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El presente trabajo se desarrolló en el municipio Cruces, provincia de Cienfuegos, Cuba. Se trazó como objetivo determinar los principales aspectos relacionados con la cría y explotación de los patos en el municipio Cruces, para promocionar su cría como fuente alternativa de alimentos e ingresos a las economías domésticas. El estudio es exploratorio y descriptivo, se parte de la observación y aplicación de encuestas a cien familias del Consejo Popular Potrerillo, elaborándose un diagrama causa-efecto, para esclarecer la situación respecto a la crianza de estas aves y una matriz FODA. Los resultados obtenidos apuntaron que la situación de la escasa producción, aprovechamiento y comercialización de los patos en el municipio Cruces, está dado por la baja comercialización de esta especie, el desconocimiento de los productos potenciales que genera y el desconocimiento de sus propiedades nutricionales. Esto trae consigo que su consumo no sea habitual, siendo relegada por otros productos cárnicos, además no se explotan los huevos y otros subproductos de esta ave. Se elaboró una propuesta de acciones para promover la crianza y el mejor aprovechamiento de los aptos por los pobladores del municipio. Se concluyó que los patos son animales rústicos, siendo factible su mantenimiento y desarrollo en los traspatios, existiendo múltiples oportunidades para la cría de patos en el territorio, por lo cual se elaboró un programa para fomentar la misma en el Consejo Popular Potrerillo, a partir de una serie de objetivos, sustentados sobre acciones concretas, a partir de la situación existente.

La presente investigación se desarrolló en la Estación de Investigaciones de la Caña de Azúcar de la provincia de Villa Clara, municipio Ranchuelo, Cuba, específicamente en la Biofábrica de la Caña de Azúcar. Se trazó como objetivo: Diagnosticar el clima organizacional en la Biofábrica de la Caña de Azúcar, perteneciente a la Estación Territorial de Investigaciones de la Caña de Azúcar de la provincia de Villa Clara. Se utilizó la metodología cualitativa, aplicándose la entrevista en profundidad, la observación participante, encuestas a los trabajadores y un cuestionario al equipo de dirección. Como resultado de la investigación se diagnosticó el estado del clima organizacional, el cual posee una serie de aspectos positivos como aplicación de medidas de protección a los trabajadores y otros. También posee aspectos negativos como exposición a sustancias químicas nocivas, limitaciones a la comunicación interpersonal impuestas por el proceso productivo, etc. Las principales conclusiones fueron que la organización posee valores propios y un adecuado desempeño en el puesto de trabajo, debiéndose trabajar en la motivación de sus miembros. El clima organizacional es susceptible de ser mejorado a través de la aplicación de acciones previamente planificadas, para satisfacer las inquietudes y expectativas de los miembros de la organización.

Bioreactors operating in fed-batch mode improve the enzymatic hydrolysis productivity at high biomass loadings. The present work aimed to apply rational feeding strategies of substrates (pretreated sugarcane straw) and enzymes (CellicCtec2®) to achieve sugar titers at industrial levels. The instantaneous substrate concentration was kept constant at 5% (w/v) along the fed-batch. The enzyme dosage inside the bioreactor was adjusted so that the reaction rate was not less than a pre-defined value (a percentage of the initial reaction rate – rmin). When r reached values below rmin, enzyme pulses were applied to return the reaction rate to its initial value (r0). The optimized feeding policy indicated a reaction rate maintained at a minimum of 70% of r0, based on the trade-off between glucose productivity and enzyme saving. Initially, it was possible to process a 21% (w/v) solid load, achieving 160 g/L of glucose concentration and 80% of glucose yield. It was verified that non-productive enzyme adsorption was the main reason for some reduction of hydrolysis yield regarding the theoretical cellulose-to-glucose conversion. An increment of 30 g/L in the final glucose concentration was achieved when a lignin-blocking additive (soybean protein) was used in the enzymatic hydrolysis.

Las inversiones constituyen una vía fundamental para el desarrollo de la base material y del crecimiento económico sostenido del país, en cuyo proceso se debe lograr la utilización más racional y eficiente de la cantidad significativa de recursos que participan en este proceso con el fin de lograr los mejores resultados técnicos, económicos y financieros, ya que se comprometen recursos actuales, deduciéndolos del consumo, con el propósito de alcanzar una expansión de éste en el futuro. El Estudio de Factibilidad es una parte integrante del proceso inversionista y constituye la culminación de los estudios de pre inversión y por lo tanto de la formulación y preparación de un proyecto, constituyendo la base de la decisión respecto a su ejecución. Los estudios de pre inversión, pueden pasar por las etapas previas de: Ideas Preliminares, Soluciones Principales o Ingeniería Básica respectivamente, en dependencia de la complejidad y características del proyecto y de los estudios que requiera. A cada una de estas etapas de pre inversión le corresponde un determinado grado de documentación de proyecto.

Introducción: El asma es una enfermedad psicosomática que reduce la calidad de vida de quien la padece, y tiene el riesgo de progresar en intensidad hasta producir daño e incapacidad permanente. Este texto recoge las experiencias de un estudio cuyo objetivo estuvo orientado a identificar las necesidades de aprendizaje de los licenciados en Enfermería del Policlínico Docente Reinol García, del consejo popular Versalles, perteneciente al municipio Matanzas, de la provincia cubana de igual nombre; acerca del manejo del paciente con asma bronquial. Método: El estudio mencionado tuvo carácter exploratorio descriptivo, desplegado como parte del Programa Nacional de Prevención del asma bronquial durante el período 2019-2020, acerca de las necesidades de aprendizaje de este personal para el manejo de tal situación de salud. El universo fue constituido por 31 licenciados, que laboran en los consultorios médicos y en el policlínico implicado en la investigación. Se aplicó un instrumento diseñado por un grupo de expertos y aplicado a la manera de un examen o prueba escrita por personal calificado, con carácter anónimo y previo consentimiento informado, sobre aspectos epidemiológicos, epistemológicos y teóricos prácticos. Resultados: Se constataron carencias y vacíos de conocimientos relacionados con el tema, de lo cual derivaronestrategias de superación profesional. Discusión: Los hallazgos constatados en la etapa experimental se corroboran con los resultados y criterios emitidos por especialistas y académicos que han profundizado en el tratamiento del tema.

Blanca Murillo-Ortiz,1 Sandra Martínez-Garza,1 Vanessa Cárdenas Landeros,1 Gerardo Cano Velázquez,1 David Suárez García2 1Clinical Epidemiology Research Unit, 2Department of Oncology, Mexican Institute of Social Security, Leon, Mexico Introduction: In recent years, epidemiological studies have strongly related obesity with an increased risk of developing postmenopausal breast cancer. The aromatization of fatty tissue increases the levels of estradiol and adiponectin, which is correlated with the body mass index (BMI). It is of interest to investigate the effect of reducing BMI on estradiol, adiponectin, and IGF-1, as reducing BMI could be a new strategy to limit the risk of recurrence during the adjuvant treatment of breast cancer.Objective: The aim of this study is to investigate the effect of reduced dietary fat on the levels of serum estradiol, adiponectin, and IGF-1 among postmenopausal Mexican women with breast cancer.Methods: In this controlled clinical trial, 100 female patients were randomly divided into two groups and followed for six months. Group 1 (n = 50) was subjected to reduced dietary fat, whereas Group 2 (n = 50) was subjected to a control diet. The levels of serum estradiol and testosterone were determined using an enzyme-linked immunosorbent assay, whereas the concentrations of adiponectin and IGF-1 were determined using a radioimmunoassay.Results: The patients subjected to reduced dietary fat showed a significant difference in BMI (27.93 ± 4.45 vs 26.05 ± 2.65; p = 0.01) and waist circumference (99.92 vs 91.59 cm; p = 0.0001) after the treatment. Moreover, a significant decrease in serum estradiol was observed (21.23 ± 14.32 vs 16.05 ± 10.25 ng/mL; p < 0.001). The adiponectin concentration also decreased significantly (47.53 ± 12.19 vs 42.52 ± 12.34 µg/mL; p = 0.004), while IGF-1 and testosterone did not show significant changes (p > 0.05). In addition, BMI had a relationship with serum adiponectin (r = −0.27; p = 0.02) and estradiol (r = 0.37; p = 0.001).Conclusion: The current study shows that reducing BMI decreases serum estradiol and adiponectin. Large clinical trials are needed to investigate the role of adiponectin in breast cancer development in obese women. Keywords: reduced dietary fat, breast cancer, hormone levels

Blanca Murillo-Ortiz,1 Sandra Martínez-Garza,1 David Suárez García,1 Rosa del Carmen Castillo Valenzuela,2 Juan Francisco García Regalado,2 Gerardo Cano Velázquez1 1Institute Mexican of Social Security, Department Oncology, Unit of Research in Clinical Epidemiology, 2Department of Medical Sciences, University of Guanajuato, León Guanajuato, Mexico Introduction: Several studies have reported an increase in breast cancer (BC) risk when patients are carriers of the CYP19 TTA polymorphism with ≥10 repeats; moreover, it has been reported that telomere length is associated with a higher susceptibility of developing cancer. Objective: The objective of this study was to understand the relationship between CYP19 TTTA repetition polymorphism and telomere length and its effects on serum estradiol, estrone and follicle-stimulating hormone (FSH). Materials and methods: A total of 180 postmenopausal healthy and 70 BC-diagnosed women were included. Telomere length was determined through real-time quantitative polymerase chain reaction, and aromatase polymorphism was analyzed through DNA; both samples were obtained from circulating leukocytes. Serum estrone, estradiol and FSH were determined by enzyme-linked immunosorbent assay. Results: Patients with a BC diagnosis showed >10 repetitions more frequently, compared with that of healthy women (50% vs 23%, Χ2 =11.44, p=0.0007). A significant difference in telomere length between healthy and BC women was observed (5,042.7 vs 2,256.7 pb, Z=4.88, p10 repeats. Moreover, telomere length showed an inverse relationship with the number of repeats of the aromatase polymorphism in healthy women (R2=0.04, r= -0.24); in contrast, BC patients did not display this relationship. In addition, telomere length presented an inverse relationship with serum levels of estradiol and estrone in BC patients (p=0.02). Conclusion: Telomere length is shorter in BC patients than in healthy patients. The CYP19 TTTA repeat polymorphism is associated with serum levels of estradiol and estrone in both healthy women and BC patients, being higher in those with polymorphism carriers >10 repeats. Telomere length has an inverse correlation with the number of repeats of the aromatase polymorphism in healthy women but not in BC women. Estradiol and estrone levels in BC women have an inverse relationship with telomere length. Keywords: telomere length, CYP19 polymorphism, breast cancer

Introduction: Urinary tract infection (UTI) is a major cause of bacterial disease in the pediatric population. Associated factors such as vesicoureteral reflux (VUR), posterior urethral valves, neurogenic bladder and other anatomical malformations increase the likelihood of developing renal scarring and dysplasia/hypoplasia, which at the same time increase in the long term the risk of hypertension (HT), proteinuria and chronic kidney disease (CKD). Objective: To describe the malformations associated with the frequency of UTI and development of CKD in pediatric patients who consulted San Vicente de Paúl Hospital, in Medellin, Colombia, between 1960 and 2010. Methods: A descriptive, retrospective study in which the clinical records of 4.476 patients with UTI were evaluated. Results: Patients with urinary tract anomalies corresponded to 78.3% of the total (predominance of women: 52.8%). Primary VUR was found in 29.9%; out of these, 5.1% progressed to CKD. Neurogenic bladder was diagnosed in 8.6%, of which 70.8% were secondary to myelomeningocele and 4.9% developed CKD. The posterior urethral valves were present in 3.5% of the total sample, of which 28.5% developed CKD. Conclusion: UTI in the pediatric population is a marker of urinary tract malformation and the prognosis is determined by the presence of VUR, obstructive anomalies and/or renal dysplasia favoring renal scarring, and increasing the risk of hypertension, proteinuria and CKD. An appropriate diagnostic approach would be the basis to implement management strategies to prevent deterioration of renal function.

Fundamento: Algunas características sociales, médicas o funcionales se asocian a mayor consumo de recursos sanitarios, sin que esto signifique un uso inapropiado de éstos. El objetivo de este trabajo es conocer la influencia del estado de salud y otros factores sobre las estancias hospitalarias y las estancias inapropiadas en la población mayor de 64 años. Método: Una cohorte representativa de la población mayor de 64 años del Partido Judicial de Toledo (n=3.214) en la que se había valorado el estado de salud, fue seguida durante 18 meses, identificando sus ingresos y estancias hospitalarias, cuya adecuación fue evaluada con el Appropiateness Evaluation Protocol. Se analizaron las asociaciones entre las características socio-demográficas, de estado de salud y morbilidad de la cohorte con las tasas de frecuentación y hospitalización y con la proporción de estancias e ingresos inadecuados. Resultados: Durante los 18 meses de seguimiento fueron hospitalizados 410 individuos (12,8%), que generaron 546 ingresos (tasa de frecuentación=17,0 ingresos/100 habitantes) y 7.015 días de estancia (tasa de hospitalización = 218,3 estancias/100 habitantes). El 18,9% de los ingresos y el 49,9% de las estancias fueron evaluadas como inadecuados. La hospitalización se asoció al peor estado de salud, institucionalización, género masculino, determinadas patologías y a la utilización previa de servicios sanitarios. No se hallaron asociaciones entre características de los pacientes y proporción de estancias inadecuadas. El 97,5% de las estancias innecesarias fue atribuido a problemas de programación hospitalaria y estilo de practica de los médicos. Conclusiones: Los factores socio-demográficos, de morbilidad, estado de salud y utilización previa de servicios se muestran como buenos predictores de hospitalización en las personas mayores, pero no se relacionan con el uso inadecuado de la hospitalización.

FUNDAMENTO: El estado de salud y algunas características clínicas configuran un grupo de ancianos que necesitan más cuidados, que podrían beneficiarse de asistencia geriátrica especializada, aunque no existe consenso para identificar estos pacientes. El objetivo de este trabajo es describir el perfil de los pacientes mayores de 64 años ingresados en una unidad geriátrica y compararlo con los mayores de esta edad ingresados en los servicios médicos y quirúrgicos. MÉTODO: Durante 18 meses se siguió una cohorte representativa de la población mayor de 64 años del Partido Judicial de Toledo (n=3214), para identificar los ingresos y estancias hospitalarias en los hospitales públicos del área sanitaria. Las variables sobre estado de salud, se recogieron por entrevista personal, y los ingresos y sus características según datos del servicio de admisiones hospitalario. RESULTADOS: Ingresaron 410 personas (12,8%), en geriatría 168 pacientes (30,7%), en servicios médicos 204 (37,3%) y en servicios quirúrgicos 174 (32,0%). En geriatría la edad media fue significativamente mayor (77,4 años), sin diferencias en la estancia media (12,8 días;IC95%:10,6-14,0), fallecieron 44 pacientes (8,1%), ingresados en geriatría 26 (59,1%). En los servicios quirúrgicos ingresaron más mujeres, pacientes más jóvenes y con déficit leve de visión y audición; en geriatría, respecto a servicios médicos, más pacientes mayores de 80 años, viviendo en residencias, sin pareja, dependencia funcional moderada-severa, deterioro cognitivo, depresión, mala calidad de vida y escasos recursos sociales. CONCLUSIONES: No se observaron diferencias en el estado de salud entre los mayores de 64 años ingresados en servicios no quirúrgicos y quirúrgicos. En geriatría, respecto a los otros grupos de servicios, los pacientes tuvieron una edad media más elevada, peor estado de salud, mayor mortalidad y estancia media similar.

Many factors control the elongation phase of transcription by RNA polymerase II (Pol II), a process that plays an essential role in regulating gene expression. We utilized cells expressing degradation tagged subunits of NELFB, PAF1 and RTF1 to probe the effects of depletion of the factors on nascent transcripts using PRO-Seq and on chromatin architecture using DFF-ChIP. Although NELF is involved in promoter proximal pausing, depletion of NELFB had only a minimal effect on the level of paused transcripts and almost no effect on control of productive elongation. Instead, NELF depletion increased the utilization of downstream transcription start sites and caused a dramatic, genome-wide loss of H3K4me3 marked nucleosomes. Depletion of PAF1 and RTF1 both had major effects on productive transcript elongation in gene bodies and also caused initiation site changes like those seen with NELFB depletion. Our study confirmed that the first nucleosome encountered during initiation and early elongation is highly positioned with respect to the major TSS. In contrast, the positions of H3K4me3 marked nucleosomes in promoter regions are heterogeneous and are influenced by transcription. We propose a model defining NELF function and a general role of the H3K4me3 modification in blocking transcription initiation., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

How human cytomegalovirus (HCMV) infection impacts the transcription of the host genome remains incompletely understood. Here, we examine the global consequences of infection of primary human foreskin fibroblasts (HFFs) on transcription by RNA polymerase I, II, and III over the course of a lytic infection using PRO-Seq. The expected rapid induction of innate immune response genes is observed with specific subsets of genes exhibiting dissimilar expression kinetics. We find minimal effects on Pol II initiation, but increased rates of the release of paused Pol II into productive elongation are detected by 24 h postinfection and pronounced at late times postinfection. Pol I transcription increases during infection and we provide evidence for a potential Pol I elongation control mechanism. Pol III transcription of tRNA genes is dramatically altered, with many induced and some repressed. All effects are partially dependent on viral genome replication, suggesting a link to viral mRNA levels and/or a viral early-late or late gene product. Changes in tRNA transcription are connected to distinct alterations in the chromatin state around tRNA genes, which were probed with high-resolution DFF-ChIP. Additionally, evidence is provided that the Pol III PIC stably contacts an upstream -1 nucleosome. Finally, we compared and contrasted our HCMV data with results from published experiments with HSV-1, EBV, KSHV, and MHV68. We report disparate effects on Pol II transcription and potentially similar effects on Pol III transcription.

Approximately half of purified mammalian RNA polymerase II (Pol II) is associated with a tightly interacting sub-stoichiometric subunit, Gdown1. Previous studies have established that Gdown1 inhibits transcription initiation through competitive interactions with general transcription factors and blocks the Pol II termination activity of transcription termination factor 2 (TTF2). However, the biological functions of Gdown1 remain poorly understood. Here, we utilized genetic, microscopic, and multi-omics approaches to functionally characterize Gdown1 in three human cell lines. Acute depletion of Gdown1 caused minimal direct effects on transcription. We show that Gdown1 resides predominantly in the cytoplasm of interphase cells, shuttles between the cytoplasm and nucleus, and is regulated by nuclear export. Gdown1 enters the nucleus at the onset of mitosis. Consistently, genetic ablation of Gdown1 is associated with partial de-repression of mitotic transcription, and Gdown1 KO cells present with evidence of aberrant mitoses coupled to p53 pathway activation. Evidence is presented demonstrating that Gdown1 modulates the combined functions of purified productive elongation factors PAF1C, RTF1, SPT6, DSIF and P-TEFb in vitro. Collectively, our findings support a model wherein the Pol II-regulatory function of Gdown1 occurs during mitosis and is required for genome integrity., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

In Colombia, the human papillomavirus (HPV) vaccine was launched in 2012 in the context of a school-based national vaccination program targeting girls ages 9 to 14 and offering catch-up vaccination for girls ages 14 to 17. In this study, we evaluated the program's impact on type-specific HPV infection by comparing HPV cervical prevalence among vaccinated and nonvaccinated women. This is a comparative cross-sectional study conducted 5 years after the quadrivalent HPV vaccination implementation in a sentinel Colombian City. This study included young women (18-25 years old) who had been vaccinated in the catch-up group and were attending universities and technical institutions, and women who attended primary health care facilities for Pap smear screening. The HPV prevalence of 1,287 unvaccinated women was compared with the prevalence of 1,986 vaccinated women. The prevalence of HPV16/18 infections was significantly lower in vaccinated compared with unvaccinated women (6.5% vs. 15.4%; P < 0.001), whereas for HPV6/11 infections, a decrease of 63.7% in vaccinated women (1.02% vs. 2.81%) was observed. The adjusted effectiveness to HPV16/18 was 61.4%; 95% CI, 54.3%-67.6%. However, the effectiveness against HPV16/18 was significantly higher among women vaccinated before their sexual debut 91.5%; 95% CI, 86.8-94.5, compared with effectiveness for vaccination after their sexual debut, 36.2%; 95% CI, 23.6-46.7. Five years after the introduction of HPV vaccines in Colombia, high effectiveness of HPV to prevent HPV16/18 infections is observed in the catch-up cohorts including virgin and sexually active women. PREVENTION RELEVANCE: Monitoring HPV vaccines post-licensure plays an important role in assessing the progress of immunization programs, demonstrating the impact of vaccines on the population, and providing data for policy needs. In Colombia, HPV vaccines showed effectiveness when administered before start of sexual activity, and two doses are sufficient to achieve good protection., (©2021 The Authors; Published by the American Association for Cancer Research.)

Although myriad studies document the benefits of parental involvement in education on various indicators of children's academic performance, less research examines parental involvement among adolescents in low-income Latino families. Incorporating a multidimensional conceptualization of parental involvement, this study examined the relation between parental involvement and academic outcomes in a sample of 223 low-income, Latino adolescents. Results indicated that three types of parental involvement (gift/sacrifice, future discussions/academic socialization, and school involvement) had significant, positive associations with academic outcomes. Moreover, our results suggest that parents' stories about struggles with poverty and immigration are an important component of parental involvement, contributing to adolescents' desire to succeed academically and "give back" to parents. Additionally, our findings indicated that the positive relations between parental involvement and academic outcomes were stronger for immigrant youth and for those with higher endorsements of the Latino cultural value of respeto (respect).

Objective: To develop a concise and statistically robust instrument to assess autonomic symptoms that provides clinically relevant scores of autonomic symptom severity based on the well-established 169-item Autonomic Symptom Profile (ASP) and its validated 84-question scoring instrument, the Composite Autonomic Symptom Score (COMPASS)., Patients and Methods: We assessed the internal consistency of COMPASS using Cronbach α coefficients based on the ASP of 405 healthy control subjects recruited and seen in the Mayo Clinic Autonomic Disorders Center between March 1, 1995, and March 31, 2010. Applying a simplified scoring algorithm, we then used exploratory factor analysis with orthogonal rotation and eigenvalue calculations to extract internally consistent domains and to reduce dimensionality. This analysis was followed by expert revisions to eliminate redundant content and to retain clinically important questions and final assessment of the new instrument., Results: The new simplified scoring algorithm alone resulted in higher Cronbach α values in all domains. Factor analysis revealed 7 domains with a total of 54 questions retained. Expert revisions resulted in further reduction of questions and domains with a remaining total of 31 questions in 6 domains (COMPASS 31). Measures of internal consistency were much improved compared to those for COMPASS. Following appropriate weighting, this instrument provides an autonomic symptom score from 0 to 100., Conclusion: COMPASS 31 is a refined, internally consistent, and markedly abbreviated quantitative measure of autonomic symptoms. It is based on the original ASP and COMPASS, applies a much simplified scoring algorithm, and is suitable for widespread use in autonomic research and practice., (Copyright © 2012 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objective: POEMS syndrome (the acronym reflects the common features: Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein and Skin changes) is a paraneoplastic disorder with a 'demyelinating' peripheral neuropathy that is often mistaken for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The nerve conduction study (NCS) and electromyography (EMG) attributes that might differentiate POEMS from CIDP and lead to earlier therapeutic intervention were explored., Methods: NCS/EMG of POEMS patients identified through retrospective review from 1960 to 2007 were compared with matched CIDP controls., Results: 138 POEMS patients and 69 matched CIDP controls were compared. POEMS patients demonstrated length dependent reduction in compound muscle action potentials, low conduction velocities, prolonged distal latencies and prolonged F wave latencies. Compared with CIDP controls, POEMS patients demonstrated: (1) greater reduction of motor amplitudes, (2) greater slowing of motor and sensory conduction velocities, (3) less prolonged motor distal latencies, (4) less frequent temporal dispersion and conduction block, (5) no sural sparing, (6) greater number of fibrillation potentials in a length dependent pattern and (7) higher terminal latency indices (TLI). TLI ≥0.38 in the median nerve demonstrated a sensitivity of 70% and specificity of 77% in discriminating POEMS from CIDP., Conclusions: NCS/EMG of POEMS syndrome suggests both axonal loss and demyelination. Compared with CIDP, there is greater axonal loss (reduction of motor amplitudes and increased fibrillation potentials), greater slowing of the intermediate nerve segments, less common temporal dispersion and conduction block, and absent sural sparing. These findings imply that the pathology of POEMS syndrome is diffusely distributed (uniform demyelination) along the nerve where the pathology of CIDP is probably predominantly proximal and distal. Median motor TLI may be useful in clinically distinguishing these disorders.

Background: Knowledge about the distribution of human papillomavirus (HPV) genotypes in invasive cervical cancer is crucial to guide the introduction of prophylactic vaccines. We aimed to provide novel and comprehensive data about the worldwide genotype distribution in patients with invasive cervical cancer., Methods: Paraffin-embedded samples of histologically confirmed cases of invasive cervical cancer were collected from 38 countries in Europe, North America, central South America, Africa, Asia, and Oceania. Inclusion criteria were a pathological confirmation of a primary invasive cervical cancer of epithelial origin in the tissue sample selected for analysis of HPV DNA, and information about the year of diagnosis. HPV detection was done by use of PCR with SPF-10 broad-spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridisation line probe assay. Sequence analysis was done to characterise HPV-positive samples with unknown HPV types. Data analyses included algorithms of multiple infections to estimate type-specific relative contributions., Findings: 22,661 paraffin-embedded samples were obtained from 14,249 women. 10,575 cases of invasive cervical cancer were included in the study, and 8977 (85%) of these were positive for HPV DNA. The most common HPV types were 16, 18, 31, 33, 35, 45, 52, and 58 with a combined worldwide relative contribution of 8196 of 8977 (91%, 95% CI 90-92). HPV types 16 and 18 were detected in 6357 of 8977 of cases (71%, 70-72) of invasive cervical cancer. HPV types 16, 18, and 45 were detected in 443 of 470 cases (94%, 92-96) of cervical adenocarcinomas. Unknown HPV types that were identified with sequence analysis were 26, 30, 61, 67, 69, 82, and 91 in 103 (1%) of 8977 cases of invasive cervical cancer. Women with invasive cervical cancers related to HPV types 16, 18, or 45 presented at a younger mean age than did those with other HPV types (50·0 years [49·6-50·4], 48·2 years [47·3-49·2], 46·8 years [46·6-48·1], and 55·5 years [54·9-56·1], respectively)., Interpretation: To our knowledge, this study is the largest assessment of HPV genotypes to date. HPV types 16, 18, 31, 33, 35, 45, 52, and 58 should be given priority when the cross-protective effects of current vaccines are assessed, and for formulation of recommendations for the use of second-generation polyvalent HPV vaccines. Our results also suggest that type-specific high-risk HPV-DNA-based screening tests and protocols should focus on HPV types 16, 18, and 45., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Neoplastic lumbosacral plexopathy occurs with some abdominal and pelvic malignancies. Patients present with severe pain radiating from the low back down to the lower extremities, and this progresses to weakness. Neoplastic lumbosacral plexopathy is virtually always associated with known malignancy or obvious pelvic metastatic disease. Uncommonly, prostate cancer can present as a lumbosacral plexopathy occurring through direct pelvic spread. We describe two cases of lumbosacral radiculoplexopathy from infiltrative prostate cancer without evidence of other pelvic or extraprostatic spread. The probable etiology of tumor spreading along prostatic nerves into the lumbosacral plexus (i.e., perineural spread) is discussed as are the potential mechanisms for this unusual mode of cancer dissemination.

Background: Midodrine hydrochloride is the only drug demonstrated in a placebo-controlled treatment trial to improve orthostatic hypotension (OH) but it significantly worsens supine hypertension. By enhancing ganglionic transmission, pyridostigmine bromide can potentially ameliorate OH without worsening supine hypertension., Objective: To evaluate the efficacy of a single 60-mg dose of pyridostigmine bromide, alone or in combination with a subthreshold (2.5 mg) or suprathreshold (5 mg) dose of midodrine hydrochloride, compared with placebo., Design: We report a double-blind, randomized, 4-way cross-over study of pyridostigmine in the treatment of neurogenic OH. A total of 58 patients with neurogenic OH were enrolled. After 1 day of baseline measurements, patients were given 4 treatments (3 active treatments [60 mg of pyridostigmine bromide; 60 mg of pyridostigmine bromide and 2.5 mg of midodrine hydrochloride; 60 mg of pyridostigmine bromide and 5 mg of midodrine hydrochloride] and a placebo) in random order on successive days. Blood pressure (BP) and heart rate were measured, both supine and standing, immediately before treatment and hourly for 6 hours after the treatment was given., Results: No significant differences were seen in the supine BP, either systolic (P = .36) or diastolic (P = .85). In contrast, the primary end point of the fall in standing diastolic BP was significantly reduced (P = .02) with treatment. Pairwise comparison showed significant reduction by pyridostigmine alone (BP fall of 27.6 mm Hg vs 34.0 mm Hg with placebo; P = .04) and pyridostigmine and 5 mg of midodrine hydrochloride (BP fall of 27.2 mm Hg vs 34.0 mm Hg with placebo; P = .002). Standing BP improvement significantly regressed with improvement in OH symptoms., Conclusions: Pyridostigmine significantly improves standing BP in patients with OH without worsening supine hypertension. The greatest effect is on diastolic BP, suggesting that the improvement is due to increased total peripheral resistance.

Postural orthostatic tachycardia syndrome (POTS) is characterized by excessive tachycardia during orthostasis. To test the hypothesis that patients with POTS have decreased sympathetic neural responses to baroreflex stimuli, we measured heart rate (HR) and muscle sympathetic nerve activity (MSNA) responses to three baroreflex stimuli including vasoactive drug boluses (modified Oxford technique), Valsalva maneuver, and head-up tilt (HUT) in POTS patients and healthy control subjects. The MSNA response to the Valsalva maneuver was significantly greater in the POTS group (controls, 26 +/- 7 vs. POTS, 48 +/- 6% of baseline MSNA/mmHg; P = 0.03). POTS patients also had an exaggerated MSNA response to 30 degrees HUT (controls, 123 +/- 24 vs. POTS, 208 +/- 30% of baseline MSNA; P = 0.03) and tended to have an exaggerated response to 45 degrees HUT (controls, 137 +/- 27 vs. POTS, 248 +/- 58% of baseline MSNA; P = 0.10). Sympathetic baroreflex sensitivity calculated during administration of the vasoactive drug boluses also tended to be greater in the POTS patients; however, this did not reach statistical significance (P = 0.15). Baseline MSNA values during supine rest were not different between the groups (controls, 23 +/- 4 vs. POTS, 16 +/- 5 bursts/100 heartbeats; P = 0.30); however, resting HR was significantly higher in the POTS group (controls, 58 +/- 3 vs. POTS, 82 +/- 4 beats/min; P = 0.0001). Our results suggest that POTS patients have exaggerated MSNA responses to baroreflex challenges compared with healthy control subjects, although resting supine MSNA values did not differ between the groups.

Objectives: To determine risk factors for sudden cardiac death and the role of diabetic autonomic neuropathy (DAN) in the Rochester diabetic neuropathy study (RDNS)., Methods: Associations between diabetic and cardiovascular complications, including DAN, and the risk of sudden cardiac death were studied among 462 diabetic patients (151 type 1) enrolled in the RDNS. Medical records, death certificates, and necropsy reports were assessed for causes of sudden cardiac death., Results: 21 cases of sudden cardiac death were identified over 15 years of follow up. In bivariate analysis of risk covariates, the following were significant: ECG 1 (evolving and previous myocardial infarctions): hazard ratio (HR) = 4.4 (95% confidence interval (CI), 1.6 to 12.1), p = 0.004; ECG 2 (bundle branch block or pacing): HR = 8.6 (2.9 to 25.4), p<0.001; ECG 1 or ECG 2: HR = 4.2 (1.3 to 13.4), p = 0.014; and nephropathy stage: HR = 2.1 (1.3 to 3.4), p = 0.002. Adjusting for ECG 1 or ECG 2, autonomic scores, QTc interval, high density lipoprotein (HDL) cholesterol, 24 hour microalbuminuria, and 24 hour total proteinuria were significant. However, adjusting for nephropathy, none of the autonomic indices, QTc interval, HDL cholesterol, microalbuminuria, or total proteinuria was significant. At necropsy, all patients with sudden cardiac death had coronary artery or myocardial disease., Conclusions: Sudden cardiac death was correlated with atherosclerotic heart disease and nephropathy, and to a lesser degree with DAN and HDL cholesterol. Although DAN is associated with sudden cardiac death, it is unlikely to be its primary cause.

Objective: The prevalence of autonomic symptoms and deficits in certain systems is known, but a comprehensive autonomic symptom profile in diabetes is not available. We aimed to estimate this using a laboratory evaluation of autonomic function and a validated self-report measure of autonomic symptoms in patients and matched control subjects from the population-based Rochester Diabetic Neuropathy Study., Research Design and Methods: Participants included 231 patients with diabetes (type 1, n=83; type 2, n=148) and 245 healthy age-matched control subjects. We assessed symptoms using a validated self-report instrument (Autonomic Symptom Profile) and evaluated the severity and distribution of autonomic deficits (cardiovagal, sudomotor, adrenergic) with the objective, laboratory-based Composite Autonomic Severity Score (CASS)., Results: Autonomic symptoms were present more commonly in type 1 than in type 2 diabetes, with symptoms of orthostatic intolerance, secretomotor, urinary control, diarrhea, and sleep disturbance and pupillomotor, vasomotor, and erectile dysfunction significantly increased over healthy control subjects in type 2 diabetic patients. The prevalence of autonomic impairment was 54% in type 1 and 73% in type 2 diabetic patients. Severity of autonomic failure was mild overall (mean CASS 2.3; maximum 10), with orthostatic hypotension occurring in 8.4 and 7.4% of type 1 and 2 diabetic patients, respectively. Fourteen percent of patients had a CASS > or =5, indicating moderate to severe generalized autonomic failure. The correlation of symptoms with autonomic deficits (CASS) was better in type 1 than type 2 diabetic subjects and was weak overall., Conclusions: These findings indicate that autonomic symptoms and deficits are common in diabetes, but mild in severity, and that the correlation between symptom scores and deficits is overall weak in mild diabetic neuropathy, emphasizing the need to separately evaluate autonomic symptoms.

POEMS syndrome is characterized by peripheral neuropathy (PN), a clonal plasma cell disorder (PCD), organomegaly, endocrinopathy, skin changes, edema, sclerotic bone lesions, and thrombocytosis. Based on the improved response rates observed with peripheral blood stem cell transplantation (PBSCT) in patients with other PCDs, autologous PBSCT may be an attractive treatment option for this syndrome. Sixteen patients with POEMS syndrome have undergone PBSCT at Mayo. Of these patients, 15 had a severe rapidly progressive sensorimotor PN (9 were wheelchair dependent) and 14 were male. Median age was 51 years (range, 19-62 years). The median number of prior therapies was 3 (range, 0-7). From first symptoms and from diagnosis of POEMS the times to transplantation were 42 months and 5 months (ranges, 8-185 months and 2-149 months), respectively. There were 15 patients who had significantly abnormal pretransplant pulmonary function tests. There was one transplant-related death. During the peritransplant period, 5 patients required intubation for respiratory compromise, including one who required intubation during his stem cell mobilization period. Another patient required noninvasive biphasic positive airway pressure throughout his course. Of the 14 evaluable patients, all have had neurologic improvement or stabilization. Other features have improved substantially. PBSCT for POEMS syndrome is effective therapy but may also be associated with significant morbidity.

The POEMS syndrome (coined to refer to polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) remains poorly understood. Ambiguity exists over the features necessary to establish the diagnosis, treatment efficacy, and prognosis. We identified 99 patients with POEMS syndrome. Minimal criteria were a sensorimotor peripheral neuropathy and evidence of a monoclonal plasmaproliferative disorder. To distinguish POEMS from neuropathy associated with monoclonal gammopathy of undetermined significance, additional criteria were included: a bone lesion, Castleman disease, organomegaly (or lymphadenopathy), endocrinopathy, edema (peripheral edema, ascites, or effusions), and skin changes. The median age at presentation was 51 years; 63% were men. Median survival was 165 months. With the exception of fingernail clubbing (P =.03) and extravascular volume overload (P =.04), no presenting feature, including the number of presenting features, was predictive of survival. Response to therapy (P <.001) was predictive of survival. Pulmonary hypertension, renal failure, thrombotic events, and congestive heart failure were observed and appear to be part of the syndrome. In 18 patients (18%), new disease manifestations developed over time. More than 50% of patients had a response to radiation, and 22% to 50% had responses to prednisone and a combination of melphalan and prednisone, respectively. We conclude that the median survival of patients with POEMS syndrome is 165 months, independent of the number of syndrome features, bone lesions, or plasma cells at diagnosis. Additional features of the syndrome often develop, but the complications of classic multiple myeloma rarely develop.

Three masked neuromuscular experts analyzed the contribution of the data from sequential evaluations in predicting specific varieties of peripheral neuropathy in 72 patients. The largest improvement (16%) in diagnostic accuracy resulted from presentation of neurologic history. By contrast, diagnostic confidence increased gradually with presentation of additional medical information. Therefore, the authors conclude that for diagnostic accuracy and certainty, expert neuromuscular judgment and extensive characterizing or discriminative testing are needed.

A 62-year-old woman presented with episodic sweating and shivering with reduced core temperature. Brain MRI demonstrated a basal forebrain malformation. Physiologic testing included EEG, SPECT, heat challenge, and autonomic testing. Glycopyrrolate aborted spells and raised core temperature. Hypothalamic dysregulation is likely the primary pathophysiology in the setting of other forebrain anomalies. These findings expand the structural abnormalities and treatment options within the temperature dysregulating conditions of Shapiro's syndrome and "diencephalic epilepsy."

The authors describe the clinical and electrophysiologic findings in a patient with synkinesis between muscles innervated by the facial and trigeminal nerves after resection of a trigeminal schwannoma. Conventional facial nerve conduction and blink reflex studies were normal. Stimulation of the supraorbital and facial nerves elicited reproducible responses in the masseter and pterygoid muscles, confirming a peripheral site of aberrant regeneration of the facial and trigeminal nerves.

We report brachial plexus biopsy findings from two Australian and two American patients with brachial plexus neuropathy. There were florid multifocal mononuclear inflammatory cell infiltrates. Present evidence suggests that these brachial neuropathies have an immune basis.

There is a family of diabetic neuropathies that mimic the entire spectrum of peripheral neuropathies. Distal sensory neuropathy is the most common. In small-fibre neuropathy, autonomic failure and loss of sense of pain and temperature are prominent. Painfulness is seen in a number of diabetic neuropathies. The asymmetric neuropathies are distinctive and are probably caused by a combination of microvascular and immune-mediated mechanisms. The pathogenesis of diabetic neuropathy is probably multifactorial. Hyperglycaemia is central to any pathogenic scheme whereby nerve blood flow is reduced by an effect on microvessels mediated by perturbations such as oxidative stress, reduction of nitric oxide, prostaglandins and an increase in endothelin. It may also affect nerve fibres directly. Recent clinical trials have clearly demonstrated the importance of strict glycaemic control. There is also support for essential fatty acids, antioxidants and aldose reductase inhibitors. Treatment of diabetic neuropathy is focused on improving glycaemic control and treatment of symptoms. The precise role of other modalities of treatment of diabetic neuropathy remain to be firmly established.

Objective: To undertake a prospective study of the clinical characteristics of orthostatic intolerant patients referred to the Mayo Autonomic Reflex Laboratory with suspected orthostatic hypotension (OH)., Design: Autonomic function tests were performed to quantify the severity of sudomotor, adrenergic, and cardiovagal failure and generate a composite autonomic symptom score (CASS). CASS was related to a symptom score, which was derived from the frequency of orthostatic intolerance and syncope and the standing time until occurrence of symptoms., Results: Three groups were defined by their response to a tilt study: group I, 90 patients with symptomatic OH, mean age, 63.6 years; group II, 60 patients who had symptoms without OH, mean age, 48.9 years; and group III, 5 patients with asymptomatic OH, mean age, 68.0 years. Group I had a significantly higher CASS (P < 0.001) than did those without OH. Further analysis was done on the 90 patients in group I. The most common symptoms were lightheadedness, weakness, impaired cognition, visual blurring, tremulousness, and vertigo. The most common aggravating factors were prolonged standing, exercise, warming, and eating. Most patients (75%) could stand for less than 5 minutes before symptoms occurred. Symptoms regressed significantly with CASS but not with the tilt grade., Conclusion: Patients with generalized autonomic failure have a recognizable pattern of symptoms and aggravating factors that relate, albeit imperfectly, to the severity of autonomic failure.

In orthostatic intolerance, the patient develops symptoms while standing that are relieved when the patient assumes a supine position. Different degrees of orthostatic intolerance exist, but not a system of grading severity. We have developed a system that grades the severity of orthostatic intolerance by the three-pronged criteria of the rapidity of development and the severity of orthostatic symptoms, the ability of the subject to withstand orthostatic stresses, and the degree of interference with daily living. In this article, this system is presented, and one disorder, postural tachycardia syndrome (POTS), is examined in some detail.