Covid-19 analysis using the Gompertz Function

This report analyses the spread of COVID-19 in european countries, focusing especially on Italy and Spain, for which short-term predictions are made for the cumulative number of hospitalizations, ICUs, discharges and deaths. Taking into account the different magnitudes considered, for 1 day predictions the mean probability of a right guess is of 0.99, 0.94 for 2 day predictions, 0.89 for 3 day predictions and 0.83 for 4 day predictions2019/202

Salud y seguridad laboral en la industria del transporte (TRANS-12): estructura factorial, fiabilidad y validez

Background: This study sets out the psychometric properties of the TRANS-18 scale and of a shorter version, the TRANS-12, both designed to detect safe behaviors (personal and vehicle-related) and psychophysiological disorders among professional drivers. Method: The investigation was divided into Study 1, into the factorial structure, reliability and validity of the TRANS-18, and Study 2, looking into the same aspects of the TRANS-12. The participants in both studies were resident in Spain. 272 professional drivers took part in Study 1, while Study 2 had 326 participants. Results: A confirmatory factor analysis was carried out for both studies. The results for Study 1 confirm an internal structure of three factors related to psychophysiological disorders and personal and vehicle-related safety behaviors, but the original TRANS-18 is discarded because it does not fit the model. With regard to Study 2, the results show a good fit of the three-factor model, appropriate reliability and evidence of validity. Conclusions: We conclude by considering the suitability of the psychometric properties of the TRANS-12 and its utility for identifying safe behaviors in work in the transport industry.Antecedentes: Este estudio expone las propiedades psicométricas de la escala TRANS-18 y de una versión más corta, el TRANS-12, ambos diseñados para detectar conductas seguras (personales y relacionadas con el vehículo) y trastornos psicofisiológicos entre conductores profesionales. Método: La investigación se divide en dos. Estudio 1, estructura factorial, fiabilidad y validez del TRANS-18, y Estudio 2, se estudian los mismos aspectos en el TRANS-12. Los participantes en ambos estudios fueron residentes en España. 272 conductores profesionales participaron en el Estudio 1, mientras que el Estudio 2 participaron 326 conductores. Resultados: Se realizó un análisis factorial confirmatorio para ambos estudios. Los resultados del Estudio 1 confirman una estructura interna de tres factores relacionados con los trastornos psicofisiológicos y las conductas de seguridad personales y con el vehículo, pero el TRANS-18 original se descarta por no ajustarse al modelo. Con respecto al Estudio 2, los resultados muestran un buen ajuste del modelo de tres factores, la fiabilidad apropiada y la evidencia de validez. Conclusiones: Concluimos considerando la idoneidad de las propiedades psicométricas del TRANS-12 y su utilidad para identificar comportamientos seguros en el trabajo en la industria del transporte

NPC1 regulates the distribution of phosphatidylinositol 4-kinases at Golgi and lysosomal membranes

Cholesterol and phosphoinositides (PI) are two critically important lipids that are found in cellular membranes and dysregulated in many disorders. Therefore, uncovering molecular pathways connecting these essential lipids may offer new therapeutic insights. We report that loss of function of lysosomal Niemann-Pick Type C1 (NPC1) cholesterol transporter, which leads to neurodegenerative NPC disease, initiates a signaling cascade that alters the cholesterol/phosphatidylinositol 4-phosphate (PtdIns4P) countertransport cycle between Golgi-endoplasmic reticulum (ER), as well as lysosome-ER membrane contact sites (MCS). Central to these disruptions is increased recruitment of phosphatidylinositol 4-kinases-PI4KIIα and PI4KIIIβ-which boosts PtdIns4P metabolism at Golgi and lysosomal membranes. Aberrantly increased PtdIns4P levels elevate constitutive anterograde secretion from the Golgi complex, and mTORC1 recruitment to lysosomes. NPC1 disease mutations phenocopy the transporter loss of function and can be rescued by inhibition or knockdown of either key phosphoinositide enzymes or their recruiting partners. In summary, we show that the lysosomal NPC1 cholesterol transporter tunes the molecular content of Golgi and lysosome MCS to regulate intracellular trafficking and growth signaling in health and disease

IP3R-driven increases in mitochondrial Ca2+ promote neuronal death in NPC disease

Ca2+ is the most ubiquitous second messenger in neurons whose spatial and temporal elevations are tightly controlled to initiate and orchestrate diverse intracellular signaling cascades. Numerous neuropathologies result from mutations or alterations in Ca2+ handling proteins; thus, elucidating molecular pathways that shape Ca2+ signaling is imperative. Here, we report that loss-of-function, knockout, or neurodegenerative disease-causing mutations in the lysosomal cholesterol transporter, Niemann-Pick Type C1 (NPC1), initiate a damaging signaling cascade that alters the expression and nanoscale distribution of IP3R type 1 (IP3R1) in endoplasmic reticulum membranes. These alterations detrimentally increase Gq-protein coupled receptor-stimulated Ca2+ release and spontaneous IP3R1 Ca2+ activity, leading to mitochondrial Ca2+ cytotoxicity. Mechanistically, we find that SREBP-dependent increases in Presenilin 1 (PS1) underlie functional and expressional changes in IP3R1. Accordingly, expression of PS1 mutants recapitulate, while PS1 knockout abrogates Ca2+ phenotypes. These data present a signaling axis that links the NPC1 lysosomal cholesterol transporter to the damaging redistribution and activity of IP3R1 that precipitates cell death in NPC1 disease and suggests that NPC1 is a nanostructural disease

Differential diagnosis between Parkinson's disease and essential tremor using the smartphone's accelerometer

Background: The differential diagnosis between patients with essential tremor (ET) and those with Parkinson's disease (PD) whose main manifestation is tremor may be difficult unless using complex neuroimaging techniques such as 123I-FP-CIT SPECT. We considered that using smartphone's accelerometer to stablish a diagnostic test based on time-frequency differences between PD an ET could support the clinical diagnosis. Methods: The study was carried out in 17 patients with PD, 16 patients with ET, 12 healthy volunteers and 7 patients with tremor of undecided diagnosis (TUD), who were re-evaluated one year after the first visit to reach the definite diagnosis. The smartphone was placed over the hand dorsum to record epochs of 30 s at rest and 30 s during arm stretching. We generated frequency power spectra and calculated receiver operating characteristics curves (ROC) curves of total spectral power, to establish a threshold to separate subjects with and without tremor. In patients with PD and ET, we found that the ROC curve of relative energy was the feature discriminating better between the two groups. This threshold was then used to classify the TUD patients. Results: We could correctly classify 49 out of 52 subjects in the category with/without tremor (97.96% sensitivity and 83.3% specificity) and 27 out of 32 patients in the category PD/ET (84.38% discrimination accuracy). Among TUD patients, 2 of 2 PD and 2 of 4 ET were correctly classified, and one patient having PD plus ET was classified as PD. Conclusions: Based on the analysis of smartphone accelerometer recordings, we found several kinematic features in the analysis of tremor that distinguished first between healthy subjects and patients and, ultimately, between PD and ET patients. The proposed method can give immediate results for the clinician to gain valuable information for the diagnosis of tremor. This can be useful in environments where more sophisticated diagnostic techniques are unavailable

Regulation of young-adult neurogenesis and neuronal differentiation by neural cell adhesion molecule 2 (NCAM2)

Adult neurogenesis persists in mammals in the neurogenic zones, where newborn neurons are incorporated into preexisting circuits to preserve and improve learning and memory tasks. Relevant structural elements of the neurogenic niches include the family of cell adhesion molecules (CAMs), which participate in signal transduction and regulate the survival, division, and differentiation of radial glial progenitors (RGPs). Here we analyzed the functions of neural cell adhesion molecule 2 (NCAM2) in the regulation of RGPs in adult neurogenesis and during corticogenesis. We characterized the presence of NCAM2 across the main cell types of the neurogenic process in the dentate gyrus, revealing different levels of NCAM2 amid the progression of RGPs and the formation of neurons. We showed that Ncam2 overexpression in adult mice arrested progenitors in an RGP-like state, affecting the normal course of young-adult neurogenesis. Furthermore, changes in Ncam2 levels during corticogenesis led to transient migratory deficits but did not affect the survival and proliferation of RGPs, suggesting a differential role of NCAM2 in adult and embryonic stages. Our data reinforce the relevance of CAMs in the neurogenic process by revealing a significant role of Ncam2 levels in the regulation of RGPs during young-adult neurogenesis in the hippocampus

Microtubules gate tau condensation to spatially regulate microtubule functions.

Tau is an abundant microtubule-associated protein in neurons. Tau aggregation into insoluble fibrils is a hallmark of Alzheimer's disease and other types of dementia1, yet the physiological state of tau molecules within cells remains unclear. Using single-molecule imaging, we directly observe that the microtubule lattice regulates reversible tau self-association, leading to localized, dynamic condensation of tau molecules on the microtubule surface. Tau condensates form selectively permissible barriers, spatially regulating the activity of microtubule-severing enzymes and the movement of molecular motors through their boundaries. We propose that reversible self-association of tau molecules, gated by the microtubule lattice, is an important mechanism of the biological functions of tau, and that oligomerization of tau is a common property shared between the physiological and disease-associated forms of the molecule

Pre‐screening models for patient engagement: The MOPEAD project

AbstractBackgroundAlzheimer's disease (AD) is a devastating condition that not only impacts greatly on the patient's health but also poses an important burden on the patient's immediate family circle. Early detection of AD allows patients to have an active role in managing their condition, and to plan how to minimize the strain on their dear ones. Despite known benefits, a large proportion of dementia cases remains undiagnosed or receives a late stage diagnosis. The MOPEAD project aims to address this issue by exploring innovative strategies to emerge "hidden" cases of cognitive impairment.MethodMemory clinics located in five different European countries participated in the project. Four innovative pre‐screening strategies were implemented to detect cognitive decline among individuals aged 65‐85 years who had never received a dementia related diagnosis: a) a web‐based pre‐screening tool along with an online marketing campaign, b) open house initiatives where people with memory complaints were invited to receive a quick evaluation at participating memory clinics, c) a primary care‐based protocol for early detection of cognitive decline using easily administered tools, and d) a tertiary care‐based pre‐screening at diabetologist clinics specifically designed to assess risk of dementia among patients with diabetes. A positive pre‐screening result implied that individuals were at high risk of having mild cognitive impairment or AD.ResultThe number of individuals enrolled, and the proportion of those with positive pre‐screening results varied across strategies. The web‐based tool evaluated the largest number of individuals (n=1487) and yielded 547 positive results (36.8%). The Open house initiative pre‐screened 661 subjects of whom 235 (35.6%) obtained a positive result. A total of 435 patients were pre‐screened in the primary care‐based strategy and 193 of them (44.4%) were found to have a positive result. Finally, 264 patients from diabetes clinics underwent pre‐screening and 154 (58.3%) showed a positive result.ConclusionUsing innovative pre‐screening strategies, we were able to identify 1129 individuals at high risk of having dementia who had otherwise remained unnoticed. Initiatives like this, show us the way to go in order to shift the paradigm of AD towards an earlier diagnosis

Complementary pre-screening strategies to uncover hidden prodromal and mild Alzheimer's disease : Results from the MOPEAD project

The Models of Patient Engagement for Alzheimer's Disease (MOPEAD) project was conceived to explore innovative complementary strategies to uncover hidden prodromal and mild Alzheimer's disease (AD) dementia cases and to raise awareness both in the general public and among health professionals about the importance of early diagnosis. Four different strategies or RUNs were used: (a) a web-based (WB) prescreening tool, (2) an open house initiative (OHI), (3) a primary care-based protocol for early detection of cognitive decline (PC), and (4) a tertiary care-based pre-screening at diabetologist clinics (DC). A total of 1129 patients at high risk of having prodromal AD or dementia were identified of 2847 pre-screened individuals (39.7%). The corresponding proportion for the different initiatives were 36.8% (WB), 35.6% (OHI), 44.4% (PC), and 58.3% (DC). These four complementary pre-screening strategies were useful for identifying individuals at high risk of having prodromal or mild AD

DNA Methylomes Reveal Biological Networks Involved in Human Eye Development, Functions and Associated Disorders

This work provides a comprehensive CpG methylation landscape of the different layers of the human eye that unveils the gene networks associated with their biological functions and how these are disrupted in common visual disorders. Herein, we firstly determined the role of CpG methylation in the regulation of ocular tissue-specification and described hypermethylation of retinal transcription factors (i.e., PAX6, RAX, SIX6) in a tissue-dependent manner. Second, we have characterized the DNA methylome of visual disorders linked to internal and external environmental factors. Main conclusions allow certifying that crucial pathways related to Wnt-MAPK signaling pathways or neuroinflammation are epigenetically controlled in the fibrotic disorders involved in retinal detachment, but results also reinforced the contribution of neurovascularization (ETS1, HES5, PRDM16) in diabetic retinopathy. Finally, we had studied the methylome in the most frequent intraocular tumors in adults and children (uveal melanoma and retinoblastoma, respectively). We observed that hypermethylation of tumor suppressor genes is a frequent event in ocular tumors, but also unmethylation is associated with tumorogenesis. Interestingly, unmethylation of the proto-oncogen RAB31 was a predictor of metastasis risk in uveal melanoma. Loss of methylation of the oncogenic mir-17-92 cluster was detected in primary tissues but also in blood from patients.The research leading to these results was supported by European Research Council Advanced Grant EPINORC, RecerCaixa Foundation, Federación Española de Enfermedades Raras (FEDER), Federación Española de Enfermedades Neuromusculares (ASEM), Fundación Isabel Gemio, COST CM1406, Instituto de Salud Carlos III (PI/00816) and Health and Sciences Departments of the Catalan Government (Generalitat de Catalunya). M.E. is an Institució Catalana de Recerca i Estudis Avançats (ICREA) Research Professor. We thank the staff of the Biobank Facility at the Bellvitge Biomedical Research Institute (IDIBELL), Spanish National Cancer Research Center (CNIO), Institute of Rare Diseases Research (BioNER-ISCIII), Vall d’Hebron Research Institute (VHIR) and Banc de Sang i Teixits (BST) of the Catalan Ministry of Health. We also thank Dr. Mercedes Hurtado (Department of Ophthalmology, University and Polytechnic Hospital La Fe) and Dr. Dolores Pinazo (Department of Ophthalmology, Dr. Peset University Hospital) for obtaining samples from glaucomatous patients. We thank the patients and their families.S