Characteristics and outcomes of people living with HIV hospitalised at tertiary healthcare institutions during the COVID-19 pandemic in Mexico City.

BACKGROUND: While existing research on people living with HIV (PWH) during the COVID-19 pandemic primarily focused on their clinical outcomes, a critical gap remains in understanding the implications of COVID-19 delivery of in-hospital care services to PWH. Our study aimed to describe the characteristics and outcomes of PWH hospitalised during 2020 in Mexico City, comparing patients admitted due to COVID-19 vs. patients admitted due to other causes. METHODS: All PWH hospitalised for ≥ 24 h at four institutions in Mexico City from January 1st to December 31st, 2020 were included. Patients were classified into two groups according to the leading cause of their first hospitalisation: COVID-19 or non-COVID-19. Characteristics among groups were compared using chi-square and Kruskal tests. A Cox model was used to describe the risk of death after hospitalisation and the characteristics associated with this outcome. Mortality and hospitalisation events were compared to data from 2019. RESULTS: Overall, we included 238 PWH hospitalised in 2020. Among them, 42 (18%) were hospitalised due to COVID-19 and 196 (82%) due to non-COVID-19 causes, mainly AIDS-defining events (ADE). PWH hospitalised due to COVID-19 had higher CD4 + cell counts (380 cells/mm3 [IQR: 184-580] vs. 97 cells/mm3 [IQR: 34-272], p < 0.01) and a higher proportion of virologic suppression (VS) compared to those hospitalised due to non-COVID-19 causes (92% vs. 55%, p < 0.01). The adjusted hazard ratio (aHR) for AIDS was 3.1 (95%CI: 1.3-7.2). COVID-19 was not associated with death (aHR 0.9 [95%CI: 0.3-2.9]). Compared to 2019, mortality was significantly higher in 2020 (19% vs. 9%, p < 0.01), while hospitalisations decreased by 57%. CONCLUSIONS: PWH with COVID-19 had higher VS and CD4 + cell counts and lower mortality compared to those hospitalised due to non-COVID-19-related causes, who more often were recently diagnosed with HIV and had ADEs. Most hospitalisations and deaths in 2020 in PWH were related to advanced HIV disease. The increased mortality and decreased hospitalisations of PWH during 2020 evidence the impact of the interruption of health services delivery for PWH with advanced disease due to the pandemic. Our findings highlight the challenges faced by PWH during 2020 in a country where advanced HIV remains a concern.

Retiring the term AIDS for more descriptive language.

The term acquired immunodeficiency syndrome (AIDS) was coined to describe a condition marked by weakened cell-mediated immunity in the absence of a clear cause. Due to unfortunate messaging during the early days of the HIV epidemic, this term became loaded with stigma. After the discovery of HIV, the term AIDS became redundant, but its use has persisted and has come to embody negative connotations in the current landscape of the HIV epidemic. People commonly associate AIDS with a terminal illness. This misconception promotes stigma by others, including health-care workers, but also self-stigma, which can prevent individuals from accessing health care. Also, the link between AIDS and gay men generated during the early epidemic with use of the term gay-related immune disorder is misleading regarding which populations are at risk, which can delay diagnosis. The use of the term AIDS is now discouraged by several professional associations, some of which ironically have the word as part of their name. Ending use of the term AIDS would not eradicate stigma. However, this term has outlasted its usefulness, and we should transition towards more descriptive language that aligns with contemporary challenges in HIV.

How the COVID-19 pandemic and the health system's response reduced HIV testing and increased late diagnoses in Mexico.

OBJECTIVES: This study aims to evaluate the disruption in HIV screening and diagnoses due to the coronavirus disease 2019 (COVID-19) pandemic and to investigate the pandemic's subsequent influence on the HIV epidemic. DESIGN: A retrospective examination of testing and confirmed diagnoses time series was undertaken from 2011 to 2022. The analysis encompassed testing, positive tests, positivity rates, and diagnosis outcomes, including new HIV diagnoses, asymptomatic HIV diagnoses, and symptomatic HIV diagnoses. METHODS: We used Autoregressive Integrated Moving Average (ARIMA) models to estimate the COVID-19 epidemic's impact on screening and diagnosis outcomes. We gauged the pandemic's effect between January 2020 and December 2022 by comparing modeled predicted results with actual outcomes. RESULTS: The advent of COVID-19 prompted a reduction of 50.7% in HIV testing, followed by a monthly escalation in testing afterward, estimated at 30.2 and 65.1% for 2021 and 2022, respectively. Although new diagnoses reported between 2020 and 2022 gradually increased to prepandemic levels, we estimate a gap of 13 207 new diagnoses, with symptomatic detections increasing more than proportionally in 2021 and 2022. CONCLUSION: Our results suggest that the COVID-19 pandemic resulted in missed HIV diagnoses and a rise in late HIV diagnoses. Implementing tailored post-COVID-19 strategies to accelerate timely HIV testing and prevention is needed to avert additional burdens and remain on track toward achieving the 2030 HIV management goals.

SARS-CoV-2 infection in health care workers during the first 2-years of the pandemic at a cancer hospital in Mexico.

BACKGROUND: Health care workers (HCWs) are occupationally exposed to severe acute respiratory syndrome coronavirus (SARS-CoV-2). This study aimed to characterize COVID-19 in HCWs at an oncology hospital in Mexico City over 2-years, identify factors associated with severity, and establish transmission dynamics. METHODS: This retrospective study included HCWs with confirmed COVID-19. Socio-demographic, clinical, and outcome data were retrieved from March 2020 to March 2022. We compared the proportion of HCWs affected in each wave. A survey on COVID-19 transmission dynamics was conducted in a subgroup. RESULTS: We included 1,058 workers. The risk of COVID-19 was higher during the Omicron odds ratio (OR 2.10, 95% confidence interval [CI] 1.77-2.50, P < .001). Age ≥41 years old (OR 6.32, 95% CI 2.4-16.62) and being administrative staff (OR 5.51, 95% CI 1.72-17.6) or medical staff (OR 6.82, CI 95% 1.77-26.23), compared to nursing staff, were associated with severity. Vaccination with ≥1 vaccine against SARS-CoV-2 was a protective factor for severe disease (OR 0.04, 95% CI 0.005-0.331). CONCLUSIONS: This study highlights the impact of COVID-19 on HCWs in a cancer hospital in Mexico City and the impact of vaccination as a protective factor against severity.

Importance of Confirmatory Tests for Sars-Cov-2 Infection in Hemodialysis Patients: A Multicenter Mexican Registry

Abstract Background: Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, patients with chronic kidney disease vulnerable to suffering more severe COVID-19 disease and worse outcomes have been identified Objectives: Our study's aim was to determine the incidence, characteristics, and outcomes of SARS-CoV-2 infection in patients of hemodialysis (HD) units in Mexico and to describe the availability of confirmatory testing Methods: This study was multicentric study of 19 HD units, conducted between March 2020 and March 2021 Results: From a total of 5779 patients, 955 (16.5%) cases of suspicious COVID-19 were detected; a SARS-CoV-2 reverse transcription polymerase chain reaction test was done in only 50.6% of patients. Forty-five percentages were hospitalized and 6% required invasive mechanical ventilation (IMV). There was no significant difference in mortality between confirmed (131/483) and suspicious (124/472) cases (p = 0.74). The percentage of patients in need of hospitalization, IMV, and deceased was greater than in the rest of the study population Conclusions: The study revealed that 49.4% of the cases were not confirmed, a worrisome observation given that this is a highly vulnerable population (higher probability of contagion and worse outcomes), in which 100% of patients should have a confirmatory test

Single-stage chromatographic clarification of Chinese Hamster Ovary cell harvest reduces cost of protein production.

A single-stage clarification was developed using a single-use chromatographic clarification device (CCD) to recover a recombinant protein from Chinese Hamster Ovary (CHO) harvest cell culture fluid (HCCF). Clarification of a CHO HCCF is a complex and costly process, involving multiple stages of centrifugation and/or depth filtration to remove cells and debris and to reduce process-related impurities such as host cell protein (HCP), nucleic acids, and lipids. When using depth filtration, the filter train consists of multiple filters of varying ratios, layers, pore sizes, and adsorptive properties. The depth filters, in combination with a 0.2-micron membrane filter, clarify the HCCF based on size-exclusion, adsorptive, and charge-based mechanisms, and provide robust bioburden control. Each stage of the clarification process requires time, labor, and utilities, with product loss at each step. Here, use of the 3M™ Harvest RC Chromatographic Clarifier, a single-stage CCD, is identified as an alternative strategy to a three-stage filtration train. The CCD results in less overall filter area, less volume for flushing, and higher yield. Using bioprocess cost modeling, the single-stage clarification process was compared to a three-stage filtration process. By compressing the CHO HCCF clarification to a single chromatographic stage, the overall cost of the clarification process was reduced by 17%-30%, depending on bioreactor scale. The main drivers for the cost reduction were reduced total filtration area, labor, time, and utilities. The benefits of the single-stage harvest process extended throughout the downstream process, resulting in a 25% relative increase in cumulative yield with comparable impurity clearance.

Risk factors associated with HCV co-infection amongst MSM and transgender women living with HIV in Mexico City: A case-control study.

INTRODUCTION AND OBJECTIVES: Hepatitis C virus infection (HCV) is a major cause of co-morbidity in people living with HIV (PLWHIV). The modes of HCV transmission in the local population of PLWHIV are still unclear. We conducted this study to identify risk factors for HCV transmission amongst PLWHIV in central Mexico. MATERIAL AND METHODS: We enrolled HIV/HCV co-infected cases and HIV controls receiving care in two outpatient clinics in Mexico City. Structured questionnaires were applied, covering demographics, history of percutaneous exposures, sexual behaviors, self-reported STD and recreational drug use. The statistical analysis for between-group comparisons were multivariate logistic regression models to assess the risk factors associated with HCV co-infection. We limited the final analysis to men who have sex with men (MSM) to avoid confounders potentially related to HCV acquisition in other populations. RESULTS: Three hundred and thirty-four MSM with HIV (175 with HCV co-infection and 159 without) were analysed. We did not identify percutaneous exposures as risk factors for HCV. Intravenous drug use (IVDU) occurred in two cases and one control case. Risk factors independently associated with acquiring HCV co-infection were: history of an ulcerative STD (aOR=2.65, 95%CI=1.44-4.88), a HCV positive partner (aOR=5.25, 95%CI=2.78-9.91), having practiced insertive fisting (aOR=2.62, 95%CI=1.01-6.90), and rectal administration of drugs during sex (aOR=2.46, 95%CI=1.25-4.84). CONCLUSIONS: Risky sexual behaviors and chemsex seem to be the main drivers of HIV/HCV co-infection amongst PLWHIV in Central Mexico. IVDU and percutaneous exposures have a minor role in the local HCV epidemic. These findings highlight the importance of testing for HCV in sexually active MSMs.

Clinical Follow-Up in People Living with HIV During the COVID-19 Pandemic in Mexico.

Clinical follow-up in people living with HIV (PLWH) has individual and public health implications. The objectives of this study were to measure variables related to follow-up failures, identify self-reported reasons to maintain adequate follow-up or for having follow-up failures, and know how the pandemic influenced patients' clinical follow-up. Participants were PLWH receiving HIV-health care at a hospital-based clinic in Mexico City which became an exclusive COVID-19 health service. Participants completed a telephone semi-structured interview and online psychological questionnaires. Lower educational and socioeconomic level, longer times of transportation to the clinic, being attended by different doctors, detectable viral load, having previous dropouts, inadequate antiretroviral adherence, and less HIV knowledge were related to follow-up failures. COVID-19 had a significant negative impact, but it also had positive repercussions for patients with adequate follow-up. These results could help develop effective psychosocial programs and improve healthcare in institutions to facilitate patient retention.

RESUMEN: El seguimiento clínico en las personas que viven con VIH (PVV) tiene implicaciones individuales y de salud pública. Los objetivos de este estudio fueron medir las variables relacionadas con las fallas en el seguimiento, identificar las razones reportadas para mantener un seguimiento adecuado o para tener fallas en el seguimiento, y conocer cómo la pandemia influyó en el seguimiento clínico de los individuos. Los participantes eran PVV que recibían atención médica para el VIH en una clínica hospitalaria de Ciudad de México que se convirtió en un servicio exclusivo para COVID-19. Los participantes completaron una entrevista semiestructurada por teléfono y cuestionarios psicológicos en línea. El nivel educativo y socioeconómico más bajo, mayor tiempo de transporte a la clínica, falta de continuidad del médico, carga viral detectable, tener abandonos previos, inadecuada adherencia al tratamiento antirretroviral y menor conocimiento del VIH se relacionaron con las fallas en el seguimiento. La pandemia demostró tener un importante impacto negativo, pero también tuvo repercusiones positivas para los pacientes con un seguimiento adecuado. Estos resultados son importantes para desarrollar programas psicosociales eficaces y mejorar la atención sanitaria en las instituciones para facilitar la retención de los pacientes.

Parenting intentions of young sexual minority men living with HIV in Mexico City, Mexico.

Young sexual minority men are disproportionately affected by HIV in Mexico. Little is known about their thoughts about childbearing, an issue complicated by sexual identity and HIV serostatus. We conducted 16 in-depth qualitative interviews to explore the parenting desires of young sexual minority men living with HIV in Mexico City. Domains of the questionnaire included (1) parenting desires, (2) preferences about different methods (e.g. adoption, in-vitro fertilisation), and (3) perceived barriers to becoming a father. A modified grounded theory approach was used for qualitative analysis. Participants ranged in age from 17 to 21 years and had been living with HIV for an average of 15 months. Most expressed the desire to have a child in the future but were uninformed as to their options for doing so. Participants largely preferred adoption, citing the perceived risk of HIV transmission as a deterrent to using assisted reproductive technologies. Some participants expressed the desire to have a child that was genetically their own, but shared doubts as to the feasibility. The majority of participants stated that the topic of childbearing had never come up during the course of their HIV care.

Importance of Confirmatory Tests for Sars-Cov-2 Infection in Hemodialysis Patients: A Multicenter Mexican Registry.

Background: Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, patients with chronic kidney disease vulnerable to suffering more severe COVID-19 disease and worse outcomes have been identified. Objectives: Our study's aim was to determine the incidence, characteristics, and outcomes of SARS-CoV-2 infection in patients of hemodialysis (HD) units in Mexico and to describe the availability of confirmatory testing. Methods: This study was multicentric study of 19 HD units, conducted between March 2020 and March 2021. Results: From a total of 5779 patients, 955 (16.5%) cases of suspicious COVID-19 were detected; a SARS-CoV-2 reverse transcription polymerase chain reaction test was done in only 50.6% of patients. Forty-five percentages were hospitalized and 6% required invasive mechanical ventilation (IMV). There was no significant difference in mortality between confirmed (131/483) and suspicious (124/472) cases (p = 0.74). The percentage of patients in need of hospitalization, IMV, and deceased was greater than in the rest of the study population. Conclusions: The study revealed that 49.4% of the cases were not confirmed, a worrisome observation given that this is a highly vulnerable population (higher probability of contagion and worse outcomes), in which 100% of patients should have a confirmatory test.

Retention in Care, Mortality, Loss-to-Follow-Up, and Viral Suppression among Antiretroviral Treatment-Naïve and Experienced Persons Participating in a Nationally Representative HIV Pre-Treatment Drug Resistance Survey in Mexico.

We describe associations of pretreatment drug resistance (PDR) with clinical outcomes such as remaining in care, loss to follow-up (LTFU), viral suppression, and death in Mexico, in real-life clinical settings. We analyzed clinical outcomes after a two-year follow up period in participants of a large 2017-2018 nationally representative PDR survey cross-referenced with information of the national ministry of health HIV database. Participants were stratified according to prior ART exposure and presence of efavirenz/nevirapine PDR. Using a Fine-Gray model, we evaluated virological suppression among resistant patients, in a context of competing risk with lost to follow-up and death. A total of 1823 participants were followed-up by a median of 1.88 years (Interquartile Range (IQR): 1.59-2.02): 20 (1%) were classified as experienced + resistant; 165 (9%) naïve + resistant; 211 (11%) experienced + non-resistant; and 1427 (78%) as naïve + non-resistant. Being ART-experienced was associated with a lower probability of remaining in care (adjusted Hazard Ratio(aHR) = 0.68, 0.53-0.86, for the non-resistant group and aHR = 0.37, 0.17-0.84, for the resistant group, compared to the naïve + non-resistant group). Heterosexual cisgender women compared to men who have sex with men [MSM], had a lower viral suppression (aHR = 0.84, 0.70-1.01, p = 0.06) ART-experienced persons with NNRTI-PDR showed the worst clinical outcomes. This group was enriched with women and persons with lower education and unemployed, which suggests higher levels of social vulnerability.

Understanding young women's experiences of gender inequality in Lucknow, Uttar Pradesh through story circles.

Gender inequality poses grave consequences for young women's health and wellbeing. The aim of this study was to understand how gender influences the lives of young women living in urban slums of Lucknow, Uttar Pradesh, India using story circles as a research methodology. Narrative-based participatory methods like story circles (which involves sharing individual stories in a group circle on a given topic) can provide the nuance and detail needed to understand young people's experiences, build trust between participants and researchers, and offer spaces to speak about culturally sensitive subjects. Six story circle sessions were conducted with 50 young women (aged 15-24) in Lucknow. Sessions were audio-recorded, transcribed, and coded. Transcriptions were analysed to identify the following salient themes, all of which act as mechanisms of gender inequality: mobility restrictions, rampant sexual harassment in the community, limited educational and work opportunities, and the utmost prioritization of marriage for young women.

Exploring young women's menstruation-related challenges in Uttar Pradesh, India, using the socio-ecological framework.

Menstruation frequently poses psychological, social, and health challenges for young women living in low- and middle-income countries. In countries such as India, where menstruation is stigmatised, it can be particularly difficult. This paper examines challenges related to menstruation for young women living in slums in Lucknow, Uttar Pradesh, India. The research was informed by the socio-ecological model. Life course interviews were conducted with 70 young women ages 15-24 living in the slums of Lucknow. Thematic analysis was used to identify salient themes regarding individual, social, and systemic challenges related to menstruation. On the individual level, young women lack knowledge about menstruation. In the social sphere, young women experience stigma around menstruation, lack opportunities to discuss menstruation, and experience limitations around mobility and other activities during menstruation. At the institutional level, for example in school, there are few resources to support menstruating young women as toilets are dirty and doors are broken. Therefore, menstruating adolescents and young women in Lucknow, Uttar Pradesh, India, face an array of challenges at multiple levels. These findings suggest that multi-level interventions are warranted to create a supportive context for menstruation.

Pretreatment HIV drug resistance spread within transmission clusters in Mexico City.

BACKGROUND: Pretreatment HIV drug resistance (HIVDR) to NNRTIs has consistently increased in Mexico City during the last decade. OBJECTIVES: To infer the HIV genetic transmission network in Mexico City to describe the dynamics of the local HIV epidemic and spread of HIVDR. PATIENTS AND METHODS: HIV pol sequences were obtained by next-generation sequencing from 2447 individuals before initiation of ART at the largest HIV clinic in Mexico City (April 2016 to June 2018). Pretreatment HIVDR was estimated using the Stanford algorithm at a Sanger-like threshold (≥20%). Genetic networks were inferred with HIV-TRACE, establishing putative transmission links with genetic distances <1.5%. We examined demographic associations among linked individuals with shared drug resistance mutations (DRMs) using a ≥ 2% threshold to include low-frequency variants. RESULTS: Pretreatment HIVDR reached 14.8% (95% CI 13.4%-16.2%) in the cohort overall and 9.6% (8.5%-10.8%) to NNRTIs. Putative links with at least one other sequence were found for 963/2447 (39%) sequences, forming 326 clusters (2-20 individuals). The inferred network was assortative by age and municipality (P < 0.001). Clustering individuals were younger [adjusted OR (aOR) per year = 0.96, 95% CI 0.95-0.97, P < 0.001] and less likely to include women (aOR = 0.46, 95% CI 0.28-0.75, P = 0.002). Among clustering individuals, 175/963 (18%) shared DRMs (involving 66 clusters), of which 66/175 (38%) shared K103N/S (24 clusters). Eight municipalities (out of 75) harboured 65% of persons sharing DRMs. Among all persons sharing DRMs, those sharing K103N were younger (aOR = 0.93, 95% CI 0.88-0.98, P = 0.003). CONCLUSIONS: Our analyses suggest age- and geographically associated transmission of DRMs within the HIV genetic network in Mexico City, warranting continuous monitoring and focused interventions.

Sociodemographic differences among HIV-positive and HIV-negative recently pregnant women in Mexico City: A case-control study.

National HIV preventive programs in Mexico focus on high-risk groups that do not consider women, apart from prenatal screening. Nonetheless, the epidemic in women is growing, and there is a need to better understand sociodemographic factors in women living with HIV (WLH). We performed a case-control study in Mexico City, including HIV+ and HIV- women with a recent pregnancy to compare their sociodemographic characteristics and describe the circumstances of diagnosis in HIV+ women, as well as prenatal screening frequency in both groups. Fifty cases and 102 controls were interviewed. HIV+ women were more frequently the only economic support of the family (20% vs 0%, P < .0001). Thirty-eight percent of cases had their first pregnancy at ≤18 years, versus 16% of controls (odds ratio 2.47, 95% confidence interval 1.07-5.72, P = .03); 16% of cases had lived in the street; 6% reported transactional sex, versus none of the controls (P < .0001). In the multivariate analysis, there was strong evidence of an association between HIV infection and age at the time of the interview, history of sexually transmitted diseases, substance abuse, history of violence, and civil status. Only 6% of controls were tested for HIV during prenatal follow-up. WLH in this study faced important social vulnerability. Targeting women living in these social contexts might increase early diagnosis and could tailor HIV prevention strategies. Prenatal coverage needs to be improved and should represent a national priority.

Regulation of Ligand and Shear Stress-induced Insulin-like Growth Factor 1 (IGF1) Signaling by the Integrin Pathway.

Mechanical loading of the skeleton, as achieved during daily movement and exercise, preserves bone mass and stimulates bone formation, whereas skeletal unloading from prolonged immobilization leads to bone loss. A functional interplay between the insulin-like growth factor 1 receptor (IGF1R), a major player in skeletal development, and integrins, mechanosensors, is thought to regulate the anabolic response of osteogenic cells to mechanical load. The mechanistic basis for this cross-talk is unclear. Here we report that integrin signaling regulates activation of IGF1R and downstream targets in response to both IGF1 and a mechanical stimulus. In addition, integrins potentiate responsiveness of IGF1R to IGF1 and mechanical forces. We demonstrate that integrin-associated kinases, Rous sarcoma oncogene (SRC) and focal adhesion kinase (FAK), display distinct actions on IGF1 signaling; FAK regulates IGF1R activation and its downstream effectors, AKT and ERK, whereas SRC controls signaling downstream of IGF1R. These findings linked to our observation that IGF1 assembles the formation of a heterocomplex between IGF1R and integrin ß3 subunit indicate that the regulation of IGF1 signaling by integrins proceeds by direct receptor-receptor interaction as a possible means to translate biomechanical forces into osteoanabolic signals.

Vitamin D and calcium regulation of epidermal wound healing.

Wound healing is essential for survival. This is a multistep process involving a number of different cell types. In the skin wounding triggers an acute inflammatory response, with the innate immune system contributing both to protection against invasive organisms and to triggering the invasion of inflammatory cells into the wounded area. These cells release a variety of cytokines and growth factors that stimulate the proliferation and migration of dermal and epidermal cells to close the wound. In particular, wounding activates stem cells in the interfollicular epidermis (IFE) and hair follicles (HF) to proliferate and send their progeny to re-epithelialize the wound. ß-catenin and calcium signaling are important for this activation process. Mice lacking the VDR when placed on a low calcium diet have delayed wound healing. This is associated with reduced ß-catenin transcriptional activity and proliferation in the cells at the leading edge of wound closure. These data suggest that vitamin D and calcium signaling are necessary components of the epidermal response to wounding, likely by regulating stem cell activation through increased ß-catenin transcriptional activity.

[In-hospital mortality in HIV-infected patients: 10 years after the implementation of universal access to HAART in Mexico]. / Mortalidad hospitalaria en pacientes con infección por VIH: a diez años del acceso universal a TARAA en México.

OBJECTIVE: To establish the characteristics and causes of death of HIV patients who die while hospitalized. MATERIALS AND METHODS: We included HIV+ patients who died during hospitalization, in three hospitals in Mexico City between 2010 and 2013. Sociodemographic and clinical data were collected as well as causes of death. We identified preventable deaths (defined as deaths that occurred in patients with less than six months of HAART, or without HAART, with less than 350 CD4 at diagnosis and/or opportunistic events as the cause of hospitalization). RESULTS: 128 deaths were analyzed. The median of CD4 count was 47 cells/mm³; 18% of the patients ignored their HIV status at the time of hospitalization, 51% had less than six months of HAART, 40.5% had never received HAART before. The main causes of death were AIDS defining events, with 65.6%. We identified 70 preventable deaths (57%). CONCLUSIONS: Despite universal access to HAART, HIV patients in Mexico are still dying of AIDS defining illnesses, an indicator of late diagnosis. It is urgent to implement HIV testing programs to allow earlier diagnosis and make HAART benefit accessible to all.

Early childbearing, human capital attainment and mortality risk: Evidence from a longitudinal demographic surveillance area in rural-KwaZulu-Natal, South Africa.

Using a rich longitudinal dataset, we examine the relationship between teen fertility and both subsequent educational outcomes and HIV related mortality risk in rural South Africa. Human capital deficits among teen mothers are large and significant, with earlier births associated with greater deficits. In contrast to many other studies from developed countries, we find no clear evidence of selectivity into teen childbearing in either schooling trajectories or pre-fertility household characteristics. Enrolment rates among teen mothers only begin to drop in the period immediately preceding the birth and future teen mothers are not behind in their schooling relative to other girls. Older teen mothers and those further ahead in school for their age pre-birth are more likely to continue schooling after the birth. In addition to adolescents' higher biological vulnerability to HIV infection, pregnancy also appears to increase the risk of contracting HIV. Following women over an extended period, we document a higher HIV related mortality risk for teen mothers that cannot be explained by household characteristics in early adulthood. Controlling for age at sexual debut, we find that teen mothers report lower condom use and older partners than other sexually active adolescents.

IGF-I Signaling in Osterix-Expressing Cells Regulates Secondary Ossification Center Formation, Growth Plate Maturation, and Metaphyseal Formation During Postnatal Bone Development.

To investigate the role of IGF-I signaling in osterix (OSX)-expressing cells in the skeleton, we generated IGF-I receptor (IGF-IR) knockout mice ((OSX)IGF-IRKO) (floxed-IGF-IR mice × OSX promoter-driven GFP-labeled cre-recombinase [(OSX)GFPcre]), and monitored postnatal bone development. At day 2 after birth (P2), (OSX)GFP-cre was highly expressed in the osteoblasts in the bone surface of the metaphysis and in the prehypertrophic chondrocytes (PHCs) and inner layer of perichondral cells (IPCs). From P7, (OSX)GFP-cre was highly expressed in PHCs, IPCs, cartilage canals (CCs), and osteoblasts (OBs) in the epiphyseal secondary ossification center (SOC), but was only slightly expressed in the OBs in the metaphysis. Compared with the control mice, the IPC proliferation was decreased in the (OSX)IGF-IRKOs. In these mice, fewer IPCs invaded into the cartilage, resulting in delayed formation of the CC and SOC. Immunohistochemistry indicated a reduction of vessel number and lower expression of VEGF and ephrin B2 in the IPCs and SOC of (OSX)IGF-IRKOs. Quantitative real-time PCR revealed that the mRNA levels of the matrix degradation markers, MMP-9, 13 and 14, were decreased in the (OSX)IGF-IRKOs compared with the controls. The (OSX)IGF-IRKO also showed irregular morphology of the growth plate and less trabecular bone in the tibia and femur from P7 to 7 weeks, accompanied by decreased chondrocyte proliferation, altered chondrocyte differentiation, and decreased osteoblast differentiation. Our data indicate that during postnatal bone development, IGF-I signaling in OSX-expressing IPCs promotes IPC proliferation and cartilage matrix degradation and increases ephrin B2 production to stimulate vascular endothelial growth factor (VEGF) expression and vascularization. These processes are required for normal CC formation in the establishment of the SOC. Moreover, IGF-I signaling in the OSX-expressing PHC is required for growth plate maturation and osteoblast differentiation in the development of the metaphysis.