Evaluation of Solubility, and Volumetric and Morphological Alterations of Bioceramic Filling Material for Primary Teeth: A New Methodological Approach.

Objective: To evaluate the solubility and the volumetric and morphological alterations of bioceramic filling material (Bio-CP) for primary teeth. Materials and Methods: Bio-CP, Calen thickened with zinc oxide (Calen-ZO), and with zinc oxide eugenol (ZOE) were placed in 1- or 2-mm-diameter polyethylene tubes and immersed in water or phosphate-buffered saline (PBS) for 30 days. The solubility (mass loss) was assessed using methodology modified from ISO 6876. Filling capacity, volumetric changes, and presence of voids were assessed by microcomputed tomography (micro-CT). The surface distribution of the chemical elements and the crystalline phases was evaluated by energy scattering X-ray scanning electron microscopy (SEM-EDX) and X-ray diffraction (XRD) to detect hydroxyapatite precipitate and components. The Shapiro-Wilk, Kruskal-Wallis, and Dunn's or two-way ANOVA and Tukey post hoc test were used (α = 0.05). Results: The solubility was ZOE > Calen-ZO = Bio-CP. Calen-ZO and Bio-CP were more soluble in water than in PBS. All the materials showed greater solubility in 2-mm tube diameter in both PBS and distilled water, except for Bio-CP in distilled water, which showed no difference between both tube diameters (1 and 2 mm). Only Calen-ZO and ZOE were analyzed by micro-CT, because Bio-CP separated into two phases during scanning. Calen-ZO had greater volumetric loss and presence of voids than ZOE in water, but there was no difference in PBS. The hydroxyapatite precipitate on the surface of Bio-CP and Calen-ZO was detected after immersion in PBS. Conclusion: Although Bio-CP had acceptable solubility and filling capacity, its composition did not allow a proper volumetric and void assessment. From a clinical perspective, Bio-CP has the potential to become a suitable material for root canal filling in primary teeth. Nonetheless, its composition must first be revised to achieve better chemical stability prior to its recommendation.

Multiple sclerosis in Central America and Caribbean countries: frequency and clinical characterization of an emergent disease.

Background: Multiple Sclerosis (MS) is a common neurological disease among white populations of European origin. Frequencies among Latin Americans continue to be studied, however, epidemiologic, and clinical characterization studies lack from Central American and Caribbean countries. Ethnicity in these countries is uniformly similar with a prevalent Mestizo population. Methods and results: Data from January 2014 to December 2019 from Guatemala, El Salvador, Honduras, Nicaragua, Costa Rica, Panama, Dominican Republic, and Aruba on demographic, clinical, MRI and phenotypic traits were determined in coordinated studies: ENHANCE, a population-based, retrospective, observational study on incidence and clinical characteristics, and from the subgroup with MS national registries (Aruba, Dominican Republic, Honduras, and Panama), data on prevalence, phenotypes and demographics. Expanded Disability Status Scale (EDSS), and therapeutic schemes were included. ENHANCE data from 758 patients disclosed 79.8% of Mestizo ethnicity; 72.4% female; median age at onset 31.0 years and 33.2 at diagnosis. The highest incidence rate was from Aruba, 2.3-3.5 × 100,000 inhabitants, and the lowest, 0.07-0.15 × 100,000, from Honduras. Crude prevalence rates per 100,000 inhabitants fluctuated from 27.3 (Aruba) to 1.0 (Honduras). Relapsing MS accounted for 87.4% of cases; EDSS <3.0 determined in 66.6% (mean disease duration: 9.1 years, SD ± 5.0); CSF oligoclonal bands 85.7%, and 87% of subjects hydroxyvitamin D deficient. Common initial therapies were interferon and fingolimod. Switching from interferon to fingolimod was the most common escalation step. The COVID-19 pandemic affected follow-up aspects of these studies. Conclusion: This is the first study providing data on frequencies and clinical characteristics from 8 countries from the Central American and Caribbean region, addressing MS as an emergent epidemiologic disorder. More studies from these areas are encouraged.

Comparing Methods for Identifying Post-Market Patient Preferences at the Point of Decision-Making: Insights from Patients with Chronic Pain Considering a Spinal Cord Stimulator Device.

Purpose: To compare three methods for identifying patient preferences (MIPPs) at the point of decision-making: analysis of video-recorded patient-clinician encounters, post-encounter interviews, and post-encounter surveys. Patients and Methods: For the decision of whether to use a spinal cord stimulator device (SCS), a video coding scheme, interview guide, and patient survey were iteratively developed with 30 SCS decision-making encounters in a tertiary academic medical center pain clinic. Burke's grammar of motives was used to classify the attributed source or justification for a potential preference for each preference block. To compare the MIPPs, 13 patients' encounters with their clinician were video recorded and subsequently analyzed by 4 coders using the final video coding scheme. Six of these patients were interviewed, and 7 surveyed, immediately following their encounters. Results: For videos, an average of 66 (range 33-106) sets of utterances potentially indicating a patient preference (a preference block), surveys 33 (range 32-34), and interviews 25 (range 18-30) were identified. Thirty-eight unique themes (75 subthemes), each a preference topic, were identified from videos, surveys 19 themes (12 subthemes), and interviews 39 themes (54 subthemes). The proportion of preference blocks that were judged as expressing a preference that was clearly important to the patient or affected their decision was highest for interviews (72.8%), surveys (68.0%), and videos (27.0%). Videos mostly attributed preferences to the patient's situation (scene) (65%); interviews, the act of receiving or living with SCS (43%); surveys, the purpose of SCS (40%). Conclusion: MIPPs vary in the type of preferences identified and the clarity of expressed preferences in their data sets. The choice of which MIPP to use depends on projects' goals and resources, recognizing that the choice of MIPP may affect which preferences are found.

Long Chain Fatty Acids Mediate Hepatic Metabolic Flux in Preruminating Dairy Calves Fed Flaxseed Oil, High Oleic Soybean Oil, or Milk Fat.

Nutrition and physiological state affect hepatic metabolism. Our objective was to determine if feeding flaxseed oil (∼50% C18:3n-3 cis), high oleic soybean oil (∼70% C18:1 cis-9), or milk fat (∼50% C16:0) alters hepatic expression of PC, PCK1, and PCK2 and the flow of carbons from propionate and pyruvate into the TCA cycle in preruminating calves. Male Holstein calves (n = 40) were assigned to a diet of skim milk with either: 3% milk fat (MF; n = 8), 3% flaxseed oil (Flax; n = 8), 3% high oleic soybean oil (HOSO; n = 8), 1.5% MF + 1.5% high oleic soybean oil (MF-HOSO; n = 8), or 1.5% MF + 1.5% flaxseed oil (MF-Flax; n = 8) from d 14 to d 21 postnatal. At d 21 postnatal, a liver biopsy was taken for gene expression and metabolic flux analysis. Liver explants were incubated in [U-13C] propionate and [U-13C] pyruvate to trace carbon flux through TCA cycle intermediates or with [U-14C] lactate, [1-14C] palmitic acid, or [2-14C] propionate to quantify substrate oxidation to CO2 and acid soluble products. Compared with other treatments, plasma C18:3n-3 cis was 10 times higher and C18:1 cis-9 was 3 times lower in both flax (Flax and MF-Flax) treatments. PC, PCK1, and PCK2 expression and flux of [U-13C] pyruvate as well as [U-13C] propionate were not different between treatments. PC expression was negatively correlated with the enrichment of citrate M+5 and malate M+3, and PCK2 was negatively correlated with citrate M+5, suggesting that when expression of these enzymes is increased, carbon from pyruvate enters the TCA cycle via PC mediated carboxylation, and then OAA is converted to phosphoenolpyruvate via PCK2. Acid soluble product formation and PC expression were reduced in HOSO (MF-HOSO and HOSO) treatments compared with flax (MF-Flax and Flax), indicating that fatty acids regulate PC expression and carbon flux, but that fatty acid flux control points are not connected to PC, PCK1, or PCK2. In conclusion, fatty acids regulate hepatic expression of PC, PCK1, and PCK2, and carbon flux, but the point of control is distinct.

Biorefinery approach with green solvents for the valorization of Citrus reticulata leaves to obtain antioxidant and anticholinergic extracts.

Citrus reticulata L leaves are one of the main post-harvest byproduct, containing bioactive compounds, that are usually undervalued. This work describes the development of a biorefinery process based on the application of supercritical CO2 (SC-CO2) followed by ultrasonic-assisted extraction (UAE) combined with Natural Deep Eutectic Solvents (NaDES) to extract bioactive terpenoids and phenolic compounds from these leaves. Extraction temperature and pressure of SC-CO2 were optimized, obtaining the highest bioactive terpenoids content using 200 bar at 60 °C. A Box-Behnken experimental design showed that 57% of water in NaDES composed of Choline Chloride and Glycerol (1:2) as extraction solvent at 25 °C for 50 min were the optimal UAE-NaDES extraction conditions to obtain the highest bioactive phenolic content from the residue of the optimal SC-CO2 extraction. The optimum extract presented the highest bioactivity and polyphenol content determined by LC-DAD-MS compared with extracts obtained using only water or NaDES as solvent.

External validation of three diabetes prediction scores in a Spanish cohort: does adding high risk for depression improve the validation of the FINDRISC score (FINDRISC-MOOD)?

OBJECTIVES: To evaluate the external validity of the FINDRISC, DESIR and ADA risk scores for the prediction of diabetes in a Spanish population aged >45 years and to test the possible improvement of FINDRISC by adding a new variable of high risk of depression when Patient Health Questionnaire-9 (PHQ-9) questionnaire score ≥10 (FINDRISC-MOOD). DESIGN: Prospective population-based cohort study. SETTING: 10 primary healthcare centres in the north of the city of Madrid (Spain). PARTICIPANTS: A total of 1242 participants without a history of diabetes and with 2-hour oral glucose tolerance test (OGTT) plasma glucose <200 mg/dL (<11.1 mmol/L) were followed up for 7.3 years (median) using their electronic health records (EHRs) and telephone contact. PRIMARY AND SECONDARY OUTCOME MEASURES: Diabetes risk scores (FINDRISC, DESIR, ADA), PHQ-9 questionnaire and 2-hour-OGTT were measured at baseline. Incident diabetes was defined as treatment for diabetes, fasting plasma glucose ≥126 mg/dL (≥7.0 mmol/L), new EHR diagnosis or self-reported diagnosis. External validation was performed according to optimal cut-off, sensitivity, specificity and Youden Index. Comparison between diabetes risk scores, including FINDRISC-MOOD (original FINDRISC score plus five points if PHQ-9 ≥10), was measured by area under the receiver operating characteristic curve (AUROC). RESULTS: During follow-up, 104 (8.4%; 95% CI, 6.8 to 9.9) participants developed diabetes and 185 had a PHQ-9 score ≥10. The AUROC values were 0.70 (95% CI, 0.67 to 0.72) for FINDRISC-MOOD and 0.68 (95% CI, 0.65 to 0.71) for the original FINDRISC. The AUROCs for DESIR and ADA were 0.66 (95% CI, 0.63 to 0.68) and 0.66 (95% CI, 0.63 to 0.69), respectively. There were no significant differences in AUROC between FINDRISC-MOOD and the other scores. CONCLUSIONS: The results of FINDRISC-MOOD were like those of the other risk scores and do not allow it to be recommended for clinical use.

Kisspeptin signaling in astrocytes modulates the reproductive axis.

Reproduction is safeguarded by multiple, often cooperative regulatory networks. Kisspeptin signaling, via KISS1R, plays a fundamental role in reproductive control, primarily by regulation of hypothalamic GnRH neurons. We disclose herein a pathway for direct kisspeptin actions in astrocytes that contributes to central reproductive modulation. Protein-protein-interaction and ontology analyses of hypothalamic proteomic profiles after kisspeptin stimulation revealed that glial/astrocyte markers are regulated by kisspeptin in mice. This glial-kisspeptin pathway was validated by the demonstrated expression of Kiss1r in mouse astrocytes in vivo and astrocyte cultures from humans, rats and mice, where kisspeptin activated canonical intracellular signaling-pathways. Cellular co-expression of Kiss1r with the astrocyte markers, GFAP and S100-ß, occurred in different brain regions, with higher percentage in Kiss1- and GnRH-enriched areas. Conditional ablation of Kiss1r in GFAP-positive cells, in the G-KiRKO mouse, altered gene expression of key factors in PGE2 synthesis in astrocytes, and perturbed astrocyte-GnRH neuronal appositions, as well as LH responses to kisspeptin and LH pulsatility, as surrogate marker of GnRH secretion. G-KiRKO mice also displayed changes in reproductive responses to metabolic stress induced by high-fat diet, affecting female pubertal onset, estrous cyclicity and LH-secretory profiles. Our data unveil a non-neuronal pathway for kisspeptin actions in astrocytes, which cooperates in fine-tuning the reproductive axis and its responses to metabolic stress.

IL17RB genetic variants are associated with acamprosate treatment response in patients with alcohol use disorder: A proteomics-informed genomics study.

Acamprosate is a Food and Drug Administration (FDA) approved medication for the treatment of alcohol use disorder (AUD). However, only a subset of patients achieves optimal treatment outcomes. Currently, no biological measures are utilized to predict response to acamprosate treatment. We applied our established pharmaco-omics informed genomics strategy to identify potential biomarkers associated with acamprosate treatment response. Specifically, our previous open-label acamprosate clinical trial recruited 442 patients with AUD who were treated with acamprosate for three months. We first performed proteomics using baseline plasma samples to identify potential biomarkers associated with acamprosate treatment outcomes. Next, we applied our established "proteomics-informed genome-wide association study (GWAS)" research strategy, and identified 12 proteins, including interleukin-17 receptor B (IL17RB), associated with acamprosate treatment response.​ A GWAS for IL17RB concentrations identified several genome-wide significant signals. Specifically, the top hit single nucleotide polymorphism (SNP) rs6801605 with a minor allele frequency of 38% in the European American population mapped 4 kilobase (Kb) upstream of IL17RB, and intron 1 of the choline dehydrogenase (CHDH) gene on chromosome 3 (p: 4.8E-20). The variant genotype (AA) for the SNP rs6801605 was associated with lower IL17RB protein expression. In addition, we identified a series of genetic variants in IL17RB that were associated with acamprosate treatment outcomes. Furthermore, the variantgenotypes for all of those IL17RB SNPs were protective for alcohol relapse. Finally, we demonstrated that the basal level of mRNA expression of IL17RB was inversely correlated with those of nuclear factor-κB (NF-κB) subunits, and a significantly higher expression of NF-κB subunits was observed in AUD patients who relapsed to alcohol use. In summary, this study illustrates that IL17RB genetic variants might contribute to acamprosate treatment outcomes. This series of studies represents an important step toward generating functional hypotheses that could be tested to gain insight into mechanisms underlying acamprosate treatment response phenotypes. (The ClinicalTrials.gov Identifier: NCT00662571).

Posterior Uveitis in Ocular-Involving Chronic Lymphocytic Leukemia and the Utility of Negative MYD88 L265P Testing in the Diagnosis.

Introduction: The aim of this study was to investigate if a negative test result for MYD88 L265P mutation, associated with vitreoretinal lymphoma (VRL) and primary CNS lymphoma, in liquid biopsies from intraocular fluids can be a useful adjuvant test to diagnose chronic lymphocytic leukemia in clinically challenging cases. Case Presentations: We selected patients with a past medical history or examinations findings suspicious for intraocular lymphoma. We evaluated both vitreous and aqueous humor-derived (AHD) MYD88 L265P mutation from patients that had suspected intraocular lymphoma that warranted a liquid biopsy procedure. Gold-standard cytopathology, flow cytometry, and gene rearrangement studies were also performed. All 4 patients had negative AHD MYD88 L265P mutation testing. Gold-standard testing (cytology) either showed paucicellular specimens (1/4) or specimens with high background inflammation (3/4). One case showed a rare B-cell clonal population (CD5+, Kappa-restricted by flow cytometry), but this was not sufficient to make any definitive diagnosis. All patients were subsequently initiated on systemic therapy and had improvement in their disease burden. Conclusions: Negative AHD MYD88 L265P mutation testing can serve as an adjuvant molecular test to diagnose difficult cases of intraocular CLL.

Healthcare systems collaborating to implement a shared decision-making tool in the electronic health record and build evidence on its adoption and use.

Introduction: Shared decision-making (SDM) is a method of care by which patients and clinicians work together to co-create a plan of care. Electronic health record (EHR) integration of SDM tools may increase adoption of SDM. We conducted a "lightweight" integration of a freely available electronic SDM tool, CV Prevention Choice, within the EHRs of three healthcare systems. Here, we report how the healthcare systems collaborated to achieve integration. Methods: This work was conducted as part of a stepped wedge randomized pragmatic trial. CV Prevention Choice was developed using guidelines for HTML5-based web applications. Healthcare systems integrated the tool in their EHR using documentation the study team developed and refined with lessons learned after each system integrated the electronic SDM tool into their EHR. CV Prevention Choice integration populates the tool with individual patient data locally without sending protected health information between the EHR and the web. Data abstraction and secure transfer systems were developed to manage data collection to assess tool implementation and effectiveness outcomes. Results: Time to integrate CV Prevention Choice in the EHR was 12.1 weeks for the first system, 10.4 weeks for the second, and 9.7 weeks for the third. One system required two 1-hour meetings with study team members and two healthcare systems required a single 1-hour meeting. Healthcare system information technology teams collaborated by sharing information and offering improvements to documentation. Challenges included tracking CV Prevention Choice use for reporting and capture of combination medications. Data abstraction required refinements to address differences in how each healthcare system captured data elements. Conclusion: Targeted documentation on tool features and resource mapping supported collaboration of IT teams across healthcare systems, enabling them to integrate a web-based SDM tool with little additional research team effort or oversight. Their collaboration helped overcome difficulties integrating the web application and address challenges to data harmonization for trial outcome analyses.

Twenty-four Month Outcomes of Extended- Versus Standard-course Antibiotic Therapy in Children Hospitalized With Pneumonia in High-Risk Settings: A Randomized Controlled Trial.

BACKGROUND: Pediatric community-acquired pneumonia (CAP) can lead to long-term respiratory sequelae, including bronchiectasis. We determined if an extended (13-14 days) versus standard (5-6 days) antibiotic course improves long-term outcomes in children hospitalized with CAP from populations at high risk of chronic respiratory disease. METHODS: We undertook a multicenter, double-blind, superiority, randomized controlled trial involving 7 Australian, New Zealand, and Malaysian hospitals. Children aged 3 months to ≤5 years hospitalized with radiographic-confirmed CAP who received 1-3 days of intravenous antibiotics, then 3 days of oral amoxicillin-clavulanate, were randomized to either extended-course (8-day oral amoxicillin-clavulanate) or standard-course (8-day oral placebo) arms. Children were reviewed at 12 and 24 months. The primary outcome was children with the composite endpoint of chronic respiratory symptoms/signs (chronic cough at 12 and 24 months; ≥1 subsequent hospitalized acute lower respiratory infection by 24 months; or persistent and/or new chest radiographic signs at 12-months) at 24-months postdischarge, analyzed by intention-to-treat, where children with incomplete follow-up were assumed to have chronic respiratory symptoms/signs ("worst-case" scenario). RESULTS: A total of 324 children were randomized [extended-course (n = 163), standard-course (n = 161)]. For our primary outcome, chronic respiratory symptoms/signs occurred in 97/163 (60%) and 94/161 (58%) children in the extended-courses and standard-courses, respectively [relative risk (RR) = 1.02, 95% confidence interval (CI): 0.85-1.22]. Among children where all sub-composite outcomes were known, chronic respiratory symptoms/signs between groups, RR = 1.10, 95% CI: 0.69-1.76 [extended-course = 27/93 (29%) and standard-course = 24/91 (26%)]. Additional sensitivity analyses also revealed no between-group differences. CONCLUSION: Among children from high-risk populations hospitalized with CAP, 13-14 days of antibiotics (versus 5-6 days), did not improve long-term respiratory outcomes.

Stratifying Risk for Postpartum Depression at Time of Hospital Discharge.

Objective: Postpartum depression (PPD) represents a major contributor to postpartum morbidity and mortality. Beyond efforts at routine screening, risk stratification models could enable more targeted interventions in settings with limited resources. Thus, we aimed to develop and estimate the performance of a generalizable risk stratification model for PPD in patients without a history of depression using information collected as part of routine clinical care. Methods: We performed a retrospective cohort study of all individuals who delivered between 2017 and 2022 in one of two large academic medical centers and six community hospitals. An elastic net model was constructed and externally validated to predict PPD using sociodemographic factors, medical history, and prenatal depression screening information, all of which was known before discharge from the delivery hospitalization. Results: The cohort included 29,168 individuals; 2,703 (9.3%) met at least one criterion for postpartum depression in the 6 months following delivery. In the external validation data, the model had good discrimination and remained well-calibrated: area under the receiver operating characteristic curve 0.721 (95% CI: 0.707-0.734), Brier calibration score 0.088 (95% CI: 0.084 - 0.092). At a specificity of 90%, the positive predictive value was 28.0% (95% CI: 26.0-30.1%), and the negative predictive value was 92.2% (95% CI: 91.8-92.7%). Conclusions: These findings demonstrate that a simple machine-learning model can be used to stratify the risk for PPD before delivery hospitalization discharge. This tool could help identify patients within a practice at the highest risk and facilitate individualized postpartum care planning regarding the prevention of, screening for, and management of PPD at the start of the postpartum period and potentially the onset of symptoms.

Comparative accuracy of four guidelines to predict high-grade dysplasia or malignancy in surgically resected pancreatic intraductal papillary mucinous neoplasms: Small nuances between guidelines lead to vastly different results.

Backgrounds/Aims: The guidelines regarding the management of intraductal papillary mucinous neoplasms (IPMNs) all have slightly different surgical indications for high-risk lesions. We aim to retrospectively compare the accuracy of four guidelines in recommending surgery for high-risk IPMNs, and assess the accuracy of elevated CA-19-9 levels and imaging characteristics of IPMNs considered high-risk in predicting malignancy or high-grade dysplasia (HGD). Methods: The final histopathological diagnosis of surgically resected high-risk IPMNs during 2013-2020 were compared to preoperative surgical indications, as enumerated in four guidelines: the 2015 American Gastroenterological Association (AGA), 2017 International Consensus, 2018 European Study Group, and 2018 American College of Gastroenterology (ACG). Surgery was considered "justified" if histopathology of the surgical specimen showed HGD/malignancy, or there was postoperative symptomatic improvement. Results: Surgery was postoperatively justified in 26/65 (40.0%) cases. All IPMNs with HGD/malignancy were detected by the 2018 ACG and the combined (absolute and relative criteria) 2018 European guidelines. The combined ("high-risk stigmata" and "worrisome features") 2017 International guideline missed 1/19 (5.3%) IPMNs with HGD/malignancy. The 2015 AGA guideline missed the most cases (11/19, 57.9%) of IPMNs with HGD/malignancy. We found the features most-associated with HGD/malignancy were pancreatic ductal dilation, and elevated CA-19-9 levels. Conclusions: Following the 2015 AGA guideline results in the highest rate of missed HGD/malignancy, but the lowest rate of operating on IPMNs without these features; meanwhile, the 2018 ACG and the combined (absolute and relative criteria) 2018 European guidelines result in more operations for IPMNs without HGD/malignancy, but the lowest rates of missed HGD/malignancy in IPMNs.

Reversible kink instability drives ultrafast jumping in nematodes and soft robots.

Entomopathogenic nematodes (EPNs) exhibit a bending-elastic instability, or kink, before becoming airborne, a feature hypothesized but not proven to enhance jumping performance. Here, we provide the evidence that this kink is crucial for improving launch performance. We demonstrate that EPNs actively modulate their aspect ratio, forming a liquid-latched closed loop over a slow timescale O (1 s), then rapidly open it O (10 µs), achieving heights of 20 body lengths (BL) and generating ∼ 10 4 W/Kg of power. Using jumping nematodes, a bio-inspired Soft Jumping Model (SoftJM), and computational simulations, we explore the mechanisms and implications of this kink. EPNs control their takeoff direction by adjusting their head position and center of mass, a mechanism verified through phase maps of jump directions in simulations and SoftJM experiments. Our findings reveal that the reversible kink instability at the point of highest curvature on the ventral side enhances energy storage using the nematode's limited muscular force. We investigated the impact of aspect ratio on kink instability and jumping performance using SoftJM, and quantified EPN cuticle stiffness with AFM, comparing it with C. elegans . This led to a stiffness-modified SoftJM design with a carbon fiber backbone, achieving jumps of ∼25 BL. Our study reveals how harnessing kink instabilities, a typical failure mode, enables bidirectional jumps in soft robots on complex substrates like sand, offering a novel approach for designing limbless robots for controlled jumping, locomotion, and even planetary exploration.

Patch and matrix striatonigral neurons differentially regulate locomotion.

Striatonigral neurons, known to promote locomotion, reside in both the patch and matrix compartments of the dorsal striatum. However, their compartment-specific contributions to locomotion remain largely unexplored. Using molecular identifier Kremen1 and Calb1 , we showed in mouse models that patch and matrix striatonigral neurons exert opposite influences on locomotion. Matrix striatonigral neurons reduced their activity before the cessation of self-paced locomotion, while patch striatonigral neuronal activity increased, suggesting an inhibitory function. Indeed, optogenetic activation of patch striatonigral neurons suppressed ongoing locomotion with reduced striatal dopamine release, contrasting with the locomotion-promoting effect of matrix striatonigral neurons, which showed an initial increase in dopamine release. Furthermore, genetic deletion of the GABA-B receptor in Aldehyde dehydrogenase 1A1-positive (ALDH1A1 + ) nigrostriatal dopaminergic neurons completely abolished the locomotion-suppressing effect of patch striatonigral neurons. Our findings unravel a compartment-specific mechanism governing locomotion in the dorsal striatum, where patch striatonigral neurons suppress locomotion by inhibiting ALDH1A1 + nigrostriatal dopaminergic neurons.

Intramedullary pediatric low-grade glioma of the spine.

PURPOSE: Pediatric intramedullary spinal cord low-grade gliomas (pLGGs) are rare diagnoses among central nervous system (CNS) tumors in the pediatric population. The classic presentation of the patients includes some degree of neurologic deficit, although many times the symptoms are vague which leads to delayed diagnosis. MATERIAL AND METHODS: The first step in the diagnosis includes special parameters in spinal imaging, particularly magnetic resonance imaging (MRI), and surgical resection remains the cornerstone for both diagnosis and treatment. Yet, recent years advancement in molecular and genetic understanding of CNS tumors allows for better adjustment of the treatment and follow-up regimens. Based on postoperative status, adjuvant therapy may provide additional therapeutic advantage for some types of tumors. CONCLUSION: Ultimately, patients have a very promising prognosis when treated appropriately in most of the cases of pediatric spinal cord LGG with continued advances arising. This manuscript summarizes the most contemporary evidence regarding clinical and treatment features of intramedullary pLGGs.

Expanding the Global Capacity for Childhood Cancer Registration: The ChildGICR Masterclass.

PURPOSE: One determinant of the paucity of data on childhood cancer in low- and middle-income countries is the lack of capacity to register these cases. Combining expertise of the Global Initiative for Cancer Registry Development (GICR) and St Jude Global, we developed a ChildGICR educational program to promote data production. METHODS: We first conducted a needs assessment to identify priority educational topics. Then, we designed the ChildGICR Masterclass, in which individuals with the potential to lead pediatric cancer registration were supported to prepare standard educational material. The outcomes were evaluated using qualitative and quantitative measures. RESULTS: On the basis of indications by 38 GICR collaborators, we identified seven topics relevant to childhood cancer: burden description, registration principles, tumor classification, tumor staging, data quality control, data analysis, and data use. The ChildGICR Masterclass was held online in 2021 over 12 weeks. The 22 nominated participants created presentations in working groups and during live sessions. They also designed future training courses tailored to the needs of their region. Nineteen participants viewed the course experience as excellent, and 20 would continue engagement in the ChildGICR training activities. The developed material was 89% useful according to the faculty of the three online end courses, taught to 88 participants in 16 countries in 2022 and 2023. Among the 75 responding participants, 72 agreed that the learning objectives were attained and 60 were keen to engage in childhood cancer registration activities. CONCLUSION: The ChildGICR Masterclass participants laid the foundation for a network of trainers. Knowledge dissemination in childhood cancer registration is the first necessary step toward evidence-based cancer control. The ChildGICR Masterclass can serve as a model to design, plan, and implement educational programs for health care professionals.

Hearing loss in Australian First Nations children at 6-monthly assessments from age 12 to 36 months: Secondary outcomes from randomised controlled trials of novel pneumococcal conjugate vaccine schedules.

BACKGROUND: In Australian remote communities, First Nations children with otitis media (OM)-related hearing loss are disproportionately at risk of developmental delay and poor school performance, compared to those with normal hearing. Our objective was to compare OM-related hearing loss in children randomised to one of 2 pneumococcal conjugate vaccine (PCV) formulations. METHODS AND FINDINGS: In 2 sequential parallel, open-label, randomised controlled trials (the PREVIX trials), eligible infants were first allocated 1:1:1 at age 28 to 38 days to standard or mixed PCV schedules, then at age 12 months to PCV13 (13-valent pneumococcal conjugate vaccine, +P) or PHiD-CV10 (10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine, +S) (1:1). Here, we report prevalence and level of hearing loss outcomes in the +P and +S groups at 6-monthly scheduled assessments from age 12 to 36 months. From March 2013 to September 2018, 261 infants were enrolled and 461 hearing assessments were performed. Prevalence of hearing loss was 78% (25/32) in the +P group and 71% (20/28) in the +S group at baseline, declining to 52% (28/54) in the +P groups and 56% (33/59) in the +S group at age 36 months. At primary endpoint age 18 months, prevalence of moderate (disabling) hearing loss was 21% (9/42) in the +P group and 41% (20/49) in the +S group (difference -19%; (95% confidence interval (CI) [-38, -1], p = 0.07) and prevalence of no hearing loss was 36% (15/42) in the +P group and 16% (8/49) in the +S group (difference 19%; (95% CI [2, 37], p = 0.05). At subsequent time points, prevalence of moderate hearing loss remained lower in the +P group: differences -3%; (95% CI [-23, 18], p = 1.00 at age 24 months), -12%; (95% CI [-30, 6], p = 0.29 at age 30 months), and -9%; (95% CI [-23, 5], p = 0.25 at age 36 months). A major limitation was the small sample size, hence low power to reach statistical significance, thereby reducing confidence in the effect size. CONCLUSIONS: In this study, we observed a high prevalence and persistence of moderate (disabling) hearing loss throughout early childhood. We found a lower prevalence of moderate hearing loss and correspondingly higher prevalence of no hearing loss in the +P group, which may have substantial benefits for high-risk children, their families, and society, but warrant further investigation. TRIAL REGISTRATION: ClinicalTrials.gov NCT01735084 and NCT01174849.

Patient Safety Culture from a Nursing Perspective in a Chilean Hospital.

Patient safety culture is relevant both in the delivery of care and in the training of nursing staff, its purpose being to prevent and reduce risks associated with health care. This research aims to evaluate patient safety culture from the perspective of the nursing teams in a highly complex public hospital in the city of Valparaíso, Chile. A cross-sectional study with a quantitative approach applying descriptive, bivariate, and inferential statistical analysis was conducted on 259 nurses and nursing assistants from 13 adult medical-surgical units of the Carlos Van Buren hospital. The participants were obtained through a non-probabilistic convenience sample, answering the hospital survey on Patient Safety Culture version 2.0 (HSOPS 2.0), adapted to the Chilean population. The best-evaluated dimension was communication and receptivity; the worst was the support administrators provide for patient safety. This study identified the weaknesses and strengths of the hospital, the most worrying weakness being the shortage of human capital, material, and financial resources necessary to improve patient safety. This study was not registered.

Occupancy Estimation from Blurred Video: A Multifaceted Approach with Privacy Consideration.

Building occupancy information is significant for a variety of reasons, from allocation of resources in smart buildings to responding during emergency situations. As most people spend more than 90% of their time indoors, a comfortable indoor environment is crucial. To ensure comfort, traditional HVAC systems condition rooms assuming maximum occupancy, accounting for more than 50% of buildings' energy budgets in the US. Occupancy level is a key factor in ensuring energy efficiency, as occupancy-controlled HVAC systems can reduce energy waste by conditioning rooms based on actual usage. Numerous studies have focused on developing occupancy estimation models leveraging existing sensors, with camera-based methods gaining popularity due to their high precision and widespread availability. However, the main concern with using cameras for occupancy estimation is the potential violation of occupants' privacy. Unlike previous video-/image-based occupancy estimation methods, we addressed the issue of occupants' privacy in this work by proposing and investigating both motion-based and motion-independent occupancy counting methods on intentionally blurred video frames. Our proposed approach included the development of a motion-based technique that inherently preserves privacy, as well as motion-independent techniques such as detection-based and density-estimation-based methods. To improve the accuracy of the motion-independent approaches, we utilized deblurring methods: an iterative statistical technique and a deep-learning-based method. Furthermore, we conducted an analysis of the privacy implications of our motion-independent occupancy counting system by comparing the original, blurred, and deblurred frames using different image quality assessment metrics. This analysis provided insights into the trade-off between occupancy estimation accuracy and the preservation of occupants' visual privacy. The combination of iterative statistical deblurring and density estimation achieved a 16.29% counting error, outperforming our other proposed approaches while preserving occupants' visual privacy to a certain extent. Our multifaceted approach aims to contribute to the field of occupancy estimation by proposing a solution that seeks to balance the trade-off between accuracy and privacy. While further research is needed to fully address this complex issue, our work provides insights and a step towards a more privacy-aware occupancy estimation system.