Microbes are now well regarded for their important role in mammalian health. The microbiology of skin--a unique interface between the host and environment--is a major research focus in human health ...and skin disorders, but is less explored in other mammals. Here, we report on a cross-population study of the skin-associated bacterial community of humpback whales (Megaptera novaeangliae), and examine the potential for a core bacterial community and its variability with host (endogenous) or geographic/environmental (exogenous) specific factors. Skin biopsies or freshly sloughed skin from 56 individuals were sampled from populations in the North Atlantic, North Pacific and South Pacific oceans and bacteria were characterized using 454 pyrosequencing of SSU rRNA genes. Phylogenetic and statistical analyses revealed the ubiquity and abundance of bacteria belonging to the Flavobacteria genus Tenacibaculum and the Gammaproteobacteria genus Psychrobacter across the whale populations. Scanning electron microscopy of skin indicated that microbial cells colonize the skin surface. Despite the ubiquity of Tenacibaculum and Psychrobater spp., the relative composition of the skin-bacterial community differed significantly by geographic area as well as metabolic state of the animals (feeding versus starving during migration and breeding), suggesting that both exogenous and endogenous factors may play a role in influencing the skin-bacteria. Further, characteristics of the skin bacterial community from these free-swimming individuals were assembled and compared to two entangled and three dead individuals, revealing a decrease in the central or core bacterial community members (Tenacibaculum and Psychrobater spp.), as well as the emergence of potential pathogens in the latter cases. This is the first discovery of a cross-population, shared skin bacterial community. This research suggests that the skin bacteria may be connected to humpback health and immunity and could possibly serve as a useful index for health and skin disorder monitoring of threatened and endangered marine mammals.
Despite a long-documented history of severe harmful algal blooms (HABs) in New England coastal waters, corresponding HAB-associated marine mammal mortality events in this region are far less frequent ...or severe relative to other regions where HABs are common. This long-term survey of the HAB toxins saxitoxin (STX) and domoic acid (DA) demonstrates significant and widespread exposure of these toxins in New England marine mammals, across multiple geographic, temporal and taxonomic groups. Overall, 19% of the 458 animals tested positive for one or more toxins, with 15% and 7% testing positive for STX and DA, respectively. 74% of the 23 different species analyzed demonstrated evidence of toxin exposure. STX was most prevalent in Maine coastal waters, most frequently detected in common dolphins (Delphinus delphis), and most often detected during July and October. DA was most prevalent in animals sampled in offshore locations and in bycaught animals, and most frequently detected in mysticetes, with humpback whales (Megaptera novaeangliae) testing positive at the highest rates. Feces and urine appeared to be the sample matrices most useful for determining the presence of toxins in an exposed animal, with feces samples having the highest concentrations of STX or DA. No relationship was found between the bloom season of toxin-producing phytoplankton and toxin detection rates, however STX was more likely to be present in July and October. No relationship between marine mammal dietary preference and frequency of toxin detection was observed. These findings are an important part of a framework for assessing future marine mammal morbidity and mortality events, as well as monitoring ecosystem health using marine mammals as sentinel organisms for predicting coastal ocean changes.
Changes in gray whale (Eschrichtius robustus) phenology and distribution are related to observed and hypothesized prey availability, bottom water temperature, salinity, sea ice persistence, ...integrated water column and sediment chlorophyll a, and patterns of wind-driven biophysical forcing in the northern Bering and eastern Chukchi seas. This portion of the Pacific Arctic includes four Distributed Biological Observatory (DBO) sampling regions. In the Bering Strait area, passive acoustic data showed marked declines in gray whale calling activity coincident with unprecedented wintertime sea ice loss there in 2017-2019, although some whales were seen there during DBO cruises in those years. In the northern Bering Sea, sightings during DBO cruises show changes in gray whale distribution coincident with a shrinking field of infaunal amphipods, with a significant decrease in prey abundance (r = -0.314, p<0.05) observed in the DBO 2 region over the 2010-2019 period. In the eastern Chukchi Sea, sightings during broad scale aerial surveys show that gray whale distribution is associated with localized areas of high infaunal crustacean abundance. Although infaunal crustacean prey abundance was unchanged in DBO regions 3, 4 and 5, a mid-decade shift in gray whale distribution corresponded to both: (i) a localized increase in infaunal prey abundance in DBO regions 4 and 5, and (ii) a correlation of whale relative abundance with wind patterns that can influence epi-benthic and pelagic prey availability. Specifically, in the northeastern Chukchi Sea, increased sighting rates (whales/km) associated with an ~110 km (60 nm) offshore shift in distribution was positively correlated with large scale and local wind patterns conducive to increased availability of krill. In the southern Chukchi Sea, gray whale distribution clustered in all years near an amphipod-krill 'hotspot' associated with a 50-60m deep trough. We discuss potential impacts of observed and inferred prey shifts on gray whale nutrition in the context of an ongoing unusual gray whale mortality event. To conclude, we use the conceptual Arctic Marine Pulses (AMP) model to frame hypotheses that may guide future research on whales in the Pacific Arctic marine ecosystem.
The feasibility of reducing the population-level incidence of human immunodeficiency virus (HIV) infection by increasing community coverage of antiretroviral therapy (ART) and male circumcision is ...unknown.
We conducted a pair-matched, community-randomized trial in 30 rural or periurban communities in Botswana from 2013 to 2018. Participants in 15 villages in the intervention group received HIV testing and counseling, linkage to care, ART (started at a higher CD4 count than in standard care), and increased access to male circumcision services. The standard-care group also consisted of 15 villages. Universal ART became available in both groups in mid-2016. We enrolled a random sample of participants from approximately 20% of households in each community and measured the incidence of HIV infection through testing performed approximately once per year. The prespecified primary analysis was a permutation test of HIV incidence ratios. Pair-stratified Cox models were used to calculate 95% confidence intervals.
Of 12,610 enrollees (81% of eligible household members), 29% were HIV-positive. Of the 8974 HIV-negative persons (4487 per group), 95% were retested for HIV infection over a median of 29 months. A total of 57 participants in the intervention group and 90 participants in the standard-care group acquired HIV infection (annualized HIV incidence, 0.59% and 0.92%, respectively). The unadjusted HIV incidence ratio in the intervention group as compared with the standard-care group was 0.69 (P = 0.09) by permutation test (95% confidence interval CI, 0.46 to 0.90 by pair-stratified Cox model). An end-of-trial survey in six communities (three per group) showed a significantly greater increase in the percentage of HIV-positive participants with an HIV-1 RNA level of 400 copies per milliliter or less in the intervention group (18 percentage points, from 70% to 88%) than in the standard-care group (8 percentage points, from 75% to 83%) (relative risk, 1.12; 95% CI, 1.09 to 1.16). The percentage of men who underwent circumcision increased by 10 percentage points in the intervention group and 2 percentage points in the standard-care group (relative risk, 1.26; 95% CI, 1.17 to 1.35).
Expanded HIV testing, linkage to care, and ART coverage were associated with increased population viral suppression. (Funded by the President's Emergency Plan for AIDS Relief and others; Ya Tsie ClinicalTrials.gov number, NCT01965470.).
This article investigates how the Housing Choice Voucher (HCV) program rations subsidies. HCV is the largest low-income housing assistance program in the United States. Despite the program's size, ...millions of HCV-eligible households go without subsidy each year. Because the demand for support exceeds the supply of subsidies, HCV assistance is rationed through several mechanisms. These mechanisms and their relationship with the HCV system from both the client and administrator perspectives will be discussed. Implications of HCV rationing will also be discussed.
Effective pain management is a priority in dental practice. Government and private agencies highlight the need to provide optimal pain relief, balancing potential benefits and harms of both opioid ...and nonopioid analgesic agents. The purpose of this study is to summarize the available evidence on the benefits and harms of analgesic agents, focusing on preexisting systematic reviews.
An overview of systematic reviews was conducted to evaluate the efficacy or reported adverse events associated with orally administered medication or medication combinations for relief of acute pain. Reviews were inclusive of all age populations but were limited to those that evaluated medication and medication combinations marketed in the United States and had moderate or high methodological quality according to the A MeaSurement Tool to Assess systematic Reviews (AMSTAR) 2 tool.
Five reviews were found eligible for inclusion. The data identified combinations of ibuprofen and acetaminophen as having the highest association with treatment benefit in adult patients and the highest proportion of adult patients who experienced maximum pain relief. Diflunisal, acetaminophen, and oxycodone were found to have the longest duration of action in adult patients. Medication and medication combinations that included opioids were among those associated most frequently with acute adverse events in both child and adult-aged patient populations.
The best available data suggested that the use of nonsteroidal medications, with or without acetaminophen, offered the most favorable balance between benefits and harms, optimizing efficacy while minimizing acute adverse events.
Posttraumatic stress disorder (PTSD) is prevalent, persistent, and disabling. Although psychotherapy and pharmacotherapy have proven efficacious in randomized clinical trials, geographic barriers ...impede rural veterans from engaging in these evidence-based treatments.
To test a telemedicine-based collaborative care model designed to improve engagement in evidence-based treatment of PTSD.
The Telemedicine Outreach for PTSD (TOP) study used a pragmatic randomized effectiveness trial design with intention-to-treat analyses. Outpatients were recruited from 11 Department of Veterans Affairs (VA) community-based outpatient clinics serving predominantly rural veterans. Inclusion required meeting diagnostic criteria for current PTSD according to the Clinician-Administered PTSD Scale. Exclusion criteria included receiving PTSD treatment at a VA medical center or a current diagnosis of schizophrenia, bipolar disorder, or substance dependence. Two hundred sixty-five veterans were enrolled from November 23, 2009, through September 28, 2011, randomized to usual care (UC) or the TOP intervention, and followed up for 12 months.
Off-site PTSD care teams located at VA medical centers supported on-site community-based outpatient clinic providers. Off-site PTSD care teams included telephone nurse care managers, telephone pharmacists, telepsychologists, and telepsychiatrists. Nurses conducted care management activities. Pharmacists reviewed medication histories. Psychologists delivered cognitive processing therapy via interactive video. Psychiatrists supervised the team and conducted interactive video psychiatric consultations.
The primary outcome was PTSD severity as measured by the Posttraumatic Diagnostic Scale. Process-of-care outcomes included medication prescribing and regimen adherence and initiation of and adherence to cognitive processing therapy.
During the 12-month follow-up period, 73 of the 133 patients randomized to TOP (54.9%) received cognitive processing therapy compared with 16 of 132 randomized to UC (12.1%) (odds ratio, 18.08 95% CI, 7.96-41.06; P < .001). Patients in the TOP arm had significantly larger decreases in Posttraumatic Diagnostic Scale scores (from 35.0 to 29.1) compared with those in the UC arm (from 33.5 to 32.1) at 6 months (β = -3.81; P = .002). Patients in the TOP arm also had significantly larger decreases in Posttraumatic Diagnostic Scale scores (from 35.0 to 30.1) compared with those in the UC arm (from 33.5 to 31.7) at 12 months (β = -2.49; P=.04). There were no significant group differences in the number of PTSD medications prescribed and adherence to medication regimens were not significant. Attendance at 8 or more sessions of cognitive processing therapy significantly predicted improvement in Posttraumatic Diagnostic Scale scores (β = -3.86 95% CI, -7.19 to -0.54; P = .02) and fully mediated the intervention effect at 12 months.
Telemedicine-based collaborative care can successfully engage rural veterans in evidence-based psychotherapy to improve PTSD outcomes.
clinicaltrials.gov Identifier: NCT00821678.
It is now established that Bcl11b specifies T cell fate. Here, we show that in developing T cells, the Bcl11b enhancer repositioned from the lamina to the nuclear interior. Our search for factors ...that relocalized the Bcl11b enhancer identified a non-coding RNA named ThymoD (thymocyte differentiation factor). ThymoD-deficient mice displayed a block at the onset of T cell development and developed lymphoid malignancies. We found that ThymoD transcription promoted demethylation at CTCF bound sites and activated cohesin-dependent looping to reposition the Bcl11b enhancer from the lamina to the nuclear interior and to juxtapose the Bcl11b enhancer and promoter into a single-loop domain. These large-scale changes in nuclear architecture were associated with the deposition of activating epigenetic marks across the loop domain, plausibly facilitating phase separation. These data indicate how, during developmental progression and tumor suppression, non-coding transcription orchestrates chromatin folding and compartmentalization to direct with high precision enhancer-promoter communication.
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•Non-coding transcription directs loop extrusion•Non-coding transcription dictates compartmentalization•Non-coding transcription directs enhancer-promoter communication•Non-coding transcription establishes T cell identity and blocks lymphoid malignancy
Transcription of a non-coding locus facilitates chromatin folding and compartmentalization to reposition T-lineage-specific enhancer and promoter elements into a single-loop domain.
Muslim Women in America Haddad, Yvonne Yazbeck; Smith, Jane I; Moore, Kathleen M
03/2006
eBook
The treatment and role of women is one of the most discussed and controversial aspects of Islam. In this volume, three scholars of Islam survey the situation of women in Islam, focusing on how Muslim ...views about and experiences of gender are changing in the Western diaspora. It offers an overview of the teachings of the Qur'an and the Prophet Muhammad on gender, analyzes the ways in which the West has historically viewed Muslim women, and examines how the Muslim world has changed in response to Western critiques. The volume then centers on the Muslim experience in America, examining Muslim American analyses of gender, Muslim attempts to form a new “American” Islam, and the legal issues surrounding equal rights for Muslim females. Such specific issues as dress, marriage, child custody, and asylum are addressed. It also looks at the ways in which American Muslim women have tried to create new paradigms of Islamic womanhood and are reinterpreting the traditions apart from the males who control the mosque institutions.
Current treatment options for progressive ovarian cancer provide limited benefit, particularly in patients whose disease has become resistant to platinum-based chemotherapy.
To assess the efficacy ...and safety of avelumab, an anti-programmed death-ligand 1 agent, in a cohort of patients with previously treated recurrent or refractory ovarian cancer.
In an expansion cohort of a phase 1b, open-label study (JAVELIN Solid Tumor), 125 patients with advanced ovarian cancer who had received chemotherapy including a platinum agent were enrolled between November 6, 2013, and August 27, 2015. Statistical analysis was performed from December 31, 2016, to October 9, 2018.
Patients received avelumab, 10 mg/kg, every 2 weeks until disease progression, unacceptable toxic effects, or withdrawal from the study.
Prespecified end points in this cohort included confirmed best overall response (per Response Evaluation Criteria In Solid Tumors, version 1.1), immune-related best overall response, duration of response, progression-free survival, overall survival, results of programmed death-ligand 1 expression-based analyses, and safety.
A total of 125 women (median age, 62.0 years range, 27-84 years) who had received a median of 3 prior lines of treatment (range, 0-10) for advanced disease were enrolled in the study. Patients received avelumab for a median of 2.8 months (range, 0.5-27.4 months), with a median follow-up of 26.6 months (range, 16-38 months). A confirmed objective response occurred in 12 patients (9.6%; 95% CI, 5.1%-16.2%), including a complete response in 1 patient (0.8%) and a partial response in 11 patients (8.8%). The 1-year progression-free survival rate was 10.2% (95% CI, 5.4%-16.7%) and median overall survival was 11.2 months (95% CI, 8.7-15.4 months). Infusion-related reactions occurred in 25 patients (20.0%). Other frequent treatment-related adverse events (any grade event occurring in ≥10% of patients) were fatigue (17 13.6%), diarrhea (15 12.0%), and nausea (14 11.2%). Grade 3 or higher treatment-related adverse events occurred in 9 patients (7.2%), of which only the level of lipase increased (3 2.4%) occurred in more than 1 patient. Twenty-one patients (16.8%) had an immune-related adverse event of any grade. No treatment-related deaths occurred.
Avelumab demonstrated antitumor activity and acceptable safety in heavily pretreated patients with recurrent or refractory ovarian cancer.
ClinicalTrials.gov identifier: NCT01772004.
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