A mutation in the PRKAR1B gene drives pathological mechanisms of neurodegeneration across species.

Protein Kinase A (PKA) neuronal function is controlled by the interaction of a regulatory (R) subunit dimer to two catalytic (C) subunits. Recently, the L50R variant in the gene encoding the RIß subunit was identified in individuals with a novel neurodegenerative disease. However, the mechanisms driving the disease phenotype remained unknown. In this study, we generated a mouse model carrying the RIß-L50R mutation to replicate the human disease phenotype and study its progression with age. We examined postmortem brains of affected individuals as well as live cell cultures. Employing biochemical assays, immunohistochemistry, and behavioral assessments, we investigated the impact of the mutation on PKA complex assembly, protein aggregation and neuronal degeneration. We reveal that RIß is an aggregation-prone protein that progressively accumulates in wildtype and Alzheimer's mouse models with age, while aggregation is accelerated in the RIß-L50R mouse model. We define RIß-L50R as a causal mutation driving an age-dependent behavioral and disease phenotype in human and mouse models. Mechanistically, this mutation disrupts RIß dimerization, leading to aggregation of its monomers. Intriguingly, interaction with the C-subunit protects the RIß-L50R from self-aggregating, in a dose-dependent manner. Furthermore, cAMP signaling induces RIß-L50R aggregation. The pathophysiological mechanism elucidated here for a newly recognized neurodegenerative disease, in which protein aggregation is the result of disrupted homodimerization, sheds light on a remarkably under-appreciated but potentially common mechanism across several neurodegenerative diseases.

Demographics and Clinical Characteristics of Adult Patients Hospitalized due to COVID-19 in a Rural/Suburban Integrated Health System in Southcentral Pennsylvania, March Through May 2020.

Existing characterizations of coronavirus disease 2019 (COVID-19) admissions have occurred primarily in urban settings. This report describes demographic and clinical characteristics of the first COVID-19 patients presenting to a 6-hospital integrated health care system in rural/suburban southcentral Pennsylvania. Medical records of adult patients admitted with COVID-19 between March and May of 2020 were retrospectively reviewed for demographics, symptomatology, imaging, and lab values. Results were largely consistent with previous studies, although gastrointestinal manifestations were more prevalent, with diarrhea reported in 25.4% of patients hospitalized due to COVID-19. Nursing home patients represented 10.1% of admissions but accounted for 35.5% of total deaths in our sample. Patients self-identifying as Hispanic were disproportionately affected. Although Hispanic ethnicity was self-reported in only 9% of the community population, Hispanic patients accounted for 34% of admissions. Our data provide a unique focused review of hospitalized COVID-19 patients in a rural/suburban setting.

The Role of Environmental Factors in the Epidemiology of Infectious Bovine Keratoconjunctivitis.

Environmental factors that contribute to the pathogenesis of infectious bovine keratoconjunctivitis (IBK) include face flies, ultraviolet (UV) radiation, and mechanical irritation from plant awns or dust. Limited research has shown face fly control to be associated with lower incidence of IBK. UV radiation is known to cause corneal irritation and damage in mammalian species. The increased formation of corneal dark cells has been observed following UV radiation in exposed calves. Moraxella bovis preferentially binds to corneal dark cells where it can be found in pits, which may be formed due to bacterial contact. Little is known about the efficacy of management of pasture plants on the prevention of IBK.

Long-Term Creep and Shrinkage Behavior of Concrete-Filled Steel Tube.

A concrete-filled steel tube (CFT) combines the advantages of concrete and steel in construction and structural applications. However, research on the time-dependent deformation of the CFT under long-term sustained loading are still limited, particularly for stress transfer between the steel tube and concrete due to creep. This study investigated the creep behavior of CFT over a long period of 400 days. The creep and shrinkage strain of CFT was significantly lower than those of concrete that was not confined within a steel tube. The vertical strains of the steel tube and concrete core were almost identical, and it was shown that they were well bonded and acted as a composite. The vertical stress of steel increased by 32.7%, whereas the vertical stress of concrete decreased by 15.8% at 375 days. The stress transfer is notable and cannot be neglected in CFT design. Moreover, the results of creep and shrinkage were compared to prediction values of the B4 model and B4-TW model to verify their validity.

Identification of Trombiculid Chigger Mites Collected on Rodents from Southern Vietnam and Molecular Detection of Rickettsiaceae Pathogen

Trombiculid “chigger” mites (Acari) are ectoparasites that feed blood on rodents and another animals. A crosssectional survey was conducted in 7 ecosystems of southern Vietnam from 2015 to 2016. Chigger mites were identified with morphological characteristics and assayed by polymerase chain reaction for detection of rickettsiaceae. Overall chigger infestation among rodents was 23.38%. The chigger index among infested rodents was 19.37 and a mean abundance of 4.61. A total of 2,770 chigger mites were identified belonging to 6 species, 3 genera, and 1 family, and pooled into 141 pools (10-20 chiggers per pool). Two pools (1.4%) of the chiggers were positive for Orientia tsutsugamushi. Ricketsia spp. was not detected in any pools of chiggers. Further studies are needed including a larger number and diverse hosts, and environmental factors to assess scrub typhus.

Verbal fluency, semantics, context and symptom complexes in schizophrenia.

Lexical-semantic access and retrieval was examined in 15 adults diagnosed with schizophrenia and matched controls. This study extends the literature through the inclusion of multiple examinations of lexical-semantic production within the same patient group and through correlating performance on these tasks with various positive and negative clinical symptoms. On tasks of verbal fluency, meaning generation, sentence production using contextual information and confrontation naming, participants with schizophrenia made significantly more semantic errors on naming tasks; produced fewer meanings for homophones; produced fewer items on semantic, phonological, cued and switching fluency tasks; and produced more errors on sentence production tasks when compared to healthy controls. Significant correlations were also observed between ratings of psychomotor poverty and measures of semantic production and mental inflexibility. This study has provided additional evidence for deficits in lexical-semantic retrieval which are not due to underlying semantic store degradation, do not involve phonological based retrieval, and at the level of sentence generation appear to vary as a function of the contextual constraints provided.