Food security status and cardiometabolic health by sex/gender and race/ethnicity among adults in the United States.

BACKGROUND: Minoritized racial/ethnic groups and women in the United States (US) are disproportionately burdened by food insecurity, which likely contributes to disparities in cardiovascular health (CVH). Disparities are projected to widen due to the worsening climate crisis that is straining the agricultural system including food supplies. Nonetheless, studies have not investigated the relationship between food security status and 'ideal' CVH in a large, nationally-representative and racially/ethnically diverse US sample. METHODS AND RESULTS: We investigated household food security status in relation to 'ideal' CVH among US adults (N = 157,001) using 2014-2018/2020 National Health Interview Survey data. Food security status was defined as very low, low, marginal, or high. A summed score of 4 health behaviors and 3 clinical factors totaling 7 different measures was dichotomized (yes/no) to assess modified 'ideal' CVH (mICVH). Using Poisson regression with robust variance, we estimated prevalence ratios (PRs) and 95% CIs of mICVH by household food security status. We stratified models by sex/gender and race/ethnicity. Very low food security prevalence was higher among non-Hispanic (NH)-Black (8.0%) compared to Hispanic/Latinx (5.1%), NH-White (3.1%) and NH-Asian (1.7%) adults. The association between very low versus high food security and mICVH was stronger among women (PR = 0.23 [95% CI: 0.17-0.31]) than men (PR = 0.48 [95% CI: 0.35-0.66]). Compared to NH-White adults with high food security, racially/ethnically minoritized groups with very low to high food security were generally less likely (range: [PRvery low = 0.25[95% CI: 0.14-0.44] - [PRhigh = 0.88 [95% CI: 0.79-0.97]) to meet mICVH criteria. CONCLUSIONS: Food insecurity was associated with lower mICVH prevalence and racially/ethnically minoritized groups were disproportionately burdened.

Evaluating spotted lanternfly (Hemiptera: Fulgoridae) infestation in the Northern Ohio Valley.

Lycorma delicatula White (spotted lanternfly; SLF) is an invasive pest insect threatening increased agricultural costs as it spreads rapidly westward across the United States. As such, surveying was conducted adjacent to the insect's westernmost quarantine area in 2021-2022 to support multi-state monitoring. Specifically, 2,077 visual and sticky-trap surveys were performed in 13 repeatedly surveyed plots strategically located near high-traffic roadways and rail-lines along the Ohio-West Virginia border. Sites were located in Jefferson (Ohio), Brooke (West Virginia), and Hancock (West Virginia) counties. Only one SLF was detected in 2021 (the third documented Ohio site containing SLF) in close proximity to a railway, consistent with rail-mediated dispersal trends recorded throughout the United States. Thirty-one SLF were captured in 2 Ohio sites in 2022, 30 of which were captured at the same railway site as in 2021. However, 1 of the 31 SLF was found in a plot on a university campus 1.25 km from the nearest railway, along with 10 additional specimens found in a follow-up visual survey of a neighboring woodlot. Failure to detect SLF at nearby survey plots nearer to the closest rail line and commuter parking lots suggests local unaided dispersal in a state with primarily train-mediated dispersal-mirroring trends in affected states with more established SLF populations. Data from this survey are valuable for establishing baselines and early-invasion patterns of SLF dispersal into Ohio, anticipating SLF expansion patterns in Ohio, and eventually contributing to improved SLF dispersal modeling in Ohio, the Midwest, and the United States.

Pharmacokinetics, Safety, and Efficacy of Ixekizumab in Chinese Patients with Moderate-to-Severe Plaque Psoriasis: A Phase 1, Single- and Multiple-Dose Study.

INTRODUCTION: We evaluated the pharmacokinetics (PK), safety, and efficacy of ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, in Chinese patients with moderate-to-severe psoriasis. METHODS: In this phase 1, multicenter, open-label study, adults (≥ 18 years) diagnosed with moderate-to-severe plaque psoriasis for ≥ 6 months involving ≥ 10% of their body surface area received ixekizumab 80 mg by subcutaneous injection and were observed for 20 weeks (single-dose phase) and then an initial dose of 160 mg followed by randomization (1:1) to 80 mg ixekizumab every 2 weeks (IXE Q2W) or every 4 weeks (IXE Q4W) for an 8-week treatment period (multiple-dose phase). RESULTS: The median time to maximum observed ixekizumab concentrations occurred 2-4 days after dosing and the geometric mean half-life was 15-16 days, after single (n = 12) and multiple (n = 29) doses. Approximately linear pharmacokinetics were observed between the 80 and 160 mg single doses. Steady-state systemic exposure to ixekizumab during a dosing interval was similar with the IXE Q2W and IXE Q4W regimens, with estimates of 224 µg·day/mL and 213 µg·day/mL for the area under the concentration-time curve from time 0 to 14 days post-dose and 0 to 28 days post-dose, respectively. Safety was consistent with the established safety profile of ixekizumab. At week 12 after multiple doses, the proportions of patients achieving a 75% or 90% improvement in Psoriasis Area and Severity Index score were 100% and 86% for IXE Q2W, respectively, and 93% and 80% for IXE Q4W, respectively. A Static Physician's Global Assessment score of 0 or 1 was achieved in 100% and 87% with IXE Q2W and IXE Q4W, respectively. CONCLUSIONS: The PK of ixekizumab in Chinese patients with moderate-to-severe plaque psoriasis was comparable to findings in global populations. After IXE Q2W or IXE Q4W for 12 weeks, clinically relevant treatment responses and an acceptable safety profile were observed. TRIAL REGISTRATION: Clinicaltrials.gov (NCT03073213).

Triple Synchronous Primary Melanomas in a 77-Year-Old Sea Captain: Importance of Total Skin Examination.

When it comes to skin diseases, melanomas are considered the most lethal. Triple synchronous primary melanomas (SPMs) are rare. Here we have reported a case of a 77-year-old white male with three SPMs. The patient presented with a nodular melanoma in the upper left back; total skin examination (TSE) revealed additional melanomas in the right retroauricular region and on the left arm. The patient was unaware of these two additional melanomas that were only found because of the routine TSE, and the index lesion focused examination would have missed both. We advocate that TSE should be practised routinely by all dermatologists for all new patients, and also, from time to time in patients attending long-term follow-up appointments. Early diagnosis means simpler treatments and more favourable outcomes.

Food security status and cardiometabolic health among pregnant women in the United States.

Introduction: Pregnant women and their offspring are particularly vulnerable to food insecurity and its adverse effects during critical periods of fetal development. Racially/ethnically minoritized women in the United States (US) who are pregnant are additionally burdened by food insecurity, which may exacerbate cardiovascular health (CVH) disparities. Despite heightened social vulnerability, few studies have employed an intersectional framework, including race and gender, to assess the food insecurity and CVH relationship. Methods: We used 2012-2018 and 2020 National Health Interview Survey data among US pregnant women aged 18-49 years old (N = 1,999) to assess the prevalence of food insecurity status by race/ethnicity and to investigate household food security status in relation to ideal CVH, using a modified ideal CVH (mICVH) metric. We categorized food security status as "very low/low", "marginal", or "high". To assess mICVH, a summary score of 7 clinical characteristics and health behaviors was dichotomized as yes [(7)] vs. no [<7]. Prevalence ratios (PRs) and 95% confidence intervals (CIs) of associations between food security status and mICVH were estimated using Poisson regression with robust variance. Models were adjusted for age, household income, educational attainment, geographic region, marital status, alcohol consumption, survey year, and race/ethnicity (in overall model). Results: The mean age ± standard error was 29.0 ± 0.2 years. Among pregnant women, 12.7% reported "very low/low", 10.6% reported "marginal", and 76.7% reported "high" food security. "Very low/low" food security prevalence was higher among NH-Black (16.2%) and Hispanic/Latina (15.2%) pregnant women compared to NH-White (10.3%) and NH-Asian (3.2%) pregnant women. The mICVH prevalence was 11.6% overall and 14.5% for NH-White, 4.1% for NH-Black, 5.0% for Hispanic/Latina, and 26.7% for NH-Asian pregnant women. Among all pregnant women, "very low/low" and "marginal" vs. "high" food security status was associated with a lower prevalence of mICVH {[PRvery low/low = 0.26 (95% CI: 0.08-0.75)]; [PRmarginal = 0.47 (95% CI: 0.23 -0.96)]}. Conclusion: Household food insecurity was higher among pregnant women in minoritized racial/ethnic groups and was associated with lower mICVH prevalence. Given the higher burden of food insecurity among minoritized racial/ethnic groups, food security may be an important intervention target to help address disparities in poor CVH among pregnant women.

Toward Soft Wearable Strain Sensors for Muscle Activity Monitoring.

The force-generating capacity of skeletal muscle is an important metric in the evaluation and diagnosis of musculoskeletal health. Measuring changes in muscle force exertion is essential for tracking the progress of athletes during training, for evaluating patients' recovery after muscle injury, and also for assisting the diagnosis of conditions such as muscular dystrophy, multiple sclerosis, or Parkinson's disease. Traditional hardware for strength evaluation requires technical training for operation, generates discrete time points for muscle assessment, and is implemented in controlled settings. The ability to continuously monitor muscle force without restricting the range of motion or adapting the exercise protocol to suit specific hardware would allow for a richer dataset that can help unlock critical features of muscle health and strength evaluation. In this paper, we employ wearable, ultra-sensitive soft strain sensors for tracking changes in muscle deformation during contractions. We demonstrate the sensors' sensitivity to isometric contractions, as well as the sensors' capacity to track changes in peak torque over the course of an isokinetic fatiguing protocol for the knee extensors. The wearable soft system was able to efficiently estimate peak joint torque reduction caused by muscle fatigue (mean NRMSE = 0.15±0.03 ).

Ixekizumab Citrate-Free Formulation: Results from Two Clinical Trials.

INTRODUCTION: Subcutaneous (SC) injection is a common route of drug administration; however, injection site pain (ISP) might create a negative patient experience. We evaluated ISP, bioequivalence, and overall safety of the citrate-free (CF) formulation of ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A. METHODS: Two phase 1, single-blind studies were conducted in healthy participants. The crossover study A (NCT03848403) evaluated pain intensity on injection as measured by visual analog scale of pain (VAS) scores. Subjects (N = 70) were randomized 1:1:1 at the beginning to three possible treatment sequences and received a 1 mL SC injection of the three formulations sequentially in the abdomen on days 1, 8, and 15, respectively. A mixed-effects repeated measures analysis model was used to analyze VAS score by time post-injection. Study B (NCT04259346) evaluated the bioequivalence of a single 80 mg dose of CF formulation compared to the original commercial formulation. Subjects (N = 245) were randomized 1:1 to either commercial or CF formulation and received a single SC injection into the abdomen, arm, or thigh. RESULTS: Primary endpoint was achieved in both studies. In study A, least-squares mean (LSM) difference of VAS scores immediately post injection between commercial (n = 61) and CF formulation (n = 63) was - 21.7 (p < 0.0001), indicating a lower degree of pain associated with CF formulation. In study B, bioequivalence of the CF formulation was established as 90% CIs for the ratio of geometric LSM AUC0-tlast, AUC0-∞, and Cmax between treatments were contained within the prespecified limits of 0.8 and 1.25. Except for less ISP in the CF formulation, overall safety profile was comparable. CONCLUSION: Ixekizumab CF formulation proved to be bioequivalent, was associated with less ISP, and had no other notable differences in the safety profile compared to the original commercial formulation. TRAIL REGISTRATION: ClinicalTrials.gov identifier NCT03848403, NCT04259346.

Image-Guided Magnetic Thermoseed Navigation and Tumor Ablation Using a Magnetic Resonance Imaging System.

Medical therapies achieve their control at expense to the patient in the form of a range of toxicities, which incur costs and diminish quality of life. Magnetic resonance navigation is an emergent technique that enables image-guided remote-control of magnetically labeled therapies and devices in the body, using a magnetic resonance imaging (MRI) system. Minimally INvasive IMage-guided Ablation (MINIMA), a novel, minimally invasive, MRI-guided ablation technique, which has the potential to avoid traditional toxicities, is presented. It comprises a thermoseed navigated to a target site using magnetic propulsion gradients generated by an MRI scanner, before inducing localized cell death using an MR-compatible thermoablative device. The authors demonstrate precise thermoseed imaging and navigation through brain tissue using an MRI system (0.3 mm), and they perform thermoablation in vitro and in vivo within subcutaneous tumors, with the focal ablation volume finely controlled by heating duration. MINIMA is a novel theranostic platform, combining imaging, navigation, and heating to deliver diagnosis and therapy in a single device.

Importance of Preserved Tricuspid Valve Function for Effective Soft Robotic Augmentation of the Right Ventricle in Cases of Elevated Pulmonary Artery Pressure.

PURPOSE: In clinical practice, many patients with right heart failure (RHF) have elevated pulmonary artery pressures and increased afterload on the right ventricle (RV). In this study, we evaluated the feasibility of RV augmentation using a soft robotic right ventricular assist device (SRVAD), in cases of increased RV afterload. METHODS: In nine Yorkshire swine of 65-80 kg, a pulmonary artery band was placed to cause RHF and maintained in place to simulate an ongoing elevated afterload on the RV. The SRVAD was actuated in synchrony with the ventricle to augment native RV output for up to one hour. Hemodynamic parameters during SRVAD actuation were compared to baseline and RHF levels. RESULTS: Median RV cardiac index (CI) was 1.43 (IQR, 1.37-1.80) L/min/m2 and 1.26 (IQR 1.05-1.57) L/min/m2 at first and second baseline. Upon PA banding RV CI fell to a median of 0.79 (IQR 0.63-1.04) L/min/m2. Device actuation improved RV CI to a median of 0.87 (IQR 0.78-1.01), 0.85 (IQR 0.64-1.59) and 1.11 (IQR 0.67-1.48) L/min/m2 at 5 min (p = 0.114), 30 min (p = 0.013) and 60 (p = 0.033) minutes respectively. Statistical GEE analysis showed that lower grade of tricuspid regurgitation at time of RHF (p = 0.046), a lower diastolic pressure at RHF (p = 0.019) and lower mean arterial pressure at RHF (p = 0.024) were significantly associated with higher SRVAD effectiveness. CONCLUSIONS: Short-term augmentation of RV function using SRVAD is feasible even in cases of elevated RV afterload. Moderate or severe tricuspid regurgitation were associated with reduced device effectiveness.

Remote and Selective Control of Astrocytes by Magnetomechanical Stimulation.

Astrocytes play crucial and diverse roles in brain health and disease. The ability to selectively control astrocytes provides a valuable tool for understanding their function and has the therapeutic potential to correct dysfunction. Existing technologies such as optogenetics and chemogenetics require the introduction of foreign proteins, which adds a layer of complication and hinders their clinical translation. A novel technique, magnetomechanical stimulation (MMS), that enables remote and selective control of astrocytes without genetic modification is described here. MMS exploits the mechanosensitivity of astrocytes and triggers mechanogated Ca2+ and adenosine triphosphate (ATP) signaling by applying a magnetic field to antibody-functionalized magnetic particles that are targeted to astrocytes. Using purpose-built magnetic devices, the mechanosensory threshold of astrocytes is determined, a sub-micrometer particle for effective MMS is identified, the in vivo fate of the particles is established, and cardiovascular responses are induced in rats after particles are delivered to specific brainstem astrocytes. By eliminating the need for device implantation and genetic modification, MMS is a method for controlling astroglial activity with an improved prospect for clinical application than existing technologies.

Skeletal muscle regeneration with robotic actuation-mediated clearance of neutrophils.

Mechanical stimulation (mechanotherapy) can promote skeletal muscle repair, but a lack of reproducible protocols and mechanistic understanding of the relation between mechanical cues and tissue regeneration limit progress in this field. To address these gaps, we developed a robotic device equipped with real-time force control and compatible with ultrasound imaging for tissue strain analysis. We investigated the hypothesis that specific mechanical loading improves tissue repair by modulating inflammatory responses that regulate skeletal muscle regeneration. We report that cyclic compressive loading within a specific range of forces substantially improves functional recovery of severely injured muscle in mice. This improvement is attributable in part to rapid clearance of neutrophil populations and neutrophil-mediated factors, which otherwise may impede myogenesis. Insights from this work will help advance therapeutic strategies for tissue regeneration broadly.

Investigating the Effect of an Oxytetracycline Treatment on the Gut Microbiome and Antimicrobial Resistance Gene Dynamics in Nile Tilapia (Oreochromis niloticus).

Antibiotics play a vital role in aquaculture where they are commonly used to treat bacterial diseases. However, the impact of antibiotic treatment on the gut microbiome and the development of antimicrobial resistance in Nile tilapia (Oreochromis niloticus) over time remains to be fully understood. In this study, fish were fed a single treatment of oxytetracycline (100 mg/kg/day) for eight days, followed by a 14-day withdrawal period. Changes in the distal gut microbiome were measured using 16S rRNA sequencing. In addition, the abundance of antimicrobial resistance genes was quantified using real-time qPCR methods. Overall, the gut microbiome community diversity and structure of Nile tilapia was resilient to oxytetracycline treatment. However, antibiotic treatment was associated with an enrichment in Plesiomonas, accompanied by a decline in other bacteria taxa. Oxytetracycline treatment increased the proportion of tetA in the distal gut of fish and tank biofilms of the treated group. Furthermore, the abundance of tetA along with other tetracycline resistance genes was strongly correlated with a number of microbiome members, including Plesiomonas. The findings from this study demonstrate that antibiotic treatment can exert selective pressures on the gut microbiome of fish in favour of resistant populations, which may have long-term impacts on fish health.

Subcutaneous Injection Site Pain of Formulation Matrices.

PURPOSE: The objective of this work was to systematically evaluate the effects of formulation composition on subcutaneous injection site pain (ISP) using matrices comprising of common pharmaceutical excipients. METHODS: Two randomized, blinded, crossover studies in healthy subjects were conducted at a single site, where subjects received 1 mL SC injections of the buffer matrices. ISP intensity was measured using a 100 mm visual analogue scale (VAS), which was then analyzed via heatmap, categorical grouping, subgroup analysis, and paired delta analysis. RESULTS: Buffer type, buffer concentration and tonicity agent showed a substantial impact on ISP. Citrate buffer demonstrated a higher ISP than acetate buffer or saline). The 20 mM citrate buffer was more painful than 10 or 5 mM citrate buffers. NaCl and propylene glycol were significantly more painful than sugar alcohols (mannitol, sucrose, trehalose or glycerol). Histidine buffers exhibited ISP in the descending order of 150 mM > 75 mM > 25 mM > 0 mM NaCl, while histidine buffers containing Arginine-HCl at 0, 50, or 150 mM all showed very low ISP. Histidine buffer at pH 6.5 showed a lower ISP than pH 5.7. CONCLUSIONS: This systematic study via orthogonal analyses demonstrated that subcutaneous ISP is significantly influenced by solution composition.

Prevention of Pruritis following Spinal Morphine for Scheduled Cesarean Birth.

BACKGROUND: Intrathecal morphine provides effective analgesia after cesarean birth, yet up to 90% of women who receive it experience excessive itching, an undesirable dose-dependent effect. Pruritis may increase nursing workload, delay breastfeeding, and decrease patient satisfaction. When 0.1 mg spinal morphine is given, pruritis is markedly reduced while analgesia is preserved. PURPOSE: The purpose of this project was to determine possible causes and solutions for pruritus after cesarean birth. METHODS: Anesthesia providers were educated and encouraged to limit spinal morphine to 0.1 mg as a strategy to prevent pruritus. In a repeated measures design, the rate of treatment-required pruritus and opioid consumption were measured 24 hours after surgery. The project included an evaluation of 30 medical records before and 30 medical records after the project intervention. RESULTS: Preintervention rate of treatment-required pruritis was 37%, all received spinal morphine ≥ 1.5 mg. Postintervention rate of treatment-required pruritis was 13% and 57% after spinal morphine 0.1 mg and 0.2 mg, respectively. Opioid consumption was similar between groups. CLINICAL IMPLICATIONS: Mother-baby nurses can have an impact on the practice of anesthesia providers by advocating for evidence-based dosing of intrathecal morphine to reduce the incidence of pruritis while maintaining effective analgesia for women after cesarean birth.

Validation of the Overactive Bladder-Bladder Assessment Tool (OAB-BAT): A Potential Alternative to the Standard Bladder Diary for Monitoring OAB Outcomes.

BACKGROUND: An advisory board concluded that a new, comprehensive overactive bladder (OAB) patient-reported outcome (PRO) measure should be developed in accordance with regulatory guidelines. The OAB-Bladder Assessment Tool (OAB-BAT) was developed with qualitative input from OAB patients and experts to measure symptoms, bother, impacts, and satisfaction with treatment. OBJECTIVE: Psychometric evaluation of the OAB-BAT assessing PRO OAB symptoms, bother, and impacts during a 7-d recall period. DESIGN, SETTING, AND PARTICIPANTS: Psychometric testing was conducted for a 28-d observational study of 170 OAB patients. Eligibility criteria included clinician-confirmed OAB diagnosis with at least eight micturitions per day. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Assessments included the OAB-BAT, a 7-d bladder diary, and co-validating OAB PROs. Analysis included classical and modern test theories. A scoring algorithm was developed and psychometric properties were assessed. RESULTS AND LIMITATIONS: The majority of participants were women (72.4%) with moderate OAB symptom severity (53.5%). More than one-third of participants (34.1%) were incontinent. Responses were well balanced across bother and impact items, while symptom frequency items showed sparse responses. Analysis supported an eight-item unidimensional model based on bother and impacts. No items performed differently by gender or continence status. The OAB-BAT showed internal consistency (ω=0.918), retest reliability (two-way random intraclass correlation coefficient=0.81), and convergent validity with the OAB-q (r>0.4). Known groups showed the expected trend. Comparisons between OAB-BAT scores and components of the bladder diary showed a moderate effect size (r>0.4). CONCLUSIONS: The eight-item OAB-BAT with 7-d recall is valid and reliable as an OAB PRO measure. Structural modeling, balanced with content validity considerations, produced robust scores. The OAB-BAT is a useful addition to the clinical assessment of patients, designed to complement the use of bladder diaries for monitoring OAB outcomes, in clinical trial and clinical practice environments. Future studies will need to assess the treatment satisfaction items in a larger sample of patients receiving OAB treatment. PATIENT SUMMARY: We tested a questionnaire designed to assess overactive bladder (OAB) symptoms, bother, satisfaction, and impacts by asking patients to complete it on a weekly basis. We found that the questionnaire accurately captures the symptoms and impacts that are most important to patients with OAB. We conclude that the questionnaire could be a useful instrument and, after further assessment in clinical practice and research, a possible alternative to a bladder diary in measuring OAB outcomes.

Comparative analysis of the lateral and posterolateral trajectories for fixation of the sacroiliac joint-a cadaveric study.

BACKGROUND: A number of minimally invasive sacroiliac (SI) joint fusion solutions for placing implants exist, with reduced post-operative pain and improved outcomes compared to open procedures. The objective of this study was to compare two MIS SI joint fusion approaches that place implants directly across the joint by comparing the ilium and sacrum bone characteristics and SI joint separation along the implant trajectories. METHODS: Nine cadaveric specimens (n = 9) were CT scanned and the left and right ilium and sacrum were segmented. The bone density, bone volume fraction, and SI joint gap distance were calculated along lateral and posterolateral trajectories and compared using analysis of variance between the two orientations. RESULTS: Iliac bone density, indicated by the mean Hounsfield Unit, was significantly greater for each lateral trajectory compared to posterolateral. The volume of cortical bone in the ilium was greater for the middle lateral trajectory compared to all others and for the top and bottom lateral trajectories compared to both posterolateral trajectories. Cortical density was greater in the ilium for all lateral trajectories compared to posterolateral. The bone fraction was significantly greater in all lateral trajectories compared to posterolateral in the ilium. No differences in cortical volume, cortical density, or cancellous density were found between trajectories in the sacrum. The ilium was significantly greater in density compared with the sacrum when compared irrespective of trajectory (p < 0.001). The posterolateral trajectories had a significantly larger SI joint gap than the lateral trajectories (p < 0.001). CONCLUSION: Use of the lateral approach for minimally invasive SI fusion allows the implant to interact with bone across a significantly smaller joint space. This interaction with increased cortical bone volume and density may afford better fixation with a lower risk of pull-out or implant loosening when compared to the posterolateral approach.

Pharmacokinetics, Safety, and Tolerability of Single- and Multiple-Dose Once-Daily Baricitinib in Healthy Chinese Subjects: A Randomized Placebo-Controlled Study.

The objective of this phase 1 study was to evaluate the pharmacokinetics, safety, and tolerability of baricitinib after single and multiple doses in healthy Chinese adults. Eligible subjects received a once-daily dose of baricitinib 2, 4, or 10 mg or placebo on day 1 (single dose) and days 4 through 10 for 7 consecutive days (multiple doses). Plasma pharmacokinetic samples were collected up to 48 hours after dosing on days 1 and 10, with predose samples collected before dosing on day 1 and days 4 through 10. Safety and tolerability were also assessed. Baricitinib was rapidly absorbed, reaching peak plasma concentrations within 0.5 to 1 hour (median). Plasma concentrations declined rapidly following the attainment of peak concentrations, with a mean terminal half-life of 5.7 to 7.3 hours. Steady-state plasma concentrations of baricitinib were achieved after the second day of once-daily dosing, with minimal accumulation of baricitinib in plasma (up to 10% increase in area under the plasma concentration-time curve). Single- and multiple-dose mean values for area under the plasma concentration-time curve from time zero to infinity and maximum plasma concentration appeared to increase in an approximately dose-proportional manner across the dose range. Single and multiple oral doses of once-daily baricitinib up to 10 mg were well tolerated by healthy Chinese subjects.

Young people's views on their role in the COVID-19 pandemic and society's recovery from it.

OBJECTIVE: There has been little formal exploration of how young people see their role in the COVID-19 pandemic. DESIGN/SETTING: Focus-group discussion with 15 Children's Hospital Young People's Forum members (23/5) to explore their perspective on the impact of COVID-19 on both their lives and those of their community, on school closures, and the role they wished to play in society's recovery from the pandemic. Audio recordings were transcribed verbatim using NVivo Software and analysed using an inductive thematic analysis approach. OUTCOME: Four major themes identified: (1) Awareness of pandemic's impact on others: participants showed mature awareness of the effects on broader society, especially the elderly, socially disadvantaged and parents. (2) Perceived impact on their own lives: principal concerns were the educational and practical repercussions of school closures and social isolation, including effects on educational prospects. (3) Views about school reopening: young people understood the broader rationale for school reopening and were generally positive about it, but expressed concerned about their safety and that of others. (4) Communication issues: a need for clear, concise, understandable information readily accessible for young people was expressed. Up to now, they felt passive recipients rather than participants. CONCLUSION: Young people were concerned about their future, their family and broader society, consistent with a high level of moral development. They want to be active participants in social recovery, including concepts around return to school but require appropriate information and a means by which their voices can be heard. The alternative suggested roles as pawns or pathfinders were discounted.

Cutaneous signs in COVID-19 patients: A review.

Coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily affects the epithelium of the airways. With the increasing involvement of dermatologist in management of this crisis, cutaneous symptoms gained more and more attention. In this review, we will describe cutaneous symptoms of patients of all ages in association with COVID-19. We will focus on such disorders that are caused by direct action of SARS-CoV-2 on tissues, complement, and coagulation system and on nonspecific eruption of the systemic viral infection. Drug-induced reactions are only mentioned in the differential diagnoses. Although more systematic investigations are warranted, it becomes clear that some symptoms are clinical signs of a milder COVID-19 course, while others are a red flag for a more severe course. Knowledge of the cutaneous manifestations of COVID-19 may help in early diagnosis, triage of patients, and risk stratification.

The role of the gut microbiome in sustainable teleost aquaculture.

As the most diverse vertebrate group and a major component of a growing global aquaculture industry, teleosts continue to attract significant scientific attention. The growth in global aquaculture, driven by declines in wild stocks, has provided additional empirical demand, and thus opportunities, to explore teleost diversity. Among key developments is the recent growth in microbiome exploration, facilitated by advances in high-throughput sequencing technologies. Here, we consider studies on teleost gut microbiomes in the context of sustainable aquaculture, which we have discussed in four themes: diet, immunity, artificial selection and closed-loop systems. We demonstrate the influence aquaculture has had on gut microbiome research, while also providing a road map for the main deterministic forces that influence the gut microbiome, with topical applications to aquaculture. Functional significance is considered within an aquaculture context with reference to impacts on nutrition and immunity. Finally, we identify key knowledge gaps, both methodological and conceptual, and propose promising applications of gut microbiome manipulation to aquaculture, and future priorities in microbiome research. These include insect-based feeds, vaccination, mechanism of pro- and prebiotics, artificial selection on the hologenome, in-water bacteriophages in recirculating aquaculture systems (RAS), physiochemical properties of water and dysbiosis as a biomarker.