Functional domains of a ribosome arresting peptide are affected by surrounding nonconserved residues.

Expression of the Escherichia coli tnaCAB operon, responsible for L-tryptophan (L-Trp) transport and catabolism, is regulated by L-Trp-directed translation arrest and the ribosome arresting peptide TnaC. The function of TnaC relies on conserved residues distributed throughout the peptide, which are involved in forming an L-Trp binding site at the ribosome exit tunnel and inhibiting the ribosome function. We aimed to understand whether nonconserved amino acids surrounding these critical conserved residues play a functional role in TnaC-mediated ribosome arrest. We have isolated two intragenic suppressor mutations that restore arrest function of TnaC mutants; one of these mutations is located near the L-Trp binding site, while the other mutation is located near the ribosome active site. We used reporter gene fusions to show that both suppressor mutations have similar effects on TnaC mutants at the conserved residues involved in forming a free L-Trp binding site. However, they diverge in suppressing loss-of-function mutations in a conserved TnaC residue at the ribosome active site. With ribosome toeprinting assays, we determined that both suppressor mutations generate TnaC peptides, which are highly sensitive to L-Trp. Puromycin-challenge assays with isolated arrested ribosomes indicate that both TnaC suppressor mutants are resistant to peptidyl-tRNA cleavage by puromycin in the presence of L-Trp; however, they differ in their resistance to puromycin in the absence of L-Trp. We propose that the TnaC peptide two functionally distinct segments, a sensor domain and a stalling domain, and that the functional versatility of these domains is fine-tuned by the nature of their surrounding nonconserved residues.

Hipertensión arterial pulmonar en pacientes con dermatomiositis juvenil y esclerosis sistémica en un centro pediátrico de tercer nivel

INTRODUCCIÓN: La hipertensión arterial pulmonar puede estar asociada secundariamente a enfermedades del tejido conectivo. Entre estas enfermedades, predominan la esclerosis sistémica y la dermatomiositis juvenil. MATERIALES Y MÉTODOS: Se realizó un estudio retrospectivo, descriptivo y transversal. Se incluyeron todos los pacientes con diagnóstico de dermatomiositis juvenil y esclerosis sistémica que acudieron a nuestro hospital. Posteriormente se verificaron los niveles de presión arterial pulmonar mediante ecocardiografía. RESULTADOS: Se incluyeron 58 pacientes, de los cuales sólo 17 pacientes tuvieron ecocardiografía diagnóstica. Entre ellos, dos pacientes presentaron hipertensión arterial pulmonar. CONCLUSIÓN: La detección oportuna de la hipertensión arterial pulmonar en las enfermedades del tejido conectivo es esencial. Generalmente es asintomático. Es necesario adherirse al protocolo internacional que sugiere realizar ecocardiografía en todos los pacientes con dermatomiositis juvenil y esclerosis sistémica.

INTRODUCTION: Pulmonary arterial hypertension may be secondary associated with connective tissue diseases. Among these diseases, systemic sclerosis and juvenile dermatomyositis predominate. MATERIALS AND METHODS: A retrospective, descriptive and cross-sectional study was carried out. All patients with a diagnosis of juvenile dermatomyositis and systemic sclerosis who attended our hospital were included. Pulmonary arterial pressure levels were subsequently verified by echocardiography. RESULTS: 58 patients were included, of which only 17 patients had a diagnostic echocardiography. Among them, two patients presented pulmonary arterial hypertension. CONCLUSION: Timely detection of pulmonary arterial hypertension in connective tissue diseases is essential. It is generally asymptomatic. It is necessary to adhere to the international protocol that suggests performing echocardiography in all patients with juvenile dermatomyositis and systemic sclerosis.

Optimizing Transitions of Care and Enhancing Surgical Education on Acute Care Surgery: A Multi-Institutional Survey Study.

OBJECTIVE: Critically ill and injured patients are routinely managed on the Trauma and Acute Care Surgery (ACS) service and receive care from numerous residents during hospital admission. The Clinical Learning Environment Review (CLER) program established by the ACGME identified variability in resident transitions of care (TC) while observing quality care and patient safety concerns. The aim of our multi-institutional study was to review surgical trainees' impressions of a specialty-specific handoff format in order to optimize patient care and enhance surgical education on the ACS service. DESIGN: A survey study was conducted with a voluntary electronic 20-item questionnaire that utilized a 5 point Likert scale regarding TC among resident peers, supervised handoffs by trauma attendings, and surgical education. It also allowed for open-ended responses regarding perceived advantages and disadvantages of handoffs. SETTING: Ten American College of Surgeons-verified Level 1 adult trauma centers. PARTICIPANTS: All general surgery residents and trauma/acute/surgical critical care fellows were surveyed. RESULTS: The study task was completed by 147 postgraduate trainees (125 residents, 14 ACS fellows, and 8 surgical critical care fellows) with a response rate of 61%. Institutional responses included: university hospital (67%), community hospital-university affiliate (16%), and private hospital-university affiliate (17%). A majority of respondents were satisfied with morning TC (62.6%) while approximately half were satisfied with evening TC (52.4%). Respondees believe supervised handoffs improved TC and prevented patient care delays (80.9% and 74.8%, respectively). A total of 35% of trainees utilized the open-ended response field to highlight specific best practices of their home institutions. CONCLUSIONS: Surgical trainees view ACS morning handoff as an effective standard to provide the highest level of clinical care and an opportunity to enhance surgical knowledge. As TC continue to be a focus of certifying bodies, identifying best practices and opportunities for improvement are critical to optimizing quality patient care and surgical education.

Prevalence of Housing Insecurity in Survivors of Traumatic Injury.

BACKGROUND: Almost 20% of the US population are housing insecure (HI) due to inadequate living conditions, imbalanced costs to income, nonsustainable shelter, or overcrowding. Housing insecure and physical trauma share similar risk factors, but their direct association is not well elucidated. The objective of our study was to determine the prevalence of HI in survivors of traumatic injury. METHODS: We conducted a prospective cohort study at an urban, level 1 trauma center. A survey on social determinants of health was administered to adult patients, and demographic, injury specifics, and clinical outcomes data were collected. HI was defined by affirmative answers to questions related to history of homelessness or concern about sustainable shelter. The cohort was stratified by HI; groups were compared using the Mann-Whitney U and Fisher exact tests, as appropriate. RESULTS: Of 116 study participants, four were excluded due to missing data. Of the 112, 42 (37.8%) reported HI and most were black (69%) males (73.8%). There were no demographic differences between groups. Conversely, HI patients had a higher rate of penetrating traumatic injury (34.1% vs 14.5%, P-value = .03) and were significantly less educated compared to secure participants (P-value = .03) [no degree (26.2% vs 10.3%), high school degrees (21.4% vs 41.2%)] with concomitant illicit drug use (63.4% vs 27.9%, P < .001), and history of addiction (52.4% vs 7.2%, P < .001). CONCLUSION: HI far exceeds national averages in our cohort. Although difficult to ascertain a cause-effect relationship, HI may be a modifiable risk factor for trauma that negatively influences outcomes.

The Identity of the Constriction Region of the Ribosomal Exit Tunnel Is Important to Maintain Gene Expression in Escherichia coli.

Mutational changes in bacterial ribosomes often affect gene expression and consequently cellular fitness. Understanding how mutant ribosomes disrupt global gene expression is critical to determining key genetic factors that affect bacterial survival. Here, we describe gene expression and phenotypic changes presented in Escherichia coli cells carrying an uL22(K90D) mutant ribosomal protein, which displayed alterations during growth. Ribosome profiling analyses revealed reduced expression of operons involved in catabolism, indole production, and lysine-dependent acid resistance. In general, translation initiation of proximal genes in several of these affected operons was substantially reduced. These reductions in expression were accompanied by increases in the expression of acid-induced membrane proteins and chaperones, the glutamate-decarboxylase regulon, and the autoinducer-2 metabolic regulon. In agreement with these changes, uL22(K90D) mutant cells had higher glutamate decarboxylase activity, survived better in extremely acidic conditions, and generated more biofilm in static cultures compared to their parental strain. Our work demonstrates that a single mutation in a non-conserved residue of a ribosomal protein affects a substantial number of genes to alter pH resistance and the formation of biofilms. IMPORTANCE All newly synthesized proteins must pass through a channel in the ribosome named the exit tunnel before emerging into the cytoplasm, membrane, and other compartments. The structural characteristics of the tunnel could govern protein folding and gene expression in a species-specific manner but how the identity of tunnel elements influences gene expression is less well-understood. Our global transcriptomics and translatome profiling demonstrate that a single substitution in a non-conserved amino acid of the E. coli tunnel protein uL22 has a profound impact on catabolism, cellular signaling, and acid resistance systems. Consequently, cells bearing the uL22 mutant ribosomes had an increased ability to survive acidic conditions and form biofilms. This work reveals a previously unrecognized link between tunnel identity and bacterial stress adaptation involving pH response and biofilm formation.

Neurodevelopmental outcome of infants without central nervous system anomalies born to symptomatic RT-PCR ZIKV positive women.

An epidemic of Zika virus (ZIKV) infection began in Colombia in October 2015. Previous studies have identified a cause-effect relationship between fetal exposure to the ZIKV and the development of microcephaly and other central nervous system (CNS) anomalies with variable degrees of neurodevelopmental delay. Less is known about the neurodevelopmental outcome of infants without CNS anomalies born to symptomatic ZIKV RT-PCR-positive women. We aimed to compare the neurodevelopmental outcome of these infants to a control group of infants without CNS anomalies born to asymptomatic ZIKV RT-PCR negative women who did not seroconvert during pregnancy. Participating infants were categorized according to ZIKV maternal exposure. Women with symptomatology suggestive of ZIKV infection and a positive RT-PCR for ZIKV were categorized as ZIKV-exposed. Maternal controls (ZIKV unexposed) from the same geographic area were subsequently captured during the tail end of the epidemic through a partner project, the ZIKAlliance, whose aim was to determine the prevalence of ZIKV in pregnant women. Infant survivors from these two groups of pregnant women had a neurodevelopmental evaluation at 12, 18, and 24 months corrected age (CA). The ZIKV-exposed women were found to be older, had less subsidized health care, had a higher percentage of women in middle-class socioeconomic strata, had higher technical and university education, were less likely to be living with a partner, and had higher rates of pregnancy comorbidity and premature births than ZIKV unexposed women. Compared to infants born to ZIKV unexposed women (unexposed), infants born to ZIKV exposed women (exposed) were of lower gestational age and required more speech and occupational therapy services. No differences between groups were observed in the proportion of cut-off scores <70 on the Bayley-III Scale at 12, 18, and 24 months for motor, language, and cognitive domains. When a cut-off of <85 was used, a higher percentage of motor and cognitive impairment was observed in unexposed infants at 12 and 24 months CA, respectively. Median and IQR score on the Bayley-III scale showed higher scores in favor of exposed infants for motor development at 12 and 18 months CA, language at 12 months, and cognitive domain at 12, 18, and 24 months. The adjusted median and IQR compound score of the difference between exposed and unexposed was higher in favor of exposed infants at 12 to 24 months CA for motor (3.8 [95% CI 1.0 to 6.7]) and cognitive domains (10.6 [95% CI 7.3 to 13.9]). We observed no differences in the language domain (1.9 [95% CI -1.2 to 5.0]). We conclude that infants with no evidence of microcephaly or other CNS anomalies born to ZIKV-exposed women had normal neurodevelopment up to 24 months of CA, supporting an all-or-nothing effect with maternal ZIKV exposure. Long-term follow-up to evaluate school performance is required. Clinical Trial Registration: www.clinicaltrials.gov, NCT02943304.

Clinical Features and Neurodevelopmental Outcomes for Infants with Perinatal Vertical Transmission of Zika Virus, Colombia.

Transplacental transmission of Zika virus has been reported during all trimesters of pregnancy and might lead to central nervous system anomalies, including microcephaly. We report 3 cases of perinatal Zika infection identified during the epidemic in Colombia and provide detailed descriptions of clinical features, diagnosis, and neurodevelopmental outcome at 18 months of age (corrected).

Fetal central nervous system anomalies according to RT-PCR and trimester of maternal infection with Zika virus: A prospective cohort study.

INTRODUCTION: In October 2015, an epidemic of Zika began in Colombia's geographic areas with a high population of mosquitoes of the genus Aedes. We aimed to describe the fetal brain ultrasound findings in pregnant women with active symptoms or a history of symptoms suggestive of Zika virus (ZIKV) infection. MATERIAL AND METHODS: Eligible pregnant women were tested with reverse transcriptase-polymerase chain reaction (RT-PCR) for ZIKV and followed prospectively using detailed anatomic ultrasound and transvaginal neurosonography to detect structural anomalies of the fetal central nervous system (CNS). RESULTS: A total of 115 symptomatic women with a positive ZIKV RT-PCR and 55 with a negative ZIKV RT-PCR were enrolled in the study; CNS compromise of the fetus occurred in 22% and 17%, respectively (p = 0.255). Callosal dysgenesis (14.5%) was the most frequent anomaly of the CNS, followed by microcephaly (13.6%) and neuronal migration disorders (8.3%). When symptomatic ZIKV RT-PCR-positive women were categorized by trimester of infection, CNS anomalies were present in 40% of first-trimester infections, compared with 21% and 7% in second- and third-trimester infections (p = 0.002). CNS anomalies were also more severe in first-trimester-infected fetuses than in second- and third-trimester-infected fetuses. The high prevalence of CNS anomalies in fetuses of symptomatic ZIKV RT-PCR negative women suggests a high rate of false-negative cases and an even higher prevalence of CNS anomalies than observed in this study. CONCLUSIONS: The prevalence of fetal CNS anomalies was higher than previously reported in the literature for both symptomatic RT-PCR-positive and -negative pregnant women. Corpus callosum anomalies, microcephaly, neuronal migration disorders, and brain parenchymal hyperechogenicities were the most frequent CNS anomalies detected. In addition, CNS anomalies were more frequent and severe in infected fetuses during the first trimester of pregnancy than during the second or third trimester.

Nevo sebáceo de Jadassohn. A propósito de un caso neonatal

RESUMEN El nevo sebáceo de Jadassohn se presenta como una lesión hamartomatosa, de extensión variable. Puede estar presente al nacimiento y generalmente se localiza en cuero cabelludo. La zona presenta alopecia. En raras ocasiones puede malignizarse en la edad adulta. Se presenta un caso neonatal y se hace revisión de la literatura.

ABSTRACT Jadassohn's sebaceous nevus presents as a hamartomatous lesion of variable extent. It can be present at birth and is generally located on the scalp. The area shows alopecia. In rare cases, it can become malignant in adulthood. A neonatal case is presented and a literature review is made.

Structural basis for the tryptophan sensitivity of TnaC-mediated ribosome stalling.

Free L-tryptophan (L-Trp) stalls ribosomes engaged in the synthesis of TnaC, a leader peptide controlling the expression of the Escherichia coli tryptophanase operon. Despite extensive characterization, the molecular mechanism underlying the recognition and response to L-Trp by the TnaC-ribosome complex remains unknown. Here, we use a combined biochemical and structural approach to characterize a TnaC variant (R23F) with greatly enhanced sensitivity for L-Trp. We show that the TnaC-ribosome complex captures a single L-Trp molecule to undergo termination arrest and that nascent TnaC prevents the catalytic GGQ loop of release factor 2 from adopting an active conformation at the peptidyl transferase center. Importantly, the L-Trp binding site is not altered by the R23F mutation, suggesting that the relative rates of L-Trp binding and peptidyl-tRNA cleavage determine the tryptophan sensitivity of each variant. Thus, our study reveals a strategy whereby a nascent peptide assists the ribosome in detecting a small metabolite.

A protein folding robot driven by a self-taught agent.

This paper presents a computer simulation of a virtual robot that behaves as a peptide chain of the Hemagglutinin-Esterase protein (HEs) from human coronavirus. The robot can learn efficient protein folding policies by itself and then use them to solve HEs folding episodes. The proposed robotic unfolded structure inhabits a dynamic environment and is driven by a self-taught neural agent. The neural agent can read sensors and control the angles and interactions between individual amino acids. During the training phase, the agent uses reinforcement learning to explore new folding forms that conduce toward more significant rewards. The memory of the agent is implemented with neural networks. These neural networks are noise-balanced trained to satisfy the look for future conditions required by the Bellman equation. In the operating phase, the components merge into a wise up protein folding robot with look-ahead capacities, which consistently solves a section of the HEs protein.

Uso de dispositivos móviles por parte de lactantes y preescolares: una revisión sistemática / Use of mobile devices by infants and preschoolers: a systematic review

Este estudio tiene como objetivo el examinar la frecuencia con la que los niños de 1 a 5 años hacen uso de los nuevos dispositivos móviles y su relación con la salud. Se realizó una revisión sistemática, retrospectiva, en Pubmed y Scielo; de un total de 145 artículos recolectados se incluyeron 43, cuyos criterios de inclusión y exclusión fueron: publicación de 2008 a 2021, sin predilección por alguna metodología en específico, variables de estudio (salud física, psicológica y social), no estudios en animales, trabajos repetidos y sin relevancia para el estudio, la calidad de la evidencia fue analizada con relación al valor de p y el índice de confianza 95% para cada variable en cuestión. El uso de Dispositivos móviles >2hrs/día se asocia a riesgo de desarrollo de alteraciones a la salud de los niños de 1 a 5 años, se necesita una vigilancia proactiva de los tutores(AU)

This study aims to examine the frequency with which children between the ages of 1 and 5 make use of new mobile devices and their relationship to health. A retrospective systematic review was carried out in Pubmed and Scielo; Of a total of 145 articles collected, 43 were included, whose inclusion and exclusion criteria were: publication from 2008 to 2021, without predilection for any specific methodology, study variables (physical, psychological and social health), no studies in animals, Repeated works without relevance to the study, the quality of the evidence was analyzed in relation to the value of p and the 95% confidence index for each variable in question. The use of mobile devices> 2hrs/day is associated with the risk of development of alterations to the health of children aged 1 to 5 years, a proactive vigilance of the tutors is needed(AU)

Morbilidad neonatal extrema y sus desenlaces en un hospital de alta complejidad en el 2013 / Extreme neonatal morbidity and its outcomes in a high complexity hospital in 2013 / Morbidade neonatal extrema e seus resultados em um hospital de alta complexidade em 2013

Introducción. La Morbilidad neonatal extrema se refiere a cualquier evento ocurrido en los primeros veintiocho días de vida con riesgo vital inminente. Es multifactorial, son relevantes los retrasos en la atención. En 2010 se describió por primera vez como indicador de salud pública en Brasil. Metodología. Estudio transversal en un hospital de alta complejidad en el año 2013. Se revisaron las características sociodemográficas y asistenciales, los eventos de morbilidad y sus desenlaces, el indicador mismo, la mortalidad neonatal y los retrasos en la atención (tipos I - IV). Resultados. Ingresaron 1,190 neonatos, se presentaron 120 casos y se analizaron los primeros 60 por saturación de datos. La tasa de morbilidad neonatal extrema fue de 59 por cada 1,000 nacidos vivos y la de mortalidad de 13.9, similares a las brasileñas y superiores a las nacionales (33 por cada 1,000). Los eventos más importantes con respecto a mortalidad fueron peso menor de 1,500 gramos, ventilación mecánica, Apgar menor de 7 a los 5 minutos y malformaciones congénitas. Los retrasos en las madres fueron predominantemente de tipo I (45.4%) por pobre control prenatal. El retraso neonatal más frecuente fue el tipo IV (40%), por mala adherencia a protocolos institucionales. Discusión. El indicador local fue mayor que el nacional por la complejidad institucional y los retrasos en la atención, los cuales causaron saturación estadística. Se puede mejorar con mayor adherencia a estrategias existentes como el control prenatal y protocolos institucionales. Conclusión. La Morbilidad neonatal extrema visibiliza las falencias en atención materno­neonatal. Cómo citar. Delgado-Beltrán AM., Beltrán-Avendaño MA., Pérez-Vera LA. Morbilidad neonatal extrema y sus desenlaces en un hospital de alta complejidad en el 2013. MedUNAB. 2021;24(1): 61-71. Doi: https://doi.org/10.29375/01237047.3960

Introduction. Extreme neonatal morbidity refers to any event that occurs in the first twenty-eight days of life with imminent vital risk. It is multifactorial and delays in treatment are relevant. It was described for the first time as a public health indicator in Brazil in 2010. Methodology. This was a cross-sectional study in a high complexity hospital in 2013. Sociodemographic and assistance characteristics, morbidity events and their outcomes, the indicator itself, neonatal mortality, and delays in treatment (types I - IV) were reviewed. Results. 1,190 neonates were entered, 120 cases occurred and the first 60 were analyzed due to data saturation. The extreme neonatal morbidity rate was 59 for every 1,000 children born alive and the mortality rate was 13.9. This was similar to the figures in Brazil and greater than national statistics (33 for every 1,000). The most significant events with respect to mortality were weight lower than 1,500 grams, mechanical ventilation, an Apgar score lower than 7 at 5 minutes and congenital anomalies. Delays from mothers were predominantly type I (45.4%) due to poor prenatal control. The most frequent neonatal delay was type IV (40%) due to bad adherence to institutional protocols. Discussion. The local indicator was greater than the national indicator due to the institutional complexity and delays in treatment, which cause statistical saturation. This can be improved with better adherence to existing strategies, such as prenatal control and institutional protocols. Conclusion. Extreme neonatal morbidity shows the flaws in maternal - neonatal healthcare. Cómo citar. Delgado-Beltrán AM., Beltrán-Avendaño MA., Pérez-Vera LA. Morbilidad neonatal extrema y sus desenlaces en un hospital de alta complejidad en el 2013. MedUNAB. 2021;24(1): 61-71. Doi: https://doi.org/10.29375/01237047.3960

Introdução. A morbidade neonatal extrema refere-se a qualquer evento que ocorra nos primeiros vinte e oito dias de vida com risco de vida iminente. É multifatorial, e os atrasos no atendimento são relevantes. Em 2010 foi descrita pela primeira vez como um indicador de saúde pública no Brasil. Metodologia. Estudo transversal em um hospital de alta complexidade em 2013. Foram revisadas as características sociodemográficas e assistenciais, os eventos de morbidade e seus resultados, o próprio indicador, a mortalidade neonatal e os atrasos no atendimento (tipos I - IV). Resultados. Foram internados 1,190 recém-nascidos, foram identificados 120 casos e os primeiros 60 foram analisados devido à saturação dos dados. A taxa de morbidade neonatal extrema foi de 59 por 1,000 nascidos vivos e a taxa de mortalidade de 13,9, semelhante às taxas brasileiras e superior às taxas nacionais (33 por 1,000). Os eventos mais importantes em relação à mortalidade foram peso inferior a 1,500 gramas, ventilação mecânica, Apgar menor que 7 em 5 minutos e malformações congênitas. Os atrasos nas mães foram predominantemente do tipo I (45.4%) devido ao cuidado pré-natal precário. O atraso neonatal mais frequente foi do tipo IV (40%), devido à falta de aderência aos protocolos institucionais. Discussão. O indicador local foi superior ao nacional devido à complexidade institucional e aos atrasos no atendimento, o que causou saturação estatística. Pode ser melhorado com uma maior adesão às estratégias existentes, como atendimento pré-natal e protocolos institucionais. Conclusão. A morbidade neonatal extrema torna visíveis as deficiências no cuidado materno-neonatal. Cómo citar. Delgado-Beltrán AM., Beltrán-Avendaño MA., Pérez-Vera LA. Morbilidad neonatal extrema y sus desenlaces en un hospital de alta complejidad en el 2013. MedUNAB. 2021;24(1): 61-71. Doi: https://doi.org/10.29375/01237047.3960

Diagnóstico y tratamiento del cáncer de mama HER2+: Guía de Práctica Clínica de la Sociedad Peruana de Cancerología / Diagnosis and treatment of HER2 + breast cancer: Clinical Practice Guide of the Peruvian Society of Cancerology

RESUMEN Introducción. En Perú, el cáncer de mama representa el tipo de cáncer más frecuente en mujeres y el sexto tipo de cáncer más letal en la población general. La sobreexpresión del receptor del factor de crecimiento epidérmico (HER2+) ocurre en 20% a 30% de los cánceres de mama, y se asocia con tumores más agresivos, con mayor recurrencia y mayor mortalidad. Objetivo. Elaborar un conjunto de recomendaciones basadas en evidencias para el diagnóstico y tratamiento del cáncer de mama HER2+, con la finalidad de contribuir a reducir la mortalidad, progresión de la enfermedad y mejorar la calidad de vida. Métodos. Se conformó un panel de especialistas clínicos y metodólogos, quienes identificaron preguntas clínicas relevantes sobre el diagnóstico y tratamiento del cáncer de mama HER2+. Se desarrolló una búsqueda sistemática de GPC en Medline (PubMed), y en organismos elaboradores y recopiladores. Para la formulación de recomendaciones, el panel de especialistas discutió la evidencia y elementos del contexto de implementación de la recomendación, siguiendo la metodología propuesta por el Ministerio de Salud del Perú. Resultados. Se priorizó nueve preguntas clínicas. Se formuló un total de 25 recomendaciones clínicas. Conclusiones. Se elaboró una GPC basada en evidencias, a través de un proceso sistemático, riguroso y transparente desarrollado por un equipo multidisciplinario.

ABSTRACT Introduction. In Peru, breast cancer represents the most common type of cancer in women and the sixth most lethal type of cancer in the general population. Overexpression of the epidermal growth factor receptor (HER2 +) occurs in 20% to 30% of breast cancers, and is associated with more aggressive tumors, with greater recurrence and greater mortality. Objective. Prepare a set of evidence-based recommendations for the diagnosis and treatment of HER2 + breast cancer, in order to help reduce mortality, disease progression and improve quality of life. Methods. A panel of clinical specialists and methodologists was formed, who identified relevant clinical questions about the diagnosis and treatment of HER2 + breast cancer. A systematic search for CPGs was carried out in Medline (PubMed), and in developing and compiling agencies. For the formulation of recommendations, the panel of specialists discussed the evidence and elements of the context of implementation of the recommendation, following the methodology proposed by the Ministry of Health of Peru. Results. Nine clinical questions were prioritized. A total of 25 clinical recommendations were made. Conclusions. An evidence-based CPG was developed through a systematic, rigorous and transparent process developed by a multidisciplinary team.

Hemangioma de colon Descripción de caso y revisión de la literatura / HEMANGIOMA OF THE COLON. Case report and literature review

El hemangioma de colon y recto es una entidad poco frecuente. El tipo cavernoso, es aún más raro por lo que existen pocos reportes de esta patología. Afecta mayormente al recto y al sigmoides, y el modo de presentación más común es la proctorragia indolora en el 90% de los casos. Más frecuente en adultos jóvenes. Esta entidad para su diagnóstico requiere alta sospecha y la realización de los estudios pertinentes ya que suele confundírsela con patologías más comunes. En esta revisión se presenta el caso de un paciente masculino de 58 años con un hemangioma cavernoso de colon transverso que se manifestó inicialmente como hematoquecia asociada a astenia. Luego de realizar estudios complementarios, se decide conducta quirúrgica. Se realizó resección de colon transverso con buena evolución postoperatoria. El resultado de anatomía patológica nos informa Hemangioma Cavernoso de colon transverso.

The hemangioma of the colon and rectum is a rare entity. The cavernous type is even more rare, so there are few reports of this pathology. It mainly affects the rectum and the sigmoid, and the most common presentation is painless proctorrhagia in 90% of cases. More frequent in young adults. This entity for its diagnosis requires high suspicion and the realization of the pertinent studies since it is usually confused with more common pathologies. In this review we present the case of a 58-year-old male patient with a cavernous hemangioma of the transverse colon that initially manifested as hematochezia associated with asthenia. After performing complementary studies, surgical behavior is decided. Transverse colon resection was performed with good postoperative evolution. The result of pathological anatomy informs us Cavernous hemangioma of transverse colon

Prevalencia y factores de riesgo asociados a la dislipidemia en pacientes diabéticos tipo 2 de la Comunidad de Cantabria / The prevalence and risk factors associated with dyslipidemia in type 2 diabetic patients in the autonomous Region of Cantabria

Antecedentes y objetivo: La dislipidemia es uno de los principales factores de riesgo de enfermedad cardiovascular en pacientes con diabetes mellitus tipo 2 (DM2). El objetivo de este estudio es evaluar la prevalencia y factores de riesgo asociados a la dislipidemia en la población con DM2 de la Comunidad de Cantabria. Material y métodos: Es un estudio transversal realizado en centros de Atención Primaria del Servicio Cántabro de Salud (n = 680). Se seleccionó una muestra aleatorizada representativa de la población con DM2 de 18 a 85 años mediante un procedimiento polietápico. Se obtuvieron de la historia clínica y mediante entrevista los datos de los factores de riesgo a estudio. Se analizó la asociación con la dislipidemia mediante regresión logística. Resultados: El 52,1% eran hombres, la edad media fue de 69,8 años, la evolución de la diabetes de 9,99 años, el 84,3% tenían HTA, el 76,6% sobrepeso/obesidad y la HbA1c media era de 6,96%. La prevalencia de dislipidemia fue del 85,3% y en el análisis bivariado se asoció con antecedente de enfermedad vascular periférica, diabetes controlada, tratamiento antihipertensivo, filtrado glomerular, HbA1c > 7%, grasa corporal estimada en sobrepeso y obesidad, antecedente de enfermedad cardiovascular, edad y HbA1c. En el análisis multivariante los factores independientes fueron el sexo femenino y el antecedente de enfermedad cardiovascular. Conclusiones: La prevalencia de dislipidemia en nuestro estudio fue del 85,3% y es consistente con la encontrada en estudios previos publicados. Los factores de riesgo asociados de forma independiente fueron el sexo femenino y el antecedente personal de enfermedad cardiovascular

Background and objective: Dyslipidemia is one of the main risk factors in cardiovascular disease in patients with diabetes mellitus type 2 (DM2). The aim of this study is to evaluate the prevalence and risk factors associated with dyslipidemia in the population with diabetes mellitus type 2 in the region of Cantabria. Material and methods: This is a transversal study carried out at Cantabrian primary health care centres (n = 680). A representative, random sample of the population with DM2, ranging from 18-85, was selected using a multistage procedure. The medical records were obtained, and by means of interviews the data of the risk factors to be studied was secured. The correlation with dyslipidemia was analysed by means of logistic regression. Results: There were 52.1% of males, the average age was 69.8, the evolution of diabetes was 9.99 years, 84.3% had arterial hypertension, 76.6% were overweight or obese and the average HbA1c was 6.96%. The prevalence of dyslipidemia was 85.3%, and in the bivariate analysis this is associated with a history of peripheral artery disease, controlled diabetes, antihypertensive treatment, glomerular filtration, HbA1c>7%, body fat estimated as being either overweight or obese, a history of cardiovascular disease, age and HbA1c. In the multivariate analysis the independent factors were being female and a history of cardiovascular disease. Conclusion: The prevalence of dyslipidemia in our study was 85.3%, and is consistent with figures found in previous published studies. The independent associated risk factors were being female and a past medical history of cardiovascular disease

The prevalence and risk factors associated with dyslipidemia in type 2 diabetic patients in the autonomous Region of Cantabria. / Prevalencia y factores de riesgo asociados a la dislipidemia en pacientes diabéticos tipo 2 de la Comunidad de Cantabria.

BACKGROUND AND OBJECTIVE: Dyslipidemia is one of the main risk factors in cardiovascular disease in patients with diabetes mellitus type 2 (DM2). The aim of this study is to evaluate the prevalence and risk factors associated with dyslipidemia in the population with diabetes mellitus type 2 in the region of Cantabria. MATERIAL AND METHODS: This is a transversal study carried out at Cantabrian primary health care centres (n=680). A representative, random sample of the population with DM2, ranging from 18-85, was selected using a multistage procedure. The medical records were obtained, and by means of interviews the data of the risk factors to be studied was secured. The correlation with dyslipidemia was analysed by means of logistic regression. RESULTS: There were 52.1% of males, the average age was 69.8, the evolution of diabetes was 9.99 years, 84.3% had arterial hypertension, 76.6% were overweight or obese and the average HbA1c was 6.96%. The prevalence of dyslipidemia was 85.3%, and in the bivariate analysis this is associated with a history of peripheral artery disease, controlled diabetes, antihypertensive treatment, glomerular filtration, HbA1c>7%, body fat estimated as being either overweight or obese, a history of cardiovascular disease, age and HbA1c. In the multivariate analysis the independent factors were being female and a history of cardiovascular disease. CONCLUSION: The prevalence of dyslipidemia in our study was 85.3%, and is consistent with figures found in previous published studies. The independent associated risk factors were being female and a past medical history of cardiovascular disease.

The regulatory TnaC nascent peptide preferentially inhibits release factor 2-mediated hydrolysis of peptidyl-tRNA.

The tnaC regulatory gene from the tna operon of Escherichia coli controls the transcription of its own operon through an attenuation mechanism relying on the accumulation of arrested ribosomes during inhibition of its own translation termination. This free l-Trp-dependent mechanism of inhibition of translation termination remains unclear. Here, we analyzed the inhibitory effects of l-Trp on the function of two known E. coli translation termination factors, RF1 and RF2. Using a series of reporter genes, we found that the in vivo l-Trp sensitivity of tnaC gene expression is influenced by the identity of its stop codon, with the UGA stop codon producing higher expression efficiency of the tnaA-lacZ gene construct than the UAG stop codon. In vitro TnaC-peptidyl-tRNA accumulation and toe-printing assays confirmed that in the presence of l-Trp, the UGA stop codon generates higher accumulation of both TnaC-peptidyl-tRNA and arrested ribosomes than does the UAG stop codon. RF-mediated hydrolysis assays corroborated that l-Trp blocks RF2 function more than that of RF1. Mutational analyses disclosed that amino acids substitutions at the 246 and 256 residue positions surrounding the RF2-GGQ functional motif reduce l-Trp-dependent expression of the tnaC(UGA) tnaA-lacZ construct and the ability of l-Trp to inhibit RF2-mediated cleavage of the TnaC-peptidyl-tRNA. Altogether, our results indicate that l-Trp preferentially blocks RF2 activity during translation termination of the tnaC gene. This inhibition depends on the identities of amino acid residues surrounding the RF2-GGQ functional motif.

History and physical exam predictors of intracranial injury in the elderly fall patient: A prospective multicenter study.

OBJECTIVES: A prior single-center study demonstrated historical and exam features predicting intracranial injury (ICI) in geriatric patients with low-risk falls. We sought to prospectively validate these findings in a multicenter population. METHODS: This is a prospective observational study of patients ≥65 years presenting after a fall to three EDs. Patients were eligible if they were at baseline mental status and were not triaged to the trauma bay. Fall mechanism, head strike history, headache, loss of consciousness (LOC), anticoagulants/antiplatelet use, dementia, and signs of head trauma were recorded. Radiographic imaging was obtained at the discretion of treating physicians. Patients were called at 30 days to determine outcome in non-imaged patients. RESULTS: 723 patients (median age 83, interquartile range 74-88) were enrolled. Although all patients were at baseline mental status, 76 had GCS <15, and 154 had dementia. 406 patients were on anticoagulation/antiplatelet agents. Fifty-two (7.31%) patients had traumatic ICI. Two study variables were helpful in predicting ICI: LOC (odds ratio (OR) 2.02) and signs of head trauma (OR 2.6). The sensitivity of these items was 86.5% (CI 73.6-94) with a specificity of 38.8% (CI 35.1-42.7). The positive predictive value in this population was 10% (CI 7.5-13.3) with a negative predictive value of 97.3% (CI 94.4-98.8). Had these items been applied as a decision rule, 273 patients would not have undergone CT scanning, but 7 injuries would have been missed. CONCLUSION: In low-risk geriatric fall patients, the best predictors of ICI were physical findings of head trauma and history of LOC.