Validation of 2006 WHO Prediction Scores for True HIV Infection in Children Less than 18 Months with a Positive Serological HIV Test

All infants born to HIV-positive mothers have maternal HIV antibodies, sometimes persistent for 18 months. When Polymerase Chain Reaction (PCR) is not available, August 2006 World Health Organization (WHO) recommendations suggest that clinical criteria may be used for starting antiretroviral treatment (ART) in HIV seropositive children <18 months. Predictors are at least two out of sepsis, severe pneumonia and thrush, or any stage 4 defining clinical finding according to the WHO staging system.From January 2005 to October 2006, we conducted a prospective study on 236 hospitalized children <18 months old with a positive HIV serological test at the national reference hospital in Kigali. The following data were collected: PCR, clinical signs and CD4 cell count. Current proposed clinical criteria were present in 148 of 236 children (62.7%) and in 95 of 124 infected children, resulting in 76.6% sensitivity and 52.7% specificity. For 87 children (59.0%), clinical diagnosis was made based on severe unexplained malnutrition (stage 4 clinical WHO classification), of whom only 44 (50.5%) were PCR positive. Low CD4 count had a sensitivity of 55.6% and a specificity of 78.5%.As PCR is not yet widely available, clinical diagnosis is often necessary, but these criteria have poor specificity and therefore have limited use for HIV diagnosis. Unexplained malnutrition is not clearly enough defined in WHO recommendations. Extra pulmonary tuberculosis (TB), almost impossible to prove in young children, may often be the cause of malnutrition, especially in HIV-affected families more often exposed to TB. Food supplementation and TB treatment should be initiated before starting ART in children who are staged based only on severe malnutrition

Magic-factor 1, a partial agonist of met, induces muscle hypertrophy by protecting myogenic progenitors from apoptosis

Hepatocyte Growth Factor (HGF) is a pleiotropic cytokine of mesenchymal origin that mediates a characteristic array of biological activities including cell proliferation, survival, motility and morphogenesis. Its high affinity receptor, the tyrosine kinase Met, is expressed by a wide range of tissues and can be activated by either paracrine or autocrine stimulation. Adult myogenic precursor cells, the so called satellite cells, express both HGF and Met. Following muscle injury, autocrine HGF-Met stimulation plays a key role in promoting activation and early division of satellite cells, but is shut off in a second phase to allow myogenic differentiation. In culture, HGF stimulation promotes proliferation of muscle precursors thereby inhibiting their differentiation. METHODOLOGY/PRINCIPAL FINDINGS: Magic-Factor 1 (Met-Activating Genetically Improved Chimeric Factor-1 or Magic-F1) is an HGF-derived, engineered protein that contains two Met-binding domains repeated in tandem. It has a reduced affinity for Met and, in contrast to HGF it elicits activation of the AKT but not the ERK signaling pathway. As a result, Magic-F1 is not mitogenic but conserves the ability to promote cell survival. Here we show that Magic-F1 protects myogenic precursors against apoptosis, thus increasing their fusion ability and enhancing muscular differentiation. Electrotransfer of Magic-F1 gene into adult mice promoted muscular hypertrophy and decreased myocyte apoptosis. Magic-F1 transgenic mice displayed constitutive muscular hypertrophy, improved running performance and accelerated muscle regeneration following injury. Crossing of Magic-F1 transgenic mice with alpha-sarcoglycan knock-out mice -a mouse model of muscular dystrophy- or adenovirus-mediated Magic-F1 gene delivery resulted in amelioration of the dystrophic phenotype as measured by both anatomical/histological analysis and functional tests. CONCLUSIONS/SIGNIFICANCE: Because of these features Magic-F1 represents a novel molecular tool to counteract muscle wasting in major muscular diseases such as cachexia or muscular dystrophy

P–430 Male fertility preservation: is there a role for cancer-induced inflammation that affects semen quality in oncological patients?

Abstract Study question What is the cause of semen quality impairment in oncological patients during fertility preservation programs? The cancer type and stadiation or the resulting inflammatory state? Summary answer The inflammatory state seems to be related to the decrease of sperm concentration, motility, morphology and viability due to the worsening of oxidative stress microenvironment. What is known already Fertility preservation acquired a great importance in the last decades due to increase survival of oncological patients, boost of diagnosis under 40 years and postponement of paternal age. At the time of cryopreservation, only one third of these males are normozoospermic. Tumor itself or other factors, added to psychological reasons, may be involved but there is no clear evidence. An imbalance of ROS (reactive oxygen species) in semen can compromise its quality. However, the correlation between cancer-related generalized stress state and fertility is poorly investigated. Inflammatory conditions induced by infections and pathologies, including cancer, increase ROS. Study design, size, duration Retrospective observational analysis was performed on 45 patients (29.0 ± 6.9 yrs) recruited during their fertility preservation program between 2016 and 2019 with written consent on use of their clinical data for research purpose. Patients presented several oncological diagnoses. Semen samples obtained from multiple collections (N = 58) were analyzed before applying standard freezing protocol. Data on semen parameters, inflammatory indices, hematological values and type/stage of tumors were collected. No exclusion criteria were applied. Participants/materials, setting, methods Routine semen analysis was performed according to the WHO standards. Sperm concentration and motility were evaluated on Makler Chamber, whereas eosin stain and Diff-quick slides were used for viability and morphology, respectively. Lymphoma was present in 72% of cases, leukemia in 8%, seminoma in 7% and other cancers in 13%. Correlations (Pearson/Spearman tests) among principal semen parameters and hematological values (leukocytes, erythrocytes, hemoglobin, RDW, albumin, etc.) were calculated with a P-value &amp;lt;0.05 considered statistically significant. Main results and the role of chance The majority of semen samples showed a severe impairment, with one or more parameters under lower reference limits (WHO): 48.3% had sperm concentration under 15 millions/ml, 43.1% had a progressive motility under 32%, 41.4% had viability under 58% and 91.4% had abnormal morphology (under 4%). The role of potential inflammatory state was analyzed by correlating semen parameters and some hematological values. No correlation was found with cancer type. Negative association resulted between progressive motility (%PR) and leukocytes (p = 0.041) or RDW% (p = 0.015), but positive one with albumin (p = 0.012). Even sperm count, total motility (%PR+NP) and morphology were significantly correlated to RDW% (p = 0.003, p = 0.032, p = 0.034, respectively). These findings suggest a possible role of inflammation and ROS related generation in semen quality impairment. Indeed, albumin exerts a protective action, but leukocytes are known to cause ROS increase. Cancer-induced oxidative stress state may alter red blood cells homeostasis and vitality and increase erythrocytes turnover resulting in high RDW values. It is likely semen is worse when blood values indicate more severe cancer-induced inflammatory condition. Limitations, reasons for caution Significant correlations with type/stage of cancer were not found due to small number of each diagnosis, in spite our study considered 3 years of patients inclusion. Moreover, we lack to analyze the same patient before the cancer onset to avoid the influence of inflammatory state generated by the tumor itself. Wider implications of the findings: Understanding the influence of cancer-induced inflammatory state on semen quality could increase the awareness that clinicians should direct patient to the fertility preservation as soon as possible, even if diagnosis is still ongoing. It should be evaluated whether offering specific treatments may reduce oxidative stress conditions. Trial registration number Not applicable </jats:sec