Extreme phenotypes approach to investigate host genetics and COVID-19 outcomes.

COVID-19 comprises clinical outcomes of SARS-CoV-2 infection and is highly heterogeneous, ranging from asymptomatic individuals to deceased young adults without comorbidities. There is growing evidence that host genetics play an important role in COVID-19 severity, including inborn errors of immunity, age-related inflammation and immunosenescence. Here we present a brief review on the known order of events from infection to severe system-wide disturbance due to COVID-19 and summarize potential candidate genes and pathways. Finally, we propose a strategy of subject's ascertainment based on phenotypic extremes to take part in genomic studies and elucidate intrinsic risk factors involved in COVID-19 severe outcomes.

Exploring honey bee toxicological data as a proxy for assessing dimethoate sensitivity in stingless bees.

The high diversity and distinctive characteristics of stingless bees pose challenges in utilizing toxicity test results for agrochemical registrations. Toxicity assessments were performed on 15 stingless bee species, along with the honey bee, using the insecticide dimethoate, following adapted OECD protocols. Median lethal doses over 24 h (24 h-LD50) were determined for exposure routes (acute oral or contact) and species. Species sensitivity distribution (SSD) curves were constructed and the 5% hazard doses (HD5) were estimated based on 24 h-LD50 values. The SSD curve was adjusted as the body weight and dimethoate response were correlated. Lighter bees (<10 mg) had lower 24 h-LD50 values. Contact exposure for adjusted HD5 suggested insufficient protection for Melipona mondury, whereas the oral exposure HD5 indicated no risks for the other 14 species. Comprehensive risk assessments are crucial for understanding the agrochemical impact on stingless bees, emphasizing the need for a broader species range in formulating conservation strategies.

Enhanced peripheral nerve regeneration by the combination of a polycaprolactone tubular prosthesis and a scaffold of collagen with supramolecular organization.

The purpose of this study was to investigate the influence of implanting collagen with a supramolecular organization on peripheral nerve regeneration, using the sciatic nerve tubulization technique. For this purpose, adult female Sprague Dawley rats were divided into five groups: (1) TP - sciatic nerve repaired with empty polyethylene tubular prothesis (n = 10), (2) TPCL - nerve repair with empty polycaprolactone (PCL) tubing (n = 8), (3) TPCLF - repair with PCL tubing filled with an implant of collagen with a supramolecular organization (n = 10), (4) AG - animals that received a peripheral nerve autograft (n = 8), and (5) Normal nerves (n = 8). The results were assessed by quantification of the regenerated fibers, nerve morphometry, and transmission electron microscopy, 60 days after surgery. Immunohistochemistry and polarization microscopy were also used to analyze the regenerated nerve structure and cellular elements. The results showed that the AG group presented a larger number of regenerated axons. However, the TPCL and TPCLF groups presented more compact regenerated fibers with a morphometric profile closer to normal, both at the tube midpoint and 2 mm distal to the prosthesis. These findings were reinforced by polarization microscopy, which indicated a better collagen/axons suprastructural organization in the TPCLF derived samples. In addition, the immunohistochemical results obtained using the antibody anti-p75NTR as a Schwann cell reactivity marker demonstrated that the Schwann cells were more reactive during the regenerative process in the TPCLF group as compared to the TPCL group and the normal sciatic nerve. Altogether, the results of this study indicated that the implant of collagen with a supramolecular organization positively influenced and stimulated the regeneration process through the nerve gap, resulting in the formation of a better morphologically arranged tissue.