The epithelial-mesenchymal transition generates cells with properties of stem cells.

The epithelial-mesenchymal transition (EMT) is a key developmental program that is often activated during cancer invasion and metastasis. We here report that the induction of an EMT in immortalized human mammary epithelial cells (HMLEs) results in the acquisition of mesenchymal traits and in the expression of stem-cell markers. Furthermore, we show that those cells have an increased ability to form mammospheres, a property associated with mammary epithelial stem cells. Independent of this, stem cell-like cells isolated from HMLE cultures form mammospheres and express markers similar to those of HMLEs that have undergone an EMT. Moreover, stem-like cells isolated either from mouse or human mammary glands or mammary carcinomas express EMT markers. Finally, transformed human mammary epithelial cells that have undergone an EMT form mammospheres, soft agar colonies, and tumors more efficiently. These findings illustrate a direct link between the EMT and the gain of epithelial stem cell properties.

SARS-CoV-2 in Nursing Homes after 3 Months of Serial, Facilitywide Point Prevalence Testing, Connecticut, USA.

Nursing homes house populations that are highly vulnerable to coronavirus disease. Point prevalence surveys (PPSs) provide information on the severe acute respiratory syndrome coronavirus 2 infection status of staff and residents in nursing homes and enable isolation of infectious persons to halt disease spread. We collected 16 weeks of public health surveillance data on a subset of nursing homes (34/212) in Connecticut, USA. We fit a Poisson regression model to evaluate the association between incidence and time since serial PPS onset, adjusting for decreasing community incidence and other factors. Nursing homes conducted a combined total of 205 PPSs in staff and 232 PPSs in residents. PPS was associated with 41%-80% reduction in incidence rate in nursing homes. Our findings provide support for the use of repeated PPSs in nursing home staff and residents, combined with strong infection prevention measures such as cohorting, in contributing to outbreak control.

Are Post-Acute Patients with Behavioral Health Disorders Admitted to Lower-Quality Nursing Homes?

OBJECTIVES: We measured the proportion of new post-acute nursing home admissions with behavioral health diagnoses and examined whether patients with these disorders (schizophrenia/psychosis, bipolar, depression/anxiety, personality disorder, and substance abuse) faced disparities in access to high quality facilities. SETTING/PARTICIPANTS: The analytical sample included 3,729,282 admissions to 15,600 facilities nationwide for 2012-2014. MEASUREMENT: Quality was measured for overall and staffing domains reported by the Centers for Medicare and Medicaid Services in the Five-Star Quality Rating System. Multinomial logistic regression models were used. The base model included the diagnostic groups of interest and state dummies. Patient sociodemographics, functional and cognitive status, and comorbid conditions were sequentially added to the base model to determine the independent effect of having a behavioral health diagnosis at admission. RESULTS: Patients with these conditions experienced disparities accessing to high-quality homes compared to patients without. For example, patients with depression/anxiety had lower access to five-star homes, for the staffing quality domain (Model 3 ORs = 0.88, 0.93, 0.92 in years 1 through 3, respectively) compared to patients with no behavioral health diagnosis. Access disparities were faced not only by patients with serious mental illness, as previously demonstrated, but also patients with substance abuse and with depression/anxiety who account for one-third of all new admissions. CONCLUSIONS: Our findings demonstrate persistence of disparities in access to high quality facilities over time and for patients with a broad range of behavioral health conditions. Further research is needed to understand the impact of these disparities on outcomes of patients with behavioral disorders.

Featured Article: The ABCDs of Pain Management: A Double-Blind Randomized Controlled Trial Examining the Impact of a Brief Educational Video on Infants' and Toddlers' Pain Scores and Parent Soothing Behavior.

Objectives: To test the efficacy of a brief behavioral pain management strategy (The ABCDs of Needle Pain Management), delivered via video, on infants' and toddlers' pain scores and on parental soothing behavior. Methods: This was a double-blind, parallel trial design. Parent-child dyads (N = 128) were recruited before their child's 6-month (infant) or 18-month (toddler) vaccination in a pediatric clinic and randomly assigned to watch a 5-min treatment video or a placebo video. The primary outcome was the Modified Behavior Pain Scale (Taddio et al., Journal of Pain and Symptom Management, 10, pp. 456-463, 1995), coded during four epochs (Pain Reactivity, Pain Regulation 1 min, Pain Regulation 2 min, and Pain Regulation 3 min) after the last vaccination needle. Secondary analyses examined parental use of distraction, rocking, and physical comforting over this same time period. Results: Results demonstrated a treatment effect for toddlers (18-month-olds) for the Pain Regulation 1 (d = 0.84) and Pain Regulation 2 (d = 0.76) postvaccination scores. Secondary analyses found differences in parental rocking and physical comforting between treatment conditions and between age-groups (d's = 0.37-0.54). Conclusions: The ABCD pain management strategy delivered via video was an effective way to reduce toddler pain after vaccination and increase parental use of rocking and physical comforting. The treatment effect was not demonstrated with infants.

Coverage and Access for Americans With Chronic Disease Under the Affordable Care Act: A Quasi-Experimental Study.

BACKGROUND: Half of Americans have at least 1 chronic disease. Many in this group, particularly racial/ethnic minorities, lacked insurance coverage and access to care before the Patient Protection and Affordable Care Act (ACA) was enacted. OBJECTIVE: To determine whether the ACA has had an effect on insurance coverage, access to care, and racial/ethnic disparities among adults with chronic disease. DESIGN: Quasi-experimental policy intervention. SETTING: Nationally representative, noninstitutionalized sample in the United States. PATIENTS: 606 277 adults aged 18 to 64 years with a chronic disease. INTERVENTION: Implementation of ACA provisions on 1 January 2014. MEASUREMENTS: Self-reported insurance coverage, having a checkup, having a personal physician, and not having to forgo a needed physician visit because of cost. RESULTS: After the ACA was implemented, insurance coverage increased by 4.9 percentage points (95% CI, 4.4 to 5.4), not having to forgo a physician visit increased by 2.4 percentage points (CI, 1.9 to 2.9), and having a checkup increased by 2.7 percentage points (CI, 2.2 to 3.4). Having a personal physician did not change (0.3 percentage points [CI, -0.2 to 0.8]). All outcomes varied considerably by state, and coverage increased more in states that expanded Medicaid. Although racial/ethnic minorities had greater improvements in some outcomes, approximately 1 in 5 black and 1 in 3 Hispanic persons with a chronic disease continued to lack coverage and access to care after ACA implementation. LIMITATION: The study examined data from only the first year of the ACA's major coverage expansion provisions. CONCLUSION: Although the ACA increased coverage and access for persons with chronic disease, substantial gaps remain, particularly for minorities and those in Medicaid nonexpansion states. PRIMARY FUNDING SOURCE: None.

Systematic Review: A Systematic Review of the Interrelationships Among Children's Coping Responses, Children's Coping Outcomes, and Parent Cognitive-Affective, Behavioral, and Contextual Variables in the Needle-Related Procedures Context.

Objective: To conduct a systematic review of the interrelationships between children's coping responses, children's coping outcomes, and parent variables during needle-related procedures. A systematic literature search was conducted. It was required that the study examined a painful needle-related procedure in children from 3 to 12 years of age, and included a children's coping response, a children's coping outcome, and a parent variable. In all, 6,081 articles were retrieved to review against inclusion criteria. Twenty studies were included. Parent coping-promoting behaviors and distress-promoting behaviors enacted in combination are the most consistent predictors of optimal children's coping responses, and less optimal children's coping outcomes, respectively. Additional key findings are presented. Children's coping with needle-related procedures is a complex process involving a variety of different dimensions that interact in unison. Parents play an important role in this process. Future researchers are encouraged to disentangle coping responses from coping outcomes when exploring this dynamic process.

Low uptake of Aboriginal interpreters in healthcare: exploration of current use in Australia's Northern Territory.

BACKGROUND: In Australia's Northern Territory, most Aboriginal people primarily speak an Aboriginal language. Poor communication between healthcare providers and Aboriginal people results in adverse outcomes including death. This study aimed to identify remediable barriers to utilisation of Aboriginal Interpreter services at the Northern Territory's tertiary hospital, which currently manages over 25,000 Aboriginal inpatients annually. METHODS: This is a multi-method study using key stakeholder discussions, medical file audit, bookings data from the Aboriginal Interpreter Service 2000-2015 and an online cross-sectional staff survey. The Donabedian framework was used to categorise findings into structure, process and outcome. RESULTS: Six key stakeholder meetings each with approximately 15 participants were conducted. A key structural barrier identified was lack of onsite interpreters. Interpreter bookings data revealed that only 7603 requests were made during the 15-year period, with completion of requests decreasing from 337/362 (93.1%) in 2003-4 to 649/831 (78.1%) in 2014-15 (p < 0.001). Non-completion was more common for minority languages (p < 0.001). Medical files of 103 Aboriginal inpatients were audited. Language was documented for 13/103 (12.6%). Up to 60/103 (58.3%) spoke an Aboriginal language primarily. Of 422 staff who participated in the survey, 18.0% had not received 'cultural competency' training; of those who did, 58/222 (26.2%) indicated it was insufficient. The Aboriginal Interpreter Service effectiveness was reported to be good by 209/368 (56.8%), but only 101/367 (27.5%) found it timely. Key process barriers identified by staff included booking complexities, time constraints, inadequate delivery of tools and training, and greater convenience of unofficial interpreters. CONCLUSION: We identified multiple structural and process barriers resulting in the outcomes of poor language documentation and low rates of interpreter bookings. Findings are now informing interventions to improve communication.

Social media use by physicians: a qualitative study of the new frontier of medicine.

BACKGROUND: A growing number of physicians are using social media as a professional platform for health communication. The purpose of this study was to understand perspectives and experiences of these "early adopter" physician bloggers and social media users. METHODS: This was an exploratory qualitative study involving in-depth semi-structured telephone interviews of physicians who were early adopters, defined as physicians who used social media to distribute health information. Participants were recruited through snowball sampling. Interview transcripts were manually analyzed for common themes by three separate investigators who came to common conclusions via the constant comparative method. RESULTS: Seventeen physicians participated in this study, including 35 % females, 76 % pediatricians and 76 % bloggers. Participants identified multiple perceived benefits and barriers to social media use by physicians; further, four major themes were identified. First, participants often saw themselves as rugged individualists who set their own rules for social media health communications. Second, participants expressed uncertainty about boundaries or strategies for social media use. Third, participants described using social media much like traditional media, as a one-way communication platform, rather than as an interactive forum. Finally, participants expressed disparate views regarding the time involved in participating in social media; some felt that time spent on social media was unproblematic to fit into their day while others felt that it was an impediment to patient care. CONCLUSIONS: Uncertainty remains regarding roles and responsibilities of physicians providing medical content within social media forums and few providers appeared to be using the platform to its full potential. Future studies may inform best practices to optimize social media health communication to benefit patients.

Disseminated Mycobacterium avium Complex With Cutaneous Lesions.

BACKGROUND: Although most commonly encountered in patients with human immunodeficiency virus infection, disseminated Mycobacterium avium complex (MAC) is becoming more common in patients receiving immunosuppressive medications. Disseminated MAC with skin lesions may occur, and several presentations have been reported, including panniculitis, cutaneous granulomas, pustules, ulcerations, and erythematous skin lesions. OBJECTIVES: The objective of this report is to describe an unusual presentation of MAC that is unlikely to be encountered frequently in the outpatient dermatology setting, especially in a patient without human immunodeficiency virus infection. METHODS: The authors present a case of disseminated MAC infection with cutaneous manifestations in an iatrogenically immunocompromised patient. CONCLUSIONS: Diagnosis of MAC infection is challenging given the varied clinical presentations and the difficulty in culturing MAC. In addition, the acid-fast stain is nonspecific. Clinicians should remember to consider MAC infection in patients with acid-fast-positive skin lesions, as the selection of appropriate antibiotic therapy is species specific.

Molecular definition of breast tumor heterogeneity.

Cells with distinct phenotypes including stem-cell-like properties have been proposed to exist in normal human mammary epithelium and breast carcinomas, but their detailed molecular characteristics and clinical significance are unclear. We determined gene expression and genetic profiles of cells purified from cancerous and normal breast tissue using markers previously associated with stem-cell-like properties. CD24+ and CD44+ cells from individual tumors were clonally related but not always identical. CD44+ cell-specific genes included many known stem-cell markers and correlated with decreased patient survival. The TGF-beta pathway was specifically active in CD44+ cancer cells, where its inhibition induced a more epithelial phenotype. Our data suggest prognostic relevance of CD44+ cells and therapeutic targeting of distinct tumor cell populations.

Does Nursing Home Ownership Change Affect Family Ratings on Experience with Care?

Person-centeredness may suffer in nursing homes (NHs) with recent ownership changes. This study identifies associations between ownership change and reported care experiences, important measures of person-centered care for long-term residents in Maryland NHs. Care experience measures and ownership change data were collected from Maryland Health Care Commission reports, which reported data on 220 Maryland NHs from 2011 and 2012. Facility and market covariates were obtained from 2011 NH Compare and Area Health Resource Files. Linear regression was used to examine whether ownership change in 2011 was associated with lower care experience ratings reported during April to June 2012. Dependent variables were overall care rating (scale 1-10), percentage of respondents answering that they would recommend the NH, and assessments of five care and resident life domains (scale 1-4). Care experiences reported in 2012 were high; however, after controlling for covariates, ownership change was associated with significant decreases in 6 out of 7 measures, including a 0.39-point decrease in overall care rating (p = .001). NH managers and policy makers should consider strategies to improve patient-centeredness after ownership change.

The PrP(C) C1 fragment derived from the ovine A136R154R171PRNP allele is highly abundant in sheep brain and inhibits fibrillisation of full-length PrP(C) protein in vitro.

Expression of the cellular prion protein (PrP(C)) is crucial for the development of prion diseases. Resistance to prion diseases can result from reduced availability of the prion protein or from amino acid changes in the prion protein sequence. We propose here that increased production of a natural PrP α-cleavage fragment, C1, is also associated with resistance to disease. We show, in brain tissue, that ARR homozygous sheep, associated with resistance to disease, produced PrP(C) comprised of 25% more C1 fragment than PrP(C) from the disease-susceptible ARQ homozygous and highly susceptible VRQ homozygous animals. Only the C1 fragment derived from the ARR allele inhibits in-vitro fibrillisation of other allelic PrP(C) variants. We propose that the increased α-cleavage of ovine ARR PrP(C) contributes to a dominant negative effect of this polymorphism on disease susceptibility. Furthermore, the significant reduction in PrP(C) ß-cleavage product C2 in sheep of the ARR/ARR genotype compared to ARQ/ARQ and VRQ/VRQ genotypes, may add to the complexity of genetic determinants of prion disease susceptibility.

Mosquito Species Diversity and Abundance Patterns in Plots with Contrasting Land Use and Land Cover in Bloomington, Indiana.

Land use and land cover (LULC) gradients are associated with differences in mosquito species composition and the entomological risk of mosquito-borne disease. Here, we present results from a season-long study of mosquito species richness and abundance with samples collected at 9 locations from 2 plots with contrasting LULC, an urban farm and a forest preserve, in Bloomington, IN, a city in the midwestern USA. With a total sampling effort of 234 trap-nights, we collected 703 mosquitoes from 9 genera and 21 species. On the farm, we collected 15 species (285 mosquitoes). In the preserve, we collected 19 species (418 mosquitoes). Thirteen species were common in both study plots, 2 were exclusive to the farm, and 6 were exclusive to the forest preserve. In both plots, we collected Aedes albopictus and Ae. japonicus. In the farm, the most common mosquito species were Culex restuans/Cx. pipiens and Coquillettidia perturbans. In the preserve, Ae. japonicus and Ae. triseriatus were the 2 most common mosquito species. Time series analysis suggests that weather factors differentially affected mosquito species richness and mosquito abundance in the plots. Temperature, relative humidity (RH), and precipitation were positively associated with richness and abundance at the farm, while increases in the SD of RH decreased both richness and abundance at the preserve. Our results highlight the importance that LULC has for mosquito species diversity and abundance and confirm the presence of Ae. albopictus and Ae. japonicus in southwestern Indiana.

Long-term outcomes by bone marrow B-cell depletion from the R2W trial of bortezomib with cyclophosphamide and rituximab in Waldenstrom macroglobulinaemia.

There remains a lack of consensus as to the most appropriate primary therapy in Waldenstrom macroglobulinemia (WM). We evaluated a novel bortezomib-based combination and developed a sensitive WM-specific flow cytometry assay (limit of detection 0.004% of leucocytes) to assess bone marrow (BM) response. Sixty treatment-naïve WM patients were enroled into this phase II trial and randomised (2:1) to receive cyclophosphamide and rituximab with either bortezomib (BRC) or fludarabine (FCR). The primary objective was to assess the overall response rate (ORR) in eligible patients receiving BRC (N = 41). An ORR of 97.6% (95%CI:87.1-99.9) was observed; 27 (65.9%) patients remain alive without progression after 62.6 months median follow-up, with 2-, 3- and 5-year progression-free survival (PFS) rates of 92.7% (95%CI:79.0-97.6), 80.5% (95%CI:64.8-89.7) and 65.5% (95%CI:48.8-77.9). Persistent WM B-cells were demonstrable in 19/38 patients at the end of treatment (median 0.24%, range 0.02-11.2%). PFS was markedly longer in patients with BM B-cell depletion (<0.004%) compared to those who had persistent BM B-cells detectable at end of treatment (HR = 0.06, 95%CI:0.01-0.47, p < 0.001), and remained independently associated after adjusting for baseline risk stratification or investigator-assessed response. BRC is a tolerable, highly efficacious regimen for treatment-naïve WM patients. BM B-cell depletion is independently associated with patient outcomes.

A preliminary randomized controlled trial of repetitive transcranial magnetic stimulation applied to the left dorsolateral prefrontal cortex in treatment seeking participants with cannabis use disorder.

BACKGROUND: Cannabis use disorder (CUD) is a common and consequential disorder. When applied to the dorsolateral prefrontal cortex (DLPFC), repetitive transcranial magnetic stimulation (rTMS) reduces craving across substance use disorders and may have therapeutic clinical effects when applied in serial-sessions. The present study sought to preliminarily determine whether serial-sessions of rTMS applied to the DLPFC had a therapeutic effect in CUD. METHODS: This study was a two-site, phase-2, double-blind, randomized-controlled-trial. Seventy-two treatment-seeking participants (37.5% Women, mean age 30.2±9.9SD) with ≥moderate-CUD were randomized to active or sham rTMS (Beam-F3, 10Hz, 20-total-sessions, two-sessions-per-visit, two-visits-per-week, with cannabis cues) while undergoing a three-session motivational enhancement therapy intervention. The primary outcome was the change in craving between pre- and post- treatment (Marijuana Craving Questionnaire Short-Form-MCQ-SF). Secondary outcomes included the number of weeks of abstinence and the number of days-per-week of cannabis use during 4-weeks of follow-up. RESULTS: There were no significant differences in craving between conditions. Participants who received active-rTMS reported numerically, but not significantly, more weeks of abstinence in the follow-up period than those who received sham-rTMS (15.5%-Active; 9.3%-Sham; rate ratio = 1.66 [95% CI: 0.84, 3.28]; p=0.14). Participants who received active-rTMS reported fewer days-per-week of cannabis use over the final two-weeks of the follow-up period than those receiving sham-rTMS (Active vs. Sham: -0.72; Z=-2.33, p=0.02). CONCLUSIONS: This trial suggests rTMS is safe and feasible in individuals with CUD and may have a therapeutic effect on frequency of cannabis use, though further study is needed with additional rTMS-sessions and a longer follow-up period.

Metagenomics and metatranscriptomics reveal broadly distributed, active, novel methanotrophs in the Gulf of Mexico hypoxic zone and in the marine water column.

The northern Gulf of Mexico (nGOM) hypoxic zone is a shallow water environment where methane, a potent greenhouse gas, fluxes from sediments to bottom water and remains trapped due to summertime stratification. When the water column is destratified, an active planktonic methanotrophic community could mitigate the efflux of methane, which accumulates to high concentrations, to the atmosphere. To investigate the possibility of such a biofilter in the nGOM hypoxic zone we performed metagenome assembly, and metagenomic and metatranscriptomic read mapping. Methane monooxygenase (pmoA) was an abundant transcript, yet few canonical methanotrophs have been reported in this environment, suggesting a role for non-canonical methanotrophs. To determine the identity of these methanotrophs, we reconstructed six novel metagenome-assembled genomes (MAGs) in the Planctomycetota, Verrucomicrobiota and one putative Latescibacterota, each with at least one pmoA gene copy. Based on ribosomal protein phylogeny, closely related microbes (mostly from Tara Oceans) and isolate genomes were selected and co-analyzed with the nGOM MAGs. Gene annotation and read mapping suggested that there is a large, diverse and unrecognized community of active aerobic methanotrophs in the nGOM hypoxic zone and in the global ocean that could mitigate methane flux to the atmosphere.

Preparing future STEM faculty through flexible teaching professional development.

We have prepared thousands of future STEM faculty around the world to adopt evidence-based instructional practices through their participation in two massive open online courses (MOOCs) and facilitated in-person learning communities. Our novel combination of asynchronous online and coordinated, structured face-to-face learning community experiences provides flexible options for STEM graduate students and postdoctoral fellows to pursue teaching professional development. A total of 14,977 participants enrolled in seven offerings of the introductory course held 2014-2018, with 1,725 participants (11.5% of enrolled) completing the course. Our results of high levels of engagement and learning suggest that leveraging the affordances of educational technologies and the geographically clustered nature of this learner demographic in combination with online flexible learning could be a sustainable model for large scale professional development in higher education. The preparation of future STEM faculty makes an important difference in establishing high-quality instruction that meets the diverse needs of all undergraduate students, and the initiative described here can serve as a model for increasing access to such preparation.

A Preliminary Investigation Of Repetitive Transcranial Magnetic Stimulation Applied To The Left Dorsolateral Prefrontal Cortex In Treatment Seeking Participants With Cannabis Use Disorder.

Background: Cannabis use disorder (CUD) is a common and consequential disorder. When applied to the dorsolateral prefrontal cortex (DLPFC), repetitive transcranial magnetic stimulation (rTMS) reduces craving across substance use disorders and may have a therapeutic clinical effect when applied in serial sessions. The present study sought to preliminarily determine whether serial sessions of rTMS applied to the DLPFC had a therapeutic effect in CUD. Methods: This study was a two-site, phase-2, double-blind, randomized-controlled-trial. Seventy-two treatment-seeking participants (37.5% Women, mean age 30.2±9.9SD) with ≥moderate-CUD were randomized to active or sham rTMS (Beam-F3, 10Hz, 20-total-sessions, with cannabis cues) while undergoing a three-session motivational enhancement therapy intervention. The primary outcome was the change in craving between pre- and post-treatment (Marijuana Craving Questionnaire Short-Form-MCQ-SF). Secondary outcomes included the number of weeks of abstinence and the number of days-per-week of cannabis use during 4-weeks of follow-up. Results: There were no significant differences in craving between conditions. Participants who received active rTMS reported numerically, but not significantly, more weeks of abstinence in the follow-up period than those who received sham rTMS (15.5%-Active; 9.3%-Sham; rate ratio = 1.66 [95% CI: 0.84, 3.28]; p=0.14). Participants who received active rTMS reported fewer days-per-week of cannabis use over the final two-weeks of the follow-up period (Active vs. Sham: -0.72; Z=-2.33, p=0.02). Conclusions: This trial suggests rTMS is safe and feasible in individuals with CUD and may have a therapeutic effect on frequency of cannabis use, though further study is needed with additional rTMS-sessions and a longer follow-up period.