Project description:The source of the severe acute respiratory syndrome (SARS) epidemic was traced to wildlife market civets and ultimately to bats. Subsequent hunting for novel coronaviruses (CoVs) led to the discovery of two additional human and over 40 animal CoVs, including the prototype lineage C betacoronaviruses, Tylonycteris bat CoV HKU4 and Pipistrellus bat CoV HKU5; these are phylogenetically closely related to the Middle East respiratory syndrome (MERS) CoV, which has affected more than 1,000 patients with over 35% fatality since its emergence in 2012. All primary cases of MERS are epidemiologically linked to the Middle East. Some of these patients had contacted camels which shed virus and/or had positive serology. Most secondary cases are related to health care-associated clusters. The disease is especially severe in elderly men with comorbidities. Clinical severity may be related to MERS-CoV's ability to infect a broad range of cells with DPP4 expression, evade the host innate immune response, and induce cytokine dysregulation. Reverse transcription-PCR on respiratory and/or extrapulmonary specimens rapidly establishes diagnosis. Supportive treatment with extracorporeal membrane oxygenation and dialysis is often required in patients with organ failure. Antivirals with potent in vitro activities include neutralizing monoclonal antibodies, antiviral peptides, interferons, mycophenolic acid, and lopinavir. They should be evaluated in suitable animal models before clinical trials. Developing an effective camel MERS-CoV vaccine and implementing appropriate infection control measures may control the continuing epidemic.
Project description:The aim of the study was to evaluate the impact of the coronavirus pandemic on the willingness, anxiety and concerns of Italian people on undergoing dental appointments. An anonymous survey was posted online on social media on 11 May 2020 and was completed by 1003 respondents in one week. Multiple correspondence analysis and multiple logistic regression were used to evaluate the association between socio-demographic characteristics, dental care access, contagion fear of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), trust in dentists regarding sanitization procedures and perception of the impact of the risk of contagion on dental care. Subjects with a high level of education, attending public dental offices and that are used to go to dental offices for urgent care would not feel comfortable in undergoing a dental appointment and would prefer to postpone or cancel dental visits, waiting for a decrease in the number of the contagions. Moreover, the risk of canceling or postponing the appointment at the dentist was 1.59 times greater in those who claimed to be strongly influenced by SARS-CoV-2. Fear of coronavirus disease (COVID-19), new cases decrease and the not urgent nature of dental visits influenced more than the lowered income household on upcoming or resuming dental appointments. In the next months, despite the forecasted economic crisis caused by coronavirus pandemic, fear and anxiety generated by the spread of the virus will impact more than the lowered familiar income with regards to access to dental care.
Project description:Recently, a novel coronavirus (2019-nCoV) has emerged from Wuhan, China, causing symptoms in humans similar to those caused by severe acute respiratory syndrome coronavirus (SARS-CoV). Since the SARS-CoV outbreak in 2002, extensive structural analyses have revealed key atomic-level interactions between the SARS-CoV spike protein receptor-binding domain (RBD) and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. Here, we analyzed the potential receptor usage by 2019-nCoV, based on the rich knowledge about SARS-CoV and the newly released sequence of 2019-nCoV. First, the sequence of 2019-nCoV RBD, including its receptor-binding motif (RBM) that directly contacts ACE2, is similar to that of SARS-CoV, strongly suggesting that 2019-nCoV uses ACE2 as its receptor. Second, several critical residues in 2019-nCoV RBM (particularly Gln493) provide favorable interactions with human ACE2, consistent with 2019-nCoV's capacity for human cell infection. Third, several other critical residues in 2019-nCoV RBM (particularly Asn501) are compatible with, but not ideal for, binding human ACE2, suggesting that 2019-nCoV has acquired some capacity for human-to-human transmission. Last, while phylogenetic analysis indicates a bat origin of 2019-nCoV, 2019-nCoV also potentially recognizes ACE2 from a diversity of animal species (except mice and rats), implicating these animal species as possible intermediate hosts or animal models for 2019-nCoV infections. These analyses provide insights into the receptor usage, cell entry, host cell infectivity and animal origin of 2019-nCoV and may help epidemic surveillance and preventive measures against 2019-nCoV.IMPORTANCE The recent emergence of Wuhan coronavirus (2019-nCoV) puts the world on alert. 2019-nCoV is reminiscent of the SARS-CoV outbreak in 2002 to 2003. Our decade-long structural studies on the receptor recognition by SARS-CoV have identified key interactions between SARS-CoV spike protein and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. One of the goals of SARS-CoV research was to build an atomic-level iterative framework of virus-receptor interactions to facilitate epidemic surveillance, predict species-specific receptor usage, and identify potential animal hosts and animal models of viruses. Based on the sequence of 2019-nCoV spike protein, we apply this predictive framework to provide novel insights into the receptor usage and likely host range of 2019-nCoV. This study provides a robust test of this reiterative framework, providing the basic, translational, and public health research communities with predictive insights that may help study and battle this novel 2019-nCoV.
Project description:β2-microglobulin (β2-m), a 11.8 kDa protein, pairs non-covalently with the α3 domain of the major histocompatibility class (MHC) I α-chain and is essential for the conformation of the MHC class I protein complex. Shed β2-m is measurable in circulation, and various disorders are accompanied by increases in β2-m levels, including several viral infections. Therefore, we explored whether β2-m levels could also be elevated in Coronavirus disease 2019 (Covid-19) and whether they predict disease severity. Serum β2-m levels were measured in a cohort of 34 patients infected with SARS-CoV-2 on admission to a tertiary care hospital in Riyadh, Saudi Arabia, as well as in an approximately age-sex matched group of 34 uninfected controls. Mean β2-m level was 3.25±1.68 mg/l (reference range 0.8-2.2 mg/l) in patients (mean age 48.2±21.6) and 1.98±0.61 mg/l in controls (mean age 48.2±21.6). 17 patients (mean age 36.9± 18.0) with mean β2-m levels of 2.27±0.64 mg/l had mild disease by WHO severity categorization, 12 patients (mean age 53.3±18.1) with mean β2-m levels of 3.57±1.39 mg/l had moderate disease, and five patients (of whom 2 died; mean age 74.4±13.8) with mean β2-m levels of 5.85±1.85 mg/l had severe disease (P < = 0.001, by ANOVA test for linear trend). In multivariate ordinal regression β2-m levels were the only significant predictor of disease severity. Our findings suggest that higher β2-m levels could be an early indicator of severity of disease and predict outcome of Covid-19. As the main limitations of the study are a single-center study, sample size and ethnicity, these results need confirmation in larger cohorts outside the Arabian Peninsula in order to delineate the value of β2-m measurements. The role of β2-m in the etiology and pathogenesis of severe Covid-19 remains to be elucidated.
Project description:In primates, yawn contagion (the yawning response elicited by others' yawn) is variably influenced by individual (e.g., sex, age) and social factors (e.g., familiarity) and possibly linked to interindividual synchronization, coordination, and emotional contagion. Two out of three studies on yawn contagion in bonobos (Pan paniscus), found the presence of the phenomenon with mixed results concerning the effect of familiarity and no replication on its modulating factors. To address this puzzling issue, we recorded all occurrences data on yawn contagion in a captive bonobo group (March-June 2021; 18 individuals; La Vallée des Singes, France). Contrary to chimpanzees and humans, the number of triggering yawns increased contagion, possibly owing to a higher stimulus threshold. This aspect may explain the interindividual variability observed in yawn contagion rates. In subjects under weaning, we did not detect yawn contagion and, as it occurs in certain human cohorts, yawn contagion declined with age, possibly due to reduced sensitivity to others. Females responded more than males and elicited more responses from females when showing sexual swelling. As reproductive females are central in bonobo society, our results support the hypothesis that-as in other Hominini-the most influential sex can influence yawn contagion. The relationship quality (measured via grooming/play) did not affect yawn contagion, possibly due to bonobos' xenophilic nature. Overall, this study confirms the presence of yawn contagion in bonobos and introduces new elements on its modulating factors, pointing toward the necessity of cross-group studies.
Project description:Set of microarray experiments used to identify an unknown coronavirus in a viral culture derived from a patient with SARS. March 2003. Keywords = SARS Keywords = coronavirus Keywords = viral discovery Keywords = viruses Keywords = respiratory infection
Project description:Several influential theories posit that improvements in emotion regulation contribute to enhanced emotional well-being in older adulthood. However, surprisingly little is known about whether there are age differences in emotion regulation strategy use. We addressed this question by testing whether older adults report using typically adaptive strategies more often and regulate more flexibly than relatively younger adults. In a two-part study, 136 married couples (N = 272) aged 23-85 years completed individual difference measures of cognitive reappraisal and expressive suppression, and then nine daily reports of a broader range of emotion regulation strategies, now including situation selection, situation modification, and distraction. Older adults reported greater habitual use of suppression, but age did not predict situation selection, situation modification, distraction, or reappraisal. In terms of emotion regulation flexibility, a similar number of strategies were reported on a daily basis regardless of the regulator's age. Unexpectedly, relatively older adults were less variable in their self-reported daily use of each strategy and middle-aged adults were the least variable in their strategy repertoire across different days. These findings counter the common notion that older adults use typically adaptive strategies more than younger adults. Instead, they suggest older adults may be more consistent in their emotion regulation patterns across situations, potentially suggestive of less flexibility. Implications for aging, emotion regulation, and well-being are discussed. (PsycINFO Database Record
Project description:PCSK9 proprotein convertase subtilisin/kexin type (PCSK9) is a crucial protein in LDL cholesterol (LDL-C) metabolism by virtue of its pivotal role in the degradation of the LDL receptor. In recent years, both in vitro and in vivo studies have greatly supplemented our understanding of the (patho)physiological role of PCSK9 in human biology. In the current review, we summarize studies published or in print before May 2012 concerning the physiological role of PCSK9 in cholesterol metabolism. Moreover, we briefly describe the clinical phenotypes encountered in carriers of mutations in the gene encoding PCSK9. As PCSK9 has emerged as a novel target for LDL-C lowering therapy, methods to inhibit PCSK9 will also be reviewed. Initial data from investigations of PCSK9 inhibition in humans are promising and indicate that PCSK9 inhibition may be a viable new therapeutic option for the treatment of dyslipidemia and associated cardiovascular diseases.