Streamlining large-scale oceanic biomonitoring using passive eDNA samplers integrated into vessel's continuous pump underway seawater systems.

Passive samplers are enabling the scaling of environmental DNA (eDNA) biomonitoring in our oceans, by circumventing the time-consuming process of water filtration. Designing a novel passive sampler that does not require extensive sample handling time and can be connected to ocean-going vessels without impeding normal underway activities has potential to rapidly upscale global biomonitoring efforts onboard the world's oceanic fleet. Here, we demonstrate the utility of an artificial sponge sampler connected to the continuous pump underway seawater system as a means to enable oceanic biomonitoring. We compared the performance of this passive sampling protocol with standard water filtration at six locations during a research voyage from New Zealand to Antarctica in early 2023. Eukaryote metabarcoding of the mitochondrial COI gene revealed no significant difference in phylogenetic α-diversity between sampling methods and both methods delineated a progressive reduction in number of Zero-Radius Operational Taxonomic Units (ZOTUs) with increased latitudes. While both sampling methods revealed comparable trends in geographical community compositions, distinct clusters were identified for passive samplers and water filtration at each location. Additionally, greater variability between replicates was observed for passive samplers, resulting in an increased estimated level of replication needed to recover 90 % of the biodiversity. Furthermore, traditional water filtration failed to detect three phyla observed by passive samplers and extrapolation analysis estimated passive samplers recover a larger number of ZOTUs compared to water filtration for all six locations. Our results demonstrate the potential of this passive eDNA sampler protocol and highlight areas where this emerging technology could be improved, thereby enabling large-scale offshore marine eDNA biomonitoring by leveraging the world's oceanic fleet without interfering with onboard activities.

Can reproductive health services be used to screen for sexual and gender-based violence in post-conflict Northern Uganda? - a pilot study.

Background: Sexual and gender-based violence (SGBV), including rape and child sexual abuse, remains a significant challenge in post-conflict northern Uganda. Many victims have never sought help. Consequently, the scale of the problem is not known, and SGBV victims' injuries, both psychological and physical, remain hidden and unresolved. Objectives: We aimed to explore whether health workers in rural Reproductive Health Services (RHS), following specific training, could provide a valuable resource for SGBV screening and subsequent referral to targeted services. Methods: Our project had three elements. First, RHS workers were trained to use a questionnaire to screen subjects for past SGBV Second, the screening questionnaire was used by RHS workers over a 3-month period, and the data collected were analysed to explore whether the screening approach was an effective one in this setting, and to record the scale and nature of the problem. Third, victims detected were offered referral as appropriate to hospital services or to a dedicated SGBV ActionAid shelter. Results: Of 1656 women screened, 778 (47%) had suffered SGBV: 123 rape, and 505 non-sexual violence. 1,254 (76%) had been directly or indirectly affected by conflict experiences; 1066 had lived in internally displaced persons camps. 145 (9%) requested referral to Gulu SGBV Shelter; 25 attended the shelter and received assistance, and 20 others received telephone counselling. Conclusion: Undetected SGBV remains a significant problem in post-conflict northern Uganda. RHS workers, following specific training, can effectively screen for and identify otherwise unrecognised survivors of SGBV. This matters because without ongoing detection, survivors have no opportunity for resolution, healing or help.

Low-Intensity Pulsed Ultrasound Versus Sham in the Treatment of Operatively Managed Scaphoid Nonunions: The SNAPU Randomized Controlled Trial.

BACKGROUND: The primary goal after open reduction and internal fixation of an established scaphoid nonunion is to achieve union. Low-intensity pulsed ultrasound (LIPUS) has been reported to increase the rate of union and to decrease the time to union for multiple fractures and nonunions in clinical and animal models. The evidence for LIPUS in the treatment of scaphoid nonunion, however, is sparse. The aim of this study was to assess whether active LIPUS (relative to sham LIPUS) accelerates the time to union following surgery for scaphoid nonunion. METHODS: Adults with a scaphoid nonunion indicated for surgery were recruited for a multicenter, prospective, double-blinded randomized controlled trial. After surgery, patients self-administered activated or sham LIPUS units beginning at their first postoperative visit. The primary outcome was the time to union on serial computed tomography (CT) scans starting 6 to 8 weeks postoperatively. Secondary outcomes included patient-reported outcome measures, range of motion, and grip strength. RESULTS: A total of 142 subjects completed the study (69 in the active LIPUS group and 73 in the sham group). The average age was 27 years, and the cohort was 88% male. There was no difference in time to union (p = 0.854; hazard ratio, 0.965; 95% confidence interval, 0.663 to 1.405). Likewise, there were no differences between the active LIPUS and sham groups with respect to any of the secondary outcomes, except for wrist flexion at baseline (p = 0.008) and at final follow-up (p = 0.043). CONCLUSIONS: Treatment with LIPUS had no effect on reducing time to union in patients who underwent surgical fixation of established scaphoid nonunions. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Deucravacitinib onset of action and maintenance of response in phase 3 plaque psoriasis trials.

AIM: In the global phase 3 POETYK PSO-1 and PSO-2 trials, significantly greater proportions of deucravacitinib-treated patients met the coprimary endpoints (PASI 75, sPGA 0/1) at Week 16 versus placebo or apremilast-treated patients. This analysis evaluated onset of action and maintenance of response in patients randomized to deucravacitinib and placebo only. METHODS: Adults with moderate to severe plaque psoriasis at baseline were randomized 1:2:1 to oral placebo, deucravacitinib, or apremilast. Onset of action was determined through changes from baseline in mean PASI, BSA, BSA × sPGA, and DLQI. Maintenance of response was assessed using PASI 75, PASI 90, PASI 100, sPGA 0/1, and sPGA 0 response rates through Week 52 in patients who were treated continuously with deucravacitinib, crossed over from placebo to deucravacitinib at Week 16, or received deucravacitinib and achieved PASI 75 by Week 24. RESULTS: Deucravacitinib showed significantly higher increases in mean percent change from baseline in PASI versus placebo by Week 1. Significant improvement versus placebo was observed in all other efficacy measures by Week 8. Efficacy with deucravacitinib was maintained through Week 52. CONCLUSION: Deucravacitinib displayed efficacy as early as 1 week and clinical responses were maintained over 52 weeks in patients with moderate to severe plaque psoriasis.

Clinical Outcomes of Immune Checkpoint Inhibitors in Unique Cohorts Underrepresented in Clinical Trials.

Regulatory approval of immune checkpoint inhibitors (ICIs) was based on results of large, randomized clinical trials, resulting in limited outcomes data in patient cohorts typically underrepresented in such trials. The objective of this study was to evaluate the efficacy and safety of ICIs in these unique patient cohorts. This is a multicenter, retrospective analysis of real-world data at six academic and community clinics in the United States from 1 January 2011 to 1 April 2018. Patients were included if they had received at least one cycle of ICI treatment. Unique patient cohorts included age > 75 years, non-White race, positive smoking history, ECOG performance status (PS) ≥ 2, BMI ≥ 30 kg/m2, autoimmune diseases (AIDs), chronic viral infections (CVI), extensive prior lines of therapy (LOTs), or >three metastatic sites. Immune-related adverse events (irAEs), overall survival (OS), and time to treatment failure were evaluated in the entire cohort and in NSCLC patients treated with PD-(L)1 monotherapy. Outcomes and their association with unique patient cohorts were compared on univariate analysis and multivariate analysis to those without a particular characteristic in the entire NSCLC PD-(L)1 monotherapy cohorts. In total, 1453 patients were included: 56.5%-smokers, 30.4%-non-White, 22.8%-elderly, 20.8%-ECOG PS ≥ 2, 15.7%-history of AIDs, and 4.7%-history of CVI. The common ICIs were nivolumab (37.1%) and pembrolizumab (22.2%). Black patients, compared to White patients, experienced fewer irAEs (OR 0.54, p < 0.001). An ECOG PS of ≥2 (HR = 2.01, p < 0.001) and an increased number of previous LOTs were associated with poor OS (the median OS of 26.2 vs. 16.2 vs. 9.6 months for one vs. two vs. three prior LOTs, p < 0.001). The above results were confirmed in anti-PD-(L)1 monotherapy non-small cell lung cancer patients (n = 384). Overall, ICIs were safe and efficacious in these typically underrepresented patient cohorts. We noted ECOG PS ≥ 2 and an increased prior LOTs were associated with poor ICI efficacy, and Black patients, compared to White patients, experienced fewer irAEs.

Native ESI-MS and Collision-Induced Unfolding (CIU) of the Complex between Bacterial Elongation Factor-Tu and the Antibiotic Enacyloxin IIa.

Collision-induced unfolding (CIU) of protein ions, monitored by ion mobility-mass spectrometry, can be used to assess the stability of their compact gas-phase fold and hence provide structural information. The bacterial elongation factor EF-Tu, a key protein for mRNA translation in prokaryotes and hence a promising antibiotic target, has been studied by CIU. The major [M + 12H]12+ ion of EF-Tu unfolded in collision with Ar atoms between 40 and 50 V, corresponding to an Elab energy of 480-500 eV. Binding of the cofactor analogue GDPNP and the antibiotic enacyloxin IIa stabilized the compact fold of EF-Tu, although dissociation of the latter from the complex diminished its stabilizing effect at higher collision energies. Molecular dynamics simulations of the [M + 12H]12+ EF-Tu ion showed similar qualitative behavior to the experimental results.

Chemical mapping of xyloglucan distribution and cellulose crystallinity in cotton textiles reveals novel enzymatic targets to improve clothing longevity.

Pilling is a form of textile mechanical damage, forming fibrous bobbles on the surface of garments, resulting in premature disposal of clothing by consumers. However, our understanding on how the structural properties of the cellulosic matrix compliment the three-dimensional shape of cotton pills remains limited. This knowledge gap has hindered the development of effective 'pillase' technologies over the past 20 years due to challenges in balancing depilling efficacy with fabric integrity preservation. Therefore, the main focus here was characterising the role of cellulose and the hemicellulose components in cotton textiles to elucidate subtle differences between the chemistry of pills and fibre regions involved in structural integrity. State-of-the-art bioimaging using carbohydrate binding modules, monoclonal antibodies, and Leica SP8 and a Nikon A1R confocal microscopes, revealed the biophysical structure of cotton pills for the first time. Identifying regions of increased crystalline cellulose in the base of anchor fibres and weaker amorphous cellulose at dislocations in their centres, enhancing our understanding of current enzyme specificity. Surprisingly, pills contained a 7-fold increase in the concentration of xyloglucan compared to the main textile. Therefore, xyloglucan offers a previously undescribed target for overcoming this benefit-to-risk paradigm, suggesting a role for xyloglucanase enzymes in future pillase systems.

Tenecteplase versus alteplase for thrombolysis in patients selected by use of perfusion imaging within 4·5 h of onset of ischaemic stroke (TASTE): a multicentre, randomised, controlled, phase 3 non-inferiority trial.

BACKGROUND: Intravenous tenecteplase increases reperfusion in patients with salvageable brain tissue on perfusion imaging and might have advantages over alteplase as a thrombolytic for ischaemic stroke. We aimed to assess the non-inferiority of tenecteplase versus alteplase on clinical outcomes in patients selected by use of perfusion imaging. METHODS: This international, multicentre, open-label, parallel-group, randomised, clinical non-inferiority trial enrolled patients from 35 hospitals in eight countries. Participants were aged 18 years or older, within 4·5 h of ischaemic stroke onset or last known well, were not being considered for endovascular thrombectomy, and met target mismatch criteria on brain perfusion imaging. Patients were randomly assigned (1:1) by use of a centralised web server with randomly permuted blocks to intravenous tenecteplase (0·25 mg/kg) or alteplase (0·90 mg/kg). The primary outcome was the proportion of patients without disability (modified Rankin Scale 0-1) at 3 months, assessed via masked review in both the intention-to-treat and per-protocol populations. We aimed to recruit 832 participants to yield 90% power (one-sided alpha=0·025) to detect a risk difference of 0·08, with an absolute non-inferiority margin of -0·03. The trial was registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000243718, and the European Union Clinical Trials Register, EudraCT Number 2015-002657-36, and it is completed. FINDINGS: Recruitment ceased early following the announcement of other trial results showing non-inferiority of tenecteplase versus alteplase. Between March 21, 2014, and Oct 20, 2023, 680 patients were enrolled and randomly assigned to tenecteplase (n=339) and alteplase (n=341), all of whom were included in the intention-to-treat analysis (multiple imputation was used to account for missing primary outcome data for five patients). Protocol violations occurred in 74 participants, thus the per-protocol population comprised 601 people (295 in the tenecteplase group and 306 in the alteplase group). Participants had a median age of 74 years (IQR 63-82), baseline National Institutes of Health Stroke Scale score of 7 (4-11), and 260 (38%) were female. In the intention-to-treat analysis, the primary outcome occurred in 191 (57%) of 335 participants allocated to tenecteplase and 188 (55%) of 340 participants allocated to alteplase (standardised risk difference [SRD]=0·03 [95% CI -0·033 to 0·10], one-tailed pnon-inferiority=0·031). In the per-protocol analysis, the primary outcome occurred in 173 (59%) of 295 participants allocated to tenecteplase and 171 (56%) of 306 participants allocated to alteplase (SRD 0·05 [-0·02 to 0·12], one-tailed pnon-inferiority=0·01). Nine (3%) of 337 patients in the tenecteplase group and six (2%) of 340 in the alteplase group had symptomatic intracranial haemorrhage (unadjusted risk difference=0·01 [95% CI -0·01 to 0·03]) and 23 (7%) of 335 and 15 (4%) of 340 died within 90 days of starting treatment (SRD 0·02 [95% CI -0·02 to 0·05]). INTERPRETATION: The findings in our study provide further evidence to strengthen the assertion of the non-inferiority of tenecteplase to alteplase, specifically when perfusion imaging has been used to identify reperfusion-eligible stroke patients. Although non-inferiority was achieved in the per-protocol population, it was not reached in the intention-to-treat analysis, possibly due to sample size limtations. Nonetheless, large-scale implementation of perfusion CT to assist in patient selection for intravenous thrombolysis in the early time window was shown to be feasible. FUNDING: Australian National Health Medical Research Council; Boehringer Ingelheim.

The Training to Improve Dyspnoea Study- Patient Experiences of Using a High Frequency Airway Oscillating Device.

Introduction: The High Frequency Airway Oscillating device (HFAO) was developed to help patients with COPD feel less breathless through flow resistive respiratory muscle training and fixed rate oscillations. Previous work has demonstrated that this device can improve inspiratory muscle strength over and above a sham device. Both groups improved their breathlessness and preserved clinical benefits though there were no statistically significant differences seen over and above the sham device. It is important to understand patient perceptions of using a device and how this may influence their treatment and therefore a qualitative analysis was conducted to understand participant experiences of a HFAO device. Methods: This was an exploratory qualitative analysis involving participants recruited to the Training to Improve Dyspnoea (TIDe) study. Participants completed a satisfaction survey and were invited to take part in a focus group. Focus groups were conducted by a researcher independent to the randomised controlled trial. Data was analysed independently by two researchers using inductive thematic analysis, and themes/sub-themes were agreed jointly. Data is presented in themes and sub themes and triangulated with survey response data. Results: Fourteen participants were recruited to two focus groups (71% male, mean [SD] age 64[9] years). The key themes were patient selection, device use, and investment. Patient selection explores the disease characteristics, emotional impact and management of care. Device use explores the device prescription and usage, routine and lifestyle and effectiveness. Investment covers accessibility, understanding, benefits vs participation and overall perceptions of the device. Conclusion: This research demonstrates the complexity of device interventions and that key considerations should be given to patient selection, the device use itself and, the time and cost investment required for participants to successfully implement the device into daily life.

Relationship between Pulmonary Gas Exchange Function and Brain Uptake Dynamics Investigated with Hyperpolarized 129Xe MR Imaging and Spectroscopy in a Murine Model of Chronic Obstructive Pulmonary Disease.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is a complex multisystem disease associated with comorbidities outside the lungs. The aim of this study was to measure changes in metrics of pulmonary gas exchange function and brain tissue metabolism in a mouse model of COPD using hyperpolarized 129Xe (HP 129Xe) MRI/MR spectroscopy (MRS) and investigate the relationship between the metrics of lung and brain. METHODS: COPD phenotypes were induced in 15 mice by 6-week administration of cigarette smoke extract (CSE) and lipopolysaccharide (LPS). A separate negative control (NC) group was formed of 6 mice administered with saline for 6 weeks. After these 6-week administrations, the pulmonary gas exchange function parameter fD (%) and the rate constant, α (s-1), which are composed of the cerebral blood flow Fi and the longitudinal relaxation rate 1/T1i in brain tissue, were evaluated by HP 129Xe MRI/MRS. RESULTS: The fD of CSE-LPS mice was significantly lower than that of NC mice, which was in parallel with an increase in bronchial wall thickness. The α in the CSE-LPS mice decreased with the decrease of fD in contrast to the trend in the NC mice. To further elucidate the opposed trend, the contribution of T1i was separately determined by measuring Fi. The T1i in the CSE-LPS mice was found to correlate negatively with fD as opposed to the positive trend in the NC mice. The opposite trend in T1i between CSE-LPS and NC mice suggests hypoxia in the brain, which is induced by the impaired oxygen uptake as indicated by the reduced fD. CONCLUSION: This study demonstrates the feasibility of using HP 129Xe MRI/MRS to study pathological mechanisms of brain dysfunction in comorbidities with COPD.

Let-7 restrains an oncogenic epigenetic circuit in AT2 cells to prevent ectopic formation of fibrogenic transitional cell intermediates and pulmonary fibrosis.

Analysis of lung alveolar type 2 (AT2) progenitor stem cells has highlighted fundamental mechanisms that direct their differentiation into alveolar type 1 cells (AT1s) in lung repair and disease. However, microRNA (miRNA) mediated post-transcriptional mechanisms which govern this nexus remain understudied. We show here that the let-7 miRNA family serves a homeostatic role in governance of AT2 quiescence, specifically by preventing the uncontrolled accumulation of AT2 transitional cells and by promoting AT1 differentiation to safeguard the lung from spontaneous alveolar destruction and fibrosis. Using mice and organoid models with genetic ablation of let-7a1/let-7f1/let-7d cluster (let-7afd) in AT2 cells, we demonstrate prevents AT1 differentiation and results in aberrant accumulation of AT2 transitional cells in progressive pulmonary fibrosis. Integration of enhanced AGO2 UV-crosslinking and immunoprecipitation sequencing (AGO2-eCLIP) with RNA-sequencing from AT2 cells uncovered the induction of direct targets of let-7 in an oncogene feed-forward regulatory network including BACH1/EZH2 which drives an aberrant fibrotic cascade. Additional analyses by CUT&RUN-sequencing revealed loss of let-7afd hampers AT1 differentiation by eliciting aberrant histone EZH2 methylation which prevents the exit of AT2 transitional cells into terminal AT1s. This study identifies let-7 as a key gatekeeper of post-transcriptional and epigenetic chromatin signals to prevent AT2-driven pulmonary fibrosis.

Multi-Subunit Repair With the Nasolabial Burow's Advancement Flap.

AIM: We will describe the use of nasolabial Burow's advancement flaps (perialar crescentic advancements) to repair multi subunit defects of the nasal sidewall including the adjacent cheek, dorsum, tip, and ala without the need of additional flaps. METHODS: This retrospective single centre study analyzed 6 month postoperative photographs using the Manchester Scar scale. The operative technique is described in detail. RESULTS: Of 355 cases, 336 were available for analysis. The median Manchester Scar scale was 7 for both sidewall defects and multi-subunit defects. There were low rates of infection or necrosis. CONCLUSIONS: With the correct technique, the nasolabial Burow's advancement alone is suitable to repair even large multi-subunit defects involving the nasal sidewall, cheek, dorsum, tip, and ala with high-level aesthetic and functional results.

Global impacts of marine heatwaves on coastal foundation species.

With increasingly intense marine heatwaves affecting nearshore regions, foundation species are coming under increasing stress. To better understand their impacts, we examine responses of critical, habitat-forming foundation species (macroalgae, seagrass, corals) to marine heatwaves in 1322 shallow coastal areas located across 85 marine ecoregions. We find compelling evidence that intense, summer marine heatwaves play a significant role in the decline of foundation species globally. Critically, detrimental effects increase towards species warm-range edges and over time. We also identify several ecoregions where foundation species don't respond to marine heatwaves, suggestive of some resilience to warming events. Cumulative marine heatwave intensity, absolute temperature, and location within a species' range are key factors mediating impacts. Our results suggest many coastal ecosystems are losing foundation species, potentially impacting associated biodiversity, ecological function, and ecosystem services provision. Understanding relationships between marine heatwaves and foundation species offers the potential to predict impacts that are critical for developing management and adaptation approaches.

Longitudinal Quality of Life and Glycemic Outcomes of Total Pancreatectomy With Islet Autotransplantation in Children With Chronic Pancreatitis Followed in a Pediatric Multidisciplinary Pancreas Clinic.

BACKGROUND: Total pancreatectomy with islet autotransplantation (TPIAT) is a potentially curative treatment for patients with chronic pancreatitis (CP) refractory to medical and endoscopic therapies. Patients often receive the initial follow-up medical care at the surgery-performing center, but then may follow up closer to where they live. We sought to describe the characteristics and outcomes of pediatric patients who underwent TPIAT at a national surgical referral center and were subsequently followed at our regional subspecialty center, the Children's Hospital Colorado. METHODS: We performed a retrospective analysis of baseline and outcomes data for the 10 pediatric patients who underwent TPIAT from 2007 to 2020 and received follow-up care at our institution. RESULTS: All patients had a diagnosis of CP, and nine of 10 patients had an identified underlying genetic risk factor. Insulin usage was common immediately following TPIAT, but at 1 year of follow-up, five of nine patients (55.6%) were insulin-independent and nine of nine had an HbA1c below 6.5%. For the four patients on insulin 1 year after TPIAT, total daily insulin dose ranged from 0.06 to 0.71 units/kg/day. All patients who underwent mixed meal tolerance testing had a robust peak C-peptide response at 1 year. There were significant improvements in nausea, school/work absences, narcotic dependence, and pancreas-related hospital admissions 1 year after TPIAT. CONCLUSIONS: Patients followed at our center had long-term improvements with low-insulin usage, detectable C-peptide, and improved pancreatitis-related outcomes after TPIAT. Pediatric patients who undergo TPIAT can be successfully co-managed in conjunction with the original surgery-performing center.

Emergency umbilical hernia management: scoping review.

BACKGROUND: Umbilical hernias, while frequently asymptomatic, may become acutely symptomatic, strangulated or obstructed, and require emergency treatment. Robust evidence is required for high-quality care in this field. This scoping review aims to elucidate evidence gaps regarding emergency care of umbilical hernias. METHODS: EMBASE, MEDLINE and CENTRAL databases were searched using a predefined strategy until November 2023. Primary research studies reporting on any aspect of emergency umbilical hernia care and published in the English language were eligible for inclusion. Studies were excluded where emergency umbilical hernia care was not the primary focus and subsets of relevant data were unable to be extracted. Two independent reviewers screened abstracts and full texts, resolving disagreements by consensus or a third reviewer. Data were charted according to core concepts addressed by each study and a narrative synthesis was performed. RESULTS: Searches generated 534 abstracts, from which 32 full texts were assessed and 14 included in the final review. This encompassed 52 042 patients undergoing emergency umbilical hernia care. Most were retrospective cohort designs (11/14), split between single (6/14) and multicentre (8/14) with only one randomized trial. Most multicentre studies were from national databases (7/8). Themes arising included risk assessment (n = 4), timing of surgery (n = 4), investigations (n = 1), repair method (n = 8, four mesh versus suture; four laparoscopic versus open) and operative outcomes (n = 11). The most commonly reported outcomes were mortality (n = 9) and morbidity (n = 7) rates and length of hospital stay (n = 5). No studies included patient-reported outcomes specific to emergency umbilical hernia repair. CONCLUSION: This scoping review demonstrates the paucity of high-quality data for this condition. There is a need for randomized trials addressing all aspects of emergency umbilical hernia repair, with patient-reported outcomes.

Long-distance movement dynamics shape host microbiome richness and turnover.

Host-associated microbial communities are shaped by host migratory movements. These movements can have contrasting impacts on microbiota, and understanding such patterns can provide insight into the ecological processes that contribute to community diversity. Furthermore, long-distance movements to new environments are anticipated to occur with increasing frequency due to host distribution shifts resulting from climate change. Understanding how hosts transport their microbiota with them could be of importance when examining biological invasions. Although microbial community shifts are well-documented, the underlying mechanisms that lead to the restructuring of these communities remain relatively unexplored. Using literature and ecological simulations, we develop a framework to elucidate the major factors that lead to community change. We group host movements into two types-regular (repeated/cyclical migratory movements, as found in many birds and mammals) and irregular (stochastic/infrequent movements that do not occur on a cyclical basis, as found in many insects and plants). Ecological simulations and prior research suggest that movement type and frequency, alongside environmental exposure (e.g. internal/external microbiota) are key considerations for understanding movement-associated community changes. From our framework, we derive a series of testable hypotheses, and suggest means to test them, to facilitate future research into host movement and microbial community dynamics.

A Case for Regularly Obtaining Nutrition History: Food for Thought.

This Teachable Moment discusses providing patients with an opportunity to initiate dietary change before prescribing statin therapy for even severely high low-density lipoprotein cholesterol levels.

Tapinarof cream 1% once daily: Significant efficacy in the treatment of moderate to severe atopic dermatitis in adults and children down to 2 years of age in the pivotal phase 3 ADORING trials.

BACKGROUND: Tapinarof cream 1% once daily (QD), a topical aryl hydrocarbon receptor agonist, downregulates pro-inflammatory Th2 cytokines, upregulates skin-barrier components, and reduces oxidative stress. OBJECTIVE: To assess tapinarof efficacy and safety in adults and children down to 2 years of age with atopic dermatitis (AD). METHODS: Eight hundred and thirteen patients were randomized to tapinarof or vehicle QD in two 8-week phase 3 trials. RESULTS: The primary efficacy endpoint, Validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1 and ≥2-grade improvement from baseline at Week 8, was met with statistical significance in both trials: 45.4% versus 13.9% and 46.4% versus 18.0% (tapinarof vs vehicle; both P < .0001). Significantly superior Eczema Area and Severity Index 75 (EASI75) responses were also observed with tapinarof versus vehicle at Week 8: 55.8% versus 22.9% and 59.1% versus 21.2% (both P < .0001). Rapid improvements in patient-reported pruritus were also significant with tapinarof versus vehicle. Common adverse events (≥5%) of folliculitis, headache, and nasopharyngitis were mostly mild or moderate, with lower discontinuations due to adverse events in the tapinarof groups than with vehicle. LIMITATIONS: Long-term efficacy was not assessed. CONCLUSION: Tapinarof demonstrated highly significant efficacy and favorable safety and tolerability in a diverse population of patients with AD down to 2 years of age.