistic thorax phantom. RESULTS: Calibration based on a very simple and inexpensive phantom with no strict requirements in its placement results in appropriate separation of the spine (a common focus in densitometry studies) and the identification of nodules as small as 6 mm, which have been reported to have a low rate of detection in radiography. CONCLUSION: The proposed method is completely automatic, avoiding the need for a radiology technician with expert knowledge of the protocol, as is the case in densitometry exams. The method provides real mass thickness values, enabling quantitative planar studies instead of relative comparisons.

Tolerance to geometrical inaccuracies in CBCT systems: A comprehensive study.

PURPOSE: The last decades have seen the consolidation of the cone-beam CT (CBCT) technology, which is nowadays widely used for different applications such as micro-CT for small animals, mammography, dentistry, or surgical procedures. Some CBCT systems may suffer mechanical strains due to the heavy load of the x-ray tube. This fact, together with tolerances in the manufacturing process, lead to different types of undesirable effects in the reconstructed image unless they are properly accounted for during the reconstruction. To obtain good quality images, it is necessary to have a complete characterization of the system geometry including the angular position of the gantry, the source-object and detector-object distances, and the position and pose of the detector. These parameters can be obtained through a calibration process done periodically, depending on the stability of the system geometry. To the best of our knowledge, there are no comprehensive works studying the effect of inaccuracies in the geometrical calibration of CBCT systems in a systematic and quantitative way. In this work, we describe the effects of detector misalignments (linear shifts, rotation, and inclinations) on the image and define their tolerance as the maximum error that keeps the image free from artifacts. METHODS: We used simulations of four phantoms including systematic and random misalignments. Reconstructions of these data with and without errors were compared to identify the artifacts introduced in the reconstructed image and the tolerance to miscalibration deemed to provide acceptable image quality. RESULTS: Visual assessment provided an easy guideline to identify the sources of error by visual inspection of the artifactual images. Systematic errors result in blurring, shape distortion and/or reduction of the axial field of view while random errors produce streaks and blurring in all cases, with a tolerance which is more than twice that of systematic errors. The tolerance corresponding to errors in position of the detector along the tangential direction, that is, skew (<0.2°) and horizontal shift (<0.4 mm), is tighter than the tolerance to those errors affecting the position along the longitudinal direction or the magnification, that is, vertical shift (<2 mm), roll (<1.5°), tilt (<2°), and SDD (<3 mm). CONCLUSION: We present a comprehensive study, based on realistic simulations, of the effects on the reconstructed image quality of errors in the geometrical characterization of a CBCT system and define their tolerance. These results could be used to guide the design of new systems, establishing the mechanical precision that must be achieved, and to help in the definition of an optimal geometrical calibration process. Also, the thorough visual assessment may be valuable to identify the most predominant sources of error based on the effects shown in the reconstructed image.

Impact of HLA in mother and child on disease progression of pediatric human immunodeficiency virus type 1 infection.

A broad Gag-specific CD8(+) T-cell response is associated with effective control of adult human immunodeficiency virus (HIV) infection. The association of certain HLA class I molecules, such as HLA-B*57, -B*5801, and -B*8101, with immune control is linked to mutations within Gag epitopes presented by these alleles that allow HIV to evade the immune response but that also reduce viral replicative capacity. Transmission of such viruses containing mutations within Gag epitopes results in lower viral loads in adult recipients. In this study of pediatric infection, we tested the hypothesis that children may tend to progress relatively slowly if either they themselves possess one of the protective HLA-B alleles or the mother possesses one of these alleles, thereby transmitting a low-fitness virus to the child. We analyzed HLA type, CD8(+) T-cell responses, and viral sequence changes for 61 mother-child pairs from Durban, South Africa, who were monitored from birth. Slow progression was significantly associated with the mother or child possessing one of the protective HLA-B alleles, and more significantly so when the protective allele was not shared by mother and child (P = 0.007). Slow progressors tended to make CD8(+) T-cell responses to Gag epitopes presented by the protective HLA-B alleles, in contrast to progressors expressing the same alleles (P = 0.07; Fisher's exact test). Mothers expressing the protective alleles were significantly more likely to transmit escape variants within the Gag epitopes presented by those alleles than mothers not expressing those alleles (75% versus 21%; P = 0.001). Reversion of transmitted escape mutations was observed in all slow-progressing children whose mothers possessed protective HLA-B alleles. These data show that HLA class I alleles influence disease progression in pediatric as well as adult infection, both as a result of the CD8(+) T-cell responses generated in the child and through the transmission of low-fitness viruses by the mother.

[Effectiveness of structural interventions to promote condom use in adolescents and young people: Systematic Review]. / Efectividad de las intervenciones estructurales para la promoción del uso del preservativo en adolescentes y jóvenes: revisión sistemática.

OBJECTIVE: Evaluate the effectiveness of structural or multicomponent interventions aimed at increasing the use of condoms in adolescents and young adults, identifying the strategies that form the interventions evaluated, and recognizing the theoretical models that support these interventions. METHODOLOGY: Design: Systematic review of literature. Data source: MEDLINE databases were consulted via OVID, Embase, and CENTRAL in order to search for studies on interventions aimed at increasing the use of condoms in adolescents and young adults. Selection of studies: A total of 7 primary investigations were selected, in which the effect of a structured or multicomponent intervention to increase the use of condoms in adolescents and young adults was evaluated. The quality of the studies was evaluated using the Cochrane bias risk assessment. RESULTS: Five investigations show changes in the percentages of condom use with values between 53% and 68%. The interventions targeted guided their actions more at individual level with strategies such as sexual health education, reproductive health counseling, knowledge about the condom, knowledge about STIs / HIV, than at organizational and environ-mental levels, which were aimed at the provision of condoms. The theoretical models proposed in the studies are focused on human behavior, individual behavior, and social learning. CONCLUSION: Structural interventions that aim to increase the use of condoms in adolescents and young adults seem to show significant changes at individual level, but possible changes generated at both organization and environment levels are unknown.

OBJETIVO: Evaluar la efectividad de las intervenciones de tipo estructural o multicomponente dirigidas al incremento del uso del preservativo en adolescentes y jóvenes, identificar las estrategias que conforman las intervenciones evaluadas y reconocer los modelos teóricos que sustentan dichas intervenciones. METODOLOGÍA: Diseño: revisión sistemática de la literatura. Fuente de datos: se consultaron las bases de datos MEDLINE vía OVID, Embase y CENTRAL para buscar estudios sobre intervenciones dirigidas al incremento del uso del preservativo en adolescentes y jóvenes. Selección de estudios: se seleccionaron un total de 7 investigaciones primarias donde se evaluaba el efecto de una intervención estructural o multicomponente para incrementar el uso del preservativo en adolescentes y jóvenes. La calidad de los estudios fue evaluada usando la herramienta para valoración de riesgo de sesgos de Cochrane. RESULTADOS: Cinco investigaciones mostraron cambios en los porcentajes del uso del preservativo con valores entre 53 % y el 68 %. Las intervenciones planteadas orientaban sus acciones más a nivel individual con estrategias como: educación sobre salud sexual, consejería en salud reproductiva, conocimientos acerca del preservativo, conocimientos acerca de las ITS/VIH. A nivel organizacional y del entorno iban dirigidas a la provisión de preservativos. Los modelos teóricos planteados en los estudios están centrados en la conducta humana, comportamiento del individuo y el aprendizaje social. DISCUSIÓN: Las intervenciones de tipo estructural que tienen como fin el incremento del uso del preservativo en adolescentes y jóvenes parecen mostrar cambios significativos a nivel individual, pero se desconocen los posibles cambios generados a nivel de la organización y del entorno.

Hemoptysis as the first symptom in the diagnosis of metastatic choriocarcinoma in the third trimester of pregnancy: A case report.

INTRODUCTION: Choriocarcinoma is a rare neoplasm (1/40000 pregnancies). In the context of a viable pregnancy, the incidence is even lower (1/160000). CASE REPORT: A woman in her second pregnancy was admitted at 31 + 6 weeks of gestation with hemoptysis and abnormal vaginal bleeding. Numerous placental venous lakes, bilateral pulmonary nodules and a pleural effusion were found. Pleural fluid ß-HCG levels were elevated and a brain-chest-abdominal-pelvic CT scan led to the diagnosis of a high-risk gestational trophoblastic neoplasm. A caesarean section at 32 + 1 weeks of gestation was performed. Six cycles of an EMA-CO chemotherapy regime were administered. ß-HCG levels normalized after 3 cycles. Placental histopathology confirmed the presence of a gestational choriocarcinoma. CONCLUSION: Choriocarcinoma is a highly aggressive tumor. In high-risk tumors, combination chemotherapy is the first-line treatment, offering high remission rates. Treatment response is evaluated by monitoring blood ß-HCG levels, which should be long-term.