GABAergic/Glycinergic and Glutamatergic Neurons Mediate Distinct Neurodevelopmental Phenotypes of STXBP1 Encephalopathy.

An increasing number of pathogenic variants in presynaptic proteins involved in the synaptic vesicle cycle are being discovered in neurodevelopmental disorders. The clinical features of these synaptic vesicle cycle disorders are diverse, but the most prevalent phenotypes include intellectual disability, epilepsy, movement disorders, cerebral visual impairment, and psychiatric symptoms ( Verhage and Sørensen, 2020; Bonnycastle et al., 2021; John et al., 2021; Melland et al., 2021). Among this growing list of synaptic vesicle cycle disorders, the most frequent is STXBP1 encephalopathy caused by de novo heterozygous pathogenic variants in syntaxin-binding protein 1 (STXBP1, also known as MUNC18-1; Verhage and Sørensen, 2020; John et al., 2021). STXBP1 is an essential protein for presynaptic neurotransmitter release. Its haploinsufficiency is the main disease mechanism and impairs both excitatory and inhibitory neurotransmitter release. However, the disease pathogenesis and cellular origins of the broad spectrum of neurological phenotypes are poorly understood. Here we generate cell type-specific Stxbp1 haploinsufficient male and female mice and show that Stxbp1 haploinsufficiency in GABAergic/glycinergic neurons causes developmental delay, epilepsy, and motor, cognitive, and psychiatric deficits, recapitulating majority of the phenotypes observed in the constitutive Stxbp1 haploinsufficient mice and STXBP1 encephalopathy. In contrast, Stxbp1 haploinsufficiency in glutamatergic neurons results in a small subset of cognitive and seizure phenotypes distinct from those caused by Stxbp1 haploinsufficiency in GABAergic/glycinergic neurons. Thus, the contrasting roles of excitatory and inhibitory signaling reveal GABAergic/glycinergic dysfunction as a key disease mechanism of STXBP1 encephalopathy and suggest the possibility to selectively modulate disease phenotypes by targeting specific neurotransmitter systems.

Medical emergencies in a dental school clinic - A 12-year review and lessons learned.

PURPOSE: The aims of this study were to estimate the type and frequency of different medical emergencies that occurred over the study period (twelve years) and discuss the lessons learned and the modifications made in the curriculum to better equip dental students and faculty in their management. MATERIALS AND METHODS: A retrospective study was conducted to evaluate all medical emergencies that needed activation of the response team at our school from 2008 to 2020. RESULTS: The emergency response system was activated 250 times during the 12-year period. There were 132 medical emergencies in the pre-doctoral clinic and 105 events in the post-doctoral clinic (p 0.0680). Most of the emergencies occurred in patients between 45 and 64 years of age. Syncope occurs most often followed by adverse cardiovascular, respiratory, anxiety, and hypoglycemic events. CONCLUSIONS: Medical emergencies occurring in a dental school provide a unique opportunity for students to gain experience in their management. The key lies in preparing the students and faculty to prevent them from occurring, but should these occur, then they should be able to promptly recognize symptoms and institute prompt intervention.

[Guidelines on atopic dermatitis for Mexico (GUIDAMEX): using the ADAPTE methodology]. / Guía de dermatitis atópica para México (GUIDAMEX): lineamientos usando metodología ADAPTE.

With the advancement of knowledge in relation to the physiopathogenesis of atopic dermatitis (AD), several new therapeutic forms have been developed. There are also new guidelines for self-care. On the other hand, there is still an underdiagnosis of AD in Mexico. Thus, the need was seen to develop a national guide, with a broad base among the different medical groups that care for patients with AD. The Atopic Dermatitis Guidelines for Mexico (GUIDAMEX) was developed with the ADAPTE methodology, with the endorsement and participation of ten national medical societies, from physicians in Primary Healthcare to allergists and dermatologists. Throughout the manuscript, key clinical questions are answered that lead to recommendations and suggestions for the diagnosis of AD (including differential diagnosis with immunodeficiency syndromes), the recognition of comorbidities and complications, non-pharmacological treatment including therapeutic education, treatment of flares and maintenance therapy. The latter encompasses general measures to avoid triggering factors, first-line treatment focussed on repair of the skin barrier, second-line treatment (topical proactive therapy), and third-line phototherapy or systemic treatment, including dupilumab and JAK inhibitors.

Con el avance de los conocimientos en relación con la fisiopatogenia de la dermatitis atópica (DA) se han desarrollado varias formas terapéuticas nuevas. Asimismo, existen nuevos lineamientos para el autocuidado. Por otro lado, aún existe un subdiagnóstico de la DA en México. Así, se vio la necesidad de desarrollar una guía nacional, con base amplia entre las diferentes agrupaciones médicos que atienden pacientes con DA. Se desarrolló la Guía de DA para México (GUIDAMEX) con la metodología ADAPTE, con el aval y la participación de diez sociedades médicas nacionales, desde médicos del primer contacto hasta alergólogos y dermatólogos. A lo largo del escrito se contestan preguntas clínicas clave que llevan a recomendaciones y sugerencias para el diagnóstico de la DA (incluyendo diagnóstico diferencial con síndromes de inmunodeficiencia), el reconocer de las comorbilidades y complicaciones, las medidas generales (tratamiento no farmacológico) incluyendo la educación terapéutica, el tratamiento de los brotes y el tratamiento de mantenimiento. Este último abarca las medidas generales de evitar agravantes, el tratamiento de primera línea reparador de la barrera cutánea, de segunda línea (manejo proactivo tópico), hasta la fototerapia y el tratamiento sistémico de la tercera línea, incluyendo dupilumab y los inhibidores de la cinasa de Jano.

Antisense oligonucleotide therapy rescues disturbed brain rhythms and sleep in juvenile and adult mouse models of Angelman syndrome.

UBE3A encodes ubiquitin protein ligase E3A, and in neurons its expression from the paternal allele is repressed by the UBE3A antisense transcript (UBE3A-ATS). This leaves neurons susceptible to loss-of-function of maternal UBE3A. Indeed, Angelman syndrome, a severe neurodevelopmental disorder, is caused by maternal UBE3A deficiency. A promising therapeutic approach to treating Angelman syndrome is to reactivate the intact paternal UBE3A by suppressing UBE3A-ATS. Prior studies show that many neurological phenotypes of maternal Ube3a knockout mice can only be rescued by reinstating Ube3a expression in early development, indicating a restricted therapeutic window for Angelman syndrome. Here, we report that reducing Ube3a-ATS by antisense oligonucleotides in juvenile or adult maternal Ube3a knockout mice rescues the abnormal electroencephalogram (EEG) rhythms and sleep disturbance, two prominent clinical features of Angelman syndrome. Importantly, the degree of phenotypic improvement correlates with the increase of Ube3a protein levels. These results indicate that the therapeutic window of genetic therapies for Angelman syndrome is broader than previously thought, and EEG power spectrum and sleep architecture should be used to evaluate the clinical efficacy of therapies.

Loss of WNT4 in the gubernaculum causes unilateral cryptorchidism and fertility defects.

Undescended testis (UDT) affects 6% of male births. Despite surgical correction, some men with unilateral UDT may experience infertility with the contralateral descended testis (CDT) showing no A-dark spermatogonia. To improve our understanding of the etiology of infertility in UDT, we generated a novel murine model of left unilateral UDT. Gubernaculum-specific Wnt4 knockout (KO) mice (Wnt4-cKO) were generated using retinoic acid receptor ß2-cre mice and were found to have a smaller left-unilateral UDT. Wnt4-cKO mice with abdominal UDT had an increase in serum follicle-stimulating hormone and luteinizing hormone and an absence of germ cells in the undescended testicle. Wnt4-cKO mice with inguinal UDT had normal hormonal profiles, and 50% of these mice had no sperm in the left epididymis. Wnt4-cKO mice had fertility defects and produced 52% fewer litters and 78% fewer pups than control mice. Wnt4-cKO testes demonstrated increased expression of estrogen receptor α and SOX9, upregulation of female gonadal genes, and a decrease in male gonadal genes in both CDT and UDT. Several WNT4 variants were identified in boys with UDT. The presence of UDT and fertility defects in Wnt4-cKO mice highlights the crucial role of WNT4 in testicular development.

Gene dosage changes in KCTD13 result in penile and testicular anomalies via diminished androgen receptor function.

Despite the high prevalence of hypospadias and cryptorchidism, the genetic basis for these conditions is only beginning to be understood. Using array-comparative-genomic-hybridization (aCGH), potassium-channel-tetramerization-domain-containing-13 (KCTD13) encoded at 16p11.2 was identified as a candidate gene involved in hypospadias, cryptorchidism and other genitourinary (GU) tract anomalies. Copy number variants (CNVs) at 16p11.2 are among the most common syndromic genomic variants identified to date. Many patients with CNVs at this locus exhibit GU and/or neurodevelopmental phenotypes. KCTD13 encodes a substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3-ubiquitin-protein-ligase complex (BCR (BTB-CUL3-RBX1) E3-ubiquitin-protein-ligase complex (B-cell receptor (BCR) [BTB (the BTB domain is a conserved motif involved in protein-protein interactions) Cullin3 complex RING protein Rbx1] E3-ubiqutin-protein-ligase complex), which has essential roles in the regulation of cellular cytoskeleton, migration, proliferation, and neurodevelopment; yet its role in GU development is unknown. The prevalence of KCTD13 CNVs in patients with GU anomalies (2.58%) is significantly elevated when compared with patients without GU anomalies or in the general population (0.10%). KCTD13 is robustly expressed in the developing GU tract. Loss of KCTD13 in cell lines results in significantly decreased levels of nuclear androgen receptor (AR), suggesting that loss of KCTD13 affects AR sub-cellular localization. Kctd13 haploinsufficiency and homozygous deletion in mice cause a significant increase in the incidence of cryptorchidism and micropenis. KCTD13-deficient mice exhibit testicular and penile abnormalities together with significantly reduced levels of nuclear AR and SOX9. In conclusion, gene-dosage changes of murine Kctd13 diminish nuclear AR sub-cellular localization, as well as decrease SOX9 expression levels which likely contribute in part to the abnormal GU tract development in Kctd13 mouse models and in patients with CNVs in KCTD13.

[Vitamin D and respiratory allergy: state of the art]. / Vitamina D y alergia respiratoria: estado del arte.

An increasing number of studies are analyzing the relationship between serum vitamin D levels and the development of sensitization and allergic diseases in genetically predisposed individuals, as well as the impact of vitamin D supplementation. This article reviews the literature on this subject. Clinical trials, meta-analyses and systematic reviews consulted in PubMed, EMBASE, Scopus, Ovid, Wiley Online Library, Springer, Cochrane and manual resources were included, with the keywords: vitamin D, 25 hydroxyvitamin D, cholecalciferol, asthma, rhinitis, allergy, 25-OH-D, 1,25 hydroxyvitamin D, supplementation. The results show a positive linear trend, however, differ. We should keep in mind that in the studies there is heterogeneity of population groups and associated factors, which may modify such studies. It is necessary to increase research to clarify this relationship and to have successful interventions from the patient's approach to the strengthening of pharmacological and immunological treatment of allergic patients with these diseases.

Cada vez son más los trabajos que analizan la relación de los niveles séricos de vitamina D y el desarrollo de sensibilizaciones y enfermedades alérgicas en los individuos con predisposición genética, así como el impacto de su suplementación. El presente artículo efectúa una revisión de la literatura acerca de este tema. Se incluyeron ensayos clínicos, metaanálisis y revisiones sistemáticas consultadas en PubMed, EMBASE, Scopus, Ovid, Wiley Online Library, Springer, Cochrane y recursos manuales, con las palabras clave: vitamina D, 25 hidroxivitamina D, colecalciferol, asma, rinitis, alergia, 25-OH-D, 1,25 hidroxivitamina D, suplementación. Los resultados muestran una tendencia lineal positiva; sin embargo, algunos difieren. Debemos tener en mente que en los estudios existe heterogeneidad de los grupos poblacionales y los factores asociados, lo que puede modificarlos. Es necesario incrementar las investigaciones para clarificar esta relación y tener intervenciones exitosas desde el abordaje del paciente hasta el fortalecimiento del tratamiento farmacológico e inmunológico de los pacientes alérgicos con estas enfermedades.

Preliminary study of the impact of elevated circulating plasma levels of catecholamines on opioid requirements for acute surgical pain.

INTRODUCTION: The objective of this study is to determine whether elevated circulating plasma catecholamine levels significantly impact opioid requirements during the first 24 hours postoperative period in individuals with acute surgical pain. METHODS: We retrospectively reviewed 15 electronic medical records (EMRs) from adults 18 years and older, with confirmed elevated plasma catecholamine levels (experimental) and 15 electronic health records (EHRs) from matched-controls for age, gender, race and type of surgery, with a follow up of 24 hours postoperatively. RESULTS: The total morphine milligram equivalents (MMEs) requirements from the experimental group were not statistically different when compared with controls [44.1 (13 to 163) mg versus 47.5 (13 to 151) mg respectively; p 0.4965]. However, the intraoperative MMEs showed a significant difference, among the two groups; [(experimental) 32.5 (13. to 130) mg, (control) 15 (6.5 to 130) mg; p 0.0734]. The intraoperative dosage of midazolam showed a highly significant positive correlation to the total MMEs (p 0.0005). The subjects with both elevated plasma catecholamines and hypertension used significantly higher intraoperative MMEs compared to controls [34.1 (13 to 130) mg versus 15 (6.5 to 130) mg, respectively; p 0.0292)]. Those 51 years and younger, with elevated circulating levels of catecholamines, required significantly higher levels of both the postoperative MMEs [29.1 (0 to 45) mg versus 12 (0 to 71.5) mg; (p 0.0553)] and total MMEs [544.05 (13 to 81) mg versus 29.42 (13 to 92.5) mg; (p 0.00018), when compared to controls with history of nicotine and alcohol use. CONCLUSION: This preliminary study evaluated a biologic factor, which have promising clinical usefulness for predicting analgesic requirements that can drive clinical decisions on acute surgical pain.

PRSS50 is a testis protease responsible for proper sperm tail formation and function.

Multiple morphological abnormalities of the sperm flagella (MMAF) are a major cause of asthenoteratozoospermia. We have identified protease serine 50 (PRSS50) as having a crucial role in sperm development, because Prss50-null mice presented with impaired fertility and sperm tail abnormalities. PRSS50 could also be involved in centrosome function because these mice showed a threefold increase in acephalic sperm (head-tail junction defect), sperm with multiple heads (spermatid division defect) and sperm with multiple tails, including novel two conjoined sperm (complete or partial parts of several flagellum on the same plasma membrane). Our data support that, in the testis, as in tumorigenesis, PRSS50 activates NFκB target genes, such as the centromere protein leucine-rich repeats and WD repeat domain-containing protein 1 (LRWD1), which is required for heterochromatin maintenance. Prss50-null testes have increased IκκB, and reduced LRWD1 and histone expression. Low levels of de-repressed histone markers, such as H3K9me3, in the Prss50-null mouse testis may cause increases in post-meiosis proteins, such as AKAP4, affecting sperm formation. We provide important insights into the complex mechanisms of sperm development, the importance of testis proteases in fertility and a novel mechanism for MMAF.

Management of Airway Obstruction in Infants With Pierre Robin Sequence.

BACKGROUND: Pierre Robin sequence (PRS)-related airway obstruction is often treated surgically; however, objective measures predicting the need for surgery are poorly defined. METHODS: A retrospective chart review was performed on 171 neonates with PRS. Infants were grouped based upon intervention modality: nonsurgical (conservative) or surgical [mandibular distraction osteogenesis (MDO) or tracheostomy]. Demographic data, physical examination findings, and study results were compared between groups to determine risk factors for surgical intervention, and to predict long-term success or failure of those interventions. RESULTS: The most significant, objective risk factor among those receiving surgery was a poor preintervention sleep study [obstructive index (OI): 42.4 versus 12.9 for the conservative treatment group; P < 0.001]. Only 11% of those treated conservatively had an OI >20, whereas 67.5% of those treated surgically met this severity measure. Of those receiving surgery, tracheostomy was associated with neurologic impairment (P = 0.030) and low birth weight (P = 0.046) compared with the MDO group. Together with syndromic status, these risk factors were useful for predicting failure of MDO to avoid subsequent tracheostomy (test sensitivity and specificity were 64.2% and 100.0%, respectively). No long-term differences in speech or micrognathia were detected between the 3 groups; however, those treated conservatively or with MDO had improved long-term feeding and airway obstruction outcomes compared with the tracheostomy group. CONCLUSIONS: Surgical intervention for PRS-related tongue-based airway obstruction should be strongly considered with an OI >20. Tracheostomy should be reserved for complex patients with concomitant syndromic diagnosis, neurologic impairment, and low birth weight.

Percepción de valores y antivalores coexistentes en el sector salud / Perception about the existing and coexisting values and anti-values in the health sector

Introducción: se muestran resultados de una investigación realizada en 4 facultades de Ciencias Médicas de La Habana y sus escenarios docentes en el periodo 2012-2014. Objetivo: explorar los valores éticos sociales y profesionales consensuados por docentes, estudiantes, profesionales, directivos y usuarios del sector salud e identificar los antivalores coexistentes. Métodos: se utilizó una metodología cualitativa, seleccionando intencionalmente una muestra correspondiente al 57 por ciento del universo de estudio, con quienes se aplicaron variadas técnicas: grupo focal y proyectiva, observación participante, encuesta y técnica de Delphi. Resultados: existió consenso en la percepción de los valores honestidad y responsabilidad coexistiendo con el antivalor deshonestidad; el valor solidaridad con antivalor egoísmo; valor responsabilidad con antivalor irresponsabilidad y valor humanismo con antivalores desidia e indiferencia. Según los expertos, las principales causas de desmotivación de los profesionales son los bajos salarios, insuficientes condiciones de trabajo y poco reconocimiento social. Conclusiones: se propone fortalecer los valores éticos ciudadanos y profesionales y combatir los antivalores. Corresponde a los decisores trazar estrategias para enfrentar las insuficiencias con la participación de los profesionales comprometidos con una mejor calidad y eficiencia de los servicios y una mayor satisfacción de los usuarios(AU)

Introduction: results are shown of a research carried out in the period from 2012 to 2014 in four Havana School of Medical Sciences and their teaching campuses. Objective: to explore the ethical, social and professional values agreed upon by teachers, students, professionals, managers and users of the health area and to identify the coexisting anti-values. Methods: a qualitative methodology was used, intentionally selecting a sample corresponding to 57 percent of the study total sample, on whom several techniques were applied: projective and focal group, participant observation, survey. and the Delphi technique. Results: there was consensus in the perception of the values of honesty and responsibility, as coexisting with the anti-value dishonesty; the value of solidarity, with anti-value selfishness; the value of responsibility, with anti-value irresponsibility, and the value of humanism with the anti-values apathy and indifference. According to the experts, the main causes of demotivation of professionals are low wages, insufficient working conditions, and little social recognition. Conclusions: the ethical values of citizens and professionals has been proposed to be strengthened, together with confronting anti-values. The decision-makers are in now in charge of drawing up strategies to put up with the shortcomings, by means of the participation of the professionals committed to better quality and efficiency of the services and greater satisfaction of the users(AU)

Caracterización del paciente neuroquirúrgico no traumático en la Unidad de Cuidados Intensivos / Characterization of the nontraumatic neurosurgical patients in the intensive care unit

Introducción: la atención y seguimiento del paciente neuroquirúrgico representa un difícil reto para los médicos que trabajan en Unidades de Cuidados Intensivos (UCI). Estos pacientes necesitan una vigilancia intensiva por la diversidad de complicaciones que pueden presentar en el posoperatorio inmediato. Los cuidados neurointensivos, deben permitir la restauración y el mantenimiento de la homeostasia cerebral, como requisito fundamental para la supervivencia neuronal y recuperación de la función neurológica.Objetivos: caracterizar los pacientes neuroquirúrgicos no traumáticos ingresados en la UCI del Hospital Universitario "General Calixto García" de La Habana. Métodos: se realizó un estudio prospectivo, descriptivo y transversal, en el período comprendido entre el 1ro. de enero de 2012 y el 31 de diciembre de 2012; el universo fue de 55 pacientes, la muestra quedó constituida por los 55 pacientes. Resultados: se encontró una tendencia creciente de ingresos de pacientes neuroquirúrgicos no traumáticos en la UCI, con predominio del sexo masculino y edades comprendidas entre la quinta y séptima décadas de la vida. Las entidades neuroquirúrgicas ingresadas con mayor frecuencia fueron los tumores cerebrales, las hemorragias intraparenquimatosas, las malformaciones arterio-venosas y los aneurismas cerebrales. Se encontró una mayor estadía y mortalidad en las pacientes femeninas. Las complicaciones tuvieron una incidencia significativa en el estudio destacándose el edema cerebral, las disrritmias cardíacas, el Sindrome de Respuesta Inflamatoria Sistemica (SRIS) no relacionado con procesos infecciosos, el Síndrome Séptico en sus diferentes estadios y las anemias. Conclusiones: existe una tendencia creciente de ingresos de pacientes neuroquirúrgicos no traumáticos en la UCI(AU)

Introduction: Caring and monitoring neurosurgical patients represents a difficult challenge for doctors working in intensive care units (ICU). These patients need intensive surveillance due to the diversity of complications that can occur in the immediate postoperative period. The neurointensive cares should allow the restoration and maintenance of brain homeostasis, as an essential requirement for neuronal survival and neurological function recovery. Objectives: To characterize nontraumatic neurosurgical patients admitted to the ICU of General Calixto García University Hospital of Havana. Methods: A prospective, descriptive study was carried out in the period from January 1, 2012 to December 31, 2012; the sample group was 55 patients, and the sample was made up by 55 patients. Results: A growing trend of nontraumatic neurosurgical patient's admissions to ICU was found, predominantly male and at ages between the fifth and seventh decades of life. The neurosurgical events more frequently admitted were brain tumors, intraparenchymal bleeding, arteriovenous malformations, and cerebral aneurysms. Greater stay time and mortality were present in female patients. Complications had a significant impact on the study, particularly cerebral edemas, cardiac dysrhythmias, the systemic inflammatory response syndrome (SIRS) not related to infectious processes, the sepsis syndrome in its different stages, and anemias.Conclusions: There is a growing trend of nontraumatic neurosurgical patients' admissions to the ICU(AU)

Caracterización del paciente neuroquirúrgico no traumático en la Unidad de Cuidados Intensivos / Characterization of the nontraumatic neurosurgical patients in the intensive care unit

Introducción: la atención y seguimiento del paciente neuroquirúrgico representa un difícil reto para los médicos que trabajan en Unidades de Cuidados Intensivos (UCI). Estos pacientes necesitan una vigilancia intensiva por la diversidad de complicaciones que pueden presentar en el posoperatorio inmediato. Los cuidados neurointensivos deben permitir la restauración y el mantenimiento de la homeostasia cerebral, como requisito fundamental para la supervivencia neuronal y recuperación de la función neurológica. Objetivos: caracterizar los pacientes neuroquirúrgicos no traumáticos ingresados en la UCI del Hospital Universitario General Calixto García de La Habana. Métodos: se realizó un estudio prospectivo, descriptivo y transversal, en el período comprendido entre el 1ro. de enero de 2012 y el 31 de diciembre de 2012; el universo fue de 55 pacientes, la muestra quedó constituida por los 55 pacientes. Resultados: se encontró una tendencia creciente de ingresos de pacientes neuroquirúrgicos no traumáticos en la UCI, con predominio del sexo masculino y edades comprendidas entre la quinta y séptima décadas de la vida. Los pacientes con mayor índice de ingreso fueron los de enfermedades como tumores cerebrales, las hemorragias intraparenquimatosas, las malformaciones arterio-venosas y los aneurismas cerebrales. Se encontró mayor estadía y mortalidad en las pacientes femeninas. Las complicaciones tuvieron una incidencia significativa en el estudio destacándose el edema cerebral, las disrritmias cardíacas, el sindrome de respuesta inflamatoria sistemica (SRIS) no relacionado con procesos infecciosos, el síndrome séptico en sus diferentes estadios y las anemias. Conclusiones: existe una tendencia creciente de ingresos de pacientes neuroquirúrgicos no traumáticos en la UCI(AU)

Introduction: Caring and monitoring neurosurgical patients represents a difficult challenge for doctors working in intensive care units (ICU). These patients need intensive surveillance due to the diversity of complications that can occur in the immediate postoperative period. The neurointensive cares should allow the restoration and maintenance of brain homeostasis, as an essential requirement for neuronal survival and neurological function recovery. Objectives: To characterize nontraumatic neurosurgical patients admitted to the ICU of General Calixto García University Hospital of Havana. Methods: A prospective, descriptive study was carried out in the period from January 1, 2012 to December 31, 2012; the sample group was 55 patients, and the sample was made up by 55 patients. Results: A growing trend of nontraumatic neurosurgical patient's admissions to ICU was found, predominantly male and at ages between the fifth and seventh decades of life. The neurosurgical events more frequently admitted were brain tumors, intraparenchymal bleeding, arteriovenous malformations, and cerebral aneurysms. Greater stay time and mortality were present in female patients. Complications had a significant impact on the study, particularly cerebral edemas, cardiac dysrhythmias, the systemic inflammatory response syndrome (SIRS) not related to infectious processes, the sepsis syndrome in its different stages, and anemias. Conclusions: There is a growing trend of nontraumatic neurosurgical patients' admissions to the ICU(AU)

Severe Cervicofacial Emphysema and Pneumomediastinum Caused by a Dental Handpiece: A Case Report and Guidelines for Management for the Dental Practitioner.

Cervicofacial emphysema (CE) is a rare but potentially serious condition that can arise iatrogenically from dental or surgical procedures. Dental handpieces with fore-exhaust can inject air into tissues at pressures at or greater than 30 psi. Since 1963, there have been approximately 100 case reports in the literature of iatrogenic CE from routine dental procedures. Prompt recognition and treatment are essential; however, many general practitioners may only be familiar with CE from their dental school curriculum. A case of unusually severe cervicofacial emphysema with concomitant pneumomediastinum is presented, along with a discussion and review of management principles for the general dentist. It is our hope that refamiliarization with this condition will give the general dentist an appreciation for and recognition of signs of CE, thereby being the first. link in a chain of successful treatment.

Expression of mouse CD47 on human cancer cells profoundly increases tumor metastasis in murine models.

BACKGROUND: Many commonly used xenograft tumor models do not spontaneously metastasize to distant organs following subcutaneous or orthotopic implantation, limiting their usefulness in preclinical studies. It is generally believed that natural killer cells are the key component of the innate immune system in determining tumor metastatic potential in xenograft models. However, recent studies suggest that macrophages may play an important role, as resident macrophages can eliminate the invading tumor cells if they do not express adequate levels of the CD47 molecule. METHODS: We investigated the effect of overexpressing murine CD47 (mCD47) in PC-3 cells, a commonly used human prostate cancer line, on the metastatic potential in three mouse strains with different genetic background and varying degrees of immunodeficiency. We implanted the tumor cells either subcutaneously or orthotopically and then examined their local and distant metastases. RESULTS: Our results show that mCD47-expressing PC-3 cells subcutaneously implanted in NSG and CB17. Scid mice metastasized to the sentinel lymph node, lung and liver significantly more efficiently than the control cells. When implanted orthotopically to NOD. Scid mice, these cells spontaneously metastasized to lung and liver. CONCLUSIONS: Our data demonstrate that mCD47 can facilitate human tumor cell metastasis in murine models, and that these mCD47-expressing tumor cells may be useful for in vivo studies where spontaneous metastases are desirable.