Running speed and REM sleep control two distinct modes of rapid interhemispheric communication.

Rhythmic gamma-band communication within and across cortical hemispheres is critical for optimal perception, navigation, and memory. Here, using multisite recordings in both rats and mice, we show that even faster ∼140 Hz rhythms are robustly anti-phase across cortical hemispheres, visually resembling splines, the interlocking teeth on mechanical gears. Splines are strongest in superficial granular retrosplenial cortex, a region important for spatial navigation and memory. Spline-frequency interhemispheric communication becomes more coherent and more precisely anti-phase at faster running speeds. Anti-phase splines also demarcate high-activity frames during REM sleep. While splines and associated neuronal spiking are anti-phase across retrosplenial hemispheres during navigation and REM sleep, gamma-rhythmic interhemispheric communication is precisely in-phase. Gamma and splines occur at distinct points of a theta cycle and thus highlight the ability of interhemispheric cortical communication to rapidly switch between in-phase (gamma) and anti-phase (spline) modes within individual theta cycles during both navigation and REM sleep.

Defect patterns on the curved surface of fish retinae suggest a mechanism of cone mosaic formation.

The outer epithelial layer of zebrafish retinae contains a crystalline array of cone photoreceptors, called the cone mosaic. As this mosaic grows by mitotic addition of new photoreceptors at the rim of the hemispheric retina, topological defects, called "Y-Junctions", form to maintain approximately constant cell spacing. The generation of topological defects due to growth on a curved surface is a distinct feature of the cone mosaic not seen in other well-studied biological patterns like the R8 photoreceptor array in the Drosophila compound eye. Since defects can provide insight into cell-cell interactions responsible for pattern formation, here we characterize the arrangement of cones in individual Y-Junction cores as well as the spatial distribution of Y-junctions across entire retinae. We find that for individual Y-junctions, the distribution of cones near the core corresponds closely to structures observed in physical crystals. In addition, Y-Junctions are organized into lines, called grain boundaries, from the retinal center to the periphery. In physical crystals, regardless of the initial distribution of defects, defects can coalesce into grain boundaries via the mobility of individual particles. By imaging in live fish, we demonstrate that grain boundaries in the cone mosaic instead appear during initial mosaic formation, without requiring defect motion. Motivated by this observation, we show that a computational model of repulsive cell-cell interactions generates a mosaic with grain boundaries. In contrast to paradigmatic models of fate specification in mostly motionless cell packings, this finding emphasizes the role of cell motion, guided by cell-cell interactions during differentiation, in forming biological crystals. Such a route to the formation of regular patterns may be especially valuable in situations, like growth on a curved surface, where the resulting long-ranged, elastic, effective interactions between defects can help to group them into grain boundaries.

Achieving self-sufficiency of red blood cells based on universal voluntary blood donation in Latin America. The case of Nicaragua.

In 2007, the blood collection rate in Nicaragua was 106.6 units per 10,000 inhabitants. Voluntary donation was 39%. The health authorities decided to pursue self sufficiency of blood by eliminating replacement donation and consolidating blood processing in two centers. Replacement donation was terminated in 2009, voluntary donation reached 100% in 2010, and the blood collection rate increased to 125.9 in 2011. The rate of red blood cell transfusion improved from 96.0 to 119.1 units per 10,000 during the 4-year period. The political will of the government, pertinent technical leadership, and a country-wide approach were essential for attaining those goals.

Duration of protection of pentavalent rotavirus vaccination in Nicaragua.

OBJECTIVE: To evaluate the duration of protection of pentavaent rotavirus vaccine (RV5) against rotavirus hospitalizations in Nicaragua, a developing country in Central America. METHODS: We conducted a case-control study at 4 hospitals from 2007 through 2010, including 1016 children hospitalized with laboratory-confirmed rotavirus diarrhea, 4930 controls with nonrotavirus diarrhea (ie, "test-negative"), and 5627 controls without diarrhea. All cases and controls were aged ≥ 6 months and born after August 2006. Outcomes included odds of antecedent vaccination between case-patients and controls, and effectiveness of vaccination (1 - adjusted odds ratio [OR] × 100). Duration of protection was assessed by comparing effectiveness among children aged <1 year compared with ≥ 1 year. RESULTS: Indicators of socioeconomic conditions and nonrotavirus vaccination (oral polio vaccine and diphtheria/tetanus/pertussis/hepatitis A/hepatitis B) for test-negative controls were more comparable to the rotavirus case-patients than nondiarrhea controls. RV5 vaccination was associated with a significantly lower risk of rotavirus hospitalization by using test-negative controls (OR: 0.55; 95% confidence interval [CI]: 0.41-0.74) and nondiarrhea controls (OR: 0.30; 95% CI: 0.22-0.40). Risk of rotavirus hospitalization was twofold lower among RV5 vaccinated children aged <1 year (OR: 0.36; 95% CI: 0.22-0.57) compared with RV5 vaccinated children aged ≥ 1 year (OR: 0.70; 95% CI: 0.47-1.05). CONCLUSIONS: RV5 provided good protection against severe rotavirus disease in Nicaragua during the first year of life, when most severe and fatal rotavirus disease in developing countries occurs. However, the decline in protection with age warrants monitoring of disease among older children and consideration of a booster dose evaluation at the end of infancy.

Cost analysis of centralized viral load testing for antiretroviral therapy monitoring in Nicaragua, a low-HIV prevalence, low-resource setting.

BACKGROUND: HIV viral load testing as a component of antiretroviral therapy monitoring is costly. Understanding the full costs and the major sources of inefficiency associated with viral load testing is critical for optimizing the systems and technologies that support the testing process. The objective of our study was to estimate the costs associated with viral load testing performed for antiretroviral therapy monitoring to both patients and the public healthcare system in a low-HIV prevalence, low-resource country. METHODS: A detailed cost analysis was performed to understand the costs involved in each step of performing a viral load test in Nicaragua, from initial specimen collection to communication of the test results to each patient's healthcare provider. Data were compiled and cross referenced from multiple information sources: laboratory records, regional surveillance centre records, and scheduled interviews with the key healthcare providers responsible for HIV patient care in five regions of the country. RESULTS: The total average cost of performing a viral load test in Nicaragua varied by region, ranging from US$99.01 to US$124.58, the majority of which was at the laboratory level: $88.73 to $97.15 per specimen, depending on batch size. The average cost to clinics at which specimens were collected ranged from $3.31 to $20.92, depending on the region. The average cost per patient for transportation, food, lodging and lost income ranged from $3.70 to $14.93. CONCLUSIONS: The quantitative viral load test remains the single most expensive component of the process. For the patient, the distance of his or her residence from the specimen collection site is a large determinant of cost. Importantly, the efficiency of results reporting has a large impact on the cost per result delivered to the clinician and utility of the result for patient monitoring. Detailed cost analysis can identify opportunities for removing barriers to effective antiretroviral therapy monitoring programmes in limited-resource countries with low HIV prevalence.

Association between pentavalent rotavirus vaccine and severe rotavirus diarrhea among children in Nicaragua.

CONTEXT: Pentavalent rotavirus vaccine (RV5), a live, oral attenuated vaccine, prevented 98% of severe rotavirus diarrhea in a trial conducted mainly in Finland and the United States. Nicaragua introduced RV5 in 2006, providing the first opportunity to assess the association between vaccination and rotavirus disease in a developing country. OBJECTIVE: To assess the association between RV5 vaccination and subsequent rotavirus diarrhea requiring overnight admission or intravenous hydration. DESIGN, SETTING, AND PARTICIPANTS: Case-control evaluation in 4 hospitals in Nicaragua from June 2007 to June 2008. Cases were children age-eligible to receive RV5 who were admitted or required intravenous hydration for laboratory-confirmed rotavirus diarrhea. For each case (n = 285), 1 to 3 neighborhood (n = 840) and hospital (n = 690) controls were selected. MAIN OUTCOME MEASURES: Primary outcome was the association of RV5 and rotavirus diarrhea requiring overnight admission or intravenous hydration in the emergency department. Secondary analysis further classified disease as severe and very severe. We computed the matched odds ratio of vaccination in cases vs controls. Vaccine effectiveness was estimated using the formula 1 - matched odds ratio x 100%. RESULTS: Of the 285 rotavirus cases, 265 (93%) required hospitalization; 251 (88%) received intravenous hydration. A single rotavirus strain (G2P[4]) was identified in 88% of the cases. Among cases and controls, respectively, 18% and 12% were unvaccinated, 12% and 15% received 1 dose of RV5, 15% and 17% received 2 doses, and 55% and 57% received 3 doses. Vaccination with 3 doses was associated with a lower risk of rotavirus diarrhea requiring overnight admission or intravenous hydration (odds ratio [OR], 0.54; 95% confidence interval [CI], 0.36-0.82). Of the 285 rotavirus cases, 191 (67%) were severe and 54 (19%) were very severe. A progressively lower risk of severe (OR, 0.42; 95% CI, 0.26-0.70) and very severe rotavirus diarrhea (OR, 0.23; 95% CI, 0.08-0.61) was observed after RV5 vaccination. Thus, effectiveness of 3 doses of RV5 against rotavirus disease requiring admission or treatment with intravenous hydration was 46% (95% CI, 18%-64%); against severe rotavirus diarrhea, 58% (95% CI, 30%-74%); and against very severe rotavirus diarrhea, 77% (95% CI, 39%-92%). CONCLUSION: Vaccination with RV5 was associated with a lower risk of severe rotavirus diarrhea in children younger than 2 years in Nicaragua but to a lesser extent than that seen in clinical trials in industrialized countries.

Mutated G4P[8] rotavirus associated with a nationwide outbreak of gastroenteritis in Nicaragua in 2005.

During February and March 2005, one of the largest national recorded outbreaks of severe acute gastroenteritis occurred in Nicaragua, affecting >or=64,000 individuals and causing >or=56 deaths, predominantly in children under 5 years of age. Through a nationwide laboratory-based study, stool samples were collected and investigated for rotavirus. Of 108 stool samples examined, 72 (67%) were positive for rotavirus. While 69% (50/72) of the positive samples were found in children less than 2 years of age, 50% (6/12) of the adult samples were positive. A mutated G4P[8] strain was the most commonly recognized strain (85%), followed by mixed G strains (8%) and G9P[8] (7%) strains. Phylogenetic analysis of the VP7 gene revealed that the G4 strains belonged to the emerging lineage Ic and was distantly related to the ST3 and VA70 G4 strains. Secondary structure predictions of the VP7 G4 protein revealed an insert of an asparagine residue in position 76, which, combined with additional mutations, surprisingly modified two downstream beta-sheets at amino acid positions 80 to 85 and 115 to 119. The 2005 G4P[8] strain compared to a G4P[8] strain from 2002 had a substitution of an asparagine residue for threonine (Asn-->Thr) at position 96 within antigenic region A, thus eliminating a potential glycosylation site. The mutated G4 virus was introduced in Nicaragua after 2002 and probably emerged from Brazil, Argentina, or Uruguay.

Differences in dengue severity in infants, children, and adults in a 3-year hospital-based study in Nicaragua.

To investigate age-related differences in dengue severity, 114 infants, 1,211 children, and 346 adults with laboratory-confirmed dengue virus (DEN) infections presenting to three hospitals in major urban centers in Nicaragua were recruited from 1999 to 2001. The age distribution of dengue cases and the circulating serotype (predominantly DEN2) were representative of national data. Similar results were obtained when either dengue hemorrhagic fever/dengue shock syndrome or its principal manifestations (vascular permeability, internal hemorrhage, marked thrombocytopenia, and/or shock) were analyzed in relation to age and immune status. The burden of disease and of severe dengue was found predominantly in infants 4-9 months of age and in children 5-9 years old, and secondary DEN infection was a risk factor for severity in children. Age-related differences were identified in the prevalence of specific clinical manifestations as well as in their association with a confirmed DEN diagnosis. This represents one of the few comprehensive studies to analyze characteristics of dengue in infants, children, and adults in the same population and highlights age-related differences in dengue severity.

First characterization of Candida albicans by random amplified polymorphic DNA method in Nicaragua and comparison of the diagnosis methods for vaginal candidiasis in Nicaraguan women.

A total of 106 women with vaginitis in Nicaragua were studied. The positive rate for the identification of Candida species was 41% (44 positive cultures out of 106 women with vaginitis). The sensitivity of microscopic examination of wet mount with the potassium hydroxide (KOH) was 61% and 70% with Gram's stain when using the culture of vaginal fluid as gold standard for diagnosis of candidiasis. Among the 44 positives cultures, isolated species of yeast from vaginal swabs were C. albicans (59%), C. tropicalis (23%), C. glabrata (14%) and C. krusei (4%). This study reports the first characterization of 26 C. albicans stocks from Nicaragua by the random amplified polymorphic DNA method. The genetic analysis in this small C. albicans population showed the existence of linkage disequilibrium, which is consistent with the hypothesis that C. albicans undergoes a clonal propagation.

First characterization of Candida albicans by random amplified polymorphic DNA method in Nicaragua and comparison of the diagnosis methods for vaginal candidiasis in Nicaraguan women

A total of 106 women with vaginitis in Nicaragua were studied. The positive rate for the identification of Candida species was 41 percent (44 positive cultures out of 106 women with vaginitis). The sensitivity of microscopic examination of wet mount with the potassium hydroxide (KOH) was 61 percent and 70 percent with Gram's stain when using the culture of vaginal fluid as gold standard for diagnosis of candidiasis. Among the 44 positives cultures, isolated species of yeast from vaginal swabs were C. albicans (59 percent), C. tropicalis (23 percent), C. glabrata (14 percent) and C. krusei (4 percent). This study reports the first characterization of 26 C. albicans stocks from Nicaragua by the random amplified polymorphic DNA method. The genetic analysis in this small C. albicans population showed the existence of linkage disequilibrium, which is consistent with the hypothesis that C. albicans undergoes a clonal propagation

Detección de IgM contra el virus del dengue en sangre entera absorbida en papel de filtro / Detection of IgM antibodies to dengue virus in whole blood absorbed on filter paper

En este trabajo se presenta la normalización del procedimiento de detección de anticuerpos IgM contra el virus del dengue en muestras de sangre tomadas en papel de filtro. Las muestras se obtuvieron de 118 pacientes, de los cuales 91 tenían un diagnóstico clínico de dengue y 27 un diagnóstico de una infección viral que no guardaba relación con esa enfermedad, siendo los primeros originarios de Costa Rica y Nicaragua y de Cuba los segundos. En todas las muestras se determinó la presencia de anticuerpos IgM contra el virus del dengue mediante un inmunoensayo enzimático (ELISA) de captura. Al analizarse en su conjunto los resultados de los pacientes de los tres países se determinaron una sensibilidad y especificidad de 98,1 por ciento y 98,5 por ciento respectivamente, para la prueba efectuada con sangre entera en papel de filtro conservada a 4 grados centígrados, y una concordancia de 96 por ciento entre los resultados de esa prueba y los del ELISA. Cuando se compararon los resultados obtenidos con las tres muestras de un mismo paciente - las de sangre en papel de filtro conservadas a la temperatura ambiental y a 4 grados centígrados, y la del suero correspondiente - también se obtuvo una concordancia de 86 por ciento. Este estudio demuestra la elevada sensibilidad y especificidad diagnósticas logradas con el procesamiento de sangre entera absorbida en papel de filtro en las condiciones detalladas en el artículo. Los autores recomiendan utilizar este métodos en los programas de vigilancia de dengue en la Región

This paper presents a standardized procedure for the detection of IgM antibodies to dengue virus in blood samples taken from filter paper. The samples were obtained from 118 patients, of whom 91 had been clinically diagnosed with dengue and 27 with a viral infection unrelated to that disease. The first group of patients came from Costa Rica and Nicaragua and the second group from Cuba. All the samples were tested for IgM antibody against dengue virus by means of a capture enzyme immunoassay (EIA). Analysis of the results for patients from all three countries together yielded a sensitivity of 98.1% and a specificity of 98.5% for the test done on whole blood on filter paper stored at 4 °C; agreement between the results of that test and those of the EIA using serum samples was 96%. In a comparison of the results obtained with three samples from the same patient­whole blood on filter paper stored at room temperature, the same type of sample stored a 4 °C, and serum­the agreement was 86%. This study demonstrates the high diagnostic sensitivity and specificity achieved when whole blood absorbed on filter paper is processed in the manner described in detail in the article. The authors recommend the use of this method in the dengue surveillance programs in the Region.

Detección de IgM contra el virus del dengue en sangre entera absorbida en papel de filtro / Detection of IgM antibodies to dengue virus in whole blood absorbed on filter paper

En este trabajo se presenta la normalización del procedimiento de detección de anticuerpos IgM contra el virus del dengue en muestras de sangre tomadas en papel de filtro. Las muestras se obtuvieron de 118 pacientes, de los cuales 91 tenían un diagnóstico clínico de dengue y 27 un diagnóstico de una infección viral que no guardaba relación con esa enfermedad, siendo los primeros originarios de Costa Rica y Nicaragua y de Cuba los segundos. En todas las muestras se determinó la presencia de anticuerpos IgM contra el virus del dengue mediante un inmunoensayo enzimático (ELISA) de captura. Al analizarse en su conjunto los resultados de los pacientes de los tres países se determinaron una sensibilidad y especificidad de 98,1 por ciento y 98,5 por ciento respectivamente, para la prueba efectuada con sangre entera en papel de filtro conservada a 4 grados centígrados, y una concordancia de 96 por ciento entre los resultados de esa prueba y los del ELISA. Cuando se compararon los resultados obtenidos con las tres muestras de un mismo paciente - las de sangre en papel de filtro conservadas a la temperatura ambiental y a 4 grados centígrados, y la del suero correspondiente - también se obtuvo una concordancia de 86 por ciento. Este estudio demuestra la elevada sensibilidad y especificidad diagnósticas logradas con el procesamiento de sangre entera absorbida en papel de filtro en las condiciones detalladas en el artículo. Los autores recomiendan utilizar este métodos en los programas de vigilancia de dengue en la Región

Evaluación de la respuesta inmune en enfermos con Leishmaniasis cutánea localizada en Nicaragua / Evaluation of the immune response in patients with cutaneous leishmaniasis located in Nicaragua

Se estudió la respuesta inmune en 16 enfermos con Leishmaniasis cutánea localizada (LCL) en fase crónica y activa de la enfermedad. Se observó que los niveles de IgG sérica de los enfermos se encuentran significativamente elevados en relación con los valores de referencia de los controles normales (p < 0,001), no así los niveles séricos de IgM, los niveles de inmunocomplejos circulantes y la actividad de la vía clásica del completamiento, que se mantienen dentro de los valores de referencia. Se observó inmunodeficiencia celular en los enfermos, caracterizada por la disminución significativa de los linfocitos CD3,CD4 y el índice CD4/CD8 (p < 0,001) en relación con los valores de referencia de los controles normales, se discute la importancia de estas alteraciones en la evaluación clínica de la enfermedad

Evaluación de la respuesta inmune en enfermos con Leishmaniasis cutánea localizada en Nicaragua / Evaluation of the immune response in patients with cutaneous leishmaniasis located in Nicaragua

Se estudió la respuesta inmune en 16 enfermos con Leishmaniasis cutánea localizada (LCL) en fase crónica y activa de la enfermedad. Se observó que los niveles de IgG sérica de los enfermos se encuentran significativamente elevados en relación con los valores de referencia de los controles normales (p < 0,001), no así los niveles séricos de IgM, los niveles de inmunocomplejos circulantes y la actividad de la vía clásica del completamiento, que se mantienen dentro de los valores de referencia. Se observó inmunodeficiencia celular en los enfermos, caracterizada por la disminución significativa de los linfocitos CD3,CD4 y el índice CD4/CD8 (p < 0,001) en relación con los valores de referencia de los controles normales, se discute la importancia de estas alteraciones en la evaluación clínica de la enfermedad(AU)

Prevalencia de Salmonela Typhi en portadores manipuladores de alimentos del mercado Israel Lewites de Managua, región III, en los meses de Enero y Febrero 1985

Trata de conocer la prevalencia de Salmonella Typhi mediante búsqueda de portadores en manipuladores de alimentos del mercado Israel Lewites de Managua, Región III; durante enero y febrero 1985; mediante obtención de muestras para coprocultivo. Se estudiaron las condiciones higiénico sociales de los manipuladores a través de encuestas; y las variables como: grupos etáreos, nivel educativo y condiciones higiene ambiental. Se encontró que en 194 muestras negativo de Salmonella Typhi y un coprocultivo positivo, en grupo antígeno E.; la frecuencia global de portadores de Salmonelosis descubierta es de 0.5 porciento; se establece un perfil reproductivo de los manipuladores de alimentos que son en su mayoría jóvenes vendedores y no procesadores y con un nivel educativo de algún grado de primaria. Se recomienda ampliar el universo de estudio e investigar el Bilicultivos en grupos de riesgo de manipuladores de alimentos; mejorar el instrumento de encuestas, ampliándolo para obtener mejor información del Perfil productivo y del Perfil Salud Enfermedad de los encuestados.