Brucella activates the host RIDD pathway to subvert BLOS1-directed immune defense.

The phagocytosis and destruction of pathogens in lysosomes constitute central elements of innate immune defense. Here, we show that Brucella, the causative agent of brucellosis, the most prevalent bacterial zoonosis globally, subverts this immune defense pathway by activating regulated IRE1α-dependent decay (RIDD) of Bloc1s1 mRNA encoding BLOS1, a protein that promotes endosome-lysosome fusion. RIDD-deficient cells and mice harboring a RIDD-incompetent variant of IRE1α were resistant to infection. Inactivation of the Bloc1s1 gene impaired the ability to assemble BLOC-1-related complex (BORC), resulting in differential recruitment of BORC-related lysosome trafficking components, perinuclear trafficking of Brucella-containing vacuoles (BCVs), and enhanced susceptibility to infection. The RIDD-resistant Bloc1s1 variant maintains the integrity of BORC and a higher-level association of BORC-related components that promote centrifugal lysosome trafficking, resulting in enhanced BCV peripheral trafficking and lysosomal destruction, and resistance to infection. These findings demonstrate that host RIDD activity on BLOS1 regulates Brucella intracellular parasitism by disrupting BORC-directed lysosomal trafficking. Notably, coronavirus murine hepatitis virus also subverted the RIDD-BLOS1 axis to promote intracellular replication. Our work establishes BLOS1 as a novel immune defense factor whose activity is hijacked by diverse pathogens.

Investigation of SARS-CoV-2 infection and associated lesions in exotic and companion animals.

Documented natural infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in exotic and companion animals following human exposures are uncommon. Those documented in animals are typically mild and self-limiting, and infected animals have only infrequently died or been euthanized. Through a coordinated One Health initiative, necropsies were conducted on 5 animals from different premises that were exposed to humans with laboratory-confirmed SARS-CoV-2 infection. The combination of epidemiologic evidence of exposure and confirmatory real-time reverse transcriptase-polymerase chain reaction testing confirmed infection in 3 cats and a tiger. A dog was a suspect case based on epidemiologic evidence of exposure but tested negative for SARS-CoV-2. Four animals had respiratory clinical signs that developed 2 to 12 days after exposure. The dog had bronchointerstitial pneumonia and the tiger had bronchopneumonia; both had syncytial-like cells with no detection of SARS-CoV-2. Individual findings in the 3 cats included metastatic mammary carcinoma, congenital renal disease, and myocardial disease. Based on the necropsy findings and a standardized algorithm, SARS-CoV-2 infection was not considered the cause of death in any of the cases. Continued surveillance and necropsy examination of animals with fatal outcomes will further our understanding of natural SARS-CoV-2 infection in animals and the potential role of the virus in development of lesions.

Nutrition Program Improves Health-Related Outcomes of Non-Diabetic Elderly at Nutritional Risk

Malnutrition or its risk affects up to 1 in 3 older adults receiving outpatient care post a hospitalization or for chronic disease management. Although malnutrition poses a negative burden on someone’s recovery and health preservation, it can be effectively addressed through cost-effective nutrition interventions delivered as comprehensive quality improvement programs (QIPs) aiding to advance healthcare professional’s nutrition education/training and improve quality of care for at-risk/malnourished individuals. Although evidence from US and Europe demonstrates nutrition-focused QIPs are effective in delivering high-quality nutrition care and improve health outcomes of outpatients at-risk/malnourished, to date, no evidence has been reported from Latin American countries. We assessed effectiveness of a comprehensive, nutrition-focused QIP in a Colombian outpatient clinic. Between 09/2019-03/2020, 504 (of total 618) QIP participants were classified at-risk/malnourished and non-diabetics. Participants were followed for 90-days either in-person or via telehealth mechanisms (during COVID-19-imposed lockdown period). QIP interventions included healthcare professional nutrition education;QIP participant continuous nutrition and exercise counselling and 60-day supply of oral nutrition supplement (Ensure®, Abbott). QIP participants were 69% female, with >2 comorbidities, and mean age of 73. Improvement or maintenance of good mental health/well-being, frailty status, cognition and quality of life was reported for 90.7% (456/503), 87.3% (407/466), 86.7% (405/467) and 47% (237/504) participants, respectively (p-values<0.05). Results support QIP effectiveness in driving improved health-related outcomes for non-diabetic, at-nutritional-risk participants. These findings highlight the importance of nutrition-focused QIPs with ONS for older adults during their recovery phase post a recent hospitalization and/or for chronic disease management.

Preoperative SARS-CoV-2 Screening Fails to Detect Viral Particles Prior to Airway Surgery.

OBJECTIVES/HYPOTHESIS: Children have higher rates of asymptomatic SARS-CoV-2 infections or milder courses of infection, and their carrier status may potentially impact viral transmission to those providing them care. The aim of this study is to compare the existing COVID-19 preoperative screening protocols to the detection of SARS-CoV-2 viral particles in surgical samples. STUDY DESIGN: Cross-sectional study. METHODS: We conducted a prospective study with consecutive convenience sampling of children undergoing adenoidectomy between January and April 2021. Total nucleic acid was extracted from adenoid tissue and real-time reverse transcription-polymerase chain reaction was conducted to test for the presence of SARS-CoV-2 viral particles. Univariate logistic regression was used to summarize the effect size of variables of interest on the odds of having SARS-CoV-2 positive adenoid tissue. RESULTS: Forty adenoid samples were collected and 11 (27.5%) had a positive SARS-CoV-2 reverse transcriptase-polymerase chain reaction. Patients with positive adenoids were older (11.8 vs. 7.9 years, odds ratio: 1.3, P = .01) and more likely to have had a positive nasopharyngeal swab in the previous 90 days (4/11 or 36% vs. 0). CONCLUSION: These data are the first report on the presence of SARS-CoV-2 particles in pediatric adenoidectomy specimens, with a high percentage of patients showing evidence of viral particles within the adenoid. This finding calls in to question the utility of preoperative COVID screening protocols which have yet to be rigorously validated in asymptomatic patients and have the potential to delay patients' surgical care. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:1665-1667, 2022.

Enzyme Therapy: Current Challenges and Future Perspectives.

In recent years, enzymes have risen as promising therapeutic tools for different pathologies, from metabolic deficiencies, such as fibrosis conditions, ocular pathologies or joint problems, to cancer or cardiovascular diseases. Treatments based on the catalytic activity of enzymes are able to convert a wide range of target molecules to restore the correct physiological metabolism. These treatments present several advantages compared to established therapeutic approaches thanks to their affinity and specificity properties. However, enzymes present some challenges, such as short in vivo half-life, lack of targeted action and, in particular, patient immune system reaction against the enzyme. For this reason, it is important to monitor serum immune response during treatment. This can be achieved by conventional techniques (ELISA) but also by new promising tools such as microarrays. These assays have gained popularity due to their high-throughput analysis capacity, their simplicity, and their potential to monitor the immune response of patients during enzyme therapies. In this growing field, research is still ongoing to solve current health problems such as COVID-19. Currently, promising therapeutic alternatives using the angiotensin-converting enzyme 2 (ACE2) are being studied to treat COVID-19.