Metastasis-free survival of uveal melanoma by tumour size category based on The Cancer Genome Atlas (TCGA) classification in 1001 cases.

BACKGROUND: Uveal melanoma (UM) can be classified by tumour size category and by The Cancer Genome Atlas (TCGA) groups (cytogenetic-based, 4-category prognostic classification into Groups A-D). This study was conducted to assess impact on metastasis-free survival (MFS) in UM by tumour size category based on correlation with TCGA classification. METHODS: Retrospective analysis of 1001 cases categorised as small (0.0-3.0 mm), medium (3.1-8.0 mm) and large (≥8.1 mm), grouped by TCGA classification. RESULTS: Of 1001 cases, TCGA Groups (A/B/C/D) included small (n = 270, 75%/11%/13%/1%), medium (n = 503, 46%/14%/27%/13%) and large (n = 228, 23%/19%/38%/20%) UM. The 5-and 10-year Kaplan-Meier MFS for small UM revealed Group A (98%, 98%), Group B (100%, 100%), Group C (86%, NA) and Group D (100%, NA). For medium UM, the values dropped with Group A (95%, 93%), Group B (90%, 90%), Group C (68%, 38%), and Group D (44%, NA). For large UM, the values dropped further with Group A (94%, 86%), Group B (85%, NA), Group C (40%, 28%), and Group D (23%, NA). Additionally, a comparison (small vs. medium vs. large tumour size category) revealed TCGA low-risk grouping (Groups A or B) in 86% vs. 60% vs. 58% cases with UM. CONCLUSION: By tumour size category, favourable cytogenetics (Groups A or B) is found in 86% of small tumours, 60% of medium tumours, and 58% of large tumours. The MFS at 10 years for favourable cytogenetics was 98% for small tumours, 92% for medium tumours, and 54% for large tumours. Tumour size category can serve as a surrogate for TCGA.

Overcoming the pitfalls of categorizing continuous variables in ecology, evolution and behaviour.

Many variables in biological research-from body size to life-history timing to environmental characteristics-are measured continuously (e.g. body mass in kilograms) but analysed as categories (e.g. large versus small), which can lower statistical power and change interpretation. We conducted a mini-review of 72 recent publications in six popular ecology, evolution and behaviour journals to quantify the prevalence of categorization. We then summarized commonly categorized metrics and simulated a dataset to demonstrate the drawbacks of categorization using common variables and realistic examples. We show that categorizing continuous variables is common (31% of publications reviewed). We also underscore that predictor variables can and should be collected and analysed continuously. Finally, we provide recommendations on how to keep variables continuous throughout the entire scientific process. Together, these pieces comprise an actionable guide to increasing statistical power and facilitating large synthesis studies by simply leaving continuous variables alone. Overcoming the pitfalls of categorizing continuous variables will allow ecologists, ethologists and evolutionary biologists to continue making trustworthy conclusions about natural processes, along with predictions about their responses to climate change and other environmental contexts.

Characteristic of clinical trials related to traumatic brain injury registered on ClinicalTrials.gov over the past two decades (2004-2023).

Objective: The aim of this report is to provide a comprehensive overview of clinical trials and protocols related to traumatic brain injury over the past two decades. Methods: We collected information on clinical trials related to traumatic brain injury (TBI) from the ClinicalTrials.gov database, identified key categorical variables, and assessed their characteristics. Results: A total of 367 TBI-related trials were identified for analysis. All identified trials were interventional clinical trials. Most trials were small-scale, with 75.2% enrolling 1-100 participants, and only about 20% were funded by industry or the National Institutes of Health (NIH). In most trials, participants were gender-neutral (96.5%), and the primary age group was adults and older adults (56.9%). Of all identified TBI trials, 78.2% were randomized, and 69.4% were blinded. Additionally, the primary purpose of 297 trials (80.9%) was treatment, with drug therapy as the most common intervention. A total of 153 trials (41.7%) were completed; however, only 58 trials submitted results to the registry. Furthermore, 81 trials (22.1%) were discontinued early, primarily due to recruitment problems. Clinical trials started between 2004 and 2013 reported a higher proportion of results compared with those started between 2014 and 2023 (35.1% vs. 11.1%, p < 0.001). In addition, between 2014 and 2023, there was an increase in trials for diagnostic purposes (2.4% vs. 6.5%, p < 0.001). Conclusion: Based on the data collected from the ClinicalTrials.gov, our study reveals that most clinical trials related to TBI focus on drug-related treatments, underreporting remains a significant concern, and greater emphasis should be placed on improving the publication and dissemination of clinical trial results.

Dengue in Pune city, India (2017-2019): a comprehensive analysis.

Objectives: To understand the dynamics of dengue disease with special reference to (1) age (2) primary/secondary infections (3) serostatus and (4) serotypes examined during three consecutive years. Methods: During 3 dengue seasons (2017-19), NS1/IgM ELISAs were used for dengue diagnosis in one of the 15 administrative wards of Pune City, India. Predefined symptoms were recorded at the time of diagnosis/hospitalization. IgG-capture ELISA (Panbio) was used to differentiate primary/secondary infections. DENV serotypes were determined for 260 viral RNA-positive patients. Results: During the 3 years, 3,014/6,786 (44.4%, 41.4-49.9%) suspected cases were diagnosed as dengue. Use of either NS1 or IgM would have missed 25.5% or 43% of the confirmed dengue cases, respectively. Notably, a higher proportion of secondary dengue cases remained mild while a substantial proportion of primary infections developed warning signs. The symptoms among Dengue/non-dengue patients and primary/secondary infections varied and influenced by age and serostatus. The number and proportion of dengue serotypes varied yearly. A remarkable decline in dengue cases was observed during the COVID-19 pandemic years. Conclusion: A substantial proportion of primary and secondary dengue patients progress to warning signs/severity or mild infection respectively, underscoring the possible role of non-ADE mechanisms in causing severe dengue that requires hospitalization. Both NS1 and IgM should be used for efficient diagnosis.

The impact of disgust learning on memory processes for neutral stimuli: a classical conditioning approach.

Disgust is a basic emotion that promotes pathogen avoidance and can contaminate nearby neutral stimuli. This study investigates how neutral stimuli, which have acquired disgust value through classical conditioning, are processed in episodic memory. The Category Conditioning paradigm was utilised to assign emotional significance to neutral stimuli, followed by a recognition test conducted immediately or 24 h after conditioning (Experiment 1). The results revealed that neutral stimuli that acquired disgust value were recognised with greater accuracy and higher liberal bias compared to other neutral stimuli in the recognition test conducted after 24 h, but not immediately. Present study also indicates that the memory enhancement observed with disgust did not manifest in the context of fear (Experiment 2). Additionally, the results varied when neutral stimuli associated with disgust were presented with disgusting stimuli in recognition test (Experiment 3). Thus, the present study demonstrates that the memory advantage of disgust extends to associated stimuli when they are presented in a list without disgusting stimuli.

Retinoblastoma Outcomes Based on the 8th Edition American Joint Committee on Cancer Pathological Classification in 1411 Patients.

PURPOSE: To evaluate the outcomes of retinoblastoma (RB) based on the 8th edition of the American Joint Committee on Cancer (AJCC) pathological classification in a global cohort of patients. DESIGN: Retrospective, multicentre, intercontinental collaborative study PARTICIPANTS: 1411 patients INTERVENTION(S): Primary enucleation with/without adjuvant chemotherapy/radiotherapy MAIN OUTCOMES(S): Orbital tumor recurrence, tumor-related metastasis, tumor-related death RESULTS: Based on the 8th edition AJCC pathological classification, 645 (46%) eyes belonged to pT1, 164 (11%) to pT2, 493 (35%) to pT3, and 109 (8%) to pT4 categories. At a mean follow-up of 38 months (median, 35 months; <1-149 months), orbital tumor recurrence was seen in 8 (1%), 5 (3%), 22 (4%) and 25 (23%) of pT1, pT2, pT3, and pT4 (p<0.001) categories, respectively; tumor-related metastasis was seen in 7 (1%), 5 (3%), 40 (8%), and 46 (43%) of pT1, pT2, pT3, and pT4 (p<0.001) categories, respectively; tumor-related death was seen in 12 (2%), 7 (4%), 64 (13%), and 64 (59%) of pT1, pT2, pT3, and pT4 (p<0.001) categories, respectively. Multivariate Cox proportional hazards analysis of outcomes revealed pT category and adjuvant therapy as independent predictors of outcomes. Categories pT3b (p=0.005), pT3c (p<0.001), pT3d (p<0.001), and pT4 (p<0.001) had a greater hazard for orbital recurrence; categories pT2a (p=0.015), pT3a (p<0.001), pT3b (p<0.001), pT3c (p<0.001), pT3d (p<0.001) and pT4 (p<0.001) had a greater hazard for tumor-related metastasis; and categories pT2a (p=0.068), pT2b (p=0.004), pT3a (p<0.001), pT3b (p<0.001), pT3c (p<0.001), pT3d (p<0.001) and pT4 (p<0.001) had a greater hazard for tumor-related death when compared to the pT1 category. Patients who did not receive adjuvant therapy had greater hazards of orbital tumor recurrence in categories pT3b (p=0.005), pT3c (p=0.003), and pT4 (p=0.002); greater hazards of tumor-related metastasis in categories pT3a (p=0.001), pT3b (p=0.01), pT3c (p=0.001), and pT4 (p=0.007); and tumor-related death in categories pT3a (p<0.001), pT3b (p=0.009), pT3c (p=0.018), and pT4 (p<0.001) when compared to those who received adjuvant therapy. CONCLUSION: The 8th edition AJCC pathological classification predicts outcomes in patients undergoing primary enucleation for RB, and adjuvant therapy is associated with a lower risk of orbital recurrence, tumor-related metastasis, and tumor-related death in the pT3 and pT4 categories.

IgG-k/IgG-λ Para-Osseous Plasmacytoma Relapsed as Soft-Tissue Plasmacytoma with IgA-k Immunophenotype: A Case Report and Review of the Literature on Related Biochemical Aspects.

Neoplastic plasma cells (PCs) proliferation at anatomic sites dislocated from the bone marrow (BM) or their contiguous growth from osseous lesions that disrupt the cortical bone is termed extramedullary multiple myeloma (EMD). EMD still remains challenging from a therapeutic and biological perspective. Pathogenesis has not been completely clarified, and it is generally associated with high-risk cytogenetics (HRCAs). In order to emphasize the clinical and biochemical complexity of this disease, we have decided to describe the case of a patient affected by relapsed-refractory (RR) EMD, which presented as para-osseous plasmacytoma with a bi-phenotypical immunoglobulin (Ig) component and lately relapsed as soft-tissue plasmacytoma with a total immunophenotype switch. We have also hypothesized a correlation between Ig patterns and prognosis and suggested the possible inclusion of these biochemical features in the general risk assessment.

More foreign-accented but more comprehensible: Attrition and amelioration of L1 speech in proficient L2 learners.

Background: There is an increasing interest in cross-linguistic influences of the second language (L2) on the first (L1), but its communicative impact remains to be elucidated. This study investigates how L2 learners' L1 pronunciation is perceived as foreign-accented and (in) comprehensible as a function of their L2 learning experience and proficiency levels. Methods: Read speech of 154 L1 Japanese learners of L2 English in the J-AESOP corpus was examined, where approximately one-third of them had lived in English-speaking countries and the rest had never lived outside of Japan. Their L1 speech was rated by another group of native Japanese listeners for accentedness and comprehensibility (from October 25, 2022 to August 20, 2023), while their L2 speech was previously rated by native American English listeners for nativelikeness or proficiency. The speakers' vowel acoustics were also examined. Results: More proficient L2 speakers were perceived as more foreign-accented in their L1, but only if they had lived overseas; their length of residence abroad predicted the degree of perceived accentedness. In contrast, more proficient L2 speakers were consistently perceived as more comprehensible in the L1, regardless of prior overseas experience. Acoustic analyses indicated that perceived accentedness is associated with a clockwise chain shift of all vowel categories in the vowel space. It was also revealed that the dispersion, rather than compactness, of vowel production contributed to perceived comprehensibility, although the degree of L1 vowel dispersion did not predict L2 proficiency. Conclusions: The overall results suggest two main conclusions. First, perceptible L1 foreign accent likely results from L1 disuse rather than L2 interference, thereby L1 pronunciation differs from native norms at a system-wide rather than category-specific level. Second, L2 learning has a positive influence on perceived L1 comprehensibility, rather than individuals with clearer and more comprehensible L1 speech being inherently better L2 learners.

Effects of alligator weed invasion on wetlands in protected areas: A case study of Lishui Jiulong National Wetland Park.

Wetlands are one of the ecosystems most easily and severely invaded by alien species. Biological invasions can have significant impacts on local plant communities and ecosystem functioning. While numerous studies have assessed the impacts of biological invasions on wetlands, relatively few have been conducted in protected areas such as national wetland parks. We conducted a field survey to investigate the effects of the invasive herb Alternanthera philoxeroides (alligator weed) on the productivity and structure of plant communities and soil microbial communities in the Lishui Jiulong National Wetland Park in Zhejiang, China. We also examined the potential influence of the distance to the river edge on the impact of the alligator weed invasion. The alligator weed invasion significantly altered the plant community structure. It reduced the coverage of co-occurring plant species, including native (-31.2 %), invasive (-70.1 %), and non-invasive alien plants (-58.4 %). However, it increased species richness by 50 %, Pielou's evenness by 20 %, and Simpson's diversity index by 29.1 % for the overall plant community. Furthermore, within the community not invaded by alligator weed, increasing the distance to the river edge decreased the number of native plants by 57.0 % and the aboveground biomass of other invasive plants by 78.6 %. Contrary to expectations, no effects of the alligator weed invasion were observed on soil fungal and bacterial communities. Therefore, the impacts of the alligator weed invasion varied with spatial context and plant category, emphasizing the need to consider multiple scales and environmental factors when assessing the effects of invasive species on plant biodiversity. These insights enhance our understanding of plant invasions in wetlands and can guide the development of effective management strategies for these important ecosystems.

Stage Evaluation of Cystic Duct Cancer.

Purpose: Cystic duct cancers (CDCs) have been classified as extrahepatic bile duct cancers or gallbladder cancers (GBCs); however, it is unclear whether their clinical behavior is similar to that of distal extrahepatic bile duct cancers (DBDCs) or GBCs. Materials and Methods: T category of the CDCs was classified using current T category scheme of the GBCs and DBDCs, and clinicopathological factors were compared among 38 CDCs, 345 GBCs, and 349 DBDCs. We modified Nakata's classifications (type 1, confined within cystic duct (CD); combined types 2-4, extension beyond CD) and compared them. Results: No significant overall survival (OS) difference was observed between the patients with CDC, GBC, and DBDC. The T category of GBC staging was more accurate at distinguishing OS in patients with CDC than the DBDC staging. Patients with T3 CDC and GBC showed a significant OS difference when using the T category for GBC staging, while those with T1-T2 CDC and GBC showed no significant difference. In contrast, the T category of DBDC staging did not show any significant OS difference between patients with T1-T2 CDC and DBDC or T3 CDC and DBDC. Patients with type 1 CDC had significantly better OS than those with combined types. Conclusion: Unlike GBCs and DBDCs, CDCs exhibit distinct clinicopathological characteristics. The OS is better when the CDC confines within the CD, compared to when it extends beyond it. Therefore, we propose a new T category scheme (T1, confined to CD; T2, invaded beyond CD) for better classifying CDCs.

Long-term survival after out-of-hospital cardiac arrest in children: outcomes in Andalusia in 2008-2019. / Supervivencia a largo plazo de la parada cardiaca extrahospitalaria en edad pediátrica: resultados en Andalucía durante el periodo 2008-2019.

OBJECTIVE: To determine survival to discharge and neurological outcomes on long-term follow-up of pediatric patients attended for out of-hospital cardiac arrest (OHCA). METHODS: Retrospective study based on an ongoing OHCA registry. Patients aged 16 years or younger were included. Futile resuscitation attempts were excluded. Neurological outcome on hospital discharge and on follow-up was based on variables in the Pediatric Cerebral Performance Category (PCPC) scale. Cases from January 1, 2008, through December 31, 2019, were extracted, and 2 surveys were carried out in May 2021 and January 2023. Patient follow-up time ranged from 1 to 13 years. RESULTS: Of the 13 778 patients in the registry, we found 277 (2.0%) who were aged 16 years or younger. One hundred thirty-seven patients (49.5%) were transported to a hospital, and spontaneous circulation was restored in 99 (35.7%). Thirty-six patients (13%) were discharged. The median (interquartile range) follow-up time was 2172 (978-3035) days. Thirty-one of these patients (86.1%) were alive at follow-up, 3 had died, and 2 were lost to follow-up. Neurological outcomes had worsened in 2 and improved in 6 patients. The neurological outcome of 27 of the 31 patients with complete follow-up data (87.1%) was good (PCPC scores of 1 or 2). CONCLUSIONS: In spite of the low incidence of shockable rhythm in pediatric OHCA, survival with a good neurological outcome is comparable to survival in adults. Children who are discharged after OHCA maintained or improved their neurological function over the long term.

OBJETIVO: Conocer la supervivencia al alta y la evolución neurológica tras seguimiento a largo plazo de pacientes pediátricos atendidos por parada cardíaca extrahospitalaria. METODO: Estudio retrospectivo basado en un registro continuo de parada cardiaca extrahospitalaria. Se incluyeron los pacientes pediátricos (edad menor o igual a 16 años). Se excluyeron reanimaciones consideradas fútiles. Se tomaron como variables resultado el estado neurológico al alta hospitalaria y al seguimiento de los pacientes, siguiendo el modelo de la Pediatric Cerebral Performance Category. El periodo fue del 1 de enero de 2008 al 31 de diciembre de 2019. Se realizaron dos encuestas, en mayo del 2021 y enero del 2023 con un periodo de seguimiento entre 1 y 13 años. RESULTADOS: De los 13.778 pacientes, 277 (2,0%) eran menores de 16 años; 137 (49,5%) trasladados al hospital, 99 de ellos (35,7%) con recuperación de circulación espontánea. Recibieron el alta hospitalaria 36 pacientes (13%). En el seguimiento, mediana (RIC) de 2.172 [978-3.035] días, 31 pacientes (86,1%) seguían con vida, 3 pacientes fallecieron y en dos casos no obtuvimos información. Dos pacientes sufrieron un empeoramiento del estado neurológico y 6 mejoraron. Finalmente, 27 de los 31 pacientes (87,1%) que completaron el seguimiento tenían una buena situación neurológica (PCPC1-2). CONCLUSIONES: A pesar de presentar una incidencia baja, la supervivencia con buen estado neurológico al alta hospitalaria de la parada cardiorrespiratoria extrahospitalaria pediátrica es comparable a la del adulto. Los pacientes pediátricos que recibieron el alta hospitalaria tras una parada cardiorrespiratoria extrahospitalaria mantuvieron o mejoraron su estado neurológico en el seguimiento a largo plazo.

2022 Equine community needs assessment survey.

To stay up-to-date with the demographics, interests, and needs of the equine community, equine extension programs commonly conduct so called "needs assessment surveys". The main goals of the 2022 Rutgers Equine Science Center (ESC) needs assessment survey were to: 1) characterize the equine community, 2) identify information sources used by the equine community, 3) assess the usefulness of selected equine-related services and programs, and 4) determine the perceived importance of selected equine-related issues. An anonymous online survey was distributed through the Rutgers ESC's email list, a press release, and social media. Analysis-eligible surveys were received from n = 493. Most participants were female (92.7 %), 36-60 years of age (48.4 %), white (88.8 %), and horse owners (87.8 %). The top three sources of equine-related information used were 1) personal knowledge (95.7 %), 2) the veterinarian (93.7 %), and 3) the farrier (83.7 %). The survey showed that the provision of horse health information is the most useful service that the Rutgers ESC specifically can provide (79.3 %). This service may also be most useful for other extension programs, but a follow-up study is needed for clarification. The five equine-related issues most often considered to be extremely important were "Lameness and Soundness" (76.5 %), "Ethical Use of Horses" (73.2 %), "Nutrition" (63.9 %), "Right to Farm" (56.8 %), and "Care of Old Horses" (55.6 %). The survey provided insights into the current demographics of the equine community, highlighted personal knowledge, veterinarians and farriers as important information sources, and elucidated "Lameness and Soundness" as the most important equine-related issue.

Preoperative multiparametric magnetic resonance imaging based risk stratification system for predicting biochemical recurrence after radical prostatectomy.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) is used as a current marker in preoperative staging and surgical decision-making, but current evidence on predicting post-surgical oncological outcomes based on preoperative mpMRI findings is limited. In this study We aimed to develop a risk classification based on mpMRI and mpMRI-derived biopsy findings to predict early biochemical recurrence (BCR) after radical prostatectomy. METHODS: Between January 2017 and January 2023, the data of 289 patients who underwent mpMRI, transrectal ultrasound-guided cognitive and fusion targeted biopsies, and subsequent radical prostatectomy (RP) with or without pelvic lymph node dissection in a single center were retrospectively re-evaluated. BCR was defined as a prostate specific-antigen (PSA) ≥ 0.2 ng/mL at least twice after RP. Multivariate logistic regression models tested the predictors of BCR. The regression tree analysis stratified patients into risk groups based on preoperative mpMRI characteristics. Receiver operating characteristic (ROC)-derived area under the curve (AUC) estimates were used to test the accuracy of the regression tree-derived risk stratification tool. RESULTS: BCR was detected in 47 patients (16.2 %) at a median follow-up of 24 months. In mpMRI based multivariate analyses, the maximum diameter of the index lesion (HR 1.081, 95%Cl 1.015-1.151, p = 0.015) the presence of PI-RADS 5 lesions (HR 2.604, 95%Cl 1.043-6.493, p = 0.04), ≥iT3a stage (HR 2.403, 95%Cl 1.013-5.714, p = 0.046) and ISUP grade ≥4 on biopsy (HR 2.440, 95%Cl 1.123-5.301, p = 0.024) were independent predictors of BCR. In regression tree analysis, patients were stratified into three risk groups: maximum diameter of index lesion, biopsy ISUP grade, and clinical stage on mpMRI. The regression tree-derived risk stratification model had moderate-good accuracy in predicting early BCR (AUC 77 %) CONCLUSION: Straightforward mpMRI and mpMRI-derived biopsy-based risk stratification for BCR prediction provide an additional clinical predictive model to the currently available pathological risk tools.

Crossmodal Correspondence Mediates Crossmodal Transfer from Visual to Auditory Stimuli in Category Learning.

This article investigated whether crossmodal correspondence, as a sensory translation phenomenon, can mediate crossmodal transfer from visual to auditory stimuli in category learning and whether multimodal category learning can influence the crossmodal correspondence between auditory and visual stimuli. Experiment 1 showed that the category knowledge acquired from elevation stimuli affected the categorization of pitch stimuli when there were robust crossmodal correspondence effects between elevation and size, indicating that crossmodal transfer occurred between elevation and pitch stimuli. Experiments 2 and 3 revealed that the size category knowledge could not be transferred to the categorization of pitches, but interestingly, size and pitch category learning determined the direction of the pitch-size correspondence, suggesting that the pitch-size correspondence was not stable and could be determined using multimodal category learning. Experiment 4 provided further evidence that there was no crossmodal transfer between size and pitch, due to the absence of a robust pitch-size correspondence. These results demonstrated that crossmodal transfer can occur between audio-visual stimuli with crossmodal correspondence, and multisensory category learning can change the corresponding relationship between audio-visual stimuli. These findings suggest that crossmodal transfer and crossmodal correspondence share similar abstract representations, which can be mediated by semantic content such as category labels.

Graspable foods and tools elicit similar responses in visual cortex.

The extrastriatal visual cortex is known to exhibit distinct response profiles to complex stimuli of varying ecological importance (e.g. faces, scenes, and tools). Although food is primarily distinguished from other objects by its edibility, not its appearance, recent evidence suggests that there is also food selectivity in human visual cortex. Food is also associated with a common behavior, eating, and food consumption typically also involves the manipulation of food, often with hands. In this context, food items share many properties with tools: they are graspable objects that we manipulate in self-directed and stereotyped forms of action. Thus, food items may be preferentially represented in extrastriatal visual cortex in part because of these shared affordance properties, rather than because they reflect a wholly distinct kind of category. We conducted functional MRI and behavioral experiments to test this hypothesis. We found that graspable food items and tools were judged to be similar in their action-related properties and that the location, magnitude, and patterns of neural responses for images of graspable food items were similar in profile to the responses for tool stimuli. Our findings suggest that food selectivity may reflect the behavioral affordances of food items rather than a distinct form of category selectivity.

Donation After Circulatory Death following Withdrawal of Life-Sustaining Treatments. Are We Ready to Break the Dead Donor Rule?

A fundamental criterion considered essential to deem the procedure of vital organ procurement for transplantation ethical is that the donor must be dead, as per the Dead Donor Rule (DDR). In the case of Donation after Circulatory Death (DCD), is the donor genuinely dead? The main aim of this article is to clarify this uncertainty, which primarily arises from the fact that in DCD, death is determined based on cardiac criteria (Circulatory Death, CD), rather than neurological criteria (Brain Death, BD), and that to allow the procurement procedure, physicians reperfuse the organs in an assisted manner. To ensure that the cessation of circulation leads to the irreversible loss of brain functions, DCD regulations require that physicians wait a certain period after CD before commencing vital organ procurement. However, during this "no-touch period," the organs are at risk of damage, potentially rendering them unsuitable for transplantation. When DCD is performed on patients whose CD follows a Withdrawal of Life-Sustaining Treatment (WLST) (DCD Maastricht III category), how long should the no-touch period last? Does its existence really make sense? Does beginning the procedure of vital organ procurement immediately after WLST constitute a violation of the DDR that can be ethically justified? The discussion aims to provide arguments in support of the non-absoluteness of the DDR.

Prediction of Neurological Outcomes in Elderly Patients With Head Trauma Using the Geriatric Trauma Outcome Score: A Retrospective Observational Study.

Introduction Head trauma in elderly people is a problem in today's aging society. Elderly people are susceptible to head trauma because of their declining physical function; this tends to be severe. Outcome prediction is important in decision-making regarding treatment strategies; however, there is no unified method for predicting neurological outcomes in elderly patients with head trauma. Methods Elderly patients with head trauma admitted to the Japan Red Cross Narita Hospital between January 2019 and August 2023 were enrolled in this single-center, retrospective observational study. A favorable neurological outcome was defined as a cerebral performance category scale of 1 or 2. Multivariate logistic regression analysis and receiver operating characteristic curve analysis were performed to investigate the association between geriatric trauma outcome scores and outcomes and to evaluate the predictive value of geriatric trauma outcome scores. The primary outcome was a favorable neurological outcome at discharge, and the secondary outcome was in-hospital mortality. Results A total of 313 elderly patients with head trauma were eligible for analysis. Multivariate logistic regression analysis revealed that the geriatric trauma outcome score was significantly associated with a favorable neurological outcome at discharge (odds ratio 0.94, P <0.0001). In the receiver operating characteristic curve analysis, the geriatric trauma outcome score had a good predictive value for favorable neurological outcomes at discharge (area under the receiver operating characteristic curve 0.83). Conclusions The geriatric trauma outcome score had good predictive value for favorable neurological outcomes at discharge in elderly patients with head trauma and has the potential to aid in decision-making regarding treatment strategies for elderly patients with head trauma.

Reliability of self-reported pubertal development scale for girls in early adolescent: a school population-based study.

OBJECTIVES: The study aimed to evaluate the correlation between self-reported pubertal developmental scale (PDS) and physically assessed Tanner staging by an experienced pediatrician among girls. METHODS: In a school population-based study in Zhongshan, China, we recruited 1,722 girls in grades 1-3 by a multistage stratified cluster random sampling method. Participants completed self-reported PDS questionnaire prior to physical examination. Breast development was evaluated by a female pediatrician combined with ultrasound examination for overweight/obese girls; pubic hair development was evaluated. Otherwise, we tested follicle-stimulating hormone (FSH) and luteinizing hormone (LH) for some participants. RESULTS: We observed a weak association between Tanner-derived composite stage (TDCS) and puberty category scores (PCS) (τ=0.288, p<0.001) among all girls. There was correlation (τ=0.314, p=0.001) between ultrasound-derived composite stage (UDCS) and PCS among overweight/obese girls. Moreover, among overweight/obese girls, PCS was positively correlated with LH (r=0.265, p=0.008), but not FSH (r=0.155, p=0.123), and when the basal LH value was greater than 0.3 mIU/mL, the proportion of PCS stage ≥2 (9/18) was higher than the proportion of TDCS ≥2 (5/18). As for the determination of pubertal onset, when UDCS was used as the gold standard, the specificity of PCS was 0.86 and positive predictive value was 90.00 %. CONCLUSIONS: There was a weak correlation between PCS and TDCS among girls early adolescence. Moreover, among overweight/obese girls, combining hormone values, ultrasonographic stage of breast, and the positive predictive value of PCS, we posit that self-reported PDS might be a more reliable method than TDCS to evaluate pubertal development among overweight/obese girls.

Assessing the Safety of a Novel Monoclonal Antibody Cocktail for Postexposure Prophylaxis in Category III Animal Exposures.

Background: TwinRab™ is a novel life-saving biological containing two monoclonal antibodies (docaravimab and miromavimab) essential for all age victims of category III animal exposures. It effectively neutralizes rabies and similar viruses at the exposure site until the body generates vaccine-induced antibodies. This postmarketing surveillance study assesses the safety of TwinRab™ in current postexposure prophylaxis (PEP) use and aims to reinforce its safety data for future applications. Methods: The prospective, open-label observational study was conducted on patients with the World Health Organization category III animal exposures at a government hospital in a northern region of India, by a suspected rabid animal. The study protocol included administering TwinRab™ (40 IU/kg) and a full course of anti-rabies vaccination as PEP. Results: Out of 405 participants, 404 completed the study as per the protocol. Adverse events (AEs) occurred in 12.35% of cases, with 9.88% local AEs (primarily pain and tenderness) and 2.47% systemic AEs (fever, malaise, and myalgia). All AEs were mild and resolved without complications. Most participants (88.9%) and investigators (89.1%) rated TwinRab™'s tolerability as excellent. Conclusion: The present study demonstrates the evidence of a satisfactory safety profile along with better tolerability of TwinRab™ (40 IU/kg) for category III animal exposures and supports its continued usage.

Microglia are Required for Developmental Specification of AgRP Innervation in the Hypothalamus of Offspring Exposed to Maternal High Fat Diet During Lactation.

Nutritional fluctuations that occur early in life dictate metabolic adaptations that will affect susceptibility to weight gain and obesity later in life. The postnatal period in mice represents a time of dynamic changes in hypothalamic development and maternal consumption of a high fat diet during the lactation period (MHFD) changes the composition of milk and leads to enhanced susceptibility to obesity in offspring. Agouti-related peptide (AgRP) neurons in the arcuate nucleus of the hypothalamus (ARH) react to changes in multiple metabolic signals and distribute neuroendocrine information to other brain regions, such as the paraventricular hypothalamic nucleus (PVH), which is known to integrate a variety of signals that regulate body weight. Development of neural projections from AgRP neurons to the PVH occurs during the lactation period and these projections are reduced in MHFD offspring, but underlying developmental mechanisms remain largely unknown. Microglia are the resident immune cells of the central nervous system and are involved in refinement of neural connections and modulation of synaptic transmission. Because high fat diet exposure causes activation of microglia in adults, a similar activation may occur in offspring exposed to MHFD and play a role in sculpting hypothalamic feeding circuitry. Genetically targeted axonal labeling and immunohistochemistry were used to visualize AgRP axons and microglia in postnatal mice derived from MHFD dams and morphological changes quantified. The results demonstrate regionally localized changes to microglial morphology in the PVH of MHFD offspring that suggest enhanced surveillance activity and are temporally restricted to the period when AgRP neurons innervate the PVH. In addition, axon labeling experiments confirm a significant decrease in AgRP innervation of the PVH in MHFD offspring and provide direct evidence of synaptic pruning of AgRP inputs to the PVH. Microglial depletion with the Colony-stimulating factor 1 receptor inhibitor PLX5622 determined that the decrease in AgRP innervation observed in MHFD offspring is dependent on microglia, and that microglia are required for weight gain that emerges as early as weaning in offspring of MHFD dams. However, these changes do not appear to be dependent on the degree of microglial mediated synaptic pruning. Together, these findings suggest that microglia are activated by exposure to MHFD and interact directly with AgRP axons during development to permanently alter their density, with implications for developmental programming of metabolic phenotype.