Formulation development of a stable influenza recombinant neuraminidase vaccine candidate.

Current influenza vaccines could be augmented by including recombinant neuraminidase (rNA) protein antigen to broaden protective immunity and improve efficacy. Toward this goal, we investigated formulation conditions to optimize rNA physicochemical stability. When rNA in sodium phosphate saline buffer (NaPBS) was frozen and thawed (F/T), the tetrameric structure transitioned from a "closed" to an "open" conformation, negatively impacting functional activity. Hydrogen deuterium exchange experiments identified differences in anchorage binding sites at the base of the open tetramer, offering a structural mechanistic explanation for the change in conformation and decreased functional activity. Change to the open configuration was triggered by the combined stresses of acidic pH and F/T. The desired closed conformation was preserved in a potassium phosphate buffer (KP), minimizing pH drop upon freezing and including 10% sucrose to control F/T stress. Stability was further evaluated in thermal stress studies where changes in conformation were readily detected by ELISA and size exclusion chromatography (SEC). Both tests were suitable indicators of stability and antigenicity and considered potential critical quality attributes (pCQAs). To understand longer-term stability, the pCQA profiles from thermally stressed rNA at 6 months were modeled to predict stability of at least 24-months at 5°C storage. In summary, a desired rNA closed tetramer was maintained by formulation selection and monitoring of pCQAs to produce a stable rNA vaccine candidate. The study highlights the importance of understanding and controlling vaccine protein structural and functional integrity.

Continuity of care in disease-related malnutrition and nutritional medical treatment.

Disease-related malnutrition (DRM) continues to be a very significant healthcare problem, both in our hospitals and in the community. It is often not properly diagnosed or treated, despite a growing body of evidence highlighting its clinical and economic consequences. The transition between clinical care in the hospital and community services (Primary Care (PC) and Nursing Homes) is a key element in the prevention, detection and treatment of DRM. In October 2020, the Spanish Society of Endocrinology and Nutrition (SEEN) and the main societies of PC physicians in our country (SEMERGEN, SEMFYC and SEMG) met for the first time within the virtual NutriSEEN forum. From that moment on, a joint working group was created for this issue. This document tries to establish joint lines of work between the Clinical Nutrition and Dietetic Units (UNCyD) and the Primary Care teams to improve the detection and treatment of DRM. The clinical consequences and costs associated with DRE, nutritional risk screening, assessment and medical nutritional treatment are considered in a coordinated way between the PC teams and the UNCyD, as well as future proposals to improve the management of DRM.

The management of lactose intolerance among primary care physicians and its correlation with management by gastroenterologists: the SEPD-SEMG national survey.

INTRODUCTION AND AIMS: The understanding of lactose intolerance (LI) is limited in some professional settings. Sociedad Española de Patología Digestiva (SEPD) and Sociedad Española de Medicina General (SEMG) have developed a survey in order to: a) Analyze primary care physicians (PCPs) knowledge and clinical management; and b) to compare results with those of a previous survey of Spanish gastroenterologists (GEs). MATERIAL AND METHODS: An online questionnaire was sent to SEMG members with 27 items on various issues: Demographics, occupational characteristics, outlook on LI, diagnostic tests, treatment, and follow-up. Results were compared to those from a survey of GEs. RESULTS: A total of 456 PCPs responded, versus 477 GEs. PCPs had an older mean age and longer professional experience. Level of understanding of LI was similar, albeit a higher proportion of PCPs lacked epidemiological awareness (p < 0.01). GEs tended to consider LI a "minor" condition (71.3 vs. 40.1%; p > 0.001), and LI symptoms as overlapping those of irritable bowel syndrome (93.5 vs. 88.2%; p = 0.005), although symptoms perceived as suspicious of LI were similar in both groups. Dietary recommendations were recognized as the primary therapeutic approach. CONCLUSION: This study reveals the outlook of PCPs on LI, and allows comparison with that of GEs, as a basis for the development of strategies aimed at improving LI understanding, approach and management in our setting.

Manejo de la intolerancia a la lactosa entre los médicos de atención primaria y su correlación con la de los especialistas en digestivo: encuesta nacional SEPD-SEMG / The management of lactose intolerance among primary care physicians and its correlation with management by gastroenterologists: The SEPD-SEMG national survey

INTRODUCCIÓN Y OBJETIVOS: el conocimiento sobre la intolerancia a la lactosa (IL) es limitado en algunos ámbitos profesionales. La Sociedad Española de Patología Digestiva (SEPD) y la Sociedad Española de Medicina General (SEMG) han elaborado una encuesta con los objetivos de: a) analizar el nivel de conocimiento y de manejo clínico de los médicos de atención primaria (MAP); y b) comparar sus resultados con los de la encuesta ya realizada entre los gastroenterólogos españoles (GE). MATERIAL Y MÉTODOS: se envió un cuestionario online a los socios de la SEMG, con 27 preguntas sobre distintas cuestiones: demografía y características laborales, actitud frente a la IL, métodos de diagnóstico, tratamiento y seguimiento. Los resultados fueron comparados con los de la encuesta a GE. RESULTADOS: se recopilaron 456 respuestas de MAP, que se compararon con las proporcionadas por 477 GE. Los MAP presentaron una edad media y experiencia profesional mayor. El nivel de conocimiento sobre IL fue parecido, si bien una mayor proporción de MAP desconocía la epidemiología del problema (p < 0,01). Los GE tendieron a considerar a la IL una patología "menor" (71,3 vs. 40,1%; p > 0,001), y a sus síntomas superponibles a los del síndrome del intestino irritable (93,5 vs. 88,2%; p = 0,005), si bien los síntomas reconocidos como sospechosos de IL fueron similares entre ambos grupos. Las recomendaciones dietéticas fueron reconocidas como la principal medida terapéutica. CONCLUSIÓN: este estudio permite conocer la actuación de los MAP ante la IL y compararla con la de los GE, como base para el desarrollo estrategias para mejorar el conocimiento, actitud y tratamiento de la IL en nuestro medio

INTRODUCTION AND AIMS:The understanding of lactose intolerance (LI) is limited in some professional settings. Sociedad Española de Patología Digestiva (SEPD) and Sociedad Española de Medicina General (SEMG) have developed a survey in order to: a) Analyze primary care physicians (PCPs) knowledge and clinical management; and b) to compare results with those of a previous survey of Spanish gastroenterologists (GEs). MATERIAL AND METHODS: An online questionnaire was sent to SEMG members with 27 items on various issues: Demographics, occupational characteristics, outlook on LI, diagnostic tests, treatment, and follow-up. Results were compared to those from a survey of GEs. RESULTS: A total of 456 PCPs responded, versus 477 GEs. PCPs had an older mean age and longer professional experience. Level of understanding of LI was similar, albeit a higher proportion of PCPs lacked epidemiological awareness (p < 0.01). GEs tended to consider LI a "minor" condition (71.3 vs. 40.1%; p > 0.001), and LI symptoms as overlapping those of irritable bowel syndrome (93.5 vs. 88.2%; p = 0.005), although symptoms perceived as suspicious of LI were similar in both groups. Dietary recommendations were recognized as the primary therapeutic approach. CONCLUSION: This study reveals the outlook of PCPs on LI, and allows comparison with that of GEs, as a basis for the development of strategies aimed at improving LI understanding, approach and management in our setting

Latina youths' perceptions of children's environmental health risks in an agricultural community.

OBJECTIVES: The objective of this study was to identify Latina youths' perceptions of local assets and concerns related to children's environmental health (EH) in an agricultural community. DESIGN AND SAMPLE: Four photovoice sessions were used to elicit 6 promotores' and 5 middle school students' perspectives on problems and strengths related to "children; environment; and health." MEASURES: Data collection was diverse and included a demographic and evaluation questionnaire, photographs, audio recordings of group photo-sharing sessions, and field notes. RESULTS: Participants identified three themes that reflected group discussion during two photo-sharing sessions: a lack of structured youth activities; poverty and stress; and benefits and detriments of agricultural work. Community assets related to creating a healthy environment for youth were identified and included the clinic, churches, and youth programs. CONCLUSIONS: Findings from this study reinforce that social background and position affect how EH issues are defined and may be addressed. Participant perspectives are valuable to nurses because they offer a lens through which to see the complexities of EH from the viewpoint of those most directly affected. Leadership training and opportunities to serve on coalitions and neighborhood councils are recommended approaches to meaningfully involving youth in environmental justice initiatives.

Antiparallel membrane topology of paired short-chain chromate transport proteins in Bacillus subtilis.

Short-chain monodomain family comprises pairs of membrane proteins of about 200 amino acid residues each that belong to the chromate ion transporter (CHR) superfamily. The short-chain CHR homologous pair Chr3N/Chr3C from Bacillus subtilis strain 168 confers chromate resistance only when both proteins are expressed. Membrane topology of the Chr3N and Chr3C proteins was determined in Escherichia coli by the analysis of translational fusions with reporter enzymes alkaline phosphatase and ß-galactosidase. Each short-chain CHR protein was found to consist of five transmembrane segments with antiparallel orientation between them. The C terminus of Chr3N is located in the cytoplasm, whereas the C terminus of Chr3C is located in the periplasm. In silico analyses suggest that this antiparallel arrangement is shared by all protein members of the short-chain CHR3 subfamily and that the two Chr3N/Chr3C proteins might carry out distinct functions for the transport of chromate.

Imidazoquinoline Toll-like receptor 8 agonists activate human newborn monocytes and dendritic cells through adenosine-refractory and caspase-1-dependent pathways.

BACKGROUND: Newborns have frequent infections and manifest impaired vaccine responses, motivating a search for neonatal vaccine adjuvants. Alum is a neonatal adjuvant but might confer a T(H)2 bias. Toll-like receptor (TLR) agonists are candidate adjuvants, but human neonatal cord blood monocytes demonstrate impaired T(H)1-polarizing responses to many TLR agonists caused by plasma adenosine acting through cyclic AMP. TLR8 agonists, including imidazoquinolines (IMQs), such as the small synthetic 3M-002, induce adult-level TNF from neonatal monocytes, but the scope and mechanisms of IMQ-induced activation of neonatal monocytes and monocyte-derived dendritic cells (MoDCs) have not been reported. OBJECTIVE: We sought to characterize IMQ-induced activation of neonatal monocytes and MoDCs. METHODS: Neonatal cord and adult peripheral blood monocytes and MoDCs were cultured in autologous plasma; levels of alum- and TLR agonist-induced cytokines and costimulatory molecules were measured. TLR8 and inflammasome function were assayed by using small interfering RNA and Western blotting/caspase-1 inhibitory peptide, respectively. The ontogeny of TLR8 agonist-induced cytokine responses was defined in rhesus macaque whole blood ex vivo. RESULTS: IMQs were more potent and effective than alum at inducing TNF and IL-1ß from monocytes. 3M-002 induced robust TLR pathway transcriptome activation and T(H)1-polarizing cytokine production in neonatal and adult monocytes and MoDCs, signaling through TLR8 in an adenosine/cyclic AMP-refractory manner. Newborn MoDCs displayed impaired LPS/ATP-induced caspase-1-mediated IL-1ß production but robust 3M-002-induced caspase-1-mediated inflammasome activation independent of exogenous ATP. TLR8 IMQs induced robust TNF and IL-1ß in whole blood of rhesus macaques at birth and infancy. CONCLUSIONS: IMQ TLR8 agonists engage adenosine-refractory TLR8 and inflammasome pathways to induce robust monocyte and MoDC activation and represent promising neonatal adjuvants.

Streptolysin O inhibits clathrin-dependent internalization of group A Streptococcus.

Group A Streptococcus (GAS) can be internalized by epithelial cells, including keratinocytes from human skin or pharyngeal epithelium. Internalization of GAS by epithelial cells has been postulated both to play a role in host defense and to provide a sanctuary site for GAS survival. The cholesterol-binding cytolysin streptolysin O (SLO) appears to enhance virulence in part by inhibiting GAS internalization by human keratinocytes and by disrupting the lysosomal degradation of internalized GAS. We now report that low-level production of SLO by an inducible expression system reduced GAS internalization by keratinocytes. Induced SLO expression also prevented lysosomal colocalization with intracellular bacteria and acidification of GAS-containing vacuoles. Exogenous recombinant SLO mimicked the inhibitory effect of SLO secretion on GAS entry but not that on colocalization with the lysosomal marker LAMP-1, implying that disruption of lysosomal degradation requires intracellular secretion of SLO. The internalization of SLO-negative GAS was blocked by the depletion of host cell cholesterol and by the inhibition or knocking down of the expression of clathrin or dynamin. SLO also inhibited the cellular uptake of other cargos that are internalized by clathrin-mediated uptake or by macropinocytosis. We conclude that SLO interferes with the internalization of GAS through local perturbation of the keratinocyte cell membrane and disruption of a clathrin-dependent uptake pathway.

Inhibition of dendritic cell maturation by group A Streptococcus.

BACKGROUND: Exposure to group A Streptococcus (GAS) has been shown to induce maturation of dendritic cells (DC). METHODS: To identify bacterial determinants that modulate DC activation in response to GAS infection, we analyzed the induction of maturation in human monocyte-derived DC following exposure to GAS clinical isolates. RESULTS: Unexpectedly, only 6 of 24 GAS strains tested induced surface expression of major histocompatibility complex class II and costimulatory molecules CD80 and CD83 to levels consistent with DC maturation. Rather, the majority of the strains did not promote DC maturation, and many triggered DC apoptosis. GAS strains that failed to induce DC maturation were those that produced abundant hyaluronic acid (HA) capsular polysaccharide and/or large amounts of the cytotoxin streptolysin O (SLO). By use of isogenic mutants deficient in HA and/or SLO, we determined that GAS inhibits DC maturation through 2 distinct mechanisms: (1) inhibition of bacterial binding and/or phagocytosis by the HA capsule and (2) SLO-mediated induction of DC apoptosis by intracellular GAS. CONCLUSIONS: These results demonstrate that GAS virulence factors modulate maturation and survival of human DC, effects that are likely to have a critical impact on activation of innate and adaptive immune responses to this important human pathogen.

[Overview of hospital mortality at the National Institute of Neurology and Neurosurgery of Mexico City]. / Panorama de la mortalidad hospitalaria en el Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez" de la ciudad de México.

BACKGROUND: Knowing the mortality of the population that goes to medical care, allows to the hospitals institutions and the government to make decisions on the services of health and the conditions of attention. Our objective was to describe the frequency and trend of the main causes of neurological hospital mortality for the period 2002-2007 in the National Institute of Neurology andNeurosurgery "Manuel Velasco Suárez". METHODS: The data was obtained from hospital discharge registers and medical records. Rates of hospital mortality and the tendency were calculated during the period of study. RESULTS: The overall mortality rate was 4.9 per each 100 discharges. The leading causes of death were cerebrovascular diseases and brain tumors and there was a tendency for increased mortality in cases associated with human immunodeficiency virus (HIV) for men p = 0.004 and p = 0.05 for women with epilepsy, and with a status of epileptic condition. CONCLUSIONS: The cerebrovascular diseases and brain tumors tend to hold the first places. The mortality for neurological complications resulting from the diseases caused by the HIV is increasing. It is necessary to promote programs to prevent cardiovascular and HIV infection risk factors, to decrease the mortality rates from these diseases.

Prevalence of metabolic syndrome and obesity in renal transplanted Mexican children.

The purpose of the study was to evaluate the prevalence of MS and obesity in Mexican children with more than one yr post-renal transplantation. Thirty-two children transplanted between January 2004 and February 2006 were included in the study. The weight and height at the time of renal transplant were obtained. A fasting blood sample was drawn for serum creatinine, adiponectin, and complete lipid profile, and a three-h glucose tolerance test was also taken. A complete nutritional evaluation was performed including anthropometry. There was a statistically significant increase in BMI at one yr post-transplant that was maintained at two yr post-transplant. Three patients exhibited obesity and were overweight. Seventeen patients had hypertension, 14 patients had low HDL, 12 patients had hypertriglyceridemia, all had normal fasting glucose, six of them had glucose intolerance, and two had waist circumference higher than 90%. Eight patients (25%) had MS. Patients with MS had higher proportion of deceased donor grafts, acute rejection episodes, and received more methylprednisolone pulses; also they had a statistically significant higher pretransplant BMI than patients without MS. There was a significant relationship between BMI at one yr post-renal transplant and creatinine clearance estimated by Schwartz formula.

Streptococcus pyogenes pharyngeal isolates with reduced susceptibility to ciprofloxacin in Spain: mechanisms of resistance and clonal diversity.

A survey of emm gene sequences and an analysis of the pulsed-field electrophoretic profiles of 30 Streptococcus pyogenes isolates with reduced susceptibilities to ciprofloxacin detected the prevalence of isolates with emm type 6 and considerable genetic diversity among isolates. The mechanism of ciprofloxacin resistance in these isolates was based on point mutations in topoisomerase IV subunit C encoded by parC, mainly replacement of serine-79 by alanine.

Interaction between complement regulators and Streptococcus pyogenes: binding of C4b-binding protein and factor H/factor H-like protein 1 to M18 strains involves two different cell surface molecules.

Streptococcus pyogenes, or group A Streptococcus, is one of the most frequent causes of pharyngitis and skin infections in humans. Many virulence mechanisms have been suggested to be involved in the infectious process. Among them is the binding to the bacterial cell surface of the complement regulatory proteins factor H, factor H-like protein 1 (FHL-1), and C4b-binding protein. Previous studies indicate that binding of these three regulators to the streptococcal cell involves the M protein encoded by the emm gene. M-type 18 strains are prevalent among clinical isolates and have been shown to interact with all three complement regulators simultaneously. Using isogenic strains lacking expression of the Emm18 or the Enn18 proteins, we demonstrate in this study that, in contradistinction to previously described S. pyogenes strains, M18 strains bind the complement regulators factor H, FHL-1, and C4b-binding protein through two distinct cell surface proteins. Factor H and FHL-1 bind to the Emm18 protein, while C4BP binds to the Enn18 protein. We propose that expression of two distinct surface structures that bind complement regulatory proteins represents a unique adaptation of M18 strains that enhances their resistance to opsonization by human plasma and increases survival of this particular S. pyogenes strain in the human host. These new findings illustrate that S. pyogenes has evolved diverse mechanisms for recruitment of complement regulatory proteins to the bacterial surface to evade immune clearance in the human host.

C3 promotes clearance of Klebsiella pneumoniae by A549 epithelial cells.

The airway epithelium represents a primary site for contact between microbes and their hosts. To assess the role of complement in this event, we studied the interaction between the A549 cell line derived from human alveolar epithelial cells and a major nosocomial pathogen, Klebsiella pneumoniae, in the presence of serum. In vitro, we found that C3 opsonization of poorly encapsulated K. pneumoniae clinical isolates and an unencapsulated mutant enhanced dramatically bacterial internalization by A549 epithelial cells compared to highly encapsulated clinical isolates. Local complement components (either present in the human bronchoalveolar lavage or produced by A549 epithelial cells) were sufficient to opsonize K. pneumoniae. CD46 could competitively inhibit the internalization of K. pneumoniae by the epithelial cells, suggesting that CD46 is a receptor for the binding of complement-opsonized K. pneumoniae to these cells. We observed that poorly encapsulated strains appeared into the alveolar epithelial cells in vivo but that (by contrast) they were completely avirulent in a mouse model of pneumonia compared to the highly encapsulated strains. Our results show that bacterial opsonization by complement enhances the internalization of the avirulent microorganisms by nonphagocytic cells such as A549 epithelial cells and allows an efficient innate defense.

Role of the htrA gene in Klebsiella pneumoniae virulence.

We recently described the use of mini-Tn5 to generate complement-sensitive mutants derived from a complement-resistant Klebsiella pneumoniae clinical isolate deficient in the lipopolysaccharide O side chain. One mutant with a reduced capacity to survive in nonimmune human sera carried the transposon inserted in the htrA gene. We cloned and sequenced the gene and predicted from the deduced amino acid sequence that the putative HtrA homolog contains structural features similar to those of previously described HtrA proteins. To investigate the biological functions and the role of the htrA gene in the virulence of K. pneumoniae, we constructed an isogenic mutant by insertion-duplication mutagenesis. Characterization of the mutant showed that it had greater sensitivity to temperature (50 degrees C) and oxidative stress (H(2)O(2)) than the parent strain. Furthermore, the htrA mutant produced less capsule, bound more molecules of complement component C3, and was more sensitive to complement and whole-blood killing than was the parent strain. Finally, disruption of the htrA gene in a virulent K. pneumoniae strain caused a reduction of its virulence in a mice model. Our results indicate that the htrA gene plays an important role in the virulence of K. pneumoniae.

Molecular analysis of the contribution of the capsular polysaccharide and the lipopolysaccharide O side chain to the virulence of Klebsiella pneumoniae in a murine model of pneumonia.

Klebsiella pneumoniae is a common cause of gram-negative bacterial nosocomial pneumonia. Two surface polysaccharides, lipopolysaccharide (LPS) O side chain and capsular polysaccharide (CPS), are critical for the microorganism in causing sepsis, but little is known about their role in pneumonia. To investigate their contribution in the pathogenesis of K. pneumoniae pneumonia, we characterized the host response to bacterial challenge with a highly virulent clinical isolate or with isogenic insertion-duplication mutants deficient in CPS or LPS O side chain in a murine model of pneumonia. Animals challenged intratracheally with the wild-type or LPS O side chain-deficient strain developed pneumonia and became bacteremic before death. Extensive lung lesions as well as pleuritis, vasculitis, and edema were observed by histopathological examination, and polymorphonuclear infiltration was also demonstrated. In contrast, none of the animals challenged with the unencapsulated strain developed pneumonia or bacteremia. Examination of tissue from this group did not identify lung lesions, and none of the infected animals died. Analysis of the early host defense mechanisms that contributed to the clearance of the unencapsulated mutant showed that the levels of C3 deposited on the unencapsulated mutant surface were threefold higher than those for the wild-type and LPS O side chain-deficient strains. Furthermore, phagocytosis of the unencapsulated mutant by human alveolar macrophages (AM) was more efficient than that of the wild-type and LPS O side chain-deficient strains. We conclude that CPS, but not LPS O side chain, is essential for Klebsiella pneumonia because it modulates the deposition of C3 and protects the microorganisms against human AM phagocytosis.

Role of lung epithelial cells in defense against Klebsiella pneumoniae pneumonia.

The airway epithelium represents a primary site for the entry of pathogenic bacteria into the lungs. It has been suggested for many respiratory pathogens, including Klebsiella pneumoniae, that adhesion and invasion of the lung epithelial cells is an early stage of the pneumonia process. We observed that poorly encapsulated K. pneumoniae clinical isolates and an isogenic unencapsulated mutant invaded lung epithelial cells more efficiently than highly encapsulated strains independent of the K type. By contrast, the unencapsulated mutant was completely avirulent in a mouse model of pneumonia, unlike the wild-type strain, which produced pneumonia and systemic infection. Furthermore, the unencapsulated mutant bound more epithelially produced complement component C3 than the wild-type strain. Our results show that lung epithelial cells play a key role as a host defense mechanism against K. pneumoniae pneumonia, using two different strategies: (i) ingestion and control of the microorganisms and (ii) opsonization of the microorganisms. Capsular polysaccharide avoids both mechanisms and enhances the virulence of K. pneumoniae.

Estudio de la eficacia y seguridad de brodimoprim vs. trimetoprim-sulfametoxazol en niños con gastroenteritis bacteriana / Study brodimoprim vs. trimetoprim-sulfatoxasol security and effectiveness in children with bacterial gastroenteritis

Se realizó un estudio comparativo de brodimoprim contra trimetoprim/sulfametoxazol para el tratamiento de niños con diarrea aguda bacteriana. Se estudiaron 30 pacientes en cada grupo. El grupo l recibió trimetoprim/sulfametoxazol en suspensión por vía oral, a dosis de 8 mg/kg/día cada 12 horas por 5 días. El grupo ll recibió brodimoprim en suspensión con dosis única inicial de 10 mg/kg de peso, seguida de 5 mg/kg cada 24 horas por 5 días. En ambos grupos, los resultados mostraron remisión de la sintomatología en todos los pacientes, y negativización en la mayoría de los coprocultivos. En efectos colaterales un paciente presentó cefalea y otros dos presentaron diarrea por brodimoprim; la diferencia no fue significativa. Se concluye que brodimoprim es una buena alternativa para tratar a niños con diarrea aguda.

Traumatismo craneo-encefálico en el servicio de emergencia del Hospital Abel Gilbert Ponton de Guayaquil

El presente es un estudio retrospectivo realizado mediante la revisión de casos que ingresaron al servicio de emergencia del Hospital Abel Gilbert Pontón, presentando algún tipo de traumatismo cráneo encefálico, durante los años comprendidos entre 1990 y 1995, un total de 435 pacientes; 276 (63.45 por ciento) correspondió al sexo femenino; 199 (36.55 por ciento)al sexo masculino; en relación con la edad, el grupo que mayor porcentaje de pacientes de TCE presentó fue el comprendido entre 0 y 10 años con 285 (21.15 por ciento). Entre las causas, los accidentes de tránsito originaron el 50 por ciento de los casos, seguidos de caídas y golpes fortuitos con el 32.8 por ciento, siendo el principal factor presdisponente el alcohol con el 10.2 por ciento. El dato clínico más frecuente fue el déficit de conciencia con el 93 por ciento, seguido de las cefaleas con el 6 por ciento los hematomas subdurales unilaterales tuvieron un 4.3 por ciento y como secuelas las neurósis con el 5.59 por ciento. El área donde mayor porcentaje se atendieron pacientes fue en cirugía con un porcentaje de 54.48 por ciento, luego fue el área de pediatría con 29.20 por ciento. El 1.15 por ciento de los pacientes fallecieron...