Competition between T cells maintains clonal dominance during memory inflation induced by MCMV

Both human cytomegalovirus (HCMV) and murine cytomegalovirus (MCMV) establish persistent infections that induce the accumulation of virus‐specific T cells over time in a process called memory inflation. It has been proposed that T cells expressing T‐cell receptors (TCRs) with high affinity for HCMV‐derived peptides are preferentially selected after acute HCMV infection. To test this in the murine model, small numbers of OT‐I transgenic T cells, which express a TCR with high affinity for the SIINFEKL peptide, were transferred into congenic mice and recipients were challenged with recombinant MCMV expressing SIINFEKL. OT‐I T cells were selectively enriched during the first 3 weeks of infection. Similarly, in the absence of OT‐I T cells, the functional avidity of SIINFEKL‐specific T cells increased from early to late times postinfection. However, even when exceedingly small numbers of OT‐I T cells were transferred, their inflation limited the inflation of host‐derived T cells specific for SIINFEKL. Importantly, subtle minor histocompatibility differences led to late rejection of the transferred OT‐I T cells in some mice, which allowed host‐derived T cells to inflate substantially. Thus, T cells with a high functional avidity are selected shortly after MCMV infection and continuously sustain their clonal dominance in a competitive manner.     

Infection Due to Mycobacterium thermoresistibile: a Case Associated with an Orthopedic Device

Mycobacterium thermoresistibile is a rapidly growing environmental nontuberculous mycobacterium, seldom reported in human infections. Here, we describe a rare case of tibial-nail-related osteomyelitis due to Mycobacterium thermoresistibile. We also review the literature about the infections caused by this pathogen.     

Developing a Sound Body: Open Trial Results of a Group Healthy Lifestyle Intervention for Young Adults with Psychosis

Community Mental Health Journal - The mortality disparity for persons with schizophrenia spectrum disorders (SSDs) due to cardiovascular disease is a devastating problem. Many risk factors are...     

Positive selection of protective variants for type 2 diabetes from the Neolithic onward: a case study in Central Asia

The high prevalence of type 2 diabetes and its uneven distribution among human populations is both a major public health concern and a puzzle in evolutionary biology. Why is this deleterious disease so common, while the associated genetic variants should be removed by natural selection? The ‘thrifty genotype'' hypothesis proposed that the causal genetic variants were advantageous and selected for during the majority of human evolution. It remains, however, unclear whether genetic data support this scenario. In this study, we characterized patterns of selection at 10 variants associated with type 2 diabetes, contrasting one herder and one farmer population from Central Asia. We aimed at identifying which alleles (risk or protective) are under selection, dating the timing of selective events, and investigating the effect of lifestyle on selective patterns. We did not find any evidence of selection on risk variants, as predicted by the thrifty genotype hypothesis. Instead, we identified clear signatures of selection on protective variants, in both populations, dating from the beginning of the Neolithic, which suggests that this major transition was accompanied by a selective advantage for non-thrifty variants. Combining our results with worldwide data further suggests that East Asia was particularly prone to such recent selection of protective haplotypes. As much effort has been devoted so far to searching for thrifty variants, we argue that more attention should be paid to the evolution of non-thrifty variants.     

Specific training improves skeletal muscle mitochondrial calcium homeostasis after eccentric exercise

There is limited understanding of the mitochondrial adaptation following repeated eccentric exercise bouts, a model resulting in muscle adaptation known as the repeat bout effect. It was hypothesized that downhill training would reduce mitochondrial calcium content (MCC) post an acute eccentric bout with concurrent improvements in mitochondrial respiratory function. Thirty-four Sprague–Dawley rats were divided into four groups: control (N), control with acute eccentric exercise (N _ecc), trained control (X) and trained with acute eccentric exercise (X _ecc). Training for X and X _ecc consisted of 30 min per day for five consecutive days of downhill treadmill running. The acute eccentric exercise bout was a ?14° treadmill exercise for 90 min performed 2 weeks after the training period. Animals were killed 48 h post-exercise. Isolated mitochondria from the red quadriceps allowed for the measure of mitochondrial respiratory indices and MCC. Calpain activity and heat shock protein 72 expression (HSP72) were also measured. MCC dramatically increased following the acute bout of eccentric exercise in N _ecc (p < 0.001), but did not change in X _ecc. Mitochondrial respiratory function tended to be slightly depressed in N _ecc (state 3 respiration, p = 0.053; respiratory control ratio, p = 0.098) and unaltered in X _ecc. Previous training altered the calpain and heat shock protein response to an acute bout of eccentric exercise. The results suggest that downhill exercise training improves mitochondrial calcium homeostasis following an acute bout of prolonged eccentric exercise and may stabilize mitochondrial respiratory function. These improvements coincide with a reduction in calpain activity and heat shock protein upregulation.     

Arthroscopic repair of type II SLAP lesions: Clinical and anatomic follow-up

Aims:The aim was to evaluate the clinical and anatomic outcome of arthroscopic repair of type II SLAP lesions.Results:At a mean follow-up of 54-month, the mean American Shoulder and Elbow Surgeons Shoulder Index (ASES) scores improved from 52.1 preoperatively to 86.1 postoperatively (P < 0.0001) and the Simple Shoulder Test (SST) scores from 7.7 to 10.6 (P < 0.0002). Twenty-two out of the 25 patients (88%) stated that they would have surgery again. Of the 21 patients who had postoperative magnetic resonance imaging arthrographys (MRAs), 9 patients (43%) demonstrated dye tracking between the labrum bone interface suggestive of a recurrent tear and 12 patients (57%) had a completely intact repair. There was no significant difference in ASES, SST, and patient satisfaction scores in patients with recurrent or intact repairs.Conclusions:Arthroscopic repair of type II SLAP lesions demonstrated improvements in clinical outcomes. However, MRA imaging demonstrated 43% of patients with recurrent tears. MRA results do not necessarily correlate with clinical outcome.     

Induced pluripotent stem cell-derived neural stem cell therapies for spinal cord injury

The greatest challenge to successful treatment of spinal cord injury is the limited regenerative capacity of the central nervous system and its inability to replace lost neurons and severed axons following injury. Neural stem cell grafts derived from fetal central nervous system tissue or embryonic stem cells have shown therapeutic promise by differentiation into neurons and glia that have the potential to form functional neuronal relays across injured spinal cord segments. However, implementation of fetal-derived or embryonic stem cell-derived neural stem cell therapies for patients with spinal cord injury raises ethical concerns. Induced pluripotent stem cells can be generated from adult somatic cells and differentiated into neural stem cells suitable for therapeutic use, thereby providing an ethical source of implantable cells that can be made in an autologous fashion to avoid problems of immune rejection. This review discusses the therapeutic potential of human induced pluripotent stem cell-derived neural stem cell transplantation for treatment of spinal cord injury, as well as addressing potential mechanisms, future perspectives and challenges.