Similar Inflammatory Responses following Sprint Interval Training Performed in Hypoxia and Normoxia

Sprint interval training (SIT) is an efficient intervention capable of improving aerobic capacity and exercise performance. This experiment aimed to determine differences in training adaptations and the inflammatory responses following 2 weeks of SIT (30 s maximal work, 4 min recovery; 4–7 repetitions) performed in normoxia or hypoxia. Forty-two untrained participants [(mean ± SD), age 21 ±1 years, body mass 72.1 ±11.4 kg, and height 173 ±10 cm] were equally and randomly assigned to one of three groups; control (CONT; no training, n = 14), normoxic (NORM; SIT in FiO2: 0.21, n = 14), and normobaric hypoxic (HYP; SIT in FiO2: 0.15, n = 14). Participants completed a V ˙ O 2peak V˙O2peak test, a time to exhaustion (TTE) trial (power = 80% V ˙ O 2peak V˙O2peak) and had hematological [hemoglobin (Hb), haematocrit (Hct)] and inflammatory markers [interleukin-6 (IL-6), tumor necrosis factor-α (TNFα)] measured in a resting state, pre and post SIT. V ˙ O 2peak V˙O2peak (mL.kg−1.min−1) improved in HYP (+11.9%) and NORM (+9.8%), but not CON (+0.9%). Similarly TTE improved in HYP (+32.2%) and NORM (+33.0%), but not CON (+3.4%) whilst the power at the anaerobic threshold (AT; W.kg−1) also improved in HYP (+13.3%) and NORM (+8.0%), but not CON (–0.3%). AT (mL.kg−1.min−1) improved in HYP (+9.5%), but not NORM (+5%) or CON (–0.3%). No between group change occurred in 30 s sprint performance or Hb and Hct. IL-6 increased in HYP (+17.4%) and NORM (+20.1%), but not CON (+1.2%), respectively. TNF-α increased in HYP (+10.8%) NORM (+12.9%) and CON (+3.4%). SIT in HYP and NORM increased V ˙ O 2peak V˙O2peak, power at AT and TTE performance in untrained individuals, improvements in AT occurred only when SIT was performed in HYP. Increases in IL-6 and TNFα reflect a training induced inflammatory response to SIT; hypoxic conditions do not exacerbate this

Short-term heat acclimation prior to a multi-day desert ultra-marathon improves physiological and psychological responses without compromising immune status

Multistage, ultra-endurance events in hot, humid conditions necessitate thermal adaptation, often achieved through short term heat acclimation (STHA), to improve performance by reducing thermoregulatory strain and perceptions of heat stress. This study investigated the physiological, perceptual and immunological responses to STHA prior to the Marathon des Sables. Eight athletes (age 42 ± 4 years and body mass 81.9 ± 15.0 kg) completed 4 days of controlled hyperthermia STHA (60 min·day‒1, 45°C and 30% relative humidity). Pre, during and post sessions, physiological and perceptual measures were recorded. Immunological measures were recorded pre-post sessions 1 and 4. STHA improved thermal comfort (P = 0.02), sensation (P = 0.03) and perceived exertion (P = 0.04). A dissociated relationship between perceptual fatigue and Tre was evident after STHA, with reductions in perceived Physical (P = 0.04) and General (P = 0.04) fatigue. Exercising Tre and HR did not change (P > 0.05) however, sweat rate increased 14% (P = 0.02). No changes were found in white blood cell counts or content (P > 0.05). Four days of STHA facilitates effective perceptual adaptations, without compromising immune status prior to an ultra-endurance race in heat stress. A greater physiological strain is required to confer optimal physiological adaptations

Preoperative bevacizumab combined with letrozole and chemotherapy in locally advanced ER- and/or PgR-positive breast cancer: clinical and biological activity

The antiangiogenic agent bevacizumab showed synergistic effects when combined with chemotherapy in advanced breast cancer. We presently investigated the activity of bevacizumab in combination with chemotherapy, including capecitabine and vinorelbine, and endocrine therapy, including letrozole (+triptorelin in premenopausal women), as primary therapy for patients with ER and/or PgR ⩾10% T2–T4a-c, N0–N2, M0 breast cancer. Biological end point included the proliferative activity (Ki67), whereas clinical end points were clinical response rate, pathological complete response (pCR) and tolerability. Circulating endothelial cells (CECs) and their progenitors, as surrogate markers of antiangiogenic activity, were measured at baseline and at surgery.Thirty-six women are evaluable. A clinical response rate of 86% (95% CI, 70–95) and no pCR were observed; Ki67 was significantly decreased by 71% (interquartile range, −82%, −62%). Toxicity was manageable: two grade 3 hypertension, four grade 3 deep venous thrombosis and no grade >2 proteinuria were observed. Treatment significantly decreased the percentage of viable CECs and prevented the chemotherapy-induced mobilisation of circulating progenitors. Basal circulating progenitors were positively associated with clinical response. In conclusion, bevacizumab is feasible and active in association with primary chemoendocrine therapy for ER-positive tumours in terms of proliferation inhibition, clinical response and antiangiogenic activity

Streptococcus iniae M-Like Protein Contributes to Virulence in Fish and Is a Target for Live Attenuated Vaccine Development

Streptococcus iniae is a significant pathogen in finfish aquaculture, though knowledge of virulence determinants is lacking. Through pyrosequencing of the S. iniae genome we have identified two gene homologues to classical surface-anchored streptococcal virulence factors: M-like protein (simA) and C5a peptidase (scpI).S. iniae possesses a Mga-like locus containing simA and a divergently transcribed putative mga-like regulatory gene, mgx. In contrast to the Mga locus of group A Streptococcus (GAS, S. pyogenes), scpI is located distally in the chromosome. Comparative sequence analysis of the Mgx locus revealed only one significant variant, a strain with an insertion frameshift mutation in simA and a deletion mutation in a region downstream of mgx, generating an ORF which may encode a second putative mga-like gene, mgx2. Allelic exchange mutagenesis of simA and scpI was employed to investigate the potential role of these genes in S. iniae virulence. Our hybrid striped bass (HSB) and zebrafish models of infection revealed that M-like protein contributes significantly to S. iniae pathogenesis whereas C5a peptidase-like protein does not. Further, in vitro cell-based analyses indicate that SiMA, like other M family proteins, contributes to cellular adherence and invasion and provides resistance to phagocytic killing. Attenuation in our virulence models was also observed in the S. iniae isolate possessing a natural simA mutation. Vaccination of HSB with the Delta simA mutant provided 100% protection against subsequent challenge with a lethal dose of wild-type (WT) S. iniae after 1,400 degree days, and shows promise as a target for live attenuated vaccine development.Analysis of M-like protein and C5a peptidase through allelic replacement revealed that M-like protein plays a significant role in S. iniae virulence, and the Mga-like locus, which may regulate expression of this gene, has an unusual arrangement. The M-like protein mutant created in this research holds promise as live-attenuated vaccine

Breast tumour angiogenesis

The central importance of tumour neovascularization has been emphasized by clinical trials using antiangiogenic therapy in breast cancer. This review gives a background to breast tumour neovascularization in in situ and invasive breast cancer, outlines the mechanisms by which this is achieved and discusses the influence of the microenvironment, focusing on hypoxia. The regulation of angiogenesis and the antivascular agents that are used in an antiangiogenic dosing schedule, both novel and conventional, are also summarized

An Internet-based self-help intervention for people with HIV and depressive symptoms: study protocol for a randomized controlled trial

BACKGROUND: Many people living with HIV suffer from depressive symptoms. In a previous pilot study, self-help cognitive behavioral therapy (in booklet format) was found to be effective in treating depressive symptoms in people with HIV. We developed an online self-help program in Dutch and English (based on the booklet) for people with HIV and depressive symptoms. Besides the main question regarding the effectiveness of the program aimed at lowering depressive symptoms, sub-questions will focus on the moderators of treatment success (for which patients is the program especially beneficial?) and the mechanisms of change underlying the treatment outcome (which mediators affect the outcome of treatment?). In this paper, the protocol of the study will be described. METHODS/DESIGN: The effectiveness of the program will be investigated by comparing the intervention group with a waiting list-control group in a randomized controlled design, by including a pretest and three post-tests. The self-help program contains four main components: activation, relaxation, changing maladaptive cognitions, and goal attainment. Participants with mild to moderate depressive symptoms will work on the program for 6 to 10 weeks, during which a coach will provide motivational support by telephone once a week. Participants in the control condition will receive weekly minimal support from a coach for 8 weeks, and after the second post-test, they can gain access to the self-help program. Depressive symptoms and possible mediators (e.g., activation, cognitive coping, self-efficacy, and goal adjustment) will be assessed by self-report three times during the intervention/waiting period and at the pretest and first post-test. DISCUSSION: The proposed study aims to evaluate the effectiveness of an online self-help intervention for people with HIV and depressive symptoms. If the intervention is shown to be effective, the program will be implemented. Consequently, many patients with HIV could be reached, and their psychological care may be improved. TRIAL REGISTRATION: Netherlands Trial Register: NTR5407 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-016-1292-6) contains supplementary material, which is available to authorized users

Exercise heat acclimation and post-exercise hot water immersion improve resting and exercise responses to heat stress in the elderly

Eastbourne Leisure Trus

Complexity of Childhood Sexual Abuse: Predictors of Current Post-Traumatic Stress Disorder, Mood Disorders, Substance Use, and Sexual Risk Behavior Among Adult Men Who Have Sex with Men

Men who have sex with men (MSM) are the group most at risk for HIV and represent the majority of new infections in the United States. Rates of childhood sexual abuse (CSA) among MSM have been estimated as high as 46%. CSA is associated with increased risk of HIV and greater likelihood of HIV sexual risk behavior. The purpose of this study was to identify the relationships between CSA complexity indicators and mental health, substance use, sexually transmitted infections (STIs) and HIV sexual risk among MSM. MSM with CSA histories (n = 162) who were screened for an HIV-prevention efficacy trial completed comprehensive psychosocial assessments. Five indicators of complex CSA experiences were created: CSA by family member, CSA with penetration, CSA with physical injury, CSA with intense fear, and first CSA in adolescence. Adjusted regression models were used to identify relationships between CSA complexity and outcomes. Participants reporting CSA by family member were at 2.6 odds of current alcohol use disorder (OR: 2.64: CI 1.24 – 5.63), 2 times higher odds of substance use disorder (OR 2.1: CI 1.02 – 2.36), and 2.7 times higher odds of reporting an STI in the past year (OR 2.7: CI 1.04 – 7.1). CSA with penetration was associated with increased likelihood of current PTSD (OR 3.17: CI 1.56 – 6.43), recent HIV sexual risk behavior (OR 2.7: CI 1.16 – 6.36) and a greater number of casual sexual partners (p = .02). Both CSA with Physical Injury (OR 4.05: CI 1.9 – 8.7) and CSA with Intense Fear (OR 5.16: CI 2.5 – 10.7) were related to increased odds for current PTSD. First CSA in adolescence was related to increased odds of major depressive disorder. These findings suggest that CSA, with one or more complexities, creates patterns of vulnerabilities for MSM, including PTSD, substance use, and sexual risk taking and suggests the need for detailed assessment of CSA and the development of integrated HIV prevention programs that address mental health and substance use comorbidities