Mortality rates immediately after severe hurricanes in Cuba have decreased over the past three decades.

OBJECTIVES: The objective of this study is to understand how Cuba responds to extreme weather events, which can help identify and disseminate good public health practice. STUDY DESIGN: The study design of this study is an observational study using routinely collected mortality data. METHODS: National daily mortality counts after severe hurricanes arrived on the Cuba landmass since 1990 were compared with baseline values. Incidence rate ratios of mortality during the hurricane and for the four weeks afterwards were calculated for four eligible hurricanes: Georges (1998), Dennis (2005), Ike (2008) and Irma (2017). RESULTS: Mortality rates decreased over time (P < 0.001 for interaction), and no excess mortality counts were observed after Hurricane Irma in 2017. CONCLUSIONS: Mortality rates for severe hurricanes that have made landfall in Cuba have decreased over three decades, despite the most recent hurricane (Irma) being one of the strongest observed in recent decades. This suggests that the Cuban public health preparations and responses to recent severe hurricanes are probably contributing to this mitigation in national mortality rates during these periods.

Breast cancer PAM50 signature: correlation and concordance between RNA-Seq and digital multiplexed gene expression technologies in a triple negative breast cancer series.

BACKGROUND: Full RNA-Seq is a fundamental research tool for whole transcriptome analysis. However, it is too costly and time consuming to be used in routine clinical practice. We evaluated the transcript quantification agreement between RNA-Seq and a digital multiplexed gene expression platform, and the subtype call after running the PAM50 assay in a series of breast cancer patients classified as triple negative by IHC/FISH. The goal of this study is to analyze the concordance between both expression platforms overall, and for calling PAM50 triple negative breast cancer intrinsic subtypes in particular. RESULTS: The analyses were performed in paraffin-embedded tissues from 96 patients recruited in a multicenter, prospective, non-randomized neoadjuvant triple negative breast cancer trial (NCT01560663). Pre-treatment core biopsies were obtained following clinical practice guidelines and conserved as FFPE for further RNA extraction. PAM50 was performed on both digital multiplexed gene expression and RNA-Seq platforms. Subtype assignment was based on the nearest centroid classification following this procedure for both platforms and it was concordant on 96% of the cases (N = 96). In four cases, digital multiplexed gene expression analysis and RNA-Seq were discordant. The Spearman correlation to each of the centroids and the risk of recurrence were above 0.89 in both platforms while the agreement on Proliferation Score reached up to 0.97. In addition, 82% of the individual PAM50 genes showed a correlation coefficient > 0.80. CONCLUSIONS: In our analysis, the subtype calling in most of the samples was concordant in both platforms and the potential discordances had reduced clinical implications in terms of prognosis. If speed and cost are the main driving forces then the preferred technique is the digital multiplexed platform, while if whole genome patterns and subtype are the driving forces, then RNA-Seq is the preferred method.

What is the association between price and economic activity with cigarette consumption in Cuba from 1980 to 2014?

OBJECTIVES: Cuba is a tobacco-producing country that has been economically isolated as a consequence of an embargo imposed by the USA. It has also experienced a severe economic depression in the 1990s after the withdrawal of support by the former Soviet Union. These characteristics provide a unique opportunity to study the relation between large changes in economic activity, cigarette price and demand for cigarettes in a relatively isolated socialist economy. STUDY DESIGN: This is an observational epidemiological study. METHODS: Data were obtained on the annual price of a packet of cigarettes and the mean number of cigarettes consumed per adult living in Cuba from 1980 to 2014. Descriptive and regression analysis were used to explore the relationship between cigarette consumption and price in Cuba. RESULTS: In 1980, the mean price of a packet of cigarettes was 1.53 Cuban peso (CUP) in 1997 prices and the mean annual per capita consumption was 2237 cigarettes. In 2014, the mean price had increased to 5.57 CUP (1997 prices) per packet of cigarettes, and consumption had fallen to 1527 cigarettes per capita. There were significant negative associations between annual cigarette consumption and both price and living through an economic depression. The elasticity was approximately -0.31 with price, and living through an economic depression was also associated with lower consumption of cigarettes (a reduction of 9%, 95% confidence intervals -0.18 to -0.001). CONCLUSIONS: Higher cigarette pricing, along with other public health interventions, are required to protect the national population from the adverse effects of tobacco smoke exposure.

Patterns of helminth infections in Rattus rattus and Mus musculus from two Mayan communities in Mexico.

The black rat Rattus rattus and the house mouse Mus musculus are two commensal rodent species that harbour and shed zoonotic pathogens, including helminths. The aim of this survey was to study the helminth community and the patterns of infections in R. rattus and M. musculus from two Mayan communities in Mexico. Gastrointestinal helminths were isolated from 322 M. musculus and 124 R. rattus, including Gongylonema neoplasticum, Hassalstrongylus aduncus, Hassalstrongylus musculi, Hydatigera taeniaeformis metacestode, Hymenolepis diminuta, Nippostrongylus brasiliensis, Oligacanthorhynchidae gen. sp., Syphacia muris, Syphacia obvelata, Rodentolepis microstoma and Trichuris muris. The overall richness of helminths was seven in R. rattus and six in M. musculus. The results of generalized linear models showed that juvenile rodents had lower probabilities of being infected with G. neoplasticum, H. taeniaeformis and H. musculi than adult rodents. A positive association between the prevalence of S. muris and rat abundance was found. The intensity of infection with S. muris was higher in the rainy season than in the dry season; the opposite result was found for H. musculi infection. Male R. rattus harboured more S. muris specimens. The intensity of infection with T. muris was inversely associated with mouse abundance. The presence of the zoonotic H. diminuta, as well as H. taeniaeformis and R. microstoma in rodent populations indicates that there is risk of transmission, and that their entire life cycle occurs in the study area.

Brominated Flame Retardants in Sediments of Four Coastal Lagoons of Yucatan, Mexico.

We examined the sediments of four coastal lagoons (Ria Lagartos, Bocas de Dzilam, Laguna de Chelem and Ria Celestun) from the state of Yucatan, Mexico, for three widely used commercial polybrominated diphenyl ethers formulations (penta-, octa- and deca-BDE). The most commonly found congeners in all four lagoons were BDEs 47, 99 and 100 (all in the penta-BDE formulation) and BDE209 (deca-BDE formulation). The greatest variety and highest concentrations of brominated flame retardants were found in Ria Lagartos, which also showed the highest BDE 100 concentration (24.129 ng/g). Hexabromocyclododecane was found in all lagoons, but at lower concentrations than those of the various polybrominated diphenyl ethers. Dispersal routes of these compounds are discussed, such as a ring of sinkholes (cenotes) adjacent to the lagoons. Moreover, electronic waste is a serious problem because municipal landfills have been the primary disposal method for these wastes and therefore represent a reservoir of brominated fire retardants.

Colonic adenosquamous carcinoma and mucinous adenocarcinoma with microsatellite instability.

A 43-year-old man presented with two-month history of fatigue, weakness, paleness, rectal bleeding, sweating, and weight loss of 10 kg in the past one month. A complete blood count revealed anaemia. The patient underwent a right hemicolectomy. The microscopic examination revealed an adenosquamous carcinoma associated with a mucinous adenocarcinoma in a patient with microsatellite instability due to loss of MLH1 and PMS2 expression and retention of MSH2 and MSH6 expression in both the squamous and glandular components. We also observed an atypical immunohistochemical phenotype in the adenocarcinoma component showing CK7 expression and reduced CK20 and CDX2 expression.

First detection of Omicron variant BA.4.1 lineage in dogs, Chile.

SARS-CoV-2's rapid global spread caused the declaration of COVID-19 as a pandemic in March 2020. Alongside humans, domestic dogs and cats are also susceptible to infection. However, limited reports on pet infections in Chile prompted a comprehensive study to address this knowledge gap. Between March 2021 and March 2023, the study assessed 65 pets (26 dogs and 39 cats) from 33 COVID-19+ households alongside 700 nasal swabs from animals in households with unknown COVID-19 status. Using RT-PCR, nasal, fecal, and environmental samples were analyzed for the virus. In COVID-19+ households, 6.06% tested positive for SARS-CoV-2, belonging to 3 dogs, indicating human-to-pet transmission. Pets from households with unknown COVID-19 status tested negative for the virus. We obtained 2 SARS-CoV-2 genomes from animals, that belonged to Omicron BA.4.1 variant, marking the first report of pets infected with this lineage globally. Phylogenetic analysis showed these sequences clustered with human sequences collected in Chile during the same period when the BA.4.1 variant was prevalent in the country. The prevalence of SARS-CoV-2 in Chilean pets was relatively low, likely due to the country's high human vaccination rate. Our study highlights the importance of upholding and strengthening human vaccination strategies to mitigate the risk of interspecies transmission. It underscores the critical role of the One Health approach in addressing emerging zoonotic diseases, calling for further research on infection dynamics and risk factors for a comprehensive understanding.

[RYR1 myopathies in childhood: phenotype-genotype correlation and incidence]. / Miopatías RYR1 en la infancia: correlación fenotipo-genotipo e incidencia.

INTRODUCTION: Ryanodine receptor type 1-related myopathies (RYR1-RM) represent the most prevalent category of congenital myopathies. The introduction of genetic techniques has shifted the diagnostic paradigm, suggesting the prioritization of molecular studies over biopsies. This study aims to explore the clinical and epidemiological characteristics of patients with RYR1 gene variants in a tertiary pediatric hospital, intending to enhance the understanding of the genotype-phenotype correlation in RYR1-RM. PATIENTS AND METHODS: An observational, descriptive, and cross-sectional study was conducted on patients under 14 years old with myopathic symptoms and potentially pathogenic RYR1 gene variants from January 2013 to December 2023. Variables such as gender, age, motor development, genetic variants, inheritance pattern, and other manifestations were considered. All variables were tabulated against the genetic variant. RESULTS: Of the nine included patients, the estimated incidence was approximately 1 in 10,000 live births. The median age at diagnosis was six years, with significant phenotypic variability. Common symptoms such as weakness and delayed motor development were observed. Genetic variants affected the RYR1 gene diversely, including five previously undescribed variants. Muscle biopsy was performed in five patients, revealing central core myopathy in two, multiminicore in one, congenital fiber-type disproportion in one, and a nonspecific pattern in another. CONCLUSIONS: RYR1-RM in our series exhibited phenotypic and involvement variability, with an incidence in our area of around 1 in 10,000 live births. Most cases were male, with dominant missense variants. We contribute five previously undescribed genetic variants.

TITLE: Miopatías RYR1 en la infancia: correlación fenotipo-genotipo e incidencia.Introducción. Las miopatías relacionadas con el receptor de rianodina de tipo 1 (RYR1-RM) constituyen la categoría más frecuente de miopatías congénitas. La introducción de técnicas genéticas ha cambiado el paradigma diagnóstico y sugiere la prioridad de estudios moleculares sobre biopsias. Este estudio busca explorar las características clinicoepidemiológicas de pacientes con variantes del gen RYR1 en un hospital pediátrico de tercer nivel con el objetivo de ampliar la comprensión de la correlación genotipo-fenotipo en las RYR1-RM. Pacientes y métodos. Estudio observacional, descriptivo y transversal, de pacientes menores de 14 años con síntomas miopáticos y variantes potencialmente patógenas del gen RYR1 entre enero de 2013 y diciembre de 2023, considerando variables como sexo, edad, desarrollo motor, variantes genéticas, patrón de herencia y otras manifestaciones. Todas las variables fueron tabuladas frente a la variante genética. Resultados. De los nueve pacientes incluidos, la incidencia estimada fue de aproximadamente 1/10.000 nacidos vivos. La mediana en el momento del diagnóstico fue de 6 años, con una variabilidad fenotípica significativa. Se observaron síntomas comunes, como debilidad y retraso del desarrollo motor. Las variantes genéticas afectaron al gen RYR1 de manera diversa, y hubo cinco variantes previamente no descritas. La biopsia muscular se realizó en cinco pacientes, en dos de ellos de tipo miopatía central core; en uno, multiminicore; en uno, desproporción congénita de fibras; y en otro, de patrón inespecífico. Conclusiones. Las RYR1-MR de nuestra serie ofrecieron variabilidad fenotípica y de afectación, con una incidencia en nuestra área de en torno a 1/10.000 recién nacidos. La mayoría de los casos fueron varones, de variantes missense dominantes. Aportamos cinco variantes genéticas no descritas con anterioridad.

Female sex hormones regulate the Th17 immune response to sperm and Candida albicans.

STUDY QUESTION: What role do female sex hormones play in the antisperm immune response? SUMMARY ANSWER: We found that sperm induce a Th17 immune response and that estradiol down-regulates the antisperm Th17 response by dendritic cells. WHAT IS KNOWN ALREADY: Estradiol down-regulates the immune response to several pathogens and impairs the triggering of dendritic cell maturation by microbial products. STUDY DESIGN, SIZE, DURATION: Ex vivo and in vivo murine models of vaginal infection with sperm and Candida albicans were used to study the induction of Th17 and its hormonal regulation. PARTICIPANTS/MATERIALS, SETTING, METHODS: We analyzed the induction of Th17 cytokines and T cells in splenocytes obtained from BALB/c mice challenged with sperm and C. albicans. For the in vivo vaginal infection models, we used ovariectomized mice treated with vehicle, estradiol or progesterone, and we assessed the effect of these hormones on the immune response in the lymph nodes. MAIN RESULTS AND THE ROLE OF CHANCE: Th17 cytokines and T cells were induced by sperm antigens in both ex vivo and in vivo experiments. Estrus levels of estradiol down-regulated the Th17 response to sperm and C. albicans in vivo. LIMITATIONS, REASONS FOR CAUTION: This study was conducted using murine models; whether or not the results are applicable to humans is not known. WIDER IMPLICATIONS OF THE FINDINGS: Our results describe an adaptive mechanism that reconciles immunity and reproduction and further explains why unregulated Th17 could be linked to infertility and recurrent infections. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by research grants from the Instituto de Salud Carlos III (ISCIII) (PI10/00897) and Fundación Mutua Madrileña to M.R. M.R. holds a Miguel Servet contract from the ISCIII (CP08/00228). M.A.M.-F. was supported by (ISCIII) INTRASALUD PI09/02029. We have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: Not required.

Identification of Races 0 and 2 of Cladosporium fulvum (syn Passalora fulva) on Tomato in the Cinturón Hortícola de La Plata, Argentina.

Surveys aimed at evaluating the incidence and severity of a new disease that developed in greenhouses cultivated with tomato (Solanum lycopersicum L.) were performed during 2009 and 2010 in greenhouses of the cultivars Elpida (Enza Zaden) and Colibrí (Clause) in an area of tomato production known as the Cinturón Hortícola de La Plata (the "horticultural belt of La Plata"). The disease had a 100% prevalence and 90% incidence within the ten 250 m2 greenhouses that were monitored in 2009, 2010, and 2011. In two consecutive assays, severity was 40%. The wide distribution of the disease suggests that the tomato hybrids under use lack resistance genes. The upper surface of diseased leaves had pale green to yellowish, 1- to 1.5-cm spots with undefined margins that progressed to a yellowish brown color, while on the lower side they had pale brown to brown sporulation of fungal conidiophores and conidia. Monosporic fungal cultures were obtained by needle transfer of conidia from sporulating areas of leaves (n = 20) to water agar medium. On 2% potato dextrose agar (PDA) the colonies of the relatively low growing fungus were strongly pigmented, greenish grey, and black on the reverse of the plate. The fungus developed one-celled, pale olive-green, ovoid conidia on long, branched chains, which arose from pigmented conidiophores, corresponding to the description of Cladosporium fulvum made by Joosten and de Wit (1). The identity of two isolates was confirmed by amplifying the 580-bp ITS sequences by means of primers ITS4 (5'-TCCTCCGCTTATTGATATGC-3') and ITS5 (5'-GAATTCGGAAGTAAAAGTCGTAACAAGG-3') (ITS sequence Race 0 JQ768324.1 and Race 2 JQ768325.1). Both were 100% homologous to the ITS sequences of C. fulvum strains ATCC44962 (AF393700) and ATCC44960 (AF303701). Monosporic cultures of four isolates, each obtained from leaves collected from different plants growing in different greenhouses, were inoculated on a set of differential genotypes of tomato: cvs. Moneymaker, Cf-0, Cf-2, Cf-4, Cf-5, and Cf-9 (kindly provided by the Laboratory of Phytopathology of Wageningen University). Three plants of each tomato genotype at the 5 to 6 true leaf stage were inoculated by spraying a 105 conidia/ml conidial suspension of C. fulvum on the leaflets of the 3rd and 4th leaf. Inoculation tests of each isolate were repeated at least twice. After inoculation, plants were grown in the greenhouse at 13 to 29°C and 99% relative humidity. However, for the first 20 h after inoculation, plants were kept in the dark. They were regularly monitored and were scored as resistant or susceptible at 20 days after inoculation. Susceptible genotypes developed pale green to yellow spots on the abaxial leaf surface and pale brown to olivaceous brown sporulation on the adaxial side. Plants lacking disease symptoms were considered resistant. Inoculated fungi were reisolated from infected tissue and the identity of the fungal cultures confirmed based on morphology and the ITS sequence. Based on the reactions of the tomato genotypes, two races were identified, three isolates (race 2) developed symptoms only in cv. MM Cf-2, while the remaining isolate (race 0) provoked symptoms only in cv. MM Cf-0. Reference: (1) M. Joosten and P. de Wit. Annu Rev Phytopathol. 37:335, 1999.

Cryopreservation of Arachis pintoi (leguminosae) somatic embryos.

In this study, we successfully cryopreserved cotyledonary somatic embryos of diploid and triploid Arachis pintoi cytotypes using the encapsulation-dehydration technique. The highest survival rates were obtained when somatic embryos were encapsulated in calcium alginate beads and precultured in agitated (80 rpm) liquid establishment medium (EM) with daily increasing sucrose concentration (0.50, 0.75, and 1.0 M). The encapsulated somatic embryos were then dehydrated with silica gel for 5 h to 20% moisture content (fresh weight basis) and cooled either rapidly (direct immersion in liquid nitrogen, LN) or slowly (1 degree C per min from 25 degree C to -30 degree C followed by immersion in LN). Beads were kept in LN for a minimum of 1 h and then were rapidly rewarmed in a 30 degree C water-bath for 2 min. Finally, encapsulated somatic embryos were post-cultured in agitated (80 rpm) liquid EM with daily decreasing sucrose concentration (0.75 and 0.5 M) and transferred to solidified EM. Using this protocol, we obtained 26% and 30% plant regeneration from cryopreserved somatic embryos of diploid and triploid cytotypes. No morphological abnormalities were observed in any of the plants regenerated from cryopreserved embryos and their genetic stability was confirmed with 10 isozyme systems and nine RAPD profiles.

An environmental analysis of public UAP sightings and sky view potential.

Sightings of unidentified flying objects (UFOs) or unidentified anomalous phenomena (UAP) have been reported throughout history. Given the potential security and safety risks they pose, as well as scientific curiosity, there is increasing interest in understanding what these sighting reports represent. We approach this problem as an important one of the human experience and that can be examined through a geographical lens: what local factors may increase or decrease the number of sighting reports? Using a Bayesian regression method, we test hypotheses based on variables representing sky view potential (light pollution, tree canopy, and cloud cover) and the potential for objects to be present in the sky (aircraft and military installations). The dependent variable includes over 98,000 publicly reported UAP sightings in the conterminous United States during the 20-year period from 2001 to 2020. The model results find credible correlations between variables that suggest people see more "phenomena" when they have more opportunity to. This analysis is one of few investigations of UAP sighting reports at a national scale providing context to help examine individual reports. Given that these objects are labeled unidentifiable in the personal sense, there are many natural and/or human based explanations worth exploring.

[Congenital myotonia. Incidence and presentation of a series of cases]. / Miotonía congénita. Incidencia y presentación de una serie de casos.

INTRODUCTION: Myotonia congenita is the most common form of genetic myotonia and is caused by mutations in the CLCN1 gene. It can be inherited in an autosomal dominant or recessive manner. We present a series of cases to update its incidence in our environment, to describe its phenotype in relation to the genotype found, and we also review the mutations found, among which we provide a new, undescribed alteration. CASES REPORT: The medical records of patients with a diagnosis of congenital myotonia studied and followed up in the pediatric neurology section in a tertiary hospital between the years 2015-2020 were reviewed. Demographic variables (age, sex), disease course (age of onset, symptoms and signs, time elapsed until diagnosis, clinical evolution), family history and evaluation of response to treatment were collected. Five cases with a clinical diagnosis of myotonia congenita were identified (three with Becker's disease and two with Thomsen's disease). The incidence in relation to the number of births is estimated at 1:15,000 newborns for cases with the Becker phenotype and 1:21,000 newborns for the Thomsen phenotypes. We found a probably pathogenic mutation not previously described (CLCN1: c.824T> C). CONCLUSIONS: the approximate incidence in our environment was higher than previously known and we describe a new, undescribed mutation: c.824T> C with pathogenicity predictors that behaved like a Becker recessive phenotype but with an earlier debut.

TITLE: Miotonía congénita. Incidencia y presentación de una serie de casos.Introducción. La miotonía congénita es la forma más común de miotonía de causa genética y se produce por mutaciones en el gen CLCN1. Puede heredarse de manera autosómica dominante o recesiva. Presentamos una serie de casos para actualizar su incidencia en nuestro medio, para describir su fenotipo en relación con el genotipo encontrado y, además, revisamos las mutaciones encontradas, entre las que aportamos una nueva alteración no descrita. Casos clínicos. Se revisaron las historias clínicas de pacientes con diagnóstico de miotonía congénita estudiados y seguidos en la consulta de neurología pediátrica en un hospital de tercer nivel entre los años 2015 y 2020. Se recogieron variables demográficas (edad y sexo), curso de la enfermedad (edad de inicio, síntomas y signos, tiempo transcurrido hasta el diagnóstico y evolución clínica), antecedentes familiares y evaluación de la respuesta al tratamiento. Se identificaron cinco casos con diagnóstico clínico de miotonía congénita (tres con enfermedad de Becker y dos con enfermedad de Thomsen). La incidencia en relación con el número de nacimientos la estimamos en 1:15.000 recién nacidos para los casos con fenotipo Becker y en 1:21.000 recién nacidos para los fenotipos Thomsen. Hallamos una mutación probablemente patogénica no descrita previamente (CLCN1: c.824T>C). Conclusiones. La incidencia aproximada en nuestro medio fue superior a la previamente conocida y describimos una nueva mutación no descrita: c.824T>C, con predictores de patogenicidad, que se comportó como un fenotipo recesivo Becker, pero con inicio más temprano.

NEUROENDOCRINE PEPTIDES IN THE PATHOGENESIS OF COLORECTAL CARCINOMA.

Colorectal carcinoma (CRC) is the third most frequent neoplasm worldwide and the second leading cause of mortality. Neuroendocrine peptides such as glucagon, bombesin, somatostatin, cholecystokinin, and gastrin as well as growth factors such as platelet-derived growth factor, epidermal growth factor, insulin-like growth factor, and fibroblast growth factor have been postulated as being involved in carcinogenesis. The fact that these neuroendocrine peptides are involved in the development of CRC through the activation of growth factors that stimulate a series of molecular pathways that activate oncogenic signaling mechanisms is emphasized in this review. Peptides such as CCK1, serotonin, and bombesin have been found to be over-expressed in human tumor tissues. Meanwhile, the expression of peptides such as GLP2 has been seen mainly in murine models. The information contained in this review provides a better understanding of the role these peptides play in the pathogenesis of CRC for basic and clinical science studies.

[KIF1A gene-associated neurological disease: the correlation between genotype and phenotype]. / Enfermedad neurológica asociada al gen KIF1A: correlación genotipo/fenotipo.

INTRODUCTION: KIF1A-associated-neurological-disorder (KAND) encephalopathy is a group of progressive neurodegenerative pathologies of varying severity caused by mutations in the KIF1A gene (Kinesin family member 1A) located on chromosome 2q37.3. This gene encodes a protein of the kinesin-3 family that participates in the ATP-dependent anterograde transport of presynaptic vesicles through neuronal microtubules. CASE REPORT: Four patients are described, aged 1-13 years, with a median onset of symptoms of 5 months (IQR 0-11 months), which represents an approximate prevalence of 1 per 64,000 children under 14 years of age for our pediatric population. Clinically, intellectual disability (ID), axial hypotonia and spastic paraparesis stood out in 4/4 and cerebellar symptoms in 2/4. Other manifestations were urinary incontinence, sensory-motor polyneuropathy, and behavioral alteration. In case 2, the alteration in the video-EEG stands out, which showed focal epilepsy with secondary generalization and right posterior occipito-parietal paroxysmal focality with contralateral transmission. She also showed instantaneous pluricotidian supraversion oculogyric seizures without EEG correlates. CONCLUSIONS: In our series, KAND encephalopathy had a predominant neurodegenerative disorder phenotype with global developmental delay, gait delay, and progressive spasticity of the lower limbs, cerebellar atrophy, and/or involvement of the visual cortex, which in one case was associated with sensory-motor polyneuropathy. The de novo missense mutation was more frequent and in three cases it is the first known description. One case showed focal epilepsy and nonepileptic oculogyric seizures.

TITLE: Enfermedad neurológica asociada al gen KIF1A: correlación genotipo/fenotipo.Introducción. La encefalopatía KIF1A-associated-neurological-disorder (KAND) es un grupo de patologías neurodegenerativas progresivas de diversa gravedad ocasionadas por mutaciones en el gen KIF1A (kinesin family member 1A) situado en el cromosoma 2q37.3. Dicho gen codifica una proteína de la familia de las cinesinas 3 que participa en el transporte anterógrado de las vesículas presinápticas dependientes del trifosfato de adenosina a través de microtúbulos neuronales. Casos clínicos. Se describen cuatro pacientes, con edades entre 1 y 13 años, con mediana de inicio de los síntomas de cinco meses (rango intercuartílico: 0-11 meses), lo que supone una prevalencia aproximada de 1 de cada 64.000 menores de 14 años para nuestra población pediátrica. Clínicamente, destacaron discapacidad intelectual, hipotonía axial y paraparesia espástica en 4/4, y síntomas cerebelosos en 2/4. Otras manifestaciones fueron incontinencia urinaria, polineuropatía sensitivomotora y alteración conductual. Destaca, en el caso 2, la alteración en el videoelectroencefalograma, que mostraba epilepsia focal con generalización secundaria y focalidad paroxística occipitoparietal posterior derecha con transmisión contralateral. También mostraba crisis oculógiras en supraversión instantáneas pluricotidianas sin correlato electroencefalográfico. Conclusiones. En nuestra serie, la encefalopatía KAND, fenotipo trastorno neurodegenerativo con retraso global del desarrollo, de la marcha y espasticidad progresiva de los miembros inferiores, atrofia cerebelosa y/o afectación de la corteza visual, fue predominante, y en uno de los casos asoció polineuropatía sensitivomotora. La mutación de novo missense fue más frecuente y en tres casos es la primera descripción conocida. Un caso mostraba epilepsia focal y crisis oculógiras no epilépticas.

Waning and boosting of antibody Fc-effector functions upon SARS-CoV-2 vaccination.

Since the emergence of SARS-CoV-2, vaccines targeting COVID-19 have been developed with unprecedented speed and efficiency. CoronaVac, utilising an inactivated form of the COVID-19 virus and the mRNA26 based Pfizer/BNT162b2 vaccines are widely distributed. Beyond the ability of vaccines to induce production of neutralizing antibodies, they might lead to the generation of antibodies attenuating the disease by recruiting cytotoxic and opsonophagocytic functions. However, the Fc-effector functions of vaccine induced antibodies are much less studied than virus neutralization. Here, using systems serology, we follow the longitudinal Fc-effector profiles induced by CoronaVac and BNT162b2 up until five months following the two-dose vaccine regimen. Compared to BNT162b2, CoronaVac responses wane more slowly, albeit the levels remain lower than that of BNT162b2 recipients throughout the entire observation period. However, mRNA vaccine boosting of CoronaVac responses, including response to the Omicron variant, induce significantly higher peak of antibody functional responses with increased humoral breadth. In summary, we show that vaccine platform-induced humoral responses are not limited to virus neutralization but rather utilise antibody dependent effector functions. We demonstrate that this functionality wanes with different kinetics and can be rescued and expanded via boosting with subsequent homologous and heterologous vaccination.

Implementation of the use of SPECT-portable for evaluation of surgical margins in breast cancer with indication of ROLL: First results.

OBJECTIVES: Main objective: To compare the effectiveness for checking surgical margins between SPECT-portable and mammography of the piece (RxM). SECONDARY OBJECTIVE: To standardize a pre-operative protocol using SPECT-portable and to evaluate the time required in the use of this technique. MATERIAL AND METHODS: Prospective longitudinal study with 36 patients (39 lesions) diagnosed with breast cancer (CM) with criteria for SNOLL/ROLL. A pre-surgical study of the tumor lesion was performed, after the eco-guided administration of 99mTc-nanocolloids of albumin/99mTc-macroaggregates of albumin, in the tumor lesion. Hybrid images (optical + SPECT) and 3D navigation images with gamma probe are obtained using freehandSPECT. In the operating room, 4-5 images are obtained with freehandSPECT, (I) on skin for tumor location, (II) after exposure of surgical bed for resection guide, (III) of the surgical bed after exeresis, (IV and V) the anterior-posterior and lateral surface of the surgical specimen. The three criteria to decide to extend the margins are: (a) residual activity (cps) at the edges of the surgical bed resection; (b) visual analysis of the uptake in the specimen; (c) a minimum distance of 10 mm from the edges of the specimen to the center of greatest uptake, plus the radius of the lesion. We study the concordance of: the depth measurement between ultrasound and freehandSPECT; the surgical margins between freehandSPECT vs. mammography of the specimen (RxM), considering anatomical pathology (AP) as the gold standard technique as reference; surgical time used with freehandSPECT and RxM. RESULTS: Intraoperative localization was performed in all cases. False negative (FN: no detection margin affected) with freehandSPECT: 9 margins; with RxM: 8. True positive (TP: detection margin affected) with freehandSPECT: 5 margins, with RxM: 6. True negative (TN: consider free margin when healthy) with freehandSPECT: 213 margins; with RxM: 196. Negative predictive value (NPV: probability of negative margin on unaffected part) with freehandSPECT: 95.9%, with RxM: 96.07%. Specificity with freehandSPECT: 96.8%, with RxM: 97%. The concordance of surgical bed margins between freehandSPECT and RxM: 94.5%. Between freehandSPECT and AP: 93.1%. Between RxM and PA: 93.5%, being all statistically significant (p-value <0.000), so we can affirm that both techniques are related or dependent on the reference technique, the PA. Degree of correlation between SPECT-portable and low PA (Kappa index: 0.34, 95% CI [0.22-0.47], and between RxM and moderate PA (Kappa index: 0.42, 95% CI [0.29-0.56], p-value <0.001. Comparison of the successes and failures of both techniques (SPECT-portable and RxM) and PA: Distribution χ2: 0.023 with degree of freedom 1, with value <0.05, so we can affirm that both techniques are similar, since there are no significant statistical differences. Median total OR time: 60.25 min (30-145). Mean freehandSPECT OR time: 5 scans = 10 min. CONCLUSIONS: There are no statistically significant differences in the probability to rule out affective margins that require a second surgery between both techniques (SPECT-portable and RxM) so, the technique performed with SPECT-Portable is a useful and effective procedure, which requires specific training with an optimized and multidisciplinary protocol. The time spent with SPECT-portable is feasible for daily practice.

Administration of Lactobacillus fermentum CRL1446 increases intestinal feruloyl esterase activity in mice.

AIMS: To evaluate the effect of oral administration of Lactobacillus fermentum CRL1446 on the intestinal feruloyl esterase (FE) activity and oxidative status of mice. METHODS AND RESULTS: Adult Swiss albino mice received Lact. fermentum CRL1446 at the doses 10(7) and 10(9) cells per day per mouse for 2, 5, 7 and 10 days. Intestinal FE activity, intestinal microbiota counts, plasmatic thiobarbituric acid-reactive substances (TBARS) percentage and glutathione reductase (GR) activity were determined. Mice that received Lact. fermentum CRL1446 at the dose 10(7) cells per day for 7 days showed a twofold increase in total intestinal FE activity, compared to the nontreated group. In large intestine content, FE activity increased up to 6·4 times. No major quantitative changes in colonic microbiota were observed in treated animals. Administration of this strain produced an approx. 30-40% decrease in the basal levels of plasmatic TBARS and an approx. twofold increase in GR activity from day 5 of feeding with both doses. CONCLUSIONS: Oral administration of Lact. fermentum CRL1446 to mice increases total intestinal FE activity, decreases the basal percentage of plasmatic lipoperoxides and increases GR activity. SIGNIFICANCE AND IMPACT OF THE STUDY: Lactobacillus fermentum CRL1446 could be orally administered as a dietary supplement or functional food for increasing the intestinal FE activity to enhance the bioavailability of ferulic acid, thus improving oxidative status.

Improving public engagement in ICZM: a practical approach.

Stakeholder engagement is at the core of successful ICZM stories. This paper proposes a practical approach to set the basis for a wide and efficient stakeholder engagement process in ICZM which was tested in Cantabria, a Region in the north of Spain. The coastal system was modelled by defining three basic interacting components: coastal units, coastal activities and coastal stakeholders. This approach allowed the identification of a very clear set of relationships emerging from a survey of stakeholders and an assessment of coastal projects. This process was also useful to inform stakeholders about a new regional coastal strategy and to consider their opinion on coastal issues and public participation. From a very ill-defined situation, a clear relationship chart was defined and a spatial database implemented which conveys all the data gathered into a useful tool for coastal managers.

Clinical research nursing: a critical resource in the national research enterprise.

Translational clinical research has emerged as an important priority for the national research enterprise, with a clearly stated mandate to more quickly deliver prevention strategies, treatments and cures based on scientific innovations to the public. Within this national effort, a lack of consensus persists concerning the need for clinical nurses with expertise and specialized training in study implementation and the delivery of care to research participants. This paper reviews efforts to define and document the role of practicing nurses in implementing studies and coordinating clinical research in a variety of clinical settings, and differentiates this clinical role from the role of nurses as scientists and principal investigators. We propose an agenda for building evidence that having nurses provide and coordinate study treatments and procedures can potentially improve research efficiency, participant safety, and the quality of research data. We also provide recommendations for the development of the emerging specialty of clinical research nursing.