High power illumination system for uniform, isotropic and real time controlled irradiance in photoactivated processes research.

In the study of photocatalytic and photoactivated processes and devices a tight control on the illumination conditions is mandatory. The practical challenges in the determination of the necessary photonic quantities pose serious difficulties in the characterization of catalytic performance and reactor designs and configurations, compromising an effective comparison between different experiments. To overcome these limitations, we have designed and constructed a new illumination system based in the concept of the integrating sphere (IS). The system provides uniform and isotropic illumination on the sample, either in batch or continuous flow modes, being these characteristics independent of the sample geometry. It allows direct, non-contact and real time determination of the photonic quantities as well as versatile control on the irradiance values and its spectral characteristics. It can be also scaled up to admit samples of different sizes without affecting its operational behaviour. The performance of the IS system has been determined in comparison with a second illumination system, mounted on an optical bench, that provides quasi-parallel beam (QPB) nearly uniform illumination in tightly controlled conditions. System performance is studied using three sample geometries: a standard quartz cuvette, a thin straight tube and a microreactor by means of potassium ferrioxalate actinometry. Results indicate that the illumination geometry and the angular distribution of the incoming light greatly affect the absorption at the sample. The sample light absorption efficiency can be obtained with statistical uncertainties of about 3% and in very good agreement with theoretical estimations.

Potential Fungal Zoonotic Pathogens in Cetaceans: An Emerging Concern.

Over 60% of emerging infectious diseases in humans are zoonotic, often originating from wild animals. This long-standing ecological phenomenon has accelerated due to human-induced environmental changes. Recent data show a significant increase in fungal infections, with 6.5 million cases annually leading to 3.7 million deaths, indicating their growing impact on global health. Despite the vast diversity of fungal species, only a few are known to infect humans and marine mammals. Fungal zoonoses, especially those involving marine mammals like cetaceans, are of global public health concern. Increased human-cetacean interactions, in both professional and recreational settings, pose risks for zoonotic disease transmission. This review focuses on the epidemiology, clinical manifestations, and zoonotic potential of major fungal pathogens shared in humans and cetaceans, highlighting their interspecies transmission capability and the challenges posed by antifungal resistance and environmental changes. It underscores the need for enhanced awareness and preventative measures in high-risk settings to protect public health and marine ecosystems.

The Ecology of Non-Candida Yeasts and Dimorphic Fungi in Cetaceans: From Pathogenicity to Environmental and Global Health Implications.

Cetaceans, which are integral to marine ecosystems, face escalating anthropogenic threats, including climate change and pollution, positioning them as critical sentinel species for ocean and human health. This review explores the neglected realm of non-Candida yeasts in cetaceans, addressing the gaps in the understanding of their prevalence, pathogenicity, and environmental impacts. By examining identified species such as Cryptococcus spp., Paracoccidioides spp., and several dimorphic fungi, this review emphasizes global prevalence, epidemiology and ecology, pathogenicity, and potential zoonotic implications. It also discusses the fine line between yeast commensalism and pathogenicity by considering environmental influences such as pollution, climate shifts, and immune suppression. Environmental impact discussions delve into how rising ocean temperatures and pollution can modify yeast mycobiota, potentially affecting marine host health and broader ecosystem dynamics. The cetacean's unique physiology and ecological niches are considered, highlighting potential impacts on behaviors, reproductive success, and survival rates. Identifying crucial knowledge gaps, the review calls for intensified research efforts, employing advanced molecular techniques to unravel the cetacean mycobiome. Systematic studies on yeast diversity, antifungal susceptibility, and their influence on environmental and ecosystem health are proposed, and the balance between commensal and pathogenic species emphasizes the significance of the One Health approach. In conclusion, as marine mammals face unprecedented challenges, unveiling non-Candida yeasts in cetaceans emerges as a critical endeavor with far-reaching implications for the conservation of marine ecosystems and for both animal and human public health.

One Health Approach: Invasive California Kingsnake (Lampropeltis californiae) as an Important Source of Antimicrobial Drug-Resistant Salmonella Clones on Gran Canaria Island.

The increase in the reptile population has led to a rise in the number of zoonotic infections due to close contact with reptiles, with reptile-associated salmonellosis being particularly relevant. California kingsnake invasion not only threatens the endemic reptile population of the island of Gran Canaria (Spain) but also poses serious public health problems by spreading zoonotic pathogens and their antimicrobial resistance (AMR) to the environment. Thus, the aim of this study was to assess the occurrence, genetic diversity, and AMR among Salmonella spp. strains isolated from California kingsnakes in Gran Canaria Island (Spain). Of 73 invasive individuals captured, 20.5% carried Salmonella spp., belonging to different subspecies and serovars, with subsp. salamae as the most abundant. Pulsed-field electrophoresis showed high genetic diversity among subsp. salamae isolates, and among these, 73.3% showed resistance to at least one of the antimicrobials tested. In conclusion, the present study revealed the importance of wild invasive California kingsnakes as reservoirs of drug-resistant Salmonella spp. that could pose a direct threat to livestock and humans. Identification of drug-resistant Salmonella strains in wildlife provides valuable information on potential routes of transmission that involve risks to public and animal health.

Kinetics of the invasion of a non-phagocytic fish cell line, RTG-2 by Yersinia ruckeri serotype O1 biotype 1.

Yersiniosis, caused by the fish pathogen Yersinia ruckeri, is a serious bacterial septicaemia affecting mainly salmonids worldwide. The acute infection may result in high mortality without apparent external disease signs, while the chronic one causes moderate to considerable mortality. Survivors of yersiniosis outbreaks become carriers. Y. ruckeri is able to adhere to, and to invade, phagocytic and non-phagocytic fish cells by using unknown molecular mechanisms. The aim of this study was to describe the kinetics of cell invasion by Y. ruckeri serotype O1 biotype 1 in a fish cell line (RTG-2) originating from rainbow trout gonads. The efficiency of invasion by Y. ruckeri was found to be temperature dependent, having a maximum at 20 °C. The bacterium was able to survive up to 96 h postinfection. The incubation of the cells at 4 °C and the pre-incubation of the bacteria with sugars or heat-inactivated antiserum significantly decreased the efficiency of invasion or even completely prevented the invasion of RTG-2 cells. These findings indicate that Y. ruckeri is capable of adhering to, entering and surviving within non-phagocytic cells, and that the intracellular environment may constitute a suitable niche for this pathogen that can favour the spread of infection and/or the maintenance of a carrier state of fish.

Salmonella enterica subsp. enterica serotypes isolated for the first time in feral cats: The impact on public health.

Stray cat populations can represent a significant threat of the transmission of zoonotic diseases such as salmonellosis. The objective of this study was to assess Salmonella carriage by free-living cats in Gran Canaria island and the Salmonella serovars involved, in order to inform to those responsible for the colonies about the possible risk factors. One hundred rectal swabs of feral cats were taken. Salmonella strains were serotyped in accordance with Kauffman-White-Le-Minor technique. Of a total of 100 animals under study, 19% were found to be positive to Salmonella spp. This is the first report that described the zoonotic serovars S. Nima, S. Bredeney, S. Grancanaria and S. Kottbus in cats. The present study demonstrates that feral cats may represent a source of risk for the spread of different Salmonella zoonotic serovars. It has been reported that there is a certain correlation between Salmonella isolates from pets and wild animals. Further studies are needed from other animal species and environmental sources to make this correlation.

Antibody Response 3 Months after 2 Doses of BNT162b2 mRNA COVID-19 Vaccine in Residents of Long-Term Care Facilities.

BACKGROUND: Older adults living in long-term care facilities (LTCFs) are at increased risk for severe outcomes from COVID-19 and were identified as a priority group in COVID-19 vaccination strategies. Emerging evidence suggests vaccine effectiveness in LTCF populations, but data about median and long-term durability of immune response after vaccination are still limited. OBJECTIVES: In this study, we assessed the humoral response to BNT162b2 mRNA COVID-19 vaccine 3 months after the second dose, in a cohort of 495 residents aged ≥65 years from 11 LTCF in Granada, Spain. METHOD: Between April 19 and April 30, 2021, we measured anti-SARS-CoV-2 Spike IgG to evaluate the humoral vaccination response. Antibody titers were reported in binding antibody units (BAU/mL). Bivariate and multivariate logistic regression models were performed to investigate the impact of age, sex, underlying health conditions, and prior COVID-19 infection on the antibody levels. RESULTS: Over 96% of the participants developed an adequate humoral response. We detected higher antibody titers in previously infected individuals, compared with those previously uninfected (B: 1,150.059 BAU/mL, p < 0.001). Moreover, we found a significant inverse association between age and antibody levels (B: -7.943 BAU/mL, p < 0.05). This negative age-dependent response was more noticeable among residents over 85 years old. In contrast, baseline health conditions and cognitive status were not associated with different antibody levels. CONCLUSIONS: These findings support monitoring COVID-19 vaccination response trend in older adults, in order to optimize future disease prevention and control strategies in this vulnerable population.

Screening of New Potential Probiotics Strains against Photobacterium damselae Subsp. piscicida for Marine Aquaculture.

On intensive fish farms, 10% of the population dies exclusively from pathogens, and Photobacterium damselae subsp. Piscicida (Ph. damselae subsp. Piscicida), the bacteria causing pasteurellosis in marine aquaculture, is one of the major pathogens involved. The objective of this study was to obtain new probiotic strains against pasteurellosis in order to limit the use of chemotherapy, avoiding the environmental repercussions generated by the abusive use of these products. In this study, 122 strains were isolated from the gills and intestines of different marine fish species and were later evaluated in vitro to demonstrate the production of antagonistic effects, the production of antibacterial substances, adhesion and growth to mucus, resistance to bile and resistance to pH gradients, as well as its harmlessness and the dynamic of expression of immune-related genes by real-time PCR after administration of the potential probiotic in the fish diet. Only 1/122 strains showed excellent results to be considered as a potential probiotic strain and continue its characterization against Ph. damselae subsp. piscicida to determine its protective effect and elucidating in future studies its use as a possible probiotic strain for marine aquaculture.

A real-world ten-week follow-up of the COVID outbreak in an outpatient drug clinic in Salamanca (Spain).

OBJECTIVE: To compare over ten weeks the number of relapses, hospital admissions, calls made, admissions to therapeutic communities, face-to-face visits, treatment adjustment, number of injectables administered, and number of emergencies attended due to emotional and behavioral alterations and/or substance use disorder, and to describe and quantify social emergencies in an outpatient drug clinic (ODC) in Salamanca (Spain) from March 16, 2020, to May 22, 2020. METHODS: This is an ecological study of the COVID pandemic over ten weeks. The study examines the set of alcohol or other drug-dependent or dual disorder patients in the population of Salamanca, Spain. The measurements were: professionals; calls made; percentage of successful calls; face-to-face visits; first visits made; reviews made; techniques; injectable treatments; other treatments; evolution; relapses. The ODC includes about 375 new patients each year and another 650 other patients annually. RESULTS: The study found the number of relapses to be greater in the last five weeks of the 10-week study period. Patients' psychopathological instability also increased, and face-to-face visits were necessary. The most frequent psychopathology that required face-to-face intervention was depressive disorder. The number of interventions with patients increased. In parallel, social workers' efforts were greater after the seventh week. There was a decrease in response to calls. Throughout this time, the ODC attended to patients who needed to be treated for the first time. CONCLUSIONS: Confinement due to the coronavirus pandemic generated maladaptive emotional responses and other behaviors, such as excessive alcohol consumption. The number of face-to-face consultations, admissions, and referrals to therapeutic communities increased. Patients under stress and in social isolation resorted more often to substance use. The ODC had to adopt a flexible approach to evaluate patients with more serious problems, by using face-to-face assessments.

The Impact of COVID-19 Pandemic on the Castile and Leon Addiction Treatment Network: A Real-Word Experience.

Background: Patients suffering from addiction are a vulnerable group in the midst of COVID-19, so their healthcare is considered essential. In this paper, the measures and responses of the Drug Addiction Assistance Network of Castile and Leon (DAACYL) in Spain during the first 6 weeks of the COVID-19 pandemic are explained. The aim is that this experience could be useful in places where this problem will continue and could help future interventions. Methods: A telephone survey was carried out as the main methodology, to collect information for the subsequent organization and repercussion on professionals and patients. This was carried out by the heads of the 18 DAACYL units. Among the interventions applied, the following stand out: implantation of telemedicine techniques, restriction of daily methadone dispensing, suspension of urine controls and initiation of care programs for the homeless. Results: As a result of these interventions, the professionals observed that patients are less demanding and mostly stable, with a low percentage of relapses. An increase in the consumption of alcohol and benzodiazepines have been reported as more common among people who relapse. Furthermore, the prevalence of COVID-19 infection in the sample is minimal; therefore, different hypotheses should be considered as an explanation (infra-diagnosis, immune system used to aggression, possible anti-inflammatory effect of some psychotropic drugs and a greater perception of danger against infection than the general population). Conclusions: The rapid adaptation and successful implementation of DAACYL have had satisfactory results. On the other hand, the prevention of the possible increase in the development of behavioral addictions and the use of homemade drugs should be considered.

The Relevance of Dual Diagnoses among Drug-Dependent Patients with Sleep Disorders.

BACKGROUND: Sleep disorders are often associated with drug use. Nearly 70% of patients admitted for detoxification report sleep problems. Dual disorder (DD) is the comorbidity between mental disorders in general and disorders related to psychoactive substance use. The association between substance use and sleep disorders (SD) appears to be bidirectional. Our objective is to analyze the association between sleep disturbance history and drug use pattern (alcohol, cannabis, opioids, and cocaine). METHODS: Analysis of data in the first interview at the Addictions Unit of the Department of Psychiatry at the University of Salamanca Health Care Complex between October 2017 and January 2020. The sample consists of 398 patients. We studied the association between different variables: origin of patients (Inpatient Dual Diagnosis Detoxification Unit (IDDDU) vs. Outpatient Drug Clinic (ODC), presence of affective disorder, psychotic disorder, type of drug used, and treatment. RESULTS: Of patients with DD, 62% had more delayed sleep induction, sleep fragmentation, early awakening, and nightmares. Outpatients had more difficulty falling asleep because, in many cases, they had not previously sought any medical assistance. On the other hand, 67% of the patients with insomnia presented depression. CONCLUSIONS: There is evidence of a harmful association between DD and SD.

Characterization of the first autochthonous dengue outbreak in Spain (August-September 2018).

On October 3rd 2018, dengue virus (DENV) infection was confirmed in three family members (symptoms onset between August 18th and 27th) without travel history outside of Spain. They had been together in the Autonomous Communities (AC) of Murcia and Andalusia. By the end of October, a second cluster of two dengue cases (symptoms onset on September 27th and 30th) was confirmed in the AC of Murcia. DENV type 1 sequence was identical to the first cluster, and the epidemiological link was a visit from a case of the first cluster to a fruit-farm neighboring the small village of residence of the second cluster. The entomological investigation found Aedes albopictus activity in this area although all mosquitoes were PCR-negative for DENV. This is the first autochthonous dengue outbreak identified in Spain. This outbreak highlights challenges to timely detect and respond to DENV transmission and opens questions on dengue dynamics in a non-endemic context.

Benzodiazepine abuse, misuse, dependence, and withdrawal among schizophrenic patients: A review of the literature.

Patients diagnosed with schizophrenia are at least three times more likely to develop a substance use disorder than controls. These patients are frequently prescribed benzodiacepines as a coadjuvant drug, which have a high potential for addiction. We performed a literature review aiming to gather evidence on various topics concerning the use of benzodiacepines in schizophrenia, with a focus on possible abuse: 1) Prevalence of prescripted and non-prescripted benzodiacepine use among patients, 2) Prevalence of abusers, 3) Effects of long-term benzodiacepine abuse in schizophrenia prognosis, 4) Possible management strategies for benzodiacepine abuse in this population. Our search revealed there is a high variability (up to 20%) in benzodiacepine abuse among patients, with cannabis and stimulants being more frequent, and no clear demographic traits have been identified among these patients. Patients with affective symptoms are more likely to abuse benzodiazepines. Its long-term effects on prognosis have been debated, with some papers hinting at a higher mortality rate. Tapering benzodiacepines has been associated with an improvement in some cognitive functions. Management strategies for potential abuse do not differ greatly for this population, and no specific pharmacological aid can be indicated, but an integral approach is proposed.

Consumo de psicofármacos y exposición a toxinas bacterianas vehiculizadas por alimentos: una asociación peligrosa / Consumption of psychoactive drugs and exposure to bacterial toxins carried by food: a dangerous association

Objetivo: Describir y analizar desde el punto de vista clínico y epidemiológico un brote de toxiinfección alimentaria en una institución de enfermos psiquiátricos de Granada, en 2015, y examinar si el tratamiento con psicofármacos constituye un factor de riesgo para desarrollar una toxiinfección alimentaria, analizando los grados de susceptibilidad según el grupo terapéutico consumido. Método: Estudio ambispectivo de cohortes. La unidad de análisis fueron los residentes. Se realizó búsqueda activa de casos, encuesta alimentaria y búsqueda de otros riesgos, e inspección alimentaria. Se estudiaron variables de persona, lugar y tiempo. Análisis descriptivo (frecuencias absolutas y relativas), cálculo de las tasas de ataque por pabellón y por menú. Análisis bivariado (ji al cuadrado, t de Student) y riesgo relativo como medida de la fuerza de asociación. Análisis multivariado mediante regresión logística para el análisis de riesgos de la medicación. Resultados: Se contabilizaron 18 casos con diarrea sin fiebre (periodo de incubación de 6-16 horas), de carácter leve y autolimitado. Las manifestaciones clínicas, la agrupación temporal de casos y las características de los alimentos ingeridos centraron la sospecha en una toxina bacteriana. A igualdad en el resto de variables, los grupos terapéuticos N03AF y N03AG confirieron mayor riesgo de enfermar (odds ratio [OR]: 8,626; intervalo de confianza del 95% [IC95%]: 2,050-36,308; p=0,003; y OR: 14,516; IC95%: 3,155-66,784; p=0,001, respectivamente). Conclusión: La disminución del tránsito intestinal causada por la administración de antiepilépticos puede aumentar el tiempo de exposición de la mucosa intestinal a la toxina, aumentando el riesgo de enfermar y de padecer complicaciones. Debe realizarse un esfuerzo higiénico suplementario en este tipo de instituciones para prevenir estas afecciones

Objective: To describe and analyse from a clinical and epidemiological point of view, a food borne outbreak in a psychiatric institution in Granada, in 2015, and to examine whether treatment with psychoactive drugs constitutes a risk factor for the development of a food borne disease, analysing the degree of susceptibility according to the therapeutic group consumed. Method: Ambispective cohort study. Residents were the unit of analysis. Our group carried out an active case search and a food survey. A search for other risks was developed as well as a food inspection. Location, time and individual variables were studied. A descriptive analysis was conducted (absolute and relative frequencies). Calculation of attack rates by building and by menu was made. Bi-variant analysis (Chi-square test, t-Student test) and relative risk were used as a measure of strength of association. For risk analysis of medication, a multivariate analysis using logistic regression was carried out. Results: 18 cases with diarrhoea without fever were found (incubation period from 6 to 16hours). Cases were mild and self-limiting. The clinical manifestations, the temporal grouping of cases and the characteristics of the ingested foods, focussed suspicion on a bacterial toxin. Being equal in the rest of variables, the N03AF, and N03AG therapeutic groups confer greater risk of disease (odds ratio [OR]: 8.626; 95% confidence interval [95%CI]: 2.050-36.308; p=0.003; and OR: 14.516; 95%CI: 3.155-66.784; p=0.001, respectively). Conclusion: Decreased intestinal transit, caused by the administration of anticonvulsants, may increase exposure time of the intestinal mucosa to the toxin, increasing the risk of disease and suffering from complications. An additional hygienic effort should be made in this type of institution to prevent these pathologies

Predictive score and probability of CTX-like toxicity in fish samples from the official control of ciguatera in the Canary Islands.

This research identifies factors associated with the contamination by ciguatoxins (CTXs) in a population of fish and proposes a predictive score of the presence of CTX-like toxicity in amberjack samples from the official control program of ciguatera in the Canary Islands of the Directorate-General (DG) Fisheries (Canary Government). Out of the 970 samples of fish studied, 177 (18.2%) samples showed CTX-like toxicity. The fish were classified according to the species, amberjack (Seriola dumerili and S. rivoliana) (n = 793), dusky grouper (Epinephelus marginatus) (n = 145) and wahoo (Acanthocybium solandri) (n = 32). The data were separated by species category and statistically examined, resulting in 137 (17.3%) amberjack and 39 (26.9%) grouper samples showing CTX-like toxicity; regarding wahoo species, only 1 toxic sample (3.1%) was found. According to fishing location the contamination rates suggested grouping the islands in four clusters; namely: {El Hierro: HI; La Gomera: LG; La Palma: LP}, {Gran Canaria: GC; Tenerife: TF}, {Fuerteventura: FU} and {Lanzarote: LZ}. For the amberjack species, the multivariate logistic regression showed the factors that maintained independent association with the outcome, which were the warm season (OR = 3.617; 95% CI = 1.249-10.474), the weight (per kg, 1.102; 95% CI = 1.069-1.136) and the island of fish catching. A prediction score was obtained for the probability of contamination by CTX in amberjack fish samples. The area under de curve (AUC) obtained using the validation data was 0.747 (95% CI = 0.662-0.833). Regarding grouper species, the island of fishing was the only factor that showed significant differences associated with the presence of CTX-like toxicity. We provide herein data for a better management and prediction of ciguatera in the Canary Islands, suggesting a review of the minimum limits of fish weight established by the Canary Government for the control program.

[Consumption of psychoactive drugs and exposure to bacterial toxins carried by food: a dangerous association]. / Consumo de psicofármacos y exposición a toxinas bacterianas vehiculizadas por alimentos: una asociación peligrosa.

OBJECTIVE: To describe and analyse from a clinical and epidemiological point of view, a food borne outbreak in a psychiatric institution in Granada, in 2015, and to examine whether treatment with psychoactive drugs constitutes a risk factor for the development of a food borne disease, analysing the degree of susceptibility according to the therapeutic group consumed. METHOD: Ambispective cohort study. Residents were the unit of analysis. Our group carried out an active case search and a food survey. A search for other risks was developed as well as a food inspection. Location, time and individual variables were studied. A descriptive analysis was conducted (absolute and relative frequencies). Calculation of attack rates by building and by menu was made. Bi-variant analysis (Chi-square test, t-Student test) and relative risk were used as a measure of strength of association. For risk analysis of medication, a multivariate analysis using logistic regression was carried out. RESULTS: 18 cases with diarrhoea without fever were found (incubation period from 6 to 16hours). Cases were mild and self-limiting. The clinical manifestations, the temporal grouping of cases and the characteristics of the ingested foods, focussed suspicion on a bacterial toxin. Being equal in the rest of variables, the N03AF, and N03AG therapeutic groups confer greater risk of disease (odds ratio [OR]: 8.626; 95% confidence interval [95%CI]: 2.050-36.308; p=0.003; and OR: 14.516; 95%CI: 3.155-66.784; p=0.001, respectively). CONCLUSION: Decreased intestinal transit, caused by the administration of anticonvulsants, may increase exposure time of the intestinal mucosa to the toxin, increasing the risk of disease and suffering from complications. An additional hygienic effort should be made in this type of institution to prevent these pathologies.

Discovery of a Novel Inhaled PI3Kδ Inhibitor for the Treatment of Respiratory Diseases.

Oral PI3Kδ inhibitors such as Idelalisib and Duvelisib have shown efficacy as anticancer agents and Idelalisib has been approved for the treatment of three B-cell cancers. However, Idelalisib has a black box warning on its product label regarding the risks of fatal and serious toxicities including hepatic toxicity, severe diarrhea, colitis, pneumonitis, infections, and intestinal perforation. Some of these side effects are mechanism-related and could hinder the development of Idelalisib for less severe conditions. For respiratory diseases, compounds administered by inhalation are delivered directly to the site of action and may improve the therapeutic index of a drug, minimizing undesired side effects. This work describes the discovery and optimization of inhaled PI3Kδ inhibitors intended for the treatment of severe asthma and COPD. Once the potency was in the desired range, efforts were focused on identifying the particular physicochemical properties that could translate into better lung retention. This medicinal chemistry exercise led to the identification of LAS195319 as a candidate for clinical development.

[Changes in Hepatitis A epidemiological pattern in Andalucía: 2007-2017]. / Cambios en el patrón epidemiológico de la Hepatitis A en Andalucía: 2007-2017.

OBJECTIVE: Sexual transmission of hepatitis A (HAV) is documented, mainly by risk behaviors in men who have sex with men (MSM). There have been HAV outbreaks in MSM in countries of the European Union in the last years. The aim of this work was to study HAV epidemiology in Andalusia in the last 10 years (2007-2017) and the outbreaks among MSM in this period. METHODS: Retrospective descriptive study of HAV cases reported in the Andalusia Epidemiological Surveillance System between January 2007 and May 2017. We calculated the annual incidence rate per 100000 habitants. We studied case distribution for gender and age. We used the male-female ratio as an indirect marker for MSM. RESULTS: The mean annual incidence rate in the study period was 4.09 cases per 100000 habitants, with a difference by sex: 4.7 per 100000 men and 2.53 per 100000 women. Two large outbreaks were detected in this period: one in 2008-2009 and another in 2016-2017. The epidemiological characteristics of these outbreaks differ from the classical pattern of the disease, affecting young MSM with associated sexual risk behaviors. CONCLUSIONS: MSM play a fundamental role in recent outbreaks of HAV. For disease control we must carry out a different strategy, assessing the introduction of systematic vaccination.

OBJETIVO: La trasmisión sexual de la hepatitis A (VHA) está documentada, principalmente en conduc- tas de riesgo en hombres que tienen sexo con hombres (HSH). En los últimos años están apareciendo brotes de VHA en HSH en países de la Unión Europea. El objetivo del trabajo fue estudiar la epidemiología del VHA en Andalucía en los últimos 10 años (2007-2017) y la de los brotes ocurridos en HSH en dicho periodo. METODOS: Estudio descriptivo retrospectivo de los casos de VHA declarados en el Sistema de Vigilancia Epidemiológica de Andalucía (SVEA) entre enero de 2007 y mayo de 2017. Se calculó la tasa de incidencia anual por 100.000 habitantes. Se estudió la distribución de los casos por grupo de edad y sexo. Se usó la razón hombre-mujer, como marcador indirecto de los HSH. RESULTADOS: La tasa de incidencia media anual en el periodo de estudio fue 4,09 casos por 100.000 habitantes, con una diferencia según sexo: 4,7 por 100.000 hombres y 2,53 por 100.000 mujeres. Aparecieron dos grandes brotes en este periodo: uno en 2008-2009 y otro en 2016-2017. Las características epidemiológicas de estos brotes difirieron del patrón clásico de la enfermedad, afectando a HSH jóvenes, colectivo que se asocia con conductas sexuales de riesgo. CONCLUSIONES: Los HSH tienen un papel fundamental en los brotes de VHA aparecidos recientemente. Para el control de la enfermedad debemos realizar una estrategia diferente, valorando la introducción de la vacunación sistemática.

4-Amino-7,8-dihydro-1,6-naphthyridin-5(6 H)-ones as Inhaled Phosphodiesterase Type 4 (PDE4) Inhibitors: Structural Biology and Structure-Activity Relationships.

Rational design of a novel template of naphthyridinones rapidly led to PDE4 inhibitors with subnanomolar enzymatic potencies. X-ray crystallography confirmed the binding mode of this novel template. We achieved compounds with double-digit picomolar enzymatic potencies through further structure-based design by targeting both the PDE4 enzyme metal-binding pocket and occupying the solvent-filled pocket. A strategy for lung retention and long duration of action based on low aqueous solubility was followed. In vivo efficacies were measured in a rat lung neutrophilia model by suspension microspray and dry powder administration. Suspension microspray of potent compounds showed in vivo efficacy with a clear dose-response. Despite sustained lung levels, dry powder administration performed much less well and without proper dose-response, highlighting clear differences between the two formulations. This indicates a deficiency in the low aqueous solubility strategy for long duration lung efficacy.

Cambios en el patrón epidemiológico de la Hepatitis A en Andalucía: 2007-2017 / Changes in Hepatitis A epidemiological pattern in Andalucía: 2007-2017

Fundamentos: La trasmisión sexual de la hepatitis A (VHA) está documentada, principalmente en conductas de riesgo en hombres que tienen sexo con hombres (HSH). En los últimos años están apareciendo brotes de VHA en HSH en países de la Unión Europea. El objetivo del trabajo fue estudiar la epidemiología del VHA en Andalucía en los últimos 10 años (2007-2017) y la de los brotes ocurridos en HSH en dicho periodo. Métodos: Estudio descriptivo retrospectivo de los casos de VHA declarados en el Sistema de Vigilancia Epidemiológica de Andalucía (SVEA) entre enero de 2007 y mayo de 2017. Se calculó la tasa de incidencia anual por 100.000 habitantes. Se estudió la distribución de los casos por grupo de edad y sexo. Se usó la razón hombre-mujer, como marcador indirecto de los HSH. Resultados: La tasa de incidencia media anual en el periodo de estudio fue 4,09 casos por 100.000 habitantes, con una diferencia según sexo: 4,7 por 100.000 hombres y 2,53 por 100.000 mujeres. Aparecieron dos grandes brotes en este periodo: uno en 2008-2009 y otro en 2016-2017. Las características epidemiológicas de estos brotes difirieron del patrón clásico de la enfermedad, afectando a HSH jóvenes, colectivo que se asocia con conductas sexuales de riesgo. Conclusiones: Los HSH tienen un papel fundamental en los brotes de VHA aparecidos recientemente. Para el control de la enfermedad debemos realizar una estrategia diferente, valorando la introducción de la vacunación sistemática

Background: Sexual transmission of hepatitis A (HAV) is documented, mainly by risk behaviors in men who have sex with men (MSM). There have been HAV outbreaks in MSM in countries of the European Union in the last years. The aim of this work was to study HAV epidemiology in Andalusia in the last 10 years (2007-2017) and the outbreaks among MSM in this period. Methods: Retrospective descriptive study of HAV cases reported in the Andalusia Epidemiological Surveillance System between January 2007 and May 2017. We calculated the annual incidence rate per 100000 habitants. We studied case distribution for gender and age. We used the male-female ratio as an indirect marker for MSM. Results: The mean annual incidence rate in the study period was 4.09 cases per 100000 habitants, with a difference by sex: 4.7 per 100000 men and 2.53 per 100000 women. Two large outbreaks were detected in this period: one in 2008-2009 and another in 2016-2017. The epidemiological characteristics of these outbreaks differ from the classical pattern of the disease, affecting young MSM with associated sexual risk behaviors. Conclusions: MSM play a fundamental role in recent outbreaks of HAV. For disease control we must carry out a different strategy, assessing the introduction of systematic vaccination