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Adolescents with ASD face numerous personal and contextual barriers that impede the development of social motivation and core competencies, warranting the need for targeted intervention. A randomized controlled trial was conducted with 40 adolescents to evaluate the merits of a multi-component socialization intervention that places emphasis on experiential learning. This investigation evaluated the impact of the 20-week START program on the social functioning of adolescents with ASD. Significant Group × Time differences between START and waitlist control groups were found across multiple measures. Secondary analyses of the entire program cohort also yielded significant improvement trends across all measures. These findings may be an important step in identifying optimal strategies to target the complex factors limiting optimal social development in ASD.

The symptoms of autism spectrum disorder are conceptualized to alter the quality of parent–children interactions, exposure to social learning exchanges, and ultimately the course of child development. There is evidence that modifying the procedures of Pivotal Response Treatment (PRT) to explicitly target social motivation enhances child engagement and parent–child synchrony in moment-by-moment exchanges. However, it is unclear if these within session improvements ultimately yield favorable developmental outcomes over time. The current investigation presents feasibility, utility, and preliminary efficacy data of a pilot randomized clinical trial (RCT) of a Pivotal Response Intervention for Social Motivation (PRISM) model. Data on participant factors, treatment protocol acceptability, and outcome variance and effect size are highly favorable and support the pursuit of a future, large scale RCT.

Medicare's Patient Driven Payment Model (PDPM) significantly altered the way skilled nursing facilities (SNFs) are paid, removing the financial incentive to maximize the volume of therapy services delivered to patients. Using federal payroll-based staffing data, we examined the effect of the PDPM on SNF therapy and nursing staff hours. After PDPM implementation, which took effect October 1, 2019, SNFs significantly reduced their therapy staff hours. Physical therapist and occupational therapist staffing levels were reduced by 5-6 percent during October-December 2019 relative to pre-PDPM levels, and physical therapy assistant and occupational therapist assistant levels were reduced by about 10 percent. These reductions were concentrated among contracted employees and were larger in SNFs with higher shares of Medicare-eligible short-stay residents. No meaningful increases in nursing staff in response to the PDPM were found. Further research is needed to determine the effect of these therapy staff reductions on SNF patient outcomes.

Despite advances in evidence-based treatment for autism spectrum disorder (ASD), disparities in service access remain a serious concern. Current treatment models may not be feasible for families who live in remote geographical regions or have limited resources. To address this, studies have begun to explore parent-implemented interventions via an online format. The current study examined a new online course designed to help parents implement Pivotal Response Treatment (PRT) for their toddler with ASD. Parents submitted videos of parent–child interactions which were coded for fidelity of implementation (FOI) and social communicative behaviors. The data indicate that PRT fidelity and child behaviors significantly improved following course participation. This suggests that an online intervention may be a feasible approach to disseminating PRT strategies.

Siroheme is the central cofactor in a conserved class of sulfite and nitrite reductases that catalyze the six-electron reduction of sulfite to sulfide and nitrite to ammonia. In Salmonella enterica serovar Typhimurium, siroheme is produced by a trifunctional enzyme, siroheme synthase (CysG). A bifunctional active site that is distinct from its methyltransferase activity catalyzes the final two steps, NAD + -dependent dehydrogenation and iron chelation. How this active site performs such different chemistries is unknown. Here, we report the structures of CysG bound to precorrin-2, the initial substrate; sirohydrochlorin, the dehydrogenation product/chelation substrate; and a cobalt-sirohydrochlorin product. We identified binding poses for all three tetrapyrroles and tested the roles of specific amino acids in both activities to give insights into how a bifunctional active site catalyzes two different chemistries and acts as an iron-specific chelatase in the final step of siroheme synthesis. Siroheme is an essential bacterial iron tetrapyrrole used by siroheme-dependent sulfite and nitrite reductases. Here the authors shed light on the catalytic mechanisms of siroheme synthase through the structures of the bifunctional dehydrogenase/chelatase CysG module bound to its substrate, precorrin-2, the product/substrate sirohydrochlorin, and cobalt-sirohydrochlorin.

Importance Staffing shortages have been widely reported in US nursing homes during the COVID-19 pandemic, but traditional quantitative research analyses have found mixed evidence of staffing shortfalls. Objective To examine whether nursing home administrator perspectives can provide context for conflicting aggregate staffing reports in US nursing homes during the COVID-19 pandemic. Design, Setting, and Participants In a qualitative study, convergent mixed-methods analysis integrating qualitative and quantitative data sets was used. Semistructured qualitative interviews were conducted between July 14, 2020, and December 16, 2021. Publicly available national Payroll Based Journal data were retrieved from January 1, 2020, to September 30, 2022, on 40 US nursing homes in 8 health care markets that varied by region and nursing home use patterns. Staffing and resident measures were derived from Payroll Based Journal data and compared with national trends for 15 436 US nursing homes. Nursing home administrators were recruited for interviews. Of the 40 administrators who consented to participate, 4 were lost to follow-up. Exposure Four repeated, semistructured qualitative interviews with participants were conducted. Interview questions focused on the changes noted during the COVID-19 pandemic in nursing homes. Main Outcomes and Measures Thematic description of nursing home administrator compensatory strategies to provide context for quantitative analyses on nursing home staffing levels during the COVID-19 pandemic. Results A total of 156 interviews were completed with 40 nursing home administrators. Administrators reported experiencing staff shortages during the COVID-19 pandemic and using compensatory strategies, such as overtime, cross-training, staff-to-resident ratio adjustments, use of agency staff, and curtailing admissions, to maintain operations and comply with minimum staffing regulations. Payroll Based Journal data measures graphed from January 1, 2020, to September 30, 2022, supported administrator reports showing that study facilities had reductions in staff hours, increased use of agency staff, and decreased resident census. Findings were similar to national trends. Conclusions and Relevance In this qualitative, convergent mixed-methods study, nursing home administrators reported the major staffing strain they experienced at their facilities and the strategies they used to offset staffing shortages. Their experiences provide context to quantitative analyses on aggregate nursing home census data. The short-term compensatory measures administrators used to comply with regulations and maintain operations may be detrimental to the long-term stability of this workforce.

In October 2019, Medicare changed its skilled nursing facility (SNF) reimbursement model to the Patient Driven Payment Model (PDPM), which has modified financial incentives for SNFs that may relate to therapy use and health outcomes. To assess whether implementation of the PDPM was associated with changes in therapy utilization or health outcomes. This cross-sectional study used a regression discontinuity (RD) approach among Medicare fee-for-service postacute-care patients admitted to a Medicare-certified SNF following hip fracture between January 2018 and March 2020. Skilled nursing facility admission after PDPM implementation. Main outcomes were individual and nonindividual (concurrent and group) therapy minutes per day, hospitalization within 40 days of SNF admission, SNF length of stay longer than 40 days, and discharge activities of daily living score. The study cohort included 201 084 postacute-care patients (mean [SD] age, 83.8 [8.3] years; 143 830 women [71.5%]; 185 854 White patients [92.4%]); 147 711 were admitted pre-PDPM, and 53 373 were admitted post-PDPM. A decrease in individual therapy (RD estimate: -15.9 minutes per day; 95% CI, -16.9 to -14.6) and an increase in nonindividual therapy (RD estimate: 3.6 minutes per day; 95% CI, 3.4 to 3.8) were observed. Total therapy use in the first week following admission was about 12 minutes per day (95% CI, -13.3 to -11.3) (approximately 13%) lower for residents admitted post-PDPM vs pre-PDPM. No consistent and statistically significant discontinuity in hospital readmission (0.31 percentage point increase; 95% CI, -1.46 to 2.09), SNF length of stay (2.7 percentage point decrease in likelihood of staying longer than 40 days; 95% CI, -4.83 to -0.54), or functional score at discharge (0.04 point increase in activities of daily living score; 95% CI, -0.19 to 0.26) was observed. Nonindividual therapy minutes were reduced to nearly zero in late March 2020, likely owing to COVID-19-related restrictions on communal activities in SNFs. In this cross-sectional study of SNF admission after PDPM implementation, a reduction of total therapy minutes was observed following the implementation of PDPM, even though PDPM was designed to be budget neutral. No significant changes in postacute outcomes were observed. Further study is needed to understand whether the PDPM is associated with successful discharge outcomes.

Several states implemented COVID-19 vaccine mandates for nursing home employees, which may have improved vaccine coverage but may have had the unintended consequence of staff departures. To assess whether state vaccine mandates for US nursing home employees are associated with staff vaccination rates and reported staff shortages. This cohort study performed event study analyses using National Healthcare Safety Network data from June 6, 2021, through November 14, 2021. Changes in weekly staff vaccination rates and reported staffing shortages were evaluated for nursing homes in states with mandates after the mandate announcement compared with changes in facilities in nonmandate states. An interaction between the mandates and county political leaning was considered. Data analysis was performed from February to March 2022. Weeks after announcement of a state's COVID-19 vaccine mandate. Weekly percentage of all health care staff at a nursing home who received at least 1 COVID-19 vaccine dose, and a weekly indicator of whether a nursing home reported a staffing shortage. Among 38 study-eligible states, 26 had no COVID-19 vaccine mandate for nursing home employees, 4 had a mandate with a test-out option, and 8 had a mandate with no test-out option. Ten weeks or more after mandate announcement, nursing homes in states with a mandate and no test-out option experienced a 6.9 percentage point (pp) increase in staff vaccination coverage (95% CI, -0.1 to 13.9); nursing homes in mandate states with a test-out option experienced a 3.1 pp increase (95% CI, 0.5 to 5.7) compared with facilities in nonmandate states. No significant increases were detected in the frequency of reported staffing shortages after a mandate announcement in mandate states with or without test-out options. Increases in vaccination rates in states with mandates were larger in Republican-leaning counties (14.3 pp if no test-out option; 4.3 pp with option), and there was no evidence of increased staffing shortages. The findings of this cohort study suggest that state-level vaccine mandates were associated with increased staff vaccination coverage without increases in reported staffing shortages. Vaccination increases were largest when mandates had no test-out option and were also larger in Republican-leaning counties, which had lower mean baseline vaccination rates. These findings support the use of state mandates for booster doses for nursing home employees because they may improve vaccine coverage, even in areas with greater vaccine hesitancy.

Eosinophils are often dominant inflammatory cells present in the lungs of asthma patients. Nonetheless, the role of these leukocytes remains poorly understood. We have created a transgenic line of mice (PHIL) that are specifically devoid of eosinophils, but otherwise have a full complement of hematopoietically derived cells. Allergen challenge of PHIL mice demonstrated that eosinophils were required for pulmonary mucus accumulation and the airway hyperresponsiveness associated with asthma. The development of an eosinophil-less mouse now permits an unambiguous assessment of a number of human diseases that have been linked to this granulocyte, including allergic diseases, parasite infections, and tumorigenesis.

Background Enhanced macromolecule biosynthesis is integral to growth and proliferation of cancer cells. Lipid biosynthesis has been predicted to be an essential process in cancer cells. However, it is unclear which enzymes within this pathway offer the best selectivity for cancer cells and could be suitable therapeutic targets. Results Using functional genomics, we identified stearoyl-CoA desaturase (SCD), an enzyme that controls synthesis of unsaturated fatty acids, as essential in breast and prostate cancer cells. SCD inhibition altered cellular lipid composition and impeded cell viability in the absence of exogenous lipids. SCD inhibition also altered cardiolipin composition, leading to the release of cytochrome C and induction of apoptosis. Furthermore, SCD was required for the generation of poly-unsaturated lipids in cancer cells grown in spheroid cultures, which resemble those found in tumour tissue. We also found that SCD mRNA and protein expression is elevated in human breast cancers and predicts poor survival in high-grade tumours. Finally, silencing of SCD in prostate orthografts efficiently blocked tumour growth and significantly increased animal survival. Conclusions Our data implicate lipid desaturation as an essential process for cancer cell survival and suggest that targeting SCD could efficiently limit tumour expansion, especially under the metabolically compromised conditions of the tumour microenvironment.