APOE genotype dictates lipidomic signatures in primary human hepatocytes.

Apolipoprotein E (APOE) genetic variants are most notably known for their divergent impact on the risk of developing Alzheimer's disease. While APOE genotype has been consistently shown to modulate lipid metabolism in a variety of cellular contexts, the effect of APOE alleles on the lipidome in hepatocytes is unknown. In this study, we investigated the contribution of APOE alleles to lipidomic profiles of donor-derived primary human hepatocytes from 77 subjects. Lipidomic data obtained by liquid chromatography-mass spectrometry were analyzed across ε2/ε3, ε3/ε3, and ε3/ε4 genotypes to reveal how APOE modulates lipid relative levels over age and between groups. Hepatic APOE concentration, measured by ELISA, was assessed for correlation with lipid abundance in subjects grouped as per APOE genotype and sex. APOE genotype-specific differential lipidomic signatures associated with age for multiple lipid classes but did not differ between sexes. Compared to ε2/ε3, ε3/ε4 hepatocytes had higher abundance of acylcarnitines (AC) and acylphosphatidylglycerol (AcylPG) as a class, as well as higher medium and long-chain ACs, AcylPG, phosphatidylglycerol (PG), bis(monoacylglycerol)phosphate (BMP), monoacylglycerol (MG) and diacylglycerol (DG) species. The ε3/ε4 hepatocytes also exhibited a higher abundance of medium and long-chain ACs compared to the ε3/ε3 hepatocytes. Only in the ε3/ε4 hepatocytes, APOE concentration was lower and showed a negative correlation with BMP levels, specifically in females. APOE genotype dictates a differential lipidome in primary human hepatocytes. The lipids involved suggest mitochondrial dysfunction with accompanying alterations in neutral lipid storage, reflective of a general disturbance of free fatty acid metabolism in human hepatocytes with the ε4 allele.

Differential atrophy along the longitudinal hippocampal axis in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that primarily affects the hippocampus. Since hippocampal studies have highlighted a differential subregional regulation along its longitudinal axis, a more detailed analysis addressing subregional changes along the longitudinal hippocampal axis has the potential to provide new relevant biomarkers. This study included structural brain MRI data of 583 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cognitively normal (CN) subjects, mild cognitively impaired (MCI) subjects and AD patients were conveniently selected considering the age and sex match between clinical groups. Structural MRI acquisitions were pre-processed and analysed with a new longitudinal axis segmentation method, dividing the hippocampus in three subdivisions (anterior, intermediate, and posterior). When normalizing the volume of hippocampal sub-divisions to total hippocampus, the posterior hippocampus negatively correlates with age only in CN subjects (r = -.31). The longitudinal ratio of hippocampal atrophy (anterior sub-division divided by the posterior one) shows a significant increase with age only in CN (r = .25). Overall, in AD, the posterior hippocampus is predominantly atrophied early on. Consequently, the anterior/posterior hippocampal ratio is an AD differentiating metric at early disease stages with potential for diagnostic and prognostic applications.

ModInterv COVID-19: An online platform to monitor the evolution of epidemic curves.

We present the software ModInterv as an informatics tool to monitor, in an automated and user-friendly manner, the evolution and trend of COVID-19 epidemic curves, both for cases and deaths. The ModInterv software uses parametric generalized growth models, together with LOWESS regression analysis, to fit epidemic curves with multiple waves of infections for countries around the world as well as for states and cities in Brazil and the USA. The software automatically accesses publicly available COVID-19 databases maintained by the Johns Hopkins University (for countries as well as states and cities in the USA) and the Federal University of Viçosa (for states and cities in Brazil). The richness of the implemented models lies in the possibility of quantitatively and reliably detecting the distinct acceleration regimes of the disease. We describe the backend structure of software as well as its practical use. The software helps the user not only to understand the current stage of the epidemic in a chosen location but also to make short term predictions as to how the curves may evolve. The app is freely available on the internet (http://fisica.ufpr.br/modinterv), thus making a sophisticated mathematical analysis of epidemic data readily accessible to any interested user.

Lung cancer staging, the established role of bronchoscopy.

PURPOSE OF REVIEW: Lung cancer is the leading cause of cancer-related deaths worldwide. In the absence of distant metastases, accurate mediastinal nodal staging determines treatment approaches to achieve most favourable outcomes for patients. Mediastinal staging differentiates N0/N1 disease from N2/N3 in surgical candidates. Likewise, presence of nodal involvement in nonsurgical candidates who are being considered for stereotactic body radiation therapy is also critical. This review article seeks to discuss the current options available for mediastinal staging in nonsmall cell lung cancer (NSCLC), particularly the role of bronchoscopy. RECENT FINDINGS: Although several techniques are available to stage the mediastinum, bronchoscopy with EBUS-TBNA with or without EUS-FNA appears to be superior in most clinical situations based on its ability to concomitantly diagnose and stage at once, safety, accessibility to the widest array of lymph node stations, cost and low risk of complications. However, training and experience are required to achieve consistent diagnostic accuracy with EBUS-TBNA. SUMMARY: EBUS-TBNA with or without EUS-FNA is considered the modality of choice in the diagnosis and staging of NSCLC in both surgical and nonsurgical candidates.

Prospective cohort of cryobiopsy in interstitial lung diseases: a single center experience.

RATIONALE: Transbronchial cryobiopsy has been increasingly used to diagnose interstitial lung diseases. However, there is uncertainty regarding its accuracy and risks, mainly due to a paucity of prospective or randomized trials comparing cryobiopsy to surgical biopsy. OBJECTIVES: To evaluate the diagnostic yield and complications of cryobiopsy in patients selected by multidisciplinary discussion. METHODS: This was a prospective cohort from 2017 to 2019. We included consecutive patients with suspected interstitial lung diseases being considered for lung biopsy presented at our multidisciplinary meeting. MEASUREMENTS AND MAIN RESULTS: Of 112 patients, we recommended no biopsy in 31, transbronchial forceps biopsy in 16, cryobiopsy in 54 and surgical biopsy in 11. By the end of the study, 34 patients had had cryobiopsy and 24 patients, surgical biopsy. Overall pathologic and multidisciplinary diagnostic yield of cryobiopsy was 47.1% and 61.8%, respectively. The yield increased over time for both pathologic (year 1: 28.6%, year 2: 54.5%, year 3: 66.7%, p = 0.161) and multidisciplinary (year 1: 50%, year 2: 63.6%, year 3: 77.8%, p = 0.412) diagnosis. Overall rate of grade 4 bleeding after cryobiopsy was 11.8%. Cryobiopsy required less chest tube placement (11.8% vs 100%, p < 0.001) and less hospitalizations compared to surgical biopsy (26.5% vs 95.7%, p < 0.001), but hospitalized patients had a longer median hospital stay (2 days vs 1 day, p = 0.004). CONCLUSIONS: Diagnostic yield of cryobiopsy increased over time but the overall grade 4 bleeding rate was 11.8%.

Serum Phospholipid Profile Changes in Gaucher Disease and Parkinson's Disease.

Alterations in the levels of serum sphingolipids and phospholipids have been reported in Gaucher disease and in Parkinson's disease, suggesting a potential role of these lipids as biomarkers. This project's objective is to detect novel associations and novel candidate biomarkers in the largest Spanish Gaucher and Parkinson diseases of the Iberian Peninsula. For that, 278 participants were included: 100 sporadic Parkinson's patients, 70 Gaucher patients, 15 GBA1-mutation-carrier Parkinson's patients and 93 controls. A serum lipidomics array including 10 phospholipid groups, 368 species, was performed using high-performance liquid chromatography-mass spectrometry. Lipid levels were compared between groups via multiple-regression analyses controlling for clinical and demographic parameters. Additionally, lipid levels were compared within the Gaucher and Parkinson's groups controlling for medication and/or disease severity. Results were controlled for robustness by filtering of non-detectable lipid values. There was an increase in the levels of phosphatidylcholine, with a simultaneous decrease in lyso-phosphatidylcholine, in the Gaucher, Parkinson's and GBA1-mutation-carrier Parkinson's patients vs. controls. Phosphatidylethanolamine, lyso- and plasmalogen-phosphatidylethanolamine were also increased in Gaucher and Parkinson's. Gaucher patients also showed an increase in lyso-phosphatidylserine and phosphatidylglycerol. While in the Gaucher and Parkinson's groups, velaglucerase alpha and dopamine agonists, respectively, showed positive associations with the lipid changes, miglustat treatment in Gaucher patients normalized the altered phosphatidylcholine/lyso-phosphatidylcholine ratio. In conclusion, Gaucher and Parkinson's patients showed changes in various serum phospholipid levels when compared with healthy controls, further supporting the role of such lipids in disease development and, possibly, as putative biomarkers. This hypothesis was reinforced by the normalizing effect of miglustat, and by controlling for data robustness, even though the limited number of participants, especially in the sub-distribution by treatment groups in GD requires validation in a larger number of patients.

Effect of Microencapsulation on Chemical Composition and Antimicrobial, Antioxidant and Cytotoxic Properties of Lemongrass (Cymbopogon flexuosus) Essential Oil.

Research background: Lemongrass (Cymbopogon flexuosus) essential oil exhibits antimicrobial and antioxidant properties due to the presence of α-citral and ß-citral. Essential oils are susceptible to volatilization and oxidation when applied to food matrices. Therefore, a barrier is needed to protect this material. The present study aims to produce microparticles containing lemongrass essential oil, with gum arabic and maltodextrin using spray drying technology. Experimental approach: Lemongrass essential oil was extracted by the hydrodistillation method and later microencapsulated with different wall materials. Free and microencapsulated lemongrass essential oil was evaluated for the cytotoxic activity (using Artemia salina as test sample), chemical composition (GC-MS), encapsulation efficiency, antioxidant activity (DPPH, ABTS and FRAP), antimicrobial activity and minimum inhibitory concentration. Results and conclusions: The lethal concentration (LC50) of lemongrass essential oil in the cytotoxic test was 8.43 µg/mL against Artemia salina; a high activity that can be associated with the presence of α-citral (~33%) and ß-citral (~21%) in the samples, since these were the main compounds with bioactive properties. The highest value of microencapsulation efficiency (88.11%) was obtained when only gum arabic was used as wall material. In general, the microparticles showed satisfactory antioxidant activity (expressed as Trolox equivalents, between 348.66 and 2042.30 µmol/100 g) and bactericidal effect in vitro against Gram-positive and Gram-negative microorganisms. In conclusion, the microencapsulated lemongrass essential oil is a promising functional additive in the food and pharmaceutical industries. Novelty and scientific contribution: This study shows that microparticles containing lemongrass essential oil can be prepared using gum arabic and maltodextrin as wall materials by spray drying, resulting in high microencapsulation efficiency. The drying process maintained the antimicrobial and antioxidant properties of the essential oil. Therefore, the microencapsulated lemongrass essential oil is considered a natural, functional and promising additive in the food industry. Its antimicrobial action can increase the shelf life of fresh and semi-fresh products such as cheese, yogurts and meat products. In addition, its antioxidant action can delay the lipid and protein oxidation in food products.

Subclinical Burkholderia pseudomallei Infection Associated with Travel to the British Virgin Islands.

Phylogenetic analysis of a clinical isolate associated with subclinical Burkholderia pseudomallei infection revealed probable exposure in the British Virgin Islands, where reported infections are limited. Clinicians should consider this geographic distribution when evaluating possible infection among persons with compatible travel history.

A Prediction Model to Help with Oncologic Mediastinal Evaluation for Radiation: HOMER.

Rationale: When stereotactic ablative radiotherapy is an option for patients with non-small cell lung cancer (NSCLC), distinguishing between N0, N1, and N2 or N3 (N2|3) disease is important.Objectives: To develop a prediction model for estimating the probability of N0, N1, and N2|3 disease.Methods: Consecutive patients with clinical-radiographic stage T1 to T3, N0 to N3, and M0 NSCLC who underwent endobronchial ultrasound-guided staging from a single center were included. Multivariate ordinal logistic regression analysis was used to predict the presence of N0, N1, or N2|3 disease. Temporal validation used consecutive patients from 3 years later at the same center. External validation used three other hospitals.Measurements and Main Results: In the model development cohort (n = 633), younger age, central location, adenocarcinoma, and higher positron emission tomography-computed tomography nodal stage were associated with a higher probability of having advanced nodal disease. Areas under the receiver operating characteristic curve (AUCs) were 0.84 and 0.86 for predicting N1 or higher (vs. N0) disease and N2|3 (vs. N0 or N1) disease, respectively. Model fit was acceptable (Hosmer-Lemeshow, P = 0.960; Brier score, 0.36). In the temporal validation cohort (n = 473), AUCs were 0.86 and 0.88. Model fit was acceptable (Hosmer-Lemeshow, P = 0.172; Brier score, 0.30). In the external validation cohort (n = 722), AUCs were 0.86 and 0.88 but required calibration (Hosmer-Lemeshow, P < 0.001; Brier score, 0.38). Calibration using the general calibration method resulted in acceptable model fit (Hosmer-Lemeshow, P = 0.094; Brier score, 0.34).Conclusions: This prediction model can estimate the probability of N0, N1, and N2|3 disease in patients with NSCLC. The model has the potential to facilitate decision-making in patients with NSCLC when stereotactic ablative radiotherapy is an option.

Complications following symptom-limited thoracentesis using suction.

BACKGROUND: Thoracentesis using suction is perceived to have increased risk of complications, including pneumothorax and re-expansion pulmonary oedema (REPO). Current guidelines recommend limiting drainage to 1.5 L to avoid REPO. Our purpose was to examine the incidence of complications with symptom-limited drainage of pleural fluid using suction and identify risk factors for REPO. METHODS: A retrospective cohort study of all adult patients who underwent symptom-limited thoracentesis using suction at our institution between January 1, 2004 and August 31, 2018 was performed, and a total of 10 344 thoracenteses were included. RESULTS: Pleural fluid ≥1.5 L was removed in 19% of the procedures. Thoracentesis was stopped due to chest discomfort (39%), complete drainage of fluid (37%) and persistent cough (13%). Pneumothorax based on chest radiography was detected in 3.98%, but only 0.28% required intervention. The incidence of REPO was 0.08%. The incidence of REPO increased with Eastern Cooperative Oncology Group performance status (ECOG PS) ≥3 compounded with ≥1.5 L (0.04-0.54%; 95% CI 0.13-2.06 L). Thoracentesis in those with ipsilateral mediastinal shift did not increase complications, but less fluid was removed (p<0.01). CONCLUSIONS: Symptom-limited thoracentesis using suction is safe even with large volumes. Pneumothorax requiring intervention and REPO are both rare. There were no increased procedural complications in those with ipsilateral mediastinal shift. REPO increased with poor ECOG PS and drainage ≥1.5 L. Symptom-limited drainage using suction without pleural manometry is safe.

Emergence of community-acquired methicillin-resistant Staphylococcus aureus EMRSA-15 clone as the predominant cause of diabetic foot ulcer infections in Portugal.

Methicillin-resistant Staphylococcus aureus (MRSA) are often found in infected diabetic foot ulcers, in which the prevalence may reach 40%. These complications are one of the main causes of morbidity in diabetic patients. The objectives of this study were to investigate the prevalence and antimicrobial resistance of MRSA strains in infected diabetic foot ulcers and to characterize their genetic lineages. Samples collected from 42 type 2 diabetic patients, presenting infected foot ulcers, were seeded onto ORSAB plates with 2 mg/L of oxacillin for MRSA isolation. Susceptibility to 14 antimicrobial agents was tested by the Kirby-Bauer disk diffusion method. The presence of resistance genes, virulence factors, and the immune evasion cluster system was studied by PCR. All isolates were characterized by MLST, accessory gene regulator (agr), spa, and staphylococcal chromosomal cassette mec (SCCmec) typing. Twenty-five MRSA strains were isolated. All isolates showed resistance to penicillin and cefoxitin. Sixteen isolates showed phenotypic resistance to erythromycin being 7 co-resistant to clindamycin. Resistance to trimethoprim-sulfamethoxazole was found in 2 isolates harboring the dfrA and dfrG genes. The IEC genes were detected in 80% of isolates, 16 of which were ascribed to IEC-type B. Isolates were assigned to 12 different spa types. The MLST analysis grouped the isolates into 7 sequence types being the majority (68%) ascribed to SCCmec type IV. In this study, there was a high prevalence of the EMRSA-15 clone presenting multiple resistances in diabetic foot ulcers making these infections complicated to treat leading to a higher morbidity and mortality in diabetic patients.

Continuous infusion chemotherapy, radiotherapy, and FDG-PET are feasible during extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) may be used in extreme circumstances for patients with a mediastinal mass and respiratory failure. We report on a young man with primary mediastinal B-cell lymphoma invading into the trachea, requiring a 40-day ECMO run who underwent fluorodeoxyglucose positron emission tomography (FDG-PET) imaging and treatment with concurrent mediastinal irradiation and continuous infusion chemotherapy while on this life-saving technology. This case illustrates that oncology patients may be managed by multidisciplinary teams for extended periods in extraordinary circumstances using multimodality therapies. Additionally, to our knowledge this is the first case to demonstrate the feasibility of FDG-PET imaging while on ECMO.

The Influence of Antiretroviral Therapy on Hepatitis C Virus Viral Load and Liver Fibrosis in Human Immunodeficiency Virus-Coinfected Patients: An Observational Study.

BACKGROUND: The role of antiretroviral therapy (ART) for Hepatitis C viral load (HCV-VL) and liver fibrosis is poorly understood. This study aimed at evaluating the influence of ART on HCV-VL and liver fibrosis in human immunodeficiency virus (HIV)/HCV-coinfected patients. METHODS: We conducted a retrospective cohort study of HIV/HCV-coinfected patients followed at a tertiary university hospital. RESULTS: In total, 143 patients were included. In 61 patients, ART initiation was accompanied by an increase in HCV-VL and a decrease in HIV viral load (HIV-VL), whereas ART suspension led to a decrease in HCV-VL and an increase in HIV-VL. Among the 55 HIV-suppressed patients who switched to a raltegravir (RAL)-containing regimen, median HCV-VL levels decreased significantly, while switching to a rilpivirine-containing regimen did not yield a significant reduction. DISCUSSION: If the -treatment of chronic hepatitis starts before ART, ART initiation should be delayed as much as possible. If ART has been started, it is advisable to wait 1 year before initiating chronic hepatitis treatment. RAL as the third agent in an ART regimen could be beneficial in HIV/HCV-coinfected patients, in comparison to other antiretroviral drugs. CONCLUSION: The start and the suspension of ART significantly interferes with HCV-VL in HIV/HCV-coinfected patients.

A Prediction Model to Help with the Assessment of Adenopathy in Lung Cancer: HAL.

RATIONALE: Estimating the probability of finding N2 or N3 (prN2/3) malignant nodal disease on endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in patients with non-small cell lung cancer (NSCLC) can facilitate the selection of subsequent management strategies. OBJECTIVES: To develop a clinical prediction model for estimating the prN2/3. METHODS: We used the AQuIRE (American College of Chest Physicians Quality Improvement Registry, Evaluation, and Education) registry to identify patients with NSCLC with clinical radiographic stage T1-3, N0-3, M0 disease that had EBUS-TBNA for staging. The dependent variable was the presence of N2 or N3 disease (vs. N0 or N1) as assessed by EBUS-TBNA. Univariate followed by multivariable logistic regression analysis was used to develop a parsimonious clinical prediction model to estimate prN2/3. External validation was performed using data from three other hospitals. MEASUREMENTS AND MAIN RESULTS: The model derivation cohort (n = 633) had a 25% prevalence of malignant N2 or N3 disease. Younger age, central location, adenocarcinoma histology, and higher positron emission tomography-computed tomography N stage were associated with a higher prN2/3. Area under the receiver operating characteristic curve was 0.85 (95% confidence interval, 0.82-0.89), model fit was acceptable (Hosmer-Lemeshow, P = 0.62; Brier score, 0.125). We externally validated the model in 722 patients. Area under the receiver operating characteristic curve was 0.88 (95% confidence interval, 0.85-0.90). Calibration using the general calibration model method resulted in acceptable goodness of fit (Hosmer-Lemeshow test, P = 0.54; Brier score, 0.132). CONCLUSIONS: Our prediction rule can be used to estimate prN2/3 in patients with NSCLC. The model has the potential to facilitate clinical decision making in the staging of NSCLC.

Challenges of an Autonomous Wildfire Geolocation System Based on Synthetic Vision Technology.

Thermographic imaging has been the preferred technology for the detection and tracking of wildfires for many years. Thermographic cameras provide some very important advantages, such as the ability to remotely detect hotspots which could potentially turn into wildfires if the appropriate conditions are met. Also, they can serve as a key preventive method, especially when the 30-30-30 rule is met, which describes a situation where the ambient temperature is higher than 30 ∘ C, the relative humidity is lower than 30%, and the wind speed is higher than 30 km/h. Under these circumstances, the likelihood of a wildfire outburst is quite high, and its effects can be catastrophic due to the high-speed winds and dry conditions. If this sort of scenario actually occurs, every possible technological advantage shall be used by firefighting teams to enable the rapid and efficient coordination of their response teams and to control the wildfire following a safe and well-planned strategy. However, most of the early detection methods for wildfires, such as the aforementioned thermographic cameras, lack a sufficient level of automation and usually rely on human interaction, imposing high degrees of subjectivity and latency. This is especially critical when a high volume of data is required in real time to correctly support decision-making scenarios during the wildfire suppression tasks. The present paper addresses this situation by analyzing the challenges faced by a fully autonomous wildfire detection and a tracking system containing a fully automated wildfire georeferencing system based on synthetic vision technology. Such a tool would provide firefighting teams with a solution capable of continuously surveilling a particular area and completely autonomously identifying and providing georeferenced information on current or potential wildfires in real time.

Artemether-lumefantrine and liver enzyme abnormalities in non-severe Plasmodium falciparum malaria in returned travellers: a retrospective comparative study with quinine-doxycycline in a Portuguese centre.

BACKGROUND: Artemisinin-based therapy is the current standard treatment for non-severe malaria due to Plasmodium falciparum. The potential for asymptomatic liver toxicity of this therapy and its implication in clinical practice is currently unknown. The aim of this study is to assess the hepatic function in patients treated with a standard three-day artemisinin-based regimen and to compare it with the quinine-doxycycline regimen. METHODS: Retrospective and comparative study of returned adult travellers admitted with non-severe P. falciparum malaria. Fifty-seven patients were included: 19 treated with artemisinin-based therapy and 38 with quinine-doxycycline therapy. RESULTS: During treatment, when compared with quinine-doxycycline group, the artemisinin-lumefantrine group presented a higher proportion of significant liver enzyme abnormalities (42 vs. 5%, p < 0.01) and a higher peak value of aspartate aminotransferase (131 vs. 64 U/L, p < 0.01) and alanine aminotransferase (99 vs. 75 U/L, p = 0.05). None of the patients was symptomatic, there were no treatment interruptions and all patients achieved clinical cure. CONCLUSIONS: Treatment of uncomplicated falciparum malaria with artemisinin-based therapy might cause asymptomatic liver enzyme abnormalities in the first days of treatment. Nevertheless, these liver enzyme abnormalities seem to be harmless, asymptomatic and self-limited.

Defects in subventricular zone pigmented epithelium-derived factor niche signaling in the senescence-accelerated mouse prone-8.

We studied potential changes in the subventricular zone (SVZ) stem cell niche of the senescence-accelerated mouse prone-8 (SAM-P8) aging model. Bromodeoxyuridine (BrdU) assays with longtime survival revealed a lower number of label-retaining stem cells in the SAM-P8 SVZ compared with the SAM-Resistant 1 (SAM-R1) control strain. We also found that in SAM-P8 niche signaling is attenuated and the stem cell pool is less responsive to the self-renewal niche factor pigmented epithelium-derived factor (PEDF). Protein analysis demonstrated stable amounts of the PEDF ligand in the SAM-P8 SVZ niche; however, SAM-P8 stem cells present a significant expression decrease of patatin-like phospholipase domain containing 2, a receptor for PEDF (PNPLA2-PEDF) receptor, but not of laminin receptor (LR), a receptor for PEDF (LR-PEDF) receptor. We observed changes in self-renewal related genes (hairy and enhancer of split 1 (Hes1), hairy and enhancer of split 1 (Hes5), Sox2] and report that although these genes are down-regulated in SAM-P8, differentiation genes (Pax6) are up-regulated and neurogenesis is increased. Finally, sheltering mammalian telomere complexes might be also involved given a down-regulation of telomeric repeat binding factor 1 (Terf1) expression was observed in SAM-P8 at young age periods. Differences between these 2 models, SAM-P8 and SAM-R1 controls, have been previously detected at more advanced ages. We now describe alterations in the PEDF signaling pathway and stem cell self-renewal at a very young age, which could be involved in the premature senescence observed in the SAM-P8 model.

Prevalence of testosterone deficiency in HIV-infected men under antiretroviral therapy.

BACKGROUND: The prevalence of hypogonadism in HIV-infected patients is still a matter of debate as there is no standardized consensual diagnostic method. In addition, the etiology and endocrine/metabolic implications of hypogonadism in this population remain controversial. This study aims to determine the prevalence of testosterone deficiency in a single-site hospital and to evaluate its association with potential risk factors, lipodystrophy, metabolic syndrome, and cardiovascular risk. METHODS: This study analyzed 245 HIV-infected men on combined antiretroviral therapy. Patients with low total testosterone (TT) levels (<2.8 ng/mL) and/or low calculated free testosterone (FT) levels (<6.5 ng/dL) were considered testosterone deficient. According to their LH and FSH levels, patients were classified as having hypogonadotropic or hypergonadotropic dysfunction. Other clinical, anthropometric, and analytic parameters were also collected and analyzed. RESULTS: The prevalence of testosterone deficiency in our population was 29.4 %. Among them, 56.9 % had hypogonadotropic dysfunction and 43.1 % presented with hypergonadotropic dysfunction. Patients with testosterone deficiency were older (p < 0.001), had higher HbA1c levels (p = 0.016) and higher systolic blood pressure (p = 0.007). Patients with lower testosterone levels had higher prevalence of isolated central fat accumulation (p = 0.015) and had higher median cardiovascular risk at 10 years as measured by the Framingham Risk Score (p = 0.004) and 10-Year ASCVD risk (p = 0.002). CONCLUSIONS: The prevalence of testosterone deficiency in this HIV population is high, with hypogonadotropic dysfunction being responsible for the majority of cases. Testosterone deficiency might predispose to, or be involved, in the pathogenesis of HIV-associated lipodystrophy. Patients with low testosterone levels have higher cardiovascular risk, highlighting the importance of early diagnosis of this condition.