Quantification of hCG Hormone Using Tapered Optical Fiber Decorated with Gold Nanoparticles.

In this study, a novel technique for the quantification of the human chorionic gonadotropin (hCG) hormone using localized surface plasmons and a tapered optical fiber decorated with gold nanoparticles (Au-NPs) is reported. The tapered optical fiber fabrication process involves stretching a single-mode optical fiber using the flame-brushing system. The waist of the tapered optical fiber reaches a diameter of 3 µm. Decoration of the taper is achieved through the photodeposition of 100 nm Au-NPs using the drop-casting technique and a radiation source emitting at 1550 nm. The presence of the hCG hormone in the sample solutions is verified by Fourier-transform infrared spectroscopy (FTIR), revealing the presence of bands related to functional groups, such as C=O (1630 cm-1), which are associated with proteins and lipids, components of the hCG hormone. Quantification tests for hormone concentrations were carried out by measuring the optical power response of the tapered optical fiber with Au-NPs under the influence of hCG hormone concentrations, ranging from 1 mIU/mL to 100,000 mIU/mL. In the waist of the tapered optical fiber, the evanescent field is amplified because of localized surface plasmons generated by the nanoparticles and the laser radiation through the optical fiber. Experimental results demonstrated a proportional relationship between measured radiation power and hCG concentration, with the optical power response decreasing from 4.45 mW down to 2.5 mW, as the hCG hormone concentration increased from 1 mIU/mL up to 100,000 mIU/mL. Furthermore, the spectral analysis demonstrated a spectral shift of 14.2 nm with the increment of the hCG hormone concentration. The measurement system exhibits promising potential as a sensor for applications in the biomedical and industrial fields.

Engineering the enzyme toolbox to tailor glycosylation in small molecule natural products and protein biologics.

Many glycosylated small molecule natural products and glycoprotein biologics are important in a broad range of therapeutic and industrial applications. The sugar moieties that decorate these compounds often show a profound impact on their biological functions, thus biocatalytic methods for controlling their glycosylation are valuable. Enzymes from nature are useful tools to tailor bioproduct glycosylation but these sometimes have limitations in their catalytic efficiency, substrate specificity, regiospecificity, stereospecificity, or stability. Enzyme engineering strategies such as directed evolution or semi-rational and rational design have addressed some of the challenges presented by these limitations. In this review, we highlight some of the recent research on engineering enzymes to tailor the glycosylation of small molecule natural products (including alkaloids, terpenoids, polyketides, and peptides), as well as the glycosylation of protein biologics (including hormones, enzyme-replacement therapies, enzyme inhibitors, vaccines, and antibodies).

A pilot randomized controlled clinical trial of Transcranial Alternating Current Stimulation in patients with multifocal pharmaco-resistant epilepsy.

Transcranial Alternating Current Stimulation (tACS) is a promising noninvasive electrical stimulation therapy for neuropsychiatric diseases. Invasive neuromodulation using alternating current has been efficacious for drug-resistant epilepsy, but it is associated with surgical and medical complications. We aimed to explore the safeness and effectivity on seizure frequency reduction of two tACS protocols against placebo in patients with multifocal refractory epilepsy. This was a randomized, double-blinded, placebo-controlled clinical trial with 3-arm parallel-group (placebo, 30 min/2 mA daily sessions for 3 days [tACS-30], and 60 min/2 mA weekday sessions [tACS-60]). The main outcome was considered a change in reducing seizure frequency at 2 months after the intervention. Secondary outcomes were the apparition of any adverse effects during follow-up. At the second month, we observed a nonsignificant reduction in the seizure frequency in the placebo (7.3 ±â€¯40.4%, p > 0.05) and the tACS-60 (26 ±â€¯37.7%, p > 0.05). While the tACS-30 group showed a nonsignificant increase in seizure frequency (63.6 ±â€¯155.3%, p > 0.05). No changes were statistically different from the placebo group. Otherwise, participants experienced only minor adverse events - the most common being an initial local transient tingling sensation (21%). This pilot study of tACS raises no severe safety issues, but provides negligible evidence for efficacy using this brief treatment protocol. Therefore, more studies are warranted testing different parameters to further verify the safety and effectivity of tACS in multifocal epilepsy.

Genome-Wide Analysis of the LRR-RLP Gene Family in a Wild Banana (Musa acuminata ssp. malaccensis) Uncovers Multiple Fusarium Wilt Resistance Gene Candidates.

Banana is the most popular fruit in the world, with a relevant role in food security for more than 400 million people. However, fungal diseases cause substantial losses every year. A better understanding of the banana immune system should facilitate the development of new disease-resistant cultivars. In this study, we performed a genome-wide analysis of the leucine-rich repeat receptor-like protein (LRR-RLP) disease resistance gene family in a wild banana. We identified 78 LRR-RLP genes in the banana genome. Remarkably, seven MaLRR-RLPs formed a gene cluster in the distal part of chromosome 10, where resistance to Fusarium wilt caused by Foc race 1 has been previously mapped. Hence, we proposed these seven MaLRR-RLPs as resistance gene candidates (RGCs) for Fusarium wilt. We also identified seven other banana RGCs based on their close phylogenetic relationships with known LRR-RLP proteins. Moreover, phylogenetic analysis of the banana, rice, and Arabidopsis LRR-RLP families revealed five major phylogenetic clades shared by these plant species. Finally, transcriptomic analysis of the MaLRR-RLP gene family in plants treated with Foc race 1 or Foc TR4 showed the expression of several members of this family, and some of them were upregulated in response to these Foc races. Our study provides novel insights into the structure, distribution, evolution, and expression of the LRR-RLP gene family in bananas as well as valuable RGCs that will facilitate the identification of disease resistance genes for the genetic improvement of this crop.

GSU1771 regulates extracellular electron transfer and electroactive biofilm formation in Geobacter sulfurreducens: Genetic and electrochemical characterization.

Type IV pili and the >100c-type cytochromes in Geobacter sulfurreducens are essential for extracellular electron transfer (EET) towards metal oxides and electrodes. A previous report about a mutation in the gsu1771 gene indicated an enhanced reduction of insoluble Fe(III) oxides coupled with increased pilA expression. Herein, a marker-free gsu1771-deficient mutant was constructed and characterized to assess the role of this regulator in EET and the formation of electroactive biofilms. Deleting this gene delayed microbial growth in the acetate/fumarate media (electron donor and acceptor, respectively). However, this mutant reduced soluble and insoluble Fe(III) oxides more efficiently. Heme staining, western blot, and RT-qPCR analyses demonstrated that GSU1771 regulates the transcription of several genes (including pilA) and many c-type cytochromes involved in EET, suggesting the broad regulatory role of this protein. DNA-protein binding assays indicated that GSU1771 directly regulates the transcription of pilA, omcE, omcS, and omcZ. Additionally, gsu1771-deficient mutant biofilms are thicker than wild-type strains. Electrochemical studies revealed that the current produced by this biofilm was markedly higher than the wild-type strains (approximately 100-fold). Thus, demonstrating the role of GSU1771 in the EET pathway and establishing a methodology to develop highly electroactive G. sulfurreducens mutants.

Increment Antimicrobial Resistance During the COVID-19 Pandemic: Results from the Invifar Network.

Aim: This study aims to assess the changes in antimicrobial resistance among some critical and high-priority microorganisms collected previously and during the coronavirus disease 2019 (COVID-19) pandemic in Mexico. Methods: We collected antimicrobial susceptibility data for critical and high-priority microorganisms from blood, urine, respiratory samples, and from all specimens, in which the pathogen may be considered a causative agent. Data were stratified and compared for two periods: 2019 versus 2020 and second semester 2019 (prepandemic) versus the second semester 2020 (pandemic). Results: In the analysis of second semester 2019 versus the second semester 2020, in blood samples, increased resistance to oxacillin (15.2% vs. 36.9%), erythromycin (25.7% vs. 42.8%), and clindamycin (24.8% vs. 43.3%) (p ≤ 0.01) was detected for Staphylococcus aureus, to imipenem (13% vs. 23.4%) and meropenem (11.2% vs. 21.4) (p ≤ 0.01), for Klebsiella pneumoniae. In all specimens, increased ampicillin and tetracycline resistance was detected for Enterococcus faecium (p ≤ 0.01). In cefepime, meropenem, levofloxacin, and gentamicin (p ≤ 0.01), resistance was detected for Escherichia coli; and in piperacillin-tazobactam, cefepime, imipenem, meropenem, ciprofloxacin, levofloxacin, and gentamicin (p ≤ 0.01), resistance was detected for Pseudomonas aeruginosa. Conclusion: Antimicrobial resistance increased in Mexico during the COVID-19 pandemic. The increase in oxacillin resistance for S. aureus and carbapenem resistance for K. pneumoniae recovered from blood specimens deserves special attention. In addition, an increase in erythromycin resistance in S. aureus was detected, which may be associated with high azithromycin use. In general, for Acinetobacter baumannii and P. aeruginosa, increasing resistance rates were detected.

Food Addiction, Saturated Fat Intake, and Body Mass Index in Peruvian Adults: A Cross-Sectional Survey.

BACKGROUND: Cardiovascular diseases (CVDs) constitute one of the main public health problems and represent a greater risk of mortality and morbidity for the world population. The objective of the study was to determine food addiction, saturated fat intake, and body mass index (BMI) in Peruvian adults. MATERIALS AND METHODS: A cross-sectional online survey was applied to 394 Peruvian adults over 18 years old residing in the three regions of the country. Participant data was collected through a prestructured online electronic survey. Food addiction was assessed using the Yale Food Addiction Scale self-administered questionnaire. A validated food frequency questionnaire was used to measure saturated fat intake. Finally, the sociodemographic and anthropometric variables were collected through a registration form. RESULTS: There were no significant differences in food addiction between men and women (p < 0.05). More than half of the participants who presented food addiction are overweight (54.1%, p < 0.001). The highest proportion of those who had a high intake of saturated fat had a food addiction (62.6%, p < 0.001). The highest percentage of men who were overweight was higher compared to women (49.7% vs. 38.4%, p < 0.05). CONCLUSION: The findings of this study suggest that addictive eating behaviors and high saturated fat intake should be considered as part of efforts to prevent problems related to eating, obesity, and CVD.

A Clinical Prognostic Scoring System for Neurocysticercosis.

Objectives In patients with neurocysticercosis (NCC), an accurate risk prediction would allow a better therapeutic approach; however, there are currently no tools that can enhance the accuracy of risk prediction. We designed a prognostic scoring system to be used by neurologists and other physicians managing patients with NCC. Materials and Methods Using data from clinical records of patients from a third-level national reference center for neurological diseases, we assessed demographic, clinical, and tomographic variables among 293 patients diagnosed with NCC. Multivariable logistic regression analyses were used to develop a clinical prognostic scoring instrument. Patients with NCC were assessed for neurological impairment at 3 months after diagnosis. Statistical Analysis Score accuracy was assessed by receiver operating characteristic (ROC) curve analysis. The primary outcome was the presence of neurological impairment, resulting in disability according to self-report or caregiver reports; this outcome was assessed during follow-up visits at 3 ± 1 months after discharge. Results The most common symptoms at presentation were headache (67%) and seizure (63%). A six-item (total score from -4 to + 2) prognostic instrument was constructed on the basis of the presence of seizures/headache at presentation, a leukocyte count above 12x 109/dL, the presence of six to ten parasites, subarachnoid localization, and the use of anthelmintic drugs. Among 113 patients with negative scores, 79.6% developed neurological deficits. Among patients with scores of 1 to 2, 64.6% recovered completely, with an overall accuracy of prediction of 74.7% and area under the ROC curve = 0.722 (95% CI, 0.664-0.780, p < 0.0001). Conclusions The clinical prognostic scoring system for NCC described in this study is a new instrument for use in daily clinical practice. It is simple to administer, and it has a prognostic accuracy of 75%. Its use has the potential to improve the quality of care by guiding appropriate decision-making and early management of patients with NCC.

Endogenous auxin accumulation/localization during zygotic and somatic embryogenesis of Capsicum chinense Jacq.

Zygotic and somatic embryogenesis in plants is a fascinating event that is finely regulated through the expression of a specific group of genes and dynamic levels of plant hormones whose concerted action determines the fate that specific cells follow towards zygotic or somatic embryo development. This work studied different stages of Capsicum chinense Jacq. zygotic and somatic embryogenesis. HPLC quantification determined that the levels of indole-3-acetic acid (IAA) increase as the zygotic or somatic embryogenesis progresses, being higher at maturity, thus supporting a positive correlation between embryo cell differentiation and IAA increase. A monoclonal anti-IAA-antibody was used to detect IAA levels. Findings revealed a dynamic pattern of auxin distribution along the different embryogenic embryonic stages. In the early stages of zygotic embryos, the IAA gradient was observed in the basal cells of the suspensor and the hypostases, suggesting that they are the initial source of the IAA hormone. As embryogenesis proceeds, the dynamic of the IAA gradient is displaced to the embryo and endosperm cells. In the case of induced somatic embryogenesis, the IAA gradient was detected in the dividing cells of the endodermis, from where pre-embryogenic cells emerge. However, the analysis of somatic embryos revealed that IAA was homogeneously distributed. This study shows evidence supporting a correlation between IAA levels during zygotic or somatic embryogenesis in Capsicum chinense species.

Development of the ovule and seed of Habanero chili pepper (Capsicum chinense Jacq.): Anatomical characterization and immunocytochemical patterns of pectin methyl-esterification.

Ovule and seed development in plants has long fascinated the scientific community given the complex cell coordination implicated in these processes. These cell events are highly conserved but are not necessarily representative of all plants. In this study, with the aim of obtaining information regarding the cellular patterns that follow the usual development of the ovule and the zygotic embryo, we carried out an integral anatomical study of the Capsicum chinense Jacq., floral buds and seeds at various days during maturation. This study allowed us to identify the main histo-morphological stages accompanying the transition of somatic cells into the macrospore, female gamete, and the zygotic embryogenesis. This knowledge is fundamental for future biotechnological research focused on solving the morphological recalcitrance observed during the in vitro induction of somatic or microspore embryogenesis in Capsicum. For the first time in C. chinense, we have described the hypostases, a putative source of plant growth regulators, and "the corrosion cavity", a space around the embryo. Additionally, the cell wall pectin-esterification status was investigated by immunohistology. At early stages of morphogenesis, the pectin is highly methyl-esterified; however, methyl-esterification decreases gradually throughout the process. A comparison of the results obtained here, together with the histo- and immunological changes occurring during the somatic and microspore embryogenesis, should help to elucidate the biochemical mechanisms that trigger the morphogenic events in Capsicum spp.

Main factors affecting the loss of multi organ potential donors for transplantation.

ANTECEDENTS: In the field of organ donation and procurement, a possible donor is a patient with severe neurological damage and appropriate medical criteria for donation, and a potential donor is a patient suspected of being brain dead. OBJECTIVE: The aim of this study is to identify specific factors that cause the loss of possible multiorgan donors in an intensive care unit (ICU). METHODS: A review of cross-sectional charts of possible liver and kidney donors was done with patients admitted to the ICU with full respiratory support and Glasgow score < 8. A multiple logistical regression model was applied to identify the loss of potential donors previously considered only as possible donors. RESULTS: A total of 44 charts were reviewed, 26 were possible, and 18 were potential donors. The mean average was 46.7 and 52.8 years for possible and potential donors, respectively (p = 0.272). The potential donors experienced frequent intracranial hemorrhage (19.2 vs. 55.6) or renal injury (3.9 vs. 27.8), and fewer invasive procedures are performed (34.6 vs. 5.6) (p <0.05). Invasive procedure resulted significant (p = 0.013) when a multivariate analysis was done. DISCUSSION AND CONCLUSIONS: Patients submitted to invasive procedures have 20 times more probabilities of being lost as kidney donors even when originally considered as possible donors. Medical or surgery procedures are the leading cause for the loss of potential donors, so an opportune detection is essential.

ANTECEDENTES: En el campo de la donación y la procuración renal, un posible donador es un paciente con daño neurológico grave y que cubre los criterios médicos para la donación; un potencial donador es el paciente que, además, cuenta con la sospecha de tener muerte cerebral. OBJETIVO: Identificar los factores específicos que causan la pérdida de posibles donadores multiorgánicos en una unidad de terapia intensiva. METODOLOGÍA: Se realizó un estudio retrospectivo transversal de los expedientes de los posibles donadores de riñón e hígado admitidos a la unidad de terapia intensiva con soporte respiratorio total y escala de Glasgow < 8. Se aplicó un modelo de regresión logística para identificar los casos perdidos de potenciales donadores previamente considerados solo como posibles donadores. RESULTADOS: Se revisaron 44 casos, 26 de posibles y 18 de potenciales donadores. La edad promedio fue de 46.7 y 52.8 años para los posibles y potenciales donadores, respectivamente (p = 0.272). Los potenciales donadores experimentaron con más frecuencia hemorragia intracraneal (19.2 vs. 55.6) o lesión renal (3.9 vs. 27.8), y fueron sometidos a menos procedimientos médicos (34.6 vs. 5.6) (p < 0.05). En el análisis multivariado, la realización de algún procedimiento invasivo fue significativa entre los dos grupos (p = 0.013). DISCUSIÓN Y CONCLUSIONES: Los pacientes sometidos a un procedimiento invasivo tienen 20 veces más probabilidades de perderse como donadores renales aun siendo considerados de manera original como posibles donadores. Los procedimientos médicos o quirúrgicos son la principal causa de pérdida de potenciales donadores, por lo que es esencial una detección precoz y oportuna de los mismos.

Potential drug-drug interactions of OMBITASVIR, PARITAPREVIR/ritonavir ± DASABUVIR ± ribavirin in clinical practice.

BACKGROUND & AIMS: Drug-drug interactions (DDIs) with ombitasvir/paritaprevir/ritonavir with or without dasabuvir and with or without ribavirin (OBV/PTV/r ± DSV ± RBV) are common in clinical trials. Our aim was to analyze the prevalence and management of potential DDIs and adverse events (AEs) related to DDIs in patients with chronic hepatitis C (CHC) receiving OBV/PTV/r ± DSV ± RBV in clinical practice. METHODS: 177 CHC patients started OBV/PTV/r ± DSV ± RBV in 4 Spanish hospitals and were screened for potential DDIs using the University of Liverpool database. Patients were classified according to the most serious potential DDIs at baseline and AEs during therapy. RESULTS: At least one potential DDI was found in 110 (62.1%) patients: 100 (56.5%) had at least one manageable potential DDI and 10 (5.6%) at least one contraindicated. Patients with potential DDIs were receiving a higher number of concomitant drugs (4 vs. 2, P < 0.001). Routine medication was modified at baseline due to potential DDIs in 49 (27.7%) patients. During antiviral treatment, 67 (37.9%) patients presented at least one AE. In 9 (4.5%) patients, a DDI was suspected between OBV/PTV/r ± DSV ± RBV and the concomitant drug, requiring antiviral discontinuation in 4 patients. CONCLUSIONS: Potential DDIs are frequent with OBV/PTV/r ± DSV ± RBV, although a change in baseline medication is made in only one-quarter of patients. More than half of potential DDIs were only followed, and only 5% of patients developed AEs in which the implication of DDIs could not be excluded.

Protection against TBI-Induced Neuronal Death with Post-Treatment with a Selective Calpain-2 Inhibitor in Mice.

Traumatic Brain Injury (TBI) is a major cause of death and disability worldwide. The calcium-dependent protease, calpain, has been shown to be involved in TBI-induced neuronal death. However, whereas various calpain inhibitors have been tested in several animal models of TBI, there has not been any clinical trial testing the efficacy of calpain inhibitors in human TBI. One important reason for this could be the lack of knowledge regarding the differential functions of the two major calpain isoforms in the brain, calpain-1 and calpain-2. In this study, we used the controlled cortical impact (CCI) model in mice to test the roles of calpain-1 and calpain-2 in TBI-induced neuronal death. Immunohistochemistry (IHC) with calpain activity markers performed at different time-points after CCI in wild-type and calpain-1 knock-out (KO) mice showed that calpain-1 was activated early in cortical areas surrounding the impact, within 0-8 h after CCI, whereas calpain-2 activation was delayed and was predominant during 8-72 h after CCI. Calpain-1 KO enhanced cell death, whereas calpain-2 activity correlated with the extent of cell death, suggesting that calpain-1 activation suppresses and calpain-2 activation promotes cell death following TBI. Systemic injection(s) of a calpain-2 selective inhibitor, NA101, at 1 h or 4 h after CCI significantly reduced calpain-2 activity and cell death around the impact site, reduced the lesion volume, and promoted motor and learning function recovery after TBI. Our data indicate that calpain-1 activity is neuroprotective and calpain-2 activity is neurodegenerative after TBI, and that a selective calpain-2 inhibitor can reduce TBI-induced cell death.

Papel de la ribavirina en la terapia libre de interferón frente al virus de la hepatitis C / Role of ribavirin in interferon-free therapy for the treatment of hepatitis C virus

Los regímenes libres de interferón ofrecen tasas de respuesta virológica sostenida (RVS) por encima del 90%, efectos adversos generalmente bien tolerados y duraciones de tratamiento de 12 semanas para la mayoría de pacientes con hepatitis C crónica, incluyendo pacientes naive o previamente tratados y pacientes con o sin cirrosis. Sin embargo, algunas de las opciones de tratamiento recomendadas por las guías requieren la adición de ribavirina (RBV) o extender la duración del tratamiento para aumentar la eficacia. El uso de RBV es una herramienta útil en aquellos pacientes difíciles de curar como los pacientes con cirrosis descompensada o infectados por el genotipo 3 y aquellos que no han logrado una RVS después de un tratamiento con antivirales de acción directa (AAD). Globalmente, la adición de RBV a las diferentes combinaciones causa efectos adversos relacionados con una disminución de la hemoglobina y añade inconvenientes como su posología, por la que los pacientes deben tomar varios comprimidos dos veces al día. Sin embargo, la anemia grave es rara y fácilmente manejable con una reducción de dosis. Además, la RBV es teratogénica. En la práctica, debido a que la RBV es barata y bien tolerada cuando se combina con un régimen sin interferón, sigue siendo una herramienta útil para optimizar los resultados de algunos regímenes de tratamiento contra el VHC. Los regímenes libres de RBV eliminan los efectos adversos relacionados con la misma, resultando en una mejor tolerabilidad, mejorando la adherencia y la calidad de vida del paciente y disminuyendo el coste del tratamiento (AU)

Interferon-free regimens achieve sustained virologic response (SVR) rates of over 90%, have generally well-tolerated adverse effects and involve 12-week treatment durations for most patients with chronic hepatitis C, including naive or previously treated patients and patients with or without cirrhosis. However, some of the treatment options recommended by the guidelines require the addition of ribavirin (RBV) or extend the duration of treatment to increase efficacy. The use of RBV is a useful tool in those difficult-to-cure patients such as patients with decompensated or genotype-3-infected cirrhosis and those who have not achieved SVR after treatment with direct-acting antivirals (DAA). Overall, adding RBV to the different combinations causes adverse effects related to a decrease in haemoglobin and involves inconveniences such as its dosage, which requires patients to take several tablets twice daily. However, severe anaemia is rare and easily manageable with a dose reduction. In addition, RBV is teratogenic. In practice, because RBV is inexpensive and well tolerated when combined with an interferon-free regimen, it continues to be a useful tool to optimise the results of some HCV treatment regimens. RBV-free regimens eliminate RBV-related adverse effects related, resulting in better tolerability, improving patient adherence and quality of life and reducing the cost of treatment (AU)

Electrocorticographic Patterns in Epilepsy Surgery and Long-Term Outcome.

PURPOSE: The role of intraoperative electrocorticography (iECoG) and of its patterns in epilepsy surgery have shown contradictory results. Our aim was to describe iECoG patterns and their association with outcome in epilepsy surgery. METHODS: We retrospectively analyzed 104 patients who underwent epilepsy surgery (2009-2015) with pre- and postresection iECoG. We described clinical findings, type of surgery, preresection iECoG patterns according to Palmini et al., 1995 (sporadic, continuous, burst, and recruiting interictal epileptiform discharges-IEDs) and postresection iECoG outcome (de novo, residual, and without IEDs). The Engel scale was used to evaluate the outcome. Descriptive statistics, Kaplan-Meier, the logistic regression model, and analysis of variance tests were used. RESULTS: We included 60.6% (63/104) females, with a mean age of 35 (±10.2) years at the time of epilepsy surgery. The etiologies were hippocampal sclerosis (63.5%), cavernomas (14.4%), cortical dysplasia (11.5%), and low-grade tumors (10.6%). The most common preresection iECoG pattern was sporadic IEDs (47%). Postresection iECoG patterns were de novo (55.7%), residual (27.8%), and without IEDs (16.3%). Mean follow-up was 19.2 months. Engel scale was as follows: Engel I (91 patients, 87.5%), Engel II (10 patients, 9.6%), and Engel III (three patients, 2.9%). Analysis by mixed-design analysis of variance showed a significant difference between etiology groups with a strong size effect (P = 0.021, η = 0.513) and also between preresection iECoG patterns (P = 0.008, η = 0.661). CONCLUSIONS: Preresection iECoG patterns and etiology influence Engel scale outcome in lesional epilepsy surgery.

Role of ribavirin in interferon-free therapy for the treatment of hepatitisC virus. / Papel de la ribavirina en la terapia libre de interferón frente al virus de la hepatitisC.

Interferon-free regimens achieve sustained virologic response (SVR) rates of over 90%, have generally well-tolerated adverse effects and involve 12-week treatment durations for most patients with chronic hepatitis C, including naive or previously treated patients and patients with or without cirrhosis. However, some of the treatment options recommended by the guidelines require the addition of ribavirin (RBV) or extend the duration of treatment to increase efficacy. The use of RBV is a useful tool in those difficult-to-cure patients such as patients with decompensated or genotype-3-infected cirrhosis and those who have not achieved SVR after treatment with direct-acting antivirals (DAA). Overall, adding RBV to the different combinations causes adverse effects related to a decrease in haemoglobin and involves inconveniences such as its dosage, which requires patients to take several tablets twice daily. However, severe anaemia is rare and easily manageable with a dose reduction. In addition, RBV is teratogenic. In practice, because RBV is inexpensive and well tolerated when combined with an interferon-free regimen, it continues to be a useful tool to optimise the results of some HCV treatment regimens. RBV-free regimens eliminate RBV-related adverse effects related, resulting in better tolerability, improving patient adherence and quality of life and reducing the cost of treatment.

Transcranial Direct Current Stimulation in Mesial Temporal Lobe Epilepsy and Hippocampal Sclerosis.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been evaluated in medication refractory epilepsy patients. The results have been inconclusive and protocols have varied between studies. OBJECTIVE: To evaluate the safety and efficacy of two protocols of tDCS in adult patients with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS). METHODS: This is a randomized placebo-controlled, double-blinded clinical trial, with 3 arms, 3 sessions, 5 sessions and placebo stimulation. Frequency of seizures (SZs), interictal epileptiform discharges (IEDs) and adverse effects (AEs) were registered before and after treatment, and at 30 and 60 days follow-up. Descriptive statistics, k-related samples, Friedman's test, and relative risk (RR) estimation were used for analysis. RESULTS: We included twenty-eight subjects (3d n = 12, 5d n = 8, placebo n = 8), 16/28 (57%) men, age 37.8(±10.9) years old. There was a significant reduction of the frequency of SZs at one (p = 0.001) and two (p = 0.0001) months following cathodal tDCS compared to baseline in the 3 arms (p = 0.0001). The mean reduction of SZ frequency at two months in both active groups was significantly higher than placebo (-48% vs. -6.25%, p < 0.008). At 3 days (-43.4% vs. -6.25%, p < 0.007) and 5 days (-54.6% vs. -6.25%, p < 0.010) individual groups showed a greater reduction of SZs. A significant IED reduction effect was found between baseline and immediately after interventions (p = 0.041) in all groups. Side effects were minor. CONCLUSIONS: Cathodal tDCS technique of 3 and 5 sessions decreased the frequency of SZs and IEDs (between baseline and immediately post-tDCS) in adult patients with MTLE-HS compared to placebo tDCS.

Deleting both PHLPP1 and CANP1 rescues impairments in long-term potentiation and learning in both single knockout mice.

Calpain-1 (CANP1) has been shown to play a critical role in synaptic plasticity and learning and memory, as its deletion in mice results in impairment in theta-burst stimulation- (TBS) induced LTP and various forms of learning and memory. Likewise, PHLPP1 (aka SCOP) has also been found to participate in learning and memory, as PHLPP1 overexpression impairs hippocampus-dependent learning. We previously showed that TBS-induced LTP was associated with calpain-1 mediated truncation of PHLPP1.To better understand the roles of these 2 genes in synaptic plasticity and learning and memory, we generated a double knockout (DKO) mouse by crossing the parent strains. Surprisingly, DKO mice exhibit normal TBS-induced LTP, and the learning impairments in fear conditioning and novel object or novel location recognition were absent in the DKO mice. Moreover, TBS-induced ERK activation in field CA1 of hippocampal slices, which is impaired in both single deletion mice, was restored in the DKO mice. These results further strengthen the roles of both CANP1 and PHLPP1 in synaptic plasticity and learning and memory, and illustrate the complexities of the interactions between multiple pathways participating in synaptic plasticity.

Defects in the CAPN1 Gene Result in Alterations in Cerebellar Development and Cerebellar Ataxia in Mice and Humans.

A CAPN1 missense mutation in Parson Russell Terrier dogs is associated with spinocerebellar ataxia. We now report that homozygous or heterozygous CAPN1-null mutations in humans result in cerebellar ataxia and limb spasticity in four independent pedigrees. Calpain-1 knockout (KO) mice also exhibit a mild form of ataxia due to abnormal cerebellar development, including enhanced neuronal apoptosis, decreased number of cerebellar granule cells, and altered synaptic transmission. Enhanced apoptosis is due to absence of calpain-1-mediated cleavage of PH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1), which results in inhibition of the Akt pro-survival pathway in developing granule cells. Injection of neonatal mice with the indirect Akt activator, bisperoxovanadium, or crossing calpain-1 KO mice with PHLPP1 KO mice prevented increased postnatal cerebellar granule cell apoptosis and restored granule cell density and motor coordination in adult mice. Thus, mutations in CAPN1 are an additional cause of ataxia in mammals, including humans.

Calpain-1 and calpain-2 play opposite roles in retinal ganglion cell degeneration induced by retinal ischemia/reperfusion injury.

Calpain has been shown to be involved in neurodegeneration, and in particular in retinal ganglion cell (RGC) death resulting from increased intraocular pressure (IOP) and ischemia. However, the specific roles of the two major calpain isoforms, calpain-1 and calpain-2, in RGC death have not been investigated. Here, we show that calpain-1 and calpain-2 were sequentially activated in RGC dendrites after acute IOP elevation. By combining the use of a selective calpain-2 inhibitor (C2I) and calpain-1 KO mice, we demonstrated that calpain-1 activity supported survival, while calpain-2 activity promoted cell death of RGCs after IOP elevation. Calpain-1 activation cleaved PH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1) and activated the Akt pro-survival pathway, while calpain-2 activation cleaved striatal-enriched protein tyrosine phosphatase (STEP) and activated STEP-mediated pro-death pathway in RGCs after IOP elevation. Systemic or intravitreal C2I injection to wild-type mice 2h after IOP elevation promoted RGC survival and improved visual function. Our data indicate that calpain-1 and calpain-2 play opposite roles in high IOP-induced ischemic injury and that a selective calpain-2 inhibitor could prevent acute glaucoma-induced RGC death and blindness.