Preterm birth and oxidative stress: Effects of acute physical exercise and hypoxia physiological responses.

Preterm birth is a global health issue that can induce lifelong medical sequela. Presently, at least one in ten newborns are born prematurely. At birth, preterm newborns exhibit higher levels of oxidative stress (OS) due to the inability to face the oxygen rich environment in which they are born into. Moreover, their immature respiratory, digestive, immune and antioxidant defense systems, as well as the potential numerous medical interventions following a preterm birth, such as oxygen resuscitation, nutrition, phototherapy and blood transfusion further contribute to high levels of OS. Although the acute effects seem well established, little is known regarding the long-term effects of preterm birth on OS. This matter is especially important given that chronically elevated OS levels may persist into adulthood and consequently contribute to the development of numerous non-communicable diseases observed in people born preterm such as diabetes, hypertension or lung disorders. The purpose of this review is to summarize the current knowledge regarding the consequences of preterm birth on OS levels from newborn to adulthood. In addition, the effects of physical activity and hypoxia, both known to disrupt redox balance, on OS modulation in preterm individuals are also explored

Profils épidémiologiques cliniques et bactériologiques des infections du tractus urinaire dans le service des maladies infectieuses et tropicales de l’hôpital Tenon de Paris: « étude préliminaire ».

Objectif : décrire les caractéristiques épidémiologiques, cliniques et bactériologiques des infections du tractus urinaire(ITU) dans le service des maladies infectieuses et tropicales du CHU de Ténon à Paris. Patients et méthodes : Il s’est agi d’une étude rétrospective réalisée le 25 Octobre 2016 dans le service des maladies infectieuses et tropicales du CHU de Ténon à Paris. Etaient inclus tous les patients hospitalisés, ayant à l’examen cytobactériologique des urines(ECBU) une leucocyturie significative et une uroculture positives. Résultats : Quatre patients avaient été recensés sur un total de 28 patients hospitalisés, soit une prévalence hospitalière de 14%. Leurs âges variaient entre 22 ans et 82 ans. Les signes urinaires étaient présents chez un seul patient, et étaient représentés par une dysurie et une douleur lombaire évoluant dans un contexte fébrile. Les bactéries isolées à l’examen cytobactériologique des urines(ECBU) étaient représentées par E. coli (2) dont 1 productrice de bétalactamase à spectre élargi(BLSE), P. aeruginosa(1), et K. pneumoniae (1) de phénotype sauvage tous les deux. Conclusion : Les ITU semblent relativement fréquentes au service des maladies infectieuses de l’hôpital Tenon. Ces infections évoluaient presque toujours avec d’autres comorbidités chez tous les patients. Elles s’accompagnaient rarement de signes d’appel urinaire d’où l’intérêt de leur recherche systématique dans le cadre de tout bilan infectieux

Exercise Overrides Blunted Hypoxic Ventilatory Response in Prematurely Born Men.

Pre-term birth provokes life-long anatomical and functional respiratory system sequelae. Although blunted hypoxic ventilatory response (HVR) is consistently observed in pre-term infants, it remains unclear if it persists with aging and, moreover, if it influences hypoxic exercise capacity. In addition, it remains unresolved whether the previously observed prematurity-related alterations in redox balance could contribute to HVR modulation. Twenty-one prematurely born adult males (gestational age = 29 ± 4 weeks], and 14 age matched controls born at full term (gestational age = 39 ± 2 weeks) underwent three tests in a randomized manner: (1) hypoxia chemo-sensitivity test to determine the resting and exercise poikilocapnic HVR and a graded exercise test to volitional exhaustion in (2) normoxia (F <sub>i</sub> O <sub>2</sub> = 0.21), and (3) normobaric hypoxia (F <sub>i</sub> O <sub>2</sub> = 0.13) to compare the hypoxia-related effects on maximal aerobic power (MAP). Selected prooxidant and antioxidant markers were analyzed from venous samples obtained before and after the HVR tests. Resting HVR was lower in the pre-term (0.21 ± 0.21 L ⋅ min <sup>-1</sup> ⋅ kg <sup>-1</sup> ) compared to full-term born individuals (0.47 ± 0.23 L ⋅ min <sup>-1</sup> ⋅ kg <sup>-1</sup> ; p < 0.05). No differences were noted in the exercise HVR or in any of the measured oxidative stress markers before or after the HVR test. Hypoxia-related reduction of MAP was comparable between the groups. These findings indicate that blunted resting HVR in prematurely born men persists into adulthood. Also, active adults born prematurely seem to tolerate hypoxic exercise well and should, hence, not be discouraged to engage in physical activities in hypoxic environments. Nevertheless, the blunted resting HVR and greater desaturation observed in the pre-term born individuals warrant caution especially during prolonged hypoxic exposures

Rapid, progressive neuropathic arthropathy of the hip in a patient co-infected with human immunodeficiency virus, hepatitis C virus and tertiary syphilis: case report

BACKGROUND: Syphilis is a chronic infection that is classified into three stages. In its tertiary stage, syphilis spreads to the brain, heart and other organs; the lesions may involve the skin, mucous membranes and bones. Neuropathic arthropathy associated with tertiary syphilis has rarely been described in Europe and its association with HIV-HCV co-infection has not been reported so far.This article reports the case of a man with tertiary syphilis presenting with rapidly evolving neuropathic arthropathy of the hip and extensive bone destruction. CASE PRESENTATION: On initial presentation, the patient complained of progressively worsening left-sided coxalgia without localized or generalized inflammation. The patient reported to have no history of previous infections, trauma or cancer. Plain x-ray films of the left coxofemoral joint showed marked degeneration with necrosis of the proximal epiphysis of femur and morphological alterations of the acetabulum without protrusion. Primary coxarthrosis was diagnosed and hip arthroplasty was offered, but the patient declined treatment. Three months later, the patient presented a marked deterioration of his general condition. He disclosed that he was seropositive for HCV and HIV, as confirmed by serology. Syphilis serology testing was also positive. A Girdlestone's procedure was performed and samples were collected for routine cultures for bacteria and acid fast bacilli, all resulting negative.Although histological findings were inconclusive, confirmed positive serology for syphilis associated with progressive arthropathy was strongly suggestive of tertiary syphilis, probably exacerbated by HIV-HCV co-infection. The patient partially recovered the ability to walk. CONCLUSIONS: Due to the resurgence of syphilis, this disease should be considered as a possible cause of neuropathic arthropathy when other infectious causes have been ruled out, particularly in patients with HIV and/or HCV co-infection

Immunization with HIV protease peptides linked to syngeneic erythrocytes

New potent vaccine adjuvants are desirable for increasing the efficacy of novel vaccine modalities such as DNA and peptides. We therefore tested if syngeneic erythrocytes could serve as delivery vectors for selected HIV peptides and compared the potency of these constructs to immunization with peptides in phosphate buffered saline or in incomplete Freunds adjuvant. Immunization of mice with peptides in a low dose (5 ng) coupled to erythrocytes induced a weak immune response in mice. These peptides alone (5 μg) gave no immune responses, while formulating the peptides (50 μg) in IFA induced strong homologous immunity as well as prominent cross reactivity to a related mutant epitope. Thus, vaccine delivery using syngeneic erythrocytes, although attractive for clinical use, might be of limited value due to the low amount of antigen that can be loaded per erythrocyte

Geographical limits of the Southeastern distribution of Aedes aegypti (Diptera, Culicidae) in Argentina

The current geographical distribution of Aedes aegypti in South America is dramatically expanding inside Argentina, reaching a wider distribution than during its early eradication in 1967. Simultaneously, cases of dengue have increased during the last few years, and the situation has been recently worsened by the confirmation of the presence of the different dengue serotypes simultaneously circulating in new regions. Here we report on the passive south-eastern dispersion of A. aegypti in Argentina.Fil: Díaz Nieto, Leonardo Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biociencias Agrícolas y Ambientales. Grupo Vinculado al Centro de Estudios de la Biodiversidad y Biotecnología de Mar del Plata- INBA. Fundación para Investigaciones Biológicas Aplicadas; ArgentinaFil: Maciá, Arnaldo. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Entomología; ArgentinaFil: Perotti, M. Alejandra. University of Reading. School of Biological Sciences; Reino UnidoFil: Berón, Corina Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biociencias Agrícolas y Ambientales. Grupo Vinculado al Centro de Estudios de la Biodiversidad y Biotecnología de Mar del Plata- INBA. Fundación para Investigaciones Biológicas Aplicadas; Argentin

Long-term efficacy and safety of fostemsavir among subgroups of heavily treatment-experienced adults with HIV-1

Objectives: The aim of this study was to understand how demographic and treatment-related factors impact responses to fostemsavir-based regimens. Design: BRIGHTE is an ongoing phase 3 study evaluating twice-daily fostemsavir 600 mg and optimized background therapy (OBT) in heavily treatment-experienced individuals failing antiretroviral therapy with limited treatment options (Randomized Cohort 1-2 and Nonrandomized Cohort 0 fully active antiretroviral classes). Methods: Virologic response rates (HIV-1 RNA <40 copies/ml, Snapshot analysis) and CD4+ T-cell count increases in the Randomized Cohort were analysed by prespecified baseline characteristics (age, race, sex, region, HIV-1 RNA, CD4+ T-cell count) and viral susceptibility to OBT. Safety results were analysed by baseline characteristics for combined cohorts (post hoc). Results: In the Randomized Cohort, virologic response rates increased between Weeks 24 and 96 across most subgroups. Virologic response rates over time were most clearly associated with overall susceptibility scores for new OBT agents (OSS-new). CD4+ T-cell count increases were comparable across subgroups. Participants with baseline CD4+ T-cell counts less than 20 cells/μl had a mean increase of 240 cells/μl. In the safety population, more participants with baseline CD4+ T-cell counts less than 20 vs. at least 200 cells/μl had grade 3/4 adverse events [53/107 (50%) vs. 24/96 (25%)], serious adverse events [58/107 (54%) vs. 25/96 (26%)] and deaths [16/107 (15%) vs. 2/96 (2%)]. There were no safety differences by other subgroups. Conclusion: Week 96 results for BRIGHTE demonstrate comparable rates of virologic and immunologic response (Randomized Cohort) and safety (combined cohorts) across subgroups. OSS-new is an important consideration when constructing optimized antiretroviral regimens for heavily treatment-experienced individuals with limited remaining treatment options

Chronic pain associated with the Chikungunya Fever: long lasting burden of an acute illness

<p>Abstract</p> <p>Background</p> <p>Chikungunya virus (CHIKV) is responsible for major epidemics worldwide. Autochthonous cases were recently reported in several European countries. Acute infection is thought to be monophasic. However reports on chronic pain related to CHIKV infection have been made. In particular, the fact that many of these patients do not respond well to usual analgesics suggests that the nature of chronic pain may be not only nociceptive but also neuropathic. Neuropathic pain syndromes require specific treatment and the identification of neuropathic characteristics (NC) in a pain syndrome is a major step towards pain control.</p> <p>Methods</p> <p>We carried out a cross-sectional study at the end of the major two-wave outbreak lasting 17 months in Réunion Island. We assessed pain in 106 patients seeking general practitioners with confirmed infection with the CHIK virus, and evaluated its impact on quality of life (QoL).</p> <p>Results</p> <p>The mean intensity of pain on the visual-analogical scale (VAS) was 5.8 ± 2.1, and its mean duration was 89 ± 2 days. Fifty-six patients fulfilled the definition of chronic pain. Pain had NC in 18.9% according to the DN4 questionnaire. Conversely, about two thirds (65%) of patients with NC had chronic pain. The average pain intensity was similar between patients with or without NC (6.0 ± 1.7 vs 6.1 ± 2.0). However, the total score of the Short Form-McGill Pain Questionnaire (SF-MPQ)(15.5 ± 5.2 vs 11.6 ± 5.2; p < 0.01) and both the affective (18.8 ± 6.2 vs 13.4 ± 6.7; p < 0.01) and sensory subscores (34.3 ± 10.7 vs 25.0 ± 9.9; p < 0.01) were significantly higher in patients with NC. The mean pain interference in life activities calculated from the Brief Pain Inventory (BPI) was significantly higher in patients with chronic pain than in patients without it (6.8 ± 1.9 vs 5.9 ± 1.9, p < 0.05). This score was also significantly higher in patients with NC than in those without such a feature (7.2 ± 1.5 vs 6.1 ± 1.9, p < 0.05).</p> <p>Conclusions</p> <p>There exists a specific chronic pain condition associated to CHIKV. Pain with NC seems to be associated with more aggressive clinical picture, more intense impact in QoL and more challenging pharmacological treatment.</p

A pilot study to investigate respiratory ill health in people living with HIV

Background: Helping people living with HIV (PLWH) to maintain long‐term health as they age is central to HIV care and involves monitoring for chronic HIV‐associated co‐morbidities. Chronic lung disease (CLD) is recognised to be more common in PLWH as they age, but UK data on CLD prevalence and phenotype in PLWH are limited, particularly in female, non‐white, never smoking groups, and studies of progression over time are lacking. This pilot study aimed to obtain preliminary data on CLD in these subgroups and establish a simple scheme for monitoring lung health of PLWH for a future longitudinal study. Methods: Cross‐sectional pilot of CLD prevalence among PLWH on ART by age, gender, ethnicity and smoking status using convenience sampling of PLWH attending routine clinics. PLWH completed a web‐based questionnaire of self‐reported chronic cough, wheeze & phlegm production using the BOLD study questions; dyspnoea using the Medical Research Council (mMRC) scale; health related quality of life (EQ‐5D‐5L); respiratory, smoking and other lung exposure history. Forced Expiratory Volume (FEV)1 and Forced Vital Capacity (FVC) were measured by spirometry and z‐scores derived from Global Lung Initiative age, sex and ethnicity predicted values. We extracted HIV data from clinical records and evaluated the suitability and acceptability of the measurements. 50 HIV negative controls matched for smoking status were also assessed. Results: We recruited 150 PLWH, median age 46, 31% female, 47% white. 65% were never smokers, 45% reported childhood exposure to solid cooking fuel. 49% reported a history of PCP, TB or pneumonia and 26% a diagnosis of COPD, asthma or bronchiectasis. All groups had lung ill‐health (table) that correlated with EQ5D5L. Conclusion: CLD may affect all PLWH subgroups. These data and methods can inform a longitudinal study of CLD in UK PLWH

Phase I Randomised Clinical Trial of an HIV-1CN54, Clade C, Trimeric Envelope Vaccine Candidate Delivered Vaginally

We conducted a phase 1 double-blind randomised controlled trial (RCT) of a HIV-1 envelope protein (CN54 gp140) candidate vaccine delivered vaginally to assess immunogenicity and safety. It was hypothesised that repeated delivery of gp140 may facilitate antigen uptake and presentation at this mucosal surface. Twenty two healthy female volunteers aged 18–45 years were entered into the trial, the first receiving open-label active product. Subsequently, 16 women were randomised to receive 9 doses of 100 µg of gp140 in 3 ml of a Carbopol 974P based gel, 5 were randomised to placebo solution in the same gel, delivered vaginally via an applicator. Participants delivered the vaccine three times a week over three weeks during one menstrual cycle, and were followed up for two further months. There were no serious adverse events, and the vaccine was well tolerated. No sustained systemic or local IgG, IgA, or T cell responses to the gp140 were detected following vaginal immunisations. Repeated vaginal immunisation with a HIV-1 envelope protein alone formulated in Carbopol gel was safe, but did not induce local or systemic immune responses in healthy women