Genetically encoded dendritic marker sheds light on neuronal connectivity in Drosophila.

In recent years, Drosophila melanogaster has emerged as a powerful model for neuronal circuit development, pathology, and function. A major impediment to these studies has been the lack of a genetically encoded, specific, universal, and phenotypically neutral marker of the somatodendritic compartment. We have developed such a marker and show that it is effective and specific in all neuronal populations tested in the peripheral and central nervous system. The marker, which we name DenMark (Dendritic Marker), is a hybrid protein of the mouse protein ICAM5/Telencephalin and the red fluorescent protein mCherry. We show that DenMark is a powerful tool for revealing novel aspects of the neuroanatomy of developing dendrites, identifying previously unknown dendritic arbors, and elucidating neuronal connectivity.

Recent Incarceration Among Individuals Infected With Hepatitis A Virus During Person-to-Person Community Outbreaks, United States, 2016-2020.

OBJECTIVES: Although many people who are incarcerated have risk factors for hepatitis A virus (HAV) infection, the proportion of hepatitis A cases among people with a recent incarceration is unknown. We examined the relationship between recent incarceration and HAV infection during community-based, person-to-person outbreaks to inform public health recommendations. METHODS: The Centers for Disease Control and Prevention surveyed health departments in 33 jurisdictions reporting person-to-person HAV outbreaks during 2016-2020 on the number of outbreak-associated cases, HAV-infected people recently incarcerated, and HAV-associated hospitalizations and deaths. RESULTS: Twenty-five health departments reported 18 327 outbreak-associated hepatitis A cases during January 11, 2016-January 24, 2020. In total, 2093 (11.4%) HAV-infected people had been recently incarcerated. Of those with complete data, 1402 of 1462 (95.9%) had been held in a local jail, and 1513 of 1896 (79.8.%) disclosed hepatitis A risk factors. Eighteen jurisdictions reported incarceration timing relative to the exposure period. Of 9707 cases in these jurisdictions, 991 (10.2%) were among recently incarcerated people; 451 of 688 (65.6%) people with complete data had been incarcerated during all (n = 55) or part (n = 396) of their exposure period. CONCLUSIONS: Correctional facilities are important settings for reaching people with risk factors for HAV infection and can also be venues where transmission occurs. Providing HAV vaccination to incarcerated people, particularly people housed in jails, can be an effective component of community-wide outbreak response.

Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer's disease correlates with increased BACE1/beta-secretase expression.

Although the role of APP and PSEN genes in genetic Alzheimer's disease (AD) cases is well established, fairly little is known about the molecular mechanisms affecting Abeta generation in sporadic AD. Deficiency in Abeta clearance is certainly a possibility, but increased expression of proteins like APP or BACE1/beta-secretase may also be associated with the disease. We therefore investigated changes in microRNA (miRNA) expression profiles of sporadic AD patients and found that several miRNAs potentially involved in the regulation of APP and BACE1 expression appeared to be decreased in diseased brain. We show here that miR-29a, -29b-1, and -9 can regulate BACE1 expression in vitro. The miR-29a/b-1 cluster was significantly (and AD-dementia-specific) decreased in AD patients displaying abnormally high BACE1 protein. Similar correlations between expression of this cluster and BACE1 were found during brain development and in primary neuronal cultures. Finally, we provide evidence for a potential causal relationship between miR-29a/b-1 expression and Abeta generation in a cell culture model. We propose that loss of specific miRNAs can contribute to increased BACE1 and Abeta levels in sporadic AD.

Distal arteriovenous fistula to preserve patency in COVID-19-associated acute limb ischemia.

The purpose of this study was to report our institutional experience with patients with COVID-19 who developed acute limb ischemia during hospitalization and to determine the characteristics and clinical outcomes. Between March 2020 and January 2021, we treated 3 patients who were COVID-19-positive and developed acute limb ischemia after they received thromboprophylaxis. We performed an embolectomy by exposing the popliteal artery below the knee to treat an occlusion of the popliteal and tibial arteries. An infusion of unfractionated heparin was initiated immediately after surgery, maintaining a partial thromboplastin time ratio > 2.5 times the normal value and transferred the patients to the intensive care unit. However, after these patients developed recurrent acute limb ischemia in the same leg, we decided to perform an embolectomy of popliteal and tibial arteries at the ankle and created an arteriovenous fistula (AVF) with tibial veins using polypropylene 7-0. The first patient died from pneumonia after 3 weeks in the intensive care unit; at that time, the foot was viable with triphasic flow in the distal posterior tibial artery and the AVF was patent. The second and third patients are doing well, they can walk without any problems, and the tibial arteries and AFV were patent on duplex ultrasound after 6 months. The AVF allowed part of the flow of tibial arteries to divert into the small veins of the foot that have a low resistance to maintain patency of tibial vessels, despite a hypercoagulable state and extensive thrombotic microangiopathy in patients with COVID-19.

MicroRNA regulation of Alzheimer's Amyloid precursor protein expression.

Gene dosage effects of Amyloid precursor protein (APP) can cause familial AD. Recent evidence suggest that microRNA (miRNA) pathways, implicated in gene transcriptional control, could be involved in the development of sporadic Alzheimer's disease (AD). We therefore investigated whether miRNAs could participate in the regulation of APP gene expression. We show that miRNAs belonging to the miR-20a family (that is, miR-20a, miR-17-5p and miR-106b) could regulate APP expression in vitro and at the endogenous level in neuronal cell lines. A tight correlation between these miRNAs and APP was found during brain development and in differentiating neurons. We thus identify miRNAs as novel endogenous regulators of APP expression, suggesting that variations in miRNA expression could contribute to changes in APP expression in the brain during development and disease. This possibility is further corroborated by the observation that a statistically significant decrease in miR-106b expression was found in sporadic AD patients.

Relevance of inflammation and matrix remodeling in abdominal aortic aneurysm (AAA) and popliteal artery aneurysm (PAA) progression.

Aneurysm is a multifactorial degenerative disease characterized by focal dilatation of blood vessels. Although abdominal aortic (AAA) and popliteal aneurysms (PAA) are the most common dilatative vascular diseases and share some features, a comparison between the different anatomical sites and the relative pathophysiological differences has not been established. In order to gain deeper insights to AAA and PAA, we have characterized the role of matrix remodelling, vascular cells phenotype depletion and the inflammatory process in both diseases. Results show a more extensive presence of T-cell, B-cell and monocyte-macrophage infiltration in AAA with respect to PAA. Concurring with this aspect, IL-6, IL-8 and MCP-1 are 10-fold increased in AAA. Moreover, MMP-9, and metalloproteinase inhibitor 3 (TIMP3) resulted up-regulated in AAA tissues. Regarding the catalytic activity, which is tightly related to the oxidative stress, we found an up-regulation of superoxide dismutase [Mn] mitochondrial (SODM), glutathione peroxidase 3 (GPX3) and peroxiredoxin-1 (PRDX1). Histological analyses clearly showed a massive elastin fragmentation in AAA. This may enhance the inflammatory response, which has a prevalent role in AAA, while PAA is mainly guided by a loss of the contractile phenotype. These findings suggest insight in these potentially devastating diseases in term of their progression, aiming to identify potential specific markers respectively for AAA and PAA treatment.

Proper connectivity of Drosophila motion detector neurons requires Atonal function in progenitor cells.

BACKGROUND: Vertebrates and invertebrates obtain visual motion information by channeling moving visual cues perceived by the retina through specific motion sensitive synaptic relays in the brain. In Drosophila, the series of synaptic relays forming the optic lobe are known as the lamina, medulla, lobula and lobula plate neuropiles. The fly's motion detection output neurons, called the T4 and T5 cells, reside in the lobula plate. Adult optic lobe neurons are derived from larval neural progenitors in two proliferating compartments known as the outer and inner proliferation centers (OPC and IPC). Important insight has been gained into molecular mechanisms involved in the development of the lamina and medulla from the OPC, though less is known about the development of the lobula and lobula plate. RESULTS: Here we show that the proneural gene Atonal is expressed in a subset of IPC progenitors that give rise to the higher order motion detection neurons, T4 and T5, of the lobula plate. We also show that Atonal does not act as a proneural gene in this context. Rather, it is required specifically in IPC neural progenitors to regulate neurite outgrowth in the neuronal progeny. CONCLUSIONS: Our findings reveal that a proneural gene is expressed in progenitors but is required for neurite development of their progeny neurons. This suggests that transcriptional programs initiated specifically in progenitors are necessary for subsequent neuronal morphogenesis.

Occupational exposures in emergency medical service providers and knowledge of and compliance with universal precautions.

BACKGROUND: Little is known about compliance with universal precautions (CUP) or occupational exposures to blood and body fluids among Emergency Medical Services (EMS) providers. The objective of this study was to obtain estimates of CUP and knowledge of universal precautions (KUP), occupational exposures, and needle and lancet sticks in the prehospital environment. METHODS: A convenience sample of workers (n=311, 51% response) from 17 agencies in Virginia that provided emergency ground transportation (volunteer, commercial, government rescue squads, and fire departments) completed a questionnaire on certification and training, KUP, CUP, exposures and needlesticks, risk perceptions, and demographic variables. RESULTS: Nearly all EMS providers reported exposures and were concerned about risk of HIV and hepatitis. Providers reported inconsistent CUP when treating patients or using needles, including failure to wear gloves (17%) and to appropriately dispose of contaminated materials (79%), including needles (87%), at all times. Certification type (advanced and basic) was related to both KUP and CUP. Of those respondents reporting current sharps use, 40% recapped needles. A lancet stick was reported by 1.4% (n=5), and 4.5% reported a needlestick (n=14). CONCLUSION: EMS providers working in the prehospital environment experience significant exposures but are not consistently using universal precautions.