The Immune Response to Mycobacterium tuberculosis in HIV-1-Coinfected Persons.

Globally, about 36.7 million people were living with HIV infection at the end of 2015. The most frequent infection co-occurring with HIV-1 is Mycobacterium tuberculosis-374,000 deaths per annum are attributable to HIV-tuberculosis, 75% of those occurring in Africa. HIV-1 infection increases the risk of tuberculosis by a factor of up to 26 and alters its clinical presentation, complicates diagnosis and treatment, and worsens outcome. Although HIV-1-induced depletion of CD4+ T cells underlies all these effects, more widespread immune deficits also contribute to susceptibility and pathogenesis. These defects present a challenge to understand and ameliorate, but also an opportunity to learn and optimize mechanisms that normally protect people against tuberculosis. The most effective means to prevent and ameliorate tuberculosis in HIV-1-infected people is antiretroviral therapy, but this may be complicated by pathological immune deterioration that in turn requires more effective host-directed anti-inflammatory therapies to be derived.

Aiming at the Global Elimination of Viral Hepatitis: Challenges Along the Care Continuum.

A recent international workshop, organized by the authors, analyzed the obstacles facing the ambitious goal of eliminating viral hepatitis globally. We identified several policy areas critical to reaching elimination targets. These include providing hepatitis B birth-dose vaccination to all infants within 24 hours of birth, preventing the transmission of blood-borne viruses through the expansion of national hemovigilance schemes, implementing the lessons learned from the HIV epidemic regarding safe medical practices to eliminate iatrogenic infection, adopting point-of-care testing to improve coverage of diagnosis, and providing free or affordable hepatitis C treatment to all. We introduce Egypt as a case study for rapid testing and treatment scale-up: this country offers valuable insights to policy makers internationally, not only regarding how hepatitis C interventions can be expeditiously scaled-up, but also as a guide for how to tackle the problems encountered with such ambitious testing and treatment programs.

Neuromuscular changes associated with superior fatigue resistance in African runners.

BACKGROUND: An enhanced ability to resist fatigue has been proposed as one of African runners' performance superiority sources, although their fatigue resistance during sustained non-running-specific activities remain unclear. This study aimed to compare fatigue resistance during sustained isometric exercise between performance-matched African and European runners. METHODS: Thirty long-distance runners (16 African, 14 European) performed submaximal fatiguing sustained isometric knee extensions. Rectus femoris electromyographic (EMG) activity was measured, and the muscle was electrically stimulated to contract at the beginning and end of the test. RESULTS: Time to task failure was greater for African than European runners (269±115 vs. 193±52 s, P=0.002; effect size [ES]=0.85, large effect). During the test, EMG amplitude increased less over time (P=0.031), and the left shift in the EMG frequency spectrum was less over time for the African runners (P<0.001). In addition, there was a lower relative reduction in stimulated force output from the first to the second stimulation in African runners (17.75±14.95 vs. 37.89±14.78%, P=0.006; ES=1.35; large effect). CONCLUSIONS: These findings of greater fatigue resistance during non-running-specific activity and the associated muscle recruitment profile may contribute to the understanding of the physiology underlying endurance performance in African runners.

Skeletal muscle monocarboxylate transporter content is not different between black and white runners.

The superior performance of black African runners has been associated with lower plasma lactate concentrations at sub-maximal intensities compared to white runners. The aim was to investigate the monocarboxylate transporters 1 (MCT1) and MCT4 content in skeletal muscle of black and white runners. Although black runners exhibited lower plasma lactate concentrations after maximum exercise (8.8 +/- 2.0 vs. 12.3 +/- 2.7 mmol l(-1), P < 0.05) and a tendency to be lower at 16 km h(-1) (2.4 +/- 0.7 vs. 3.8 +/- 2.4 mmol l(-1), P = 0.07) than the white runners, there were no differences in MCT1 or MCT4 levels between the two groups. For black and white runners together, MCT4 content correlated significantly with 10 km personal best time (r = -0.74, P < 0.01) and peak treadmill speed (r = 0.88, P < 0.001), but MCT1 content did not. Although whole homogenate MCT content was not different between the groups, more research is required to explain the lower plasma lactate concentrations in black runners.

Impaired exercise performance in the heat is associated with an anticipatory reduction in skeletal muscle recruitment.

Exercise in the heat causes "central fatigue", associated with reduced skeletal muscle recruitment during sustained isometric contractions. A similar mechanism may cause fatigue during prolonged dynamic exercise in the heat. The aim of this study was to determine whether centrally regulated skeletal muscle recruitment was altered during dynamic exercise in hot (35 degrees C) compared with cool (15 degrees C) environments. Ten male subjects performed two self-paced, 20-km cycling time-trials, one at 35 degrees C (HOT condition) and one at 15 degrees C (COOL condition). Rectal temperature rose significantly in both conditions, reaching maximum values at 20 km of 39.2+/-0.2 degrees C in HOT and 38.8+/-0.1 degrees C in COOL (P<0.005 HOT vs. COOL). Core temperatures at all other distances were not different between conditions. Power output and integrated electromyographic activity (iEMG) of the quadriceps muscle began to decrease early in the HOT trial, when core temperatures, heart rates and ratings of perceived exertion (RPE) were similar in both conditions. iEMG was significantly lower in HOT than in COOL at 10 and 20 km, while power output was significantly reduced in the period from 80% to 100% of the trial duration in the HOT compared with COOL condition. Thus, reduced power output and iEMG activity during self-paced exercise in the heat occurs before there is any abnormal increase in rectal temperature, heart rate or perception of effort. This adaptation appears to form part of an anticipatory response which adjusts muscle recruitment and power output to reduce heat production, thereby ensuring that thermal homeostasis is maintained during exercise in the heat.

The conscious perception of the sensation of fatigue.

In this review, fatigue is described as a conscious sensation rather than a physiological occurrence. We suggest that the sensation of fatigue is the conscious awareness of changes in subconscious homeostatic control systems, and is derived from a temporal difference between subconscious representations of these homeostatic control systems in neural networks that are induced by changes in the level of activity. These mismatches are perceived by consciousness-producing structures in the brain as the sensation of fatigue. In this model, fatigue is a complex emotion affected by factors such as motivation and drive, other emotions such as anger and fear, and memory of prior activity. It is not clear whether the origin of the conscious sensation of fatigue is associated with particular localised brain structures, or is the result of electrophysiological synchronisation of entire brain activity.