Consistent Phosphenes Generated by Electrical Microstimulation of the Visual Thalamus. An Experimental Approach for Thalamic Visual Neuroprostheses

Most work on visual prostheses has centered on developing retinal or cortical devices. However, when retinal implants are not feasible, neuroprostheses could be implanted in the lateral geniculate nucleus (LGN) of the thalamus, the intermediate relay station of visual information from the retina to the visual cortex (V1). The objective of the present study was to determine the types of artificial stimuli that when delivered to the visual thalamus can generate reliable responses of the cortical neurons similar to those obtained when the eye perceives a visual image. Visual stimuli {Si} were presented to one eye of an experimental animal and both, the thalamic {RThi} and cortical responses {RV1i} to such stimuli were recorded. Electrical patterns {RThi*} resembling {RThi} were then injected into the visual thalamus to obtain cortical responses {RV1i*} similar to {RV1i}. Visually- and electrically generated V1 responses were compared. Results: During the course of this work we: (i) characterized the response of V1 neurons to visual stimuli according to response magnitude, duration, spiking rate, and the distribution of interspike intervals; (ii) experimentally tested the dependence of V1 responses on stimulation parameters such as intensity, frequency, duration, etc., and determined the ranges of these parameters generating the desired cortical activity; (iii) identified similarities between responses of V1 useful to compare the naturally and artificially generated neuronal activity of V1; and (iv) by modifying the stimulation parameters, we generated artificial V1 responses similar to those elicited by visual stimuli. Generation of predictable and consistent phosphenes by means of artificial stimulation of the LGN is important for the feasibility of visual prostheses. Here we proved that electrical stimuli to the LGN can generate V1 neural responses that resemble those elicited by natural visual stimuli

Preparation of Dipteran Larvae for Scanning Electron Microscopy with Special Reference to Myiasigen Dipteran Species

Although controversy exists concerning the role of chemical fixatives in scanning electron microscopy (SEM) studies of Dipteran larvae, we have observed that filtered 10% formaldehyde solution gives excellent results as a preservative. After immersing in vivo in formaldehyde, the larvae material is preserved for prolonged periods (up to 8 months), before examination with SEM. As a fixative, formaldehyde preserves the structure of the larval cuticle and produces no visible artifacts. Moreover, postfixation is not necessary. Due to pecularities of the way of life of Wohlfahrtia magnifica (principally the accumulations of necrotic tissue, purulent particles, and other types of substances that often adhere to the numerous spines of larvae), this species must be cleaned before examination by SEM. Manual cleaning with alternating bidistilled water and 0.9% saline solution proved to be a rapid, easy and inexpensive method that gave good results. Both lyophilization drying and critical point drying were used before sputtering the material. While lyophilization drying proved to be the most effective method for instars II and III, critical point drying was the best technique for study of specimens belonging to instar I. The optimum time for drying and conditions for lyophilization and sputter-coating with gold were determined experimentally. Samples were mounted on SEM stubs with double-sided adhesive and silver conductive paint. The method proposed is easy and effective for the SEM study of larvae myiasis-producing diptera

Biochemical characterization of recombinant Candida albicans mannosyltransferases Mnt1, Mnt2 and Mnt5 reveals new functions in O- and N-mannan biosynthesis

Peer reviewedPublisher PD

MSSM Higgs Boson Phenomenology at the Tevatron Collider

The Higgs sector of the minimal supersymmetric standard model (MSSM) consists of five physical Higgs bosons, which offer a variety of channels for their experimental search. The present study aims to further our understanding of the Tevatron reach for MSSM Higgs bosons, addressing relevant theoretical issues related to the SUSY parameter space, with special emphasis on the radiative corrections to the down--quark and lepton couplings to the Higgs bosons for large $\tan\beta$. We performed a computation of the signal and backgrounds for the production processes $W\phi$ and $b \bar{b} \phi$ at the upgraded Tevatron, with $\phi$ being the neutral MSSM Higgs bosons. Detailed experimental information and further higher order calculations are demanded to confirm/refine these predictions.Comment: 47 pages, REVTex format, 15 figures; spacing changed to reduce length, references added or moved within manuscript for clarity, some rewording, labelling corrected on two figures, results unchange

BDNF and NGF Signalling in Early Phases of Psychosis: Relationship with Inflammation and Response to Antipsychotics after 1 Year

Previous studies have indicated systemic deregulation of the proinflammatory or anti-inflammatory balance in individuals with first-episode psychosis (FEP) that persists 12 months later. To identify potential risk/protective factors and associations with symptom severity, we assessed possible changes in plasma levels of neurotrophins (brain-derived neurotrophic factor BDNF] and nerve growth factor NGF]) and their receptors in peripheral blood mononuclear cells (PBMCs). Expression of the 2 forms of BDNF receptors (active TrkB-FL and inactiveTrkB-T1) in PBMCs of FEP patients changed over time, TrkB-FL expression increasing by 1 year after diagnosis, while TrkB-T1 expression decreased. The TrkB-FL/TrkB-T1 ratio (hereafter FL/T1 ratio) increased during follow-up in the nonaffective psychosis group only, suggesting different underlying pathophysiological mechanisms in subgroups of FEP patients. Further, the expression of the main NGF receptor, TrkA, generally increased in patients at follow-up. After adjusting for potential confounders, baseline levels of inducible isoforms of nitric oxide synthase, cyclooxygenase, and nuclear transcription factor were significantly associated with the FL/T1 ratio, suggesting that more inflammation is associated with higher values of this ratio. Interestingly, the FL/T1 ratio might have a role as a predictor of functioning, a regression model of functioning at 1 year suggesting that the effect of the FL/T1 ratio at baseline on functioning at 1 year depended on whether patients were treated with antipsychotics. These findings may have translational relevance; specifically, it might be useful to assess the expression of TrkB receptor isoforms before initiating antipsychotic treatment in FEPs

BDNF and NGF signalling in early phases of psychosis: relationship with inflammation and response to antipsychotics after a 1 year

Previous studies have indicated systemic deregulation of the proinflammatory or anti-inflammatory balance in individuals with first-episode psychosis (FEP) that persists 12 months later. To identify potential risk/protective factors and associations with symptom severity, we assessed possible changes in plasma levels of neurotrophins (brain-derived neurotrophic factor [BDNF] and nerve growth factor [NGF]) and their receptors in peripheral blood mononuclear cells (PBMCs). Expression of the 2 forms of BDNF receptors (active TrkB-FL and inactiveTrkB-T1) in PBMCs of FEP patients changed over time, TrkB-FL expression increasing by 1 year after diagnosis, while TrkB-T1 expression decreased. The TrkB-FL/TrkB-T1 ratio (hereafter FL/T1 ratio) increased during follow-up in the nonaffective psychosis group only, suggesting different underlying pathophysiological mechanisms in subgroups of FEP patients. Further, the expression of the main NGF receptor, TrkA, generally increased in patients at follow-up. After adjusting for potential confounders, baseline levels of inducible isoforms of nitric oxide synthase, cyclooxygenase, and nuclear transcription factor were significantly associated with the FL/T1 ratio, suggesting that more inflammation is associated with higher values of this ratio. Interestingly, the FL/T1 ratio might have a role as a predictor of functioning, a regression model of functioning at 1 year suggesting that the effect of the FL/T1 ratio at baseline on functioning at 1 year depended on whether patients were treated with antipsychotics. These findings may have translational relevance; specifically, it might be useful to assess the expression of TrkB receptor isoforms before initiating antipsychotic treatment in FEP

Gender differences in adaptation to heat in Spain (1983-2018)

In Spain the average temperature has increased by 1.7 °C since pre-industrial times. There has been an increase in heat waves both in terms of frequency and intensity, with a clear impact in terms of population health. The effect of heat waves on daily mortality presents important territorial differences. Gender also affects these impacts, as a determinant that conditions social inequalities in health. There is evidence that women may be more susceptible to extreme heat than men, although there are relatively few studies that analyze differences in the vulnerability and adaptation to heat by sex. This could be related to physiological causes. On the other hand, one of the indicators used to measure vulnerability to heat in a population and its adaptation is the minimum mortality temperature (MMT) and its temporal evolution. The aim of this study was to analyze the values of MMT in men and women and its temporal evolution during the 1983-2018 period in Spain's provinces. An ecological, longitudinal retrospective study was carried out of time series data, based on maximum daily temperature and daily mortality data corresponding to the study period. Using cubic and quadratic fits between daily mortality rates and the temperature, the minimum values of these functions were determined, which allowed for determining MMT values. Furthermore, we used an improved methodology that provided for the estimation of missing MMT values when polynomial fits were inexistent. This analysis was carried out for each year. Later, based on the annual values of MMT, a linear fit was carried out to determine the rate of evolution of MMT for men and for women at the province level. Average MMT for all of Spain's provinces was 29.4 °C in the case of men and 28.7 °C in the case of women. The MMT for men was greater than that of women in 86 percent of the total provinces analyzed, which indicates greater vulnerability among women. In terms of the rate of variation in MMT during the period analyzed, that of men was 0.39 °C/decade, compared to 0.53 °C/decade for women, indicating greater adaptation to heat among women, compared to men. The differences found between men and women were statistically significant. At the province level, the results show great heterogeneity. Studies carried out at the local level are needed to provide knowledge about those factors that can explain these differences at the province level, and to allow for incorporating a gender perspective in the implementation of measures for adaptation to high temperatures.The authors wish to thank the funding provided by the ENPY 304/20, ENPY 376/18 and ENPY 107/18 projects of the Carlos III Health Institute III (ISCIII). They also wish to thank the UNED for funding this publication in open access.S

Characterization of Patients with Chronic Diseases and Complex Care Needs: A New High-Risk Emergent Population

Background: To analyze the prevalence and main epidemiological, clinical and outcome features of in-Patients with Complex Chronic conditions (PCC) in internal medicine areas, using a pragmatic working definition. Methods: Prospective study in 17 centers from Spain, with 97 in-hospital, monthly prevalence cuts. A PCC was considered when criteria of polypathological patient (two or more major chronic diseases) were met, or when a patient suffered one major chronic disease plus one or more of nine predefined complexity criteria like socio-familial risk, alcoholism or malnutrition among others (PCC without polypathology). A complete set of baseline features as well as 12-months survival were collected. Then, we compared clinical, outcome variables, and PROFUND index accuracy between polypathological patients and PCC without polypathology. Results: The global prevalence of PCC was 61% (40% of them were polypathological patients, and 21% PCC withouth polypathology) out of the 2178 evaluated patients. Their median age was 82 (59.5% men), suffered 2.3 ± 1.1 major diseases (heart diseases (70.5%), neurologic (41.5%), renal (36%), and lung diseases (26%)), 5.5 ± 2.5 other chronic conditions, met 2.5 ± 1.5 complexity criteria, and presented functional decline (Barthel index 55 (25-90)). Compared to polypathological patients, the subgroup of PCC without polypathology were younger, with a different pattern of major diseases and comorbidities, a better functional status, and lower 12-months mortality rates ((36.2% vs 46.8%; p = .003; OR 0.7(0.48-0.86). The PROFUND index obtained adequate calibration and discrimination power (AUC-ROC 0.67 (0.63-0.69)) in predicting 12-month mortality of PCC. Conclusion: Patients with complex chronic conditions are highly prevalent in internal medicine areas; their clinical pattern has changed in parallel to socio-epidemiological modifications, but their death-risk is still adequately predicted by PROFUND index