Climate change and postglacial human dispersals in southeast Asia

Modern humans have been living in Island Southeast Asia (ISEA) for at least 50,000 years. Largely because of the influence of linguistic studies, however, which have a shallow time depth, the attention of archaeologists and geneticists has usually been focused on the last 6,000 years--in particular, on a proposed Neolithic dispersal from China and Taiwan. Here we use complete mitochondrial DNA (mtDNA) genome sequencing to spotlight some earlier processes that clearly had a major role in the demographic history of the region but have hitherto been unrecognized. We show that haplogroup E, an important component of mtDNA diversity in the region, evolved in situ over the last 35,000 years and expanded dramatically throughout ISEA around the beginning of the Holocene, at the time when the ancient continent of Sundaland was being broken up into the present-day archipelago by rising sea levels. It reached Taiwan and Near Oceania more recently, within the last approximately 8,000 years. This suggests that global warming and sea-level rises at the end of the Ice Age, 15,000-7,000 years ago, were the main forces shaping modern human diversity in the region

Effect of room temperature transport vials on DNA quality and phylogenetic composition of faecal microbiota of elderly adults and infants

Background: Alterations in intestinal microbiota have been correlated with a growing number of diseases. Investigating the faecal microbiota is widely used as a non-invasive and ethically simple proxy for intestinal biopsies. There is an urgent need for collection and transport media that would allow faecal sampling at distance from the processing laboratory, obviating the need for same-day DNA extraction recommended by previous studies of freezing and processing methods for stool. We compared the faecal bacterial DNA quality and apparent phylogenetic composition derived using a commercial kit for stool storage and transport (DNA Genotek OMNIgene GUT) with that of freshly extracted samples, 22 from infants and 20 from older adults. Results: Use of the storage vials increased the quality of extracted bacterial DNA by reduction of DNA shearing. When infant and elderly datasets were examined separately, no differences in microbiota composition were observed due to storage. When the two datasets were combined, there was a difference according to a Wilcoxon test in the relative proportions of Faecalibacterium, Sporobacter, Clostridium XVIII, and Clostridium XlVa after 1 week's storage compared to immediately extracted samples. After 2 weeks' storage, Bacteroides abundance was also significantly different, showing an apparent increase from week 1 to week 2. The microbiota composition of infant samples was more affected than that of elderly samples by storage, with significantly higher Spearman distances between paired freshly extracted and stored samples (

Healthcare Workers Hospitalized with COVID-19: Outcomes from the Burden of COVID-19 study at the University of Louisville Center of Excellence for Research in Infectious Diseases [CERID]

Introduction: On March 6, 2020, the current ongoing pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) also known as COVID-19 reached the commonwealth of Kentucky. Within days the first cases of infection and hospitalization were identified among healthcare workers (HCW) in Kentucky, other states in the U.S., and around the world. There is little information available regarding the impact of COVID-19 on the HCW population within this area. The objective of this study is to describe the baseline characteristics of hospitalized HCWs infected with COVID-19. Methods: Data collection was performed as part of a retrospective study of patients hospitalized with COVID-19 in any of nine acute care hospitals in Louisville. COVID-19 infection was confirmed using Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). Descriptive statistics were performed on clinical and epidemiological characteristics of hospitalized patients with COVID-19 who had indicated healthcare as their occupation. Results: Of the 700 adults hospitalized with COVID-19 from March 7 through July 1, 2020, 23 were HCWs. The mean age was 51 years and 78% were female. The majority of hospitalized HCWs had comorbidities including obesity (70%), hypertension (57%), hyperlipidemia (35%) and diabetes (26%). Common symptoms reported were fever (70%), dyspnea (78%), cough (78%) and fatigue (57%). Nine HCWs (39%) were admitted to the intensive care unit (ICU) and 6 (26%) developed acute respiratory distress syndrome (ARDS). Two (9%) patients developed a new, serious arrhythmia, two sustained cardiac arrest (9%), and two (9%) died in-hospital. Conclusions: Older adult HCWs with underlying health conditions such as obesity and hypertension were more likely to be hospitalized and have severe in-hospital complications. One HCW death due to COVID-19 was identified in this small population. These findings can help to identify and strengthen approaches to protect HCWs from SARS-CoV-2 infection and from long term effects of COVID-19

Bone marrow lesions and magnetic resonanceImaging–detected structural abnormalities in patients with midfoot pain and osteoarthritis: A cross-sectional study

To compare magnetic resonance imaging (MRI)–detected structural abnormalities in patients withsymptomatic midfoot osteoarthritis (OA), patients with persistent midfoot pain, and asymptomatic controls, and toexplore the association between MRI features, pain, and foot-related disability. One hundred seven adults consisting of 50 patients with symptomatic and radiographically confirmedmidfoot OA, 22 adults with persistent midfoot pain but absence of radiographic OA, and 35 asymptomatic adultsunderwent 3T MRI of the midfoot and clinical assessment. MRIs were read for the presence and severity of abnormal-ities (bone marrow lesions [BMLs], subchondral cysts, osteophytes, joint space narrowing [JSN], effusion-synovitis,tenosynovitis, and enthesopathy) using the Foot Osteoarthritis MRI Score. Pain and foot-related disability wereassessed with the Manchester Foot Pain and Disability Index. The severity sum score of BMLs in the midfoot was greater in patients with midfoot pain and no signs ofOA on radiography compared to controls (P= 0.007), with a pattern of involvement in the cuneiform–metatarsal jointssimilar to that in patients with midfoot OA. In univariable models, BMLs (ρ= 0.307), JSN (ρ= 0.423), and subchondralcysts (ρ= 0.302) were positively associated with pain (P< 0.01). In multivariable models, MRI abnormalities were notassociated with pain and disability when adjusted for covariates. In individuals with persistent midfoot pain but no signs of OA on radiography, MRIfindings suggestedan underrecognized prevalence of OA, particularly in the second and third cuneiform–metatarsal joints, where BMLpatterns were consistent with previously recognized sites of elevated mechanical loading. Joint abnormalities werenot strongly associated with pain or foot-related disability

Paracetamol use in early life and asthma: prospective birth cohort study

Objective To determine if use of paracetamol in early life is an independent risk factor for childhood asthma

The importance of sleep: attentional problems in school-aged children with Down syndrome and Williams syndrome

Authors: Anna Ashworth ; Catherine M. Hill ; Annette Karmiloff-Smith ; Dagmara Dimitriou Article URL: http://www.tandfonline.com/doi/full/10.1080/15402002.2014.940107?ai=2gs&mi=3h6sxt&af=R Citation: Behavioral Sleep Medicine Publication Date: Fri, 15 Aug 2014 14:22:59 GM

Evaluation of AaDOP2 Receptor Antagonists Reveals Antidepressants and Antipsychotics as Novel Lead Molecules for Control of the Yellow Fever Mosquito, Aedes aegypti s

ABSTRACT The yellow fever mosquito, Aedes aegypti, vectors disease-causing agents that adversely affect human health, most notably the viruses causing dengue and yellow fever. The efficacy of current mosquito control programs is challenged by the emergence of insecticideresistant mosquito populations, suggesting an urgent need for the development of chemical insecticides with new mechanisms of action. One recently identified potential insecticide target is the A. aegypti D 1 -like dopamine receptor, AaDOP2. The focus of the present study was to evaluate AaDOP2 antagonism both in vitro and in vivo using assay technologies with increased throughput. The in vitro assays revealed AaDOP2 antagonism by four distinct chemical scaffolds from tricyclic antidepressant or antipsychotic chemical classes, and elucidated several structure-activity relationship trends that contributed to enhanced antagonist potency, including lipophilicity, halide substitution on the tricyclic core, and conformational rigidity. Six compounds displayed previously unparalleled potency for in vitro AaDOP2 antagonism, and among these, asenapine, methiothepin, and cis-(Z)-flupenthixol displayed subnanomolar IC 50 values and caused rapid toxicity to A. aegypti larvae and/or adults in vivo. Our study revealed a significant correlation between in vitro potency for AaDOP2 antagonism and in vivo toxicity, suggesting viability of AaDOP2 as an insecticidal target. Taken together, this study expanded the repertoire of known AaDOP2 antagonists, enhanced our understanding of AaDOP2 pharmacology, provided further support for rational targeting of AaDOP2, and demonstrated the utility of efficiency-enhancing in vitro and in vivo assay technologies within our genome-to-lead pipeline for the discovery of next-generation insecticides

Age and gender differences in disabling foot pain using different definitions of the manchester foot pain and disability index

Extent: 9p.Background: The Manchester Foot Pain and Disability Index (MFPDI) has been used to determine the prevalence of disabling foot pain in several studies, however there is some debate as to which case definition is most appropriate. The objective of this study was to explore age and gender differences in the proportion of people with disabling foot pain using three different case definitions of the MFPDI and for each individual MFPDI item. Methods: A random sample of 223 participants aged 27 to 90 years (88 males and 135 females) from the North West Adelaide Health Study, who reported having pain, aching or stiffness in either of their feet on most days in the last month, completed the MFPDI by telephone interview. The proportion of people with disabling foot pain was determined using three definitions: (i) Definition A-at least one of the 17 items documented on at least some days in the last month; (ii) Definition B-at least one of the 17 items documented on most/every day(s) in the last month, and; (iii) Definition C-at least one of the ten functional limitation items documented on most/every day(s) in the last month. Cross-tabulations and chi-squared statistics were used to explore differences in responses to the MFPDI items according to age and gender. Results: The proportion of people with disabling foot pain according to each definition was as follows: Definition A (100%), Definition B (95.1%) and Definition C (77.6%). Definition C was most sensitive to age and gender differences. Exploration of individual MFPDI items indicated that age significantly affected both the pain intensity and functional limitation items, with younger people more likely to report their foot pain being worse in the morning, and older people more likely to report functional limitations. Although gender did not influence responses to the personal appearance items, women were more likely report functional limitations than men. Conclusions: Definition C of the MFPDI is more sensitive to age and gender differences in the proportion of people with disabling foot pain, and would therefore seem to be the most appropriate case definition to use in epidemiological studies involving a broad age range of participants.Hylton B Menz, Tiffany K Gill, Anne W Taylor and Catherine L Hil

Immunolocalization of NLRP3 Inflammasome in Normal Murine Airway Epithelium and Changes following Induction of Ovalbumin-Induced Airway Inflammation

Little is known about innate immunity and components of inflammasomes in airway epithelium. This study evaluated immunohistological evidence for NLRP3 inflammasomes in normal and inflamed murine (Balb/c) airway epithelium in a model of ovalbumin (OVA) induced allergic airway inflammation. The airway epithelium of control mice exhibited strong cytoplasmic staining for total caspase-1, ASC, and NLRP3, whereas the OVA mice exhibited strong staining for active caspase-1, with redistribution of caspase-1, IL-1β and IL-18, indicating possible activation of the NLRP3 inflammasome. Active caspase-1, NLRP3, and other inflammasome components were also detected in tissue eosinophils from OVA mice, and may potentially contribute to IL-1β and IL-18 production. In whole lung, inRNA expression of NAIP and procaspase-1 was increased in OVA mice, whereas NLRP3, IL-1β and IL-18 decreased. Some OVA-treated mice also had significantly elevated and tightly correlated serum levels of IL-1β and TNFα. In cultured normal human bronchial epithelial cells, LPS priming resulted in a significant increase in NLRP3 and II-lp protein expression. This study is the first to demonstrate NLRP3 inflammasome components in normal airway epithelium and changes with inflammation. We propose activation and/or luminal release of the inflammasome is a feature of allergic airway inflammation which may contribute to disease pathogenesis