In several long-lived Caenorhabditis elegans strains, such as insulin/IGF-1 receptor daf-2 mutants, enhanced proteostatic mechanisms are accompanied by elevated intestinal lipid stores, but their ...role in longevity is unclear. Here, while determining the regulatory network of the selective autophagy receptor SQST-1/SQSTM1, we uncovered an important role for lipid droplets in proteostasis and longevity. Using genome-wide RNAi screening, we identified several SQST-1 modulators, including lipid droplets-associated and aggregation-prone proteins. Expansion of intestinal lipid droplets by silencing the conserved cytosolic triacylglycerol lipase gene atgl-1/ATGL enhanced autophagy, and extended lifespan. Notably, a substantial amount of ubiquitinated proteins were found on lipid droplets. Reducing lipid droplet levels exacerbated the proteostatic collapse when autophagy or proteasome function was compromised, and significantly reduced the lifespan of long-lived daf-2 animals. Altogether, our study uncovered a key role for lipid droplets in C. elegans as a proteostatic mediator that modulates ubiquitinated protein accumulation, facilitates autophagy, and promotes longevity.
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•Elevated levels of SQST-1/SQSTM1 are detrimental to lifespan in C. elegans•Low lipid stores challenge the ability of SQST-1 to facilitate protein degradation•High lipid droplet content stabilizes aggregation-prone proteins•Age-related proteostatic decline is mitigated by lipid droplets
Biological sciences; Biochemistry
As concerns about Covid-19 rapidly escalated in March 2020 in the United States, all levels of education were impacted. A unique population (student teachers) faced challenges from two perspectives: ...as students and as teachers forced to teach and learn from a distance. Student Teachers, or preservice teachers (PST), are university students finishing a degree and/or teacher certification program by serving as an intern in a school setting. As schools were closed, these PSTs may not have been given access to the online learning platforms of their cooperating teachers (CT) and were no longer included in classroom instruction. The purpose of this study was to examine how the sudden shift away from traditional face-to-face instruction, co-teaching, and mentorship affected the involvement of music PSTs and their CT mentors in one region of the United States. Specifically, the research questions were: (1) How and in what ways were PSTs involved in planning, instruction, and/or assessment synchronously and asynchronously after school closures? (2) In what subdomains (performance, music theory/ear-training, etc.) were PSTs engaged in instruction and learning activities? (3) What challenges and solutions did PSTs report related to Covid-19 closures? A survey was sent,
email, to PSTs attending teacher preparation programs at universities in the state of Georgia at the end of the spring semester. Thirty-seven participants responded to the survey questions representing about 32% of all PSTs in Georgia in Spring 2020. Twenty-one were not given access to the online teaching platform of their placement school. A thematic analysis of the open-ended questions identified common themes including whether experiences were perceived as negative or positive. Of the PSTs given access, the majority of their responsibilities and experiences were creating assignments, additional help videos, participating in Zoom meetings, and assessing student assignment submissions. Of these experiences, interestingly, most were classified as positive by the PSTs. However, the importance of face-to-face interactions for both PST and the P-12 students was mentioned throughout survey responses. Approximately 10 PSTs mentioned their CT relationship/interaction and four of the respondents noted that their CT never reached out for help; however, six noted collaborative meetings or teaching with their CT. Importantly, some PSTs reported a lack of knowledge related to the planning and implementation of music instruction in the online modality. Therefore, teacher preparation programs should consider incorporating technology including online solutions into the music curriculum so that future music educators may more flexibly incorporate both in-person and distance learning.
Utility of syndromic case management (SCM) in women visiting obstetrics & gynecology department needs to be evaluated as it is subjective and imperfect. Consequently, antibiotic resistance has ...accelerated along with increased risk of infection to the partners. To understand the effectiveness and/or inadequacies of SCM, 11000 women were recruited and examined by clinicians for infection by Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV), Bacterial vaginosis (BV) and others. Amongst these patients, 1797 (16.3%) reported vaginal discharge (VD). Other symptoms included: vaginitis (97%), cervicitis (75%), genital ulcers (60%), abnormal vaginal discharge (55%) and lower abdominal pain (48%). The patients were treated for single or co-infections using pre-packed National Aids Control Program III STI/RTI Kits. However, based on PCR diagnostics, 1453/1797 (81%) subjects were uninfected for NG/TV/CT. Amongst 344 (19%) infected patients, 257 (75%) carried infection with single pathogen (TV/NG/CT) while 87/344 (25%) were co-infected with multiple pathogens. Prevalence of TV, NG & CT was 4%, 7% and 8% respectively. Co-infection with CT + NG was highest, 51% (44/87), whereas, co-infection with CT + TV was 21% and NG + TV was 18% while co-infection with all three pathogens was 1.3%. We conclude that SCM is imprecise and successful intervention requires accurate and confirmatory diagnostic approach.
There is little data about treatment practices for relapsed/refractory Hodgkin Lymphoma (HL) in nonacademic settings. We describe sequential treatments and outcomes among HL patients who experienced ...treatment failure in an integrated community-oncology setting. We performed a retrospective cohort study among patients ≥12 years diagnosed with Stage II-IV HL from 2007 to 2012 at Kaiser Permanente Southern California (KPSC). Of 463 HL patients, 75 (16.1%) experienced treatment failure. Patients with failure received between 1 and 8 salvage therapies; 28% received ≥4 lines of therapy. Fifty-nine of 75 (79%) were initially salvaged with ifosfamide-based therapy, 44 of whom underwent hematopoietic cell transplant. Ultimately, 47% of patients died, with most deaths due to HL. Survival was shorter with increasing age at diagnosis (p = 0.02) and with greater number of lines of therapy (p = 0.02). In a community oncology setting, HL patients received multiple lines of salvage. Despite extensive treatment, nearly half of patients died of HL following relapsed/refractory disease.
Little is known about the characteristics of patients, physicians, and organizations that influence treatment decisions in older patients with AML. We conducted qualitative interviews with community ...oncologists and older patients with AML to elicit factors that influence their treatment decision-making. Recruitment was done via purposive sampling and continued until theoretical saturation was reached, resulting in the inclusion of 15 patients and 15 oncologists. Participants' responses were analyzed using directed content analysis. Oncologists and patients considered comorbidities, functional status, emotional health, cognition, and social factors when deciding treatment; most oncologists evaluated these using clinical gestalt. Sixty-seven percent of patients perceived that treatment was their only option and that they had not been offered a choice. In conclusion, treatment decision-making is complex and influenced by patient-related factors. These factors can be assessed as part of a geriatric assessment which can help oncologists better determine fitness and guide treatment decision-making.
The assessment of the severity of upper gastrointestinal hemorrhage in emergency department (ED) patients is difficult to assess with commonly available diagnostic tools. Small studies have shown ...that video capsule endoscopy (VCE) is a promising risk-stratification method and may be better than current clinical decision rules such as the Rockall score and the Glasgow Blatchford score. This review aims to assess the accuracy of VCE to detect active upper gastrointestinal hemorrhage compared to a reference standard.
The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodology was used to perform a review of studies that have measured the diagnostic accuracy of VCE. Studies were included if they measured ED use of VCE for upper GI hemorrhage as compared to a reference standard of an esophagogastroduodenoscopy (EGD). A meta-analysis was performed on select patients using a fixed effects and random-effects model to determine the primary outcome of diagnostic test accuracy.
40 studies were screened for eligibility and five studies representing 193 patients met the inclusion and exclusion criteria. All patients received both a VCE and an EGD. The sensitivity and specificity of VCE were 0.724 and 0.748, respectively. The diagnostic odds ratio was 6.29 (95% CI: 3.23–12.25) and the summary receiver operating characteristic curve was 0.782.
VCE demonstrated high accuracy for detecting upper GI hemorrhage in this meta-analysis of existing studies. In light of the potential advantages of VCE in the ED, further research is warranted to further establish its role.
Medicaid state dental programs have experienced changes related to provider practice settings with the increased growth of dental support organizations (DSOs). The authors conducted this study to ...assess the impact of state Medicaid reform on the dental practice environment by examining provider activity and practice setting.
This was a retrospective cohort study of more than 13 million dental claims in the Virginia Medicaid program. It included children and dental care providers in the Virginia dental Medicaid program at some time during a 9-year period (fiscal years 2003-2011). The independent variable was the provider practice setting: private practice, DSO, and safety-net practice. The outcomes included annual measures of claims, patients, and payments per provider. The outcomes were examined over 3 phases of the study period: prereform (2003-2005), implementation phase (2006-2008), and postreform maturation (2009-2011).
Provider activity increased after dental program reform, with private-practice providers delivering most of the dental care in the Medicaid program. There was a significant penetration of DSO providers in number of providers, claims per provider, and patients per provider (P < .001). Regression results found that providers in DSO settings had an increased number of patients and claims compared with private-practice providers.
Medicaid reform has resulted in a significant increase in provider participation and growth of DSO-affiliated providers.
Areas of the state with more dense population had a higher penetrance of dentists practicing in DSO settings providing dental services to children enrolled in Medicaid.
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