Alimentary Treatment with Trehalose in a Pharmacological Model of Alzheimer's Disease in Mice: Effects of Different Dosages and Treatment Regimens.

In the treatment of experimental neurodegeneration with disaccharide trehalose, various regimens are used, predominantly a 2% solution, drunk for several weeks. We studied the effects of different regimens of dietary trehalose treatment in an amyloid-ß (Aß) 25-35-induced murine model of Alzheimer's disease (AD). Aß-treated mice received 2% trehalose solution daily, 4% trehalose solution daily (continuous mode) or every other day (intermittent mode), to drink for two weeks. We revealed the dose-dependent effects on autophagy activation in the frontal cortex and hippocampus, and the restoration of behavioral disturbances. A continuous intake of 4% trehalose solution caused the greatest activation of autophagy and the complete recovery of step-through latency in the passive avoidance test that corresponds to associative long-term memory and learning. This regimen also produced an anxiolytic effect in the open field. The effects of all the regimens studied were similar in Aß load, neuroinflammatory response, and neuronal density in the frontal cortex and hippocampus. Trehalose successfully restored these parameters to the levels of the control group. Thus, high doses of trehalose had increased efficacy towards cognitive impairment in a model of early AD-like pathology. These findings could be taken into account for translational studies and the development of clinical approaches for AD therapy using trehalose.

Post-Fire Coleoptera Fauna in Central Russian Forests after the 2021 Fires (Study Using Beer Traps).

Fires can significantly impact forest ecosystems. However, studies on the effects of fires on insect communities in post-fire plots in natural forests are rare. This study presents an analysis of the Coleoptera fauna in the forests of the Mordovia State Nature Reserve (European Russia) in 2022 and 2023 after a fire. Insects were sampled from burned plots (9) in 2010 and 2021, as well as unburned (control) plots (2), and alpha diversity was compared. After processing the material, we examined a total of 12,218 Coleoptera specimens from 38 families and identified 194 species. The families Nitidulidae, Cerambycidae, Elateridae, and Scarabaeidae were the most abundant across all plots. Cerambycidae, Elateridae, Nitidulidae, Staphylinidae, Coccinellidae, and Scarabaeidae exhibited the greatest species diversity. In total, 17 species were found on all plots, including Cetonia aurata, Protaetia cuprea volhyniensis, Trogoderma glabrum, Carpophilus hemipterus, Epuraea biguttata, Glischrochilus grandis, Glischrochilus hortensis, Glischrochilus quadripunctatus, Soronia grisea, Pediacus depressus, Chrysanthia geniculata, Anastrangalia reyi, Leptura quadrifasciata, Leptura thoracica, Lepturalia nigripes, Rhagium mordax, and Anisandrus dispar. Only five species exhibited preferences for certain plots. Maximum abundance and species diversity were observed on unburned (control) plots. The plots where fires occurred in 2010 and 2021 had the lowest total abundance values for Coleoptera. These fires destroyed almost all potential sites for beetle settlement, feeding, breeding, and shelter. Traps recorded a higher abundance of Coleoptera in the first year after fires compared to the second year. The Coleoptera fauna showed the greatest similarity on the control plots.

Scaling high-speed counter-current chromatography for preparative neodymium purification: Insights and challenges.

Efficient rare earth element (REE) separations are becoming increasingly important to technologies ranging from renewable energy and high-performance magnets to applied radioisotope separations. These separations are made challenging by the extremely similar chemical and physical characteristics of the individual elements, which almost always occupy the 3+ oxidation state under ambient conditions. Herein, we discuss the development of a novel REE separation aimed at obtaining purified samples of neodymium (Nd) on a multi-milligram scale using high-speed counter-current chromatography (HSCCC). The method takes advantage of the subtle differences in ionic radii between neighboring REEs to tune elution rates in dilute acid through implementation of the di-(2-ethylhexyl)phosphoric acid (HDEHP)-infused stationary phase (SP) of the column. A La/Ce/Nd/Sm separation was demonstrated at a significantly higher metal loading than previously accomplished by HSCCC (15 mg, RNd/REE > 0.85), while the Pr/Nd separation was achieved at lower metal loadings (0.3 mg, RNd/Pr = 0.75 - 0.83). The challenges associated with scaling REE separations via HSCCC are presented and discussed within.

Individual differences in uncertainty evaluation explain opposing exploratory behaviors in anxiety and apathy.

Navigating uncertain environments is a fundamental challenge for adaptive behavior, and affective states such as anxiety and apathy can profoundly influence an individual's response to uncertainty. Uncertainty encompasses both volatility and stochasticity, where volatility refers to how rapidly the environment changes and stochasticity describes outcomes resulting from random chance. This study investigates how anxiety and apathy modulate perceptions of environmental volatility and stochasticity and how these perceptions impact exploratory behavior. In a large online sample (N = 1001), participants completed a restless three-armed bandit task, and their choices were analyzed using latent state models to quantify the computational processes. We found that anxious individuals attributed uncertainty more to environmental volatility than stochasticity, leading to increased exploration, particularly after reward omission. Conversely, apathetic individuals perceived uncertainty as more stochastic than volatile, resulting in decreased exploration. The ratio of perceived volatility to stochasticity mediated the relationship between anxiety and exploratory behavior following adverse outcomes. These findings reveal distinct computational mechanisms underlying anxiety and apathy in uncertain environments. Our results provide a novel framework for understanding the cognitive and affective processes driving adaptive and potentially maladaptive behaviors under uncertainty, with implications for the characterization and treatment of neuropsychiatric disorders.

Small molecule in situ resin capture provides a compound first approach to natural product discovery.

Culture-based microbial natural product discovery strategies fail to realize the extraordinary biosynthetic potential detected across earth's microbiomes. Here we introduce Small Molecule In situ Resin Capture (SMIRC), a culture-independent method to obtain natural products directly from the environments in which they are produced. We use SMIRC to capture numerous compounds including two new carbon skeletons that were characterized using NMR and contain structural features that are, to the best of our knowledge, unprecedented among natural products. Applications across diverse marine habitats reveal biome-specific metabolomic signatures and levels of chemical diversity in concordance with sequence-based predictions. Expanded deployments, in situ cultivation, and metagenomics facilitate compound discovery, enhance yields, and link compounds to candidate producing organisms, although microbial community complexity creates challenges for the later. This compound-first approach to natural product discovery provides access to poorly explored chemical space and has implications for drug discovery and the detection of chemically mediated biotic interactions.

Staged Hip Arthroscopy with Labral Repair, Femoroplasty, and Capsular Plication Followed by Periacetabular Osteotomy for Hip Dysplasia Results in Improved Outcomes and 100% Survivorship at Minimum 2-Year Follow-Up.

PURPOSE: To assess patient-reported outcomes (PROs), clinically significant outcomes (CSOs), and survivorship following staged hip arthroscopy with labral repair, femoroplasty, and capsular plication followed by periacetabular osteotomy (PAO) for the management of femoroacetabular impingement syndrome (FAIS) and hip dysplasia (lateral center edge angle ≤25°). METHODS: A prospectively maintained database was queried to retrospectively identify patients who underwent staged primary hip arthroscopy and PAO between 1/2018-10/2021 and had a minimum 2-year follow-up. PROs collected included, Hip Outcome Score Activities of Daily Living/Sports Subscale (HOS-ADL/SS), international Hip Outcome Tool-12 item questionnaire (iHOT-12), and Visual Analog Scale for Pain (VAS Pain). CSO achievement for minimal clinical important difference (MCID) and patient acceptable symptom state (PASS) were determined through cohort specific thresholds. Rates of reoperation, including, revision hip arthroscopy and conversion to total hip arthroplasty (THA) were evaluated to determine short-term survivorship. RESULTS: Thirty-nine hips met criteria for inclusion, of which 35 hips had minimum 2-year follow up (89.7% compliance). Mean age was 25±9.1 years and 91.7% of patients were female. Respective pre- and postoperative radiographic outcomes were: Alpha angle 59.8±5.9 to 39.7±2.6°, Tönnis angle 14.6±5.6° to -1.0±2.9°, lateral center-edge angle 16.6±5.5° to 36.6±4.6°, and anterior center-edge angle 15.6±9.1° to 36.1±3.8°, with statistically significant differences pre- to postoperatively for all (P<0.001). Patients demonstrated significant improvement in all PROs pre- to postoperatively (P ≤0.004). MCID and PASS achievement rates for any PRO were 93.9% and 78.8%, respectively. There were no revision hip surgeries or conversion to THA at a mean 2.7±1.0-year follow-up. Four patients (11.1%) underwent hardware removal. One patient (2.8%) experienced a postoperative infection treated with incision and drainage. CONCLUSIONS: Staged hip arthroscopy and PAO for the management of hip dysplasia demonstrated improvement in PROs, high CSO achievement rates, and 100% survivorship at minimum 2-year follow-up.

Necrotizing Fasciitis Masquerading as Stroke: A Diagnostic Dilemma.

Necrotizing fasciitis (NF) poses a diagnostic challenge due to its rarity and similarity in presentation with other critical conditions. We report a case of a 79-year-old male who initially presented with altered mental status and stroke-like symptoms; he was ultimately diagnosed with abdominal wall NF spreading to the lower extremity. Despite a history of cecal mass perforation noted in prior imaging, the patient had been discharged from an outside emergency room on antibiotics, highlighting a missed opportunity for early intervention. Subsequent deterioration led to sepsis, organ failure, and ultimately, the detection of NF. Prompt recognition of subtle skin changes and laboratory abnormalities, along with a detailed physical examination, is essential for a timely and accurate diagnosis. Surgical debridement, coupled with broad-spectrum antibiotics, remains the cornerstone of treatment. Delays in surgical management significantly increase mortality, emphasizing the importance of prompt diagnosis and intervention. This case underscores the necessity for heightened awareness among healthcare providers to recognize NF promptly, especially when its clinical presentation overlaps with other critical conditions. Multidisciplinary collaboration and continued education are imperative to improve outcomes and prevent delays in the diagnosis and treatment of NF.

Live chicken egg embryos as an alternative in vivo tumour model for deep surface enhanced Raman spectroscopy.

Live chicken egg embryos offer new opportunities for evaluation and continuous monitoring of tumour growth for in vivo studies compared to traditional rodent models. Here, we report the first use of surface enhanced Raman scattering (SERS) mapping and surface enhanced spatially offset Raman scattering (SESORS) for the detection and localisation of targeted gold nanoparticles in live chicken egg embryos bearing a glioblastoma tumour.

High-throughput single-cell transcriptomics of bacteria using combinatorial barcoding.

Microbial split-pool ligation transcriptomics (microSPLiT) is a high-throughput single-cell RNA sequencing method for bacteria. With four combinatorial barcoding rounds, microSPLiT can profile transcriptional states in hundreds of thousands of Gram-negative and Gram-positive bacteria in a single experiment without specialized equipment. As bacterial samples are fixed and permeabilized before barcoding, they can be collected and stored ahead of time. During the first barcoding round, the fixed and permeabilized bacteria are distributed into a 96-well plate, where their transcripts are reverse transcribed into cDNA and labeled with the first well-specific barcode inside the cells. The cells are mixed and redistributed two more times into new 96-well plates, where the second and third barcodes are appended to the cDNA via in-cell ligation reactions. Finally, the cells are mixed and divided into aliquot sub-libraries, which can be stored until future use or prepared for sequencing with the addition of a fourth barcode. It takes 4 days to generate sequencing-ready libraries, including 1 day for collection and overnight fixation of samples. The standard plate setup enables single-cell transcriptional profiling of up to 1 million bacterial cells and up to 96 samples in a single barcoding experiment, with the possibility of expansion by adding barcoding rounds. The protocol requires experience in basic molecular biology techniques, handling of bacterial samples and preparation of DNA libraries for next-generation sequencing. It can be performed by experienced undergraduate or graduate students. Data analysis requires access to computing resources, familiarity with Unix command line and basic experience with Python or R.

The Association Between Surgeon Volume and Dislocation After Total Hip Arthroplasty: A Nationwide Evaluation of 5,106 Orthopaedic Surgeons.

INTRODUCTION: The relationship between surgeon volume and risk of dislocation after total hip arthroplasty (THA) is debated. This study sought to characterize this association and assess patient outcomes using a nationwide patient and surgeon registry. METHODS: The Premier Healthcare Database was queried for adult primary elective THA patients from January 1, 2016, to December 31, 2019. Annual surgeon volume and 90-day risk of dislocation were modeled using multivariable logistic regression with restricted cubic splines. Bootstrap analysis identified a threshold annual case volume, corresponding to the maximum decrease in dislocation risk. Surgeons with an annual volume greater than the threshold were deemed high volume, and those with an annual volume less than the threshold were low volume. Each surgeon within a given year was treated as a unique entity (surgeon-year unit). 90-day complications of patients treated by high-volume and low-volume surgeons were compared. RESULTS: From 2016 to 2019, 352,131 THAs were performed by 5,106 surgeons. The restricted cubic spline model demonstrated an inverse relationship between risk of dislocation and surgeon volume (threshold: 109 cases per year). A total of 9,967 (87.8%) low-volume surgeon-year units had individual dislocation rates lower than the average of the entire surgeon cohort. Patients treated by high-volume surgeons had decreased risk of dislocation (adjusted odds ratio [aOR], 0.60; 95% CI, 0.54 to 0.67), periprosthetic fracture (aOR, 0.87; 95% CI, 0.76 to 0.99), periprosthetic joint infection (aOR, 0.63; 95% CI, 0.56 to 0.69), readmission (aOR, 0.70; 95% CI, 0.67 to 0.73), and in-hospital death (aOR, 0.60; 95% CI, 0.46 to 0.80). CONCLUSION: While most of the low-volume surgeons had dislocation rates lower than the cohort average, increasing annual surgeon case volume was associated with a reduction in risk of dislocation after primary elective THA. THERAPEUTIC LEVEL OF EVIDENCE: Level IV.

Association of Patient Satisfaction 2 Years After Hip Arthroscopy for Femoroacetabular Impingement Syndrome With Minimum 10-Year Patient-Reported Outcomes and Survivorship.

BACKGROUND: Previous studies have shown that short-term outcomes after hip arthroscopy for femoroacetabular impingement syndrome (FAIS) predict midterm outcomes, but a limited number of studies have evaluated whether short-term outcomes predict long-term outcomes and survivorship. PURPOSE: To evaluate whether achieving clinically significant outcomes at 2 years after hip arthroscopy for FAIS can predict patient-reported outcomes (PROs) and survivorship at 10 years. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Patients who underwent primary hip arthroscopy for FAIS between June 2012 and December 2012 with a minimum 10-year follow-up were identified. Using previously established thresholds, we classified patients who achieved the 2-year Patient Acceptable Symptom State (PASS) for the visual analog scale (VAS) for satisfaction as the high satisfaction group and patients who did not as the low satisfaction group. Minimum 10-year PROs were then compared between the groups, including scores for the Hip Outcome Score (HOS)-Activities of Daily Living and -Sports Specific, the modified Harris Hip Score, the VAS for pain, and the VAS for satisfaction. Reoperation-free survivorship was compared. RESULTS: Of 120 eligible consecutive patients, 85 patients were included (70.8% follow-up rate), of whom 61.2% were female. The mean age was 34.0 ± 12.8 years, and the mean body mass index was 25.4 ± 4.6. Of the 85 patients, 29 (34.1%) did not achieve PASS for the VAS for satisfaction at 2 years postoperatively compared with 56 (65.9%) who did. The low satisfaction group had significantly worse acetabular chondral grades at the time of surgery (P = .008). At minimum 10-year follow-up, the high satisfaction group showed significantly better HOS-Activities of Daily Living, HOS-Sports Specific, modified Harris Hip Score, VAS pain, and VAS satisfaction scores (P≤ .031). Compared with the low satisfaction group, the high satisfaction group had a significantly lower rate of secondary surgery (1.8% vs 24.1%, respectively; P = .002). CONCLUSION: Patients who achieved PASS for the VAS for satisfaction at 2 years after hip arthroscopy demonstrated superior minimum 10-year outcomes compared with patients who did not, including greater PRO scores and a higher survivorship rate. The high satisfaction group had lower grade acetabular cartilage damage at the time of surgery compared with those who did not achieve PASS for the VAS for satisfaction at 2 years.

The speech neuroprosthesis.

Loss of speech after paralysis is devastating, but circumventing motor-pathway injury by directly decoding speech from intact cortical activity has the potential to restore natural communication and self-expression. Recent discoveries have defined how key features of speech production are facilitated by the coordinated activity of vocal-tract articulatory and motor-planning cortical representations. In this Review, we highlight such progress and how it has led to successful speech decoding, first in individuals implanted with intracranial electrodes for clinical epilepsy monitoring and subsequently in individuals with paralysis as part of early feasibility clinical trials to restore speech. We discuss high-spatiotemporal-resolution neural interfaces and the adaptation of state-of-the-art speech computational algorithms that have driven rapid and substantial progress in decoding neural activity into text, audible speech, and facial movements. Although restoring natural speech is a long-term goal, speech neuroprostheses already have performance levels that surpass communication rates offered by current assistive-communication technology. Given this accelerated rate of progress in the field, we propose key evaluation metrics for speed and accuracy, among others, to help standardize across studies. We finish by highlighting several directions to more fully explore the multidimensional feature space of speech and language, which will continue to accelerate progress towards a clinically viable speech neuroprosthesis.

Efficacy and Safety of Local Liver Radioablation in Hepatocellular Carcinoma Lesions within and beyond Limits of Thermal Ablation.

INTRODUCTION: CT-guided interstitial brachytherapy (iBT) radiotherapy has been established in the treatment of liver tumors. With iBT, hepatocellular carcinoma (HCC) lesions can be treated beyond the limits of thermal ablation (i.e., size and location). However, a comprehensive analysis of the efficacy of iBT in patients within and beyond thermal ablation limits is lacking. MATERIALS AND METHODS: A total of 146 patients with 216 HCC lesions have been analyzed retrospectively. Clinical and imaging follow-up data has been collected. Lesions were evaluated in terms of suitability for thermal ablation or not. The correlation between local tumor control (LTC), time to progression (TTP), overall survival (OS), and clinical and imaging parameters have been evaluated using univariable and multivariable Cox regression analyses. RESULTS: LTC rates at 12 months, 24 months, and 36 months were 87%, 75%, and 73%, respectively. 65% of lesions (n = 141) were not suitable for radiofrequency ablation (RFA). The median TTP was 13 months, and the median OS was not reached (3-year OS rate: 70%). No significant difference in LTC, TTP, or OS regarding RFA suitability existed. However, in the overall multivariable analysis, lesion diameter >5 cm was significantly associated with lower LTC (HR: 3.65, CI [1.60-8.31], p = 0.002) and shorter TTP (HR: 2.08, CI [1.17-3.70], p = 0.013). Advanced BCLC stage, Child-Pugh Stage, and Hepatitis B were associated with shorter OS. CONCLUSION: iBT offers excellent LTC rates and OS in local HCC treatment regardless of the limits of thermal ablation, suggesting further evidence of its alternative role to thermal ablation in patients with early-stage HCC.

Charting Tomorrow's Healthcare: A Traditional Literature Review for an Artificial Intelligence-Driven Future.

Electronic health record (EHR) systems have developed over time in parallel with general advancements in mainstream technology. As artificially intelligent (AI) systems rapidly impact multiple societal sectors, it has become apparent that medicine is not immune from the influences of this powerful technology. Particularly appealing is how AI may aid in improving healthcare efficiency with note-writing automation. This literature review explores the current state of EHR technologies in healthcare, specifically focusing on possibilities for addressing EHR challenges through the automation of dictation and note-writing processes with AI integration. This review offers a broad understanding of existing capabilities and potential advancements, emphasizing innovations such as voice-to-text dictation, wearable devices, and AI-assisted procedure note dictation. The primary objective is to provide researchers with valuable insights, enabling them to generate new technologies and advancements within the healthcare landscape. By exploring the benefits, challenges, and future of AI integration, this review encourages the development of innovative solutions, with the goal of enhancing patient care and healthcare delivery efficiency.

Drivers of dune formation control ecosystem function and response to disturbance in a barrier island system.

Barrier islands are landscape features that protect coastlines by reducing wave energy and erosion. Quantifying vegetation-topographic interactions between adjacent habitats are essential for predicting long-term island response and resilience to sea-level rise and disturbance. To understand the effects of dune dynamics on adjacent interior island ecosystem processes, we quantified how sediment availability and previous disturbance regime interact with vegetation to influence dune building and ease of seawater and sediment movement into the island interior on two US mid-Atlantic coast barrier islands. We conducted field surveys of sediment accretion, vegetative cover, and soil characteristics in dune and swale habitats. Digital elevation models provided assessment of water flow resistance from the mean high water mark into the island interior. We found that geographic location impacted sediment accretion rates and Panicum amarum (a species increasing in abundance over time in the Virginia barrier islands) accreted sediment at a significantly lower rate compared to other dune grasses. Dune elevation impacted the ease of seawater flow into the island interior, altering soil chlorides, annual net primary productivity, and soil carbon and nitrogen. Our work demonstrates the importance of incorporating biological processes and cross-island connectivity into future scenario modeling and predictions of rising sea-levels and increased disturbance.

Testing the hypothesis that solvent exchange limits the rates of calcite growth and dissolution.

It is established that the rates of solvent exchange at interfaces correlate with the rates of a number of mineral reactions, including growth, dissolution and ion sorption. To test if solvent exchange is limiting these rates, quasi-elastic neutron scattering (QENS) is used here to benchmark classical molecular dynamics (CMD) simulations of water bound to nanoparticulate calcite. Four distributions of solvent exchanges are found with residence times of 8.9 ps for water bound to calcium sites, 14 ps for that bound to carbonate sites and 16.7 and 85.1 ps for two bound waters in a shared calcium-carbonate conformation. By comparing rates and activation energies, it is found that solvent exchange limits reaction rates neither for growth nor dissolution, likely due to the necessity to form intermediate states during ion sorption. However, solvent exchange forms the ceiling for reaction rates and yields insight into more complex reaction pathways.

Cost of sterility: probe covers should not be mandated for single-shot peripheral nerve blocks.

Ultrasound guidance has become ubiquitous with regional anesthesia, but little consistency exists on necessary ultrasound probe hygiene and sterility barriers. Fear of possible infection has led to calls for universal use of sterile ultrasound probe covers. Available data seems to suggest that single-shot peripheral nerve blocks have a low infectious risk. The widespread use of single-use disposable probe covers would carry an associated cost, increased environmental impact, and little evidence to suggest that they are effective at preventing infection if proper technique is used. While various parties have labeled single-shot nerve blocks as a sterile procedure, in practice, it is a clean technique. In this article, we argue that mandating the use of probe covers is unnecessary and that it should be left to the anesthesiologist to determine what type of anti-infection equipment is necessary for single-shot nerve blocks based on their practice situation and expertize.

Influence of sports on cortical excitability in patients with spinal cord injury: a TMS study.

Background: Patients with spinal cord injury (SCI) show abnormal cortical excitability that might be caused by deafferentation. We hypothesize a reduced short-interval intracortical inhibition preceding movement in patients with SCI compared with healthy participants. In addition, we expect that neuroplasticity induced by different types of sports can modulate intracortical inhibition during movement preparation in patients with SCI. Methods: We used a reaction test and paired-pulse transcranial magnetic stimulation to record cortical excitability, assessed by measuring amplitudes of motor-evoked potentials in preparation of movement. The participants were grouped as patients with SCI practicing wheelchair dancing (n = 7), other sports (n = 6), no sports (n = 9), and healthy controls (n = 24). Results: There were neither significant differences between healthy participants and the patients nor between the different patient groups. A non-significant trend (p = .238), showed that patients engaged in sports have a stronger increase in cortical excitability compared with patients of the non-sportive group, while the patients in the other sports group expressed the highest increase in cortical excitability. Conclusion: The small sample sizes limit the statistical power of the study, but the trending effect warrants further investigation of different sports on the neuroplasticity in patients with SCI. It is not clear how neuroplastic changes impact the sensorimotor output of the affected extremities in a patient. This needs to be followed up in further studies with a greater sample size.