Efficient Enzymatic Synthesis of Carbamates in Water Using Promiscuous Esterases/Acyltransferases.

Biocatalysis provides an attractive approach to facilitate synthetic reactions in aqueous media. Motivated by the discovery of promiscuous aminolysis activity of esterases, we exploited the esterase from Pyrobaculum calidifontis VA1 (PestE) for the synthesis of carbamates from different aliphatic, aromatic, and arylaliphatic amines and a set of carbonates such as dimethyl-, dibenzyl-, or diallyl carbonate. Thus, aniline and benzylamine derivatives, aliphatic and even secondary amines could be efficiently converted into the corresponding benzyloxycarbonyl (Cbz)- or allyloxycarbonyl (Alloc)-protected products in bulk water, with (isolated) yields of up to 99%.

Comparison of 3T and 7T magnetic resonance imaging for direct visualization of finger flexor pulley rupture: an ex-vivo study.

OBJECTIVE: To compare image quality and diagnostic performance of 3T and 7T magnetic resonance imaging (MRI) for direct depiction of finger flexor pulleys A2, A3 and A4 before and after artificial pulley rupture in an ex-vivo model using anatomic preparation as reference. MATERIALS AND METHODS: 30 fingers from 10 human cadavers were examined at 3T and 7T before and after being subjected to iatrogenic pulley rupture. MRI protocols were comparable in duration, both lasting less than 22 min. Two experienced radiologists evaluated the MRIs. Image quality was graded according to a 4-point Likert scale. Anatomic preparation was used as gold standard. RESULTS: In comparison, 7T versus 3T had a sensitivity and specificity for the detection of A2, A3 and A4 pulley lesions with 100% vs. 95%, respectively 98% vs. 100%. In the assessment of A3 pulley lesions sensitivity of 7T was superior to 3T MRI (100% vs. 83%), whereas specificity was lower (95% vs. 100%). Image quality assessed before and after iatrogenic rupture was comparable with 2.74 for 7T and 2.61 for 3T. Visualization of the A3 finger flexor pulley before rupture creation was significantly better for 7 T (p < 0.001). Interobserver variability showed substantial agreement at 3T (κ = 0.80) and almost perfect agreement at 7T (κ = 0.90). CONCLUSION: MRI at 3T allows a comparable diagnostic performance to 7T for direct visualization and characterization of finger flexor pulleys before and after rupture, with superiority of 7T MRI in the visualization of the normal A3 pulley.

Lower odds of successful community discharge after medical hospitalization for Veterans with schizophrenia: A retrospective cohort study of national data.

Medical comorbidity, particularly cardiovascular diseases, contributes to high rates of hospital admission and early mortality in people with schizophrenia. The 30 days following hospital discharge represents a critical period for mitigating adverse outcomes. This study examined the odds of successful community discharge among Veterans with schizophrenia compared to those with major affective disorders and those without serious mental illness (SMI) after a heart failure hospital admission. Data for Veterans hospitalized for heart failure were obtained from the Veterans Health Administration (VHA) and Centers for Medicare & Medicaid Services between 2011 and 2019. Psychiatric diagnoses and medical comorbidities were assessed in the year prior to hospitalization. Successful community discharge was defined as remaining in the community without hospital readmission, death, or hospice for 30 days after hospital discharge. Logistic regression analyses adjusting for relevant factors were used to examine whether individuals with a schizophrenia diagnosis showed lower odds of successful community discharge versus both comparison groups. Out of 309,750 total Veterans in the sample, 7377 (2.4%) had schizophrenia or schizoaffective disorder and 32,472 (10.5%) had major affective disorders (bipolar disorder or recurrent major depressive disorder). Results from adjusted logistic regression analyses demonstrated significantly lower odds of successful community discharge for Veterans with schizophrenia compared to the non-SMI (Odds Ratio [OR]: 0.63; 95% Confidence Interval [CI]: 0.60, 0.66) and major affective disorders (OR: 0.65, 95%; CI: 0.62, 0.69) groups. Intervention efforts should target the transition from hospital to home in the subgroup of Veterans with schizophrenia.

Fusion Imaging of Non-Invasive and Invasive Cardiac Electroanatomic Mapping in Patients with Ventricular Ectopic Beats: A Feasibility Analysis in a Case Series.

In patients with premature ventricular contractions (PVCs), non-invasive mapping could locate the PVCs' origin on a personalized 3-dimensional (3D) heart model and, thus, facilitate catheter ablation therapy planning. The aim of our report is to evaluate its accuracy compared to invasive mapping in terms of assessing the PVCs' early activation zone (EAZ). For this purpose, non-invasive electrocardiographic imaging (ECGI) was performed using the Amycard 01C system (EP Solutions SA, Switzerland) in three cases. In the first step, a multichannel ECG (up to 224 electrodes) was recorded, and the dominant PVCs were registered. Afterward, a cardiac computed tomography (in two cases) or magnetic resonance imaging (in one case) investigation was carried out acquiring non-contrast torso scans for 8-electrode strip visualization and contrast heart acquisition. For the reconstructed epi/endocardial meshes of the heart, non-invasive isochronal maps were generated for the selected multichannel ECG fragments. Then, the patients underwent an invasive electrophysiological study, and the PVCs' activation was evaluated by a 3D mapping system (EnSite NavX Precision, Abbott). Finally, using custom-written software, we performed 3D fusion of the non-invasive and invasive models and compared the resulting isochronal maps. A qualitative analysis in each case showed the same early localization of the dominant PVC on the endocardial surface when comparing the non-invasive and invasive isochronal maps. The distance from the EAZ to the mitral or tricuspid annulus was comparable in the invasive/non-invasive data (36/41 mm in case N1, 73/75 mm in case N2, 9/12 mm in case N3). The area of EAZ was also similar between the invasive/non-invasive maps (4.3/4.5 cm2 in case N1, 7.1/7.0 cm2 in case N2, 0.4/0.6 cm2 in case N3). The distances from the non-invasive to invasive earliest activation site were 4 mm in case N1, 7 mm in case N2, and 4 mm in case N3. Such results were appropriate to trust the clinical value of the preoperative data in these cases. In conclusion, the non-invasive identification of PVCs before an invasive electrophysiological study can guide clinical and interventional decisions, demonstrating appropriate accuracy in the estimation of focus origin.

Detection of femoropopliteal arterial steno-occlusion at MR angiography: initial experience with artificial intelligence.

BACKGROUND: This study evaluated a deep learning (DL) algorithm for detecting vessel steno-occlusions in patients with peripheral arterial disease (PAD). It utilised a private dataset, which was acquired and annotated by the authors through their institution and subsequently validated by two blinded readers. METHODS: A single-centre retrospective study analysed 105 magnetic resonance angiography (MRA) images using an EfficientNet B0 DL model. Initially, inter-reader variability was assessed using the complete dataset. For a subset of these images (29 from the left side and 35 from the right side) where digital subtraction angiography (DSA) data was available as the ground truth, the model's accuracy and the area under the curve at receiver operating characteristics analysis (ROC-AUC) were evaluated. RESULTS: A total of 105 patient examinations (mean age, 75 years ±12 [mean ± standard deviation], 61 men) were evaluated. Radiologist-DL model agreement had a quadratic weighted Cohen κ ≥ 0.72 (left side) and ≥ 0.66 (right side). Radiologist inter-reader agreement was ≥ 0.90 (left side) and ≥ 0.87 (right side). The DL model achieved a 0.897 accuracy and a 0.913 ROC-AUC (left side) and 0.743 and 0.830 (right side). Radiologists achieved 0.931 and 0.862 accuracies, with 0.930 and 0.861 ROC-AUCs (left side), and 0.800 and 0.799 accuracies, with 0.771 ROC-AUCs (right side). CONCLUSION: The DL model provided valid results in identifying arterial steno-occlusion in the superficial femoral and popliteal arteries on MRA among PAD patients. However, it did not reach the inter-reader agreement of two radiologists. RELEVANCE STATEMENT: The tested DL model is a promising tool for assisting in the detection of arterial steno-occlusion in patients with PAD, but further optimisation is necessary to provide radiologists with useful support in their daily routine diagnostics. KEY POINTS: • This study focused on the application of DL for arterial steno-occlusion detection in lower extremities on MRA. • A previously developed DL model was tested for accuracy and inter-reader agreement. • While the model showed promising results, it does not yet replace human expertise in detecting arterial steno-occlusion on MRA.

Serious mental illness is associated with elevated risk of hospital readmission in veterans with heart failure.

OBJECTIVE: Adults with serious mental illness (SMI) have high rates of cardiovascular disease, particularly heart failure, which contribute to premature mortality. The aims were to examine 90- and 365-day all-cause medical or surgical hospital readmission in Veterans with SMI discharged from a heart failure hospitalization. The exploratory aim was to evaluate 180-day post-discharge engagement in cardiac rehabilitation, an effective intervention for heart failure. METHODS: This study used administrative data from the Veterans Health Administration (VHA) and Centers for Medicare & Medicaid Services between 2011 and 2019. SMI status and medical comorbidity were assessed in the year prior to hospitalization. Cox proportional hazards models (competing risk of death) were used to evaluate the relationship between SMI status and outcomes. Models were adjusted for VHA hospital site, demographics, and medical characteristics. RESULTS: The sample comprised 189,767 Veterans of which 23,671 (12.5%) had SMI. Compared to those without SMI, Veterans with SMI had significantly higher readmission rates at 90 (16.1% vs. 13.9%) and 365 (42.6% vs. 37.1%) days. After adjustment, risk of readmission remained significant (90 days: HR: 1.07, 95% CI: 1.03, 1.11; 365 days: HR: 1.10, 95% CI: 1.07, 1.12). SMI status was not significantly associated with 180-day cardiac rehabilitation engagement (HR: 0.98, 95% CI: 0.91, 1.07). CONCLUSIONS: Veterans with SMI and heart failure have higher 90- and 365-day hospital readmission rates even after adjustment. There were no differences in cardiac rehabilitation engagement based on SMI status. Future work should consider a broader range of post-discharge interventions to understand contributors to readmission.

Changes in the burden of medications that may impair driving among older adults before and after a motor vehicle crash.

BACKGROUND: Medications are one of the most easily modifiable risk factors for motor vehicle crashes (MVCs) among older adults, yet limited information exists on how the use of potentially driver-impairing (PDI) medications changes following an MVC. Therefore, we examined the number and types of PDI medication classes dispensed before and after an MVC. METHODS: This observational study included Medicare fee-for-service beneficiaries aged ≥67 years who were involved in a police-reported MVC in New Jersey as a driver between 2008 and 2017. Analyses were conducted at the "person-crash" level because participants could be involved in more than one MVC. We examined the use of 36 PDI medication classes in the 120 days before and 120 days after MVC. We described the number and prevalence of PDI medication classes in the pre-MVC and post-MVC periods as well as the most common PDI medication classes started and stopped following the MVC. RESULTS: Among 124,954 person-crashes, the mean (SD) age was 76.0 (6.5) years, 51.3% were female, and 83.9% were non-Hispanic White. The median (Q1 , Q3 ) number of PDI medication classes was 2 (1, 4) in both the pre-MVC and post-MVC periods. Overall, 20.3% had a net increase, 15.9% had a net decrease, and 63.8% had no net change in the number of PDI medication classes after MVC. Opioids, antihistamines, and thiazide diuretics were the top PDI medication classes stopped following MVC, at incidences of 6.2%, 2.1%, and 1.7%, respectively. The top medication classes started were opioids (8.3%), skeletal muscle relaxants (2.2%), and benzodiazepines (2.1%). CONCLUSIONS: A majority of crash-involved older adults were exposed to multiple PDI medications before and after MVC. A greater proportion of person-crashes were associated with an increased rather than decreased number of PDI medications. The reasons why clinicians refrain from stopping PDI medications following an MVC remain to be elucidated.

Ossification and Bone Regeneration in a Canine GBR Model, Part 2: Glycated Cross-Linked Collagenated Alloplastic Hydroxyapatite Scaffold vs Non-Cross-Linked Collagenated Xenographic Bone Hydroxyapatite.

PURPOSE: To compare bone substitutes composed of glycated collagen with synthetic micro-sized (1 to 10 µm) hydroxyapatite (OB) vs non-cross-linked collagen matrix with large-particle (250 to 1,000 µm) bovine-derived hydroxyapatite (BOC). MATERIALS AND METHODS: The P1 to P4 premolars were bilaterally extracted from the mandibles of 19 Beagle dogs. After 21 days, osteotomies were created in each dog that received OB or BOC and were covered with a collagen membrane or were left untreated. The animals were randomly divided into three groups based on sacrifice time (4, 12, or 24 weeks). The right and left hemimandibles were trimmed to facilitate imaging and histology, and all tissues were placed in 10% neutral-buffered formalin. Microcomputed tomography (MicroCT 40 Scanner, Scanco) was used to analyze bone sections. Bone volume, residual material volume, and bone mineral density were determined for each treatment site (OB and BOC) based on a volume of interest that encompassed the original defect. Additionally, blinded histopathologic assessment (based on the ISO 10993-6 scoring system) and histomorphometry were performed on sections ground to < 100 µm thick and stained with Stevenel's blue. RESULTS: No clinical side effects were noted. No statistical differences were observed for OB vs BOC regarding the mineral volume percentage. Compared to OB, BOC had significantly higher mean mineralization densities at 12 weeks (P < .01), but this difference did not extend to 24 weeks. For residual grafting material, bone maturation, alveolar ridge restoration, and inflammatory response, OB showed a residual amount of bone graft and no statistical differences compared to BOC. CONCLUSION: Both OB and BOC represent valid treatment options for critically sized bone defects. Both bone fillers outperformed the sham-operated, ungrafted (empty) control, demonstrating statistically improved bone growth and ridge restoration.

Evaluation of finger cartilage composition in recreational climbers with 7 Tesla T2 mapping magnetic resonance imaging.

Purpose: Sport climbing may lead to tissue adaptation including finger cartilage before apparent surface damage is detectable. The main aim was to assess finger cartilage composition with T2 mapping in young, active climbers and to compare the results to a non-climbers' collective. A secondary aim was to compare whether differences in cartilage T2 times are observed between older vs. younger volunteers. Methods and materials: 7 Tesla MRI of the fingers Dig.2-4 was performed using a multi-echo spin echo sequence. Manual segmentation of 3 ROIs at the metacarpal heads, 1 ROI at the base phalanx and 1 ROI at the proximal interphalangeal joint was performed. Included were 13 volunteers without history of trauma who are regularly performing climbing activities as a recreational sport (>20 h/month). These were age-matched with 10 control subjects not performing climbing activities. Results: Mean age was 32.4 years for the climbing group and 25.8 years for the controls. Mean T2 values for the 5 different ROIs were 42.2 ± 7.8 msec for climbers and 41.4 ± 6.8 msec for non-climbers. No significant differences were observed for T2 values between both groups. However, higher age had a significant impact on T2 values for all assessed ROIs (higher age 44.2 ± 9.5, younger age 32.9 ± 5.7, p = 0.001). Discussion: This study evaluated the cartilage composition of young, engaged climbers with a T2 mapping MRI technique with the purpose to depict early onset joint changes. No negative impact on cartilage composition due to the sport activity was found, whereas age-related effects on the cartilage seemed to be more prominent.

Ossification and Bone Regeneration in a Canine GBR Model, Part 1: Thick vs Thin Glycated Cross-Linked Collagen Devices.

Purpose: To compare glycated multilayered membranes (OV) to a commercially available thin-layer membrane (OP) in a lateral ridge augmentation model in dogs. Materials and Methods: This was designed as a three-arm study, where one negative control (empty defect) was compared to two test arms: alveolar bone defects grafted with a mixture of 90% deproteinized bovine bone mineral and 10% porcine collagen, then covered with either a thick- (OV) or thin-layered (OP) membrane. Animals were randomly divided into three groups corresponding to the final sacrifice times of 4 weeks, 12 weeks, and 24 weeks. Sections underwent microCT, histology, histopathology, and histomorphometry. Results: No statistical differences were observed for OV compared to OP regarding the percentage of mineral volume and mean mineral density, amount of bone maturation, percentage of bone graft and membrane remaining in the grafted area, alveolar ridge width measurements, membrane mineralization, or ossification. Test groups presented significantly higher values compared to the empty control for all the endpoints. Conclusions: Within its limitations, this in vivo study highlighted that multilayered thick glycated membranes can serve as effective occlusive barriers for up to 6 months.

Development of an interactive elective "altered anatomy" for students as part of the Z-curriculum according to the NKLM 2.0.

Objective: Many patients have undergone visceral surgery. The effects on anatomy and physiology, which can result in further surgical or gastroenterological clinical pictures, are equally significant and require special knowledge. This content should be taught in an interdisciplinary elective course. The draft of the new 2025 approval regulation and the current approval regulation specify that preclinical and clinical content should specifically be combined within the framework of a Z-curriculum and that the new elective course should meet these requirements. Methodology: Practical and theoretical aspects of recognising and treating patients with postoperative modified anatomy are to be taught and the findings are to be demonstrated using anatomical and artificial preparations. The curriculum of the preclinical course covers anatomy and physiology. The target group of the curriculum is all participating students with a special interest in topics such as anatomy, visceral surgery and gastroenterology. However, the goal is to involve student tutors of the anatomical dissection courses, who, in turn, will pass on knowledge of modified anatomy to the supervised preclinical students. Results: According to Thomas and Kern, the curriculum development process entails the following six stages: general needs assessment, targeted needs assessment, the formulation of goals and content, the description of strategies, planned implementation and evaluation. Conclusion: A "modified anatomy" curriculum for an interdisciplinary elective course in surgery, gastroenterology, and anatomy was developed. Through the training of anatomy table tutors, a "dovetailing" with the preclinical stage is to be achieved. In addition, new concepts related to the transfer of knowledge and competencies were introduced and should be evaluated for suitability.

Comparing Lookback Periods to Ascertain Alzheimer's Disease and Related Dementias.

Claims data are a valuable resource for studying Alzheimer's disease and related dementias (ADRD). Alzheimer's disease and related dementias is often identified using a list of claims codes and a fixed lookback period of 3 years of data. However, a 1-year lookback or an approach using all-available lookback data could be beneficial based on different research questions. Thus, the purpose of this study was to compare 1-year and all-available lookback approaches to ascertaining ADRD compared to the standard 3-year approach. Using a cohort of Veterans hospitalized for heart failure (N = 373, 897), our results suggested high agreement (93% or greater) between the lookback periods. The 1-year lookback period had lower sensitivity (60%) and underestimated the prevalence of ADRD. These results suggest that 1-year and all-available lookback periods are viable approaches when using claims data.

Incidence of New Dementia Diagnosis in Veterans Admitted to Nursing Homes After Heart Failure Hospitalization.

BACKGROUND: Hospitalization with heart failure (HF) may signal an increased risk of Alzheimer's disease and related dementias (ADRD). Nursing homes routinely assess cognition but the association of these results with new ADRD diagnosis in a population at high risk of ADRD is not known. OBJECTIVE: To determine the association between nursing home cognitive assessment results and new diagnosis of dementia after heart failure hospitalization. METHODS: This retrospective cohort study included Veterans hospitalized for HF and discharged to nursing homes, from 2010 to 2015, without a prior diagnosis of ADRD. We determined mild, moderate, or severe cognitive impairment using multiple items of the nursing home admission assessment. We used Cox regression to determine the association of cognitive impairment with new ADRD diagnosis during 365 days of follow-up. RESULTS: The cohort included 7,472 residents, new diagnosis of ADRD occurred in 4,182 (56%). The adjusted hazard ratio of ADRD diagnosis was 4.5 (95% CI 4.2, 4.8) for the mild impairment group, 5.4 (95% CI 4.8, 5.9) for moderate impairment, and 4.0 (95% CI 3.2, 5.0) for severe impairment compared to the cognitively intact group. CONCLUSION: New ADRD diagnoses occurred in more than half of Veterans with HF admitted to nursing homes for post-acute care.

In Vivo Detection of Low Molecular Weight Platform Chemicals and Environmental Contaminants by Genetically Encoded Biosensors.

Genetically encoded biosensor systems operating in living cells are versatile, cheap, and transferable tools for the detection and quantification of a broad range of small molecules. This review presents state-of-the-art biosensor designs and assemblies, featuring transcription factor-, riboswitch-, and enzyme-coupled devices, highly engineered fluorescent probes, and emerging two-component systems. Importantly, (bioinformatic-assisted) strategies to resolve contextual issues, which cause biosensors to miss performance criteria in vivo, are highlighted. The optimized biosensing circuits can be used to monitor chemicals of low molecular mass (<200 g mol-1) and physicochemical properties that challenge conventional chromatographical methods with high sensitivity. Examples herein include but are not limited to formaldehyde, formate, and pyruvate as immediate products from (synthetic) pathways for the fixation of carbon dioxide (CO2), industrially important derivatives like small- and medium-chain fatty acids and biofuels, as well as environmental toxins such as heavy metals or reactive oxygen and nitrogen species. Lastly, this review showcases biosensors capable of assessing the biosynthesis of platform chemicals from renewable resources, the enzymatic degradation of plastic waste, or the bioadsorption of highly toxic chemicals from the environment. These applications offer new biosensor-based manufacturing, recycling, and remediation strategies to tackle current and future environmental and socioeconomic challenges including the wastage of fossil fuels, the emission of greenhouse gases like CO2, and the pollution imposed on ecosystems and human health.

Distribution of Adult Day Health Centers and Persons Living with Dementia Among Hospital Service Areas in Rhode Island.

INTRODUCTION: Adult day health centers (ADHCs) provide an important service to community-dwelling adults with functional dependency. This includes persons living with dementia (PLWD) and their caregivers, but we don't know how well ADHC capacity matches the distribution of PLWD. METHODS: For this cross-sectional study, we identified community-dwelling PLWD using Medicare claims, and ADHC capacity using licensure data. We aggregated both features by Hospital Service Area. By linear regression, we determined the association between ADHC capacity and community-dwelling PLWD. RESULTS: We identified 3836 community-dwelling Medicare beneficiaries living with dementia. We included 28 ADHCs, with licensed capacity for 2127 clients. The linear regression coefficient (95% Confidence Interval) for number of community-dwelling beneficiaries with dementia was 1.07 (0.6-1.53). DISCUSSION: Rhode Island's ADHC capacity distribution roughly approximates the distribution of persons with dementia. Plans for the future of dementia care in Rhode Island should consider these findings.