Background
The relationship between inadequate sleep and mood has been well‐established in adults and is supported primarily by correlational data in younger populations. Given that adolescents often ...experience shortened sleep on school nights, we sought to better understand the effect of experimentally induced chronic sleep restriction on adolescents’ mood and mood regulation.
Methods
Fifty healthy adolescents, ages 14–17, completed a 3‐week sleep manipulation protocol involving a baseline week, followed by a sleep restriction (SR) condition (6.5 hr in bed per night for five nights) and healthy sleep duration (HS) condition (10 hr in bed per night for five nights). The study used a randomized, counterbalanced, crossover experimental design. Participants’ sleep was monitored at home via self‐report and actigraphy. At the end of each condition, participants and their parents completed questionnaires of mood and mood regulation. To assess for expectancy effects, we also analyzed parent and teen ratings of hyperactivity/impulsivity, which prior research suggests is not sensitive to SR in adolescents. Wilcoxon Signed Rank tests compared questionnaire outcomes across the two conditions.
Results
Participants averaged 2.5 more hours of sleep per night during HS relative to SR. Compared with HS, adolescents rated themselves as significantly more tense/anxious, angry/hostile, confused, and fatigued, and as less vigorous (p = .001–.01) during SR. Parents and adolescents also reported greater oppositionality/irritability and poorer emotional regulation during SR compared with HS (p < .05). There were no cross‐condition differences in depression or hyperactivity/impulsivity (p > .05).
Conclusions
Findings complement prior correlational study results to show that after only a few days of shortened sleep, at a level of severity that is experienced regularly by millions of adolescents on school nights, adolescents have worsened mood and decreased ability to regulate negative emotions.
Targeting the interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor is a promising ...therapeutic strategy. We designed inhibitors using two de novo design approaches. Computer-generated scaffolds were either built around an ACE2 helix that interacts with the spike receptor binding domain (RBD) or docked against the RBD to identify new binding modes, and their amino acid sequences were designed to optimize target binding, folding, and stability. Ten designs bound the RBD, with affinities ranging from 100 picomolar to 10 nanomolar, and blocked SARS-CoV-2 infection of Vero E6 cells with median inhibitory concentration (IC
) values between 24 picomolar and 35 nanomolar. The most potent, with new binding modes, are 56- and 64-residue proteins (IC
~ 0.16 nanograms per milliliter). Cryo-electron microscopy structures of these minibinders in complex with the SARS-CoV-2 spike ectodomain trimer with all three RBDs bound are nearly identical to the computational models. These hyperstable minibinders provide starting points for SARS-CoV-2 therapeutics.
Examine the effect of experimental sleep restriction (SR) on adolescents' subjective hunger and perceived appeal of sweet/dessert foods versus other foods. A secondary goal was to replicate previous ...findings on the effects of SR on dietary intake.
Randomized cross-over sleep restriction-extension paradigm.
Sleep was obtained and monitored at home. Outcome measures were gathered during office visits.
31 typically-developing adolescents aged 14-17 years.
The three-week protocol consisted of a baseline week, followed randomly by five consecutive nights of SR (6.5 hours in bed) versus healthy sleep duration (HS; 10 hours in bed), a 2-night wash-out period, and a 5-night cross-over.
Sleep was monitored via actigraphy. The morning after each experimental condition, teens rated their hunger, underwent a 24-hour diet recall interview, and rated the appeal of a series of pictures of sweet/dessert foods (e.g., ice cream, candy) and non-sweets (meat, eggs, fruits, vegetables).
Teens rated pictures of sweet/dessert foods to be more appealing after SR than after HS (Cohen's d = .41, t = 2.07, p = .045). The sleep manipulation did not affect self-reported hunger or the appeal of non-sweet foods (p >.10). Consistent with our prior work, intake of overall calories was 11% higher and consumption of sweet/dessert servings was 52% greater during SR than HS.
Adolescent SR appears to increase the subjective appeal of sweet/dessert foods, indicating a potential mechanism by which SR might contribute to weight gain and the risk for obesity and chronic illness.
Aggregates of the protein tau are proposed to drive pathogenesis in neurodegenerative diseases. Tau can be targeted by using passively transferred antibodies (Abs), but the mechanisms of Ab ...protection are incompletely understood. In this work, we used a variety of cell and animal model systems and showed that the cytosolic Ab receptor and E3 ligase TRIM21 (T21) could play a role in Ab protection against tau pathology. Tau-Ab complexes were internalized to the cytosol of neurons, which enabled T21 engagement and protection against seeded aggregation. Ab-mediated protection against tau pathology was lost in mice that lacked T21. Thus, the cytosolic compartment provides a site of immunotherapeutic protection, which may help in the design of Ab-based therapies in neurodegenerative disease.
Current health and social care systems do not always meet the needs of the dying in our communities. As a result, patients and families are choosing to place their trust in those who can advocate for ...them or fill the gaps in care. Birth Doulas have been working with women during pregnancy and after birth for many years, and we are now seeing a new role, that of a Death Doula emerging in the end‐of‐life care space. How Death Doulas work within health and social care systems is not understood and we conducted a systematic review to explore the published literature to explore the role and potential implications for models of care delivery. Following the PRISMA recommendations, we searched the literature in January 2018 via bibliographic databases and the grey literature without search date parameters to capture all published literature. We looked for articles that describe the role/work of a death doula or a death midwife in the context of end‐of‐life care, or death and dying. Our search retrieved 162 unique records of which five papers were included. We analysed the papers in relation to relationship to health service, funding source, number and demand for services, training, licensing and ongoing support, and tasks undertaken. Death Doulas are working with people at the end of life in varied roles that are still little understood, and can be described as similar to that of “an eldest daughter” or to a role that has similarities to specialist palliative care nurses. Death doulas may represent a new direction for personalised care directly controlled by the dying person, an adjunct to existing services, or an unregulated form of care provision without governing oversight.
Objectives/Hypothesis
Determine if antibiotic prescribing patterns differ for in‐person versus virtual clinic visits for acute rhinosinusitis (ARS).
Study Design
Cross sectional study.
Methods
All ...adult virtual clinical encounters from March to May 2020 with a principal diagnosis of ARS were reviewed for demographic data and the presence or absence of an antibiotic prescription during the coronavirus shut down in Massachusetts. In‐person clinical encounters from March to May 2019 were similarly examined as a control. The rate of antibiotic prescription was compared between virtual (2020) and in‐person (2019) visits for ARS diagnoses.
Results
There were 2,075 patients in March to May 2020 and 3,654 patients March to May 2019 who received an ARS principal diagnosis at their virtual and in‐person outpatient visits, respectively. There was a statistically significant lower rate of antibiotic prescriptions for ARS in 2020 (72.1%) versus 2019 (76.7%).The odds ratio for an antibiotic prescription for ARS was 0.783 (95% confidence interval, 0.693–0.86; P < .001) for patients seen in the 2020 cohort versus the 2019 cohort. The compared rates for antibiotic prescribing for 2020 versus 2019 were not different in individual month‐to‐month comparisons. When stratified by otolaryngology providers there was no statistically significant difference of antibiotic prescriptions between the 2019 and 2020 cohort (P = .781).
Conclusions
During the massive transition to virtual visits for March to May 2020 due to the coronavirus pandemic shut down in Massachusetts, the total rate of outpatient antibiotic prescribing for ARS was lower in the virtual visit environment compared to the traditional in‐person visit. In this scenario, telemedicine did not result in an increase in antibiotic prescribing despite the lack of an in‐person physical exam.
Level of Evidence
IV Laryngoscope, 131:E2121–E2124, 2021
Chronic rhinosinusitis (CRS) management frequently comprises conservative treatment, including a combination of topical and oral corticosteroids (OCSs). However, in the midst of the coronavirus ...disease 2019 (COVID-19) pandemic, providers may have been reluctant to prescribe OCSs out of possible concern for an increased risk of contracting COVID-19 or developing more severe COVID-19 symptoms. This study thus sought to explore the association between the use of OCSs and the development of COVID-19 in patients with CRS. We found no statistically significant difference in the rates of patients with a positive diagnosis of COVID-19 who underwent an OCS treatment regimen compared to those who did not, both within 28 days (
= .389) and 14 days (
= .676) prior to the COVID-19 test. Given OCSs are often a major component of medical management of CRS, this study proves helpful in counseling patients on risks of steroid use in CRS treatment during the COVID-19 pandemic.
Pleural effusions are common cytologic specimens that can be leveraged to make diagnoses of malignancy that drive appropriate patient management. However, the overlap in morphologic features of ...reactive mesothelial proliferations, mesotheliomas, and adenocarcinomas can create diagnostic pitfalls in the cytologic evaluation of pleural fluids.
To review the morphologic spectrum of benign and malignant mesothelial proliferations in pleural effusions, as well as relevant clinicoradiologic contexts and ancillary tests.
Existing scientific and clinical literature as of January 2023.
We can leverage the knowledge of several overlapping morphologic features, clinicoradiologic scenarios, and immunohistochemical studies to enhance the diagnostic accuracy of pleural effusion cytology to appropriately delineate cases of adenocarcinoma, reactive mesothelial proliferation, and mesothelioma. Earlier diagnosis through cytology, particularly in cases of mesothelioma, may positively impact patient treatment options and prognosis.
Assemblies of tau can transit between neurons, seeding aggregation in a prion-like manner. To accomplish this, tau must cross cell-limiting membranes, a process that is poorly understood. Here, we ...establish assays for the study of tau entry into the cytosol as a phenomenon distinct from uptake, in real time, and at physiological concentrations. The entry pathway of tau is cell type specific and, in neurons, highly sensitive to cholesterol. Depletion of the cholesterol transporter Niemann-Pick type C1 or extraction of membrane cholesterol renders neurons highly permissive to tau entry and potentiates seeding even at low levels of exogenous tau assemblies. Conversely, cholesterol supplementation reduces entry and almost completely blocks seeded aggregation. Our findings establish entry as a rate-limiting step to seeded aggregation and demonstrate that dysregulated cholesterol, a feature of several neurodegenerative diseases, potentiates tau aggregation by promoting entry of tau assemblies into the cell interior.
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•Cytosolic entry is rate limiting to the seeded aggregation of tau•Tau assemblies enter the cytosol of neurons via a clathrin-independent pathway•Low membrane cholesterol renders neurons extremely permissive to entry and seeding•NPC1 protects against entry and seeded aggregation
Tuck et al. measure the entry of tau assemblies into the cytosol of neurons with high sensitivity. They identify a critical role for membrane cholesterol in preventing the entry and downstream seeded aggregation of tau. The results provide mechanistic insights into the role of cholesterol in neurodegenerative disease.
‘Death Doulas’ have emerged as a relatively new role supporting dying people and their family members; however there is a lack of clarity around how the role is enacted, and around the death doula ...role within health and social care systems. This study aimed to explore the ambiguity of the role of death doulas in end‐of‐life care including the skills, training and experience of death doulas; how the role is communicated to the community; and the relationships to palliative care providers and other health professionals. People identifying as death doulas were invited to participate in an online survey between April and June 2018. Ethical approval was obtained. A descriptive cross‐sectional study was conducted, and purposive sampling was used to survey death doulas registered with death doula training organisations, newsletters and email distribution lists. Questions were based on the researchers’ previous findings about the role. One hundred and ninety completed or partially completed surveys were received. Results showed diversity within, and some commonalities across the sample in terms of: training, experience and skills; Death doulas have emerged not only as a response to the overwhelming demands on families and carers, but also demands placed on health care professionals (including palliative care) at the end‐of‐life. They have identified gaps in health and social care provision, perhaps taking on tasks that health professionals don't have responsibility for. However, the roles and scope of practice of death doulas is not clear‐cut even within their cohort, which can then make it hard for patients and families when choosing a death doula, especially as a lack of regulation and standardised training means that doulas are working without oversight, and often in isolation.
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