CD34+ cell yield among healthy donors: Large-scale model development and validation.

BACKGROUND: Successful engraftment in hematopoietic stem cell transplantation necessitates the collection of an adequate dose of CD34+ cells. Thus, the precise estimation of CD34+ cells harvested via apheresis is critical. Current CD34+ cell yield prediction models have limited reproducibility. This study aims to develop a more reliable and universally applicable model by utilizing a large dataset, enhancing yield predictions, optimizing the collection process, and improving clinical outcomes. MATERIALS AND METHODS: A secondary analysis was conducted using the Center for International Blood and Marrow Transplant Research database, involving data from over 17 000 healthy donors who underwent filgrastim-mobilized hematopoietic progenitor cell apheresis. Linear regression, gradient boosting regressor, and logistic regression classification models were employed to predict CD34+ cell yield. RESULTS: Key predictors identified include pre-apheresis CD34+ cell count, weight, age, sex, and blood volume processed. The linear regression model achieved a coefficient of determination (R2) value of 0.66 and a correlation coefficient (r) of 0.81. The gradient boosting regressor model demonstrated marginally improved results with an R2 value of 0.67 and an r value of 0.82. The logistic regression classification model achieved a predictive accuracy of 96% at the 200 × 106 CD34+ cell count threshold. At thresholds of 400, 600, 800, and 1000 × 106 CD34+ cell count, the accuracies were 88%, 83%, 83%, and 88%, respectively. The model demonstrated a high area under the receiver operator curve scores ranging from 0.90 to 0.93. CONCLUSION: This study introduces advanced predictive models for estimating CD34+ cell yield, with the logistic regression classification model demonstrating remarkable accuracy and practical utility.

Impact of abdominal compression on heart and stomach motion for stereotactic arrhythmia radioablation.

PURPOSE: To evaluate the effectiveness of abdominal compression (AC) as a respiratory motion management method for the heart and stomach during stereotactic arrhythmia radioablation (STAR). METHODS: 4D computed tomography (4DCT) scans of patients imaged with AC or without AC (free-breathing: FB) were obtained from ventricular-tachycardia (VT) (n = 3), lung cancer (n = 18), and liver cancer (n = 18) patients. Patients treated for VT were imaged both FB and with AC. Lung and liver patients were imaged once with FB or with AC, respectively. The heart, left ventricle (LV), LV components (LVCs), and stomach were contoured on each phase of the 4DCTs. Centre of mass (COM) translations in the left/right (LR), ant/post (AP), and sup/inf (SI) directions were measured for each structure. Minimum distances between LVCs and the stomach over the respiratory cycle were also measured on each 4DCT phase. Mann-Whitney U-tests were performed between AC and FB datasets with a significance of α = 0.05. RESULTS: No statistical difference (all p values were >0.05) was found in COM translations between FB and AC patient datasets for all contoured cardiac structures. A reduction in COM translation with AC relative to FB was patient, direction, and structure specific for the three VT patients. A significant decrease in the AP range of motion of the stomach was observed under AC compared to FB. No statistical difference was found between minimum distances to the stomach and LVCs between FB and AC. CONCLUSIONS: AC was not a consistent motion management method for STAR, nor does not uniformly affect the separation distance between LVCs and the stomach. If AC is employed in future STAR protocols, the motion of the target volume and its relative distance to the stomach should be compared on two 4DCTs: one while the patient is FB and one under AC.

Radiographic Cortical Thickness Index Predicts Fragility Fracture in Gaucher Disease.

Background Patients with Gaucher disease (GD) have a high risk of fragility fractures. Routine evaluation of bone involvement in these patients includes radiography and repeated dual-energy x-ray absorptiometry (DXA). However, osteonecrosis and bone fracture may affect the accuracy of DXA. Purpose To assess the utility of DXA and radiographic femoral cortical thickness measurements as predictors of fragility fracture in patients with GD with long-term follow-up (up to 30 years). Materials and Methods Patients with GD age 16 years and older with a detailed medical history, at least one bone image (DXA and/or radiographs), and minimum 2 years follow-up were retrospectively identified using three merged UK-based registries (Gaucherite study, enrollment 2015-2017; Clinical Bone Registry, enrollment 2003-2006; and Mortality Registry, enrollment 1993-2019). Cortical thickness index (CTI) and canal-to-calcar ratio (CCR) were measured by two independent observers, and inter- and intraobserver reliability was calculated. The fracture-predictive value of DXA, CTI, CCR, and cutoff values were calculated using receiver operating characteristic curves. Statistical differences were assessed using univariable and multivariable analysis. Results Bone imaging in 247 patients (123 men, 124 women; baseline median age, 39 years; IQR, 27-50 years) was reviewed. The median follow-up period was 11 years (IQR, 7-19 years; range, 2-30 years). Thirty-five patients had fractures before or at first bone imaging, 23 patients had fractures after first bone imaging, and 189 patients remained fracture-free. Inter- and intraobserver reproducibility for CTI/CCR measurements was substantial (range, 0.96-0.98). In the 212 patients with no baseline fracture, CTI (cutoff, ≤0.50) predicted future fractures with higher sensitivity and specificity (area under the receiver operating characteristic curve [AUC], 0.96; 95% CI: 0.84, 0.99; sensitivity, 92%; specificity, 96%) than DXA T-score at total hip (AUC, 0.78; 95% CI: 0.51, 0.91; sensitivity, 64%; specificity, 93%), femoral neck (AUC, 0.73; 95% CI: 0.50, 0.86; sensitivity, 64%; specificity, 73%), lumbar spine (AUC, 0.69; 95% CI: 0.49, 0.82; sensitivity, 57%; specificity, 63%), and forearm (AUC, 0.78; 95% CI: 0.59, 0.89; sensitivity, 70%; specificity, 70%). Conclusion Radiographic cortical thickness index of 0.50 or less was a reliable independent predictor of fracture risk in Gaucher disease. Clinical trial registration no. NCT03240653 © RSNA, 2022 Supplemental material is available for this article.

Investigating Variability in Microbial Fuel Cells.

In scientific studies, replicas should replicate, and identical conditions should produce very similar results which enable parameters to be tested. However, in microbial experiments which use real world mixed inocula to generate a new "adapted" community, this replication is very hard to achieve. The diversity within real-world microbial systems is huge, and when a subsample of this diversity is placed into a reactor vessel or onto a surface to create a biofilm, stochastic processes occur, meaning there is heterogeneity within these new communities. The smaller the subsample, the greater this heterogeneity is likely to be. Microbial fuel cells are typically operated at a very small laboratory scale and rely on specific communities which must include electrogenic bacteria, known to be of low abundance in most natural inocula. Microbial fuel cells (MFCs) offer a unique opportunity to investigate and quantify variability as they produce current when they metabolize, which can be measured in real time as the community develops. In this research, we built and tested 28 replica MFCs and ran them under identical conditions. The results showed high variability in terms of the rate and amount of current production. This variability perpetuated into subsequent feeding rounds, both with and without the presence of new inoculate. In an attempt to control this variability, reactors were reseeded using established "good" and "bad" reactors. However, this did not result in replica biofilms, suggesting there is a spatial as well as a compositional control over biofilm formation. IMPORTANCE The research presented, although carried out in the area of microbial fuel cells, reaches an important and broadly impacting conclusion that when using mixed inoculate in replica reactors under replicated conditions, different communities emerge capable of different levels of metabolism. To date there has been very little research focusing on this, or even reporting it, with most studies using duplicate or triplicate reactors, in which this phenomenon is not fully observed. Publishing data in which replicas do not replicate will be an important and brave first step in the research into understanding this fundamental microbial process.

The efficacy of cariprazine on cognition: a post hoc analysis from phase II/III clinical trials in bipolar mania, bipolar depression, and schizophrenia.

OBJECTIVE: To investigate the effect of cariprazine on cognitive symptom change across bipolar I disorder and schizophrenia. METHODS: Post hoc analyses of 3- to 8-week pivotal studies in bipolar I depression and mania were conducted; one schizophrenia trial including the Cognitive Drug Research System attention battery was also analyzed. Outcomes of interest: Montgomery-Åsberg Depression Rating Scale [MADRS], Functioning Assessment Short Test [FAST], Positive and Negative Syndrome Scale [PANSS]). LSMDs in change from baseline to end of study were reported in the overall intent-to-treat population and in patient subsets with specified levels of baseline cognitive symptoms or performance. RESULTS: In patients with bipolar depression and at least mild cognitive symptoms, LSMDs were statistically significant for cariprazine vs placebo on MADRS item 6 (3 studies; 1.5 mg=-0.5 [P<.001]; 3 mg/d=-0.2 [P<.05]) and on the FAST Cognitive subscale (1 study; 1.5 mg/d=-1.4; P=.0039). In patients with bipolar mania and at least mild cognitive symptoms, the LSMD in PANSS Cognitive subscale score was statistically significant for cariprazine vs placebo (3 studies; -2.1; P=.001). In patients with schizophrenia and high cognitive impairment, improvement in power of attention was observed for cariprazine 3 mg/d vs placebo (P=.0080), but not for cariprazine 6 mg/d; improvement in continuity of attention was observed for cariprazine 3 mg/d (P=.0012) and 6 mg/d (P=.0073). CONCLUSION: These post hoc analyses provide preliminary evidence of greater improvements for cariprazine vs placebo across cognitive measures in patients with bipolar I depression and mania, and schizophrenia, suggesting potential benefits for cariprazine in treating cognitive symptoms.

Patterns and outcomes of weekend admission for acute ischemic stroke.

BACKGROUND AND OBJECTIVES: The "weekend effect" describes worse care delivery during off-hours or weekends and has been demonstrated in multiple sub-specialties. Off-hours care for acute ischemic stroke (AIS) has been associated with poorer outcomes. However, there is less data about the "weekend effect" on endovascular thrombectomy (ET) outcomes. METHODS: We used Medicare 100% sample datasets and included all AIS admissions from 2018-2019, using validated International Classification of Diseases, 10th Revision, Clinical Modification codes to identify AIS and comorbidities. Medicare provides the date of admission for all hospitalizations, and the day of the week was determined and assigned to weekend (Saturday or Sunday) or weekday (Monday through Friday). We defined 3 major outcomes: inpatient mortality, discharge home (vs. other destination), and 30-day mortality. RESULTS: Among 471427 AIS admissions,13.0% and 12.9% of all AIS admissions occurred on a Saturday and Sunday, respectively, less than the expected 14.3% occurring on any given day (p-value <0.0001). AIS admissions on a weekend were less likely to receive IV thrombolysis (13.6% on Saturday and 12.9% on Sunday) and ET (13.1% on Saturday and 13.2% on Sunday), p-value <0.0001. Among all AIS admissions, weekend admission was associated with worse outcomes, including higher odds of inpatient mortality (adjusted OR 1.04 [95% CI 1.01-1.08, p<0.0001]), lower odds of discharge home (0.94 [0.93-0.96, p<0.0001]), and higher odds of 30-day mortality (1.06 [1.04-1.08, p<0.0001]). However, among AIS patients treated with ET, there was no association of weekend admission with outcomes. CONCLUSIONS: In this national and contemporary dataset, we observed that the proportion of thrombolysis and ET cases was less over the weekend, and outcomes (inpatient mortality, 30-day mortality and odds of discharge home) were worse overall. We did not observe this association among AIS patients undergoing ET on a weekend vs. weekday.

Relationships among hospital acute ischemic stroke volumes, hospital characteristics, and outcomes in the US.

BACKGROUND AND OBJECTIVES: Prior research on volume-based patient outcomes related to acute ischemic stroke (AIS) have demonstrated contradictory results and fail to reflect recent advances in stroke care. We sought to examine contemporary relationships between hospital AIS volumes and outcomes. METHODS: We used complete Medicare datasets in a retrospective cohort study using validated International Classification of Diseases Tenth Revision codes to identify patients admitted with AIS from January 1, 2016 through December 31, 2019. AIS volume was calculated as the total number of AIS admissions per hospital during the study period. We examined several hospital characteristics by AIS volume quartile. We performed adjusted logistic regressions testing associations of AIS volume quartiles with: inpatient mortality, receipt of tissue plasminogen activator (tPA) and endovascular therapy (ET), discharge home, and 30-day outpatient visit. We adjusted for sex, age, Charlson comorbidity score, teaching hospital status, MDI, hospital urban-rural designation, stroke certification status and ICU and neurologist availability at the hospital. RESULTS: There were 952400 AIS admissions among 5084 US hospitals; AIS 4-year volume quartiles were: 1st: 1-8 AIS admissions; 2nd: 9-44; 3rd: 45-237; 4th: 238+. Highest quartile hospitals more often were stroke-certified (49.1% vs 8.7% in lowest quartile, p<0.0001), with ICU bed availability (19.8% vs 4.1%, p<0.0001) and with neurologist expertise (91.1% vs 3%, p<0.0001). In the highest AIS quartile (compared to the lowest quartile), there was lower inpatient mortality (odds ratio [OR] 0.71 [95%CI 0.57-0.87, p<0.0001]), lower 30-day mortality (0.55 [0.49-0.62], p<0.0001), greater receipt of tPA (6.60 [3.19-13.65], p<0.0001) and ET (16.43 [10.64-25.37], p<0.0001, and greater likelihood of discharge home (1.38 [1.22-1.56], p<0.0001). However, when the highest quartile hospitals were examined separately, higher volumes were associated with higher mortality despite higher rates of tPA and ET receipt. CONCLUSIONS: High AIS-volume hospitals have greater utilization of acute stroke interventions, stroke certification and availability of neurologist and ICU care. These features likely play a role in the better outcomes observed at such centers, including inpatient and 30-day mortality and discharge home. However, the highest volume centers had higher mortality despite greater receipt of interventions. Further research is needed to better understand volume-outcome relationships in AIS to improve care at lower volume centers.

KNOWLEDGE, AND ACCEPTANCE OF THE COVID-19 VACCINE AMONG WOMEN ATTENDING ANTENATAL AT PRIMARY HEALTHCARE CENTRES, JOS-PLATEAU STATE; NIGEIRA.

Introduction: COVID-19 Vaccination has been met with a variation in acceptability for various reasons, ranging from spiritual to physical perception of the vaccines, false information, and lack of information. Adequate knowledge and positivity will lead to high acceptance and willingness to take the vaccine. Acceptance of the vaccine by the general public and healthcare workers appears to play a major role in controlling the pandemic. Vaccine hesitancy is viewed by the World Health Organization as the world's top threat to public health, particularly in low- and middle-income countries. Objective: This study is aimed at assessing the knowledge, acceptance, and perception of the COVID-19 vaccine among women attending Antenatal at Primary Healthcare Centers in Jos-Plateau State; Nigeria. Methodology: A descriptive cross-sectional study was done in 2021 among 250 pregnant women using a multistage sampling technique. A structured self-administered questionnaire was used. Data analysis was done using SPSS version 20. Sociology-demographic variables were presented on tables using frequencies and proportions. Knowledge, attitude, and perception were scored and graded appropriately. The level of significance was set at a p-value≤0.05. Results: The majority, 224 (89.6%) were aware that there is a vaccine for coronavirus. Majority, 173 (69.2%) of the respondents had a fair knowledge of the vaccine, 45 (18%) had good knowledge while 32 (12.8%) had poor knowledge. Majority 151 (60.4%) of the respondents were willing to receive the vaccine if it was made available while 99 (39.6%) were not willing. Although only about 60 (24%) had received the vaccine with 83% of these being before pregnancy, 23 (24.0%) experienced allergic symptoms after taking the coronavirus vaccine, and 13 (13.5%) took the vaccine during pregnancy. Of these pregnant women, 14 (25.0) experienced side effects. The major misconception among the women was centered around false information from social media, such as magnetic properties of the vaccine. The major systemic side effects that were experienced by those who had received the vaccine were headaches (47.6%), catarrh (28.6%), injection site swelling (22.2%), fever (20.5%), and fatigue (16.0%). Abdominal pains (18.8%), preterm contraction (15.6%), bleeding per vagina (15.6%), miscarriage (9.4%), reduced or poor fetal kicks (9.4%) occurred after taking the vaccine during pregnancy. Conclusion: The government and the PHC board should intensify sensitization of communities and patients about the COVID-19 vaccine using television, and radio and enlighten the persons who come for Ante Natal Care (ANC) through posters and oral awareness.

Evaluation of Adult Neurology Residency Program Websites.

OBJECTIVE: Neurology residency program websites often serve as the initial face of a program for prospective residents early in the application process. We evaluated adult neurology residency program websites to determine their comprehensiveness to identify areas for improvement. METHODS: A list of adult neurology residency programs in the United States was compiled using information on the Electronic Residency Application Service (ERAS) and Fellowship and Residency Electronic Interactive Database (FREIDA) websites. A total of 24 website criteria covering educational, recruitment, and compensation content were assessed for comprehensiveness. Programs' website comprehensiveness was compared based on geographic location, program affiliation (community and/or academic), program size, and program/hospital Doximity and U.S. News & World Report rankings. RESULTS: A total of 153 US adult neurology residency program websites were evaluated. Fewer than one-half of program websites were accessible with a direct link from either FREIDA or ERAS. The number of residency program websites reporting each content criterion varied greatly. Mean percentage of overall website comprehensiveness among neurology residency programs was 65.9%. Northeast location, academic affiliation, larger programs, and top-ranked programs on Doximity were associated with greater program website comprehensiveness. INTERPRETATION: There is opportunity for all neurology residency programs to improve their websites to provide prospective applicants with a more informed and comprehensive perspective of programs during the application process. ANN NEUROL 2021;89:637-642.

Why is oral-induced RNAi inefficient in Diatraea saccharalis? A possible role for DsREase and other nucleases.

The efficiency of RNAi technology in insects varies considerably, particularly in lepidopterans. An important limiting factor of RNAi-mediated gene silencing is the degradation of dsRNA by insect nucleases before cellular uptake. To date, few studies have reported effective gene knockdown in the sugarcane borer Diatraea saccharalis. However, yielding contradictory results when using oral delivery. Further, the RNAi efficiency in D. saccharalis and presumed activity of gut nucleases remain poorly understood. Therefore, we investigated whether gene silencing was feasible via dsRNA feeding in D. saccharalis. Two different genes were tested, juvenile hormone esterase (DsJHE) and chitin synthase 1 (DsCHS1). Discrete knockdown was verified only for DsCHS1 with high dsRNA dosages and long exposure times. Neither mortality nor abnormal phenotypes were observed after treatment with any tested dsRNA. It was also verified that dsRNAs were quickly degraded when incubated with gut juice. Furthermore, we identified four possible nucleases that could reduce the knockdown efficiency in D. saccharalis. Three of them had the endonuclease_NS domain (DsNucleases), and one had the PIN domain (DsREase), with REase-like genes being scarcely represented in databanks. We further remark that DsNuclease1 and DsREase are highly expressed in the larval gut, and DsREase was upregulated as insects were fed with artificial diet (without dsRNA), and also when injected with dsRNA. Conversely, no nuclease was triggered when insects were fed with a sucrose droplet containing dsRNA. Thus, our findings suggest that nuclease activity within the gut is one of the possible reasons for the inefficiency of RNAi in D. saccharalis. Our data may shed light on the challenges to overcome when introducing RNAi as a strategy for controlling lepidopteran pests.

Variability in Intensive Care Utilization for Intracerebral Hemorrhage in the United States: Retrospective Cohort Study.

OBJECTIVES: There are urban-rural geographic health disparities in intracerebral hemorrhage (ICH) outcomes. However, there is limited data regarding the relationship between intensive care (ICU) availability and ICH outcomes. We examined whether ICU availability was a significant contributor to ICH outcomes by US geographic region. MATERIALS AND METHODS: We used de-identified Medicare inpatient datasets from January 2016 to December 2019 and identified all index ICH admissions, stratifying by ICU care received during the hospitalization. Distributions of teaching hospital status, quartile of ICH volume, hospital urban-rural designation, and ICU availability were obtained using chi-square test. Propensity-score matching was utilized to compare outcomes of more favorable outcome, inpatient mortality, and 30-day all-cause readmissions by ICU availability at each hospital. RESULTS: Out of a total of 119,891 hospitalizations for ICH, 66,306 (55.3%) received ICU-level care. Of hospitals that treated at least one ICH, 42.6% did not provide ICU level care for any ICH admission during the study period. Teaching hospitals (48.0% vs 7.0%; p<0.0001), hospitals with higher ICH case volumes (p<0.0001) and in larger metropolitan areas (p<0.0001) were more likely to have an ICU available. Propensity score-matched models showed that hospital ICU availability was associated with a lower likelihood of inpatient mortality (29.4% vs 33.7%; p=0.0016) CONCLUSIONS: Rural-urban disparities in ICH outcomes are likely multifactorial, but ICU availability likely contributes to the disparity. Additional studies are necessary to elucidate other contributing mechanisms.

Evaluation of single and combined effects of two pharmaceuticals on the marine gastropod Phorcus lineatus enzymatic activity under two different exposure periods.

Pharmaceutical drugs are among the most used chemicals for human and veterinary medicines, aquaculture and agriculture. Pharmaceuticals are environmentally persistent, biologically active molecules, thereby having the potential to exert biological effects on non-target species. Among the most used pharmaceuticals, one may find salicylic acid (SA), a non-steroid anti-inflammatory drug (NSAID) that acts by inhibiting the enzymes cyclooxigenases; it is also possible to identify acetazolamide (ACZ), a diuretic that acts by inhibiting the activity of carbonic anhydrase (CA). In this work, the effects of both single and combined effects of these drugs were assessed on the marine gastropod Phorcus lineatus, by measuring key enzymatic activities, namely carbonic anhydrase (CA) and cyclooxygenase (COX), under two different exposure periods (14 and 28 days). We observed no straightforward pattern of enzymatic response in all treatments of both pharmaceuticals, on both analyzed tissues (gut and gills), and for both exposure regimes. We assume that this species is not responsive to the hereby tested pharmaceuticals, a finding that may be due to general mechanisms of response to adverse conditions, such as reduction of metabolism, of heart rate, of filtration rates, and to the increase production of mucus. All these functional adaptations can mitigate the deleterious effects caused by adverse conditions, without triggering biochemical responses. In conclusion, the species P. lineatus seems not to be sensitive in terms of these specific enzymatic pathways to these contaminants, under the adopted conditions.

Treatment outcomes after uncomplicated and complicated crown fractures in permanent teeth.

OBJECTIVES: The objectives of this retrospective clinical study were to describe characteristics of crown fractures in permanent teeth and to investigate the survival of pulp vitality and restorations in uncomplicated and complicated crown fractures. MATERIALS AND METHODS: This retrospective study collected information from patients suffering from dental trauma who were treated between January 2004 and June 2017. The study population consisted of 434 patients (253 males/181 females; mean age 20.7 years) with 489 uncomplicated and 127 complicated crown fractures. The Kaplan-Meier survival curves and Cox proportional hazard regression analyses were performed to explore the data statistically. RESULTS: The mean observation time was 522 days. Uncomplicated crown fractures without luxation showed a higher success rate of 82.3% (345/419) than complicated crown fractures without luxation (72.3%, 73/101). An additional luxation in uncomplicated crown fractures resulted in significantly reduced success rates in terms of survival of the pulp and restoration. Direct restorations survived significantly better independent of the fracture mode than did adhesively reattached crown fragments. No superiority of mineral trioxide aggregate or calcium hydroxide as pulp capping agent in complicated crown fractures was documented. Approximately 85.5% of all complications occurred within 2 years after the accident. CONCLUSION: The treatment of crown fractures resulted mostly in successful outcomes and only a moderate number of complications were observed. CLINICAL RELEVANCE: Primary dental management of crown fractures should follow recently published clinical guidelines, and close monitoring over at least 2 years seems to be justified.

Survival analysis of adhesive reattachments in permanent teeth with crown fractures after dental trauma.

BACKGROUND/AIM: When patients have saved tooth fragments in case of crown fractures, reattachment is considered as the treatment of choice. With respect to the need to provide clinical outcome data regarding adhesively reattached fragments, the aim of this practice-based clinical study was to evaluate the survival of reattached fragments after crown fractures in permanent teeth. MATERIALS AND METHODS: Records from patients treated at Ludwig-Maximilians-University between 2004 and 2017 were analyzed to collect clinical and radiographic data regarding the management of fractured teeth that were treated with an adhesive reattachment. The study population consisted of 109 patients comprising 135 reattached fragments divided into uncomplicated (N = 84/135) and complicated (N = 51/135) crown fractures. The Kaplan-Meier Survival estimator was used to estimate the survival probability of primary reattachments after uncomplicated and complicated crown fractures. RESULTS: Overall, 77.4% (N = 65/84) and 66.6% (N = 34/51) of the primarily applied reattachments in uncomplicated fractured teeth and complicated fractured teeth, respectively, survived over the period of observation. The survival rate for adhesive reattachment in all teeth was 84.4% (N = 114/135) after 608.2 days (±983.1 days). The data further suggest that in the case of a detachment, repeated reattachment might be a valuable restoration strategy. CONCLUSIONS: Adhesive reattachment is a good first-choice treatment option in cases of crown fractures when the fractured fragment has been saved.

Exascale applications: skin in the game.

As noted in Wikipedia, skin in the game refers to having 'incurred risk by being involved in achieving a goal', where 'skin is a synecdoche for the person involved, and game is the metaphor for actions on the field of play under discussion'. For exascale applications under development in the US Department of Energy Exascale Computing Project, nothing could be more apt, with the skin being exascale applications and the game being delivering comprehensive science-based computational applications that effectively exploit exascale high-performance computing technologies to provide breakthrough modelling and simulation and data science solutions. These solutions will yield high-confidence insights and answers to the most critical problems and challenges for the USA in scientific discovery, national security, energy assurance, economic competitiveness and advanced healthcare. This article is part of a discussion meeting issue 'Numerical algorithms for high-performance computational science'.

The Effect of Propofol on a Forced Swim Test in Mice at 24 Hours.

BACKGROUND: There are few rapidly acting treatments for acute suicidality or treatment-resistant depression. Propofol (2,6-diisopropylphenol) is an intravenous anesthetic agent used in outpatient settings. It is a gamma-aminobutyric acid type A agonist and has affinity at the N-methyl-D-aspartate receptor. Elevation in mood and sociality in humans has been observed following propofol-induced anesthesia. Other authors reported an open-label study of repeated dosing of propofol in treatment-resistant depression in which several patients experienced sustained improvement. Recently, we reported that in a rodent model of despair, a forced swim test, 45 minutes after administration of 50 mg/kg propofol, immobility time was significantly reduced. OBJECTIVE: The objective of the experiment was to determine whether the antidepressant-like effects of a single dose of propofol in mice are sustained for 24 hours. METHODS: The time spent immobile during a forced swim test 24 hours after intraperitoneal administration of a single dose of propofol 50 mg/kg or 0.9% saline was evaluated in 24 adult male mice (C57/BL6). Immobility time was quantified and evaluated with a custom video analysis software program. RESULTS: Propofol-treated mice were immobile for a mean (SEM) time of 115 (13) seconds, whereas saline-treated mice were immobile for a mean (SEM) time of 94 (14) seconds. A 2-tailed unpaired t test found no significant difference between the treatment groups (t = 1.07, df = 22; P = 0.30). CONCLUSIONS: Twenty-four hours after intraperitoneal administration, the effect of propofol on immobility time was not statistically significantly different from vehicle. However, given our previous report of at least a short-term benefit of propofol on struggling time in the forced swim time and an encouraging pilot study in humans with treatment-resistant depression, further evaluation of propofol's antidepressant potential may be warranted.

The AIRE Ser196Ser synonymous variant is a risk factor for systemic lupus erythematosus.

The AIRE gene influences the expression of a wide array of self-antigens in the thymus, and is essential to the negative selection of self-reactive T cells and establishment of central tolerance. Single nucleotide variants (SNVs) such as rs878081C/T (Ser196Ser) and rs2075876G/T at this locus have been associated with susceptibility to rheumatoid arthritis, mainly in Asian populations, but its role in systemic lupus erythematosus (SLE) has not been documented. We performed a case-control association study with 379 SLE patients and 460 controls from central Mexico. In addition, we replicated our finding in another group of 179 SLE patients and 97 controls from the same region of Mexico. In the first group, we identified that the AIRE Ser196Ser synonymous variant was associated with SLE (OR 1.4, p = 0.009), meanwhile, in the second group we observed the following: OR 1.7, p = 0.024. No association was found between these AIRE SNVs and lupus nephritis. Our results suggest that AIRE is a risk factor for SLE in our population. This study is the first to document an association between AIRE and SLE susceptibility.

Sensitive Bacterial Detection via Dielectrophoretic-Enhanced Mass Transport Using Surface-Plasmon-Resonance Biosensors.

The performance of surface plasmon resonance (SPR)-based bacterial biosensors is often compromised as a result of diffusion-limited mass transport of bacteria to the sensing surface. In this work, dually functional interdigitated electrodes (IDEs) were developed to sustain SPR and increase bacterial mass transport through external application of dielectrophoresis (DEP). IDEs were defined into 50 nm Au films with fixed electrode gaps ( EG = 5 µm) and varied electrode widths ( EW = 10, 20, and 100 µm),  referred to as interdigitated SPR (iSPR) chips. The iSPR chips with EW = 100 µm effectively supported SPR, with comparable sensitivity to those of conventional SPR chips. The surfaces of iSPR chips ( EW = 100 µm) were modified with mannose to target the FimH adhesin of Escherichia coli and increase cellular adhesion. An LOD of ∼3.0 × 102 CFU/mL E. coli was achieved on mannosylated iSPR chips under positive-DEP conditions, which is about a 5 order of magnitude improvement compared with those of mannosylated conventional SPR chips without DEP. Furthermore, secondary antibody amplification enabled selective enhancement of dilute (103 CFU/mL) E. coli suspensions, whereas no amplification was observed for concentrated (108 CFU/mL) nontarget ( Staphylococcus epidermidis) bacterial suspensions. The results presented here indicate the great potential of the incorporation of DEP into SPR biosensors for rapid, sensitive, and specific detection of bacteria with broad applications in areas of biomedical diagnostics, environmental monitoring, food safety, and homeland security.