19th Workshop of the International Stroke Genetics Consortium, April 28-29, 2016, Boston, Massachusetts, USA: 2016.001 MRI-defined cerebrovascular genomics-The CHARGE consortium.
19th Workshop of the International Stroke Genetics Consortium, April 28-29, 2016, Boston, Massachusetts, USA: 2016.001 MRI-defined cerebrovascular genomics-The CHARGE consortium.
Project description:The cellular protein quality control machinery with its central constituents of chaperones and proteases is vital to maintain protein homeostasis under physiological conditions and to protect against acute stress conditions. Imbalances in protein homeostasis also are keys to a plethora of genetic and acquired, often age-related, diseases as well as aging in general. At the EMBO Workshop, speakers covered all major aspects of cellular protein quality control, from basic mechanisms at the molecular, cellular, and organismal level to medical translation. In this report, the highlights of the meeting will be summarized.
Project description:ImportancePrevious studies have shown high mortality rates among homeless people in general, but little is known about the patterns of mortality among "rough sleepers," the subgroup of unsheltered urban homeless people who avoid emergency shelters and primarily sleep outside.ObjectivesTo assess the mortality rates and causes of death for a cohort of unsheltered homeless adults from Boston, Massachusetts.Design, setting, and participantsA 10-year prospective cohort study (2000-2009) of 445 unsheltered homeless adults in Boston, Massachusetts, who were seen during daytime street and overnight van clinical visits performed by the Boston Health Care for the Homeless Program's Street Team during 2000. Data used to describe the unsheltered homeless cohort and to document causes of death were gathered from clinical encounters, medical records, the National Death Index, and the Massachusetts Department of Public Health death occurrence files. The study data set was linked to the death occurrence files by using a probabilistic record linkage program to confirm the deaths. Data analysis was performed from May 1, 2015, to September 6, 2016.ExposureBeing unsheltered in an urban setting.Main outcomes and measuresAge-standardized all-cause and cause-specific mortality rates and age-stratified incident rate ratios that were calculated for the unsheltered adult cohort using 2 comparison groups: the nonhomeless Massachusetts adult population and an adult homeless cohort from Boston who slept primarily in shelters.ResultsOf 445 unsheltered adults in the study cohort, the mean (SD) age at enrollment was 44 (11.4) years, 299 participants (67.2%) were non-Hispanic white, and 72.4% were men. Among the 134 individuals who died, the mean (SD) age at death was 53 (11.4) years. The all-cause mortality rate for the unsheltered cohort was almost 10 times higher than that of the Massachusetts population (standardized mortality rate, 9.8; 95% CI, 8.2-11.5) and nearly 3 times higher than that of the adult homeless cohort (standardized mortality rate, 2.7; 95% CI, 2.3-3.2). Non-Hispanic black individuals had more than half the rate of death compared with non-Hispanic white individuals, with a rate ratio of 0.4 (95% CI, 0.2-0.7; P < .001). The most common causes of death were noncommunicable diseases (eg, cancer and heart disease), alcohol use disorder, and chronic liver disease.Conclusions and relevanceMortality rates for unsheltered homeless adults in this study were higher than those for the Massachusetts adult population and a sheltered adult homeless cohort with equivalent services. This study suggests that this distinct subpopulation of homeless people merits special attention to meet their unique clinical and psychosocial needs.
Project description:BackgroundDespite the importance of domesticated animals in the generation and transmission of antibiotic-resistant Staphylococcus aureus, the role of wild animals, specifically rodents, in the ecology of S. aureus remains unclear. We recovered and genotyped S. aureus isolates from wild Norway rats (Rattus norvegicus) in Boston, Massachusetts to examine genetic relationships between common human and animal S. aureus isolates in a large US metropolitan area.MethodsWe collected and necropsied 63 rats from June 2016 to June 2017. Nasal, foot pad, fur, and fecal swabs were collected. Staphylococcus aureus was isolated using culture-based methods and polymerase chain reaction confirmation. S. aureus isolates were spa typed, tested for antibiotic susceptibility, and whole genome sequenced. Assembled sequences were uploaded to the Comprehensive Antibiotic Resistance Database to identify antibiotic resistance elements. A phylogenetic tree was constructed using the neighbor-joining method with the maximum composite likelihood distance in MEGA7.ResultsWe recovered 164 Gram-positive bacterial isolates from Norway rats. Nineteen isolates from eight individual rats were confirmed as S. aureus (prevalence: 12.9% (8/63)). All S. aureus isolates were methicillin-susceptible S. aureus (MSSA), pvl-negative, and resistant to penicillin. Two isolates displayed resistance to erythromycin. Four different S. aureus spa types were detected (t933, t10751, t18202, and t189). Thirteen unique antibiotic resistance elements were identified, and all isolates shared genes mepR, mgrA, arlR, and S. aureus norA. Phylogenetic analysis if the 19 S. aureus isolates revealed they were genetically similar to four clades of S. aureus with similar resistance gene profiles isolated from both human- and animal-derived S. aureus, as well as formed a distinct phylogenetic cluster composed only of rat isolates.ConclusionsWild rodents may serve as a reservoir or vector of antibiotic resistance genes in the urban environment with relevance for human and animal health.
Project description:Solar panel surfaces, although subjected to a range of extreme environmental conditions, are inhabited by a diverse microbial community adapted to solar radiation, desiccation and temperature fluctuations. This is the first time a new bacterial species has been isolated from this environment. Strain R4DWNT belongs to the genus Sphingomonas and was isolated from a solar panel surface in Boston, MA, USA. Strain R4DWNT is a Gram-negative, non-motile and rod-shaped bacteria that tested positive for oxidase and catalase and forms round-shaped, shiny and orange-coloured colonies. It is mesophilic, neutrophilic and non-halophilic, and presents a more stenotrophic metabolism than its closest neighbours. The major fatty acids in this strain are C18:1ω7c/C18:1ω6c, C16:1ω7c/C16:1ω6c, C14:0 2OH and C16:0. Comparison of 16S rRNA gene sequences revealed that the closest type strains to R4DWNT are Sphingomonas fennica, Sphingomonas formosensis, Sphingomonas prati, Sphingomonas montana and Sphingomonas oleivorans with 96.3, 96.1, 96.0, 95.9 and 95.7 % pairwise similarity, respectively. The genomic G+C content of R4DWNT is 67.9 mol%. Based on these characteristics, strain R4DWNT represents a novel species of the genus Sphingomonas for which the name Sphingomonas solaris sp. nov. is proposed with the type strain R4DWNT (=CECT 9811T=LMG 31344T).
Project description:Influenza A virus (IAV) is known to circulate among human and animal reservoirs, yet there are few studies that address the potential for urban rodents to carry and shed IAV. Rodents are often used as influenza models in the lab, but the few field studies that have looked for evidence of IAV in rodents have done so primarily in rural areas following outbreaks of IAV in poultry. This study sought to assess the prevalence of IAV recovered from wild Norway rats in a dense urban location (Boston). To do this, we sampled the oronasal cavity, paws, and lungs of Norway rats trapped by the City of Boston's Inspectional Services from December 2016 to September 2018. All samples were screened by real-time, reverse transcriptase PCR targeting the conserved IAV matrix segment. A total of 163 rats were trapped, 18 of which (11.04%) were RT-PCR positive for IAV in either oronasal swabs (9), paw swabs (9), both (2), or lung homogenates (2). A generalized linear model indicated that month and geographic location were correlated with IAV-positive PCR status of rats. A seasonal trend in IAV-PCR status was observed with the highest prevalence occurring in the winter months (December-January) followed by a decline over the course of the year, reaching its lowest prevalence in September. Sex and weight of rats were not significantly associated with IAV-PCR status, suggesting that rodent demography is not a primary driver of infection. This pilot study provides evidence of the need to further investigate the role that wild rats may play as reservoirs or mechanical vectors for IAV circulation in urban environments across seasons.
Project description:Housing quality is a primary determinant of asthma disparities by race and social class in the US. We sought to assess how housing code enforcement systems in Boston, Massachusetts, address tenants' reports of asthma triggers. After adjustment for income and other neighborhood characteristics, racial demographics were significantly associated with asthma trigger incidence. For each 10 percent decrease in neighborhood proportion of White residents, trigger incidence increased by 3.14 reports per thousand residents. These disparities persisted during the study period (from 2011 through 2021), and for mold, which is an established asthma trigger, regressions showed that racial disparities are widening. The municipal response also demonstrated disparities: In neighborhoods with the fewest White residents compared to neighborhoods with the most White residents, adjusted models showed a 17 percent (3.51 days) slower median time until cases (tenant requests for inspections to the Inspectional Services Department) were closed, a 14 percent higher probability of being flagged as overdue, and a 54.4 percent lower probability of a repair. We found evidence that in Boston, despite several healthy housing initiatives, current regulatory systems are insufficient to address disparities in access to healthy housing. To reduce disparities in asthma burden, stronger inspectional standards and further enforcement policies to increase landlords' accountability and support tenants' rights to have repairs made are essential.
Project description:The asymmetric unit of the title compound, C30H48O2, contains two independent mol-ecules, the main difference between them being that the isopropenyl group is rotated by approximately 180°. In each mol-ecule, the fused six-membered rings have chair-chair-chair-chair conformations and the cyclo-pentane ring adopts an envelope conformation with the C atom bearing the hy-droxy-methyl group as the flap. All ring junctions are trans-fused. With the exception of one of the methyl groups adjacent to the C=O group, all the methyl groups are in axial positions. The isopropenyl group is equatorial and the hy-droxy-methyl group is in an axial orientation. In the crystal, weak C-H⋯O inter-actions link the mol-ecules into chains along [010]. Weak intra-molecular C-H⋯O hydrogen bonds are also observed but the hy-droxy groups are not involved in hydrogen bonds.
Project description:The rate of infection by methicillin-resistant Staphylococcus aureus (MRSA) has declined over the past decade, but it is unclear whether this represents a decline in S. aureus infections overall. To evaluate the trends in the annual rates of infection by S. aureus subtypes and mean antibiotic resistance, we conducted a 15-year retrospective observational study at two tertiary care institutions in Boston, MA, of 31,753 adult inpatients with S. aureus isolated from clinical specimens. We inferred the gain and loss of methicillin resistance through genome sequencing of 180 isolates from 2016. The annual rates of infection by S. aureus declined from 2003 to 2014 by 4.2% (2.7% to 5.6%), attributable to an annual decline in MRSA of 10.9% (9.3% to 12.6%). Penicillin-susceptible S. aureus (PSSA) increased by 6.1% (4.2% to 8.1%) annually, and rates of methicillin-susceptible penicillin-resistant S. aureus (MSSA) did not change. Resistance in S. aureus decreased from 2000 to 2014 by 0.8 antibiotics (0.7 to 0.8). Within common MRSA clonal complexes, 3/14 MSSA and 2/21 PSSA isolates arose from the loss of resistance-conferring genes. Overall, in two tertiary care institutions in Boston, MA, a decline in S. aureus infections has been accompanied by a shift toward increased antibiotic susceptibility. The rise in PSSA makes penicillin an increasingly viable treatment option.
Project description:Integration of genetic, social network, and spatial data has the potential to improve understanding of transmission dynamics in established HCV epidemics. Sequence data were analyzed from 63 viremic people who inject drugs recruited in the Boston area through chain referral or time-location sampling. HCV subtype 1a was most prevalent (57.1%), followed by subtype 3a (33.9%). The phylogenetic distances between sequences were no shorter comparing individuals within versus across networks, nor by location or time of first injection. Social and spatial networks, while interesting, may be too ephemeral to inform transmission dynamics when the date and location of infection are indeterminate.