The second moment of Sn(t)S_n(t) on the Riemann hypothesis

Let $S(t) = \tfrac{1}{\pi} \arg \zeta \big(\frac{1}{2} + it \big)$ be the argument of the Riemann zeta-function at the point $\tfrac12 + it$. For $n \geq 1$ and $t>0$ define its antiderivatives as \begin{equation*} S_n(t) = \int_0^t S_{n-1}(\tau) \hspace{0.08cm} \rm d\tau + \delta_n , \end{equation*} where $\delta_n$ is a specific constant depending on $n$ and $S_0(t) := S(t)$. In 1925, J. E. Littlewood proved, under the Riemann Hypothesis, that $$\int_{0}^{T}|S_n(t)|^2 \hspace{0.06cm} \rm dt = O(T),$$ for $n\geq 1$. In 1946, Selberg unconditionally established the explicit asymptotic formulas for the second moments of $S(t)$ and $S_1(t)$. Assuming the Riemann Hypothesis, we give the explicit asymptotic formula for the second moment of $S_n(t)$ up to the second-order term, for $n\geq 1$. Our result conditionally refines Selberg's formula for $S_1(t)$ and makes explicit the estimates given by Littlewood. This extends previous work by Goldston in $1987$, where the case $n=0$ was considered

Adrenalectomy promotes a permanent decrease of plasma corticoid levels and a transient increase of apoptosis and the expression of Transforming Growth Factor β1 (TGF-β1) in hippocampus: effect of a TGF-β1 oligo-antisense

BACKGROUND: Corticosterone reduction produced by adrenalectomy (ADX) induces apoptosis in dentate gyrus (DG) of the hippocampus, an effect related to an increase in the expression of the pro-apoptotic gene bax. However it has been reported that there is also an increase of the anti-apoptotic gene bcl-2, suggesting the promotion of a neuroprotective phenomenon, perhaps related to the expression of transforming growth factor β1 (TGF-β1). Thus, we have investigated whether TGF-β1 levels are induced by ADX, and whether apoptosis is increased by blocking the expression of TGF-β1 with an antisense oligonucleotide (ASO) administered intracerebrally in corticosterone depleted rats. RESULTS: It was observed an increase of apoptosis in DG, 2 and 5 days after ADX, in agreement with a reduction of corticosterone levels. However, the effect of ADX on the number of apoptotic positive cells in DG was decreased 5 days after the lesion. In CA1–CA3 regions, the effect was only observed 2 days after ADX. TGF-β1 mRNA levels were increased 2 days after ADX. The sustained intracerebro-ventricular administration of a TGF-β1 ASO via an osmotic mini pump increased apoptosis levels in CA and DG regions 5 days after ADX as well as sham-operated control animals. No significant effect was observed following a scrambled-oligodeoxynucleotide treatment. CONCLUSION: The changes in both the pattern and the magnitude of apoptotic-cell morphology observed 2 and 5 days after ADX suggest that, as a consequence of the reduction of corticosteroids, some trophic mechanisms restricting cell death to a particular time window are elicited. Sustained intracerebral administration of TGF-β1 ASO increased the apoptosis promoted by ADX, suggesting that TGF-β1 plays an anti-apoptotic role in vivo in hippocampus

El acceso a los servicios de salud bucodental para la población adulta mayor en la red hospitalaria pública de Medellín (Colombia)

Antecedentes/Objetivos: La población adulta mayor es un grupo poblacional significativo teniendo en cuenta los cambios demográficos de las últimas décadas. En el país y en la ciudad de Medellín, este grupo presenta alta vulnerabilidad social, así mismo se observan necesidades en salud bucal, descritas en los estudios nacionales y regionales en el tema. Aunque se han realizado investigaciones que tratan de identificar determinantes que afectan el acceso y la utilización de los servicios de salud, los estudios en salud bucal son más escasos y en especial en la población adulta mayor. Objetivo: identificar barreras y facilitadores de acceso a los servicios de salud bucal en población adulta mayor atendida en la red hospitalaria pública de Medellín desde la perspectiva del personal de salud. Métodos: Estudio cualitativo. Se realizaron 34 entrevistas semiestructuradas en personal que presta servicios de salud en la red Metrosalud de Medellín. Se identificaron barreras y facilitadores según el modelo de Tanahashi sobre cobertura en los servicios de salud a través de 4 categorías: disponibilidad (D), accesibilidad (A), aceptabilidad (P) y contacto con el servicio (C). Se utilizó la herramienta informática AtlasTi. Resultados: Se identificaron barreras relacionadas con: dificultades en la implementación de políticas sociales debido a que la salud bucal no es una prioridad; se han priorizado otras poblaciones para dar atención en salud bucal y existe insuficiente recurso humano para prestar los servicios de salud (D); la situación de discapacidad de los adultos mayores (A); aspectos educativos, culturales y de género (P); y la crisis del sector salud como una barrera estructural del sistema (C). En cuanto a los facilitadores se mencionan: la existencia de programas que facilitan la demanda inducida a programas de salud bucal y de mecanismos para hacer valer los derechos en salud a través de instancias gubernamentales y otras (D); la ubicación de las unidades y centros de salud en zonas de fácil acceso (A); la capacidad de los profesionales para atender esta población (P) y la articulación de la odontología con otras áreas (C). Conclusiones: Se identificaron determinantes que afectan el acceso a servicios sanitarios en la población adulta mayor, por lo que se requieren estrategias para mejorar la calidad de la atención en salud bucal en este grupo socialmente vulnerable.E.S.E Metrosalud. Medellín (Código: C02-E11-L3-01)

Snakebites mapping in municipalities of the Coffee Triangle Region in Colombia using Geographic Information Systems (GIS)

Objective: We sought to develop epidemiological maps using geographical information systems (GIS) for the incidence of reported venomous snakebites in the Coffee-Triangle region of Colombia, between 2007 and 2011. Methods: Surveillance cases data (2007-2011) were used to estimate annual incidence rates of snakebites (cases/100,000 pop) to develop the first maps in the 53 municipalities of this region (departments Caldas, Quindío, Risaralda). The GIS software used was Kosmo Desktop 3.0RC1®. Thirty thematic maps were developed according to municipalities and years. Results: A total of 617 cases were reported (56.08% from Caldas, 32.58% from Risaralda and 11.35% from Quindío), for a cumulated regional rate of 25. 25 cases/100,000 pop (35.43 for Caldas, 21.86 for Risaralda and 12.81% for Quindío). The highest cumulated rate was reported in the less developed and more rural municipality of one department (Pueblo Rico, Risaralda) with 265.64 cases/100,000 pop. Between 2007 and 2011, a considerable increase was seen in the rates. At Pueblo Rico, Risaralda, there was a change from 41.04 cases/100,000pop in 2007 up to 63.11 cases/100,000pop in 2011 (1.54 times higher). From Caldas, Samaná showed a high variation from 19.47 to 77.7 (3.99 times higher). Conclusions: Morbidity of snakebites is highly concentrated in one department (Caldas). Use of GIS-based epidemiological maps allows guiding decisions-taking for prevention and control of public health problems that still represents a significant issue in the region and the country, such as snakebites

Snakebites mapping in municipalities of the Coffee Triangle Region in Colombia using Geographic Information Systems (GIS)

Objective: We sought to develop epidemiological maps using geographical information systems (GIS) for the incidence of reported venomous snakebites in the Coffee-Triangle region of Colombia, between 2007 and 2011. Methods: Surveillance cases data (2007-2011) were used to estimate annual incidence rates of snakebites (cases/100,000 pop) to develop the first maps in the 53 municipalities of this region (departments Caldas, Quindío, Risaralda). The GIS software used was Kosmo Desktop 3.0RC1®. Thirty thematic maps were developed according to municipalities and years. Results: A total of 617 cases were reported (56.08% from Caldas, 32.58% from Risaralda and 11.35% from Quindío), for a cumulated regional rate of 25. 25 cases/100,000 pop (35.43 for Caldas, 21.86 for Risaralda and 12.81% for Quindío). The highest cumulated rate was reported in the less developed and more rural municipality of one department (Pueblo Rico, Risaralda) with 265.64 cases/100,000 pop. Between 2007 and 2011, a considerable increase was seen in the rates. At Pueblo Rico, Risaralda, there was a change from 41.04 cases/100,000pop in 2007 up to 63.11 cases/100,000pop in 2011 (1.54 times higher). From Caldas, Samaná showed a high variation from 19.47 to 77.7 (3.99 times higher). Conclusions: Morbidity of snakebites is highly concentrated in one department (Caldas). Use of GIS-based epidemiological maps allows guiding decisions-taking for prevention and control of public health problems that still represents a significant issue in the region and the country, such as snakebites

El diplomado su dinámica y diseño curricular. The diploma course: its dynamic and curricular design

Se realiza una investigación partiendo de la insuficiencia que presentan en la formación pedagógica los docentes de la Facultad de Ciencias Médicas "Dr. Ernesto Che Guevara de la Serna", con el propósito de contribuir al perfeccionamiento de la Educación Médica Superior, específicamente en el postgrado, al determinar la fundamentación teórica-pedagógica y didáctica para el proceso docente - educativo postgraduado de los profesionales de la Salud que ejercen función docente, que tome en cuenta su estructura y dinámica, el sistema de leyes que lo rigen y las regularidades que se manifiesten en este proceso en particular, a través del diseño de un programa de Diplomado en Ciencias de la Educación Médica Superior que tiende a eliminar todo carácter empírico. Se tomarán en consideración los métodos científicos de investigación: histórico, lógico, dialéctico, análisis documental, empíricos y sistémico-estructural entre otros. Se arriban a conclusiones y recomendaciones. DeCS: EDUCACIÓN MÉDICA, ESCUELAS MÉDICAS, DOCENCIA MÉDICA, PEDAGOGÍA. ABSTRACT A research paper was carried out considering the inadequacies present in the pedagogical training of the teaching staff at “Dr. Ernesto Guevara de la Serna” Medical School to contribute to the improvements of Higher Medical Education, specifically post-graduate education, determining the theoretical, pedagogical and didactic bases to the teaching-educational postgraduate process of the health professionals with the practice of teaching activities, taking into account its structure and dynamics, the system of laws to its function and the regularities that determine this process in particular, carrying it by means of a syllabus design for a Diploma course in Higher Medical Education; which course might tend to eliminate all of the empiric character. Scientific methods of research such as: historical, logical, dialectic, documentary analysis, empiric and systemic-structural were taken into consideration. Conclusions and recommendations were given. DeCS: Medical education; medical schools; medical teaching; pedagogy

El diplomado su dinámica y diseño curricular. The diploma course: its dynamic and curricular design

Se realiza una investigación partiendo de la insuficiencia que presentan en la formación pedagógica los docentes de la Facultad de Ciencias Médicas "Dr. Ernesto Che Guevara de la Serna", con el propósito de contribuir al perfeccionamiento de la Educación Médica Superior, específicamente en el postgrado, al determinar la fundamentación teórica-pedagógica y didáctica para el proceso docente - educativo postgraduado de los profesionales de la Salud que ejercen función docente, que tome en cuenta su estructura y dinámica, el sistema de leyes que lo rigen y las regularidades que se manifiesten en este proceso en particular, a través del diseño de un programa de Diplomado en Ciencias de la Educación Médica Superior que tiende a eliminar todo carácter empírico. Se tomarán en consideración los métodos científicos de investigación: histórico, lógico, dialéctico, análisis documental, empíricos y sistémico-estructural entre otros. Se arriban a conclusiones y recomendaciones. DeCS: EDUCACIÓN MÉDICA, ESCUELAS MÉDICAS, DOCENCIA MÉDICA, PEDAGOGÍA. ABSTRACT A research paper was carried out considering the inadequacies present in the pedagogical training of the teaching staff at “Dr. Ernesto Guevara de la Serna” Medical School to contribute to the improvements of Higher Medical Education, specifically post-graduate education, determining the theoretical, pedagogical and didactic bases to the teaching-educational postgraduate process of the health professionals with the practice of teaching activities, taking into account its structure and dynamics, the system of laws to its function and the regularities that determine this process in particular, carrying it by means of a syllabus design for a Diploma course in Higher Medical Education; which course might tend to eliminate all of the empiric character. Scientific methods of research such as: historical, logical, dialectic, documentary analysis, empiric and systemic-structural were taken into consideration. Conclusions and recommendations were given. DeCS: Medical education; medical schools; medical teaching; pedagogy

Neurogenic inducers based on the chromone scaffold, a new family of multitarget directed ligands for Alzheimer's disease

Resumen del trabajo presentado a la XXXVIII Reunión Anual del Grupo Español de Neurotransmisión y Neuroprotección (GENN), celebrada en Almagro (Ciudad Real) del 13 al 15 de diciembre de 2017.The highly complex pathophysiology of Alzheimer's disease (AD) and other neurodegenerative illnesses have led to replace the traditional one-drug - one-target by the multi-target-directed ligands (MTDLs) paradigm, in which a single molecule is designed to be active against several pharmacological targets. Continuing with our interest in neuroprotective and neurogenic compounds, in this work we describe a new family of donepezil flavonoid hybrids exhibiting nanomolar affinities for the sigma-1 receptor and a combined inhibition of key enzymes in AD, such as 5-lipoxygenase, acetylcholinesterase, and monoaminoxidases. In general, they scavenge free radical species and are predicted to be brain-permeable. In phenotypic assays, new hybrids protect neuronal cells against mitochondrial oxidative stress and promote maturation of neural stem cells into a neuronal phenotype. Therefore, new donepezil - flavonoid hybrids could contribute to the protection and even, the reparation of neuronal tissues, of great therapeutic interest in AD and neurodegenerative diseases.Spanish Ministry of Economy and Competitiveness MINECO (grant SAF2015-64948-C2-1-R) and Spanish National Research Council CSIC (grant PIE-201580E109).Peer Reviewe

Analyse der Arzneimitteltherapie von Rheumapatienten im Erwachsenenalter : das Versorgungsgeschehen im Lichte der Leitlinienempfehlungen

The aim of this dissertation is to demonstrate the further developments in the provision of rheumatological health care with particular focus on evidence-based guideline recommendations. One of the issues to be examined is to identify gaps - defined as conditions of insufficient medical care between practical daily care and (theoretical) guideline recommendations differentiating various aspects of care. Are there still references about a lack of provison of medical care or is it possible to reveal further developments that can be assessed as positive respectively? Avenues for future action are to be pointed out against the background of these findings with regard to measures which have already been established as well as to aspired solutions in order to optimate the provision of rheumatological health care. A further glimpse of the future is disclosed by taking up the biosimilar-issue: As many bio-pharmaceuticals lose patent protection in coming years, biosimilar products are expected to play a key role in controlling pharmaceutical expenditure - while maintaining consistent quality of medical care. Assessing opportunities and challenges of these new medical products will round off this dissertation