Joubert syndrome and related disorders (JSRDs) are genetically heterogeneous and characterized by a distinctive mid-hindbrain malformation. Causative mutations lead to primary cilia dysfunction, ...which often results in variable involvement of other organs such as the liver, retina, and kidney. We identified predicted null mutations in CSPP1 in six individuals affected by classical JSRDs. CSPP1 encodes a protein localized to centrosomes and spindle poles, as well as to the primary cilium. Despite the known interaction between CSPP1 and nephronophthisis-associated proteins, none of the affected individuals in our cohort presented with kidney disease, and further, screening of a large cohort of individuals with nephronophthisis demonstrated no mutations. CSPP1 is broadly expressed in neural tissue, and its encoded protein localizes to the primary cilium in an in vitro model of human neurogenesis. Here, we show abrogated protein levels and ciliogenesis in affected fibroblasts. Our data thus suggest that CSPP1 is involved in neural-specific functions of primary cilia.
Many SARS-CoV-2 variants have emerged during the course of the COVID-19 pandemic. These variants have acquired mutations conferring phenotypes such as increased transmissibility or virulence, or ...causing diagnostic, therapeutic, or immune escape. Detection of Alpha and the majority of Omicron sublineages by PCR relied on the so-called S gene target failure due to the deletion of six nucleotides coding for amino acids 69-70 in the spike (S) protein. Detection of hallmark mutations in other variants present in samples relied on whole genome sequencing. However, whole genome sequencing as a diagnostic tool is still in its infancy due to geographic inequities in sequencing capabilities, higher cost compared to other molecular assays, longer turnaround time from sample to result, and technical challenges associated with producing complete genome sequences from samples that have low viral load and/or high background. Hence, there is a need for rapid genotyping assays. In order to rapidly generate information on the presence of a variant in a given sample, we have created a panel of four triplex RT-qPCR assays targeting 12 mutations to detect and differentiate all five variants of concern: Alpha, Beta, Gamma, Delta, and Omicron. We also developed an expanded pentaplex assay that can reliably distinguish among the major sublineages (BA.1-BA.5) of Omicron.
, analytical and clinical testing of the variant panel indicate that the assays exhibit high sensitivity and specificity. This panel can help fulfill the need for rapid identification of variants in samples, leading to quick decision making with respect to public health measures, as well as treatment options for individuals. Compared to sequencing, these genotyping PCR assays allow much faster turn-around time from sample to results-just a couple hours instead of days or weeks.
Two novel genotypes of species human mastadenovirus D designated 109 and 110 were isolated from three epidemiologically unrelated cases of acute respiratory disease detected in January 2018 by ...surveillance efforts at the California/Mexico border. Both genotypes represent examples of intertypic recombination. Genotype D109 is most closely related to genotype D56 (97.68% genomic similarity) and features a type D22‐like penton base, a type D19‐like hexon gene, and a type D9‐like fiber P22/H19/F9. On the other hand, genotype D110 is most closely related to type D22 (96.94% genomic similarity) and features a type D67‐like penton base, a novel hexon gene, and a type D9‐like fiber P67/H110/F9. Importantly, the fibers of both novel genotypes are highly similar to those of genotypes D56 and D59, which have also been isolated from a few cases of respiratory infections. The present report shows data contributing to the understanding of the molecular determinants of the expanded tissue tropism of certain members of species HAdV‐D.
The volume is based on papers presented at a workshop on the green transport agenda and its implications for Chinese cities, organised by the World Conference on Transport Research Society in ...September 2010. The five sections of this volume review the challenges facing urban transport internationally and in China. It considers approaches to policy formulation, the challenge of urban mobility and the development of green sustainable transportation, by reviewing best practice in objective setting, strategy analysis and policy selection, and comparing these with current practice in China. The authors examine passenger transport, and considers a number of current policy interventions in China and compare these with western experience with demand management and new vehicle technologies. Topics include 5D land-use transport model for a high density, rapidly growing city and Contextual requirements for electric vehicles in developed and developing countries. Finally freight and logistics is addressed, including the role of freight villages and milk run strategies, and challenges and policy recommendations for road freight in Shanghai.
•A significant reduction in psychological impact 4 weeks after COVID outbreak.•The mean scores of respondents in both surveys were above PTSD cut-offs.•Female gender, physical symptoms associated ...with a higher psychological impact.•Hand hygiene, mask-wearing & confidence in doctors reduced psychological impact.•Online trauma-focused psychotherapy may be helpful to public during COVID-19.
In addition to being a public physical health emergency, Coronavirus disease 2019 (COVID-19) affected global mental health, as evidenced by panic-buying worldwide as cases soared. Little is known about changes in levels of psychological impact, stress, anxiety and depression during this pandemic. This longitudinal study surveyed the general population twice - during the initial outbreak, and the epidemic's peak four weeks later, surveying demographics, symptoms, knowledge, concerns, and precautionary measures against COVID-19. There were 1738 respondents from 190 Chinese cities (1210 first-survey respondents, 861 s-survey respondents; 333 respondents participated in both). Psychological impact and mental health status were assessed by the Impact of Event Scale-Revised (IES-R) and the Depression, Anxiety and Stress Scale (DASS-21), respectively. IES-R measures PTSD symptoms in survivorship after an event. DASS -21 is based on tripartite model of psychopathology that comprise a general distress construct with distinct characteristics. This study found that there was a statistically significant longitudinal reduction in mean IES-R scores (from 32.98 to 30.76, p < 0.01) after 4 weeks. Nevertheless, the mean IES-R score of the first- and second-survey respondents were above the cut-off scores (>24) for PTSD symptoms, suggesting that the reduction in scores was not clinically significant. During the initial evaluation, moderate-to-severe stress, anxiety and depression were noted in 8.1%, 28.8% and 16.5%, respectively and there were no significant longitudinal changes in stress, anxiety and depression levels (p > 0.05). Protective factors included high level of confidence in doctors, perceived survival likelihood and low risk of contracting COVID-19, satisfaction with health information, personal precautionary measures. As countries around the world brace for an escalation in cases, Governments should focus on effective methods of disseminating unbiased COVID-19 knowledge, teaching correct containment methods, ensuring availability of essential services/commodities, and providing sufficient financial support.
The 2019 coronavirus disease (COVID-19) epidemic is a public health emergency of international concern and poses a challenge to psychological resilience. Research data are needed to develop ...evidence-driven strategies to reduce adverse psychological impacts and psychiatric symptoms during the epidemic. The aim of this study was to survey the general public in China to better understand their levels of psychological impact, anxiety, depression, and stress during the initial stage of the COVID-19 outbreak. The data will be used for future reference.
From 31 January to 2 February 2020, we conducted an online survey using snowball sampling techniques. The online survey collected information on demographic data, physical symptoms in the past 14 days, contact history with COVID-19, knowledge and concerns about COVID-19, precautionary measures against COVID-19, and additional information required with respect to COVID-19. Psychological impact was assessed by the Impact of Event Scale-Revised (IES-R), and mental health status was assessed by the Depression, Anxiety and Stress Scale (DASS-21).
This study included 1210 respondents from 194 cities in China. In total, 53.8% of respondents rated the psychological impact of the outbreak as moderate or severe; 16.5% reported moderate to severe depressive symptoms; 28.8% reported moderate to severe anxiety symptoms; and 8.1% reported moderate to severe stress levels. Most respondents spent 20-24 h per day at home (84.7%); were worried about their family members contracting COVID-19 (75.2%); and were satisfied with the amount of health information available (75.1%). Female gender, student status, specific physical symptoms (e.g., myalgia, dizziness, coryza), and poor self-rated health status were significantly associated with a greater psychological impact of the outbreak and higher levels of stress, anxiety, and depression (
< 0.05). Specific up-to-date and accurate health information (e.g., treatment, local outbreak situation) and particular precautionary measures (e.g., hand hygiene, wearing a mask) were associated with a lower psychological impact of the outbreak and lower levels of stress, anxiety, and depression (
< 0.05).
During the initial phase of the COVID-19 outbreak in China, more than half of the respondents rated the psychological impact as moderate-to-severe, and about one-third reported moderate-to-severe anxiety. Our findings identify factors associated with a lower level of psychological impact and better mental health status that can be used to formulate psychological interventions to improve the mental health of vulnerable groups during the COVID-19 epidemic.
Living in high expressed emotion (EE) environments tends to increase the relapse rate in schizophrenia (SZ). At present, the neural substrates responsible for high EE in SZ remain poorly understood. ...Functional near-infrared spectroscopy (fNIRS) may be of great use to quantitatively assess cortical hemodynamics and elucidate the pathophysiology of psychiatric disorders. In this study, we designed novel low- (positivity and warmth) and high-EE (criticism, negative emotion, and hostility) stimulations, in the form of audio, to investigate cortical hemodynamics. We used fNIRS to measure hemodynamic signals while participants listened to the recorded audio. Healthy controls (HCs, Formula: see text) showed increased hemodynamic activation in the major language centers across EE stimulations, with stronger activation in Wernicke's area during the processing of negative emotional language. Compared to HCs, people with SZ (Formula: see text) exhibited smaller hemodynamic activation in the major language centers across EE stimulations. In addition, people with SZ showed weaker or insignificant hemodynamic deactivation in the medial prefrontal cortex. Notably, hemodynamic activation in SZ was found to be negatively correlated with the negative syndrome scale score at high EE. Our findings suggest that the neural mechanisms in SZ are altered and disrupted, especially during negative emotional language processing. This supports the feasibility of using the designed EE stimulations to assess people who are vulnerable to high-EE environments, such as SZ. Furthermore, our findings provide preliminary evidence for future research on functional neuroimaging biomarkers for people with psychiatric disorders.
The physical and mental health of citizens living in a country that encouraged face masks (China) and discouraged face masks (Poland) during the initial stage of the COVID-19 pandemic remained ...unknown. We conducted a cross-country study to compare the psychological impact of the COVID-19 pandemic on Poles and Chinese. This study aimed to compare the levels of psychological impact of pandemic and levels of anxiety and depression between China and Poland.
The survey collected information on demographic data, physical symptoms, contact history, and precautionary measures. The psychological impact was assessed using the Impact of Event Scale-Revised (IES-R), and mental health status was assessed by the Depression, Anxiety and Stress Scale (DASS-21). The chi-squared test was used to analyze the differences in categorical variables between the two populations. Linear regression was used to calculate the bivariate associations between independents variables (e.g., physical symptoms and precautionary measures) and dependent variables (e.g., mental health outcomes).
This study included a total of 2,266 respondents from both countries (1,056 Poles and 1,210 Chinese). There were significantly less Polish respondents who wore face masks (Poles: 35.0%; Chinese: 96.8% p < 0.001). Significantly more Polish respondents reported physical symptoms resembling COVID-19 infection (p < 0.001), recent medical consultation (p < 0.01), recent COVID-19 testing (p < 0.001), and hospitalization (p < 0.01). Furthermore, Polish respondents had significantly higher levels of anxiety, depression and stress (p < 0.001) than Chinese. The mean IES-R scores of Poland and China were above the cut-off for post-traumatic stress disorder (PTSD) symptoms. Besides precautionary measures, unemployment, retirement, physical symptoms resembling COVID-19 infection, recent medical consultation or COVID-19 testing, and long daily duration of home confinement were risk factors for PTSD symptoms, anxiety, depression, or stress for Polish respondents.
Use of face masks at the community level may safeguard better physical and mental health during the COVID-19 pandemic. There is a need of health education with scientific information from Polish health authority on the proper use of face masks and reduce social stigma. This study was limited by the respondent sampling method that had compromised the representativeness of samples.
Severe acute respiratory syndrome coronavirus 2 causes direct damage to the airway epithelium, enabling aspergillus invasion. Reports of COVID-19-associated pulmonary aspergillosis have raised ...concerns about it worsening the disease course of COVID-19 and increasing mortality. Additionally, the first cases of COVID-19-associated pulmonary aspergillosis caused by azole-resistant aspergillus have been reported. This article constitutes a consensus statement on defining and managing COVID-19-associated pulmonary aspergillosis, prepared by experts and endorsed by medical mycology societies. COVID-19-associated pulmonary aspergillosis is proposed to be defined as possible, probable, or proven on the basis of sample validity and thus diagnostic certainty. Recommended first-line therapy is either voriconazole or isavuconazole. If azole resistance is a concern, then liposomal amphotericin B is the drug of choice. Our aim is to provide definitions for clinical research and up-to-date recommendations for clinical management of the diagnosis and treatment of COVID-19-associated pulmonary aspergillosis.
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