Family centeredness of care: a cross-sectional study in intensive care units part of the European society of intensive care medicine.

PURPOSE: To identify key components and variations in family-centered care practices. METHODS: A cross-sectional study, conducted across ESICM members. Participating ICUs completed a questionnaire covering general ICU characteristics, visitation policies, team-family interactions, and end-of-life decision-making. The primary outcome, self-rated family-centeredness, was assessed using a visual analog scale. Additionally, respondents completed the Maslach Burnout Inventory and the Ethical Decision Making Climate Questionnaire to capture burnout dimensions and assess the ethical decision-making climate. RESULTS: The response rate was 53% (respondents from 359/683 invited ICUs who actually open the email); participating healthcare professionals (HCPs) were from Europe (62%), Asia (9%), South America (6%), North America (5%), Middle East (4%), and Australia/New Zealand (4%). The importance of family-centeredness was ranked high, median 7 (IQR 6-8) of 10 on VAS. Significant differences were observed across quartiles of family centeredness, including in visitation policies availability of a waiting rooms, family rooms, family information leaflet, visiting hours, night visits, sleep in the ICU, and in team-family interactions, including daily information, routine day-3 conference, and willingness to empower nurses and relatives. Higher family centeredness correlated with family involvement in rounds, participation in patient care and end-of-life practices. Burnout symptoms (41% of respondents) were negatively associated with family-centeredness. Ethical climate and willingness to empower nurses were independent predictors of family centeredness. CONCLUSIONS: This study emphasizes the need to prioritize healthcare providers' mental health for enhanced family-centered care. Further research is warranted to assess the impact of improving the ethical climate on family-centeredness.

Overexpression of the schizophrenia risk gene C4 in PV cells drives sex-dependent behavioral deficits and circuit dysfunction.

Fast-spiking parvalbumin (PV)-positive cells are key players in orchestrating pyramidal neuron activity, and their dysfunction is consistently observed in myriad brain diseases. To understand how immune complement dysregulation - a prevalent locus of brain disease etiology - in PV cells may drive disease pathogenesis, we have developed a transgenic mouse line that permits cell-type specific overexpression of the schizophrenia-associated complement component 4 (C4) gene. We found that overexpression of mouse C4 (mC4) in PV cells causes sex-specific behavioral alterations and concomitant deficits in synaptic connectivity and excitability of PV cells of the prefrontal cortex. Using a computational network, we demonstrated that these microcircuit deficits led to hyperactivity and disrupted neural communication. Finally, pan-neuronal overexpression of mC4 failed to evoke the same deficits in behavior as PV-specific mC4 overexpression, suggesting that C4 perturbations in fast-spiking neurons are more harmful to brain function than pan-neuronal alterations. Together, these results provide a causative link between C4 and the vulnerability of PV cells in brain disease.

A pipeline for STED super-resolution imaging and Imaris analysis of nanoscale synapse organization in mouse cortical brain slices.

Advances in super-resolution imaging enable us to delve into its intricate structural and functional complexities with unprecedented detail. Here, we present a pipeline to visualize and analyze the nanoscale organization of cortical layer 1 apical dendritic spines in the mouse prefrontal cortex. We describe steps for brain slice preparation, immunostaining, stimulated emission depletion super-resolution microscopy, and data analysis using the Imaris software package. This protocol allows the study of physiologically relevant brain circuits implicated in neuropsychiatric disorders.

Co-design of a Community-based Rehabilitation Program to Decrease Musculoskeletal Disabilities in a Mayan-Yucateco Municipality.

BACKGROUND: Chronic musculoskeletal (MSK) diseases are an important cause of disability in the Mayan community of Chankom in Yucatán, Mexico. OBJECTIVE: To understand a community-based participatory research (CBPR) strategy implemented in Chankom to design a community-based rehabilitation (CBR) program for people living with MSK diseases. METHODS: Qualitative descriptive thematic analysis from an ethnographic work conducted in Chankom, during the implementation of a CBPR strategy from 2014 to 2017. RESULTS: Four main themes describe the main processes that formed our CBPR strategy: 1) forming and maintaining an alliance between academic and community members, 2) prioritizing community needs, 3) integrating local and global knowledge and 4) shared-decision-making. This CBPR strategy allowed the design of a CBR program formed by six main interventions: 1) health services coordination, 2) personal support, 3) community venous blood sampling services, 4) community specialized services, 5) health promotion, and 6) health transportation services. CONCLUSIONS: Co-designing a CBR program for people living with chronic MSK diseases in Chankom was possible through an extensive community engagement work structured around four main processes, including the essential principles of CBPR. The designed CBR program includes culturally sensitive interventions aimed at improving the quality, availability, accessibility, and acceptability of health care services. Moreover, the program mainly addressed the "health" component of the World Health Organization-CBR matrix, suggesting a need for a new CBPR cycle after it is implemented and evaluated in the future.

C4 induces pathological synaptic loss by impairing AMPAR trafficking.

During development, activation of the complement pathway, an extracellular proteolytic cascade, results in microglia-dependent synaptic elimination via complement receptor 3 (CR3). Here, we report that decreased connectivity caused by overexpression of C4 (C4-OE), a schizophrenia-associated gene, is CR3 independent. Instead, C4-OE triggers GluR1 degradation through an intracellular mechanism involving endosomal trafficking protein SNX27, resulting in pathological synaptic loss. Moreover, the connectivity deficits associated with C4-OE were rescued by increasing levels of SNX27, linking excessive complement activity to an intracellular endolysosomal recycling pathway affecting synapses.

Disaster day: a simulation-based competition for educating emergency medicine residents and medical students on disaster medicine.

BACKGROUND: Disaster medicine is a growing field within the specialty of emergency medicine, but educational training typically focuses on hospital drills or other educational strategies, such as didactics, simulation, or tabletop exercises. With the success of gamification in other medical education applications, we sought to investigate if a novel gamified curricular innovation would lead to improved test performance and confidence in the ability to manage a real mass casualty incident (MCI). METHODS: This was a prospective observational study of medical students and emergency medicine residents who participated in a 4-h simulation-based competition consisting of 4 unique stations. Each station had learning objectives associated with the content taught. Learners completed a pre-event survey, followed by participation in the competitive gamification event, and subsequently completed a post-event survey. Differences between pre- and post-event responses were matched and analyzed using paired and unpaired t tests for medical knowledge assessments, the Mann-Whitney U test for perceptions of confidence in the ability to manage an MCI event, and descriptive statistics provided on perceptions of the effectiveness of this educational strategy. RESULTS: We analyzed data from 49 learners with matched (and unmatched) pre- and post-event survey responses. There was a statistically significant increase in medical knowledge assessment scores in both unmatched group means and available matched data (47 to 69%, p < 0.01, and 50 to 69%, p < 0.05). Self-reported confidence in the ability to handle an MCI scenario also significantly increased (p < 0.01). Finally, 100% of respondents indicated they "agreed" or "strongly agreed" that the event was an effective education tool for disaster preparedness and training. CONCLUSIONS: In this study, we found that learners perceived a novel gamification event as an effective educational tool, which led to improved learner knowledge and self-reported confidence in the ability to manage a real MCI.

REVEALS: An Open Source Multi Camera GUI For Rodent Behavior Acquisition.

Understanding the rich behavioral data generated by mice is essential for deciphering the function of the healthy and diseased brain. However, the current landscape lacks effective, affordable, and accessible methods for acquiring such data, especially when employing multiple cameras simultaneously. We have developed REVEALS (Rodent BEhaVior Multi-camErA Laboratory AcquiSition), a graphical user interface (GUI) written in python for acquiring rodent behavioral data via commonly used USB3 cameras. REVEALS allows for user-friendly control of recording from one or multiple cameras simultaneously while streamlining the data acquisition process, enabling researchers to collect and analyze large datasets efficiently. We release this software package as a stand-alone, open-source framework for researchers to use and modify according to their needs. We describe the details of the GUI implementation, including the camera control software and the video recording functionality. We validate results demonstrating the GUI's stability, reliability, and accuracy for capturing and analyzing rodent behavior using DeepLabCut pose estimation in both an object and social interaction assay. REVEALS can also be incorporated into other custom pipelines to analyze complex behavior, such as MoSeq. In summary, REVEALS provides an interface for collecting behavioral data from one or multiple perspectives that, combined with deep learning algorithms, will allow the scientific community to discover and characterize complex behavioral phenotypes to understand brain function better.

Ingestion of Toxic Iron Dose With Benign Outcome.

Iron poisoning is a significant and potentially life-threatening condition that is commonly encountered in the emergency department. The severity of toxicity is based on the amount of iron ingested, and symptoms can range from mild gastrointestinal discomfort to multi-organ failure. Although current guidelines recommend therapy for patients with estimated ingestion of >60 mg/kg, the most useful laboratory test to determine toxicity is the serum iron level measured at four to six hours after ingestion. In this report, we present a case of a 28-year-old female who ingested a toxic dose of iron (88 mg/kg) but was only minimally symptomatic and managed with supportive care alone. The case highlights the importance of a high index of suspicion, careful clinical evaluation in patients with iron toxicity, and the need for individualized treatment decisions based on the patient's clinical presentation and laboratory values.

Organophosphate Toxicity Presenting as a Stroke Alert.

Altered mental status is a common emergency department presentation. It has a broad differential and can be particularly challenging when the patient is unable to give a history and collateral information is not immediately available. The authors present a case of altered mental status initially brought in as a stroke alert but later discovered to be intentional organophosphate ingestion. Although organophosphate poisoning is relatively rare in the United States, it should be considered in patients with altered mental status with miosis who are unresponsive to naloxone, especially in the setting of bradycardia or copious secretions.

Functional improvement in individuals with chronic spinal cord injury treated with 4-aminopyridine: A systematic review.

Study design: Systematic review. Objective: To provide current evidence on the efficacy of 4-aminopyridine (4-AP) to bring about functional improvement in individuals with chronic traumatic spinal cord injury (SCI). Methods: The Medline (PubMed), Web of Science and SCOPUS databases were systematically searched for relevant articles on the efficacy of 4-AP to treat SCI, from the dates such articles were first published until May 2022. Full-text versions of all the articles selected were examined independently by two reviewers. Methodological quality was rated using the Modified Jadad Scale, and risk of bias was assessed with the RoB-2 test. Data extracted included human models/types, PRISMA assessment protocols, and the results of each study. Descriptive syntheses are provided. Results: In total, 28 articles were initially identified, 10 of which were included after screening. Most of the studies reviewed reported some degree of patient improvement in one or more of the following parameters: motor, sensitivity and sexual function, sphincter control, spasticity, ability to function independently, quality of life, central motor conduction, pain, and pulmonary function. Conclusions: This review confirms the efficacy of 4-AP in improving several conditions resulting from SCI but further research on this topic is warranted. Additional randomized clinical trials with 4-AP involving larger sample sizes are needed, as are consistent outcome measures in order to obtain adequate data for analysis with a view to enhance treatment benefits. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=334835, PROSPERO CRD42022334835.

Molecular Targeted Therapy in Oncology Focusing on DNA Repair Mechanisms.

DNA repair mechanisms are essential for maintaining cellular homeostasis. Malfunction of these repair mechanisms leads to cellular DNA mutations, carcinogenic transformation, and cell death. These same defects also create vulnerabilities that are relatively specific to cancer cells, and which could potentially be exploited to increase the therapeutic index of anticancer treatments and thereby improve patient outcomes. The targeted therapy based on inhibiting the DNA damage response (DDR) opens a new therapeutic landscape for patients with deficient DDR. Currently there are two DNA repair mechanisms that are used as targets for molecular therapies: Mitsmach Repair (MMR) and Homologous Recombination Repair (HRR). These molecular targets allow for immunotherapy treatments based on "checkpoint inhibitors" (ICIs) drugs and "PARP inhibitor" (PARPi) drugs in different solid tumors. In this review we will describe the state of the art of this interesting mechanism and explain the options for treatment based on these alterations. Moreover, many clinical trials are currently underway exploring better treatment options for dMMR and HRD patients with different solid tumours.

Compartment Syndrome Secondary to Vascular Transection from a Knee Dislocation.

Acute knee dislocation is a rare orthopedic injury with an incidence of <0.02% annually. The authors discuss a case involving a vascular injury sustained from a mechanical fall at home causing compartment syndrome. The case illustrates known complications associated with knee dislocations: vascular injury and compartment syndrome as well as the high suspicion needed in certain patient populations, such as Down's syndrome. It highlights the importance of rapid diagnosis, a complete physical exam, and the need to involve consultants in a timely fashion. A high index of suspicion for vascular injury following trauma to the knee, regardless of the mechanism is imperative.

Clinical and organizational factors associated with mortality during the peak of first COVID-19 wave: the global UNITE-COVID study.

PURPOSE: To accommodate the unprecedented number of critically ill patients with pneumonia caused by coronavirus disease 2019 (COVID-19) expansion of the capacity of intensive care unit (ICU) to clinical areas not previously used for critical care was necessary. We describe the global burden of COVID-19 admissions and the clinical and organizational characteristics associated with outcomes in critically ill COVID-19 patients. METHODS: Multicenter, international, point prevalence study, including adult patients with SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) and a diagnosis of COVID-19 admitted to ICU between February 15th and May 15th, 2020. RESULTS: 4994 patients from 280 ICUs in 46 countries were included. Included ICUs increased their total capacity from 4931 to 7630 beds, deploying personnel from other areas. Overall, 1986 (39.8%) patients were admitted to surge capacity beds. Invasive ventilation at admission was present in 2325 (46.5%) patients and was required during ICU stay in 85.8% of patients. 60-day mortality was 33.9% (IQR across units: 20%-50%) and ICU mortality 32.7%. Older age, invasive mechanical ventilation, and acute kidney injury (AKI) were associated with increased mortality. These associations were also confirmed specifically in mechanically ventilated patients. Admission to surge capacity beds was not associated with mortality, even after controlling for other factors. CONCLUSIONS: ICUs responded to the increase in COVID-19 patients by increasing bed availability and staff, admitting up to 40% of patients in surge capacity beds. Although mortality in this population was high, admission to a surge capacity bed was not associated with increased mortality. Older age, invasive mechanical ventilation, and AKI were identified as the strongest predictors of mortality.

Methodology of a Large Multicenter Observational Study of Patients with COVID-19 in Spanish Intensive Care Units.

INTRODUCTION: The COVID-19 pandemic created tremendous challenges for health-care systems. Intensive care units (ICU) were hit with a large volume of patients requiring ICU admission, mechanical ventilation, and other organ support with very high mortality. The Centro de Investigación Biomédica en Red-Enfermedades Respiratorias (CIBERES), a network of Spanish researchers to investigate in respiratory disease, commissioned the current proposal in response to the Instituto de Salud Carlos III (ISCIII) call. METHODS: CIBERESUCICOVID is a multicenter, observational, prospective/retrospective cohort study of patients with COVID-19 admitted to Spanish ICUs. Several work packages were created, including study population and ICU data collection, follow-up, biomarkers and miRNAs, data management and quality. RESULTS: This study included 6102 consecutive patients admitted to 55 ICUs homogeneously distributed throughout Spain and the collection of blood samples from more than 1000 patients. We enrolled a large population of COVID-19 ICU-admitted patients including baseline characteristics, ICU and MV data, treatments complications, and outcomes. The in-hospital mortality was 31%, and 76% of patients required invasive mechanical ventilation. A 3-6 month and 1 year follow-up was performed. Few deaths after 1 year discharge were registered. Low anti-SARS-CoV-2 S antibody levels predict mortality in critical COVID-19. These antibodies contribute to prevent systemic dissemination of SARS-CoV-2. The severity of COVID-19 impacts the circulating miRNA profile. Plasma miRNA profiling emerges as a useful tool for risk-based patient stratification in critically ill COVID-19 patients. CONCLUSIONS: We present the methodology used in a large multicenter study sponsored by ISCIII to determine the short- and long-term outcomes in patients with COVID-19 admitted to more than 50 Spanish ICUs.

Koebner Phenomenon: Café-au-Lait Spots Developing after a Secondary-Degree Burn in a Patient with Neurofibromatosis Type 1.

An 18-year-old woman with an established history of neurofibromatosis type 1 (NF-1) presented for her 1-year dermatologic follow-up. Physical examination revealed two subcutaneous nodules on her right arm, axillary freckling, scattered café-au-lait macules (CALMs) on the trunk, and a 12 cm × 17 cm hyperpigmented rectangular region on her right flank (Figure 1). The pigmented patch contained numerous new CALMs that were morphologically consistent with CALMs identified on prior examinations; neither the patch nor the CALMs within it were present at prior examinations. Interestingly, the appearance of the patch and associated CALMs was preceded by a rectangular-shaped, second-degree thermal burn. On further questioning, the patient revealed that she had burned herself with hot water 4 months prior to her presentation in clinic, and noted the development of multiple CALMs within the skin area of her prior burn approximately 4 weeks after the incident. Of note, her left flank had sparsely scattered CALMs, which was consistent with her prior skin examinations (Figure 2). A depigmenting cream was to be applied to the rectangular pigmented patch; unfortunately, post-inflammatory hyperpigmentation from the burn and the adjoining lesions resulting from the Koebner phenomenon continue to be refractory to treatment.

Development of a Predictive Model for the Diagnosis of Lower Urinary Tract Obstruction in Men.

PURPOSE: We sought to develop and validate a bladder outlet obstruction predictive model for men with nonneurogenic lower urinary tract symptoms. MATERIALS AND METHODS: We retrospectively included 1,148 patients who underwent a urodynamic study in the Urology Service of the Burgos University Hospital from January 2007 to December 2019. Obstruction was defined using the Abrams-Griffiths number. A multivariable logistic regression analysis was conducted to determine the predictors of bladder outlet obstruction. We transferred these data to a model to calculate the individual probability of obstruction. RESULTS: A first group with 563 patients randomly divided was selected for the design of the predictive risk model and a second group of 585 patients for the validation. A total of 331 patients (58.8%) in the development group and 381 (65.1%) in the validation group had a diagnosis of obstruction. A multivariable logistic regression model showed that age, history of previous surgical intervention, presence of voiding symptoms, preserved anal tone, maximum urinary flow rate and voiding efficiency were significant for predicting obstruction. The model had an area under the receiver operating characteristic curve of 0.78 (95% CI 0.75-0.82) and a model validation of 0.78 (0.72-0.83). CONCLUSIONS: Our proposed model based on clinical and noninvasive urodynamics parameters allows us to predict the risk of presenting bladder outlet obstruction in patients with lower urinary tract symptoms.

Highly unstable heterogeneous representations in VIP interneurons of the anterior cingulate cortex.

A hallmark of the anterior cingulate cortex (ACC) is its functional heterogeneity. Functional and imaging studies revealed its importance in the encoding of anxiety-related and social stimuli, but it is unknown how microcircuits within the ACC encode these distinct stimuli. One type of inhibitory interneuron, which is positive for vasoactive intestinal peptide (VIP), is known to modulate the activity of pyramidal cells in local microcircuits, but it is unknown whether VIP cells in the ACC (VIPACC) are engaged by particular contexts or stimuli. Additionally, recent studies demonstrated that neuronal representations in other cortical areas can change over time at the level of the individual neuron. However, it is not known whether stimulus representations in the ACC remain stable over time. Using in vivo Ca2+ imaging and miniscopes in freely behaving mice to monitor neuronal activity with cellular resolution, we identified individual VIPACC that preferentially activated to distinct stimuli across diverse tasks. Importantly, although the population-level activity of the VIPACC remained stable across trials, the stimulus-selectivity of individual interneurons changed rapidly. These findings demonstrate marked functional heterogeneity and instability within interneuron populations in the ACC. This work contributes to our understanding of how the cortex encodes information across diverse contexts and provides insight into the complexity of neural processes involved in anxiety and social behavior.