Neurological monitoring and management for adult extracorporeal membrane oxygenation patients: Extracorporeal Life Support Organization consensus guidelines.

BACKGROUND: Critical care of patients on extracorporeal membrane oxygenation (ECMO) with acute brain injury (ABI) is notable for a lack of high-quality clinical evidence. Here, we offer guidelines for neurological care (neurological monitoring and management) of adults during and after ECMO support. METHODS: These guidelines are based on clinical practice consensus recommendations and scientific statements. We convened an international multidisciplinary consensus panel including 30 clinician-scientists with expertise in ECMO from all chapters of the Extracorporeal Life Support Organization (ELSO). We used a modified Delphi process with three rounds of voting and asked panelists to assess the recommendation levels. RESULTS: We identified five key clinical areas needing guidance: (1) neurological monitoring, (2) post-cannulation early physiological targets and ABI, (3) neurological therapy including medical and surgical intervention, (4) neurological prognostication, and (5) neurological follow-up and outcomes. The consensus produced 30 statements and recommendations regarding key clinical areas. We identified several knowledge gaps to shape future research efforts. CONCLUSIONS: The impact of ABI on morbidity and mortality in ECMO patients is significant. Particularly, early detection and timely intervention are crucial for improving outcomes. These consensus recommendations and scientific statements serve to guide the neurological monitoring and prevention of ABI, and management strategy of ECMO-associated ABI.

Blockade of the CCR3 receptor reduces neutrophil recruitment to the lung during acute inflammation.

Neutrophils represent one of the host's first lines of defense against invading pathogens. However, an aberrant activation can cause damage to the host. In the case of respiratory infections with viral or bacterial pathogens, one of the most common complications is the development of acute respiratory distress syndrome (ARDS), in which neutrophil infiltration into the lung is a hallmark. Neutrophils gain expression of chemokine receptors under inflammatory conditions, and their activation can amplify the neutrophil responses. Earlier studies showed that neutrophils recruited to the lung mucosa during bacterial infection upregulate expression of CCR3 and ex vivo stimulation of CCR3 results in an increased neutrophil activation. Therefore, the modulation of effector functions or migration of neutrophils to target sites through chemokine receptors constitutes an opportunity for pharmacological intervention. We aimed to determine whether the blockade of the CCR3 using the specific antagonist SB-328437 reduces neutrophil recruitment and inflammation in the lung in the LPS-induced lung injury model and influenza infection in mice. We found that neutrophils acquire CCR3 expression in the lung alveolar space. The intraperitoneal administration of SB-328437 reduced neutrophil recruitment to the lung alveolar space and reduced tissue damage in both the LPS-induced lung injury model and influenza infection. Moreover, treatment with SB-328437 reduced the percentage of neutrophils producing TNFα and neutrophil activation in the alveolar space. Together, these data suggest that CCR3 blockade might be a pharmacological strategy to prevent the aberrant neutrophil activation that results detrimental for the host but preserves sufficient effector response to control the pathogen.

CCL28 modulates neutrophil responses during infection with mucosal pathogens.

The chemokine CCL28 is highly expressed in mucosal tissues, but its role during infection is not well understood. Here, we show that CCL28 promotes neutrophil accumulation in the gut of mice infected with Salmonella and in the lung of mice infected with Acinetobacter. Neutrophils isolated from the infected mucosa expressed the CCL28 receptors CCR3 and, to a lesser extent, CCR10, on their surface. The functional consequences of CCL28 deficiency varied between the two infections: Ccl28-/- mice were highly susceptible to Salmonella gut infection but highly resistant to otherwise lethal Acinetobacter lung infection. In vitro, unstimulated neutrophils harbored pre-formed intracellular CCR3 that was rapidly mobilized to the cell surface following phagocytosis or inflammatory stimuli. Moreover, CCL28 stimulation enhanced neutrophil antimicrobial activity, production of reactive oxygen species, and formation of extracellular traps, all processes largely dependent on CCR3. Consistent with the different outcomes in the two infection models, neutrophil stimulation with CCL28 boosted the killing of Salmonella but not Acinetobacter. CCL28 thus plays a critical role in the immune response to mucosal pathogens by increasing neutrophil accumulation and activation, which can enhance pathogen clearance but also exacerbate disease depending on the mucosal site and the infectious agent.

Neurologic complications in patients receiving aortic versus subclavian versus femoral arterial cannulation for post-cardiotomy extracorporeal life support: results of the PELS observational multicenter study.

BACKGROUND: Cerebral perfusion may change depending on arterial cannulation site and may affect the incidence of neurologic adverse events in post-cardiotomy extracorporeal life support (ECLS). The current study compares patients' neurologic outcomes with three commonly used arterial cannulation strategies (aortic vs. subclavian/axillary vs. femoral artery) to evaluate if each ECLS configuration is associated with different rates of neurologic complications. METHODS: This retrospective, multicenter (34 centers), observational study included adults requiring post-cardiotomy ECLS between January 2000 and December 2020 present in the Post-Cardiotomy Extracorporeal Life Support (PELS) Study database. Patients with Aortic, Subclavian/Axillary and Femoral cannulation were compared on the incidence of a composite neurological end-point (ischemic stroke, cerebral hemorrhage, brain edema). Secondary outcomes were overall in-hospital mortality, neurologic complications as cause of in-hospital death, and post-operative minor neurologic complications (seizures). Association between cannulation and neurological outcomes were investigated through linear mixed-effects models. RESULTS: This study included 1897 patients comprising 26.5% Aortic (n = 503), 20.9% Subclavian/Axillary (n = 397) and 52.6% Femoral (n = 997) cannulations. The Subclavian/Axillary group featured a more frequent history of hypertension, smoking, diabetes, previous myocardial infarction, dialysis, peripheral artery disease and previous stroke. Neuro-monitoring was used infrequently in all groups. Major neurologic complications were more frequent in Subclavian/Axillary (Aortic: n = 79, 15.8%; Subclavian/Axillary: n = 78, 19.6%; Femoral: n = 118, 11.9%; p < 0.001) also after mixed-effects model adjustment (OR 1.53 [95% CI 1.02-2.31], p = 0.041). Seizures were more common in Subclavian/Axillary (n = 13, 3.4%) than Aortic (n = 9, 1.8%) and Femoral cannulation (n = 12, 1.3%, p = 0.036). In-hospital mortality was higher after Aortic cannulation (Aortic: n = 344, 68.4%, Subclavian/Axillary: n = 223, 56.2%, Femoral: n = 587, 58.9%, p < 0.001), as shown by Kaplan-Meier curves. Anyhow, neurologic cause of death (Aortic: n = 12, 3.9%, Subclavian/Axillary: n = 14, 6.6%, Femoral: n = 28, 5.0%, p = 0.433) was similar. CONCLUSIONS: In this analysis of the PELS Study, Subclavian/Axillary cannulation was associated with higher rates of major neurologic complications and seizures. In-hospital mortality was higher after Aortic cannulation, despite no significant differences in incidence of neurological cause of death in these patients. These results encourage vigilance for neurologic complications and neuromonitoring use in patients on ECLS, especially with Subclavian/Axillary cannulation.

Post-cardiotomy extracorporeal life support: A cohort of cannulation in the general ward.

OBJECTIVES: Post-cardiotomy extracorporeal life support (ECLS) cannulation might occur in a general post-operative ward due to emergent conditions. Its characteristics have been poorly reported and investigated This study investigates the characteristics and outcomes of adult patients receiving ECLS cannulation in a general post-operative cardiac ward. METHODS: The Post-cardiotomy Extracorporeal Life Support (PELS) is a retrospective (2000-2020), multicenter (34 centers), observational study including adult patients who required ECLS for post-cardiotomy shock. This PELS sub-analysis analyzed patients´ characteristics, in-hospital outcomes, and long-term survival in patients cannulated for veno-arterial ECLS in the general ward, and further compared in-hospital survivors and non-survivors. RESULTS: The PELS study included 2058 patients of whom 39 (1.9%) were cannulated in the general ward. Most patients underwent isolated coronary bypass grafting (CABG, n = 15, 38.5%) or isolated non-CABG operations (n = 20, 51.3%). The main indications to initiate ECLS included cardiac arrest (n = 17, 44.7%) and cardiogenic shock (n = 14, 35.9%). ECLS cannulation occurred after a median time of 4 (2-7) days post-operatively. Most patients' courses were complicated by acute kidney injury (n = 23, 59%), arrhythmias (n = 19, 48.7%), and postoperative bleeding (n = 20, 51.3%). In-hospital mortality was 84.6% (n = 33) with persistent heart failure (n = 11, 28.2%) as the most common cause of death. No peculiar differences were observed between in-hospital survivors and nonsurvivors. CONCLUSIONS: This study demonstrates that ECLS cannulation due to post-cardiotomy emergent adverse events in the general ward is rare, mainly occurring in preoperative low-risk patients and after a postoperative cardiac arrest. High complication rates and low in-hospital survival require further investigations to identify patients at risk for such a complication, optimize resources, enhance intervention, and improve outcomes.

Five-Year Survivorship of Total Hip Arthroplasty With a Proximally Coated, Medially Collared, Triple-Tapered Femoral Stem: A Retrospective, Multicenter Registry Review.

Background The anterior approach for total hip arthroplasty (THA) has gained popularity in recent years. Some surgeons have been hesitant to adopt the approach due to concerns over increased complications such as intraoperative fracture, stem loosening, and stem revision. This study aims to evaluate the all-cause revision rate and survivorship of a collared, triple-tapered stem that was designed specifically for use with the anterior approach in THA to enhance outcomes and reduce adverse events. Methodology A retrospective outcomes review was conducted to assess survivorship and clinical outcomes for a specific proximally coated, medially collared triple-tapered (MCTT) femoral stem. Results In a cohort of 5,264 hips, Kaplan-Meier survivorship estimates (95% confidence interval [CI]; N with further follow-up), with survivorship defined as no revision of any component for any reason at five years after the index procedure, were 98.9% (97.8%-99.4%; 43) under the clinical assumption and 99.6% (99.4%-99.7%; 894) under the registry assumption. With survivorship defined as stem revision for any reason, survivorship estimates at five years postoperatively were 99.6% (99.3%-99.8%; 43) under the clinical assumption and 99.8% (99.7%-99.9%; 894) under the registry assumption. The mean follow-up time was 94.52 days (standard deviation [SD] 2.24, range 90.03-96.02). At five years postoperatively, the mean Harris Hip Score was 95.19, and the mean Hip Disability and Osteoarthritis Outcome Score Junior (HOOS JR) score was 98.66. Conclusions Our evaluation demonstrates excellent construct and stem survivorship and very low complication rates at midterm postoperative follow-up.

Characteristics and Outcomes of Prolonged Venoarterial Extracorporeal Membrane Oxygenation After Cardiac Surgery: The Post-Cardiotomy Extracorporeal Life Support (PELS-1) Cohort Study.

OBJECTIVES: Most post-cardiotomy (PC) extracorporeal membrane oxygenation (ECMO) runs last less than 7 days. Studies on the outcomes of longer runs have provided conflicting results. This study investigates patient characteristics and short- and long-term outcomes in relation to PC ECMO duration, with a focus on prolonged (> 7 d) ECMO. DESIGN: Retrospective observational cohort study. SETTING: Thirty-four centers from 16 countries between January 2000 and December 2020. PATIENTS: Adults requiring post PC ECMO between 2000 and 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Characteristics, in-hospital, and post-discharge outcomes were compared among patients categorized by ECMO duration. Survivors and nonsurvivors were compared in the subgroup of patients with ECMO duration greater than 7 days. The primary outcome was in-hospital mortality. Two thousand twenty-one patients were included who required PC ECMO for 0-3 days ( n = 649 [32.1%]), 4-7 days ( n = 776 [38.3%]), 8-10 days ( n = 263 [13.0%]), and greater than 10 days ( n = 333 [16.5%]). There were no major differences in the investigated preoperative and procedural characteristics among ECMO duration groups. However, the longer ECMO duration category was associated with multiple complications including bleeding, acute kidney injury, arrhythmias, and sepsis. Hospital mortality followed a U-shape curve, with lowest mortality in patients with ECMO duration of 4-7 days ( n = 394, 50.8%) and highest in patients with greater than 10 days ECMO support ( n = 242, 72.7%). There was no significant difference in post-discharge survival between ECMO duration groups. In patients with ECMO duration greater than 7 days, age, comorbidities, valvular diseases, and complex procedures were associated with nonsurvival. CONCLUSIONS: Nearly 30% of PC ECMO patients were supported for greater than 7 days. In-hospital mortality increased after 7 days of support, especially in patients undergoing valvular and complex surgery, or who had complications, although the long-term post-discharge prognosis was comparable to PC ECMO patients with shorter support duration.

Features and outcomes of female and male patients requiring postcardiotomy extracorporeal life support.

OBJECTIVES: Although cardiogenic shock requiring extracorporeal life support after cardiac surgery is associated with high mortality, the impact of sex on outcomes of postcardiotomy extracorporeal life support remains unclear with conflicting results in the literature. We compare patient characteristics, in-hospital outcomes, and overall survival between females and males requiring postcardiotomy extracorporeal life support. METHODS: This retrospective, multicenter (34 centers), observational study included adults requiring postcardiotomy extracorporeal life support between 2000 and 2020. Preoperative, procedural, and extracorporeal life support characteristics, complications, and survival were compared between females and males. Association between sex and in-hospital survival was investigated through mixed Cox proportional hazard models. RESULTS: This analysis included 1823 patients (female: 40.8%; median age: 66.0 years [interquartile range, 56.2-73.0 years]). Females underwent more mitral valve surgery (females: 38.4%, males: 33.1%, P = .019) and tricuspid valve surgery (feamales: 18%, males: 12.4%, P < .001), whereas males underwent more coronary artery surgery (females: 45.9%, males: 52.4%, P = .007). Extracorporeal life support implantation was more common intraoperatively in feamales (females: 64.1%, females: 59.1%) and postoperatively in males (females: 35.9%, males: 40.9%, P = .036). Ventricular unloading (females: 25.1%, males: 36.2%, P < .001) and intra-aortic balloon pumps (females: 25.8%, males: 36.8%, P < .001) were most frequently used in males. Females had more postoperative right ventricular failure (females: 24.1%, males: 19.1%, P = .016) and limb ischemia (females: 12.3%, males: 8.8%, P = .23). In-hospital mortality was 64.9% in females and 61.9% in males (P = .199) with no differences in 5-year survival (females: 20%, 95% CI, 17-23; males: 24%, 95% CI, 21-28; P = .069). Crude hazard ratio for in-hospital mortality in females was 1.12 (95% CI, 0.99-1.27; P = .069) and did not change after adjustments. CONCLUSIONS: This study demonstrates that female and male patients requiring postcardiotomy extracorporeal life support have different preoperative and extracorporeal life support characteristics, as well as complications, without a statistical difference in in-hospital and 5-year survivals.

Effect of Cannabis sativa L. extracts, phytocannabinoids and their acetylated derivates on the SHSY-5Y neuroblastoma cells' viability and caspases 3/7 activation.

BACKGROUND: There is a need for novel treatments for neuroblastoma, despite the emergence of new biological and immune treatments, since refractory pediatric neuroblastoma is still a medical challenge. Phyto cannabinoids and their hemisynthetic derivatives have shown evidence supporting their anticancer potential. The aim of this research was to examine Phytocannabinoids or hemisynthetic cannabinoids, which reduce the SHSY-5Y, neuroblastoma cell line's viability. METHODS: Hexane and acetyl acetate extracts were produced starting with Cannabis sativa L. as raw material, then, 9-tetrahidrocannabinol, its acid counterpart and CBN were isolated. In addition, acetylated derivatives of THC and CBN were synthesized. The identification and purity of the chemicals was determined by High Performance Liquid Chromatography and 1H y 13C Magnetic Nuclear Resonance. Then, the capacity to affect the viability of SHSY-5Y, a neuroblastoma cell line, was examined using the resazurin method. Finally, to gain insight into the mechanism of action of the extracts, phytocannabinoids and acetylated derivatives on the examined cells, a caspase 3/7 determination was performed on cells exposed to these compounds. RESULTS: The structure and purity of the isolated compounds was demonstrated. The extracts, the phytocannabinoids and their acetylated counterparts inhibited the viability of the SHSY 5Y cells, being CBN the most potent of all the tested molecules with an inhibitory concentration of 50 percent of 9.5 µM. CONCLUSION: Each of the evaluated molecules exhibited the capacity to activate caspases 3/7, indicating that at least in part, the cytotoxicity of the tested phytocannabinoids and their hemi-synthetic derivatives is mediated by apoptosis.

Detection of Ochyromera ligustri (Coleoptera: Curculionidae: Curculioninae) in Ligustrum spp. (Oleaceae) Using Newly Developed PCR Primers.

Ligustrum spp. (Oleaceae) have become invasive species in the US and negatively affect native plant diversity and richness in forests. Ochyromera ligustri (Coleoptera: Curculionidae) is considered a potential biological control agent in the US because adults feed on the foliage and larvae are seed-feeders of Ligustrum spp. To discover the relationships between O. ligustri and Ligustrum spp., fruit dissections or rearing and field observations are required. In the current research project, novel PCR primers were developed to rapidly detect the DNA of O. ligustri in molecular analyses without rearing and observation. The developed PCR primers worked even with 0.01 ng of DNA and did not amplify the DNA of the other five curculionid species tested. When the novel primers were tested with three Ligustrum spp. species common in the southeastern US, the DNA of O. ligustri was detected from all three species. We expect that the novel primers will be utilized to find out the presence and impact of O. ligustri on Ligustrum spp rapidly and accurately.

Diagnostico de competencia transversal autoevaluada de las y los tutores clínicos de Especializaciones en Enfermería / Diagnóstico da competência transversal autoavaliada dos tutores clínicos das Especializações de Enfermagem / Diagnosis of self-assessed transversal competence of clinical tutors of Nursing Specializations

Introducción: La evaluación diagnóstica de competencias transversales de los tutores clínicos de especialización en enfermería es necesaria para sistematizar la práctica clínica, en la cual un especialista acompaña a sus estudiantes. Objetivo: Analizar la competencia transversal de las y los Tutores Clínicos del Programa Único de Especializaciones en Enfermería de la UNAM. Metodología: Cuantitativo, descriptivo y transversal. Se diseñó y validó por jueces la "Escala de Autoevaluación de Competencias Transversales de la y el Tutor Clínico de Especialización en Enfermería". La muestra se obtuvo a partir de la fórmula de poblaciones finitas, y participaron 95 Tutores Clínicos del PUEE-UNAM. La recolección de los datos se llevó a cabo en noviembre del 2022 y se analizaron los datos a través del programa estadístico "IBM SPSS Statistics". Resultados: Los resultados muestran que 73% fueron mujeres y 27% hombres, 56% cuenta con actualización docente mediante cursos, diplomados o certificaciones. Con respecto a la competencia transversal, las y los tutores clínicos promediaron un 88.87% en "Nivel alto". Aunque en general la valoración de las competencias fue alta, se identificaron competencias con porcentajes bajos: Capacidad para diseñar escenarios de aprendizaje del cuidado especializado (68.40%), Capacidad para evaluar el aprendizaje en el entorno práctico (71.60%), Capacidad para promover el trabajo colaborativo (76.80%). Conclusiones: El diagnóstico de la competencia transversal de las y los tutores clínicos del PUEE-UNAM muestra que existen áreas de fortaleza y de oportunidad que demandan capacitación y formación continua en capacidades docentes, socioafectivas e interpersonales

Introduction: The diagnostic evaluation of transversal competencies of clinical tutors specializing in nursing is necessary to systematize clinical practice, in which a specialist accompanies their students. Objective: Analyze the transversal competence of the Clinical Tutors of the Unique Program of Specializations in Nursing of the UNAM. Methodology: Quantitative, descriptive and transversal. The "Self-Evaluation Scale of Transversal Competencies of the Nursing Specialization Clinical Tutor" was designed and validated by judges. The sample was obtained from the finite population formula, and 95 Clinical Tutors from PUEE-UNAM participated. Data collection took place in November 2022 and the data was analyzed through the statistical program "IBM SPSS Statistics". Results: The results show that 73% were women and 27% men, 56% have teaching updating through graduate courses or certifications. Regarding transversal competence, the clinical tutors averaged 88.87% in "High level". Although in general the assessment of the competencies was high, competencies with low percentages were identified: Ability to design specialized care learning scenarios (68.40%), Ability to evaluate learning in the practical environment (71.60%), Ability to promote collaborative work (76.80%). Conclusions: The diagnosis of the transversal competence of the PUEE-UNAM clinical tutors shows that there are areas of strength and opportunity that demand training and continuous training in teaching, socio-affective and interpersonal skills

Introdução: A avaliação diagnóstica das proficiências interdisciplinares dos tutores clínicos de especialização em enfermagem é necessária para sistematizar a prática clínica, na qual um especialista acompanha os seus estudantes. Objetivo: Analisar a proficiência transversal das e dos Tutores Clínicos do Programa Único de Especializações em Enfermagem da UNAM. Metodologia: Quantitativa, descritiva e interdisciplinar. Juízes desenharam e validaram a "Escala de Autoavaliação de Competências Transversais da e do Tutor Clínico de Especialização em Enfermagem. A amostra foi obtida a partir da fórmula de populações finitas, da qual participaram 95 Tutores Clínicos do PUEE-UNAM. A compilação de dados foi feita em novembro de 2022, na qual foram analisados dados mediante o programa estatístico "IBM SPSS". Resultados: Os resultados mostram que, do total de participantes, 73% foi de mulheres e 27% de homens; 56% conta com atualização docente ­ obtida mediante cursos, programas de graduação ou certificações. No que diz respeito à competência transversal, 88,87% das e dos tutores clínicos atingiu o "Nível Alto". Embora a apreciação tenha sido alta em geral, foram também identificadas percentagens baixas: Capacidade para projetar cenários de aprendizado de cuidado especializado (68,40%), Capacidade para avaliar o aprendizado em uma atmosfera prática (71,60%), Capacidade para promover o trabalho colaborativo (76,80%). Conclusões: O diagnóstico da competência transversal das e dos tutores clínicos do PUEE-UNAM demonstra que existem áreas de fortaleza e de oportunidade para melhorar que precisam de capacitação e de formatura contínua em capacidades docentes, socioafetivas e interpessoais

Vegetation dieback in the Mississippi River Delta triggered by acute drought and chronic relative sea-level rise.

Vegetation dieback and recovery may be dependent on the interplay between infrequent acute disturbances and underlying chronic stresses. Coastal wetlands are vulnerable to the chronic stress of sea-level rise, which may affect their susceptibility to acute disturbance events. Here, we show that a large-scale vegetation dieback in the Mississippi River Delta was precipitated by salt-water incursion during an extreme drought in the summer of 2012 and was most severe in areas exposed to greater flooding. Using 16 years of data (2007-2022) from a coastwide network of monitoring stations, we show that the impacts of the dieback lasted five years and that recovery was only partial in areas exposed to greater inundation. Dieback marshes experienced an increase in percent time flooded from 43% in 2007 to 75% in 2022 and a decline in vegetation cover and species richness over the same period. Thus, while drought-induced high salinities and soil saturation triggered a significant dieback event, the chronic increase in inundation is causing a longer-term decline in cover, more widespread losses, and reduced capacity to recover from acute stressors. Overall, our findings point to the importance of mitigating the underlying stresses to foster resilience to both acute and persistent causes of vegetation loss.

Extensive and deep granulomatous ulcers as an atypical manifestation of cartilage-hair hypoplasia syndrome: A diagnostic and therapeutic challenge.

Cartilage hypoplasia syndrome is a primary immunodeficiency disease characterized by short stature, hypoplastic hair and a variable degree of immunodeficiency. Noninfectious cutaneous granulomas represent an uncommon yet well-recognized manifestation within the spectrum of primary immunodeficiency diseases. However, cutaneous granulomas as a manifestation of cartilage-hair hypoplasia syndrome, are extremely rare. We present a case of a middle-aged man with cartilage hypoplasia syndrome featuring cutaneous granulomas, manifesting as chronic, extensive and deep cutaneous ulcers. The patient was treated with anti-TNF-alpha adalimumab with partial improvement. Our case underscores the broad spectrum of clinical manifestations associated with cartilage hypoplasia syndrome and adds new evidence to the potential therapeutic efficacy of anti-TNF-alpha drugs in its treatment.

De novo variants in SP9 cause a novel form of interneuronopathy characterized by intellectual disability, autism spectrum disorder, and epilepsy with variable expressivity.

PURPOSE: Interneuronopathies are a group of neurodevelopmental disorders characterized by deficient migration and differentiation of gamma-aminobutyric acidergic interneurons resulting in a broad clinical spectrum, including autism spectrum disorders, early-onset epileptic encephalopathy, intellectual disability, and schizophrenic disorders. SP9 is a transcription factor belonging to the Krüppel-like factor and specificity protein family, the members of which harbor highly conserved DNA-binding domains. SP9 plays a central role in interneuron development and tangential migration, but it has not yet been implicated in a human neurodevelopmental disorder. METHODS: Cases with SP9 variants were collected through international data-sharing networks. To address the specific impact of SP9 variants, in silico and in vitro assays were carried out. RESULTS: De novo heterozygous variants in SP9 cause a novel form of interneuronopathy. SP9 missense variants affecting the glutamate 378 amino acid result in severe epileptic encephalopathy because of hypomorphic and neomorphic DNA-binding effects, whereas SP9 loss-of-function variants result in a milder phenotype with epilepsy, developmental delay, and autism spectrum disorder. CONCLUSION: De novo heterozygous SP9 variants are responsible for a neurodevelopmental disease. Interestingly, variants located in conserved DNA-binding domains of KLF/SP family transcription factors may lead to neomorphic DNA-binding functions resulting in a combination of loss- and gain-of-function effects.

Dieback and dredge soils of Phragmites australis in the Mississippi River Delta negatively impact plant biomass.

Phragmites australis is exhibiting extensive dieback in the Lower Mississippi River Delta (MRD). We explored the potential for restoration of these marshes by (1) characterizing the chemical profiles of soils collected from healthy and dieback stands of P. australis and from sites recently created from dredge-disposal soils that were expected to be colonized by P. australis and (2) experimentally testing the effects of these soil types on the growth of three common P. australis lineages, Delta, Gulf and European. Soil chemical properties included Al, Ca, Cu, Fe, K, Mg, Mn, Na, P, S, Zn, % organic matter, % carbon, % nitrogen, and pH. Dieback soils were characterized by higher % organic matter, % carbon, % nitrogen, and higher S and Fe concentrations, whereas healthy soils had higher Cu, Al, P and Zn. In comparison, dredge sites were low in nutrients and organic matter compared to healthy soils. Rhizomes of each P. australis lineage were planted in each soil type in a common garden and greenhouse and allowed to grow for five months. Aboveground biomass was 16% lower in dieback and 44% lower in dredge soils than in healthy soils. However, we could detect no significant differences in response to soil types among lineages. Although dredge and dieback sites are not optimal for P. australis growth, plants can thrive on these soils, and we recommend restorative measures be initiated as soon as possible to minimize soil erosion.

Factor XII Deficiency in Mexico: High Prevalence in the General Population and Patients with Venous Thromboembolic Disease.

INTRODUCTION: Thrombosis is one of the leading causes of morbidity and mortality worldwide. Venous thromboembolic disease (VTD) is considered a new epidemic. FXII deficiency is supposed to be a cause of thrombosis. To search for unknown causes of thrombosis in our population, our aim was to determine if FXII deficiency can be considered a risk factor for VTD. METHODS: Young adult Mexican patients with at least one VTD episode and healthy controls were included in this prospective, observational, controlled study. Liver and renal function tests, blood cytometry, and blood coagulation assays were performed. Plasma FXII activity and its concentration were evaluated. RESULTS: Over a two-year period, 250 patients and 250 controls were included. FXII activity was significantly lower in the control group compared to patients with VTD (p = 0.005). However, percentage of patients and controls with FXII deficiency was 8.8 and 9.2%, respectively (p = 1.000). No significant association was found between FXII deficiency and VTD (p = 1.0). FXII plasma concentration was lower in controls vs. patients with VTD: 4.05 vs. 6.19 ng/mL (p <0.001). Percentage of patients with low FXII plasma concentration was 1.6% and 6.0% in patients and controls, respectively (p = 0.010). CONCLUSIONS: FXII deficiency is a frequent finding in patients with VTD and controls in Mexico. Some patients with FXII deficiency had normal APTT result, an effect not described above. FXII plasma concentration was lower in patients with low activity.

From nuclear track characterization to machine learning based image classification in neutron autoradiography for boron neutron capture therapy.

Knowledge of the 10B microdistribution is of great relevance in BNCT studies. Since 10B concentration assesment through neutron autoradiography depends on the correct quantification of tracks in a nuclear track detector, image acquisition and processing conditions should be controlled and verified, in order to obtain accurate results to be applied in the frame of BNCT. With this aim, an image verification process was proposed, based on parameters extracted from the quantified nuclear tracks. Track characterization was performed by selecting a set of morphological and pixel-intensity uniformity parameters from the quantified objects (area, diameter, roundness, aspect ratio, heterogeneity and clumpiness). Their distributions were studied, leading to the observation of varying behaviours in images generated by different samples and acquisition conditions. The distributions corresponding to samples coming from the BNC reaction showed similar attributes in each analyzed parameter, proving to be robust to the experimental process, but sensitive to light and focus conditions. Considering those observations, a manual feature extraction was performed as a pre-processing step. A Support Vector Machine (SVM) and a fully dense Neural Network (NN) were optimized, trained, and tested. The final performance metrics were similar for both models: 93%-93% for the SVM, vs 94%-95% for the NN in accuracy and precision respectively. Based on the distribution of the predicted class probabilities, the latter had a better capacity to reject inadequate images, so the NN was selected to perform the image verification step prior to quantification. The trained NN was able to correctly classify the images regardless of their track density. The exhaustive characterization of the nuclear tracks provided new knowledge related to the autoradiographic images generation. The inclusion of machine learning in the analysis workflow proves to optimize the boron determination process and paves the way for further applications in the field of boron imaging.

Fulminant myocarditis proven by early biopsy and outcomes.

BACKGROUND AND AIMS: While endomyocardial biopsy (EMB) is recommended in adult patients with fulminant myocarditis, the clinical impact of its timing is still unclear. METHODS: Data were collected from 419 adult patients with clinically suspected fulminant myocarditis admitted to intensive care units across 36 tertiary centres in 15 countries worldwide. The diagnosis of myocarditis was histologically proven in 210 (50%) patients, either by EMB (n = 183, 44%) or by autopsy/explanted heart examination (n = 27, 6%), and clinically suspected cardiac magnetic resonance imaging confirmed in 96 (23%) patients. The primary outcome of survival free of heart transplantation (HTx) or left ventricular assist device (LVAD) at 1 year was specifically compared between patients with early EMB (within 2 days after intensive care unit admission, n = 103) and delayed EMB (n = 80). A propensity score-weighted analysis was done to control for confounders. RESULTS: Median age on admission was 40 (29-52) years, and 322 (77%) patients received temporary mechanical circulatory support. A total of 273 (65%) patients survived without HTx/LVAD. The primary outcome was significantly different between patients with early and delayed EMB (70% vs. 49%, P = .004). After propensity score weighting, the early EMB group still significantly differed from the delayed EMB group in terms of survival free of HTx/LVAD (63% vs. 40%, P = .021). Moreover, early EMB was independently associated with a lower rate of death or HTx/LVAD at 1 year (odds ratio of 0.44; 95% confidence interval: 0.22-0.86; P = .016). CONCLUSIONS: Endomyocardial biopsy should be broadly and promptly used in patients admitted to the intensive care unit for clinically suspected fulminant myocarditis.

Emergency and sequalae management of traumatic dental injuries: a systematic survey of clinical practice guidelines.

BACKGROUND: The prevalence and consequences of traumatic dental injuries (TDI) make them a public health problem. Trustworthy TDI clinical practice guidelines (CPGs) assist clinicians in determining a diagnosis and guide them to the most appropriate therapy. The aim of this systematic survey was to identify and evaluate the quality of CPGs for the diagnosis, emergency management, and follow-up of TDIs. MATERIALS AND METHODS: A systematic search was carried out in MEDLINE, EMBASE, Epistemonikos, Trip database, CPG websites, and dental societies to identify documents providing recommendations for the emergency and sequelae management of TDIs. Reviewers assessed the included guidelines independently and in duplicate, using the AGREE II instrument. ANOVA or Student's t-tests were used to determine the attributes of CPGs associated with the total score in AGREE II. RESULTS: Ten CPGs published between 2010 and 2020 were included, mostly from Europe (n = 6). The overall agreement between reviewers was very good (0.94; 95%CI 0.91-0.97). The mean scores (the higher the score, the better the domain assessment) per domain were as follows: Scope and purpose 78.0 ± 18.9%; stakeholder involvement 46.9 ± 29.6%; rigour of development 41.8 ± 26.7%; clarity of presentation 75.8 ± 17.6%; applicability 15.3 ± 18.8%; and editorial independence 41.7 ± 41.7%. The overall mean rate was 4 ± 1.3 out of a maximum score of 7. Two guidelines were recommended by the reviewers for use in practice and rated as high quality. CPGs developed by government organizations showed a significantly higher overall score. CONCLUSIONS: The overall quality of CPGs on TDI was suboptimal. CPG developers should synthesize the evidence and formulate recommendations using high-quality methodologies and standards in a structured, transparent, and explicit way.