Changing the phospholipid composition of lipid droplets alters localization of select lipid droplet proteins.

Our experiments aim to determine if decreasing the amount of phosphatidylcholine (PC) relative to phosphatidylethanolamine (PE) at the lipid droplet surface changes the localization of specific lipid droplet proteins. We manipulate lipid droplet phospholipids in both a cultured mouse hepatocyte (AML12) cell line and on synthetic lipid droplets. Decreasing the PC:PE ratio increases perilipin 2, decreases DGAT2, and does not change rab18 or lanosterol synthase levels on lipid droplets. These differences may be explained by the distinct structural motifs that mediate the protein-lipid droplet interactions.

Vestibular tunnel approach in restoring non-carious cervical lesion gingival recessions with combination of bioceramics and collagen matrix: A case report with a 1-year follow-up.

INTRODUCTION: Non-carious cervical lesions (NCCLs) can compromise the integrity to both hard and soft tissues of teeth. This case report introduces a novel interdisciplinary technique by utilizing bioceramics-based cement (BBC) and porcine collagen matrix (CM) to reconstruct the dentogingival complex where enamel, dentin, and soft tissues were involved. CASE PRESENTATION: A 38-year-old healthy male was referred to the periodontics department for gingival recessions teeth #27-29 and a deep (NCCL) on the facial (F) #28 involving the loss of the cementoenamel junction (CEJ). The F #28 was restored with BBC according to manufacturing instructions. Soft tissues of #27-29 were simultaneously augmented with two CM strips via a coronally advanced tunnel utilizing suspended sutures. At the 6-month follow-up, approximately 100% root coverages were obtained for #27 and 29. The F #28 gingival tissue stabilized at the anticipated level of maximum root coverage (MRC), 1 mm apical to the coronally displaced CEJ. The exposed layer of BBC, F #28, was veneered with resin-modified glass ionomer to re-establish the original position of the CEJ. At the one-year follow-up visit root coverage for #28 remained stable and probing depths remained unchanged at 2 mm F #27-29. A sectional cone beam computed tomography scan illustrated the BBC restoration remained intact and well adapted. CONCLUSION: The 12-month follow-up illustrated that the BBC may be a viable restorable material while performing simultaneous gingival grafting with CM in deep NCCLs with gingival recessions. KEY POINTS: Why is this case new information? A novel approach treating the deep non-carious cervical lesion with BBC and CM. What are the keys to successful management of this case? The BBC placement needs to be flat. Secure the surgical site with non-resorbable suspensory sutures fixed by flowable composite. What are the primary limitations to success in this case? The primary limitation to success is the blood moisture control which may limit the placement of collagen matrix strips via the portal entry.

Citizen Science as an Approach for Responding to the Threat of Anopheles stephensi in Africa.

Even as novel technologies emerge and medicines advance, pathogen-transmitting mosquitoes pose a deadly and accelerating public health threat. Detecting and mitigating the spread of Anopheles stephensi in Africa is now critical to the fight against malaria, as this invasive mosquito poses urgent and unprecedented risks to the continent. Unlike typical African vectors of malaria, An. stephensi breeds in both natural and artificial water reservoirs, and flourishes in urban environments. With An. stephensi beginning to take hold in heavily populated settings, citizen science surveillance supported by novel artificial intelligence (AI) technologies may offer impactful opportunities to guide public health decisions and community-based interventions. Coalitions like the Global Mosquito Alert Consortium (GMAC) and our freely available digital products can be incorporated into enhanced surveillance of An. stephensi and other vector-borne public health threats. By connecting local citizen science networks with global databases that are findable, accessible, interoperable, and reusable (FAIR), we are leveraging a powerful suite of tools and infrastructure for the early detection of, and rapid response to, (re)emerging vectors and diseases.

Integrating Global Citizen Science Platforms to Enable Next-Generation Surveillance of Invasive and Vector Mosquitoes.

Mosquito-borne diseases continue to ravage humankind with >700 million infections and nearly one million deaths every year. Yet only a small percentage of the >3500 mosquito species transmit diseases, necessitating both extensive surveillance and precise identification. Unfortunately, such efforts are costly, time-consuming, and require entomological expertise. As envisioned by the Global Mosquito Alert Consortium, citizen science can provide a scalable solution. However, disparate data standards across existing platforms have thus far precluded truly global integration. Here, utilizing Open Geospatial Consortium standards, we harmonized four data streams from three established mobile apps­Mosquito Alert, iNaturalist, and GLOBE Observer's Mosquito Habitat Mapper and Land Cover­to facilitate interoperability and utility for researchers, mosquito control personnel, and policymakers. We also launched coordinated media campaigns that generated unprecedented numbers and types of observations, including successfully capturing the first images of targeted invasive and vector species. Additionally, we leveraged pooled image data to develop a toolset of artificial intelligence algorithms for future deployment in taxonomic and anatomical identification. Ultimately, by harnessing the combined powers of citizen science and artificial intelligence, we establish a next-generation surveillance framework to serve as a united front to combat the ongoing threat of mosquito-borne diseases worldwide.

Real-world use of the Breathing Pattern Assessment Tool in assessment of breathlessness post-COVID-19.

INTRODUCTION: Breathing pattern disorders (BPDs) are a common cause of chronic breathlessness, including after acute respiratory illnesses such as COVID pneumonia. BPD is however underdiagnosed, partly as a result of difficulty in clinically assessing breathing pattern. The Breathing Pattern Assessment Tool (BPAT) has been validated for use in diagnosing BPD in patients with asthma but to date has not been validated in other diseases. METHODS: Patients undergoing face-to-face review in a post-COVID clinic were assessed by a respiratory physician and specialist respiratory physiotherapist. Assessment included a Dyspnoea-12 (D12) questionnaire to assess breathlessness, physiotherapist assessment of breathing pattern including manual assessment of respiratory motion, and BPAT assessment. The sensitivity and specificity of BPAT for diagnosis of BPD in post-COVID patients was assessed. RESULTS: BPAT had a sensitivity of 89.5% and specificity of 78.3% for diagnosing BPD in post-COVID breathlessness. Patients with a BPAT score above the diagnostic cut-off had higher levels of breathlessness than those with lower BPAT scores (D12 score mean average 19.4 vs 13.2). CONCLUSION: BPAT has high sensitivity and moderate specificity for BPD in patients with long COVID. This would support its use as a screening test in clinic, and as a diagnostic tool for large cohort studies.

Impact of fan therapy during exercise on breathlessness and recovery time in patients with COPD: a pilot randomised controlled crossover trial.

BACKGROUND: Patients with COPD reduce physical activity to avoid the onset of breathlessness. Fan therapy can reduce breathlessness at rest, but the efficacy of fan therapy during exercise remains unknown in this population. The aim of the present study was to investigate 1) the effect of fan therapy on exercise-induced breathlessness and post-exercise recovery time in patients with COPD and 2) the acceptability of fan therapy during exercise; and 3) to assess the reproducibility of any observed improvements in outcome measures. METHODS: A pilot single-centre, randomised, controlled, crossover open (nonmasked) trial (clinicaltrials.gov NCT03137524) of fan therapy versus no fan therapy during 6-min walk test (6MWT) in patients with COPD and a modified Medical Research Council (mMRC) dyspnoea score ≥2. Breathlessness intensity was quantified before and on termination of the 6MWT, using the numerical rating scale (NRS) (0-10). Post-exertional recovery time was measured, defined as the time taken to return to baseline NRS breathlessness score. Oxygen saturation and heart rate were measure pre- and post-6MWT. RESULTS: 14 patients with COPD completed the trial per protocol (four male, 10 female; median (interquartile range (IQR)) age 66.50 (60.75 to 73.50) years); mMRC dyspnoea 3 (2 to 3)). Fan therapy resulted in lower exercise-induced breathlessness (ΔNRS; Δ modified Borg scale) (within-individual differences in medians (WIDiM) -1.00, IQR -2.00 to -0.50; p<0.01; WIDiM -0.25, IQR -2.00 to 0.00; p=0.02), greater distance walked (metres) during the 6MWT (WIDiM 21.25, IQR 12.75 to 31.88; p<0.01), and improved post-exertional breathlessness (NRS) recovery time (WIDiM -10.00, IQR -78.75 to 50.00; p<0.01). Fan therapy was deemed to be acceptable by 92% of participants. CONCLUSION: Fan therapy was acceptable and provided symptomatic relief to patients with COPD during exercise. These data will inform larger pilot studies and efficacy studies of fan therapy during exercise.

Effects of Sex and Load Carried per Kilogram of Body Mass on Landing Technique.

Sex differences and heavy load carriage may contribute to the high rate of musculoskeletal injury in military recruits, particularly within the female population. Thus, the purposes of this study were to determine if load influenced landing quality differently in females compared to males and if load carried per kg body mass was associated to quality of landing. Twenty-eight participants were recruited for this study (males: n = 14; females: n = 14). Participants were grouped by sex. All twenty-eight participants performed three drop-jumps (DJ) under unloaded and loaded conditions. The loaded condition included a combat helmet, tactical vest, and rucksack (22 kg). Two cameras recorded in the frontal and sagittal directions during the three DJ trials. DJ trials were scored using the LESS. There was no significant difference in LESS difference scores between males and females, t(26) = -1.014, p = 0.320, 95% CI = -2.01 to 0.68. Load carried per kg body mass (r s = 0.401, p = 0.034) was significantly correlated to LESS rank order. The results suggest load does not significantly alter landing quality as measured by the LESS. However, participant body mass and load per kg of body may play a role in a person's ability to adapt to heavy loads.

The Effects of Firefighter Equipment and Gear on the Static and Dynamic Postural Stability of Fire Cadets.

BACKGROUND: Slips, trips, falls, and jumps were the second leading cause of injuries at the fireground. RESEARCH QUESTION: The purpose of this study was to explore the effects of firefighter equipment and gear (EQG) on postural stability and determine if load per kg of body mass (L/BM) is associated with postural stability. METHODS: 26 male fire cadets (26.15 ±â€¯4.16 yr., 178.92 ±â€¯6.92 cm, 86.61 ±â€¯9.09 kg) were included in the analyses. Participants performed 3 single-leg landings (SLL) with and without EQG. The first 3 seconds of ground reaction forces following initial ground contact were used to calculate dynamic postural stability index (DPSI). Participants completed 2 static balance tasks (normal stability and limits of stability (LoS)) with and without EQG. Main outcome measures were overall LoS score (LoSS), direction-specific LoSS, and LoS distance (cm) of COP excursion (LoSD) in the anterior, posterior, right, and left directions. Separate paired-samples t-tests were run to determine the differences between load conditions for DPSI, overall LoSS, direction-specific LoSS, and LoSD in all directions. Bivariate correlations were conducted to determine the relationship of L/BM to DPSI, overall LoSS, and LoSS and LoSD in the anterior, posterior, right and left directions. RESULTS: Due to the use of multiple statistical tests, a Bonferroni correction was used, and the alpha level of .05 was adjusted to .005. DPSI was significantly higher loaded than unloaded, t(25) = -13.965, p < .001, d = 7.032, 95% CI, -0.133 to -0.099. No other comparisons were significant. A significant strong positive correlation (r(24) = .665, p < .001) was observed between L/BM and DPSI. No other correlations were significant. SIGNIFICANCE: This study demonstrates that firefighter EQG may significantly impact a cadet's ability to maintain postural stability while performing their duties.

Incidence and outcome of post-transplant lymphoproliferative disorders in lung transplant patients: Analysis of ISHLT Registry.

BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication following lung transplant. We studied incidence and risk factors for PTLD in adult lung transplant recipients (LTRs) using the International Society for Heart and Lung Transplantation Registry. METHODS: The International Society for Heart and Lung Transplantation Registry was used to identify adult, first-time, single and bilateral LTRs with at least 1 year of follow-up between 2006 and 2016. Kaplan-Meier method was used to describe the timing and distribution of PTLD. Univariable and multivariable Cox proportional hazards regression models were used to examine clinical characteristics associated with PTLD. RESULTS: Of 19,309 LTRs in the analysis cohort, we identified 454 cases of PTLD. Cumulative incidence of PTLD was 1.1% (95% CI = 1.0%-1.3%) at 1 year and 4.1% (95% CI = 3.6%-4.6%) at 10 years. Of the PTLD cases, 47.4% occurred within the first year following lung transplantation. In the multivariable model, independent risk factors for PTLD included age, Epstein-Barr virus serostatus, restrictive lung diseases, and induction. Risk of PTLD during the first year after transplant increased with increasing age in patients between 45 and 62 years at time of transplantation; the inverse was true for ages <45 years or >62 years. Finally, receiving a donor organ with human leukocyte antigen types A1 and A24 was associated with an increased risk of PTLD, whereas the recipient human leukocyte antigen type DR11 was associated with a decreased risk. CONCLUSIONS: Our study indicates that PTLD is a relatively rare complication among adult LTRs. We identified clinical characteristics that are associated with an increased risk of PTLD.

Trace metals in green sea turtles (Chelonia mydas) inhabiting two southern California coastal estuaries.

Foraging aggregations of east Pacific green sea turtles (Chelonia mydas) inhabit the Seal Beach National Wildlife Refuge (SBNWR) and San Diego Bay (SDB), two habitats in southern California, USA, located near urbanized areas. Both juvenile and adult green turtles forage in these areas and exhibit high site fidelity, which potentially exposes green turtles to anthropogenic contaminants. We assessed 21 trace metals (TM) bioaccumulated in green turtle scute and red blood cell (RBC) samples collected from SBNWR (n = 16 turtles) and SDB (n = 20 turtles) using acid digestion and inductively coupled plasma mass spectrometry. Principal component analyses of TM composition indicate that SBNWR and SDB turtles have location-specific contaminant signatures, characterized by differences in cadmium and selenium concentrations: SBNWR turtles had significantly more cadmium and selenium in RBC and more selenium in scute samples, than SDB turtles. Cadmium and selenium concentrations in RBC had a strong positive relationship, regardless of location. SBNWR turtles had higher selenium in RBCs than previously measured in other green turtle populations globally. Due to different retention times in blood vs. scute, these results suggest that SBNWR turtles have high long- and short-term selenium exposure. Turtles from SBNWR and SDB had higher trace metal concentrations than documented in green turtle populations that inhabit non-urbanized areas, supporting the hypothesis that coastal cities can increase trace metal exposure to local green turtles. Our study finds evidence that green turtle TM concentrations can differ between urbanized habitats and that long-term monitoring of these green turtles may be necessary.

Multiple connections between Amazonia and Atlantic Forest shaped the phylogenetic and morphological diversity of Chiasmocleis Mehely, 1904 (Anura: Microhylidae: Gastrophryninae).

Chiasmocleis is the most species-rich genus of Neotropical microhylids. Herein, we provide the first comprehensive multilocus phylogeny for the genus, including all but 3 of the 34 recognized species and multiple individuals per species. We discuss cryptic speciation, species discovery, patterns of morphological evolution, and provide a historical biogeographic analysis to account for the current distribution of the genus. Diversification of Chiasmocleis from other New World microhylids began during the Eocene, app. 40 mya, in forested areas, and current diversity seems to be a product of recurrent connections between the Atlantic Forest and Amazonia. Small-sized species evolved independently three times in Chiasmocleis. Furthermore, the extremely small-bodied (i.e. miniaturized) species with associated loss of digits, phalanges, and pectoral girdle cartilages evolved only once and are restricted to Amazonia. Using the phylogeny, we recognized three subgenera within Chiasmocleis: Chiasmocleis Méhely, 1904, Relictus subg. nov., and Syncope Walker, 1973. The recognition of the subgenus Syncope informs future research on patterns of miniaturization in the genus, and the subgenus Relictus highlights isolation of an endemic and species-poor lineage to the Atlantic Forest, early (about 40 mya) in the history of Chiasmocleis.

Self-Directed Walk With Ease Workplace Wellness Program - Montana, 2015-2017.

Arthritis occurs in 27% of adults in Montana, among whom 50% have activity limitations, 16% have social participation restrictions, and 23% have severe joint pain attributable to arthritis (1). Physical activity is beneficial in managing arthritis symptoms and in preventing other chronic diseases (2). Walk With Ease is a 6-week evidence-based physical activity program recommended by CDC to increase physical activity and help improve arthritis symptoms (3). In 2015, Walk With Ease was added to an ongoing workplace wellness program for Montana state employees; the results for five outcomes (minutes spent walking, engaging in other physical activity [including swimming, bicycling, other aerobic equipment use, and other aerobic exercise], stretching, pain, and fatigue) were analyzed by the Montana Department of Public Health and Human Services and CDC. Outcomes at baseline (pretest), 6 weeks after the program (posttest), and 6 months later (follow-up) were analyzed by self-reported arthritis status at the time the participant enrolled in the program. Significant increases (p<0.05) in the mean number of minutes spent per week walking and engaging in other physical activity were observed among participants with and without arthritis at the 6-week posttest. Time spent stretching did not change significantly at posttest for either group. Mean pain levels among participants without arthritis increased significantly both at the 6-week posttest and 6-month follow-up; however, pain and fatigue decreased significantly at posttest and follow-up for participants with or without arthritis who began the program with moderate or severe pain and fatigue levels. The data from these analyses suggest that, as a component of a workplace wellness program, self-directed Walk With Ease might be effective in increasing physical activity not only among adults with arthritis, but also among persons without arthritis.

Daily spirometry in an acute exacerbation of adult cystic fibrosis patients.

To help answer the question of length of intravenous antibiotics during an acute exacerbation of cystic fibrosis (CF), we had subjects to follow daily home spirometry while on intravenous antibiotics. CF patients, 18 and older, with an acute exacerbation requiring intravenous antibiotics had a daily FEV1. The average time to a 10% increase over their initial sick FEV1 was calculated, as well as the time to a new baseline. A total of 25 subjects completed the study. Ten of the 25 subjects did not have a sustainable 10% increase in FEV1. Of the 15 subjects with a sustainable 10% increase in FEV1, it took 5.2 days (±4.5) after day 1, while a new baseline was achieved on average at 6.6 days (±4.8) after day 1. Given the wide range of time to a 10% improvement and new baseline, it is recommended there should be flexibility in length of intravenous antibiotics in CF, not by a preset number.

Tar Barreler's Hump: An Unusual Presentation of a Posttraumatic Pseudolipoma.

This is an interesting paper of a 4 cm posttraumatic pseudolipoma on the back of the neck of an adult man who has participated in "tar barrel rolling" since adolescence. To the best of our knowledge, this is the first case of a pseudolipoma to be reported in the literature in association with tar barreling.

Structure-Based Design of Potent and Selective CK1γ Inhibitors.

Aberrant activation of the Wnt pathway is believed to drive the development and growth of some cancers. The central role of CK1γ in Wnt signal transduction makes it an attractive target for the treatment of Wnt-pathway dependent cancers. We describe a structure-based approach that led to the discovery of a series of pyridyl pyrrolopyridinones as potent and selective CK1γ inhibitors. These compounds exhibited good enzyme and cell potency, as well as selectivity against other CK1 isoforms. A single oral dose of compound 13 resulted in significant inhibition of LRP6 phosphorylation in a mouse tumor PD model.