Association among practice frequency on depression and stress among competitive US male wheelchair rugby athletes with tetraplegia.

STUDY DESIGN: Cross-sectional. OBJECTIVES: To determine whether frequency of training is related to self-reported lower psychological distress, defined as depressive symptomology and perceived stress, among the US male wheelchair rugby athletes with tetraplegia. SETTING: United States. METHODS: Survey data were collected on a convenience sample at wheelchair rugby tournaments from January-April 2016. Participants self-reported depressive symptomology (CES-D-10), perceived stress scale (PSS), and frequency of rugby practice. Covariate-adjusted regression models were conducted among the full sample and a subsample of individuals who reported spinal cord injury (SCI) as the nature of their disability. RESULTS: Participants included 150 males with tetraplegia, and 87% identified the nature of their disability as SCI. Participants were primarily Caucasian with an average age of ~35 years. Participants scored low on measures of depressive symptomology (mean=5.63; s.d.=4.35) and perceived stress (mean=4.63; s.d.=2.73). Sixty-seven percent of the participants practiced two or more times per week. Results of the main analyses indicated that practicing wheelchair rugby two times or more (compared to once a week or less) was significantly associated with lower depressive symptomology and perceived stress among the full sample and subsample of individuals with SCI. CONCLUSIONS: Greater frequency of wheelchair rugby participation was associated with lower levels of psychological distress. Future research should examine the directional and mechanistic relationship between frequency of sports participation and psychological distress to inform the benefits of adaptive sport.

Comparative assessment of transmission-blocking vaccine candidates against Plasmodium falciparum.

Malaria transmission-blocking vaccines (TBVs) target the development of Plasmodium parasites within the mosquito, with the aim of preventing malaria transmission from one infected individual to another. Different vaccine platforms, mainly protein-in-adjuvant formulations delivering the leading candidate antigens, have been developed independently and have reported varied transmission-blocking activities (TBA). Here, recombinant chimpanzee adenovirus 63, ChAd63, and modified vaccinia virus Ankara, MVA, expressing AgAPN1, Pfs230-C, Pfs25, and Pfs48/45 were generated. Antibody responses primed individually against all antigens by ChAd63 immunization in BALB/c mice were boosted by the administration of MVA expressing the same antigen. These antibodies exhibited a hierarchy of inhibitory activity against the NF54 laboratory strain of P. falciparum in Anopheles stephensi mosquitoes using the standard membrane feeding assay (SMFA), with anti-Pfs230-C and anti-Pfs25 antibodies giving complete blockade. The observed rank order of inhibition was replicated against P. falciparum African field isolates in A. gambiae in direct membrane feeding assays (DMFA). TBA achieved was IgG concentration dependent. This study provides the first head-to-head comparative analysis of leading antigens using two different parasite sources in two different vector species, and can be used to guide selection of TBVs for future clinical development using the viral-vectored delivery platform.

Modified vaccinia virus Ankara-based vaccine vectors induce apoptosis in dendritic cells draining from the skin via both the extrinsic and intrinsic caspase pathways, preventing efficient antigen presentation.

Dendritic cells (DC) are potent antigen-presenting cells and central to the induction of immune responses following infection or vaccination. The collection of DC migrating from peripheral tissues by cannulation of the afferent lymphatic vessels provides DC which can be used directly ex vivo without extensive in vitro manipulations. We have previously used bovine migrating DC to show that recombinant human adenovirus 5 vectors efficiently transduce afferent lymph migrating DEC-205(+) CD11c(+) CD8(-) DC (ALDC). We have also shown that recombinant modified vaccinia virus Ankara (MVA) infects ALDC in vitro, causing downregulation of costimulatory molecules, apoptosis, and cell death. We now show that in the bovine system, modified vaccinia virus Ankara-induced apoptosis in DC draining from the skin occurs soon after virus binding via the caspase 8 pathway and is not associated with viral gene expression. We also show that after virus entry, the caspase 9 pathway cascade is initiated. The magnitude of T cell responses to mycobacterial antigen 85A (Ag85A) expressed by recombinant MVA-infected ALDC is increased by blocking caspase-induced apoptosis. Apoptotic bodies generated by recombinant MVA (rMVA)-Ag85A-infected ALDC and containing Ag85A were phagocytosed by noninfected migrating ALDC expressing SIRPα via actin-dependent phagocytosis, and these ALDC in turn presented antigen. However, the addition of fresh ALDC to MVA-infected cultures did not improve on the magnitude of the T cell responses; in contrast, these noninfected DC showed downregulation of major histocompatibility complex class II (MHC-II), CD40, CD80, and CD86. We also observed that MVA-infected ALDC promoted migration of DEC-205(+) SIRPα(+) CD21(+) DC as well as CD4(+) and CD8(+) T cells independently of caspase activation. These in vitro studies show that induction of apoptosis in DC by MVA vectors is detrimental to the subsequent induction of T cell responses.

Effect of oral contraceptives on peripheral blood flow in untrained women at rest and during exercise.

BACKGROUND: Endothelium-derived nitric oxide is an important mediator of exercise-induced changes in skeletal muscle blood flow. Given the recently documented effects of estrogens on nitric oxide synthase, it is hypothesized that oral contraceptives (OC) containing estrogen would increase nitric oxide production at rest and after endurance exercise. Further, we postulated that OC use would augment skeletal muscle blood flow at rest and during exercise. METHODS: Fourteen women (non-smokers) were divided into two groups: control (CON; sedentary, normal menstrual-cycling women who have not used oral contraceptives for > or = 12 mons; 18-38 yrs old; n = 7), and oral contraceptive users (OC; sedentary women who have been using low-dose estrogen/progestin oral contraceptives for > or = 12 mons; 19-38 yrs old; n = 7). Measurements of forearm blood flow were obtained from each group, using strain gauge plethysmography, at rest and during an exercise protocol in which intermittent handgrip exercise was performed at 15%, 30%, and 45% of maximum voluntary contraction (MVC). Additionally, venous blood samples were taken before and after a 90 min treadmill walk for measurement of serum nitrate/nitrite, an indirect assessment of steady-state nitric oxide production. RESULTS: There was no difference in forearm blood flow (ml/min/ 100 cc tissue) at rest (CON = 2.7; OC = 2.8); however, the hyperemic response to handgrip exercise was significantly (p < 0.05) lower in the OC group at 30% (9.0 vs CON = 14.2) and 45% (12.0 vs CON=17.0) of MVC. Serum nitrate values at rest and following 90 min of treadmill walking did not differ between groups (p > 0.05). CONCLUSIONS: Contrary to our hypotheses, these data indicate a compromised hyperemic response in the forearm of OC users. Further, chronic OC use may not affect nitric oxide production during low intensity treadmill exercise.

Ebola (subtype Reston) virus among quarantined nonhuman primates recently imported from the Philippines to the United States.

In April 1996, laboratory testing of imported nonhuman primates (as mandated by quarantine regulations) identified 2 cynomolgus macaques (Macaca fascicularis) infected with Ebola (subtype Reston) virus in a US-registered quarantine facility. The animals were part of a shipment of 100 nonhuman primates recently imported from the Philippines. Two additional infected animals, who were thought to be in the incubation phase, were identified among the remaining 48 animals in the affected quarantine room. The other 50 macaques, who had been held in a separate isolation room, remained asymptomatic, and none of these animals seroconverted during an extended quarantine period. Due to the rigorous routine safety precautions, the facility personnel had no unprotected exposures and remained asymptomatic, and no one seroconverted. The mandatory quarantine and laboratory testing requirements, put in place after the original Reston outbreak in 1989-1990, were effective for detecting and containing Ebola virus infection in newly imported nonhuman primates and minimizing potential human transmission.