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BackgroundTobacco smoke may affect atopic dermatitis (AD) because of its known effects on humoral and cellular immunity, but prior studies lack data on disease severity and biomarkers over time.ObjectiveWe investigated the association between passive and active tobacco smoke exposure (TSE) during childhood and adolescence and the activity and severity of AD.MethodsA birth cohort of 10,521 individuals was followed through adolescence as part of the Avon Longitudinal Study of Parents and Children. We used mixed-effect models to determine the risk of AD (based on repeated assessments) with passive smoke exposure during childhood, active TSE during adolescence, and using a serum biomarker of tobacco exposure (cotinine) at 3 time points.ResultsAfter adjusting for confounding factors, there was no evidence of a relationship between passive TSE and concurrent AD activity in childhood (adjusted odds ratio, 0.95; 95% confidence interval, 0.83, 1.07) or of an increased risk between active smoking and AD activity in adolescence (adjusted odds ratio, 0.57; 95% confidence interval, 0.44, 0.75). Secondary analyses demonstrated no dose-response relationship and no increased severity of AD with passive or active TSE. Furthermore, we found no increased risk of AD with a cumulative measure of passive TSE across childhood (adjusted relative risk ratio, 0.98; 95% confidence interval, 0.96, 1.00).ConclusionNeither active nor passive TSE was associated with AD during childhood and adolescence.

BackgroundUpper cervical instability (UCI) is a potentially disabling complication of the connective tissue disorders hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders (hEDS/HSD). UCI can impact various neurological structures, including the brainstem, spinal cord, cranial nerves, and blood supply to and from the brain, resulting in complex neurological signs and symptoms in this population. The current study was an observational study applying recent expert consensus recommendations for physical therapy assessment and management of patients with UCI associated with hEDS/HSD.MethodsThis was a retrospective observational study describing how the clinical decision-making model was used to screen, examine, and treat three patients with highly irritable hEDS/HSD-related UCI, resulting in complex neurological presentation. The treatment used a neuroplasticity approach, including proprioception and motor control training emphasizing patient education and biofeedback. Outcome measures tracked progress.ResultsAll patients started with significant disability associated with UCI. One patient returned to full function with intermittent flares that he was able to manage. The second patient continued to have mild-moderate irritability but returned to parenting responsibilities and full-time work. The third patient required cervical fusion and remained disabled but was better able to minimize flares. The number of initial red and yellow flags was associated with the final outcomes, suggesting that the decision-making model might be useful for predicting patient prognosis.ConclusionThis brief report applies recent recommendations for safely evaluating and managing hypermobility-related UCI and provides a first step in experimental studies to test both the assessment and physical therapy treatment approaches.

ABSTRACT: Cerebral palsy (CP) is an impairment in motor function and coordination due to a nonprogressive brain injury that occurs pre-, peri-, or postnatally until 2 years of age with a prevalence of 1 to 4 per 1,000 live births. Along with impaired motor function, decreased bone mineral density (BMD) in children with CP is of concern for providers. An algorithm has been created to help identify patients at risk for decreased BMD who are seen by providers. Factors included in the algorithm are medication history, fracture history, ketogenic diet, ambulation status, history of endocrinopathy, and pubertal stage.BMD levels are measured using dual-energy x-ray absorptiometry scans. Once a patient is identified as having decreased BMD several treatment options are available. BMD can be increased through stander use, diet, and bisphosphonate treatment. This paper serves as a summary of the current ways in which children with CP are assessed at each visit, as well as how to treat low BMD once it has been identified. Key Concepts: (1) Explain the algorithm used to identify patients at risk for decreased BMD. (2) Review how to assess patients with decreased BMD. (3) Summarize treatment recommendations to increase BMD in children with CP.

Abstract There is a marked disparity in the state of knowledge of Holartic x Neotropical species of the freshwater snail family Physidae; the incipiency of data on Neotropical physids reflecting the lower number of dedicated specialists. The gaps in the knowledge on Neotropical physids have led to historical uncertainty about species validity. Revisiting the species is essential to reduce taxonomic impediment and delineating their probable distribution is the first step to attain this purpose. We aimed at critically analyze occurrence records of South American physids, compiled through an intensive search in the literature, biodiversity and molecular databases. We present a provisional characterization of the distribution of this family in South America, considering the probable versus the poorly documented distribution of the species. The critical underrepresentation of South American physids in collections, molecular databases and literature reinforces the role of taxonomic impediment in delaying the advance of the knowledge on species diversity. Malacological collections represented the main source of records, evidencing the relevance of unpublished data associated to specimens to assess distributional information on neglected groups. As most of the species are represented by shells, the reassessment of species identity and distribution must be done, using molecular and anatomical criteria for species delimitation.

A recently introduced national policy in China, "Opinions on Promoting the Rotation of Principals and Teachers in Compulsory Education Schools within the County/District," mandates teacher mobility between urban and rural areas, thereby ensuring a more equitable distribution of human resources. This study investigated a key but understudied issue in the Chinese school system: factors influencing teachers' willingness to move. A survey questionnaire was distributed among 650 teachers in urban areas, since they are considered as more experienced, prepared, and qualified than their rural peers. Data were analysed using the chi-square test, Spearman and Pearson correlation analyses, and binary logistic regression analysis. Results showed significant differences in teachers' willingness to move, based on their teaching experiences, family status, and professional titles. The social responsibility of promoting educational equality and expectations of professional development encourage mobility, while familial obligations and adaptability concerns discourage them. The findings provide insight into the implementation of a policy compelling teachers to serve in unfamiliar settings and emphasize the necessity of appropriate physical, psychological, and professional support to encourage such mobility.

This paper explores how teacher leaders enact leadership practice across a regional learning network, Master Teacher Studios, an officially initiated teacher learning program in Shanghai. It investigates the leadership strategies that are employed for cross-boundary endeavors in the network. The concepts of "boundary" and "boundary crossing," as expounded by Wenger and others, are used to guide an examination of the process of teacher leadership enactment across a network, which is elucidated as interpreting the boundaries, selecting/designing boundary objects, and participating in communities of practice. The paper fosters an understanding of teacher leadership practice as boundary work in a network context, and delineates a process of teacher leadership enactment, as well as the importance of teacher leader identity in the process.

BackgroundAtopic dermatitis is known to be common among children, but there are few studies examining the epidemiology across the life course. In particular, there is a paucity of data on atopic dermatitis among older adults.ObjectiveTo evaluate participant characteristics, patterns of disease activity and severity, and calendar trends in older adult atopic dermatitis in comparison to other age groups in a large population-based cohort.MethodsThis was a cohort study of 9,154,936 individuals aged 0-99 years registered in The Health Improvement Network, a database comprised of electronic health records from general practices in the United Kingdom between 1994 and 2013. Atopic dermatitis was defined by a previously validated algorithm using a combination of at least one recorded atopic dermatitis diagnostic code in primary care and two atopic dermatitis therapies recorded on separate days. Cross-sectional analyses of disease prevalence were conducted at each age. Logistic mixed effect regression models were used to identify predictors of prevalent disease over time among children (0-17 years), adults (18-74 years), and older adults (75-99 years).ResultsPhysician-diagnosed atopic dermatitis was identified in 894,454 individuals with the following proportions in each age group: 18.3% of children, 7.7% of adults, and 11.6% of older adults. Additionally, atopic dermatitis prevalence increased across the 2-decade period (beta from linear regression test for trend in the change in proportion per year = 0.005, p = 0.044). In older adults, atopic dermatitis was 27% less common among females (adjusted OR 0.73, 95% CI 0.70-0.76) and was more likely to be active (59.7%, 95% CI 59.5-59.9%) and of higher severity (mean annual percentage with moderate and severe disease: 31.8% and 3.0%, respectively) than in other age groups.ConclusionIn a large population-based cohort, the prevalence of physician-diagnosed atopic dermatitis has increased throughout adulthood and was most common among males age 75 years and above. Compared to children ages 0-17 and adults ages 18-74, older adult atopic dermatitis was more active and severe. Because the prevalence of atopic dermatitis among older adults has increased over time, additional characterization of disease triggers and mechanisms and targeted treatment recommendations are needed for this population.

Teacher resilience is regarded as a professional attribute that enables school teachers to cope with adversities in their work life in order to sustain continuous professional development. This paper aims to investigate the development of resilience among novice teachers in a primary school in rural China from a social ecological perspective. It attempts to trace the developmental paths of resilience among Chinese teachers working in an economically deprived area, and to elucidate their trials and tribulations as interactions with different social ecosystems affect the growth of their resilience. The paper's findings suggest that novice teachers working in rural education in China have to deal with context-specific adversities that are shaped by educational tradition and school reform. Accordingly, the resilience development of novice teachers follows three discernible pathways, which lead to different capabilities. In the process, the interplay of multifaceted situational factors and the interaction among different ecosystems yield a range of cumulative influences on their resilience development.

Mitral valve (MV) tissue engineering is still in its early stage, and one major challenge in MV tissue engineering is to identify appropriate scaffold materials. With the potential of acellular MV scaffolds being demonstrated recently, it is important to have a full understanding of the biomechanics of the native MV components and their acellular scaffolds. In this study, we have successfully characterized the structural and mechanical properties of porcine MV components, including anterior leaflet (AL), posterior leaflet (PL), strut chordae, and basal chordae, before and after decellularization. Quantitative DNA assay showed more than 90% reduction in DNA content, and Griffonia simplicifolia (GS) lectin immunohistochemistry confirmed the complete lack of porcine α-Gal antigen in the acellular MV components. In the acellular AL and PL, the atrialis, spongiosa, and fibrosa trilayered structure, along with its ECM constitutes, i.e., collagen fibers, elastin fibers, and portion of GAGs, were preserved. Nevertheless, the ECM of both AL and PL experienced a certain degree of disruption, exhibiting a less dense, porous ECM morphology. The overall anatomical morphology of the strut and basal chordae were also maintained after decellularization, with longitudinal morphology experiencing minimum disruption, but the cross-sectional morphology exhibiting evenly-distributed porous structure. In the acellular AL and PL, the nonlinear anisotropic biaxial mechanical behavior was overall preserved; however, uniaxial tensile tests showed that the removal of cellular content and the disruption of structural ECM did result in small decreases in maximum tensile modulus, tissue extensibility, failure stress, and failure strain for both MV leaflets and chordae.

PurposeTo assess safety and tolerability of a subconjunctival penciclovir implant in cats infected with feline herpesvirus type 1 (FHV-1).MethodsSubconjunctival blank (n = 4 cats) or penciclovir-impregnated (n = 6) silicone implants were placed bilaterally in 10 normal, FHV-1-naive cats 7-8 days before viral inoculation. Outcomes included disease score, FHV-1 serology, conjunctival viral load, Schirmer tear tests (STT), tear film break-up times (TFBUTs), conjunctival histology, goblet cell density (GCD), body weight, tear and plasma penciclovir concentration, and corneal ulcer evaluation.ResultsBoth groups had similar clinical and histologic disease scores, STT values, TFBUTs, GCD, FHV-1 titers, viral loads, and body weight changes. No ocular or systemic signs of toxicity were noted. Tear penciclovir concentration varied widely among cats and across time points. Tear penciclovir concentrations exceeded the lowest published half maximal inhibitory concentration (IC50) in 5/6 treated cats. Plasma penciclovir concentrations remained below 10 ng/mL. Cats with higher tear penciclovir concentrations at inoculation and/or time of peak disease had fewer corneal ulcers than cats in which tear penciclovir concentrations were inconsistent, low, or unrecordable.ConclusionsSubconjunctival blank and penciclovir-impregnated implants were well tolerated at the ocular surface and not associated with systemic toxicity, adverse effect, or appreciable plasma penciclovir concentrations. Tear penciclovir concentrations >IC50 were sometimes achieved, especially during burst release soon after implant placement. Further study is necessary to determine efficacy of locally delivered penciclovir when penciclovir concentration is consistently maintained above IC50. This will be especially useful in patients unable to receive systemic therapy.

Safely opening university campuses has been a major challenge during the COVID-19 pandemic. Here, the authors describe a program of public health measures employed at a university in the United States which, combined with other non-pharmaceutical interventions, allowed the university to stay open in fall 2020 with limited evidence of transmission.

Background: Upper cervical instability (UCI) is a potentially disabling complication of the connective tissue disorders hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders (hEDS/HSD). UCI can impact various neurological structures, including the brainstem, spinal cord, cranial nerves, and blood supply to and from the brain, resulting in complex neurological signs and symptoms in this population. The current study was an observational study applying recent expert consensus recommendations for physical therapy assessment and management of patients with UCI associated with hEDS/HSD. Methods: This was a retrospective observational study describing how the clinical decision-making model was used to screen, examine, and treat three patients with highly irritable hEDS/HSD-related UCI, resulting in complex neurological presentation. The treatment used a neuroplasticity approach, including proprioception and motor control training emphasizing patient education and biofeedback. Outcome measures tracked progress. Results: All patients started with significant disability associated with UCI. One patient returned to full function with intermittent flares that he was able to manage. The second patient continued to have mild-moderate irritability but returned to parenting responsibilities and full-time work. The third patient required cervical fusion and remained disabled but was better able to minimize flares. The number of initial red and yellow flags was associated with the final outcomes, suggesting that the decision-making model might be useful for predicting patient prognosis. Conclusion: This brief report applies recent recommendations for safely evaluating and managing hypermobility-related UCI and provides a first step in experimental studies to test both the assessment and physical therapy treatment approaches. [ABSTRACT FROM AUTHOR]

In late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China, ultimately leading to a global pandemic (1). Since January 2020, the United States has observed a dramatic [...]

Abstract PHY34 is a synthetic small molecule, inspired by a compound naturally occurring in tropical plants of the Phyllanthus genus. PHY34 was developed to have potent in vitro and in vivo anticancer activity against high grade serous ovarian cancer (HGSOC) cells. Mechanistically, PHY34 induced apoptosis in ovarian cancer cells by late-stage autophagy inhibition. Furthermore, PHY34 significantly reduced tumor burden in a xenograft model of ovarian cancer. In order to identify its molecular target/s, we undertook an unbiased approach utilizing mass spectrometry-based chemoproteomics. Protein targets from the nucleocytoplasmic transport pathway were identified from the pulldown assay with the cellular apoptosis susceptibility (CAS) protein, also known as CSE1L, representing a likely candidate protein. A tumor microarray confirmed data from mRNA expression data in public databases that CAS expression was elevated in HGSOC and correlated with worse clinical outcomes. Overexpression of CAS reduced PHY34 induced apoptosis in ovarian cancer cells based on PARP cleavage and Annexin V staining. Compounds with a diphyllin structure similar to PHY34 have been shown to inhibit the ATP6V0A2 subunit of V(vacuolar)-ATPase. Therefore, ATP6V0A2 wild-type and ATP6V0A2 V823 mutant cell lines were tested with PHY34, and it was able to induce cell death in the wild-type at 246 pM while the mutant cells were resistant up to 55.46 nM. Overall, our data demonstrate that PHY34 is a promising small molecule for cancer therapy that targets the ATP6V0A2 subunit to induce autophagy inhibition while interacting with CAS and altering nuclear localization of proteins.

Experts in symptomatic generalized joint hypermobility (S-GJH) agree that upper cervical instability (UCI) needs to be better recognized in S-GJH, which commonly presents in the clinic as generalized hypermobility spectrum disorder and hypermobile Ehlers-Danlos syndrome. While mild UCI may be common, it can still be impactful; though considerably less common, severe UCI can potentially be debilitating. UCI includes both atlanto-occipital and atlantoaxial instability. In the absence of research or published literature describing validated tests or prediction rules, it is not clear what signs and symptoms are most important for diagnosis of UCI. Similarly, healthcare providers lack agreed-upon ways to screen and classify different types or severity of UCI and how to manage UCI in this population. Consequently, recognition and management of UCI in this population has likely been inconsistent and not based on the knowledge and skills of the most experienced clinicians. The current work represents efforts of an international team of physical/physiotherapy clinicians and a S-GJH expert rheumatologist to develop expert consensus recommendations for screening, assessing, and managing patients with UCI associated with S-GJH. Hopefully these recommendations can improve overall recognition and care for this population by combining expertise from physical/physiotherapy clinicians and researchers spanning three continents. These recommendations may also stimulate more research into recognition and conservative care for this complex condition.