PGC-1α overexpression is not sufficient to mitigate cancer cachexia in either male or female mice.

Cancer cachexia (CC) accounts for 20%-40% of cancer-related deaths. Mitochondrial aberrations have been shown to precede muscle atrophy in different atrophy models, including cancer. Therefore, this study investigated potential protection from the cachectic phenotype through overexpression of peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1α). First, to establish potential of mitochondria-based approaches we showed that the mitochondrial antioxidant MitoTEMPO (MitoT) attenuates myotube atrophy induced by Lewis lung carcinoma (LLC) cell conditioned media. Next, cachexia was induced in muscle-specific PGC-1α overexpressing (MCK-PCG1α) or wildtype (WT) littermate mice by LLC implantation. MCK-PCG1α did not protect LLC-induced muscle mass loss. In plantaris, Atrogin mRNA content was 6.2-fold and ∼11-fold greater in WT-LLC vs WT-phosphate-buffered saline (PBS) for males and females, respectively (p < 0.05). MitoTimer red:green ratio for male PGC was ∼65% higher than WT groups (p < 0.05), with ∼3-fold more red puncta in LLC than PBS (p < 0.05). Red:green ratio was ∼56% lower in females WT-LLC vs PGC-LLC (p < 0.05). In females, no change in red puncta was noted across conditions. Lc3 mRNA content was ∼73% and 2-fold higher in male and female LLC mice, respectively, vs PBS (p < 0.05). While MitoT could mitigate cancer-induced atrophy in vitro, PGC-1α overexpression was insufficient to protect muscle mass and mitochondrial health in vivo despite mitigation of cachexia-associated signaling pathways.

A dynamic COVID-19 immune signature includes associations with poor prognosis.

Improved understanding and management of COVID-19, a potentially life-threatening disease, could greatly reduce the threat posed by its etiologic agent, SARS-CoV-2. Toward this end, we have identified a core peripheral blood immune signature across 63 hospital-treated patients with COVID-19 who were otherwise highly heterogeneous. The signature includes discrete changes in B and myelomonocytic cell composition, profoundly altered T cell phenotypes, selective cytokine/chemokine upregulation and SARS-CoV-2-specific antibodies. Some signature traits identify links with other settings of immunoprotection and immunopathology; others, including basophil and plasmacytoid dendritic cell depletion, correlate strongly with disease severity; while a third set of traits, including a triad of IP-10, interleukin-10 and interleukin-6, anticipate subsequent clinical progression. Hence, contingent upon independent validation in other COVID-19 cohorts, individual traits within this signature may collectively and individually guide treatment options; offer insights into COVID-19 pathogenesis; and aid early, risk-based patient stratification that is particularly beneficial in phasic diseases such as COVID-19.

Effects of high-sugar and high-fiber meals on physical activity behaviors in Latino and African American adolescents.

OBJECTIVE: This crossover experimental study examined the acute effects of high-sugar/low-fiber (HSLF) vs. low-sugar/high-fiber (LSHF) meals on sedentary behavior (SB) and light-plus activity (L+) in minority adolescents with overweight and obesity. METHODS: 87 Latino and African American adolescents (mean age = 16.3 ± 1.2 years, mean BMI z-score = 2.02 ± 0.52, 56.8% Latino, 51.1% male) underwent two experimental meal conditions during which they consumed HSLF or LSHF meals. Physical activity and SB were measured using accelerometers, and blood glucose and insulin were collected every 30 minutes over 5 hours. Mixed models were used to examine the temporal trends of SB and L+, whether the temporal trends of SB and L+ differed by meal condition, and the influence of blood glucose and insulin on the activity behaviors. RESULTS: SB and L+ fluctuated over time during the HSLF condition but were stable during the LSHF condition. SB and L+ were influenced by the blood glucose response to the HSLF meals. Insulin did not influence SB or L+ in either meal condition. CONCLUSIONS: Sugar and fiber content of meals can have differing acute impacts on activity behaviors in minority adolescents with overweight and obesity, possibly due to differing metabolic responses.

Solitary supratentorial Listeria monocytogenes brain abscess in an immunocompromised patient.

We describe an 81-year-old man receiving azacitidine monotherapy for myelodysplastic syndrome who was improving from Listeria monocytogenes bacteremia after receiving antibiotic therapy during an earlier hospital admission. Shortly after discharge he developed new-onset seizure activity, with brain imaging on subsequent admissions demonstrating a posterior right frontal lobe mass. Specimen cultures after resection of the mass revealed this to be a cerebral abscess related to L. monocytogenes. Brain abscesses related to this organism are rare.