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Hypoxia contributes to numerous pathophysiological conditions including inflammation-associated diseases. We characterized the impact of hypoxia on the immunometabolic cross-talk between cholesterol and interferon (IFN) responses. Specifically, hypoxia reduced cholesterol biosynthesis flux and provoked a compensatory activation of sterol regulatory element-binding protein 2 (SREBP2) in monocytes. Concomitantly, a broad range of interferon-stimulated genes (ISGs) increased under hypoxia in the absence of an inflammatory stimulus. While changes in cholesterol biosynthesis intermediates and SREBP2 activity did not contribute to hypoxic ISG induction, intracellular cholesterol distribution appeared critical to enhance hypoxic expression of chemokine ISGs. Importantly, hypoxia further boosted chemokine ISG expression in monocytes upon infection with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). Mechanistically, hypoxia sensitized toll-like receptor 4 (TLR4) signaling to activation by SARS-CoV-2 spike protein, which emerged as a major signaling hub to enhance chemokine ISG induction following SARS-CoV-2 infection of hypoxic monocytes. These data depict a hypoxia-regulated immunometabolic mechanism with implications for the development of systemic inflammatory responses in severe cases of coronavirus disease-2019 (COVID-19).

During the pandemic, nursing homes in the Netherlands were heavily affected by COVID-19. This study assesses the impact of COVID-19 on infection rate, survival rate, and daily functioning over the course of two years among residents of a nursing home in the Netherlands that was amongst the first nursing homes to be affected by the pandemic. This retrospective study followed 70 residents during a two-year period, starting in March 2020. Data were collected on baseline characteristics of participants and the onset, duration, and sequelae of COVID-19 infections. Primary outcomes were mortality and infection rate. The secondary outcome was daily functioning using the Barthel Index at intervals of six months. Within two years, 44 (62.9%) residents were diagnosed with COVID-19. During this study, 72.7% (n = 32) of the COVID-positive residents died, of which 22 deaths were related to the COVID-19 infection. Overall mortality was 60% (n = 42), while COVID-related mortality was 31.4% (n = 22). COVID-19 and multimorbidity (>3 morbidities) were independent risk factors for mortality. Barthel Index scores showed no significant difference in daily functioning. Overall, a high COVID-19 infection rate was seen and was the most common cause of death. COVID-19 did not affect functional status over time.

Topological insulator (TI) nanoribbons with proximity-induced superconductivity are a promising platform for Majorana bound states (MBSs). In this work, we consider a detailed modeling approach for a TI nanoribbon in contact with a superconductor via its top surface, which induces a superconducting gap in its surface-state spectrum. The system displays a rich phase diagram with different numbers of end-localized MBSs as a function of chemical potential and magnetic flux piercing the cross section of the ribbon. These MBSs can be robust or fragile upon consideration of electrostatic disorder. We simulate a tunneling spectroscopy setup to probe the different topological phases of top-proximitized TI nanoribbons. Our simulation results indicate that a top-proximitized TI nanoribbon is ideally suited for realizing fully gapped topological superconductivity, in particular when the Fermi level is pinned near the Dirac point. In this regime, the setup yields a single pair of MBSs, well separated at opposite ends of the proximitized ribbon, which gives rise to a robust quantized zero-bias conductance peak.

The decline in the population of ring-necked pheasants (Phasianus colchicus) in northwestern Germany since 2007 raises questions about the underlying causes. We therefore studied the growth and immune status of ring-necked pheasant chicks dependent on different feed composition. Here, 490 ring-necked pheasant chicks were raised in five groups up to nine weeks. While control groups C1 and C2 received sufficient crude protein (28%) and energy (12.5 MJ/Kg feed) according to current standards, group C2 was treated with cyclosporine eight hours prior to phythemagglutination (PHA) testing, serving as a positive immune suppressed control. Group V1 was fed with reduced protein (20%) but optimal energy content (12.5 MJ/Kg feed), group V2 was fed with sufficient protein (28%) and reduced energy content (10 MJ/kg feed) whereas group V3 was fed reduced crude protein (20%) and reduced energy content (10MJ/kg feed). On all chicks, health status was checked each week, and 20 birds of each group were weighed randomly per week. PHA-testing was performed on 12 birds of each group to study the in vivo non-specific activation of lymphocytes at week 2, 4, 6, 7, 8 and 9. In addition, hemolysis-hemagglutination-assay (HHA) was performed on each of the PHA-tested chicks, which were subsequently euthanized and dissected. Histopathologic examinations of 5 birds that were randomly chosen were performed. The PHA-test results demonstrate significant differences between control (C1, C2) and experimental groups (V1-V3) in several developmental stages. According to the HHA results, weekly testing detected a significant increase of titres per week in all groups without significant differences. Here, only hemagglutination and no lysis of samples was observed. It seems appropriate to conclude that during their first weeks of life, protein content is of higher importance in ring-necked pheasant chicks than energy intake. In particular T-cell response is significantly reduced, which indicate a weaker immune system resulting in a higher risk for clinical diseases. Therefore, we assume that protein i.e. insect availability is a highly important co-factor in the free-ranging population dynamics, and is linked to declines of the northwestern German population.

Abstract Background Nursing home residents with early-onset neurodegenerative diseases are often younger in comparison with other residents, and need different, often more complex care. Accordingly, the measurements currently used for measuring quality of care in nursing homes may not be suitable for use in this target group. Little is known about the experiences of these residents and of their (in) formal caregivers regarding the quality of care they receive. Therefore, the aim of this scoping review is to explore which instruments are available for measuring the quality of care for nursing home residents with early-onset neurodegenerative diseases (excluding dementia), from the perspective of the resident and of (in) formal caregivers. Methods A literature search was performed in the databases Pubmed, Embase, Web of Science and Cinahl. The search strategy consisted of four main concepts: neurodegenerative diseases, quality of care, nursing homes and perspectives of residents, (in) formal caregivers. Studies were included if they used instruments and/or strategies to measure quality of care, focused on nursing home residents with early-onset neurodegenerative diseases and the perspective of either the resident or (in) formal caregiver. Results From a total of 809 identified articles, 87 full text articles were screened for eligibility. Five studies were included, only one of which described an instrument. The other four used topic lists and/or themes to measure quality of care. In total, 60 items related to quality of care could be derived. From these 60 items, eight overarching domains were found, with a subdivision into items derived, respectively, from the residents’, informal and formal caregivers’ perspective: ‘emotional support’, ‘physical support’, ‘social support’, ‘care’, ‘care content’, ‘expertise’, ‘communication’ and ‘organization of care’. Conclusions Currently, there are no methods for assessing the quality of care specifically focused on nursing home residents with early-onset neurodegenerative diseases. Therefore, the items retrieved in this review give an overview of important topics for measuring the quality of care for this target group, from the perspective of the resident, and of the informal and formal caregivers. These items might be used to develop a tailored instrument for assessing the quality of care for nursing home residents with early-onset neurodegenerative diseases.

Parrot bornavirus (PaBV) might be transmitted vertically. Cockatiel embryonic brain cells and embryonated eggs of cockatiels (ECE) were infected with PaBV-2 and PaBV-4. In embryonic brain cells, PaBV-2 and PaBV-4 showed no differences in viral spread despite the slower growth of PaBV-2 compared with PaBV-4 in CEC-32 cells. ECE were inoculated with PaBV-4 and 13–14 dpi, organs were sampled for RT-PCR, immunohistochemistry/histology, and virus isolation. In 28.1% of the embryos PaBV-4-RNA and in 81.3% PaBV-4-antigen was detected in the brain. Virus isolation failed. Division of organ samples and uneven tissue distribution of the virus limited the results. Therefore, 25 ECE were inoculated with PaBV-4 (group 1) and 15 ECE with PaBV-2 (group 3) in the yolk sac, and 25 ECE were inoculated with PaBV-4 (group 2) and 15 eggs with PaBV-2 (group 4) in the chorioallantoic membrane to use the complete organs from each embryo for each examination method. PaBV-RNA was detected in the brain of 80% of the embryos in groups 1, 2, 3 and in 100% of the embryos in group 4. In 90% of the infected embryos of group 1, and 100% of group 2, 3 and 4, PaBV antigen was detected in the brain. PaBV antigen–positive brain cells were negative for anti-neuronal nuclear protein, anti-glial fibrillary acidic protein, and anti S-100 staining. Virus was not re-isolated. These results demonstrated a specific distribution pattern and spread of PaBV-4 and PaBV-2 in the brain when inoculated in ECE. These findings support a potential for vertical transmission.

During the pandemic, nursing homes in the Netherlands were heavily affected by COVID-19. This study assesses the impact of COVID-19 on infection rate, survival rate, and daily functioning over the course of two years among residents of a nursing home in the Netherlands that was amongst the first nursing homes to be affected by the pandemic. This retrospective study followed 70 residents during a two-year period, starting in March 2020. Data were collected on baseline characteristics of participants and the onset, duration, and sequelae of COVID-19 infections. Primary outcomes were mortality and infection rate. The secondary outcome was daily functioning using the Barthel Index at intervals of six months. Within two years, 44 (62.9%) residents were diagnosed with COVID-19. During this study, 72.7% (n = 32) of the COVID-positive residents died, of which 22 deaths were related to the COVID-19 infection. Overall mortality was 60% (n = 42), while COVID-related mortality was 31.4% (n = 22). COVID-19 and multimorbidity (>3 morbidities) were independent risk factors for mortality. Barthel Index scores showed no significant difference in daily functioning. Overall, a high COVID-19 infection rate was seen and was the most common cause of death. COVID-19 did not affect functional status over time. [ABSTRACT FROM AUTHOR]

Samenvatting Verpleeghuis Mariënburght in Budel is, ondanks navolging van de RIVM-richtlijnen, hard getroffen tijdens de eerste COVID-19 golf met 68 (68%) besmette bewoners. Dit leidde tot grote emotionele impact bij (zorg)medewerkers. Dit onderzoek beoogt de ervaringen van (zorg)medewerkers te beschrijven, net als de uitslagen van serologische testen op COVID-19 die zijn afgenomen bij medewerkers. Alle medewerkers (n=281) werden uitgenodigd voor een groepsinterview om ervaringen tijdens de COVID-19 uitbraak te bespreken en voor afname van een serologische test op COVID-19. De 29 personen die deelnamen aan de groepsinterviews benoemden negatieve en positieve ervaringen over hun angst en ongerustheid, de veranderde zorg voor bewoners, het teamgevoel, inzet van persoonlijke beschermingsmiddelen en het testbeleid. Van de 240 medewerkers die een serologische test hebben ondergaan en een vragenlijst invulden, hadden 94 medewerkers (39%) antistoffen tegen COVID-19. Hiervan gaven er 18 (19%) aan geen klachten te hebben gehad. Inzicht in de ervaringen van medewerkers heeft geleid tot evidente leerpunten, met name het belang van een heldere communicatie met en emotionele ondersteuning van het personeel. Uit dit onderzoek blijkt ook dat veel medewerkers van verpleeghuis Mariënburght getroffen zijn door COVID-19. Opvallend is het percentage asymptomatische medewerkers (19% van 94 geïnfecteerden). Deze resultaten hebben mede bijgedragen aan de aanpassing van het landelijke testbeleid en de wijze van inzet van persoonlijke beschermingsmiddelen in verpleeghuizen. Abstract Despite compliance with national (RIVM) guidelines, nursing home Mariënburght (the Netherlands) was severely affected during the first COVID-19 wave: 68 (68%) of the residents were infected. This resulted in a large emotional impact on the (nursing) staff. This study aims to describe the experiences of (nursing) staff, as well as the results of serological tests on COVID-19 that have been administered to professionals. All professionals (n=281) were invited for group interviews to share their experiences concerning the COVID-19 outbreak and for a serological test for COVID-19. The 29 professionals participating in the group interviews mentioned negative and positive experiences about their fear and anxiety, the changed care for residents, the team spirit, the use of personal protective equipment and the testing policy. Out of 240 professionals who underwent the serological test and completed a questionnaire, 94 professionals (39%) had COVID-19 antibodies. In this group, 18 professionals (19%) indicated not having experienced any (physical) complaints related to COVID. Insight into the experiences of professionals resulted in essential learning points, in particular the importance of clear communication with and emotional support for staff. This study also reveals that many professionals of nursing home Mariënburght were affected by COVID-19. An important finding is the high percentage of asymptomatic employees (19% of 94 infected). Our results contributed to changed national testing policies and adapted recommendations in the use of personal protective equipment in nursing homes.

Infectious diseases in captive pheasants (Phasianus colchicus) are well known, but there is a lack of knowledge about occurrence and distribution of pathogens in free-ranging pheasants in Germany. We investigated 604 sera from hunted pheasants and 152 sera from wild caught pheasants between 2011 to 2015, with the aim to determine the prevalence of specific antibodies against different viruses: Avian influenza virus (AIV) of subtypes H5, H7, H9, paramyxovirus type 1 (PMV-1), avian encephalomyelitis virus (AEV), infectious bursitis disease virus (IBDV), infectious bronchitis virus (IBV), infectious laryngotracheitis virus (ILTV), avian metapneumovirus (aMPV) and Salmonella sp., Mycoplasma synoviae (MS) and Mycoplasma gallisepticum (MG). In addition, 178 caeca were investigated for Histomonas meleagridis. The study reveals an ongoing circulation of IBV in the wild pheasant population during the study. Also high seroprevalences of specific antibodies against aMPV depending on the area and a strong increase in prevalence of IBDV antibodies in sera of pheasants in Lower Saxony were detected. ILTV antibody prevalences differed between areas and AEV antibody detection differed between years significantly, whereas specific antibodies against PMV-1 could not be detected and antibodies against AIV-H5, -H7 and -H9 and Mycoplasma spp. were detected in very few cases.

Being a typical ground-breeding bird of the agricultural landscape in Germany, the pheasant has experienced a strong and persistent population decline with a hitherto unexplained cause. Contributing factors to the ongoing negative trend, such as the effects of pesticides, diseases, predation, increase in traffic and reduced fallow periods, are currently being controversially discussed. In the present study, 62 free-ranging pheasant chicks were caught within a two-year period in three federal states of Germany; Lower Saxony, North Rhine-Westphalia and Schleswig-Holstein. The pheasant chicks were divided into three age groups to detect differences in their development and physical constitution. In addition, pathomorphological, parasitological, virological, bacteriological and toxicological investigations were performed. The younger chicks were emaciated, while the older chicks were of moderate to good nutritional status. However, the latter age group was limited to a maximum of three chicks per hen, while the youngest age class comprised up to ten chicks. The majority of chicks suffered from dermatitis of the periocular and caudal region of the head (57-94%) of unknown origin. In addition, intestinal enteritis (100%), pneumonia (26%), hepatitis (24%), perineuritis (6%), tracheitis (24%), muscle degeneration (1%) and myositis (1%) were found. In 78% of the cases, various Mycoplasma spp. were isolated. Mycoplasma gallisepticum (MG) was not detected using an MG-specific PCR. Parasitic infections included Philopteridae (55%), Coccidia (48%), Heterakis/Ascaridia spp. (8%) and Syngamus trachea (13%). A total of 8% of the chicks were Avian metapneumovirus (AMPV) positive using RT-PCR, 16% positive for infectious bronchitis virus (IBV) using RT-PCR, and 2% positive for haemorrhagic enteritis virus (HEV) using PCR. All samples tested for avian encephalomyelitis virus (AEV), infectious bursal disease virus (IBDV) or infectious laryngotracheitis virus (ILTV) were negative. The pool samples of the ten chicks were negative for all acid, alkaline-free and derivative substances, while two out of three samples tested were positive for the herbicide glyphosate. Pheasant chick deaths may often have been triggered by poor nutritional status, probably in association with inflammatory changes in various tissues and organs as well as bacterial and parasitic pathogens. Theses impacts may have played a major role in the decline in pheasant populations.