Excess mortality in Europe coincides with peaks of COVID-19, influenza and respiratory syncytial virus (RSV), November 2023 to February 2024.

Since the end of November 2023, the European Mortality Monitoring Network (EuroMOMO) has observed excess mortality in Europe. During weeks 48 2023-6 2024, preliminary results show a substantially increased rate of 95.3 (95% CI:  91.7-98.9) excess all-cause deaths per 100,000 person-years for all ages. This excess mortality is seen in adults aged 45 years and older, and coincides with widespread presence of COVID-19, influenza and respiratory syncytial virus (RSV) observed in many European countries during the 2023/24 winter season.

Persistence of the Staphylococcus aureus epidemic European fusidic acid-resistant impetigo clone (EEFIC) in Belgium.

OBJECTIVES: In August 2018, a public health alert was issued in Belgium regarding clusters of impetigo cases caused by the epidemic European fusidic acid-resistant impetigo clone (EEFIC) of Staphylococcus aureus. As a result, the Belgian national reference centre (NRC) was commissioned to update the epidemiology of S. aureus causing community-onset skin and soft tissues infection (CO-SSTI) to assess the proportion of EEFIC among them. METHODS: For 1 year, Belgian clinical laboratories were asked to send their first three S. aureus isolated from CO-SSTI each month. Isolates were tested for antimicrobial susceptibility to oxacillin, mupirocin and fusidic acid. Resistant isolates were also spa typed and tested for the presence of the genes encoding the Panton-Valentine leucocidin, the toxic shock syndrome toxin and the exfoliatins A and B. MLST clonal complexes were deduced from the spa types. RESULTS: Among the 518 S. aureus strains analysed, 487 (94.0%) were susceptible to oxacillin. Of these, 79 (16.2%) were resistant to fusidic acid, of which 38 (48.1%) belonged to the EEFIC. EEFIC isolates were mostly isolated from young patients with impetigo and showed a seasonal late summer peak. CONCLUSIONS: These results suggest the persistence of EEFIC in Belgium. Furthermore, its prevalence may lead to reconsideration of the treatment guidelines for impetigo.

Noninvasive integrative approach applied to children in the context of recent air pollution exposure demonstrates association between fractional exhaled nitric oxide (FeNO) and urinary CC16.

Exposure to the air pollutant particulate matter (PM) is associated with increased risks of respiratory diseases and enhancement of airway inflammation in children. In the context of large scale air pollution studies, it can be challenging to measure fractional exhaled nitric oxide (FeNO) as indicator of lung inflammation. Urinary CC16 (U-CC16) is a potential biomarker of increased lung permeability and toxicity, increasing following short-term PM2.5 exposure. The single nucleotide polymorphism (SNP) CC16 G38A (rs3741240) affects CC16 levels and respiratory health. Our study aimed at assessing the use of U-CC16 (incl. CC16 G38A from saliva) as potential alternative for FeNO by investigating their mutual correlation in children exposed to PM. Samples from a small-scale study conducted in 42 children from urban (n = 19) and rural (n = 23) schools examined at two time points, were analysed. When considering recent (lag1) low level exposure to PM2.5 as air pollution measurement, we found that U-CC16 was positively associated with FeNO (ß = 0.23; 95% CI [-0.01; 0.47]; p = 0.06) in an adjusted analysis using a linear mixed effects model. Further, we observed a positive association between PM2.5 and FeNO (ß = 0.56; 95% CI [0.02; 1.09]; p = 0.04) and higher FeNO in urban school children as compared to rural school children (ß = 0.72; 95% CI [0.12; 1.31]; p = 0.02). Although more investigations are needed, our results suggest that inflammatory responses evidenced by increased FeNO are accompanied by potential increased lung epithelium permeability and injury, evidenced by increased U-CC16. In future large scale studies, where FeNO measurement is less feasible, the integrated analysis of U-CC16 and CC16 G38A, using noninvasive samples, might be a suitable alternative to assess the impact of air pollution exposure on the respiratory health of children, which is critical for policy development at population level.

COVID-19 mortality, excess mortality, deaths per million and infection fatality ratio, Belgium, 9 March 2020 to 28 June 2020.

BackgroundCOVID-19 mortality, excess mortality, deaths per million population (DPM), infection fatality ratio (IFR) and case fatality ratio (CFR) are reported and compared for many countries globally. These measures may appear objective, however, they should be interpreted with caution.AimWe examined reported COVID-19-related mortality in Belgium from 9 March 2020 to 28 June 2020, placing it against the background of excess mortality and compared the DPM and IFR between countries and within subgroups.MethodsThe relation between COVID-19-related mortality and excess mortality was evaluated by comparing COVID-19 mortality and the difference between observed and weekly average predictions of all-cause mortality. DPM were evaluated using demographic data of the Belgian population. The number of infections was estimated by a stochastic compartmental model. The IFR was estimated using a delay distribution between infection and death.ResultsIn the study period, 9,621 COVID-19-related deaths were reported, which is close to the excess mortality estimated using weekly averages (8,985 deaths). This translates to 837 DPM and an IFR of 1.5% in the general population. Both DPM and IFR increase with age and are substantially larger in the nursing home population.DiscussionDuring the first pandemic wave, Belgium had no discrepancy between COVID-19-related mortality and excess mortality. In light of this close agreement, it is useful to consider the DPM and IFR, which are both age, sex, and nursing home population-dependent. Comparison of COVID-19 mortality between countries should rather be based on excess mortality than on COVID-19-related mortality.

Identification of a Potential Inhibitor of the FIV p24 Capsid Protein and Characterization of Its Binding Site.

Feline immunodeficiency virus (FIV) is a veterinary infective agent for which there is currently no efficient drug available. Drugs targeting the lentivirus capsid are currently under development for the treatment of human immunodeficiency virus 1 (HIV-1). Here we describe a lead compound that interacts with the FIV capsid. This compound, 696, modulates the in vitro assembly of and stabilizes the assembled capsid protein. To decipher the mechanism of binding of this compound to the protein, we performed the first nuclear magnetic resonance (NMR) assignment of the FIV p24 capsid protein. Experimental NMR chemical shift perturbations (CSPs) observed after the addition of 696 enabled the characterization of a specific binding site for 696 on p24. This site was further analyzed by molecular modeling of the protein:compound interaction, demonstrating a strong similarity with the binding sites of existing drugs targeting the HIV-1 capsid protein. Taken together, we characterized a promising capsid-interacting compound with a low cost of synthesis, for which derivatives could lead to the development of efficient treatments for FIV infection. More generally, our strategy combining the NMR assignment of FIV p24 with NMR CSPs and molecular modeling will be useful for the analysis of future compounds targeting p24 in the quest to identify an efficient treatment for FIV.

Establishing an ad hoc COVID-19 mortality surveillance during the first epidemic wave in Belgium, 1 March to 21 June 2020.

BackgroundCOVID-19-related mortality in Belgium has drawn attention for two reasons: its high level, and a good completeness in reporting of deaths. An ad hoc surveillance was established to register COVID-19 death numbers in hospitals, long-term care facilities (LTCF) and the community. Belgium adopted broad inclusion criteria for the COVID-19 death notifications, also including possible cases, resulting in a robust correlation between COVID-19 and all-cause mortality.AimTo document and assess the COVID-19 mortality surveillance in Belgium.MethodsWe described the content and data flows of the registration and we assessed the situation as of 21 June 2020, 103 days after the first death attributable to COVID-19 in Belgium. We calculated the participation rate, the notification delay, the percentage of error detected, and the results of additional investigations.ResultsThe participation rate was 100% for hospitals and 83% for nursing homes. Of all deaths, 85% were recorded within 2 calendar days: 11% within the same day, 41% after 1 day and 33% after 2 days, with a quicker notification in hospitals than in LTCF. Corrections of detected errors reduced the death toll by 5%.ConclusionBelgium implemented a rather complete surveillance of COVID-19 mortality, on account of a rapid investment of the hospitals and LTCF. LTCF could build on past experience of previous surveys and surveillance activities. The adoption of an extended definition of 'COVID-19-related deaths' in a context of limited testing capacity has provided timely information about the severity of the epidemic.

High impact of COVID-19 in long-term care facilities, suggestion for monitoring in the EU/EEA, May 2020.

Residents in long-term care facilities (LTCF) are a vulnerable population group. Coronavirus disease (COVID-19)-related deaths in LTCF residents represent 30-60% of all COVID-19 deaths in many European countries. This situation demands that countries implement local and national testing, infection prevention and control, and monitoring programmes for COVID-19 in LTCF in order to identify clusters early, decrease the spread within and between facilities and reduce the size and severity of outbreaks.

Excess all-cause and influenza-attributable mortality in Europe, December 2016 to February 2017.

Since December 2016, excess all-cause mortality was observed in many European countries, especially among people aged ≥ 65 years. We estimated all-cause and influenza-attributable mortality in 19 European countries/regions. Excess mortality was primarily explained by circulation of influenza virus A(H3N2). Cold weather snaps contributed in some countries. The pattern was similar to the last major influenza A(H3N2) season in 2014/15 in Europe, although starting earlier in line with the early influenza season start.

Magnitude and determinants of excess total, age-specific and sex-specific all-cause mortality in 24 countries worldwide during 2020 and 2021: results on the impact of the COVID-19 pandemic from the C-MOR project.

INTRODUCTION: To examine the impact of the COVID-19 pandemic on mortality, we estimated excess all-cause mortality in 24 countries for 2020 and 2021, overall and stratified by sex and age. METHODS: Total, age-specific and sex-specific weekly all-cause mortality was collected for 2015-2021 and excess mortality for 2020 and 2021 was calculated by comparing weekly 2020 and 2021 age-standardised mortality rates against expected mortality, estimated based on historical data (2015-2019), accounting for seasonality, and long-term and short-term trends. Age-specific weekly excess mortality was similarly calculated using crude mortality rates. The association of country and pandemic-related variables with excess mortality was investigated using simple and multilevel regression models. RESULTS: Excess cumulative mortality for both 2020 and 2021 was found in Austria, Brazil, Belgium, Cyprus, England and Wales, Estonia, France, Georgia, Greece, Israel, Italy, Kazakhstan, Mauritius, Northern Ireland, Norway, Peru, Poland, Slovenia, Spain, Sweden, Ukraine, and the USA. Australia and Denmark experienced excess mortality only in 2021. Mauritius demonstrated a statistically significant decrease in all-cause mortality during both years. Weekly incidence of COVID-19 was significantly positively associated with excess mortality for both years, but the positive association was attenuated in 2021 as percentage of the population fully vaccinated increased. Stringency index of control measures was positively and negatively associated with excess mortality in 2020 and 2021, respectively. CONCLUSION: This study provides evidence of substantial excess mortality in most countries investigated during the first 2 years of the pandemic and suggests that COVID-19 incidence, stringency of control measures and vaccination rates interacted in determining the magnitude of excess mortality.

Breast myiasis in an elderly male patient: a case report.

Fly larvae cause myiasis. The most common of these are Cordylobia anthropophaga and Dermatobia hominis. Clinically, myiasis manifests as an erythematous papule that may become ulcerated and form furuncular lesions. In patients who have been in endemic areas, these larvae are to be suspected. Below, we present a 75-year-old male with a clinical picture of a palpable mass in the areola associated with the outflow of serohematic fluid through a central orifice. A breast intraductal lesion was suspected, so a breast ultrasound and biopsy were performed, which showed a structure compatible with myiasis. The diagnostic challenge was the high number of different diagnoses and the little knowledge of health professionals about tropical diseases.

[Spanish opinions on tobacco smoke-free areas]. / Actitudes de los españoles frente a los espacios libres de humo de tabaco.

OBJECTIVE: To determine the number of passive smokers, the environments where exposure to second-hand smoke (SHS) is higher, the opinion of smokers and non-smokers with regard to these spaces and their influence on smoking. DESIGN: Descriptive and cross-sectional observational study of a convenience sample. LOCATION: Multi-centre, Spanish Health-care Centres. PARTICIPANTS: A total of 9733 people older than 16 years who were seen or were working in Spanish Health-care Centres in April 2008. MAIN MEASUREMENTS: Smoker condition, gender, profession and their opinion with regard to second-hand smoke (SHS) exposure. RESULTS: A total of 42.4% of participants considered themselves second-hand (passive) smokers in public places and 96.8% in indoor areas. Almost all of them (91.8%) considered SHS exposure harmful for non-smokers, Smoke-free environments were considered to be good for discouraging people from starting to smoke (70.3%), and for quitting smoking (71.8%). Smoke-free environments were preferred by 81.1%. They felt more exposed SHS inside a car (79.8%) and in cafes (34.7%). Non-smokers, both men and women, shared these opinions significantly (P<.05). CONCLUSIONS: Altogether, those surveyed considered themselves as second-hand smokers and think that smoke-free environments reduce the impact of smoking and help in quitting smoking. Besides, they prefer living in those environments. Considering the preferences of most of the population, this stresses the need to urge governments to establish legislative measures promoting smoke-free environments.

Identification of 2-(4-N,N-Dimethylaminophenyl)-5-methyl-1-phenethyl-1H-benzimidazole targeting HIV-1 CA capsid protein and inhibiting HIV-1 replication in cellulo.

The capsid (CA) subunit of the HIV-1 Gag polyprotein is involved in several steps of the viral cycle, from the assembly of new viral particles to the protection of the viral genome until it enters into the nucleus of newly infected cells. As such, it represents an interesting therapeutic target to tackle HIV infection. In this study, we screened hundreds of compounds with a low cost of synthesis for their ability to interfere with Gag assembly in vitro. Representatives of the most promising families of compounds were then tested for their ability to inhibit HIV-1 replication in cellulo. From these molecules, a hit compound from the benzimidazole family with high metabolic stability and low toxicity, 2-(4-N,N-dimethylaminophenyl)-5-methyl-1-phenethyl-1H-benzimidazole (696), appeared to block HIV-1 replication with an IC50 of 3 µM. Quantitative PCR experiments demonstrated that 696 does not block HIV-1 infection before the end of reverse transcription, and molecular docking confirmed that 696 is likely to bind at the interface between two monomers of CA and interfere with capsid oligomerization. Altogether, 696 represents a promising lead molecule for the development of a new series of HIV-1 inhibitors.

Assessment of the Feasibility of a Future Integrated Larger-Scale Epidemiological Study to Evaluate Health Risks of Air Pollution Episodes in Children.

Air pollution exposure can lead to exacerbation of respiratory disorders in children. Using sensitive biomarkers helps to assess the impact of air pollution on children's respiratory health and combining protein, genetic and epigenetic biomarkers gives insights on their interrelatedness. Most studies do not contain such an integrated approach and investigate these biomarkers individually in blood, although its collection in children is challenging. Our study aimed at assessing the feasibility of conducting future integrated larger-scale studies evaluating respiratory health risks of air pollution episodes in children, based on a qualitative analysis of the technical and logistic aspects of a small-scale field study involving 42 children. This included the preparation, collection and storage of non-invasive samples (urine, saliva), the measurement of general and respiratory health parameters and the measurement of specific biomarkers (genetic, protein, epigenetic) of respiratory health and air pollution exposure. Bottlenecks were identified and modifications were proposed to expand this integrated study to a higher number of children, time points and locations. This would allow for non-invasive assessment of the impact of air pollution exposure on the respiratory health of children in future larger-scale studies, which is critical for the development of policies or measures at the population level.

[Juvenile myoclonic epilepsy and associated neurocognitive and executive dysfunctions]. / La epilepsia mioclónica juvenil y las disfunciones neurocognitivas y ejecutivas asociadas.

Juvenile myoclonic epilepsy (JME) is a benign disorder with a good response to antiepileptic drugs. Neuropsychological evaluations revealed mild cognitive deficits. The objective of this study is to determine the cognitive profile and mood symptoms in JME compared to normal controls. 30 patients with JME and 29 controls matched for age, gender, and education level were prospectively evaluated. The clinical characteristics were analysed. They were given a complete cognitive battery, a self-administered questionnaire of executive difficulties (DEX), the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), Beck Depression Inventory (BDI), Generalized Anxiety Disorder Scale (GAD-7) and suicide risk scale (MINI). No significant differences in age and education were observed between JME and controls. Average time of evolution of the disease 18 years, 53% have three types of seizures: myoclonic, absence seizures and tonic-clonic seizures. Significant differences were found with greater failures in attention, executive function, a significantly higher score values in DEX in JME subjects. A higher score was found in the NDDI-E; BDI and GAD-7. No differences were found in the risk of suicide with respect to controls. The study confirms that JME presents greater failures in attentional functioning and executive skills related to flexibility and inhibition, with patients being aware of their difficulties in most cases. Knowing these difficulties would allow a better therapeutic approach to improve symptoms usually dismissed.

La epilepsia mioclónica juvenil (EMJ) es un trastorno benigno con buena respuesta a la medicación antiepiléptica. Evaluaciones neuropsicológicas revelaron trastornos cognitivos leves. El objetivo de este estudio es determinar el desempeño cognitivo y síntomas anímicos de la EMJ comparados con controles normales. Se evaluaron en forma prospectiva 30 pacientes con EMJ y 29 controles pareados por edad, género, y escolaridad. Se analizaron las características clínicas de la EMJ. Se administró una batería cognitiva completa, un cuestionario auto-administrado de dificultades ejecutivas (DEX), un inventario de depresión validado para epilepsia NDDI-E, escala de depresión de Beck (BDI), escala de ansiedad (GAD-7) y escala de riesgo de suicidio (MINI). Sin diferencias significativas en edad y escolaridad ent re EMJ y controles. Tiempo medio de evolución de la enfermedad, 18 años. El 53% presentó tres tipos de crisis, mioclonías, ausencias y convulsiones tónico-clónicas generalizadas. Hubo diferencias significativas con mayores fallas en atención, funciones ejecutivas, un puntaje significativamente mayor en el DEX en pacientes con EMJ. Se encontró un mayor puntaje en el NDDI-E, BDI y GAD-7 en EMJ. No se hallaron diferencias en el riesgo de suicidio respecto a controles. El estudio confirma que la EMJ presenta mayores fallas en el funcionamiento atencional y las habilidades ejecutivas relacionadas con la flexibilidad e inhibición, siendo en la mayoría de los casos los pacientes conscientes de sus dificultades. Conocer estas dificultades permitirá un mejor abordaje terapéutico, y mejorar síntomas muchas veces desestimados.

All-cause mortality supports the COVID-19 mortality in Belgium and comparison with major fatal events of the last century.

BACKGROUND: The COVID-19 mortality rate in Belgium has been ranked among the highest in the world. To assess the appropriateness of the country's COVID-19 mortality surveillance, that includes long-term care facilities deaths and deaths in possible cases, the number of COVID-19 deaths was compared with the number of deaths from all-cause mortality. Mortality during the COVID-19 pandemic was also compared with historical mortality rates from the last century including those of the Spanish influenza pandemic. METHODS: Excess mortality predictions and COVID-19 mortality data were analysed for the period March 10th to June 21st 2020. The number of COVID-19 deaths and the COVID-19 mortality rate per million were calculated for hospitals, nursing homes and other places of death, according to diagnostic status (confirmed/possible infection). To evaluate historical mortality, monthly mortality rates were calculated from January 1900 to June 2020. RESULTS: Nine thousand five hundred ninety-one COVID-19 deaths and 39,076 deaths from all-causes were recorded, with a correlation of 94% (Spearman's rho, p < 0,01). During the period with statistically significant excess mortality (March 20th to April 28th; total excess mortality 64.7%), 7917 excess deaths were observed among the 20,159 deaths from all-causes. In the same period, 7576 COVID-19 deaths were notified, indicating that 96% of the excess mortality were likely attributable to COVID-19. The inclusion of deaths in nursing homes doubled the COVID-19 mortality rate, while adding deaths in possible cases increased it by 27%. Deaths in laboratory-confirmed cases accounted for 69% of total COVID-19-related deaths and 43% of in-hospital deaths. Although the number of deaths was historically high, the monthly mortality rate was lower in April 2020 compared to the major fatal events of the last century. CONCLUSIONS: Trends in all-cause mortality during the first wave of the epidemic was a key indicator to validate the Belgium's high COVID-19 mortality figures. A COVID-19 mortality surveillance limited to deaths from hospitalised and selected laboratory-confirmed cases would have underestimated the magnitude of the epidemic. Excess mortality, daily and monthly number of deaths in Belgium were historically high classifying undeniably the first wave of the COVID-19 epidemic as a fatal event.

Short-term effects of nitrogen dioxide on hospital admissions for cardiovascular disease in Wallonia, Belgium.

Many studies have shown a short-term association between NO2 and cardiovascular disease. However, few data are available on the delay between exposure and a health-related event. The aim of the present study is to determine the strength of association between NO2 and cardiovascular health in Wallonia for the period 2008-2011. This study also seeks to evaluate the effects of age, gender, season and temperature on this association. The effect of the delay between exposure and health-related event was also investigated. The daily numbers of hospital admissions for arrhythmia, acute myocardial infarction, ischemic and haemorrhagic stroke were taken from a register kept by Belgian hospitals. Analyses were performed using the quasi-Poisson regression model adjusted for seasonality, long-term trend, day of the week, and temperature. Our study confirms the existence of an association between NO2 and cardiovascular disease. Apart from haemorrhagic stroke, the strongest association between NO2 concentrations and number of hospital admissions is observed at lag 0. For haemorrhagic stroke, the association is strongest with a delay of 2days. All associations calculated without stratification are statistically significant and range from an excess relative risk of 2.8% for myocardial infarction to 4.9% for haemorrhagic strokes. The results of this study reinforce the evidence of the short-term effects of NO2 on hospital admissions for cardiovascular disease. The different delay between exposure and health-related event for haemorrhagic stroke compared to ischemic stroke suggests different mechanisms of action.

Data on short-term effect of nitrogen dioxide on cardiovascular health in Wallonia, Belgium.

Data presented in this article are related to the research paper entitled "Short-term effects of nitrogen dioxide on hospital admissions for cardiovascular disease in Wallonia, Belgium." (Collart et al., in press) [1]. Nitrogen dioxide concentrations showed a strong seasonal pattern with higher levels in the cold period than in the warm period. A minimum of 13.1 µg/m3 in July and a maximum of 26.9 µg/m3 in January were observed. The coldest months are December, January and February and the hottest months are June, July and August. Temperature and nitrogen dioxide were negatively correlated in the cold period and positively correlated in the warm period. For the period 2008-2011 there were 113 147 hospital admissions for cardiovascular disease. Forty-five percent of patients were women and 66.5% were 65 and older. Heart rhythm disorders account for the majority of hospital admissions for cardiovascular disease. Our data confirms the existence of an association between NO2 and cardiovascular disease. Apart from haemorrhagic stroke, the strongest association between NO2 concentrations and number of hospital admissions is observed at lag 0. For haemorrhagic stroke, the association is strongest with a delay of 2 days. All associations calculated without stratification are statistically significant and range from an excess relative risk of 2.8% for myocardial infarction to 4.9% for haemorrhagic strokes.

Looking for Novel Capsid Protein Multimerization Inhibitors of Feline Immunodeficiency Virus.

Feline immunodeficiency virus (FIV) is a member of the retroviridae family of viruses. It causes acquired immunodeficiency syndrome (AIDS) in worldwide domestic and non-domestic cats and is a cause of an important veterinary issue. The genome organization of FIV and the clinical characteristics of the disease caused by FIV are similar to human immunodeficiency virus (HIV). Both viruses infect T lymphocytes, monocytes, and macrophages, with a similar replication cycle in infected cells. Thus, the infection of cats with FIV is also a useful tool for the study and development of novel drugs and vaccines against HIV. Anti-retroviral drugs studied extensively with regards to HIV infection have targeted different steps of the virus replication cycle: (1) disruption of the interaction with host cell surface receptors and co-receptors; (2) inhibition of fusion of the virus and cell membranes; (3) blocking of the reverse transcription of viral genomic RNA; (4) interruption of nuclear translocation and integration of viral DNA into host genomes; (5) prevention of viral transcript processing and nuclear export; and (6) inhibition of virion assembly and maturation. Despite the great success of anti-retroviral therapy in slowing HIV progression in humans, a similar therapy has not been thoroughly investigated for FIV infection in cats, mostly because of the little structural information available for FIV proteins. The FIV capsid protein (CA) drives the assembly of the viral particle, which is a critical step in the viral replication cycle. During this step, the CA protein oligomerizes to form a protective coat that surrounds the viral genome. In this work, we perform a large-scale screening of four hundred molecules from our in-house library using an in vitro assembly assay of p24, combined with microscale thermophoresis, to estimate binding affinity. This screening led to the discovery of around four novel hits that inhibited capsid assembly in vitro. These may provide new antiviral drugs against FIV.

Crystal Structure of the Full-Length Feline Immunodeficiency Virus Capsid Protein Shows an N-Terminal ß-Hairpin in the Absence of N-Terminal Proline.

Feline immunodeficiency virus (FIV) is a member of the Retroviridae family. It is the causative agent of an acquired immunodeficiency syndrome (AIDS) in cats and wild felines. Its capsid protein (CA) drives the assembly of the viral particle, which is a critical step in the viral replication cycle. Here, the first atomic structure of full-length FIV CA to 1.67 Å resolution is determined. The crystallized protein exhibits an original tetrameric assembly, composed of dimers which are stabilized by an intermolecular disulfide bridge induced by the crystallogenesis conditions. The FIV CA displays a standard α-helical CA topology with two domains, separated by a linker shorter than other retroviral CAs. The ß-hairpin motif at its amino terminal end, which interacts with nucleotides in HIV-1, is unusually long in FIV CA. Interestingly, this functional ß-motif is formed in this construct in the absence of the conserved N-terminal proline. The FIV CA exhibits a cis Arg-Pro bond in the CypA-binding loop, which is absent in known structures of lentiviral CAs. This structure represents the first tri-dimensional structure of a functional, full-length FIV CA.

La epilepsia mioclónica juvenil y las disfunciones neurocognitivas y ejecutivas asociadas / Juvenile myoclonic epilepsy and associated neurocognitive and executive dysfunctions

Resumen La epilepsia mioclónica juvenil (EMJ) es un trastorno benigno con buena respuesta a la medicación antiepiléptica. Evaluaciones neuropsicológicas revelaron trastornos cognitivos leves. El objetivo de este estudio es determinar el desempeño cognitivo y síntomas anímicos de la EMJ comparados con controles normales. Se evaluaron en forma prospectiva 30 pacientes con EMJ y 29 controles pareados por edad, género, y escolaridad. Se analizaron las características clínicas de la EMJ. Se administró una batería cognitiva completa, un cuestionario auto-administrado de dificultades ejecutivas (DEX), un inventario de depresión validado para epilepsia NDDI-E, escala de depresión de Beck (BDI), escala de ansiedad (GAD-7) y escala de riesgo de suicidio (MINI). Sin diferencias significativas en edad y escolaridad ent re EMJ y controles. Tiempo medio de evolución de la enfermedad, 18 años. El 53% presentó tres tipos de crisis, mioclonías, ausencias y convulsiones tónico-clónicas generalizadas. Hubo diferencias significativas con mayores fallas en atención, funciones ejecutivas, un puntaje significativamente mayor en el DEX en pacientes con EMJ. Se encontró un mayor puntaje en el NDDI-E, BDI y GAD-7 en EMJ. No se hallaron diferencias en el riesgo de suicidio respecto a controles. El estudio confirma que la EMJ presenta mayores fallas en el funcionamiento atencional y las habilidades ejecutivas relacionadas con la flexibilidad e inhibición, siendo en la mayoría de los casos los pacientes conscientes de sus dificultades. Conocer estas dificultades permitirá un mejor abordaje terapéutico, y mejorar síntomas muchas veces desestimados.

Abstract Juvenile myoclonic epilepsy (JME) is a benign disorder with a good response to antiepileptic drugs. Neurop sychological evaluations revealed mild cognitive deficits. The objective of this study is to determine the cognitive profile and mood symptoms in JME compared to normal controls. 30 patients with JME and 29 controls matched for age, gender, and education level were prospectively evaluated. The clinical characteristics were analysed. They were given a complete cognitive battery, a self-administered questionnaire of executive difficulties (DEX), the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), Beck Depression Inventory (BDI), Generalized Anxiety Disorder Scale (GAD-7) and suicide risk scale (MINI). No significant differences in age and education were observed between JME and controls. Average time of evolution of the disease 18 years, 53% have three types of seizures: myoclonic, absence seizures and tonic-clonic seizures. Significant differences were found with greater failures in attention, executive function, a significantly higher score values in DEX in JME subjects. A higher score was found in the NDDI-E; BDI and GAD-7. No differences were found in the risk of suicide with respect to controls. The study confirms that JME presents greater failures in attentional functioning and executive skills related to flexibility and inhibition, with patients being aware of their difficulties in most cases. Knowing these difficulties would allow a better therapeutic approach to improve symptoms usually dismissed.