Caveats of chimpanzee ChAdOx1 adenovirus-vectored vaccines to boost anti-SARS-CoV-2 protective immunity in mice.

Several COVID-19 vaccines use adenovirus vectors to deliver the SARS-CoV-2 spike (S) protein. Immunization with these vaccines promotes immunity against the S protein, but against also the adenovirus itself. This could interfere with the entry of the vaccine into the cell, reducing its efficacy. Herein, we evaluate the efficiency of an adenovirus-vectored vaccine (chimpanzee ChAdOx1 adenovirus, AZD1222) in boosting the specific immunity compared to that induced by a recombinant receptor-binding domain (RBD)-based vaccine without viral vector. Mice immunized with the AZD1222 human vaccine were given a booster 6 months later, with either the homologous vaccine or a recombinant vaccine based on RBD of the delta variant, which was prevalent at the start of this study. A significant increase in anti-RBD antibody levels was observed in rRBD-boosted mice (31-61%) compared to those receiving two doses of AZD1222 (0%). Significantly higher rates of PepMix™- or RBD-elicited proliferation were also observed in IFNγ-producing CD4 and CD8 cells from mice boosted with one or two doses of RBD, respectively. The lower efficiency of the ChAdOx1-S vaccine in boosting specific immunity could be the result of a pre-existing anti-vector immunity, induced by increased levels of anti-adenovirus antibodies found both in mice and humans. Taken together, these results point to the importance of avoiding the recurrent use of the same adenovirus vector in individuals with immunity and memory against them. It also illustrates the disadvantages of ChAdOx1 adenovirus-vectored vaccine with respect to recombinant protein vaccines, which can be used without restriction in vaccine-booster programs. KEY POINTS: • ChAdOx1 adenovirus vaccine (AZD1222) may not be effective in boosting anti-SARS-CoV-2 immunity • A recombinant RBD protein vaccine is effective in boosting anti-SARS-CoV-2 immunity in mice • Antibodies elicited by the rRBD-delta vaccine persisted for up to 3 months in mice.

Menstrual characteristics and associations with sociodemographic factors and self-rated health in Spain: a cross-sectional study.

BACKGROUND: Evidence on how menstrual characteristics may differ based on socioeconomic factors and self-rated health is significantly scarce. The main aim of this study was to investigate the associations between menstrual characteristics, sociodemographic factors and self-rated health among women and people who menstruate (PWM) aged 18-55 in Spain. METHODS: This cross-sectional study includes data from an online survey collected in March-July 2021 across Spain. Descriptive statistical analyses and multivariate logistic regression models were performed. RESULTS: The analyses included a total of 19,358 women and PWM. Mean age at menarche was 12.4 (SD = 1.5). While 20.3% of our participants experienced a menstrual abundance over 80 ml, 64.1% reported having menstrual blood clots; 6.4% menstruated for longer than 7 days. 17.0% had menstrual cycles that were shorter than 21 days or longer than 35 days. Reports of moderate (46.3%) and high (22.7%) intensity menstrual pain were common. 68.2% of our participants experienced premenstrual symptoms in all or most cycles. The odds for lighter menstrual flow, shorter bleeding days and menstrual cycles were higher as age increased, and amongst participants with less educational attainment. Caregivers presented higher odds for abundant menstrual flow and longer menstruations. Reporting financial constraints and a poorer self-rated health were risk factors for abundant menstrual flow, menstrual blood clots, shorter/longer menstruations and menstrual cycles, premenstrual symptoms, moderate and intense menstrual pain. CONCLUSIONS: This study suggests that age, educational attainment, caregiving, experiencing financial hardship and a poorer self-rated health may shape or mediate menstrual characteristics. It thus highlights the need to investigate and address social inequities of health in menstrual research.

Perspectives on menstrual policymaking and community-based actions in Catalonia (Spain): a qualitative study.

BACKGROUND: Menstrual research and policymaking have become imperative worldwide. It is necessary that these are informed by women and people who menstruate (PWM) alongside expert professionals and activists. METHODS: The main aim of this study was to identify and propose policies and community-based actions to address menstrual inequity and promote menstrual health in Catalonia (Spain). This study consisted of two qualitative studies: (a) 34 individual photoelicitation interviews with women and PWM, (b) a World Café study with 22 professionals and activists. Sampling for both studies was purposive and selective. Recruitment was conducted through healthcare centres, social media, key contacts, and snowball sampling techniques. Data were collected in December 2020-September 2022, and analysed using Framework Analysis. RESULTS: Participants considered the implementation of menstrual policies that address the taboo and stigma of menstruation to be crucial. They stressed the need for menstrual education, which should be integrated into formal education curricula. Participants, and especially women and PWM, highlighted the need to improve the access and quality of healthcare services, so that the menstrual cycle and menstruation are seen as health indicators. Health professionals should encourage agentic informed decisions, hence why both participant groups considered menstrual health education amongst health professionals to be pivotal. Taking action to improve the access and affordability of menstrual products was also imperative for participants, especially for socioeconomically vulnerable populations. Participants agreed on guaranteeing fully equipped menstrual management facilities, and and professionals discussed gender-neutral and sex-segregated bathrooms. Workplace menstrual policies to accommodate and ensure menstrual self-care were also suggested. CONCLUSIONS: Our study highlights the need for multi-dimensional menstrual policies. These should include actions to address menstrual taboo and stigma, to promote menstrual education that goes beyond the hegemonic biomedical prism, to improve the access and quality of menstrual health services, along with policies ensuring adequate menstrual management facilities in public spaces and the access to menstrual products. Policymaking should also focus on how to ensure menstrual management and care in workplaces. Menstrual policies and community-based actions should be framed within intersectionality, to consider how societal structures of power and oppression influence menstrual experiences.

RESUMEN: INTRODUCCIóN: Siendo la investigación y la implementación de políticas menstruales imprescindibles, es necesario que estos procesos estén informados por mujeres y personas que menstrúan (PM), así como por profesionales expertas y activistas. MéTODOS: El objetivo principal de este estudio fue identificar y proponer políticas y acciones comunitarias para abordar la inequidad menstrual y promover la salud menstrual en Cataluña (España). Este estudio consistió en dos estudios cualitativos: (a) 34 entrevistas individuales de fotoelicitación con mujeres y PM, (b) un World Café con 22 profesionales y activistas. El muestreo para ambos estudios fue intencional y selectivo. El reclutamiento se realizó a través de centros de salud, redes sociales, contactos clave y técnicas de bola de nieve. Los datos se recogieron entre diciembre de 2020 y septiembre de 2022 y se analizaron mediante Framework Analysis. RESULTADOS: Las participantes consideraron crucial la implementación de políticas menstruales para abordar el tabú y el estigma menstrual. Destacaron la necesidad de una educación menstrual, que debería integrarse en los currículums escolares. Las participantes, y especialmente las mujeres y PM, resaltaron la necesidad de mejorar el acceso y la calidad de los servicios de salud, de manera que el ciclo menstrual y la menstruación sean consideradas indicadores de salud. Mencionaron que el personal sanitario debe fomentar las decisiones informadas, de ahí que ambos grupos de participantes consideraran fundamental la educación sobre la salud menstrual entre los profesionales de la salud. También, para las participantes fue imperativo asegurar el acceso y asequibilidad de productos menstruales, especialmente para las poblaciones socioeconómicamente vulnerabilizadas. Las participantes estuvieron de acuerdo en la necesidad de garantizar espacios equipadas para el manejo menstrual, y se llevaron a cabo debates entre las profesionales sobre los baños inclusivos y segregados por sexo. También se sugirieron y debatieron políticas menstruales en entornos laborales, para adaptar y garantizar el autocuidado menstrual. CONCLUSIONES: Nuestro estudio destaca la necesidad de políticas menstruales multidimensionales. Estas deberían incluir acciones para abordar el tabú y el estigma menstrual, promover una educación menstrual que vaya más allá de la perspectiva biomédica hegemónica, mejorar el acceso y la calidad de los servicios de salud menstrual, junto con políticas para garantizar la disponibilidad de instalaciones adecuadas para el manejo menstrual en espacios públicos, así como el acceso a productos menstruales. La creación de políticas también debería centrarse en cómo garantizar el manejo y los cuidados menstruales en entornos laborales. Finalmente, estas políticas menstruales y acciones comunitarias deben enmarcarse desde la interseccionalidad, para considerar cómo las estructuras y poderes sociales operan e influyen en las experiencias menstruales.

Detection of gender-based violence in primary care in Central Catalonia: a descriptive cross-sectional study.

BACKGROUND: Violence against women is a serious public health problem. Primary care could be one of the ideal places for the detection of gender-based violence (GBV), since women come into contact with PC at some point in their lives to look after their sexual and reproductive health. The increase in initiatives promoted by the health authorities regarding GBV offers the possibility of observing its evolution over the last few years. METHODS: A descriptive cross-sectional study of reported cases of GBV in the region of Central Catalonia, during the period from 2017 to 2021, was carried out. All women of legal age, belonging to the specified health region and suffering episodes of GBV, were included. The variables analysed were age, area of residence, health diagnoses related to GBV, whether or not they were pregnant at the time of the attack, and mental health history. RESULTS: Of the total number of women studied, 1,467 presented some type of diagnosis of GBV, with a total of 3,452 episodes reported. We found an increase in the detection of cases, although it must be noted that there is an underreporting of cases in PC. The prevalence according to the total number of women assigned per year over the period studied was 0.42% in 2017 and 0.48% in 2021. It has also been observed that the average number of episodes per woman increased from 1.03 in 2017 to 1.15 in 2021. During the 5 years analysed, the minimum number of episodes per woman was 1 and the maximum was 10. In reference to the duration of the episodes, the minimum was 1 day, and the maximum was 32 years. The mean age of the women was 42.10 years, the most frequent nationality was Spanish (46.60%), and 54.15% of them lived in rural areas. CONCLUSIONS: Despite the established protocols and procedures, it seems that primary health care is not the most frequent place for its detection. It is necessary to continue working to raise awareness and train professionals, and to ensure coordination among all the parties involved in accompanying women in these processes. TRIAL REGISTRATION: CEIm: 21/278-P.

Long-term changes in the diurnal temporal regulation and set points of metabolic parameters associated with chronic maternal overnutrition in rabbits.

Metabolic syndrome (MS) and obesity have become a worldwide epidemic with an alarming prevalence in women of reproductive age. Maternal metabolic condition is considered a risk factor for adverse birth outcomes and long-term MS. In this study, we developed a rabbit model of maternal overnutrition via the chronic intake of a high-fat and carbohydrate diet (HFCD), and we determined the effects of this diet on maternal metabolism and offspring metabolic set points and temporal metabolic regulation in adult life. Before and during pregnancy, the female rabbits that consumed the HFCD exhibited significant changes in body weight, serum levels of analytes associated with carbohydrate and lipid metabolism, levels of liver and kidney damage markers, and liver histology. Our data suggest that rabbits are a valuable model for studying the development of MS associated with the chronic intake of unbalanced diets and fetal metabolic programming. Furthermore, the offspring of overnourished dams exhibited considerable changes in 24-h serum metabolite profiles in adulthood, with notable sexual dimorphism. These data suggest that maternal nutritional conditions due to the chronic intake of an HFCD adversely impact key elements related to the development of circadian rhythmicity in offspring.NEW & NOTEWORTHY Maternal overnutrition previous and during pregnancy leads to long-term changes in the 24-h regulation and setpoint of metabolic profiles of the offspring.

A Sex- and Gender-Based Approach to Chronic Conditions in Central Catalonia (Spain): A Descriptive Cross-Sectional Study.

The growth of chronic conditions worldwide poses a challenge for both health systems and the quality of life of people with these conditions. However, sex- and gender-based approaches are scarce in this field. Adopting this perspective, this study aims to describe the prevalence of chronic conditions in the Bages-Moianès region (Catalonia, Spain), and analyse the associations of chronic conditions with sex and age. This cross-sectional study used data from the population assigned to the Catalan Health Institute primary care settings in this area between 2018 and 2021 (n = 163,024). A total of 26 chronic conditions (grouped into 7 typologies), sex and age were the analysis variables. A total of 75,936 individuals presented at least one chronic condition, representing 46.6% of the analysed population. The prevalence was higher among women and older individuals. Being male was associated with a greater probability of presenting cardiovascular diseases, neurodevelopmental disorders and metabolic diseases and a lower probability of presenting neurodegenerative diseases, chronic pain and mental health disorders. Adjusting by sex, a positive age gradient was observed in most groups, except for respiratory diseases and mental health disorders. Chronic conditions have a high prevalence in the Bages-Moianès region, showing differences in typology, sex and age. Adopting gender perspectives (both in health systems and future research) is crucial when dealing with chronic conditions in order to take into account their differential impact.

Increased TSPO expression, pyroglutamate-modified amyloid beta (AßN3(pE)) accumulation and transient clustering of microglia in the thalamus of Tg-SwDI mice.

Epidemiological studies showed that Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) frequently co-occur; however, the precise mechanism is not well understood. A unique animal model (Tg-SwDI mice) was developed to investigate the early-onset and robust accumulation of both parenchymal and vascular Aß in the brain. Tg-SwDI mice have been extensively used to study the mechanisms of cerebrovascular dysfunction, neuroinflammation, neurodegeneration, and cognitive decline observed in AD/CAA patients and to design biomarkers and therapeutic strategies. In the present study, we documented interesting new features in the thalamus of Tg-SwDI mice: 1) a sharp increase in the expression of ionized calcium-binding adapter molecule 1 (Iba-1) in microglia in 6-month-old animals; 2) microglia clustering at six months that disappeared in old animals; 3) N-truncated/modified AßN3(pE) peptide in 9-month-old female and 12-month-old male mice; 4) an age-dependent increase in translocator protein (TSPO) expression. These findings reinforce the versatility of this model for studying multiple pathological issues involved in AD and CAA.

Creation of a Laboratory for Statistics and Analysis of Dependence and Chronic Conditions: Protocol for the Bages Territorial Specialization and Competitiveness Project (PECT BAGESS).

BACKGROUND: With the increasing prevalence of chronic diseases, partly due to the increase in life expectancy and the aging of the population, the complexity of the approach faced by the structures, dynamics, and actors that are part of the current care and attention systems is evident. The territory of Bages (Catalonia, Spain) presents characteristics of a highly complex ecosystem where there is a need to develop new, more dynamic structures for the various actors in the health and social systems, aimed at incorporating new actors in the technological and business field that would allow innovation in the management of this context. Within the framework of the Bages Territorial Specialization and Competitiveness Project (PECT BAGESS), the aim is to address these challenges through various entities that will develop 7 interrelated operations. Of these, the operation of the IDIAP Jordi Gol-Catalan Health Institute focuses on the creation of a Laboratory for Statistics and Analysis of Dependence and Chronic Conditions in the Bages region, in the form of a database that will collect the most relevant information from the different environments that affect the management of chronic conditions and dependence: health, social, economic, and environment. OBJECTIVE: This study aims to create a laboratory for statistical, dependence, and chronic condition analysis in the Bages region, to determine the chronic conditions and conditions that generate dependence in the Bages area, in order to propose products and services that respond to the needs of people in these situations. METHODS: PECT BAGESS originated from the Shared Agenda initiative, which was established in the Bages region with the goal of enhancing the quality of life and fostering social inclusion for individuals with chronic diseases. This study presents part of this broader project, consisting of the creation of a database. Data from chronic conditions and dependence service providers will be combined, using a unique identifier for the different sources of information. A thorough legal analysis was conducted to establish a secure data sharing mechanism among the entities participating in the project. RESULTS: The laboratory will be a key piece in the structure generated in the environment of the PECT BAGESS, which will allow relevant information to be passed on from the different sectors involved to respond to the needs of people with chronic conditions and dependence, as well as to generate opportunities for products and services. CONCLUSIONS: The emerging organizational dynamics and structures are expected to demonstrate a health and social management model that may have a remarkable impact on these sectors. Products and services developed may be very useful for generating synergies and facilitating the living conditions of people who can benefit from all these services. However, secure data sharing circuits must be considered. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/46542.

Standardizing an Experimental Murine Model of Extraparenchymal Neurocysticercosis That Immunologically Resembles Human Infection.

BACKGROUND: Neurocysticercosis (NCC) is endemic in non-developed regions of the world. Two forms of NCC have been described, for which neurological morbidity depends on the location of the lesion, which can be either within the cerebral parenchyma or in extraparenchymal spaces. The extraparenchymal form (EXP-NCC) is considered the most severe form of NCC. EXP-NCC often requires several cycles of cysticidal treatment and the concomitant use of glucocorticoids to prevent increased inflammation, which could lead to intracranial hypertension and, in rare cases, to death. Thus, the improvement of EXP-NCC treatment is greatly needed. METHODS: An experimental murine model of EXP-NCC, as an adequate model to evaluate new therapeutic approaches, and the parameters that support it are described. EXP-NCC was established by injecting 30 Taenia crassiceps cysticerci, which are less than 0.5 mm in diameter, into the cisterna magna of male and female Wistar rats. RESULTS: Cyst implantation and infection progression were monitored by detecting the HP10 antigen and anti-cysticercal antibodies in the serum and cerebral spinal fluid (CSF) of infected rats and by magnetic resonance imaging. Higher HP10 levels were observed in CSF than in the sera, as in the case of human EXP-NCC. Low cell recruitment levels were observed surrounding established cysticerci in histological analysis, with a modest increase in GFAP and Iba1 expression in the parenchyma of female animals. Low cellularity in CSF and low levels of C-reactive protein are consistent with a weak inflammatory response to this infection. After 150 days of infection, EXP-NCC is accompanied by reduced levels of mononuclear cell proliferation, resembling the human disease. EXP-NCC does not affect the behavior or general status of the rats. CONCLUSIONS: This model will allow the evaluation of new approaches to control neuroinflammation and immunomodulatory treatments to restore and improve the specific anti-cysticercal immunity in EXP-NCC.

Endometriosis prevalence and incidence trends in a large population-based study in Catalonia (Spain) from 2009 to 2018.

OBJECTIVE: Endometriosis greatly impacts women's health and quality of life. However, research on the prevalence and incidence of endometriosis remains inconclusive. This study assesses time trends in the prevalence and incidence of endometriosis diagnoses in Catalonia (Spain) from 2009 to 2018, considering differences by age and socioeconomic status. METHODS: Population-based cohort study using data from the Information System for Research in Primary Care (SIDIAP) database. Data were included from over 2.4 million women aged 15-55 years between 1 January 2006 and 31 December 2018. RESULTS: A total of 2,337,717 women were selected as the incident population; 0.7% had an endometriosis diagnosis. Median (interquartile range) age at diagnosis was 37 (32-43) years. Most women were European (92.3%) and lived in urban areas (73.6%). Overall prevalence of endometriosis consistently increased during the 2009-2018 period, and it was 1.24% in 2018. Trends were the highest for women with less socioeconomic deprivation and for the 35-44 years age group. Median incidence rates were 94.9 (92.6-102.9) per 100,000 women-years, being the highest in women aged 35-44 years throughout the whole study period. Overall, incidence increased between 2015 and 2017, and plateaued or decreased in 2018. Incidence rates in women from the most deprived and rural areas were lower, although incidence time trends by socioeconomic status were unclear. CONCLUSION: Healthcare services and public health strategies need to be strengthened to ensure timely endometriosis diagnosis and treatment. Special attention should be given to the most affected populations and the social inequities of health.

Towards the development of an epitope-focused vaccine for SARS-CoV-2.

The rapid spread of COVID-19 on all continents and the mortality induced by SARS-CoV-2 virus, the cause of the pandemic coronavirus disease 2019 (COVID-19) has motivated an unprecedented effort for vaccine development. Inactivated viruses as well as vaccines focused on the partial or total sequence of the Spike protein using different novel platforms such us RNA, DNA, proteins, and non-replicating viral vectors have been developed. The high global need for vaccines, now and in the future, and the emergence of new variants of concern still requires development of accessible vaccines that can be adapted according to the most prevalent variants in the respective regions. Here, we describe the immunogenic properties of a group of theoretically predicted RBD peptides to be used as the first step towards the development of an effective, safe and low-cost epitope-focused vaccine. One of the tested peptides named P5, proved to be safe and immunogenic. Subcutaneous administration of the peptide, formulated with alumina, induced high levels of specific IgG antibodies in mice and hamsters, as well as an increase of IFN-γ expression by CD8+ T cells in C57 and BALB/c mice upon in vitro stimulation with P5. Neutralizing titers of anti-P5 antibodies, however, were disappointingly low, a deficiency that we will attempt to resolve by the inclusion of additional immunogenic epitopes to P5. The safety and immunogenicity data reported in this study support the use of this peptide as a starting point for the design of an epitope restricted vaccine.

Misadjustment of diurnal expression of core temperature and locomotor activity in lactating rabbits associated with maternal over-nutrition before and during pregnancy.

Metabolic parameters ranging from circulating nutrient levels and substrate utilization to energy expenditure and thermogenesis are temporally modulated by the circadian timing system. During critical embryonic developmental periods, maternal over-nutrition could alter key elements in different tissues associated with the generation of circadian rhythmicity, compromising normal rhythmicity development. To address this issue, we determine whether maternal over-nutrition leads to alterations in the development of circadian rhythmicity at physiological and behavioral levels in the offspring. For this, female rabbits were fed a standard diet (SD) or high-fat and carbohydrate diet (HFCD) before mating and during gestation. Core body temperature and gross locomotor activity were continuously recorded in newborn rabbits, daily measurements of body weight and the amount of milk ingested was carried out. At the end of lactation, tissue samples, including brown adipose tissue (BAT) and white adipose tissue (WAT), were obtained for determining the expression of uncoupling protein-1 (UCP1) and cell death-inducing DNA fragmentation factor-like effector A (CIDEA) genes. HFCD pups exhibited conspicuous differences in the development of the daily rhythm of temperature and locomotor activity compared to the SD pups, including a significant increase in the daily mean core temperature, changes in the time when temperature or activity remains above the average, shifts in the acrophase, decrease in the duration and intensity of the anticipatory rise previous to nursing, and changes in frequency of the rhythms. HFCD pups exhibited a significant increase in BAT thermogenesis markers, and a decrease of these markers in WAT, indicating more heat generation by brown adipocytes and alterations in the browning process. These results indicate that maternal over-nutrition alters offspring homeostatic and chronostatic regulation at the physiological and behavioral levels. Further studies are needed to determine whether these alterations are associated with the changes in the organization of the circadian system of the progeny.

Temporal variations of nucleosides and nucleotides in rabbit milk.

Nucleotides and nucleosides have a preeminent role in physiological and biochemical processes for newborns, the major source of these during early development is the breast milk. Different biomolecules exhibit daily fluctuations in maternal milk that could transfer temporal information that synchronize newborn circadian system. As a first approach, we characterized the diurnal profile of nucleotides and nucleosides contained in maternal milk of rabbits during the first week of lactation. It is possible that some nucleosides, such as adenosine, play a relevant role in setting up the emerging circadian rhythmicity, whereas uridine and guanosine could participate in the maintenance of rhythmicity.

Recovery from an acute systemic and central LPS-inflammation challenge is affected by mouse sex and genetic background.

Genetic and sexual factors influence the prevalence and the pathogenesis of many inflammatory disorders. In this study their relevance on the peripheral and central inflammatory status induced by a peripheral injection of lipopolysaccharide (LPS) was evaluated. BALB/c and CD-1 male and female mice were intraperitoneally injected with LPS. Spleens and brains were collected 2 and 72 hours later to study the levels of IL-6, TNF-α and IL-1ß. Percentage of microglia and astrocytes was determined in the cortex and hippocampus. Locomotor activity was registered before and during the 72 hours after LPS-treatment. Two hours after LPS-injection, a peripheral increase of the three cytokines was found. In brains, LPS increased TNF-α only in males with higher levels in CD-1 than BALB/c. IL-1ß increased only in CD-1 males. IL-6 increased in both strains with lower levels in BALB/c females. Peripheral and central levels of cytokines decline 72 hrs after LPS-treatment whilst a significantly increase of Iba-1 expression was detected. A dramatic drop of the locomotor activity was observed immediately after LPS injection. Our results show that acute systemic administration of LPS leads to peripheral and central increase of pro-inflammatory cytokines and microglia activation, in a strain and sex dependent manner.

Participation of the Olfactory Bulb in Circadian Organization during Early Postnatal Life in Rabbits.

Experimental evidence indicates that during pre-visual stages of development in mammals, circadian regulation is still not under the control of the light-entrainable hypothalamic pacemaker, raising the possibility that the circadian rhythmicity that occurs during postnatal development is under the control of peripheral oscillators, such as the main olfactory bulb (MOB). We evaluated the outcome of olfactory bulbectomy on the temporal pattern of core body temperature and gross locomotor activity in newborn rabbits. From postnatal day 1 (P1), pups were randomly assigned to one of the following conditions: intact pups (INT), intact pups fed by enteral gavage (INT+ENT), sham operated pups (SHAM), pups with unilateral lesions of the olfactory bulb (OBx-UNI), and pups with bilateral lesions of the olfactory bulb (OBx-BI). At the beginning of the experiment, from P1-8, the animals in all groups were fed at 11:00, from P9-13 the feeding schedule was delayed 6 h (17:00), and finally, from P14-15 the animals were subjected to fasting conditions. The rabbit pups of the INT, INT+ENT, SHAM and OBx-UNI groups exhibited a clear circadian rhythmicity in body temperature and locomotor activity, with a conspicuous anticipatory rise hours prior to the nursing or feeding schedule, which persisted even during fasting conditions. In addition, phase delays in the nursing or feeding schedule induced a clear phase shift in both parameters. In contrast, the OBx-BI group exhibited atypical rhythmicity in both parameters under entrained conditions that altered the anticipatory component, as well as deficient phase control of both rhythms. The present results demonstrate that the expression of circadian rhythmicity at behavioral and physiological levels during early stages of rabbit development largely depends on the integrity of the main olfactory bulb.

Biotin deficiency and biotin excess: effects on the female reproductive system.

Biotin deficiency and biotin excess have both been found to affect reproduction and cause teratogenic effects. In the reproductive tract, however, the effects of biotin have not been well established yet. We investigated the effects of varying biotin content diets on the oestrus cycle, ovarian morphology, estradiol and progesterone serum levels, and the uterine mRNA abundance of their nuclear receptors, as well as on the activity of the estradiol-degrading group of enzymes cytochrome P450 (CYP) in the liver. Three-week-old female BALB/cAnN Hsd mice were fed a biotin-deficient, a biotin-control, or a biotin-supplemented diet (0, 7.2 or 400 micromol of free biotin/kg diet, respectively) over a period of nine weeks. Striking effects were observed in the biotin-deficient group: mice showed arrested estrous cycle on the day of diestrus and changes in ovary morphology. Estradiol serum concentration increased 49.2% in biotin-deficient mice compared to the control group, while the enzymatic activities of CYP1A2 and CYP2B2 increased (P<0.05). The mRNA abundance of nuclear estrogen and progesterone receptors decreased in the biotin-deficient mice. In the biotin-supplemented group we found that, in spite of a significant (P<0.05) decrease in the number of primary and Graafian follicles and in CYP1A2 activities, mice exhibited 105.4% higher serum estradiol concentration than the control group. No changes in the expression of the nuclear receptors were observed. No significant differences were observed in serum progesterone among the groups. Our results indicate that both the deficiency and the excess of biotin have significant effects on the female mouse reproductive system.

Prevalencia de asma y enfermedades atópicas en niños de Panamá. Estudio Nacional de Asma y Atopia en niños (ISAAC) fase III

Objetivo: Describir comparativamente la prevalencia del asma y enfermedades atómicas basado en el estudio ISAAC FASE 1 y FASE 111 en niños de 6-7 años y 13-14 años de edad en la República de Panamá Metodología : Se seleccionaron al azar 35 escuelas y colegios en la provincia de Panamá, Herrera, Chiriquí y Veraguas, de la República de Panamá. La información se obtuvo por un cuestionario elaborado usando el protocolo del Estudio Internacional de Asma y Alergia en la niñez (ISAAC). Todos los cuestionarios fueron revisados y los datos fueron transferidos a una base de datos en Epi-Info 6.0 , usando el formato y la codificación de ISAAC. El análisis estadístico de los resultados se efectuó obteniendo las frecuencias de las variables y aplicando la prueba de chi cuadrado. Resultados: Se estudiaron un total de 6155 niños de dos grupos etareos ,de 6-7 años (2941) y de 13 -14 años (3214). La prevalencia del asma en la República de Panamá puede estimarse en niños escolares de 6 a 7 años en 22.7% y de 13-14 años en 22.9% con una prevalencia general de 22.8% (p<0.001). La prevalencia de enfermedades atópicas relacionadas a asma se estimó en 52.6% para la rinitis, conjuntivitis 30.2% y eczema en 27.4% Conclusión: La prevalencia de asma en la República de Panamá comparando los resultados del estudio ISAAC 1997 y 2003 es de 22.8% en niños de 6-7 años y de 20% en niños de 13-14 años.

Objectives: Define the prevalence of asthma and atopic diseases in children 6-7 years and 13-14 years of age in the Republic of Panama according to ISAAC protocols FASE 1 and FASE 111 studies. Material and Methods: We randomly selected 35 elementary schools and junior high schools in the province of Panama, Herrera, Chiriquí and Veraguas of the Republic of Panama. The information was gotten by a questionnaire using the protocol of the International Study of Asthma and Allergy in Children (ISAAC). All questionnaires were reviewed and the data were transferred to a database in Epi-Info 6.0, using the format and the ISAAC code. The Statistical analysis of the results was made obtaining the frequencies of the variables and applying the chi-square test. Results: A total of 6155 children from two age groups, aged 6-7 years (2941) and 13-14 years (3214) were studied. The prevalence of asthma in the Republic of Panama can be estimated in school children from 6 to 7 years in 22.7% and 13-14 years in 22.9% (p<0.001)with a general prevalence of 22.8% (p <0.001). The prevalence of atopic diseases related to asthma was estimated at 52.6% (p<0.001)for rhinitis, conjunctivitis 30.2% and eczema in 27.4%(p<0.001) Conclusion: The data gotten in this study demonstrate a high prevalence of asthma in the Republic of Panama. These data be used in order to evaluate the present and future behavior of these diseases in Panama, and most call attention on the necessity of taking specific measurements for their prevention and management.

José Assef Yara: vida y obra / José Assef Yara Multimedia: life and work

La investigación "Dr José Assef Yara, vida y obra" forma parte del proyecto “Historia de la Educación en la provincia de Ciego de Ávila” que pretende estudiar esta personalidad que trasciende de lo local a lo nacional por su participación en las acciones del 13 de Marzo, por su protagonismo en el Directorio Revolucionario, como dirigente político y activo integrante de la Federación Estudiantil Universitaria, médico especialista de Ortopedia y que constituye un paradigma de personalidad multifacética al que se le confirió la condición de Hijo Ilustre de la Provincia de Ciego de Ávila post morten. El poco conocimiento de esta figura por parte de los estudiantes que ingresan a la Facultad de Ciencias Médicas de Ciego de Ávila que lleva su nombre desde el año 2002, motivó a los autores a realizar este trabajo, donde se utilizaron métodos y técnicas propias de la investigación cualitativa e histórica tales como: El histórico-lógico, analítico-sintético, el biográfico o historia de vida, la revisión bibliográfica, el análisis documental y la entrevista.

The little knowledge on the part of the students that enter to the Faculty of Medical Sciences on the life and work of "Dr. José Assef Yara", who this institution is called after, constituted the driving motor for the execution of this work. It was compiled a series of data, photos and materials related to his fertile life ,most of them unpublished and dispersed; Through the qualitative and historical investigation techniques by the help of the new information technologies and communications, through a multimedia in which: Adobe Photoshop, as main graphic publisher; Adobe Firework as accessory graphic publisher; Goldwave like the publisher of audio; Adobe Dreamweaver as publisher of files XML; Adobe Flash 8,0 as final publisher were used. As a consequence a computing product was obtained, undertaking in its different sections: its Biography, a section dedicated to the Youths of March 13, ¿Why José Assef Yara?, a Gallery of images, a section of deepening: Something more and other informative sections: Bibliography, Gratitudes and Credits.

La Investigación en Sitemas y Servicios de Salud: revisión bibliográgica / Research on systems and services: bibliographic review

Se realizó una revisión bibliográfica sobre la Investigación en Sistemas y Servicios de Salud(ISSS) viendo ésta como una forma práctica y necesaria de investigación. Se muestra la metodología y los pasos a seguir con la intención de que sea un material útil a la hora de planificar un estudio y de obtener resultados que sirvan para la toma de decisiones científicamente fundamentadas.

A bibliographic review which makes reference to research and systems and health services as a practical and necessary form of investigation, given its characteristics was performed. The methodology as well as the steps in this type of investigation are shown, so that it serves as a useful guide to correctly plan a survey and than attain results to allow for the scientifically grounded decision-making process.

Reflexión crítica de un instrumento de evaluación escrito en la especialidad de Medicina General Integral / A critical analysis of written evaluation instrument in the Integral General Medicine

En el trabajo realizado se hace un bosquejo acerca de la importancia de la evaluación de la competencia profesional como uno de los cuatros pilares fundamentales en el incremento de la calidad de los Recursos Humanos en Salud. Se realiza un análisis crítico de un instrumento de evaluación escrito en la Especialidad de Medicina General Integral. Para la confección del instrumento evaluativo se identificaron un listado de problemas que incluyen entre otros: la familia, el análisis de la situación de salud, la higiene del trabajo, las enfermedades transmisibles, las crónicas no transmisibles y el adulto mayor