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Summary: Background: Vaccine co-administration can increase vaccination coverage. We assessed the safety, reactogenicity, and immunogenicity of concomitant administration of Ad26.COV2.S COVID-19 vaccine with seasonal influenza vaccines. Methods: This non-inferiority, Phase 3, randomised, double-blind study enrolled 859 healthy adults and was conducted between 02 November 2021 and 28 November 2022. Participants aged ≥18–64 years were randomised to receive a seasonal quadrivalent standard dose (SD) influenza vaccine (Afluria Quadrivalent, Seqirus) concomitantly with Ad26.COV2.S (Coad_SD) or placebo (0.9% NaCl; Control_SD) on Day 1 and placebo or Ad26.COV2.S on Day 29. Participants aged ≥65-years were randomised to the Coad_SD or Control_SD groups, or to Coad_HD or Control_HD groups that received a seasonal quadrivalent HD (high-dose) influenza vaccine (Fluzone High-Dose Quadrivalent, Sanofi Pasteur Inc) in the same schedules. The primary outcomes were haemagglutinin inhibition titres against the four influenza vaccine strains at Day 29, and SARS-CoV-2 Spike-specific antibodies at Day 29 in the Coad_SD group and Day 57 in the Control-SD group, with a non-inferiority margin (Control-SD group/Coad_SD group) of 1.5. Reactogenicity and safety were assessed in all participants (NCT05091307). Findings: Non-inferiority criteria for concomitant administration in the SD groups were met for SARS-CoV-2 Spike-specific antibodies (ratio 1.11, 95% CI 0.97–1.26) and haemagglutinin inhibition titres for all influenza strains (A/H3N2 1.23, 95% CI 1.05–1.45; B/Victoria 0.99, 95% CI 0.84–1.19; B/Yamagata, 1.03, 95% CI 0.88–1.21) except A/H1N1 (1.28, 95% CI 1.09–1.53) for which the upper limit of the 95% CI was >1.5. Concomitant administration of Ad26.COV2.S and SD influenza vaccine induced robust immune responses in terms of SARS-CoV-2 Spike-specific antibodies and haemagglutinin inhibition to all four influenza strains. Seroconversion and seroprotection rates against all influenza vaccine strains were comparable in the Coad and Control groups. Anti-Spike antibodies 28 days after receiving Ad26.COV2.S were similar whether administered with influenza vaccine or alone. Antibody responses persisted at least 6 months post-vaccination in all groups. The reactogenicity and safety profile following co-administration was consistent with the known safety profiles of the study vaccines. No safety concerns were identified. Coadministration was immunogenic and well tolerated in adults aged ≥65 years who received HD influenza vaccine. Interpretation: Co-administration of seasonal influenza vaccine with Ad26.COV2.S was immunogenic with an acceptable safety profile, supporting co-administration of these vaccines. Funding: Janssen Vaccines & Prevention BV and Biomedical Advanced Research and Development Authority.

Abstract Endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) is an established technique for lung cancer staging and the diagnosis of mediastinal diseases. Recently, the paradigm of EBUS guided mediastinal sampling with conventional cytology has shifted over to histology specimens through the use of cryobiopsy. This case series explores the novel technique, key enablers, and potential advantages of endoscopic ultrasound with bronchoscope‐guided transesophageal cryobiopsy (EUS‐B‐TEC). The findings of this case series suggest that EUS‐B‐TEC is a safe and valuable addition to the bronchoscopic procedural armamentarium. Further studies are warranted to validate the potential of EUS‐B‐TEC.

PurposeCurrent evidence supports the use of integrative oncology (IO) interventions in cancer supportive care. The demand for outpatient IO services in Hong Kong is expected to soar following the surge in cancer incidence due to population ageing. This study identified the factors influencing the delivery and utilisation of outpatient IO from local stakeholders’ perspectives and developed corresponding implementation strategies.MethodsThis study involved two sequential stages. First, with individual semi-structured interviews guided by the Theoretical Domains Framework (TDF), we explored stakeholders’ views on the barriers to and facilitators for implementing IO. Second, guided by a TDF-based qualitative data analysis of interview transcripts, we performed intervention mapping to develop Behaviour Change Wheel-based implementation strategies that may overcome the barriers and strengthen the facilitators.ResultsWe interviewed 31 stakeholders, including traditional Chinese medicine (TCM) practitioners (n = 8), biomedically-trained doctors (n = 7), nurses (n = 6), administrators (n = 4), caregivers (n = 4), and pharmacists (n = 2). The key local factors influencing outpatient IO are (1) lacking nursing and administrative workforce supporting IO service delivery, (2) lacking awareness of IO services among healthcare professionals, administrators, patients, and caregivers, and (3) lacking knowledge among healthcare professionals of herb–drug interaction and herbal toxicities.ConclusionWe recommended a multi-faceted implementation strategies package that included arranging funding to train, recruit, and retain nursing and administrative staff, devolving resources into promoting interprofessional collaborations and evidence on IO effectiveness and safety, integrating evidence on herb–drug interactions and herbal toxicities into automated electronic health record systems monitored by pharmacists with dual qualifications in TCM and conventional pharmacy.

Introduction Upper limb problems have a significant impact on the global population leading to pain and restricted joint mobility, ultimately impacting their quality of life. Traditional treatments, such as non-steroidal anti-inflammatory drugs and corticosteroids, often come with undesirable side effects, prompting patients to seek alternative therapies. In this trial, we hypothesise that soothing cream gel (SCG) will improve range of motion and chronic pain in the shoulder and elbow. The objective of this trial is to evaluate the efficacy of SCG in improving the range of motion and chronic pain in the shoulder and elbow.Methods and analysis A double-blinded, randomised, placebo-controlled trial is conducted to compare the effects of SCG and placebo gel. SCG contains Vitis vinifera essence, Melaleuca viridiflora essential oil, etc, and is manufactured according to Good Manufacturing Practice standards. The placebo gel will be processed with similar appearance, texture and scent but will lack active ingredients. 70 participants with upper limb problems will be recruited from four study sites, including clinical centres and a sport department at the Chinese University of Hong Kong (CUHK). Participants will be randomly assigned to either treatment group or placebo group for 2 weeks. Primary outcome will be the range of motion in the upper limb, assessed by a goniometer, to measure active flexion and abduction for the shoulder, and active flexion and extension for the elbow. The primary efficacy analyses will be based on the full analysis set following the intention-to-treat principle.Ethics and dissemination The trial has obtained approval from the joint CUHK–New Territories East Cluster (CRE-2023.142), and the patient enrolment commenced in July 2023. Written informed consent will be obtained from all participants prior to participation. Study results will be disseminated through publication in peer-reviewed journals and presentations at conference.Trial registration number NCT05799391.

Background: The Coronavirus disease 2019 (COVID-19) is the largest global epidemic in recent time. Chinese medicine has been recognized by the World Health Organization as an effective treatment for COVID-19, but there is still a lack of high-quality randomized, double-blind trials using placebo as the control to support its application, which may hinder its further promotion locally and internationally.Objectives: This study will evaluate the efficacy and safety of Yinqiao Powder-Maxing Ganshi Decoction with variation in relieving major symptoms of mild and moderate COVID-19 by telemedicine.Methods and design: This clinical study is a randomized, double-blind, placebo-controlled trial that applies telemedicine to evaluate the efficacy and safety of Yinqiao Powder-Maxing Ganshi Decoction in the treatment of mild and moderate COVID-19. Eligible subjects will be randomly divided into either treatment or placebo groups for up to 14 days after stratification according to age (A:18–49, B:50–65) and the number of vaccinations (a: ≥3 doses, b: ≤2 doses). The treatment group will receive Yinqiao Powder-Maxing Ganshi Decoction granules along with certain variation based on their symptoms, and the placebo group will receive the same amount of placebo granules. Subjects will be prescribed different additions based on their symptoms and pathogenesis at the inclusion. The oral temperature, oximeter, result of rapid antigen test and symptom score will be recorded by subjects until they have stopped the medication. Subjects are required to have follow-up assessment by video-conference on days 7, 14 and 35. The time for the body temperature returning to normal will be used as the primary outcome.Discussion: This trial will provide scientific evidence on the use of Yinqiao Powder-Maxing Ganshi Decoction for the treatment of COVID-19, and the results would help raise the awareness in Hong Kong and the international community on the use of Chinese herbal medicine for treating COVID-19.Clinical Trial Registration:clinicaltrials.gov, identifier NCT05787327.

Abstract The global high prevalence of COVID-19 is a major challenge for health professionals and patients. SARS-CoV-2 virus has four structural protein components: the spike protein, envelope protein, membrane protein, and nucleocapsid protein. The SARS-CoV-2 virus mutates predominantly in the spike proteins, whilst the other key viral components usually remain stable. Essentially the pathological functions of the SARS-CoV-2 virus on different cell types are still largely unknown. Previous studies have shown that the human oral cavity can potentially act as reservoir of the SARS-CoV-2 virus. However, the consequence of SARS-CoV-2 viral infection on human oral health has not been systematically examined. COVID-19 can cause severe oral mucosa lesions and is likely to be connected with poor periodontal conditions. Fibroblasts are the major cell type inside periodontal ligament (PDL) and express the SARS-CoV-2 receptor: Angiotensin-converting enzyme 2 (ACE2), whose expression level can increase upon bacterial infection hence potentially provide a direct route of SARS-CoV-2 infection to PDL fibroblasts. In this research, we aimed to study the pathogenicity of SARS-CoV-2 viral components on human fibroblasts. We found that by exposing to SARS-CoV-2, especially to the viral envelope and membrane proteins, the human periodontal fibroblasts could develop fibrotic pathogenic phenotypes, including hyperproliferation that was simultaneously induced with increased apoptosis and senescence. The fibrotic degeneration was mediated by a down-regulation of mitochondrial β-oxidation in the fibroblasts. Fatty acid β-oxidation inhibitor, etomoxir treatment could mirror the same pathological consequence on the cells, similar to SARS-CoV-2 infection. Our results therefore provide novel mechanistic insights into how SARS-CoV-2 infection can affect human periodontal health at the cell and molecular level with potential new therapeutic targets for COVID-19 induced fibrosis.

Abstract Background Chinese medicine (CM) modalities, including acupuncture and Chinese herbal medicine (CHM), are popular palliative interventions among patients with cancer, but further clinical research is required to assess their effectiveness and safety. Objective To prioritize top ten important CM clinical research questions from patients with cancer, cancer survivors and caregivers’ perspectives via a face‐to‐face prioritization workshop in Hong Kong. Methods A list of 25 CM clinical research questions for cancer palliative care, which were identified from existing systematic reviews (SRs) and overview of SRs, was presented to 17 participants (patients with cancer [n = 5], cancer survivors [n = 6] and caregivers [n = 6]). The participants were then invited to establish consensus on prioritizing top ten research questions. Results Among the top ten priorities, five (50%) focused on acupuncture and related therapies, while five (50%) were on CHM. The three most important research priorities were (i) manual acupuncture plus opioids for relieving pain; (ii) CHM for improving quality of life among patients receiving chemotherapy; and (iii) concurrent use of CHM plus loperamide for reducing stomatitis. Conclusion The top ten participant‐endorsed CM clinical research priorities for cancer palliative care can guide local researchers on future direction. They can also inform local research funders on patient‐centred allocation of limited funding. Under limited research funding, the most important co‐prioritized research question from professional and patient perspectives may be addressed first. Patient or Public Contribution Patients with cancer, cancer survivors and caregivers participated in conduct of the study to prioritize CM clinical research questions.

ObjectiveTo investigate the seasonal variation of disease onset and presentation in an ethno-geographically homogeneous cohort of patients with anti-MDA5 positive dermatomyositis (DM).MethodsThis was a multi-centered, retrospective cohort study. Adult Chinese anti-MDA5 positive DM patients were identified from the Hong Kong Myositis Registry and the Clinical Data Analysis and Reporting System from 2015 to 2020. Equal number of IIM patients without anti-MDA5 antibody were selected as controls. Line blot immunoassay was used to detect the autoantibodies. The onset of disease, presenting clinical features and subsequent complications were analyzed for any seasonality.ResultsA total of 110 patients with anti-MDA5 positive DM were studied. The mean age at diagnosis was 53.0 ± 12.3 years and the mean follow-up duration was 20.6 ± 23.1 months. Two third of the patients (66%) had the clinically amyopathic phenotype. Most patients (86%) had interstitial lung disease (ILD) and 42% developed rapidly progressive ILD (RP-ILD). The mortality was 40% and the commonest cause was RP-ILD. Chi-square test showed significantly less patients had symptom onset in July to September. However, no particular seasonal pattern was observed in the anti-MDA5 negative IIM controls. RP-ILD occurred more frequently in patients with disease onset in October to December. Anti-MDA5 positive DM patients with disease onset in warmer months (April to September) were more likely to have clinical muscle involvement.ConclusionApparent seasonal patterns were noted in our ethno-geographically identical anti-MDA5 positive DM patients, but not in IIM patients in general. Certain environmental factors, particularly infection, might be implicated.

This paper offers a synthesis on computing identity and the experiences of women and minoritized populations in computing and computer science in higher education. Examining computing identity and its role in the computing experiences of minoritized undergraduates can help us better understand ways to engage and support women and minoritized individuals in the computing field thus increasing participation and persistence of these groups in computing. In this article, we present a review of research literature on computing identity within the experiences of women and minoritized undergraduate students in computing. The research questions guiding this work are: (1) What research literature exists about computing identity?, (2) According to existing literature, what are the experiences of women and racially minoritized undergraduates in computing (e.g., persons who identify as Black, Hispanic/Latinx, Indigenous people)?, and (3) What theoretical frameworks are used to guide existing computing identity literature? Emergent themes include the need to focus on exposure to computing, persistence, career expectations, and engagement. While there is no consensus on a computer identity framework, there is research guided by social cognitive career theory, social identity theory, and practice theory. We conclude that computing identity, including its multiple conceptualizations, offers multiple opportunities for informing and broadening participation of minoritized populations in computing. Future research should include further conceptual exploration of computing identity.

Mouse incisor growth depends upon mesenchymal stromal cells (MSCs) and transit amplifying cells (TACs). Here the authors describe a distinct population of MSCs that is maintained by TACs through Dlk1 ligand and that contribute to MTACs and mesenchymal lineages including dental pulp and odontoblasts.

In 1937–38, Igor V. Sposobin and three co-authors at the Moscow Conservatory published Uchebnik garmonii [Harmony Textbook]. This was the first officially approved harmony textbook in the USSR, which came to be adopted as “the basic textbook for courses on harmony in the music schools of the Soviet Union” (Vladimir Protopopov, 1960). Characterized by its promulgation of the “scientifically based” theory of harmonic functions, this book was destined to be read by many more musicians in a foreign land. In 1955–56, Boris A. Arapov decreed at meetings held at the Central Conservatory of Music in China that the problem posed by the ethnicization of harmony should be solved by combining musical elements that are considered ethnically distinct with functional harmony. Wu Zuqiang, who had studied at the Moscow Conservatory in the 1950s before he headed the Central Conservatory in the 1980s, published a chapter from Uchebnik garmonii already in 1955. The first Chinese translation of the whole book by Zhu Shimin was then published in 1957–58. The book soon attained canonic status in China and has been used in virtually all Chinese music institutions up to the present day. It is listed in the entrance examination syllabi of selected conservatories and reputable music theorists have published model answers to the exercises it contains. This article investigates how the Chinese reception of Uchebnik garmonii diverges from the sources that had inspired Sposobin and his colleagues to compose it in the first place, and throws light on the far-reaching impacts and ramifications of Uchebnik garmonii in China. // 1937–38 publizierte Igor V. Sposobin gemeinsam mit drei Ko-Autoren Uchebnik garmonii [Lehrbuch der Harmonik] am Moskauer Konservatorium. Diese erste offiziell anerkannte Harmonielehre der UdSSR wurde zum “grundlegenden Lehrbuch für Harmonielehrekurse an Musikausbildungsstätten der Sowjetunion” (Vladimir Protopopov, 1960). Charakterisiert durch seine Verbreitung einer als “wissenschaftlich fundiert” erachteten Funktionstheorie, sollte das Buch noch von vielen weiteren Musiker*innen in einem anderen Land gelesen werden: Boris A. Arapov erklärte 1955–56 bei einer Konferenz am Zentralkonservatorium Beijing, dass das Problem einer “Ethnisierung” von Harmonik gelöst werden solle, indem musikalische Elemente, die als ethnisch different aufgefasst werden, mit Funktionsharmonik kombiniert werden. Wu Zuqiang, der in den 1950er Jahren am Moskauer Konservatorium studierte und in den 1980er Jahren dann Präsident des Beijinger Zentralkonservatoriums wurde, legte bereits 1955 die Übersetzung eines Kapitels aus Uchebnik garmonii vor, worauf 1957–58 dann die erste vollständige Übersetzung von Zhu Shimin folgte. Das Lehrbuch erhielt rasch einen kanonischen Status in China und ist in nahezu allen Musikinstitutionen des Landes bis zum heutigen Tag in Verwendung. Es ist in den Anforderungen zur Zulassungsprüfung und den Lehrplänen einiger Konservatorien angeführt, und angesehene Musiktheoretiker haben Modelllösungen zu den Übungen des Buchs veröffentlicht. Dieser Beitrag untersucht wie die chinesische Rezeption von Uchebnik garmonii sich von den Quellen entfernte, die Sposobin und seine Kollegen ursprünglich motiviert hatten, das Buch zu verfassen. Dadurch wird deutlich, welche weitreichenden und unvorhersehbaren Auswirkungen Uchebnik garmonii in China mit sich brachte.

Abstract Angelman syndrome (AS) is a genetic neurodevelopmental disorder, most commonly caused by deletion or mutation of the maternal allele of the UBE3A gene, with behavioral phenotypes and seizures as key features. Currently no treatment is available, and therapeutics are often ineffective in controlling AS-associated seizures. Previous publications using the Ube3a maternal deletion model have shown behavioral and seizure susceptibility phenotypes, however findings have been variable and merit characterization of electroencephalographic (EEG) activity. In this study, we extend previous studies comparing the effect of genetic background on the AS phenotype by investigating the behavioral profile, EEG activity, and seizure threshold. AS C57BL/6J mice displayed robust behavioral impairments, spontaneous EEG polyspikes, and increased cortical and hippocampal power primarily driven by delta and theta frequencies. AS 129 mice performed poorly on wire hang and contextual fear conditioning and exhibited a lower seizure threshold and altered spectral power. AS F1 hybrid mice (C57BL/6J × 129) showed milder behavioral impairments, infrequent EEG polyspikes, and fewer spectral power alterations. These findings indicate the effect of common genetic backgrounds on the Ube3a maternal deletion behavioral, EEG, and seizure threshold phenotypes. Our results will inform future studies on the optimal strain for evaluating therapeutics with different AS-like phenotypes.

In vitro and in vivo research based on cell lines and animals are likely to be insufficient in elucidating authentic biological and physiological phenomena mimicking human systems, especially for generating pre-clinical data on targets and biomarkers. There is an obvious need for a model that can further bridge the gap in translating pre-clinical findings into clinical applications. We have previously generated a model of in vitro differentiated human nasal epithelial cells (hNECs) which elucidated the nasal-initiated repertoire of immune responses against respiratory viruses such as influenza A virus and rhinovirus. To assess their clinical utility, we performed a microarray analysis of influenza virus-infected hNECs to elucidate nasal epithelial-initiated responses. This was followed by a metagenomic analysis which revealed transcriptomic changes comparable with clinical influenza datasets. The primary target of influenza infection was observed to be the initiator of innate and adaptive immune genes, leaning toward type-1 inflammatory activation. In addition, the model also elucidated a down-regulation of metabolic processes specific to the nasal epithelium, and not present in other models. Furthermore, the hNEC model detected all 11 gene signatures unique to influenza infection identified from a previous study, thus supporting the utility of nasal-based diagnosis in clinical settings. In conclusion, this study highlights that hNECs can serve as a model for nasal-based clinical translational studies and diagnosis to unravel nasal epithelial responses to influenza in the population, and as a means to identify novel molecular diagnostic markers of severity.

Although mentoring interventions have helped to advance diversity, equity, and inclusion (DEI) goals within STEM fields, even the most efficacious programs can be undermined without intentional cultivation of the broader mentoring ecosystem. This study examines participants from eight campus teams that engaged in a multi-session process of learning about a STEM-mentoring ecosystem (STEM-ME) framework, learning particular terminology, including 'champions' and 'stewards' within the system (i.e. who is advocating for and resourcing mentoring, respectively), and tools to inventory, map and analyze their mentoring ecosystem. Qualitative research, guided by interpretive phenomenological analysis, focused on (a) completed inventory tools, (b) visual mapping exercises, and (c) field notes from meeting sessions. The results indicate that the STEM-ME framework and new terminology facilitated important insights into possible synergies within the system. The opportunity to visualize an institutional ecosystem for concentrations of and gaps in activity helped to identify potential vulnerabilities and places to invest.

Purpose: The purpose of this study was to examine the experiences of multiple campus teams as they engaged in the assessment of their science, technology, engineering and mathematics (STEM) mentoring ecosystems within a peer assessment dialogue exercise. Design/methodology/approach: This project utilized a qualitative multicase study method involving six campus teams, drawing upon completed inventory and visual mapping artefacts, session observations and debriefing interviews. The campuses included research universities, small colleges and minority-serving institutions (MSIs) across the United States of America. The authors analysed which features of the peer assessment dialogue exercise scaffolded participants' learning about ecosystem synergies and threats. Findings: The results illustrated the benefit of instructor modelling, intra-team process time and multiple rounds of peer assessment. Participants gained new insights into their own campuses and an increased sense of possibility by dialoguing with peer campuses. Research limitations/implications: This project involved teams from a small set of institutions, relying on observational and self-reported debriefing data. Future research could centre perspectives of institutional leaders. Practical implications: The authors recommend dedicating time to the institutional assessment of mentoring ecosystems. Investing in a campus-wide mentoring infrastructure could align with campus equity goals. Originality/value: In contrast to studies that have focussed solely on programmatic outcomes of mentoring, this study explored strategies to strengthen institutional mentoring ecosystems in higher education, with a focus on peer assessment, dialogue and learning exercises.

Summary: Background and aims: Salmonella infections remain a major public health problem in developing countries. The occurrence of infections caused by antimicrobial-resistant Salmonella has been on the rise complicating the available therapeutic options. The study aimed to determine the antibiograms and genotypes of prevalent Salmonella serotypes. Methods: A retrospective study involving 80 stool and extra-intestinal Salmonella strains collected over a 18-month period (January 2005–June 2006) from a tertiary hospital in Penang, Malaysia was conducted. Isolates were examined for resistance to 14 antimicrobial drugs and the clonality of the strains was determined by PFGE. Results: Twenty-one serotypes were identified, the most common being S. enteritidis (42.5%) followed by S. corvallis (11.25%) and S. braenderup (11.25%). S. enteritidis was significantly more common amongst the extra-intestinal isolates compared to stool isolates (74.2% versus 22.4%, p

A novel dedicated outdoor air system (DOAS) comprising a multi-stage direct expansion coil to produce extra-low temperature (XT) outdoor air to handle the entire space cooling demand has been confirmed more efficient than conventional systems. To further enhance the performance of XT-DOAS, the optimum number of cooling stages and treated outdoor air temperature need to be determined. This process requires the development of a coil performance model that takes into account the extra-high and extra-low entering air temperatures at the first and the last cooling stages. In this study, factory test data and field measurement data were used to develop such a performance model. Different statistical analyses were employed to validate the developed model. Based on the developed model, energy and exergy analyses were conducted to evaluate use of XT-DOAS for space cooling of a typical office building in Hong Kong. EnergyPlus was employed for the energy analysis. The laws of thermodynamics were used for the exergy analysis. Their combined results indicate that for better energy efficiency and performance for air-conditioning of office buildings in subtropical region, the optimum configuration for XT-DOAS is two cooling stages with a treated outdoor air temperature of 7 °C. The model developed and the energy and exergy analyses described will contribute significantly to future research in this area.

Health services research (HSR) seeks to shed light on healthcare as a system, focusing on the cost of, the quality of and access to health services. While there is recognition that the practice of medicine should be evidence-based, there has been limited progress in implementing evidence-based healthcare management. This review proposes a conceptual framework of putting HSR into practice through culture change; human capability capacity building and sustaining change via a supportive environment and reinforcing infrastructure

CD1d is a MHC I like molecule which presents glycolipid to natural killer T (NKT) cells, a group of cells with diverse but critical immune regulatory functions in the immune system. These cells are required for optimal defence against bacterial, viral, protozoan, and fungal infections, and control of immune-pathology and autoimmune diseases. CD1d is expressed on antigen presenting cells but also found on some non-haematopoietic cells. However, it has not been observed on bronchial epithelium, a site of active host defence in the lungs. Here, we identify for the first time, CD1D mRNA variants and CD1d protein expression on human bronchial epithelial cells, describe six alternatively spliced transcripts of this gene in these cells; and show that these variants are specific to epithelial cells. These findings provide the basis for investigations into a role for CD1d in lung mucosal immunity.

BACKGROUND:The cause of severe disease in some patients infected with pandemic influenza A virus is unclear. METHODOLOGY/PRINCIPAL FINDINGS:We present the cellular immunology profile in the blood, and detailed clinical (and post-mortem) findings of three patients with rapidly progressive infection, including a pregnant patient who died. The striking finding is of reduction in natural killer (NK) cells but preservation of activated effector CD8 T lymphocytes; with viraemia in the patient who had no NK cells. Comparison with control groups suggests that the reduction of NK cells is unique to these severely ill patients. CONCLUSION/SIGNIFICANCE:Our report shows markedly reduced NK cells in the three patients that we sampled and raises the hypothesis that NK may have a more significant role than T lymphocytes in controlling viral burden when the host is confronted with a new influenza A virus subtype.

Purpose: A draft guidance on tape stripping for assessing the bioavailability/bioequivalence of topical formulations was issued by the United States Food and Drug Administration in 1998 but has since been withdrawn. This was due to problems associated with the method and also inconsistencies and variability in the resulting data. The purpose of this study was to re-visit the tape stripping technique, incorporate refinements to reduce variability and validate the method using bioequivalence data obtained from the assessment of a topical corticosteroid cream containing 0.05% clobetasol propionate using the human skin-blanching assay. Methods: A pilot tape stripping study was conducted to establish the variability of the formulations.The bioequivalence of two different commercially available clobetasol propionate cream formulations and a clobetasol propionate ointment formulation were subsequently investigated using the tape stripping method. Results: The data from the pilot tape stripping study correlated well with data from the human skin-blanching assay. A subsequent pivotal tape stripping study confirmed bioequivalence between the two cream formulations whereas bio-inequivalence was demonstrated between the cream and ointment formulations.Conclusions: These studies show that the results from tape stripping concur with data from the human skin blanching assay and demonstrate the potential of a well-controlled tape stripping study as an option for the assessment of bioequivalence of topical corticosteroid formulations.

ABSTRACT - PURPOSE: The assessment of the degree of skin blanching following the application of a formulation containing a topical corticosteroid has been established as a surrogate method for the determination of bioequivalence of such topical preparations. Whereas initially the procedure involved visual assessment of the blanching response, an instrumental procedure using a chromameter was subsequently recommended as the method of choice in such evaluations. In this study, both visual and chromametric assessments have been carried out on two topical creams containing clobetasol propionate (0.05%) and the results from both methods are compared and discussed. METHODS: Human subjects (volunteers) were subjected to screening using a cream containing 0.05% clobetasol propionate, in order to identify appropriate subjects for inclusion in the study. Subsequently the study was implemented according to the FDA guidance using both visual and chromameter assessment techniques. Blanching responses were assessed visually by three trained, independent observers and instrumentally using a Chromameter. An ED50 of 36 min was used as the dose duration based upon data previously obtained from a pilot study using the same topical corticosteroid reference product. A visual rating scale of 0-4 and the a-scale readings from the chromameter were used. RESULTS: The visual and chromameter blanching profiles showed similar blanching responses and corresponded well with each other. The 90% confidence interval for the visual and chromameter data were calculated using Lock's method and when only the data obtained from 23 subjects who were identified as "detectors" (according to the FDA guidance) were used, the products fell within the bioequivalence acceptance range of 80-125% using the visual assessment method (99.3-111.6%) whereas the data using a chromameter (86.5-129.3%) were just outside the acceptance limits. However, when all subjects (n=34) were included in the calculations, both the visual (97.9-109.2) and chromameter (90.2-120.7) data fell within the acceptance range for the declaration of bioequivalence.CONCLUSIONS: Whereas visual data indicated bioequivalence using either data from "detectors" or data from all subjects, the chromameter data from "detectors" only indicated bioinequivalence but inclusion of all subject data fell within the acceptance range to be declared bioequivalent.

Angelman syndrome (AS) is a neurodevelopmental disorder with unique behavioral phenotypes, seizures, and distinctive electroencephalographic (EEG) patterns. Recent studies identified motor, social communication, and learning and memory deficits in a CRISPR engineered rat model with a complete maternal deletion of the Ube3a gene. It is unknown whether this model recapitulates other aspects of the clinical disorder. We report here the effect of Ube3a maternal deletion in the rat on epileptiform activity, seizure threshold, and quantitative EEG. Using video-synchronized EEG (vEEG) monitoring, we assessed spectral power and epileptiform activity early postnatally through adulthood. While EEG power was similar to wild-type (WT) at 1.5 weeks postnatally, at all other ages analyzed, our findings were similar to the AS phenotype in mice and humans with significantly increased δ power. Analysis of epileptiform activity in juvenile and adult rats showed increased time spent in epileptiform activity in AS compared with WT rats. We evaluated seizure threshold using pentylenetetrazol (PTZ), audiogenic stimulus, and hyperthermia to provoke febrile seizures (FSs). Behavioral seizure scoring following PTZ induction revealed no difference in seizure threshold in AS rats, however behavioral recovery from the PTZ-induced seizure was longer in the adult group with significantly increased hippocampal epileptiform activity during this phase. When exposed to hyperthermia, AS rat pups showed a significantly lower temperature threshold to first seizure than WT. Our findings highlight an age-dependence for the EEG and epileptiform phenotypes in a preclinical model of AS, and support the use of quantitative EEG and increased δ power as a potential biomarker of AS.

While research has documented the tremendous success of graduate-level Bridge programs for boosting the numbers of minoritized students earning doctorates in science, technology, engineering, and mathematics (STEM) fields, less is understood about the challenges participants face along their graduate journey while participating in Bridge programs. Anzalduán concepts including "nepantla" frame minoritized STEM Bridge students' experiences. This study included interviews with 29 student participants (the majority of whom were African American or Latina/o/x1) and 19 faculty mentors or staff program coordinators drawn from five Bridge-to-the-Doctorate STEM programs. Participants described two key challenges: (a) othering by non-bridge peers and (b) intense scrutiny by faculty and staff. Findings show that the presence of Bridge programs alone does not disrupt traditional norms and practices in STEM fields. Implications are discussed for intentionally constructing graduate Bridge programs and supporting departments as they strive to improve inclusion and equity within graduate STEM education.