Effects and action mechanism of gonadotropins on ovarian follicular cells: A novel role of Sphingosine-1-Phosphate (S1P). A review.

Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) control antral follicular growth by regulating several processes, such as the synthesis of hormones and signaling molecules, proliferation, survival, apoptosis, luteinization, and ovulation. To exert these effects, gonadotropins bind to their respective Gs protein-coupled receptors, activating the protein kinase A (PKA) pathway or recruiting Gq proteins to activate protein kinase C (PKC) signaling. Although the action mechanism of FSH and LH is clear, recently, it has been shown that both gonadotropins promote the synthesis of sphingosine-1-phosphate (S1P) in granulosa and theca cells through the activation of sphingosine kinase 1. Moreover, the inhibition of SPHKs reduces S1P synthesis, cell viability, and the proliferation of follicular cells in response to gonadotropins, and the addition of S1P to the culture medium increases the proliferation of granulosa and theca cells without apparent effects on sexual steroid synthesis. Therefore, we consider that S1P is a crucial signaling molecule that complements the canonical gonadotropin pathway to promote the proliferation and viability of granulosa and theca cells.

Effect of polygenic risk score, family load of schizophrenia and exposome risk score, and their interactions, on the long-term outcome of first-episode psychosis.

BACKGROUND: Consistent evidence supports the involvement of genetic and environmental factors, and their interactions, in the etiology of psychosis. First-episode psychosis (FEP) comprises a group of disorders that show great clinical and long-term outcome heterogeneity, and the extent to which genetic, familial and environmental factors account for predicting the long-term outcome in FEP patients remains scarcely known. METHODS: The SEGPEPs is an inception cohort study of 243 first-admission patients with FEP who were followed-up for a mean of 20.9 years. FEP patients were thoroughly evaluated by standardized instruments, with 164 patients providing DNA. Aggregate scores estimated in large populations for polygenic risk score (PRS-Sz), exposome risk score (ERS-Sz) and familial load score for schizophrenia (FLS-Sz) were ascertained. Long-term functioning was assessed by means of the Social and Occupational Functioning Assessment Scale (SOFAS). The relative excess risk due to interaction (RERI) was used as a standard method to estimate the effect of interaction of risk factors. RESULTS: Our results showed that a high FLS-Sz gave greater explanatory capacity for long-term outcome, followed by the ERS-Sz and then the PRS-Sz. The PRS-Sz did not discriminate significantly between recovered and non-recovered FEP patients in the long term. No significant interaction between the PRS-Sz, ERS-Sz or FLS-Sz regarding the long-term functioning of FEP patients was found. CONCLUSIONS: Our results support an additive model of familial antecedents of schizophrenia, environmental risk factors and polygenic risk factors as contributors to a poor long-term functional outcome for FEP patients.

Influence of social cognition as a mediator between cognitive reserve and psychosocial functioning in patients with first episode psychosis.

BACKGROUND: Social cognition has been associated with functional outcome in patients with first episode psychosis (FEP). Social cognition has also been associated with neurocognition and cognitive reserve. Although cognitive reserve, neurocognitive functioning, social cognition, and functional outcome are related, the direction of their associations is not clear. Therefore, the main aim of this study was to analyze the influence of social cognition as a mediator between cognitive reserve and cognitive domains on functioning in FEP both at baseline and at 2 years. METHODS: The sample of the study was composed of 282 FEP patients followed up for 2 years. To analyze whether social cognition mediates the influence of cognitive reserve and cognitive domains on functioning, a path analysis was performed. The statistical significance of any mediation effects was evaluated by bootstrap analysis. RESULTS: At baseline, as neither cognitive reserve nor the cognitive domains studied were related to functioning, the conditions for mediation were not satisfied. Nevertheless, at 2 years of follow-up, social cognition acted as a mediator between cognitive reserve and functioning. Likewise, social cognition was a mediator between verbal memory and functional outcome. The results of the bootstrap analysis confirmed these significant mediations (95% bootstrapped CI (-10.215 to -0.337) and (-4.731 to -0.605) respectively). CONCLUSIONS: Cognitive reserve and neurocognition are related to functioning, and social cognition mediates in this relationship.

Evaluating the impact of the biocontrol agent Trichoderma harzianum ITEM 3636 on indigenous microbial communities from field soils.

AIM: To investigate the impact of inoculating peanut seeds with the biocontrol agent Trichoderma harzianum ITEM 3636 on the structure of bacterial and fungal communities from agricultural soils. METHODS AND RESULTS: Polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (PCR-DGGE) and next-generation sequencing (NGS) of amplicons (or marker gene amplification metagenomics) were performed to investigate potential changes in the structure of microbial communities from fields located in a peanut-producing area in the province of Córdoba, Argentina. Fields had history of peanut smut (caused by Thecaphora frezii) incidence. The Shannon indexes (H'), which estimate diversity, obtained from the PCR-DGGE assays did not show significant differences neither for bacterial nor for fungal communities between control and inoculation treatments. On the other hand, the number of operational taxonomic units obtained after NGS was similar between all the analysed samples. Moreover, results of alpha and beta diversity showed that there were no significant variations between the relative abundances of the most representative bacterial and fungal phyla and genera, in both fields. CONCLUSIONS: Trichoderma harzianum ITEM 3636 decreases the incidence and severity of agriculturally relevant diseases without causing significant changes in the microbial communities of agricultural soils. SIGNIFICANCE AND IMPACT OF THE STUDY: Our investigations provide information on the structure of bacterial and fungal communities in peanut-producing fields after inoculation of seeds with a biocontrol agent.

Elevation of isoprostanes in polycystic ovary syndrome and its relationship with cardiovascular risk factors.

PURPOSE: To evaluate the plasma level of 8-isoprostanes in women with polycystic ovary syndrome. To also investigate whether there is a relationship between 8-isoprostanes and several cardiovascular risk factors. METHODS: A total of 125 women with polycystic ovary syndrome and 169 healthy women were enrolled in this case-control study. 8-Isoprostanes and different parameters were measured in all subjects. Patients were evaluated for the presence of polycystic ovary syndrome according to the Rotterdam Consensus Conference criteria. RESULTS: 8-Isoprostanes levels were significantly higher in patients with polycystic ovary syndrome (138.4 ± 104.1 pg/mL) compared with control group (68.6 ± 34.3 pg/mL) (p < 0.001). The mean of triglycerides, lipid accumulation product, C-reactive protein, homocysteine, insulin, and homeostatic model assessment for insulin resistance were significantly higher in polycystic ovary syndrome patients with high 8-isoprostanes than those with normal 8-isoprostanes (p < 0.05). The Pearson correlation analyses showed that 8-isoprostanes levels in polycystic ovary syndrome group had a positive correlation with waist circumference, triglycerides, low-density lipoprotein cholesterol, apolipoprotein B, homocysteine, insulin, homeostatic model assessment for insulin resistance. CONCLUSIONS: Patients with polycystic ovary syndrome have higher 8-isoprostanes levels and it is associated with several cardiovascular risk factors.

Cognitive reserve as an outcome predictor: first-episode affective versus non-affective psychosis.

OBJECTIVE: Cognitive reserve (CR) refers to the brain's capacity to cope with pathology in order to minimize the symptoms. CR is associated with different outcomes in severe mental illness. This study aimed to analyze the impact of CR according to the diagnosis of first-episode affective or non-affective psychosis (FEP). METHOD: A total of 247 FEP patients (211 non-affective and 36 affective) and 205 healthy controls were enrolled. To assess CR, common proxies have been integrated (premorbid IQ; education-occupation; leisure activities). The groups were divided into high and low CR. RESULTS: In non-affective patients, those with high CR were older, had higher socioeconomic status (SES), shorter duration of untreated psychosis, and a later age of onset. They also showed greater performance in most cognitive domains. In affective patients, those with a greater CR showed a higher SES, better functioning, and greater verbal memory performance. CONCLUSION: CR plays a differential role in the outcome of psychoses according to the diagnosis. Specifically, in order to address the needs of non-affective patients with low CR, cognitive rehabilitation treatments will need to be 'enriched' by adding pro-cognitive pharmacological agents or using more sophisticated approaches. However, a functional remediation therapy may be of choice for those with an affective psychosis and low CR.

Individual trajectories of cognitive performance in first episode psychosis: a 2-year follow-up study.

Individual changes over time in cognition in patients with psychotic disorders have been studied very little, especially in the case of first episode psychosis (FEP). We aimed to establish whether change in individual trajectories in cognition over 2 years of a sample of 159 FEP patients was reliable and clinically significant, using the reliable change index (RCI) and clinically significant change (CSC) methods. We also studied a sample of 151 matched healthy controls. Patients and controls were assessed with a set of neuropsychological tests, as well as premorbid, clinical and functionality measures. We analysed the course of cognitive measures over time, using analysis of variance, and the individual trajectories in the cognitive measures with the regression-based RCI (RCISRB) and the CSC. The RCISRB showed that between 5.4 and 31.2% of the patients showed deterioration patterns, and between 0.6 and 8.8% showed improvement patterns in these tests over time. Patients showing better cognitive profiles according to RCISRB (worsening in zero to two cognitive measures) showed better premorbid, clinical and functional profiles than patients showing deterioration patterns in more than three tests. When combining RCISRB and CSC values, we found that less than 10% of patients showed improvement or deterioration patterns in executive function and attention measures. These results support the view that cognitive impairments are stable over the first 2 years of illness, but also that the analysis of individual trajectories could help to identify a subgroup of patients with particular phenotypes, who may require specific interventions.

Tolerance of triazole-based fungicides by biocontrol agents used to control Fusarium head blight in wheat in Argentina.

Fusarium head blight (FHB) caused by Fusarium graminearum species complex is a devastating disease that causes extensive yield and quality losses to wheat around the world. Fungicide application and breeding for resistance are among the most important tools to counteract FHB. Biological control is an additional tool that can be used as part of an integrated management of FHB. Bacillus velezensisRC 218, Brevibacillus sp. RC 263 and Streptomyces sp. RC 87B were selected by their potential to control FHB and deoxynivalenol production. The aim of this work was to test the tolerance of these biocontrol agents to triazole-based fungicides such as prothioconazole, tebuconazole and metconazole. Bacterial growth was evaluated in Petri dishes using the spread plating technique containing the different fungicides. Bacillus velezensisRC 218 and Streptomyces sp. RC 87B showed better tolerance to fungicides than Brevibacillus sp. RC 263. Complete growth inhibition was observed at concentrations of 20 µg ml-1 for metconazole, 40 µg ml-1 for tebuconazole and 80 µg ml-1 for prothioconazole. The results obtained indicate the possibility of using these biocontrol agents in combination with fungicides as part of an integrated management to control FHB of wheat. SIGNIFICANCE AND IMPACT OF THE STUDY: This study evaluates the possibility to use biocontrol agents (Bacillus velezensisRC 218, Brevibacillus sp. RC 263 and Streptomyces sp. RC 87B) in combination with triazole-based fungicides to control Fusarium head blight in wheat. The evaluation of biocontrol agents' growth under in vitro conditions was carried out in Petri dishes containing either prothioconazole, tebuconazole or metconazole. Viability studies demonstrated that B. velezensisRC 218 and Streptomyces sp. RC 87B were more tolerant to the fungicides evaluated. Results obtained reflect the possibility to use fungicides at low doses combined with biocontrol agents.

Saturation mapping of regions determining resistance to Ascochyta blight and broomrape in faba bean using transcriptome-based SNP genotyping.

KEY MESSAGE: Transcriptome-based SNP markers were genotyped in a faba bean map to saturate regions bearing QTL for Ascochyta fabae and broomrape and distinguish positional and functional candidates underlying both resistances. Faba bean is an important food crop worldwide. Marker-assisted selection for disease resistance is a top priority in current faba bean research programs, with pathogens such as Ascochyta fabae and broomrape (Orobanche crenata) being among the major constraints in global faba bean production. However, progress in genetics and genomics in this species has lagged behind that of other grain legumes. Although genetic maps are available, most markers are not in or are too distant from target genes to enable an accurate prediction of the desired phenotypes. In this study, a set of SNP markers located in gene coding regions was selected using transcriptomic data. Ninety-two new SNP markers were genotyped to obtain the most complete map reported so far in the 29H × Vf136 faba bean population. Most of the QTL regions previously described in this cross were enriched with SNP markers. Two QTLs for O. crenata resistance (Oc7 and Oc8) were confirmed. Oc7 and Oc10 located nearby a QTL for A. fabae resistance suggested that these genomic regions might encode common resistance mechanisms and could be targets for selection strategies against both pathogens. We also confirmed three regions in chromosomes II (Af2), III (Af3) and VI associated with Ascochyta blight resistance. The QTLs ratified in the present study are now flanked by or include reliable SNP markers in their intervals. This new information provides a valuable starting point in the search for relevant positional and functional candidates underlying both types of resistance.

Short-term methionine supplementation during the early post-partum period in primiparous rabbits improves prolificacy associated with an increase in serum concentrations of IGF-I.

The aim of this study was to evaluate the effects of methionine supplementation on energy metabolism and reproductive performance during the early post-partum period in primiparous does. Forty nulliparous New Zealand White does were used. Females were randomized in two groups at calving: the control group (n = 20) was fed with the basal diet, and the methionine group (n = 20) was fed the basal diet plus 1 g/animal/day of methionine from the day of calving to 4 days post-partum. Results showed that methionine supplementation increased (p = 0.032) the concentration of insulin-like growth factor-1 with respect to control group 4 days post-partum. It similarly increased the prolificacy (p = 0.03), the number of kits born alive per litter (p = 0.06) and the body gain weight of the litter during supplementation (p = 0.035). These results were observed despite the does in the methionine group having a deeper negative energy balance than the does in the control group. Finally, methionine supplementation did not affect receptivity (p = 0.23), fertility (p = 0.49), the number of kits born dead per litter (p = 0.86) insulin and metabolites as glucose, non-esterified fatty acids and triglycerides. In conclusion, our results show that methionine supplementation during the first 4 days of the post-partum period in rabbits increases total litter size and the corporal weight of kits and is associated with an increase in blood concentration of IGF-1.

Short-term dietary concentrate supplementation during estrus synchronization treatment in beef cows increased IGF-I serum concentration but did not affect the reproductive response.

The objective of this study was to evaluate if short-term dietary concentrate supplementation increased IGF-I serum concentration and resulted in a reproductive response during estrus synchronization treatment in non-lactating beef cows. Thirty non-lactating beef cows (Bos indicus × Bos taurus) were allocated to the same pastureland and fed native tropical grasses as a basal diet. Cows were synchronized using a 7-day CO-Synch plus controlled internal drug release (CIDR) protocol and received fixed time artificial insemination (FTAI). Cows were divided into two groups; the control group (n = 16) received 0.5 kg of concentrate/cow/day, whereas the supplemented group (n = 14) received 4.0 kg of concentrate/cow/day. The period of supplementation was 10 days from the day of CIDR insert to FTAI. The concentration of IGF-I increased (P < 0.05) in the supplemented group, while no significant changes were observed in the control group. Moreover, at the time of insemination, IGF-I serum concentrations were higher in supplemented cows compared with control cows (P < 0.05). Notably, metabolite and insulin concentrations did not differ (P > 0.05) between treatment groups or sampling day. The response to estrus induction, measured as estrus presentation, ovulation rate, and pregnancy rate, was similar between experimental groups (P > 0.05). In conclusion, our results indicated that supplementation with dietary concentrate for 10 days in non-lactating beef cows changed the endocrine milieu, specifically increasing IGF-I serum concentration. However, these endocrine changes did not affect response to estrous induction treatment.

Sphingosine-1-phosphate, regulated by FSH and VEGF, stimulates granulosa cell proliferation.

Sphingosine-1-phosphate (S1P) is a bioactive polar sphingolipid which stimulates proliferation, growth and survival in various cell types. In the ovary S1P has been shown protect the granulosa cells and oocytes from insults such as oxidative stress and radiotherapy, and S1P concentrations are greater in healthy than atretic large follicles. Hence, we postulate that S1P is fundamental in follicle development and that it is activated in ovarian granulosa cells in response to FSH and VEGF. To test this hypothesis we set out: i) to evaluate the effect of FSH and VEGF on S1P synthesis in cultured bovine granulosa cells and ii) to analyse the effect of S1P on proliferation and survival of bovine granulosa cells in vitro. Seventy five thousand bovine granulosa cells from healthy medium-sized (4-7mm) follicles were cultured in 96-well plates in McCoy's 5a medium containing 10ng/mL of insulin and 1ng/mL of LR-IGF-I at 37°C in a 5% CO2/air atmosphere at 37°C. Granulosa cell production of S1P was tested in response to treatment with FSH (0, 0.1, 1 and 10ng/mL) and VEGF (0, 0.01, 0.1, 1, 10 and 100ng/mL) and measured by HPLC. Granulosa cells produced S1P at 48 and 96h, with the maximum production observed with 1ng/mL of FSH. Likewise, 0.01ng/mL of VEGF stimulated S1P production at 48, but not 96h of culture. Further, the granulosa cell expression of sphingosine kinase-1 (SK1), responsible for S1P synthesis, was demonstrated by Western blot after 48h of culture. FSH increased the expression of phosphorylated SK1 (P<0.05) and the addition of a SK1 inhibitor reduced the constitutive and FSH-stimulated S1P synthesis (P<0.05). Sphingosine-1-phosphate had a biphasic effect on granulosa cell number after culture. At low concentration S1P (0.1µM) increased granulosa cell number after 48h of culture (P<0.05) and the proportion of cells in the G2 and M phase of the cell cycle (P<0.05), whereas higher concentrations decreased cell number (10µM; P<0.05) by an increase (P<0.05) in the proportion of cells in apoptosis (hypodiploid cells). In addition, treatment with SK-178 suppressed the FSH- and VEGF-stimulated rise of the granulosa cells number (P<0.05). Interestingly, the effect of 0.1µM S1P on granulosa cell number and their proportion in G2/M phases is similar to that observed with 1ng/mL FSH. The results of this study are the first to demonstrate sphingosine-1-phosphate (S1P) synthesis in granulosa cells under the control of FSH and VEGF. The later achieved through the regulation of sphingosine kinase 1 expression. This S1P augments the proportion of cells in the G2/M phase of the cell cycle that translates in increased granulosa cell proliferation.

Reduction in the mRNA expression of sVEGFR1 and sVEGFR2 is associated with the selection of dominant follicle in cows.

The vascular endothelial growth factor (VEGF) is essential for follicular development by promoting follicular angiogenesis, as well as for the proliferation and survival of granulosa cells. The biological effects of VEGF are regulated by two membrane receptors, VEGFR1 and VEGFR2, and two soluble receptors, sVEGFR1 and sVEGFR2, which play an antagonistic role. Thus, the objective of this study was to identify the mRNA expression pattern of total VEGF, VEGFR1, VEGFR2, sVEGFR1 and sVEGFR2 in bovine preselected follicles (PRF) and post-selected follicles (POF). The mRNA expression of these five genes in both granulosa cells (GC) and theca cells (TC) was compared between follicles classified as PRF and POF based on their diameter and on their ratio of estradiol/progesterone (E2/P4). Results showed a lower expression of mRNA of sVEGFR1 and sVEGFR2 in POF than in PRF (p < .05). Regarding the mRNA expression of total VEGF, VEGFR1 and VEGFR2, there was no difference between POF and PRF follicles (p > .05). Our results showed that the mRNA expression of VEGFR2 and sVEGFR1 was more abundant than the expression of VEGFR1 and sVEGFR2, while GC was the main source of mRNA for total VEGF. On the other hand, TC was the follicular compartment where the receptors were most expressed. Our results suggest that non-dominant follicles maintain a greater concentration of the mRNA expression of both membrane and soluble VEGF receptors. On the other hand, follicular dominance is related to a reduction in the mRNA expression of sVEGFR1 and sVEGFR2, which may favour VEGF binding with VEGFR2 and, hence, improve the follicular health and development.

Percentage of ubiquitinated spermatozoa does not correlate with fertilizing capacity of thawed bovine semen.

In the spermatozoa of some species, the ubiquitin-proteasome system detects altered proteins and tags them for elimination by the proteasome. In some species' ejaculates, a high proportion of ubiquitinated spermatozoa (i.e. those having ubiquitin bound to the altered or damaged membrane proteins) has been related to infertility. The aim of this study was to assess whether the percentage of ubiquitinated spermatozoa relates to fertility of dairy bulls and whether ubiquitination increases during protein remodelling that occurs during in vitro spermatic capacitation. Thirty-two frozen semen straws from four high-fertility (ReproMax(®) ) and four normal-fertility (Normal) Holstein-Friesian sires were evaluated. Ubiquitinated and capacitated spermatozoa were quantified by sperm ubiquitin tag immunoassay and chlortetracycline stain, respectively. Fertilizing capacity of sires was assessed by in vitro fertilization. No differences were found between Normal and ReproMax(®) sires with regard to the observed percentage of ubiquitinated spermatozoa (42.97 ± 3.69% and 49.68 ± 9.27%, respectively; p > 0.05). Additionally, no differences were found in the percentage of ubiquitinated spermatozoa as a consequence of spermatic capacitation in either Normal (42.97 ± 3.69% before capacitation vs 44.67 ± 7.5% after; p > 0.05) or ReproMax(®) sires (49.68 ± 9.27% before vs 45.05 ± 7.51% after; p > 0.05). The percentage of ubiquitinated spermatozoa in a thawed sperm samples did not correlate with its in vitro fertilizing capacity; thus, this assay does not prove useful to detect in vivo fertility differences between sires. Additionally, protein degradation occurring during remodelling of the spermatozoon plasma membrane during the capacitation process does not seem to involve the ubiquitin-proteasome system.

Characterization and seminal cryopreservation of three species of birds of prey.

Background: Assisted reproduction techniques in birds have contributed to many species' conservation and sustainable use. One of these techniques is semen cryopreservation, which is possible following the discovery of suitable cryoprotectants. Aims: This study aimed to characterize the fresh and post-thaw ejaculates of different species of birds of prey. Methods: The following species were included in the study: red-tailed hawk (Buteo jamaicensis) n=3, golden eagle (Aquila chrysaetos) n=3, and Harris's hawk (Parabuteo unicinctus) n=3. Twenty-five ejaculates were obtained for each species. The percentage of spermatozoa motility, viability, and morphology were evaluated. Results: Evident differences were observed among the ejaculates of the three species, particularly in sperm length and between the fresh and post-thaw parameters of the same species in which the motility reduced to approximately 40% after thawing. It was demonstrated that sperm cryopreservation of the studied species was possible using the same freezing protocol. Conclusion: This study showed that sperm characteristics could influence the parameters obtained during their in vitro conservation, both in the fresh and post-thaw states.

Empirical validity of Leonhard's psychoses: A long-term follow-up study of first-episode psychosis patients.

The validation of nosological diagnoses in psychiatry remains a conundrum. Leonhard's (1979) nosology seems to be one of the few acceptable alternative categorical models to current DSM/ICD systems. We aimed to empirically validate Leonhard's four classes of psychoses: systematic schizophrenia (SSch), unsystematic (USch), cycloid psychosis (Cyclo), and manic-depressive illness (MDI) using a comprehensive set of explanatory validators. 243 patients with first-episode psychosis were followed between 10 and 31 years. A wide-ranging assessment was carried out by collecting data on antecedent, illness-related, concurrent, response to treatment, neuromotor abnormalities, and cognitive impairment variables. Compared with USch, Cyclo, and MDI, SSch displayed a pattern of impairments significantly larger across the seven blocks of explanatory variables. There were no significant differences between Cyclo and MDI in explanatory variables. Except for the majority of illness-onset features, USch displayed more substantial abnormalities in the explanatory variables than Cyclo and MDI. SSch and MDI showed higher percentages of correctly classified patients than USch and Cyclo in linear discriminant analyses. Partial validation of Leonhard's classification was found. SSch showed differences in explanatory variables with respect to Cyclo and MDI. USch showed also significant differences in explanatory variables regarding Cyclo and MDI, although with a lower strength than SSch. There was strong empirical evidence of the separation between both Leonhard's schizophrenia subtypes; however, the distinction between the Cyclo and MDI groups was not empirically supported. A mild to moderate discriminative ability between Leonhard's subtypes on the basis of explanatory blocks of variables was observed.

Consensus statement of the Spanish Society of Neurology on the treatment of multiple sclerosis and holistic patient management in 2023.

The last consensus statement of the Spanish Society of Neurology's Demyelinating Diseases Study Group on the treatment of multiple sclerosis (MS) was issued in 2016. Although many of the positions taken remain valid, there have been significant changes in the management and treatment of MS, both due to the approval of new drugs with different action mechanisms and due to the evolution of previously fixed concepts. This has enabled new approaches to specific situations such as pregnancy and vaccination, and the inclusion of new variables in clinical decision-making, such as the early use of high-efficacy disease-modifying therapies (DMT), consideration of the patient's perspective, and the use of such novel technologies as remote monitoring. In the light of these changes, this updated consensus statement, developed according to the Delphi method, seeks to reflect the new paradigm in the management of patients with MS, based on the available scientific evidence and the clinical expertise of the participants. The most significant recommendations are that immunomodulatory DMT be started in patients with radiologically isolated syndrome with persistent radiological activity, that patient perspectives be considered, and that the term "lines of therapy" no longer be used in the classification of DMTs (> 90% consensus). Following diagnosis of MS, the first DMT should be selected according to the presence/absence of factors of poor prognosis (whether epidemiological, clinical, radiological, or biomarkers) for the occurrence of new relapses or progression of disability; high-efficacy DMTs may be considered from disease onset.

Development of amplified fragment length polymorphism (AFLP)-derived specific primer for the detection of Fusarium solani aetiological agent of peanut brown root rot.

AIMS: The objective of this work was to design an amplified fragment length polymorphism (AFLP)-derived specific primer for the detection of Fusarium solani aetiological agent of peanut brown root rot (PBRR) in plant material and soil. METHODS AND RESULTS: Specific primers for the detection of the pathogen were designed based on an amplified region using AFLPs. The banding patterns by AFLPs showed that isolates from diseased roots were clearly distinguishable from others members of the F. solani species complex. Many bands were specific to F. solani PBRR, one of these fragments was selected and sequenced. Sequence obtained was used to develop specific PCR primers for the identification of pathogen in pure culture and in plant material and soil. Primer pair FS1/FS2 amplified a single DNA product of 175 bp. Other fungal isolates occurring in soil, included F. solani non-PBRR, were not detected by these specific primers. The assay was effective for the detection of pathogen from diseased root and infected soils. CONCLUSIONS: The designed primers for F. solani causing PBRR can be used in a PCR diagnostic protocol to rapidly and reliably detect and identify this pathogen. SIGNIFICANCE AND IMPACT OF THE STUDY: These diagnostic PCR primers will aid the detection of F. solani causing PBRR in diseased root and natural infected soils. The method developed could be a helpful tool for epidemiological studies and to avoid the spread of this serious disease in new areas.

Chytridiomycosis: a global threat to amphibians.

Chytridiomycosis, which is caused by Batrachochytrium dendrobatidis, is an emerging infectious disease of amphibians. The disease is one of the main causes of the global decline in amphibians. The aetiological agent is ubiquitous, with worldwide distribution, and affects a large number of amphibian species in several biomes. In the last decade, scientific research has substantially increased knowledge of the aetiological agent and the associated infection. However, important epidemiological aspects of the environment-mediated interactions between the aetiological agent and the host are not yet clear. The objective of the present review is to describe chytridiomycosis with regard to the major features of the aetiological agent, the host and the environment.

Prediction of patients with idiopathic generalized epilepsy from healthy controls using machine learning from scalp EEG recordings.

Epilepsy detection is essential for patients with epilepsy and their families, as well as for researchers and medical staff. The use of electroencephalogram (EEG) as a tool to support the diagnosis of patients with epilepsy is fundamental. Today, machine learning (ML) techniques are widely applied in neuroscience. The main objective of our study is to differentiate patients with idiopathic generalized epilepsy from healthy controls by applying machine learning techniques on interictal electroencephalographic recordings. Our research predicts which patients have idiopathic generalized epilepsy from a scalp EEG study. In addition, this study focuses on using the extreme gradient boosting (XGB) method applied to scalp EEG. XGB is one of the variants of gradient boosting and is a supervised learning algorithm. This type of system is developed to increase performance and processing speed. Through this proposed method, an attempt is made to recognize patterns from scalp EEG recordings that would allow the detection of IGE with high accuracy and differentiate IGE patients from healthy controls, creating an additional tool to support clinicians in their decision-making. Among the ML methods applied, the proposed XGB method achieves a better prediction of the distinct features in EEG signals from patients with IGE. XGB was 6.26% more accurate than the k-Nearest Neighbours method and was more accurate than the support vector machine (10.61%), decision tree (9.71%) and Gaussian Naïve Bayes (11.83%). Besides, the proposed XGB method showed the highest area under the curve (AUC 98%) and balanced accuracy (98.13%) of all methods tested. Application of ML technique in EEG of patients with epilepsy is very recent and is emerging with promising results. In this research work, we showed the usefulness of ML techniques to identify and predict generalized epilepsy from healthy controls in scalp EEG studies. These findings could help develop automated tools that integrate these ML techniques to assist clinicians in differentiating between patients with IGE from healthy controls in daily practice.