Country-report pattern corrections of new cases allow accurate 2-week predictions of COVID-19 evolution with the Gompertz model.

Accurate short-term predictions of COVID-19 cases with empirical models allow Health Officials to prepare for hospital contingencies in a two-three week window given the delay between case reporting and the admission of patients in a hospital. We investigate the ability of Gompertz-type empiric models to provide accurate prediction up to two and three weeks to give a large window of preparation in case of a surge in virus transmission. We investigate the stability of the prediction and its accuracy using bi-weekly predictions during the last trimester of 2020 and 2021. Using data from 2020, we show that understanding and correcting for the daily reporting structure of cases in the different countries is key to accomplish accurate predictions. Furthermore, we found that filtering out predictions that are highly unstable to changes in the parameters of the model, which are roughly 20%, reduces strongly the number of predictions that are way-off. The method is then tested for robustness with data from 2021. We found that, for this data, only 1-2% of the one-week predictions were off by more than 50%. This increased to 3% for two-week predictions, and only for three-week predictions it reached 10%.

Family with recurrent cases of neural tube defects in Niamey (Niger).

A series of patients affected by neural tube defects have been studied in Niamey (Niger). This population is highly consanguineous and we try estimating the number of cases in which a previous identical malformation has been reported in the family. We found only 4 families indicating that the percentage of such families is not increased in our population. However, we think that studying genetic factors in this specific population could allow to demonstrate susceptibility genes that can act on this pathology.

Detección de nefrotóxicos y ajuste de dosis en pacientes con filtrado glomerular bajo realizado en farmacia comunitaria: metodología / Detection of nephrotoxicants and dose adjustment in patients with low glomerular filtration rate performed in community pharmacy: methodology

La enfermedad renal crónica es un problema prevalente y sin tratamiento específico. La detección tem prana es importante, siendo el Filtrado Glomerular estimado (FGe) una prueba muy asequible que puede realizarse en farmacia comunitaria. Si se presenta, es muy importante no dañar más el riñón evitando el uso de medicamentos nefrotóxicos y ajustar las dosis de otros medicamentos de eliminación renal, y la farmacia comunitaria está muy bien posicionada para ello. Objetivo: describir la metodología utilizada para detectar nefrotóxicos y ajustar dosis de otros medica mentos en farmacia comunitaria para su posterior derivación a atención primaria. Método: estudio experimental de seguimiento no controlado multicéntrico realizado en farmacias comunitarias de 4 comunidades autónomas de España. Se incluyen pacientes que cumplen criterios de inclusión y firman el consentimiento informado. Se estudian aquellos con FGe<60 ml/min/1,73m2 y se analiza su medicación utilizando el BOT Plus y otras 4 fuentes de información. Resultado: se incluyen 670 pacientes, 215 de ellos con FGe<60ml/min/1,73m2. De ellos 90 (41,9 %) necesitaron algún tipo de ajuste a juicio del farmacéutico. De estos 90 el 43,3 % (39) tuvieron algún tipo de cambio posteriormente a la intervención del farmacéutico. Conclusión: en pacientes con filtrado glomerular bajo, con la metodología adecuada, el farmacéutico comunitario es capaz de detectar la utilización de medicamentos nefrotóxicos o la utilización de medicamentos a dosis superiores a las recomendadas en función de su estado renal. Detección de nefrotóxicos y ajuste de dosis en pacientes con filtrado glomerular bajo realizado en farmacia comunitaria: metodología (AU)

Chronic kidney disease is a prevalent problem without specific treatment. Early detection is important and estimated glomerular filtration rate (eGFR) is a very affordable test that can be performed in community pharmacies. If present, it is very important not to further damage the kidney by avoiding the use of neph rotoxic drugs and adjusting the doses of other renal elimination drugs and the community pharmacy is very well positioned to do this. Objective: To describe the methodology used to detect nephrotoxic drugs and adjust doses of other drugs in community pharmacies for subsequent referral to primary care. Method: Multicentre experimental multicentre uncontrolled follow-up study carried out in communi ty pharmacies in 4 autonomous communities in Spain. Patients who met the inclusion criteria and signed the informed consent form were included. Those with eGFR <60 ml/min/1.73m2 were studied and their medication was analysed using the BOT Plus and 4 other sources of information. Result: 670 patients were included, 215 of them with eGFR<60ml/min/1.73m2. Of these 90 (41.9%) needed some type of adjustment in the pharmacist’s judgement. Of these 90, 43.3% (39) had some kind of change after the pharmacist’s intervention C onclusion: In patients with low glomerular filtration rate, with the appropriate methodology, the community pharmacist is able to detect the use of nephrotoxic drugs or the use of drugs at doses higher than those recommended according to their renal status (AU)

Hepatitis C Virus positivity prediction from serum samples using NIRS and L1-penalized classification.

AIMS: The hepatitis C virus (HCV) has developed a strategy to coexist with its host resulting in varying degrees of tissue and cell damage, which generate different pathological phenotypes, such as varying degrees of fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). However, there is no integrated information that can predict the evolutionary course of the infection. We propose to combine Near-infrared spectroscopy (NIRS) and machine learning techniques to provide a predictive model. In this work, we propose to discriminate HCV positivity in biobank patient serum samples. METHODS: 126 serum samples from 38 HCV patients in different stages of the disease were obtained from the Biobank of Hospital Universitario Fundación Alcorcon. NIRS spectrum was captured by a FT-NIRS Spectrum 100 (Perkin Elmer) device in reflectance mode. For each patient, the HCV positivity was identified (PCR) and labeled as detectable =1 and undetectable =0. We propose an L1-penalized logistic regression model to classify each spectrum as positive (1) or negative (0) for HCV presence (x). The regularization parameter is selected using 5- fold cross-validation. The penalized model will induce sparsity in the solution so that only a few relevant wavelengths will be different from zero. RESULTS: L1-penalized logistic regression model provided 167 wavelengths different from zero. The accuracy on an independent test set was 0.78. CONCLUSIONS: We present a straightforward promising approach to detect HCV positivity from patient serum samples combining NIRS and machine learning techniques. This result is encouraging to predict HCV progression, among other applications. Clinical relevance- We presented a simple while promising approach to use machine learning and NIRS to analyze viral presence on sample serums.

Polymicrogyria, aventriculy, polydactyly, encephalocele, callosal agenesis (PAPEC): a new syndrome?

INTRODUCTION: Aventriculy is a very rare observation and is generally associated with holoprosencephaly. We report here a case of polymalformation affecting the brain, hands, and feet observed in a highly consanguineous family in Niger. CASE REPORT: A boy was born from a highly consanguineous family presenting multiple malformations (aventriculy, extreme microcephaly, polydactyly, polymicrogyria, callosal agenesis, and parietal encephalocele). To the best of our knowledge, such association has never been reported so far. DISCUSSION: We propose to name this association PAPEC (for polymicrogyria, aventriculy, polydactyly, encephalocele, and callosal agenesis). The occurrence of this disease in a highly consanguineous family suggests a genetic origin. Furthermore, we propose hypotheses that could explain pathophysiology of this defect.

Effect of follicle size on hormonal status of follicular fluid, oocyte ATP content, and in vitro embryo production in prepubertal sheep.

The aim of this study was to assess the effect of follicular size on estradiol (E2) and progesterone (P4) levels in intrafollicular fluid, ATP content in oocytes, and the embryo development rate in prepubertal sheep. Slaughterhouse ovaries were dissected to recover the follicles, which were classified according to the follicle diameter as <3 mm (n = 20) and ≥3 mm (n = 17). Then, follicular fluid was obtained and analyzed by radioimmunoassay to determine the E2 and P4 concentrations. Another group of ovaries was used to recover cumulus-oocyte complexes according to follicle size. In vitro maturation (IVM), in vitro fertilization (IVF), and embryo culture were performed using standard procedures, and ATP level was assessed at 0 and 24 h of IVM. Intrafollicular concentrations of E2 and P4 and E2:P4 ratio were higher in ≥3 mm (18.7 ± 5.9 ng/mL, 7.8 ± 1.2 ng/mL, and 3.6 ± 1.3, respectively) than <3 mm (1.8 ± 0.4 ng/mL, 2.6 ± 0.3 ng/mL and 0.9 ± 0.3, respectively) follicles. The rate of ATP increased during IVM and was higher in oocytes from ≥3 mm than <3 mm (22.4 ± 0.7 and 8.6 ± 2.2-fold change; respectively) follicles. After IVF, the blastocyst development was higher in oocytes recovered from ≥3 mm (11.1 ± 0.9%) than from <3 mm (6.5 ± 0.7%) follicles. These results indicate an improvement in the competence and development of oocytes from ≥3 mm follicles with a higher E2:P4 ratio. Thus, this ratio could be used as reference to design IVM medium and to enhance the in vitro embryo production in lambs.

Endogenous NO Is Involved in Dissimilar Responses to Rehydration and Pb(NO3)2 in Ramalina farinacea Thalli and Its Isolated Phycobionts.

Lichens undergo desiccation/rehydration cycles and are permeable to heavy metals, which induce free radicals. Nitrogen monoxide (NO) regulates important cellular functions, but the research on lichen NO is still very scarce. In Ramalina farinacea thalli, NO seems to be involved in the peroxidative damage caused by air pollution, antioxidant defence and regulation of lipid peroxidation and photosynthesis. Our hypothesis is that NO also has a critical role during the rehydration and in the responses to lead of its isolated phycobionts (Trebouxia sp. TR9 and Trebouxia jamesii). Therefore, we studied the intracellular reactive oxygen species (ROS) production, lipid peroxidation and chlorophyll autofluorescence during rehydration of thalli and isolated microalgae in the presence of a NO scavenger and Pb(NO3)2. During rehydration, NO scavenging modulates free radical release and chlorophyll autofluorescence but not lipid peroxidation in both thalli and phycobionts. Pb(NO3)2 reduced free radical release (hormetic effect) both in the whole thallus and in microalgae. However, only in TR9, the ROS production, chlorophyll autofluorescence and lipid peroxidation were dependent on NO. In conclusion, Pb hormetic effect seems to depend on NO solely in TR9, while is doubtful for T. jamesii and the whole thalli.

Colaboración farmacéutico-médico en la elaboración de protocolos consensuados para el tratamiento de síntomas menores: programa 'INDICA+PRO' / Collaborative care protocols for the management of minor ailments agreed between pharmacists and medical practitioners: INDICA+PRO Study

Introducción: la colaboración entre médicos y farmacéuticos es necesaria en el manejo de los síntomas menores, ya que el paciente acude a ambos profesionales sanitarios para su tratamiento. El objetivo del estudio fue elaborar protocolos de trabajo consensuados entre farmacéuticos comunitarios y médicos de atención primaria para el Servicio de Indicación Farmacéutica (SIF). Material y método: se utilizaron dos metodologías: revisión bibliográfica y grupo de expertos para el consenso. Estos protocolos se actualizaron y diseñaron a partir de un documento previo de 2008. En el grupo de expertos se incluyeron cuatro farmacéuticos comunitarios de SEFAC (2), MICOF (2) y cuatro médicos de atención primaria de semFYC (2) y SEMERGEN (2). Resultados: se consensuaron protocolos de trabajo para 31 síntomas menores distribuidos en cinco grupos: respiratorios, dolor moderado, digestivos, dermatológicos y otros. Se añadieron cinco síntomas nuevos al documento de partida. Respecto a la estructura de cada síntoma se consideró: concepto, causas más frecuentes, criterios de derivación al médico (edad, síntomas de alarma, duración de los síntomas, otros problemas de salud y/o medicamentos y situaciones especiales), recomendaciones para la prevención y tratamiento (no farmacológico y farmacológico). Conclusión: el documento desarrollado mediante colaboración entre profesionales de la medicina y la farmacia es una herramienta que contribuye a la mejora de la actuación del farmacéutico en el manejo de los síntomas menores desde la farmacia comunitaria, con énfasis en la definición de indicadores que señalan la necesidad de derivar el paciente al médico de atención primaria

Background: To increase the collaboration between community pharmacists and medical practitioners working in primary care it is critical to have collaborative protocols in place. Minor ailments could be a good example where this collaboration would benefit patient care as patients are seeking treatment in both settings. These collaborative protocols would assist in diminishing the variability of treatments in both settings. The aim of the study was to develop care protocols for minor ailments agreed between medical practitioners and pharmacists Methods: Two different methodologies were used to arrive at a consensus for the proto-cols: literature review and expert group. Some of the clinical protocols were updated from a previous document created in 2008. Expert group was composed of four community pharma-cists (SEFAC, MICOF) and four medical practitioners (SemFyC y Semergen). Results: Thirty-one protocols for minor ailments were agreed and allocated to five groups (five new minor ailments protocols were added: respiratory tract-related conditions, gastrointestinal disturbance, pain, dermatological problems and others.Protocols were structured following: definition, more frequent causes, referral criteria (pa-tient’s age, red flags, symptom’s duration, patient’s health problems and treatments and physiological situations), recommendations for management (prevention, non-pharmacological and pharmacological treatment) and references used. Conclusions: Clinical protocols agreed between health professionals of medicine and phar-macy are a tool that contribute to better management of minor ailments in community pharmacy

[Development and growth of the skull base]. / Développement et croissance de la base du crâne.

The skull base is a part of the neuro-cranium formed by endochondral ossification. The embryological origin of the skull base is not perfectly known, but there seems to be an anterior region derived from the neural crest and a posterior part derived from the mesoderm. Further studies are needed to define reliable presumptive maps. The origin of the different components of the occipital bone is just as poorly known. Much fundamental work remains to be done to suggest any solution to these problems in humans.

[Development and growth of the vault of the skull]. / Développement et croissance de la voûte du crâne.

The vault of the skull is a region of the neurocranium formed by a process of membranous ossification. It consists of several bones: frontal bone, parietal bone, squamous part of the temporal bone, lamina ascendens of the sphenoid, and interparietal bone. The embryological origin of the bones of the skull vault is still the subject of controversy. This can be explained by the different animal models used for these purposes, but also by the various techniques applied to this problem. At all events, it seems that the cells of the neural crest generate some of the bones of the vault and that the others are derived from the mesoderm. This uncertainty should lead readers to be extremely cautious before using the presumptive maps published in the literature. Several tissues interact with osteo-progenitor cells: neural tube, surface ectoderm and dura mater. Analysis of genes in which mutations lead to abnormalities of the skull vault has partly revealed the molecular interactions. These are very complex and are the field of very numerous experimental investigations. In the relatively near future, we can hope to discover some of the molecular networks leading to the formation of these bony structures.

Epigenetics and periodontics: A systematic review.

BACKGROUND: Despite decades of research, our knowledge of several important aspects of periodontal pathogenesis remains incomplete. Epigenetics allows to perform dynamic analysis of different variations in gene expression, providing this great advantage to the static measurement provided by genetic markers. The aim of this systematic review is to analyze the possible relationships between different epigenetic mechanisms and periodontal diseases, and to assess their potential use as biomarkers of periodontitis. MATERIAL AND METHODS: A systematic search was conducted in six databases using MeSH and non-MeSH terms. The review fulfilled PRISMA criteria (Preferred Reporting Items for Systematic reviews and Meta-analysis). RESULTS: 36 studies met the inclusion criteria. Due to the heterogeneity of the articles, it was not possible to conduct quantitative analysis. Regarding qualitative synthesis, however, it was found that epigenetic mechanisms may be used as biological markers of periodontal disease, as their dynamism and molecular stability makes them a valuable diagnostic tool. CONCLUSIONS: Epigenetic markers alter gene expression, producing either silencing or over-expression of molecular transcription that respond to the demands of the cellular surroundings. Gingival crevicular fluid collection is a non-invasive and simple procedure, which makes it an ideal diagnostic medium for detection of both oral and systemic issues. Although further research is needed, this seems to be a promising field of research in the years to come.

GJA1 Variants Cause Spastic Paraplegia Associated with Cerebral Hypomyelination.

Oculodentodigital dysplasia is an autosomal dominant disorder due to GJA1 variants characterized by dysmorphic features. Neurologic symptoms have been described in some patients but without a clear neuroimaging pattern. To understand the pathophysiology underlying neurologic deficits in oculodentodigital dysplasia, we studied 8 consecutive patients presenting with hereditary spastic paraplegia due to GJA1 variants. Clinical disease severity was highly variable. Cerebral MR imaging revealed variable white matter abnormalities, consistent with a hypomyelination pattern, and bilateral hypointense signal of the basal ganglia on T2-weighted images and/or magnetic susceptibility sequences, as seen in neurodegeneration with brain iron accumulation diseases. Patients with the more prominent basal ganglia abnormalities were the most disabled ones. This study suggests that GJA1-related hereditary spastic paraplegia is a complex neurodegenerative disease affecting both the myelin and the basal ganglia. GJA1 variants should be considered in patients with hereditary spastic paraplegia presenting with brain hypomyelination, especially if associated with neurodegeneration and a brain iron accumulation pattern.

Potenciar la lectura desde la farmacia comunitaria en personas mayores para protegerlos del deterioro cognitivo / No disponible

Introducción: El deterioro cognitivo (DC) es una enfermedad que aumenta con la edad. Es importante conocer los factores protectores y de riesgo de esta enfermedad. Metodología: Estudio observacional realizado a 729 personas mayores de 65 años en 13 farmacias comunitarias durante dos años. Se recogieron datos demográficos (sexo, edad, nivel de estudios) y de estilos de vida (afición a la lectura, realización de pasatiempos, horas de televisión) y para el cribaje de los pacientes se realizaron los test SPMSQ (Short-Portable Mental State Questionaire) de Pfeiffer y Mini-Mental State Examination (MMSE) versión NORMADERM. También se realizó una revisión bibliográfica del tema. Resultados: Se detectó un 17,6% de DC. Se encontró una asociación estadísticamente significativa como protección frente al DC con la afición a la lectura y el nivel de estudios. No se encontró asociación con las horas de televisión (TV) ni con la realización de pasatiempos. La revisión bibliográfica aportó más factores protectores y de riesgo. Discusión: Con nuestros datos podemos afirmar que tanto la reserva cognitiva (años de estudio) como la estimulación cognitiva (horas de lectura) protegen del DC. Sobre los demás datos obtenidos no se han encontrado coincidencias, por lo que sería necesario aumentar el tamaño muestral para poder realizar una comparación más eficaz. Conclusiones: El nivel educativo bajo es un factor de riesgo de DC, mientras que estudios superiores serían un factor preventivo. La lectura es un factor protector de DC

Introduction: Cognitive Dysfunction (CD) is a disease that increases with age. It is important to know the protective and risk factors for this disease. Methodology: Observational study carried out on 729 people over 65 years of age in community 13 pharmacies for two years. Demographic data were collected (sex, age, level of studies) and lifestyles (love of reading, hobbies such as crossword puzzles or sudokus etc, TV hours), and the SPMSQ (Short-Portable Mental State Questionaire) test of Pfeiffer and MiniMental State Examination (MMSE) were carried out to check the patient's CD. A bibliographic review of the subject was also conducted. Results: 17.6% of CD was detected. A statistically significant association was found as a protection against CD with a love of reading and the level of studies. No association was found with TV hours or hobbies. The literature review provided more protective and risk factors. Discussion: With our data we can affirm that both cognitive reserve (years of study) and cognitive stimulation (hours of reading) protect from CD. No coincidences were found on the other data obtained, so it would be necessary to increase the sample size in order to make a more effective comparison. Conclusions: Low educational level is a risk factor for CD while higher education would be a preventive factor. Reading is a protective factor of CD

The role of stress-regulation genes in moderating the association of stress and daily-life psychotic experiences.

OBJECTIVE: The interaction of single nucleotide polymorphisms with both distal and proximal environmental factors across the extended psychosis phenotype is understudied. This study examined (i) the interaction of relevant SNPs with both early-life adversity and proximal (momentary) stress on psychotic experiences (PEs) in an extended psychosis sample; and (ii) differences between early-psychosis and non-clinical groups for these interactions. METHODS: Two hundred and forty-two non-clinical and 96 early-psychosis participants were prompted randomly eight times daily for 1 week to complete assessments of current experiences, including PEs and stress. Participants also reported on childhood trauma and were genotyped for 10 SNPs on COMT, RGS4, BDNF, FKBP5, and OXTR genes. RESULTS: Unlike genetic variants, distal and proximal stressors were associated with PEs in both samples and were more strongly associated with PEs in the early-psychosis than in the non-clinical group. The RGS4 TA and FKBP5 CATT haplotypes interacted with distal stress, whereas the A allele of OXTR (rs2254298) interacted with proximal stress, increasing momentary levels of PEs in the early-psychosis group. No interactions emerged with COMT or BDNF variants. CONCLUSION: Individual differences in relevant stress-regulation systems interact with both distal and proximal psychosocial stressors in shaping the daily-life manifestation of PEs across the psychosis continuum.

Notomelia and related neural tube defects in a baby born in Niger: case report and literature review.

INTRODUCTION: Notomelia associated with neural tube defects are rare diseases. CASE REPORT: A baby was born in Niger with multiple congenital embryonic malformations on the posterior midline. The most rostral malformation was an accessory limb (polymelia) at the level of the lumbar vertebrae composed of two long bones, a foot and three toes. Accessory male genitalia were present at the base of this malformed accessory limb which had no apparent motor or sensory innervation. The second malformation was a sacral vestigial appendage with an adjacent dermal sinus opening onto the posterior midline and extending internally to the dura through a defect of the vertebral arches. From the published literature and this particular case, we conclude that notomelia is a rare clinical sequela of a neural tube defect (NTD) and is correctly classified as a dysraphic appendage. CONCLUSION: The recent occurrence of three similar cases in the same ethnic group from Niger, three from consanguineous parents, suggests that genetic factors are likely to contribute significantly to the genesis of this syndrome, consistent with a recent report that mutation of the bovine NHLRC2 gene resulting in a V311A substitution at a highly conserved locus in the NHLRC2 protein is, when homozygous, causally associated with several forms of polymelia including notomelia, with heteropagus conjoined twinning and with other NTD-related embryonic malformations. Detailed genome-wide studies of children with dysraphic appendages are indicated.

Hypomineralized Second Primary Molars as Predictor of Molar Incisor Hypomineralization.

Molar incisor hypomineralization (MIH) is a developmental defect of dental enamel that shares features with hypomineralized second primary molars (HSPM). Prior to permanent tooth eruption, second primary molars could have predictive value for permanent molar and incisor hypomineralization. To assess this possible relationship, a cross-sectional study was conducted in a sample of 414 children aged 8 and 9 years from the INMA cohort in Valencia (Spain). A calibrated examiner (linear-weighted Kappa 0.83) performed the intraoral examinations at the University of Valencia between November 2013 and 2014, applying the diagnostic criteria for MIH and HSPM adopted by the European Academy of Paediatric Dentistry. 100 children (24.2%) presented MIH and 60 (14.5%) presented HSPM. Co-occurrence of the two defects was observed in 11.1% of the children examined. The positive predictive value was 76.7% (63.9-86.6) and the negative predictive value 84.7% (80.6-88.3). The positive likelihood ratio (S/1-E) was 10.3 (5.9-17.9) and the negative likelihood ratio (1-S/E) 0.57 (0.47-0.68). The odds ratio was 18.2 (9.39-35.48). It was concluded that while the presence of HSPM can be considered a predictor of MIH, indicating the need for monitoring and control, the absence of this defect in primary dentition does not rule out the appearance of MIH.

The endocrine disruptor nonylphenol induces sublethal toxicity in vascular plant development at environmental concentrations: A risk for riparian plants and irrigated crops?

In recent years, there is a growing concern among the scientific community about the presence of the so-called emergent pollutants in waters of different countries, especially endocrine-disrupting compounds (EDCs) that have the ability to alter the hormonal system. One of the substances found almost ubiquitously and in higher concentrations is the alkylphenol nonylphenol. Albeit this compound is included in priority lists as a probable risk for human health and the environment, little is known about its effects on developing plants. The aim of this work is to assess the acute and sub-chronic toxicity of environmental concentrations of nonylphenol in riparian vascular plant development using spores of the fern Polystichum setiferum and a biomarker-based approach: mitochondrial activity (cell viability), chlorophyll (plant physiology) and DNA content (growth). Mitochondrial activity and DNA content show that nonylphenol induces acute and sub-chronic toxicity at 48 h and after 1 week, respectively. Significant effects are observed in both parameters in fern spores at ng L(-1) but chlorophyll autofluorescence shows little changes. The inhibition of germination by natural allelochemicals has been reported to be related with the active hydroxyl group of phenolic compounds and largely independent of the structural nucleus to which it is attached. Results presented in this study suggest that environmental concentrations of nonylphenol could interfere with higher plant germination development by mimicking natural allelochemicals and/or phytohormones acting as a "phytoendocrine disruptor" likely posing ecophysiological risks.