Summary
With increasing life expectancy and technological advancement, provision of anaesthesia for elderly patients has become a significant part of the overall case‐load. These patients are unique, ...not only because they are older with more propensity for comorbidity but a decline in physiological reserve and cognitive function invariably accompanies ageing; this can substantially impact peri‐operative outcome and quality of recovery. Furthermore, it is not only morbidity and mortality that matters; quality of life is also especially relevant in this vulnerable population. Comprehensive geriatric assessment is a patient‐centred and multidisciplinary approach to peri‐operative care. The assessment of frailty has a central role in the pre‐operative evaluation of the elderly. Other essential domains include optimisation of nutritional status, assessment of baseline cognitive function and proper approach to patient counselling and the decision‐making process. Anaesthetists should be proactive in multidisciplinary care to achieve better outcomes; they are integral to the process.
Abstract
Motivation
In 2018, Google published an innovative variant caller, DeepVariant, which converts pileups of sequence reads into images and uses a deep neural network to identify ...single-nucleotide variants and small insertion/deletions from next-generation sequencing data. This approach outperforms existing state-of-the-art tools. However, DeepVariant was designed to call variants within a single sample. In disease sequencing studies, the ability to examine a family trio (father-mother-affected child) provides greater power for disease mutation discovery.
Results
To further improve DeepVariant’s variant calling accuracy in family-based sequencing studies, we have developed a family-based variant calling pipeline, dv-trio, which incorporates the trio information from the Mendelian genetic model into variant calling based on DeepVariant.
Availability and implementation
dv-trio is available via an open source BSD3 license at GitHub (https://github.com/VCCRI/dv-trio/).
Contact
e.giannoulatou@victorchang.edu.au
Supplementary information
Supplementary data are available at Bioinformatics online.
Many fishes are ammonotelic but some species can detoxify ammonia to glutamine or urea. Certain fish species can accumulate high levels of ammonia in the brain or defense against ammonia toxicity by ...enhancing the effectiveness of ammonia excretion through active NH4+transport, manipulation of ambient pH, or reduction in ammonia permeability through the branchial and cutaneous epithelia. Recent reports on ammonia toxicity in mammalian brain reveal the importance of permeation of ammonia through the blood-brain barrier and passages of ammonia and water through transporters in the plasmalemma of brain cells. Additionally, brain ammonia toxicity could be related to the passage of glutamine through the mitochondrial membranes into the mitochondrial matrix. On the other hand, recent reports on ammonia excretion in fish confirm the involvement of Rhesus glycoproteins in the branchial and cutaneous epithelia. Therefore, this review focuses on both the earlier literature and the up-to-date information on the problems and mechanisms concerning the permeation of ammonia, as NH(3), NH4+ or proton-neutral nitrogenous compounds, across mitochondrial membranes, the blood-brain barrier, the plasmalemma of neurons, and the branchial and cutaneous epithelia of fish. It also addresses how certain fishes with high ammonia tolerance defend against ammonia toxicity through the regulation of the permeation of ammonia and related nitrogenous compounds through various types of membranes. It is hoped that this review would revive the interests in investigations on the passage of ammonia through the mitochondrial membranes and the blood-brain barrier of ammonotelic fishes and fishes with high brain ammonia tolerance, respectively.
Background. Little is known about the community psychological and behavioral responses to influenza pandemics. Methods. Using random digit dialing, we sampled 12,965 Hong Kong residents in 13 ...cross-sectional telephone surveys between April and November 2009, covering the entire first wave of the 2009 influenza A(H1N1) pandemic. We examined trends in anxiety, risk perception, knowledge on modes of transmission, and preventive behaviors. Results. Respondents reported low anxiety levels throughout the epidemic. Perceived susceptibility to infection and perceived severity of H1N1 were initially high but declined early in the epidemic and remained stable thereafter. As the epidemic grew, knowledge on modes of transmission did not improve, the adoption of hygiene measures and use of face masks did not change, and social distancing declined. Greater anxiety was associated with lower reported use of hygiene measures but greater social distancing. Knowledge that H1N1 could be spread by indirect contact was associated with greater use of hygiene measures and social distancing. Conclusion. The lack of substantial change in preventive measures or knowledge about the modes of H1N1 transmission in the general population suggests that community mitigation measures played little role in mitigating the impact of the first wave of 2009 influenza A(H1N1) pandemic in Hong Kong.
Summary Background The novel influenza A H7N9 virus emerged recently in mainland China, whereas the influenza A H5N1 virus has infected people in China since 2003. Both infections are thought to be ...mainly zoonotic. We aimed to compare the epidemiological characteristics of the complete series of laboratory-confirmed cases of both viruses in mainland China so far. Methods An integrated database was constructed with information about demographic, epidemiological, and clinical variables of laboratory-confirmed cases of H7N9 (130 patients) and H5N1 (43 patients) that were reported to the Chinese Centre for Disease Control and Prevention until May 24, 2013. We described disease occurrence by age, sex, and geography, and estimated key epidemiological variables. We used survival analysis techniques to estimate the following distributions: infection to onset, onset to admission, onset to laboratory confirmation, admission to death, and admission to discharge. Findings The median age of the 130 individuals with confirmed infection with H7N9 was 62 years and of the 43 with H5N1 was 26 years. In urban areas, 74% of cases of both viruses were in men, whereas in rural areas the proportions of the viruses in men were 62% for H7N9 and 33% for H5N1. 75% of patients infected with H7N9 and 71% of those with H5N1 reported recent exposure to poultry. The mean incubation period of H7N9 was 3·1 days and of H5N1 was 3·3 days. On average, 21 contacts were traced for each case of H7N9 in urban areas and 18 in rural areas, compared with 90 and 63 for H5N1. The fatality risk on admission to hospital was 36% (95% CI 26–45) for H7N9 and 70% (56–83%) for H5N1. Interpretation The sex ratios in urban compared with rural cases are consistent with exposure to poultry driving the risk of infection—a higher risk in men was only recorded in urban areas but not in rural areas, and the increased risk for men was of a similar magnitude for H7N9 and H5N1. However, the difference in susceptibility to serious illness with the two different viruses remains unexplained, since most cases of H7N9 were in older adults whereas most cases of H5N1 were in younger people. A limitation of our study is that we compared laboratory-confirmed cases of H7N9 and H5N1 infection, and some infections might not have been ascertained. Funding Ministry of Science and Technology, China; Research Fund for the Control of Infectious Disease and University Grants Committee, Hong Kong Special Administrative Region, China; and the US National Institutes of Health.
Background. Influenza virus infections are associated with a wide spectrum of disease. However, few studies have investigated in detail the epidemiological and virological characteristics of ...asymptomatic and mild illness with influenza virus infections. Methods. In a community-based study in Hong Kong from 2008 to 2014, we followed up initially healthy individuals who were household contacts of symptomatic persons with laboratory-confirmed influenza, to identify secondary infections. Information from daily symptom diaries was used to classify infections as symptomatic (≥2 signs/symptoms, including fever ≥37.8°C, headache, myalgia, cough, sore throat, runny nose and sputum), paucisymptomatic (1 symptom only), or asymptomatic (none of these symptoms). We compared the patterns of influenza viral shedding between these groups. Results. We identified 235 virologically confirmed secondary cases of influenza virus infection in the household setting, including 31 (13%) paucisymptomatic and 25 (11%) asymptomatic cases. The duration of viral RNA shedding was shorter and declined more rapidly in paucisymptomatic and asymptomatic than in symptomatic cases. The mean levels of influenza viral RNA shedding in asymptomatic and paucisymptomatic cases were approximately 1–2 log10 copies lower than in symptomatic cases. Conclusions. The presence of influenza viral shedding in patients with influenza who have very few or no symptoms reflects their potential for transmitting the virus to close contacts. These findings suggest that further research is needed to investigate the contribution of persons with asymptomatic or clinically mild influenza virus infections to influenza virus transmission in household, institutional, and community settings.
Rett syndrome (RTT) is a severe neurological disorder caused by mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2). Almost two decades of research into RTT have greatly advanced our ...understanding of the function and regulation of the multifunctional protein MeCP2. Here, we review recent advances in understanding how loss of MeCP2 impacts different stages of brain development, discuss recent findings demonstrating the molecular role of MeCP2 as a transcriptional repressor, assess primary and secondary effects of MeCP2 loss and examine how loss of MeCP2 can result in an imbalance of neuronal excitation and inhibition at the circuit level along with dysregulation of activity-dependent mechanisms. These factors present challenges to the search for mechanism-based therapeutics for RTT and suggest specific approaches that may be more effective than others.
Organ-specific colonization suggests that specific cell–cell recognition is essential. Yet, very little is known about this particular interaction. Moreover, tumor cell lodgement requires binding ...under shear stress, but not static, conditions. Here, we successfully isolate the metastatic populations of cancer stem/tumor-initiating cells (M-CSCs). We show that the M-CSCs tether more and roll slower than the non-metastatic (NM)-CSCs, thus resulting in the preferential binding to the peritoneal mesothelium under ascitic fluid shear stress. Mechanistically, this interaction is mediated by P-selectin expressed by the peritoneal mesothelium. Insulin-like growth factor receptor-1 carrying an uncommon non-sulfated sialyl-Lewisx (sLex) epitope serves as a distinct P-selectin binding determinant. Several glycosyltransferases, particularly α1,3-fucosyltransferase with rate-limiting activity for sLex synthesis, are highly expressed in M-CSCs. Tumor xenografts and clinical samples corroborate the relevance of these findings. These data advance our understanding on the molecular regulation of peritoneal metastasis and support the therapeutic potential of targeting the sLex-P-selectin cascade.Tumor cell in the peritoneum are often exposed to shear forces generated by ascitic flow during metastasis. Here, the authors show that metastatic cancer stem cells tether more and roll slower than the non-metastatic counterparts, and that sialyl-Lewisx -P-selectin axis mediates peritoneal metastasis.
Abstract Background Circadian disturbances may play a key role in the pathogenesis of some forms of mood disorders. Despite marked changes in circadian rhythms during the normal course of adolescence ...and young adulthood, less is known about changes in the 24-h sleep–wake cycle in young persons with mood disorders. Methods Seventy-five young participants with mood disorders (unipolar: n =46, 20.1±4.7 years old; bipolar I or II: n =29, 23.2±4.3) and 20 healthy participants (24.8±2.5 years old) underwent actigraphy monitoring during a depressive phase over seven consecutive days and nights. Sleep phase delay was defined as mean sleep onset ≥1:30 am and/or sleep offset ≥10:00 am. Results A delayed sleep phase was found in 62% of participants with bipolar disorders when depressed, compared with 30% of those with unipolar depression ( χ2 =6.0, p =0.014) and 10% of control participants ( χ2 =11.2, p <0.001). Sleep offset times were significantly later in subjects with mood disorders compared to the control group, and later in those with bipolar as compared with unipolar disorders (all p ≤0.043). Limitations This study was cross-sectional and the depressed groups were somewhat younger compared to the healthy controls. Longitudinal studies are required to determine the predictive significance of these findings. Conclusions Young patients with mood disorders, especially those with bipolar disorders, are particularly likely to have a delayed sleep phase. Therapies focused on advancing sleep phase may be of specific benefit to these young persons.
During water-land transition, ancient fishes acquired the ability to breathe air, but air-breathing engendered problems in nitrogenous waste excretion. Nitrogen is a fundamental component of amino ...acids, proteins, and nucleic acids, and the degradation of these nitrogen-containing compounds releases ammonia. Ammonia is toxic and must be removed. Fishes in water excrete ammonia as the major nitrogenous waste through gills, but gills of air-breathing fishes are modified for air-breathing or largely replaced by air-breathing organs. Notably, fishes emerged from water can no longer excrete ammonia effectively because of a lack of water to flush the gills. Hence, ancient fishes that participated in water-land transition must have developed means to deal with ammonia toxicity. Extant air-breathing fishes, particularly amphibious ones, can serve as models to examine adaptations which might have facilitated the emergence of ancient fishes from water. Some of these fishes can actively emerge from water and display complex behaviors on land, while a few can burrow into mud and survive for years during drought. Many of them are equipped with mechanisms to ameliorate ammonia toxicity during emersion. In this review, the mechanisms adopted by air-breathing fishes to deal with ammonia toxicity during emersion were organized into seven disparate strategies. In addition, eight extant air-breathing fishes with distinctive terrestrial behaviors and peculiar natural habitats were selected to describe in detail how these seven strategies could be adopted in disparate combinations to ameliorate ammonia toxicity during emersion.
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