Realizing the clinical utility of saliva for monitoring oral diseases.

In the era of personalized/precision health care, additional effort is being expended to understand the biology and molecular mechanisms of disease processes. How these mechanisms are affected by individual genetics, environmental exposures, and behavioral choices will encompass an expanding role in the future of optimally preventing and treating diseases. Considering saliva as an important biological fluid for analysis to inform oral disease detection/description continues to expand. This review provides an overview of saliva as a diagnostic fluid and the features of various biomarkers that have been reported. We emphasize the use of salivary biomarkers in periodontitis and transport the reader through extant literature, gaps in knowledge, and a structured approach toward validating and determine the utility of biomarkers in periodontitis. A summation of the findings support the likelihood that a panel of biomarkers including both host molecules and specific microorganisms will be required to most effectively identify risk for early transition to disease, ongoing disease activity, progression, and likelihood of response to standard periodontal therapy. The goals would be to develop predictive algorithms that serve as adjunctive diagnostic tools which provide the clinician and patient important information for making informed clinical decisions.

Spatiotemporal alterations in the brain oscillations of Arctic explorers.

BACKGROUND: The limited understanding of the physiology and psychology of polar expedition explorers has prompted concern over the potential cognitive impairments caused by exposure to extreme environmental conditions. Prior research has demonstrated that such stressors can negatively impact cognitive function, sleep quality, and behavioral outcomes. Nevertheless, the impact of the polar environment on neuronal activity remains largely unknown. METHODS: In this study, we aimed to investigate spatiotemporal alterations in brain oscillations of 13 individuals (age range: 22-48 years) who participated in an Arctic expedition. We utilized electroencephalography (EEG) to record cortical activity before and during the Arctic journey, and employed standardized low resolution brain electromagnetic tomography to localize changes in alpha, beta, theta, and gamma activity. RESULTS: Our results reveal a significant increase in the power of theta oscillations in specific regions of the Arctic, which differed significantly from pre-expedition measurements. Furthermore, microstate analysis demonstrated a significant reduction in the duration of microstates (MS) D and alterations in the local synchrony of the frontoparietal network. CONCLUSION: Overall, these findings provide novel insights into the neural mechanisms underlying adaptation to extreme environments. These findings have implications for understanding the cognitive consequences of polar exploration and may inform strategies to mitigate potential neurological risks associated with such endeavors. Further research is warranted to elucidate the long-term effects of Arctic exposure on brain function.

Isolation and characterization of a Halomonas species for non-axenic growth-associated production of bio-polyesters from sustainable feedstocks.

Biodegradable plastics are urgently needed to replace petroleum-derived polymeric materials and prevent their accumulation in the environment. To this end, we isolated and characterized a halophilic and alkaliphilic bacterium from the Great Salt Lake in Utah. The isolate was identified as a Halomonas species and designated "CUBES01." Full-genome sequencing and genomic reconstruction revealed the unique genetic traits and metabolic capabilities of the strain, including the common polyhydroxyalkanoate (PHA) biosynthesis pathway. Fluorescence staining identified intracellular polyester granules that accumulated predominantly during the strain's exponential growth, a feature rarely found among natural PHA producers. CUBES01 was found to metabolize a range of renewable carbon feedstocks, including glucosamine and acetyl-glucosamine, as well as sucrose, glucose, fructose, and further glycerol, propionate, and acetate. Depending on the substrate, the strain accumulated up to ~60% of its biomass (dry wt/wt) in poly(3-hydroxybutyrate), while reaching a doubling time of 1.7 h at 30°C and an optimum osmolarity of 1 M sodium chloride and a pH of 8.8. The physiological preferences of the strain may not only enable long-term aseptic cultivation but also facilitate the release of intracellular products through osmolysis. The development of a minimal medium also allowed the estimation of maximum polyhydroxybutyrate production rates, which were projected to exceed 5 g/h. Finally, also, the genetic tractability of the strain was assessed in conjugation experiments: two orthogonal plasmid vectors were stable in the heterologous host, thereby opening the possibility of genetic engineering through the introduction of foreign genes. IMPORTANCE: The urgent need for renewable replacements for synthetic materials may be addressed through microbial biotechnology. To simplify the large-scale implementation of such bio-processes, robust cell factories that can utilize sustainable and widely available feedstocks are pivotal. To this end, non-axenic growth-associated production could reduce operational costs and enhance biomass productivity, thereby improving commercial competitiveness. Another major cost factor is downstream processing, especially in the case of intracellular products, such as bio-polyesters. Simplified cell-lysis strategies could also further improve economic viability.

Clinical Practice Recommendations for Hematopoietic Cell Transplantation and Cellular Therapies in Follicular Lymphoma: A Collaborative Effort on Behalf of the American Society for Transplantation and Cellular Therapy and the European Society for Blood and Marrow Transplantation.

Follicular lymphoma (FL) is the most common indolent B-cell non-Hodgkin lymphoma (NHL), accounting for nearly one-third of all NHL. The therapeutic landscape for patients with FL has significantly expanded over the past decade, but the disease continues to be considered incurable. Hematopoietic cell transplantation (HCT) is potentially curative in some cases. Recently, the emergence of chimeric antigen receptor T-cell therapy (CAR-T) for patients with relapsed/refractory (R/R) FL has yielded impressive response rates and long-term remissions, but definitive statement on the curative potential of CAR-T is currently not possible due to limited patient numbers and relatively short follow up. A consensus on the contemporary role, optimal timing, and sequencing of HCT (autologous or allogeneic) and cellular therapies in FL is needed. As a result, the American Society of Transplantation and Cellular Therapy (ASTCT) Committee on Practice Guidelines endorsed this effort to formulate consensus recommendations to address this unmet need. The RAND-modified Delphi method was used to generate 15 consensus statements/recommendations. These clinical practice recommendations will help guide clinicians managing patients with FL. Of note, the use of bispecific antibodies in R/R FL was not in the scope of this project.

Statistical analysis plan for the Chinese Herbal medicine in Acute INtracerebral haemorrhage (CHAIN) trial.

INTRODUCTION: The traditional Chinese medicine (TCM) herbal compound FYTF-919 (Zhong Feng Xing Nao prescription) may improve outcome from acute intracerebral hemorrhage (ICH) by reducing brain edema, hematoma absorption, and enhancement of the immune system. We outline the statistical analysis plan (SAP) for the Chinese Herbal medicine in Acute INtracerebral haemorrhage (CHAIN) study. DESIGN: CHAIN is a multicenter, prospective, randomized, double-blind, placebo-controlled trial being undertaken at 20-30 hospitals in China. After the completion of eligibility checks, patients are randomly allocated to FYTF-919 (100 mL per day, oral) or matching placebo over 28 days. A sample size of 1504 patients is estimated to provide 90% power (α 0.05) for a 0.06 absolute improvement in the primary outcome of utility-weighted modified Rankin scale scores at 90 days, analyzed by general linear regression. METHODS: The statistical analysis plan was developed by the study statistician, principal investigators, international experts, and the study project manager. The plan provides details for analyzing baseline characteristics, patient management, and outcomes. It includes provisions for covariate adjustments, subgroup analysis, the handling missing data, and in the conduct of sensitivity analyzes. RESULTS: A predefined statistical analysis plan was established for CHAIN, facilitating transparent and verifiable analysis. CONCLUSIONS: The CHAIN statistical analysis plan was prospectively developed with a focus on maintaining high-quality standards of internal validity to minimise potential analysis biases. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05066620).

Recommendations for Implementing the INTERACT3 Care Bundle for Intracerebral Hemorrhage in Latin America: Results of a Delphi Method.

INTRODUCTION: The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT3) showed that the implementation of a care bundle improves outcomes after acute intracerebral hemorrhage (ICH). We aimed to establish consensus-based recommendations for the broader integration of the care bundle across Latin American countries (LAC). METHODS: A 3-phase Delphi study allowed a panel of 32 healthcare workers from 14 LAC to sequentially rank statements relevant to 7 domains (training, resources/infrastructure, patient education, blood pressure, temperature, glycemic control, and anticoagulation reversal). The pre-defined consensus threshold was 75%. RESULTS: A total of 43 statements reached consensus by the third round, with 12 new statements emerging through rounds. The highest-ranked statements in each domain emphasized critical aspects, but successful implementation requires appropriate resourcing. Key priorities were continuous training of all healthcare workers in ICH management, establishing protocols aligned with available resources, and collaborative interdisciplinary care supported by institutional networks. Statements related to anticoagulation reversal had the highest priority. CONCLUSIONS: Consensus statements are provided to facilitate integration of the INTERACT3 care bundle to reduce disparities in ICH outcomes in LAC.

Self-normalization for a 1-mm3resolution clinical PET system using deep learning.

Normalization in positron emission tomography (PET) corrects for non-uniformity of sensitivity across all system lines of response (LOR). Self-normalization is a framework that aims to estimate normalization components from the emission data without a separate scan of a normalization phantom. In this work, we propose for the first time an image-based end-to-end self-normalization framework using conditional generative adversarial networks (cGAN). We evaluated different approaches by exploring each of the following three methodologies. First, we used images that were either unnormalized or corrected for geometric factors, which encompass all time-invariant factors, as input data types. Second, we set the input tensor shape as either a single axial slice (2-D) or three contiguous axial slices (2.5-D). Third, we chose either Pix2Pix or polarized self-attention (PSA) Pix2Pix, which we developed for this work, as a deep learning network. The targets for all approaches were the axial slices of images normalized using the direct normalization method. We performed Monte Carlo simulations of ten voxelized phantoms with the SimSET simulation tool and produced 26,000 pairs of axial image slices for training and testing. The results showed that 2.5-D PSA Pix2Pix trained with geometric-factors-corrected input images achieved the best performance among all the methods we tested. All approaches improved general image quality figures of merit peak signal to noise ratio (PSNR) and structural similarity index (SSIM) from ~15% to ~55%, and 2.5-D PSA Pix2Pix showed the highest PSNR (28.074) and SSIM (0.921). Lesion detectability, measured with region of interest (ROI) PSNR, SSIM, normalized contrast recovery coefficient (NCRC), and contrast-to-noise ratio (CNR), was generally improved for all approaches, and 2.5-D PSA Pix2Pix trained with geometric-factors-corrected input images achieved the highest ROI PSNR (28.920) and SSIM (0.973).

Prevalence of Decay and Tooth Condition Changes Adjacent to Restored Dental Implants: A Retrospective Radiographic Study.

This study examined the association between a dental implant and changes in adjacent teeth over time. Electronic health records of 1818 patients who received a dental implant were retrospectively evaluated over 14 years (2005-2019) in a university setting. The status of the adjacent tooth and vertical and horizontal distance from the implant platform to adjacent teeth were determined using digital intraoral radiographs taken at baseline and the last follow-up visit (1-14 years, median four years). In total, 1085 dental implants were evaluated. There were 234 instances of a change in the adjacent tooth. Decay was observed in 83 (7.6%) of adjacent teeth; the mean time to development was four years (range 1 to 14 years). Approximately 9% of adjacent teeth received direct restorations, 4.8% received indirect restorations, 1% received endodontic root canal treatment (RCT), and 5.6% were extracted. The mean horizontal distance between the implant platform and the adjacent teeth was 3.56 mm; the mean vertical distance from the contact point to the alveolar crest on the tooth side was 6.2 mm at the 1st time of the reported decay on x-ray. These distances did not significantly influence the occurrence of caries. The prevalence of interproximal contact loss (ICL) was higher on the mesial of the implant crown at 63% compared to 20% on the distal side. This large retrospective analysis identified that teeth adjacent to a dental implant were at risk of decay and changes in their condition. In addition, the implant-to-tooth distance and inadequate emergence profile may contribute as caries risk factors in addition to hygiene and a high sugar level diet. These findings appear essential for clinicians when making treatment decisions and discussing outcomes with patients.

CD19-directed CART Therapy for T cell/Histiocyte Rich Large B-cell Lymphoma.

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare histologic variant of LBCL. Limited data regarding CD19-directed chimeric antigen receptor T-cell (CART) therapy in relapsed/refractory (R/R) THRLBCL suggest poor efficacy. We investigated CART outcomes for R/R THRLBCL through the CIBMTR registry. A total of 58 adult patients with R/R THRLBCL who received commercial CD19-CART between 2018-2022 were identified. Most patients (67%) had early relapse of disease (45% primary refractory) with a median of 3 (range: 1-7) prior therapies and were treated with Axicabtagene ciloleucel (69%). At median follow-up of 23 months post-CART, 2-year overall and progression-free survival were 42% (95% CI: 27-57) and 29% (95% CI: 17-43), respectively. In univariable analysis, poor performance status pre-CART was associated with higher mortality (HR 2.35, 95%CI 1.02-5.5). The 2-year cumulative incidences of relapse/progression and non-relapse mortality were 69% and 2%, respectively. Grade ≥3 CRS and ICANS occurred in 7% and 15% of patients, respectively. In this largest analysis of CD19-CART for R/R THRLBCL, approximately 30% of patients were alive and progression-free 2 years post-CART. Despite a high incidence of progression (69% at 2 years), these results suggest a subset of patients with R/R THRLBCL may have durable responses with CART.

Sex Differences in Profile and In-Hospital Death for Acute Stroke in Chile: Data From a Nationwide Hospital Registry.

BACKGROUND: Knowledge of local contextual sex differences in the profile and outcome for stroke can improve service delivery. We aimed to determine sex differences in the profile of patients with acute stroke and their associations with in-hospital death in the national hospital database of Chile. METHODS AND RESULTS: We present a retrospective cohort based on the analysis of the 2019 Chilean database of Diagnosis-Related Groups, which represents 70% of the operational expenditure of the public health system. Random-effects multiple logistic regression models were used to determine independent associations of acute stroke (defined by main diagnosis International Classification of Diseases, Tenth Revision [ICD-10] codes) and in-hospital death, and reported with odds ratios (ORs) and 95% CIs. Of 1 048 575 hospital discharges, 15 535 were for patients with acute stroke (7074 [45.5%] in women), and 2438 (15.6%) of them died during hospitalization. Differences by sex in sociodemographic and clinical characteristics were identified for stroke and main subtypes. After fully adjusted model, women with ischemic stroke had lower in-hospital death (OR, 0.79 [95% CI, 0.69-0.91]) compared with men; other independent predictors included age per year increase (OR, 1.03 [95% CI, 1.03-1.04]), chronic kidney disease (OR, 1.47 [95% CI, 1.20-1.80]), atrial fibrillation (OR, 1.50 [95% CI, 1.26-1.80]), and other risk factors. Conversely, for intracerebral hemorrhage, women had a higher in-hospital mortality rate than men (OR, 1.19 [95% CI, 1.02-1.40]); other independent predictors included age per year increase (OR, 1.009 [95% CI, 1.003-1.01]), chronic kidney disease (OR, 1.55 [95% CI, 1.23-1.97]), oral anticoagulant use (OR, 1.88 [95% CI, 1.37-2.58]), and other risk factors. CONCLUSIONS: Sex differences in characteristics and in-hospital death of hospitalized patients exist for acute stroke in Chile. In-hospital death is higher for acute ischemic stroke in men and higher for intracerebral hemorrhage in women. Future research is needed to better identify contributing factors.

Characterization of the preweaned Holstein calf fecal microbiota prior to, during, and following resolution of uncomplicated gastrointestinal disease.

Little is known about shifts in the fecal microbiome of dairy calves preceding and following the incidence of gastrointestinal disease. The objective of this cohort study was to describe the fecal microbiome of preweaned dairy calves before, during, and after gastrointestinal disease. A total of 111 Holstein dairy calves were enrolled on 2 dairies (D1 and D2) and followed until 5 weeks old. Health assessments were performed weekly and fecal samples were collected every other week. Of the 111 calves, 12 calves from D1 and 12 calves from D2 were retrospectively defined as healthy, and 7 calves from D1 and 11 calves from D2 were defined as diarrheic. Samples from these calves were sequenced targeting the 16S rRNA gene and compared based on health status within age groups and farms: healthy (0-1 week old) vs. pre-diarrheic (0-1 week old), healthy (2-3 weeks old) vs. diarrheic (2-3 weeks old), and healthy (4-5 weeks old) vs. post-diarrheic (4-5 weeks old) calves. Healthy and diarrheic samples clustered together based on age rather than health status on both farms. Based on linear discriminant analysis, a few species were identified to be differently enriched when comparing health status within age groups and farm. Among them, Bifidobacterium sp. was differently enriched in pre-diarrheic calves at D1 (0-1 week old) whereas healthy calves of the same age group and farm showed a higher abundance of Escherichia coli. Bifidobacterium sp. was identified as a biomarker of fecal samples from healthy calves (2-3 weeks old) on D1 when compared with diarrheic calves of the same age group and farm. Feces from diarrheic calves on D2 (2-3 weeks old) were characterized by taxa from Peptostreptococcus and Anaerovibrio genera whereas fecal samples of age-matched healthy calves were characterized by Collinsella aerofaciens and Bifidobacterium longum. After resolution of uncomplicated diarrhea (4-5 weeks old), Collinsella aerofaciens was more abundant in D2 calves whereas Bacteriodes uniformis was more abundant in D1 calves. Taken together, these findings suggest that the age of the preweaned calf is the major driver of changes to fecal microbiome composition and diversity even in the face of uncomplicated gastrointestinal disease.

Anti-CD19 chimeric antigen receptor T-cell therapy has less efficacy in Richter transformation than in de novo large B-cell lymphoma and transformed low-grade B-cell lymphoma.

The activity of anti-CD19 CAR T cell therapy in chronic lymphocytic leukemia (CLL) with Richter's transformation (RT) to aggressive large B cell lymphoma (LBCL) is largely unknown. In a multicenter retrospective study, we report the safety and efficacy of CAR T cell therapy in patients with RT (n=30) compared to patients with aggressive B cell lymphoma (n=283) and patients with transformed indolent Non-Hodgkins Lymphoma (iNHL) (n=141) between April 2016 and January 2023. Two-thirds of patients received prior therapy for CLL before RT and 89% of them received B-cell receptor and B-cell lymphoma 2 (BCL-2) inhibitors. Toxicities of CAR T cell therapy in RT were similar to other lymphomas, with no fatalities related to cytokine release syndrome or immune effector-cell associated neurotoxicity synderome. The 100-day overall response rate and complete response rates in patients with RT were 57% and 47%, respectively. With a median follow up of 19 months, the median overall survival (OS) was 9.9 months in patients with RT compared to 18 months in de-novo LBCL and not reached in patients with transformed iNHL. The OS at 12 months was 45% in patients with RT compared with 62% and 75% in patients with de novo LBCL and transformed iNHL, respectively. In a multivariate analysis, worse OS was associated with RT histology, elevated LDH, and more prior lines of therapy. CAR T cell therapy can salvage a proportion of patients with CLL and RT exposed to prior targeted agents; however, efficacy in RT is inferior compared to de novo LBCL and transformed iNHL.

Impact of COVID-19 monoclonal antibodies on outcomes of COVID-19 infection in hematopoietic stem cell transplant and chimeric antigen receptor therapy recipients.

BACKGROUND: Hematopoietic stem cell transplant (HSCT) and chimeric antigen receptor T-cell therapy (CAR-T) recipients are at higher risk of serious complications of COVID-19 infection than the general population. Though there is evidence that monoclonal antibodies (MCA) against COVID-19 reduce the risk of death and hospitalization in the general population, data regarding their efficacy in HSCT and CAR-T recipients remains scarce. METHODS: We conducted a retrospective review of HSCT and CAR-T recipients to compare 30-day outcomes between patients who did and did not receive MCA after their first episode of COVID-19 between May 1, 2020 and December 31, 2022. Outcomes were defined as the most severe complication experienced out of the following: 30-day emergency department visit, hospitalization, intensive care unit admission, and death after COVID-19 infection. RESULTS: We identified 166 patients comprised of 53.6% allogeneic HSCT, 35.5% autologous HSCT, and 10.8% CAR-T recipients; 107 had received a COVID-19 vaccine >2 weeks prior to testing positive, and 40 were treated with MCA. After adjusting for age, presence of symptoms at the initial positive test, and COVID-19 vaccination status, patients who did not receive MCA were five times more likely to develop complications after COVID-19 infection (adjusted odds ratio 5.0 [95% CI, 1.9-12.8], p = .001). CONCLUSION: HSCT and CAR-T recipients who received MCA following COVID-19 infection were far less likely to develop COVID-related complications than those who did not receive MCA, regardless of vaccination status. This underscores the potential benefit of developing novel MCA with efficacy against circulating COVID-19 strains.

Association between Salt-Related Knowledge, Attitudes, and Behaviours and 24 h Urinary Salt Excretion in Nepal.

This study examined the association between salt-related knowledge, attitudes, and behaviors (KAB) and salt excretion using the 24-hour (24 h) urinary collection method. Data were utilized from the Community-Based Management of Non-Communicable Diseases in Nepal (COBIN) Salt Survey, a community-based cross-sectional study conducted among a sub-sample of COBIN cohort in Pokhara Metropolitan City, Western Nepal, from July to December 2018, among adults aged 25-70 years. A total of 451 adults participated in the study, and a single 24 h urine sample was collected from each participant. The mean [(standard deviation (SD)] age of the participants was 49.6 (9.82) years, and the majority were female (65%). The mean urinary salt excretion was 13.28 (SD: 4.72) g/day, with 98% of participants consuming ≥5 g of salt/day. Although 83% of participants knew the risks of high salt intake and 87% believed it was important to reduce their intake, only 10% reported doing so. Salt-related attitude i.e., self-perceived salt intake was significantly associated with urinary salt excretion, adding extra salt to food, consuming processed foods, and taking actions to salt control. Participants who perceived themselves as consuming high salt had higher urinary salt excretion [(14.42 g/day; 95% confidence interval (95% CI): 13.45, 15.39, p = 0.03)], were more likely to add extra [(Odds ratio (OR) = 3.59; 95% CI: 2.03, 6.33, p < 0.001)], and consume processed foods more often (OR = 1.90; 95% CI: 1.06, 3.40, p < 0.05) compared to those who self-perceived consuming a normal amount of salt. Conversely, participants who perceived themselves as consuming low salt were more likely to take actions to control salt intake (OR = 4.22; 95% CI: 1.90, 9.37, p < 0.001) compared to their counterparts who perceived consuming a normal amount of salt. There existed a gap between salt-related knowledge, attitudes, and actual behaviors, resulting in a high salt intake among the Nepalese population. Nepal urgently requires tailored national salt reduction programs that comprise both policy and community-level interventions to achieve a 30% reduction in mean population salt intake by 2025. Further validation studies are needed to assess the effectiveness of community-based intervention in Nepal.

Cardiovascular Outcomes in Fontan Patients With Right vs Left Univentricular Morphology: A Multicenter Study.

Background: There is a paucity of data on long-term outcomes after Fontan palliation in patients with a dominant morphological univentricular right (uRV) vs left (uLV) ventricle. Objectives: The purpose of this study was to compare the incidence of atrial arrhythmias, thromboembolic events, cardiac transplantation, and death following Fontan palliation in patients with uRV vs uLV. Methods: The Alliance for Adult Research in Congenital Cardiology conducted a multicenter retrospective cohort study on patients with total cavopulmonary connection Fontan palliation across 12 centers in North America. All components of the composite outcome, that is, atrial arrhythmias, thromboembolic events, cardiac transplantation, and death, were reviewed and classified by a blinded adjudicating committee. Time-to-event analyses were performed that accounted for competing risks. Results: A total of 384 patients were followed for 10.5 ± 5.9 years. The composite outcome occurred in 3.7 vs 1.7 cases per 100 person-years for uRV (N = 171) vs uLV (N = 213), respectively (P < 0.001). In multivariable analyses, uRV conferred a >2-fold higher risk of the composite outcome (HR: 2.17, 95% CI: 1.45-3.45, P < 0.001). In secondary analyses of components of the primary outcome, uRV was significantly associated with a greater risk of cardiac transplantation or death (HR: 9.09, 95% CI: 2.17-38.46, P < 0.001) and atrial arrhythmias (HR: 2.17, 95% CI: 1.20-4.00, P = 0.010) but not thromboembolic events (HR: 1.64, 95% CI: 0.86-3.16, P = 0.131). Conclusions: Fontan patients with uRV vs uLV morphology have a higher incidence of adverse cardiovascular events, including atrial arrhythmia, cardiac transplantation, and all-cause mortality.

A simple system change to reduce delays in emergency calls for assistance during anaesthesia in the operating theatre.

Promptly calling for assistance in an anaesthetic emergency is important. However, emergency call systems are not present in all locations where anaesthesia is administered, and in those that do have an emergency call system, the call button is often obscured by other equipment or in an unfamiliar location. Placing a red stripe from the ceiling, down the wall, to the emergency call button significantly reduces delays in activating an emergency call, demonstrating a simple but effective system change to the layout of operating theatres.

Sustainability of the Subspecialty of Anesthesiology Critical Care: An Expert Consensus and Review of the Literature.

While considerable literature exists with respect to clinical aspects of critical care anesthesiology (CCA) practice, few publications have focused on how anesthesiology-based critical care practices are organized and the challenges associated with the administration and management of anesthesiology critical care units. Currently, numerous challenges are affecting the sustainability of CCA practice, including decreased applications to fellowship positions and decreased reimbursement for critical care work. This review describes what is known about the subspecialty of CCA and leverages the experience of administrative leaders in adult critical care anesthesiologists in the United States to describe potential solutions.

Learning pathways composed of core subjects with features of reducing cognitive load have better learning outcomes.

BACKGROUND: Changing the course duration or timing of subjects in learning pathways would influence medical students' learning outcomes. Curriculum designers need to consider the strategy of reducing cognitive load and evaluate it continuously. Our institution underwent gradual curricular changes characterized by reducing cognitive load since 2000. Therefore, we wanted to explore the impact of this strategy on our previous cohorts. METHODS: This cohort study explored learning pathways across academic years of more than a decade since 2000. Eight hundred eighty-two medical students between 2006 and 2012 were included eventually. Learning outcomes included an average and individual scores of subjects in different stages. Core subjects were identified as those where changes in duration or timing would influence learning outcomes and constitute different learning pathways. We examined whether the promising learning pathway defined as the pathway with the most features of reducing cognitive load has higher learning outcomes than other learning pathways in the exploring dataset. The relationship between features and learning outcomes was validated by learning pathways selected in the remaining dataset. RESULTS: We found nine core subjects, constituting four different learning pathways. Two features of extended course duration and increased proximity between core subjects of basic science and clinical medicine were identified in the promising learning pathway 2012, which also had the highest learning outcomes. Other pathways had some of the features, and pathway 2006 without such features had the lowest learning outcomes. The relationship between higher learning outcomes and cognitive load-reducing features was validated by comparing learning outcomes in two pathways with and without similar features of the promising learning pathway. CONCLUSION: An approach to finding a promising learning pathway facilitating students' learning outcomes was validated. Curricular designers may implement similar design to explore the promising learning pathway while considering potential confounding factors, including students, medical educators, and learning design of the course.

Alcohol consumption and its correlation with medical conditions: a UK Biobank study.

Background: Alcohol consumption has been associated with the occurrence of many health conditions. We analyzed UK Biobank data to explore associations of various conditions to type and amount of alcohol consumed. UK Biobank is a large biomedical database providing information from UK participants, including lifestyle questionnaires and diagnosis data. Methods: Using UK Biobank, we examined the relationship between weekly alcohol consumption, alcohol type and the incidence of eight select conditions. We calculated counts of individuals consuming each type diagnosed with these conditions. To assess the effect of alcohol consumption on each condition's prevalence, we used log-logistic regression models to generate dose-response models for each alcohol type. Results: The alcohol consumed included: red wine (228,439 participants), white wine (188811), beer (182648), spirits (129418), and fortified wine (34598). We observed increased condition prevalence with increasing amounts of alcohol. This was especially seen for chronic obstructive lung disease, cirrhosis of liver, hypertension, gastritis, and type 2 diabetes. Beer consumers showed higher prevalence for most conditions while fortified wine had the largest increases in incidence rates. Only white wine showed decreased incidence for acute myocardial infarction. In general, the prevalence of many conditions was higher among alcohol consumers, particularly for hypertension, 33.8%, compared to 28.6% for non-drinkers. Conclusion: Although many conditions were already prevalent among non-drinkers, participants consuming increasing amounts of alcohol had increased incidence rates for many of the studied conditions. This was especially true for consumers of beer and fortified wine, but also true to a lesser extent for consumers of spirits, red and white wine.

Autoimmune hepatitis: Current and future therapies.

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that can lead to cirrhosis and liver failure. AIH can present in all ages, races, and ethnicities, but it predominantly affects women. As a heterogeneous disease, AIH presents variably in different patients, making diagnosis and treatment a challenge. Currently, the standard treatment for AIH comprises immunosuppressants; however, their long-term use is associated with adverse effects. The pathogenesis of AIH is complex, involving T cells, macrophages, and plasma cells that invade the periportal parenchyma and lead to an inflammatory cascade that can result in liver damage. Due to the complexity of AIH pathogenesis, treatment targets several inflammatory pathways. However, unlike other autoimmune diseases in which targeted treatments have been approved, there has been little progress made in advancing the treatment paradigm for AIH. Major obstacles to progress include challenges in conducting clinical trials, particularly patient recruitment and ensuring a diverse range of backgrounds; poorly defined outcomes to assess treatment response and improved quality of life; and a lack of study designs that account for the stage of disease and variations in treatment. A focus on individualized and steroid-free treatment approaches is needed to improve AIH prognosis and minimize steroid-associated adverse effects.