Comparison Study of FNAC Using the Milan System Cytopathology versus Definitive Histology for the Diagnosis of Salivary Gland Tumors.

INTRODUCTION: Salivary gland tumors (SGT) represent 6 to 8 percent of head and neck tumors. The cytologic diagnosis of SGT is performed by fine-needle aspiration cytology (FNAC) with variable sensitivity and specificity. The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) categorizes the cytological results and provides the risk of malignancy (ROM). The aim of our study was to evaluate the cytological findings with the definitive pathological findings to assess the sensitivity, specificity, and diagnostic accuracy of FNAC in SGT according to MSRSGC classification. METHOD: An observational, retrospective, single-center study was carried out at a tertiary referral hospital over a period of 10 years. Patients that underwent FNAC for major SGT and that have undergone surgery to remove the tumor were included. A histopathological follow-up was performed on the surgically excised lesions. Results from the FNAC were categorized into one of the six MSRSGC categories. The sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of FNAC for determining benign and malignant cases were calculated. RESULTS: A total of 417 cases were analyzed. The cytological prediction of ROM was 10% in nondiagnostic, 12.12% in non-neoplastic, 3.58% in neoplasm benign group, 60% in AUS and SUMP groups, and 100% in suspicious and malignant group. The statistical analysis of sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for determining benign cases was 99%, 55%, 94%, 93%, and 94%, respectively, and for determining malignant neoplasm was 54%, 99%, 93%, 94%, and 94%, respectively. CONCLUSION: In our hands, MSRSGC is highly sensitive for benign tumors and highly specific for malignant tumors. The low sensitivity to differentiate malignant from benign cases makes it necessary to apply an adequate anamnesis, physical examination, and imaging tests to consider surgical treatment in most cases.

Oportunistic diagnosis based on age and hepatitis C virus clearance: an essential step to improve the overall health of the liver.

Back in January 2022, an EASL-Lancet Commission on the impact of liver disorders in the European region commissioned by the WHO demonstrated that this condition is, actually, the second leading cause of loss of labor years in Europe after ischemic heart disease (1). This is a very relevant piece of information since this is something that is going to impact the new generations of Europeans unless a significant change is made in public health policies. Despite the advances made over the last few years in hepatitis C virus clearance-understood as a significant reduction of morbidity and mortality associated with Hepatitis B and C viruses-there are still challenges ahead to improve liver health due to the high use of alcohol, and the inseparable triad obesity / diabetes mellitus / metabolic associated fatty liver disease. Also, access to healthcare for several population groups at risk of presenting higher rates of liver disease has become a problem.

[Management from Primary Care of monkeypox infection (MPOX) in humans]. / Manejo desde atención primaria de la infección por la viruela del mono (MPOX) en humanos.

Monkeypox (MPOX) is a viral zoonosis endemic in West or Central African countries that is sporadically exported to another area. In May 2022, a global outbreak of MPOX smallpox began to occur in several countries in Europe and North America. Most of the reported cases are identified at the outpatient level and mainly affect men who have sex with men (MSM). Transmission is by close contact with lesions, body fluids, respiratory secretions or contaminated material from an infected person or animal. The clinical picture is similar to human smallpox, with less severity. Mild, self-limiting skin involvement predominates after 2-4 weeks. In MSM, atypical skin lesions appear due to the mode of infection. Severe forms or complications may appear in certain risk groups. The case fatality rate is 3%-6% depending on the clade responsible. The diagnosis of suspicion is confirmed by detection of the virus from exudates of lesions or scabs, with nucleic acid amplification techniques by conventional or real-time PCR. Clinical management in most cases is performed in primary care (PC), by monitoring the main symptoms. Between 5-10% require hospital management and there are some specific antiviral treatment options. Human smallpox vaccines protect against MPOX and are used as pre- and post-exposure prophylaxis for persons at risk. Measures to reduce exposure to the virus are the main MPOX prevention strategy. In addition, the role of the family physician is key to controlling the spread of MPOX through active surveillance and early diagnosis of the disease.

Implementation of a neonatal donation protocol in the neonatal intensive care unit: A single-center experience.

BACKGROUND: Lack of specific protocols for neonatal donation contributes to the rarity of neonatal donors. In this study, we evaluate the impact of the implementation of a neonatal donation protocol in our NICU. METHODS: In this single-center study, we conducted a retrospective chart review of neonatal deaths in our NICU from January 2013 to January 2022. The study was divided into two periods: before and after the implementation of a neonatal donation protocol. The referral rates of potential neonatal donors to the OPO in the two periods were compared using the chi-square test. A p value < .05 was considered statistically significant. RESULTS: Sixty-four infants were reviewed. Seven (10.9%) met the inclusion criteria for potential neonatal donors after DCC. The referral rate of potential neonatal donors increased from 2.5% to 16.7% after the implementation of this protocol (p = .041), and one infant (4.1%) became an effective heart-valve donor. CONCLUSION: The implementation of a local neonatal donation protocol could have contributed to increase the referral rate of potential neonatal donors in our NICU. Following the implementation of a local neonatal donation protocol, we were able to perform a heart-valve donation for the first time in our unit.

Dopamine D2R is Required for Hippocampal-dependent Memory and Plasticity at the CA3-CA1 Synapse.

Dopamine receptors play an important role in motivational, emotional, and motor responses. In addition, growing evidence suggests a key role of hippocampal dopamine receptors in learning and memory. It is well known that associative learning and synaptic plasticity of CA3-CA1 requires the dopamine D1 receptor (D1R). However, the specific role of the dopamine D2 receptor (D2R) on memory-related neuroplasticity processes is still undefined. Here, by using two models of D2R loss, D2R knockout mice (Drd2-/-) and mice with intrahippocampal injections of Drd2-small interfering RNA (Drd2-siRNA), we aimed to investigate how D2R is involved in learning and memory as well as in long-term potentiation of the hippocampus. Our studies revealed that the genetic inactivation of D2R impaired the spatial memory, associative learning, and the classical conditioning of eyelid responses. Similarly, deletion of D2R reduced the activity-dependent synaptic plasticity in the hippocampal CA1-CA3 synapse. Our results demonstrate the first direct evidence that D2R is essential in behaving mice for trace eye blink conditioning and associated changes in hippocampal synaptic strength. Taken together, these results indicate a key role of D2R in regulating hippocampal plasticity changes and, in consequence, acquisition and consolidation of spatial and associative forms of memory.

Totally laparoscopic simultaneous resection of colorectal cancer and synchronous liver metastases: a single-center case series.

BACKGROUND: The aim of the study is to analyze the feasibility, the safety and short- and medium-term survival of totally laparoscopic simultaneous resections (LSR) of colorectal cancer (CRC) and synchronous liver metastases (LM). METHODS: This is a retrospective study of a single-center series. Patients ASA IV, ECOG ≥ 2, major hepatectomies (≥ 3 segments), symptomatic CRC as well as low rectal tumors were excluded from indication. The difficulty level of all liver resections was classified as low or intermediate according to the Iwate Criteria. Dindo-Clavien classification for postoperative complications evaluation was used. RESULTS: 15 Patients with 21 liver lesions were included. Laparoscopic liver surgery was performed first in every case. Median size of the lesions was 20 mm (r 8-69). Major complications (Dindo-Clavien ≥ 3) occurred in 3 patients (20%); median hospital stay was 7 days (r 4-35), and only one patient (6.6%) was readmitted upon the first month from the surgery. 90-day mortality rate was 0%. After a median follow-up of 24 months (r 7-121), disease-free survival at 1, 2 and 3 years was 58%, 36% and 24%, respectively; overall survival at 1, 2 and 3 years was 92.3%. CONCLUSIONS: In selected patients, LSR of CRC and LM is technically feasible and has an acceptable morbidity rate and mid-term survival.

Recognition Memory Induces Natural LTP-like Hippocampal Synaptic Excitation and Inhibition.

Synaptic plasticity is a cellular process involved in learning and memory by which specific patterns of neural activity adapt the synaptic strength and efficacy of the synaptic transmission. Its induction is governed by fine tuning between excitatory/inhibitory synaptic transmission. In experimental conditions, synaptic plasticity can be artificially evoked at hippocampal CA1 pyramidal neurons by repeated stimulation of Schaffer collaterals. However, long-lasting synaptic modifications studies during memory formation in physiological conditions in freely moving animals are very scarce. Here, to study synaptic plasticity phenomena during recognition memory in the dorsal hippocampus, field postsynaptic potentials (fPSPs) evoked at the CA3-CA1 synapse were recorded in freely moving mice during object-recognition task performance. Paired pulse stimuli were applied to Schaffer collaterals at the moment that the animal explored a new or a familiar object along different phases of the test. Stimulation evoked a complex synaptic response composed of an ionotropic excitatory glutamatergic fEPSP, followed by two inhibitory responses, an ionotropic, GABAA-mediated fIPSP and a metabotropic, G-protein-gated inwardly rectifying potassium (GirK) channel-mediated fIPSP. Our data showed the induction of LTP-like enhancements for both the glutamatergic and GirK-dependent components of the dorsal hippocampal CA3-CA1 synapse during the exploration of novel but not familiar objects. These results support the contention that synaptic plasticity processes that underlie hippocampal-dependent memory are sustained by fine tuning mechanisms that control excitatory and inhibitory neurotransmission balance.

Experiences and mediating factors in nurses' responses to electronic device alarms: A phenomenological study.

AIM: This study aims to explore the experiences and mediating factors of nurses' responses to electronic device alarms in critical care units (CCUs). BACKGROUND: Alarm fatigue occasionally has adverse consequences for patient safety. METHODS: This qualitative study was designed and analysed following Giorgi's descriptive phenomenological approach. Seventeen nurses were theoretically sampled, reaching information saturation. Semistructured interviews were used to collect the data. RESULTS: Three central themes explained nurses' experiences: general perceptions about alarms (basic equipment of the CCU), strategies to reduce false alarms (training in the configuration of monitors, customization of the alarms to fit he patient's condition. teamwork and taking advantage of the development of technology) and key elements of the response to alarms (information about patient's condition, nurses' clinical experience, type of CCU, 'cry-wolf' phenomenon and nurse/patient ratio). CONCLUSIONS: To reduce false alarms, nurses need further postgraduate training, training on monitors and customizing alarms to fit the patient's health status. The complex process of deciding to respond to an alarm includes environmental, professional variables and patient status. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers should ensure that nurses have sufficient experience and training in the CCU, improve the nurse/patient ratio, promote teamwork and ensure that the devices are the latest generation.

Archaeal overdominance close to life-limiting conditions in geothermally influenced hypersaline lakes at the Danakil Depression, Ethiopia.

The Dallol protovolcanic area on the Danakil Depression (Afar region, Ethiopia) exhibits unique hydrothermal manifestations in hypersaline context, yielding varied polyextreme physicochemical conditions. Previous studies identified a wide archaeal diversity in less extreme brines but failed to identify microorganisms thriving in either high-chaotropicity, low-water-activity brines or hyperacidic-hypersaline Na-Fe-rich brines. Recently, we accessed several small lakes under intense degassing activity adjacent to the Round Mountain, west to the Dallol dome [Western Canyon Lakes (WCL); WCL1-5]. They exhibited intermediate parameter combinations (pH ~ 5, 34%-41% (weight/volume) NaCl-dominated salts with relatively high levels of chaotropic Mg-Ca salts) that should allow to better constrain life limits. These lakes were overwhelmingly dominated by Archaea, encompassing up to 99% of prokaryotic 16S rRNA gene amplicon sequences in metabarcoding studies. The majority belonged to Halobacteriota and Nanohaloarchaeota, the latter representing up to half of prokaryotic sequences. Optical and epifluorescence microscopy showed active cells in natural samples and diverse morphotypes in enrichment cultures. Scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy revealed tiny cells (200-300 nm diameter) epibiotically associated with somewhat larger cells (0.6-1 µm) but also the presence of silica-dominated precipitates of similar size and shape, highlighting the difficulty of distinguishing microbes from mineral biomorphs in this kind of low-biomass systems.

International survey of human herpes virus 8 screening and management in solid organ transplantation.

BACKGROUND: HHV-8/Kaposi Sarcoma herpesvirus has been associated with a broad spectrum of diseases in solid organ transplant (SOT) recipients. Primary donor-derived infection can be associated with severe and rapidly fatal non-neoplastic disease, and diagnosis is made with high HHV-8 DNAemia. METHODS: We carried out an international survey to investigate the current approach to HHV-8 screening, and management in SOT since a protocol has not been established by international guidelines. RESULTS: A total of 51 transplant centers from 15 countries filled out the survey. HHV-8-associated diseases in SOT have been diagnosed during the previous 5 years in 67% of centers. Pretransplant serological screening is performed in 17 centers (33%), and posttransplant HHV-8 nucleic acid testing (NAT) monitoring is performed in 21 centers (41%). Performing HHV-8 NAT monitoring and serological screening were found associated with having diagnosed in the previous 5 years a non-malignant HHV-8-associated disease. CONCLUSIONS: Serological pretransplant screening of donors and recipients and post-transplant HHV-8 NAT monitoring recommendations should be standardized. Even though serological assays are not optimal, they could contribute to increasing knowledge on epidemiology and management of HHV-8-associated diseases after SOT.

Usability Evaluation by Nurses of a Knowledge-Based System of Care Plans for People Hospitalized by COVID-19.

The aim of this study is to analyze the usability by nurses of the Knowledge-Based System "Diagnostics care for COVID-19." A convenience sample of 16 nurses was selected, among hospital workers and external experts. The group was divided into three subgroups intentionally to obtain different usability perspectives. Usability was evaluated by the System Usability Scale questionnaire. The participants completed the questionnaire on general usability, data inputs, and information output, after completing a minimum of 12 care plans. The first subgroup used real cases and the "think aloud" technique, the second simulated cases from the same hospital, and the third subgroup performed the external simulation. The highest scores were obtained in data inputs (94.38-97.50); and the lowest, in general usability (90.00-95.00). The subgroup of external experts scored the highest (93.13-95.63), and the first subgroup, which carried out real cases, gave the lowest score (90.00-94.38). The "think aloud" technique found an improvement in including more diagnoses and being able to carry out several plans for one person at the same time. The usability obtained was "excellent" in all subgroups and questionnaires, although the application showed limitations related to its characteristics imposed in the requirements specification.

[Basic aspects of COVID-19 for management from primary care]. / Aspectos básicos de la COVID-19 para el manejo desde atención primaria.

SARS-CoV-2 is transmitted from person to person by inhalation or contact with respiratory droplets and aerosols. The median incubation period is 5.1 days. Fever, dry cough, dyspnea and fatigue are the most common symptoms. Almost half of the cases are asymptomatic. The spectrum of disease varies from mild (81%) to critical (5%). Older age, male gender and comorbidities negatively impact on the severity and mortality of COVID-19. The diagnosis of acute COVID-19 is made with RT-PCR or antigenic detection tests. In hospital patients, remdesivir reduces recovery time. Oral steroids are recommended for severe or critical cases requiring oxygen therapy or mechanical ventilation. Thromboprophylaxis is recommended in all severe and non-severe cases with high thrombotic risk. Antibiotherapy is limited to cases of high suspicion of bacterial superinfection. Mild-moderate and severe cases after discharge from hospital should be clinically monitored for a minimum period of two weeks.

Conditional BDNF Delivery from Astrocytes Rescues Memory Deficits, Spine Density, and Synaptic Properties in the 5xFAD Mouse Model of Alzheimer Disease.

It has been well documented that neurotrophins, including brain-derived neurotrophic factor (BDNF), are severely affected in Alzheimer's disease (AD), but their administration faces a myriad of technical challenges. Here we took advantage of the early astrogliosis observed in an amyloid mouse model of AD (5xFAD) and used it as an internal sensor to administer BDNF conditionally and locally. We first demonstrate the relevance of BDNF release from astrocytes by evaluating the effects of coculturing WT neurons and BDNF-deficient astrocytes. Next, we crossed 5xFAD mice with pGFAP:BDNF mice (only males were used) to create 5xFAD mice that overexpress BDNF when and where astrogliosis is initiated (5xF:pGB mice). We evaluated the behavioral phenotype of these mice. We first found that BDNF from astrocytes is crucial for dendrite outgrowth and spine number in cultured WT neurons. Double-mutant 5xF:pGB mice displayed improvements in cognitive tasks compared with 5xFAD littermates. In these mice, there was a rescue of BDNF/TrkB downstream signaling activity associated with an improvement of dendritic spine density and morphology. Clusters of synaptic markers, PSD-95 and synaptophysin, were also recovered in 5xF:pGB compared with 5xFAD mice as well as the number of presynaptic vesicles at excitatory synapses. Additionally, experimentally evoked LTP in vivo was increased in 5xF:pGB mice. The beneficial effects of conditional BDNF production and local delivery at the location of active neuropathology highlight the potential to use endogenous biomarkers with early onset, such as astrogliosis, as regulators of neurotrophic therapy in AD.SIGNIFICANCE STATEMENT Recent evidence places astrocytes as pivotal players during synaptic plasticity and memory processes. In the present work, we first provide evidence that astrocytes are essential for neuronal morphology via BDNF release. We then crossed transgenic mice (5xFAD mice) with the transgenic pGFAP-BDNF mice, which express BDNF under the GFAP promoter. The resultant double-mutant mice 5xF:pGB mice displayed a full rescue of hippocampal BDNF loss and related signaling compared with 5xFAD mice and a significant and specific improvement in all the evaluated cognitive tasks. These improvements did not correlate with amelioration of ß amyloid load or hippocampal adult neurogenesis rate but were accompanied by a dramatic recovery of structural and functional synaptic plasticity.

Worldwide Effects of Coronavirus Disease Pandemic on Tuberculosis Services, January-April 2020.

Coronavirus disease has disrupted tuberculosis services globally. Data from 33 centers in 16 countries on 5 continents showed that attendance at tuberculosis centers was lower during the first 4 months of the pandemic in 2020 than for the same period in 2019. Resources are needed to ensure tuberculosis care continuity during the pandemic.

Methylene blue-treated plasma, versus quarantine fresh frozen plasma, for acute thrombotic thrombocytopenic purpura treatment: Comparison between centres and critical review on longitudinal data.

INTRODUCTION: Therapeutic plasma exchange (TPE) is the first-line treatment for acute thrombotic thrombocytopenic purpura (TTP). Methylene blue-plasma (MBP) has been used for over 20 years, but its efficacy in this setting remains controversial. PATIENTS AND METHODS: this is a comparative analysis of the experience of two Centres, with different plasma products, to evaluate their efficacy in TTP. One centre used quarantine plasma (QP), and MBP the other. We performed a retrospective longitudinal study, analysing the clinical files of TTP patients of a 13-year data evaluation period. Duration of treatment and transfusion parameters, medical record, laboratory testing, concomitant medication, and survival rate, were assessed for every episode. RESULTS: During the study period, 12 (55.5 %) and 10 (45.5 %) new cases were treated with QP and MBP, respectively. There were no significant differences between the mean numbers of TPE processes, days elapsed from diagnosis to TPE, and plasma volume transfused. The QP TPE episodes of treatment were significantly associated with an increased time to recovery compared with MBP episodes of treatment (p = 0.004). CONCLUSION: MBP was as effective as QP in the treatment of TTP patients. Since recovery was more favourable when MBP was used, we consider MBP remains a suitable alternative to treat TTP patients.

Tongue peak pressure: a tool to aid in the identification of obstruction sites in patients with obstructive sleep apnea/hypopnea syndrome.

Purpose of this study was to evaluate whether tongue peak pressure measured using the Iowa Oral Performance Instrument is correlated with the topographic site of obstruction in patients with obstructive sleep apnea/hypopnea syndrome observed during drug-induced sleep endoscopy. Thirty-five consecutive adult patients (29 men, 6 women) were prospectively enrolled after having been diagnosed with severe obstructive sleep apnea/hypopnea syndrome by polysomnography. An apnea-hypopnea index > 30 was confirmed, and age, gender, and body mass index were recorded by Epworth Sleepiness Scale questionnaire, and a thorough evaluation of the upper airway by video-flexible endoscopy. Twenty healthy controls according to age and sex were chosen for IOPI measurements. After drug-induced sleep endoscopy, a topographic diagnosis was done using the VOTE classification. Tongue and lip peak pressures were both measured using the Iowa Oral Performance Instrument in all patients and in 20 healthy controls. Main outcomes and measures: the correlations between office findings, Iowa Oral Performance Instrument measures, and the VOTE tongue classification during drug-induced sleep endoscopy (T0, T1, T2) were then investigated. RESULTS: The average Iowa Oral Performance Instrument tongue and lip pressure were 44.02 ± 12.29 and 15.03 ± 3.71 kPa, respectively. The Iowa Oral Performance Instrument scores were both significantly lower than values in healthy controls (P < 0.001). The VOTE classification referring to the tongue position was T0 in 13 cases (37.1%), T1 in 12 cases (34.3%), and T2 in 10 cases (28.6%). A significant correlation was found between the Iowa Oral Performance Instrument tongue pressure and the T size during drug-induced sleep endoscopy (Kruskal-Wallis χ2 25.82; P ≤ 0.001). CONCLUSIONS: In our experience, the Iowa Oral Performance Instrument is a useful tool for evaluating tongue collapse for the topographic diagnosis of patients with obstructive sleep apnea/hypopnea syndrome.

Taxonomic Triangulation of Care in Healthcare Protocols: Mapping of Diagnostic Knowledge From Standardized Language.

Taxonomic triangulation is a data mining technique for the management of care knowledge. This technique uses standardized languages, such as North American Nursing Diagnosis Association International, Nursing Outcomes Classification, and Nursing Interventions Classification, as well as logic. Its purpose is to find patterns in the data and identify care diagnoses. Triangulation can be applied to databases (clinical records) or to bibliographic sources (eg, protocols). The objective of this study is to identify the care diagnoses implicit in the nursing care protocols of the Community of Madrid. The method followed has three phases: knowledge extraction for mapping of variables, linking to diagnoses, and triangulation with analysis. The study analyzes six protocols, and 344 variables (167 assessment, 29 planning, and 148 intervention) and 6118 links have been extracted. Triangulation identified 165 NANDA diagnoses (68.48%), and only 25 labels were not revealed through this process. As a limitation, the results depend on the knowledge presented in protocols and change with language editions. Some labels included in the sample are recent and are not included in the links with nursing outcomes classification and nursing interventions classification. In conclusion, taxonomic triangulation makes it possible to manage knowledge, discover data patterns, and represent care situations.

Internet addiction and Facebook addiction in Spanish women with eating disorders.

AIM: We aim to investigate the association between the presence of eating disorders and both Internet addiction (IA) and Facebook addiction (FA) in women suffering from eating disorders. METHODS: A total of 124 women completed three instruments: the Internet Addiction Test (IAT), the Bergen Facebook Addiction Scale (BFAS) and a sociodemographic questionnaire. RESULTS: The proportion of FA was 37.9%. The distribution of risk of IA was 21.8%. When the risk of Internet or Facebook addiction was compared with respect to eating disorders, no significant differences were found between groups (P = 0.146 and P = 0.086, respectively). Age and Body Mass Index (BMI) were predictors of BFAS scores; the standardized beta coefficient (ß) for age was -0.463 (P ≤ 0.001), while for BMI it was 3.44; (P = 0.001) being a positive predictor of BFAS scores. For IAT scores, ß age (negatively) = -0.415; (P < 0.001) and ß for weight (positively) 3.657; (P < 0.001) were identified. CONCLUSIONS: The presence of an eating disorder does not seem to be a factor that characterizes the risk of Internet or Facebook addiction in our sample. As information regarding the potential association between Internet and Facebook addiction and the presence of eating disorders is limited, we encourage further studies on this topic.

Principles for implementing a population screening strategy for hepatitis C in Spain.

BACKGROUND: hepatitis C, besides health impairment, results in significant loss of productivity and diminished quality of life, and noticeably contributes to health expenditure increases. Because of all this, the Spanish Ministry of Health (Ministerio de Sanidad, Consumo y Bienestar Social - MSCBS) implemented in 2015 a strategic plan for managing hepatitis C (Plan Estratégico para el Abordaje de la Hepatitis C - PEAHC) within the National Health System. However, the PEAHC includes no screening plan. The MSCBS developed a framework document on population screening (Documento Marco sobre Cribado Poblacional) that defines the criteria a disease must meet in order to consider implementing a screening program. Specifically, it defines 4 criteria related to the health issue, 4 related to the screening test, and 3 criteria dealing with diagnosis confirmation and treatment. OBJECTIVE: to identify whether there is scientific evidence to support hepatitis C meeting the criteria to be considered a disease qualifying for a population screening strategy in Spain. METHODS: a literature search for scientific evidence concerning each required criterion for implementing a population screening plan for hepatitis C in Spain. RESULTS: sufficient scientific evidence was found to support hepatitis C meeting the criteria required by the MSCBS for the implementation of a population screening program. CONCLUSIONS: according to the available scientific evidence, hepatitis C in Spain meets the required criteria to qualify for consideration of population screening plan.

R-Ras1 and R-Ras2 Are Essential for Oligodendrocyte Differentiation and Survival for Correct Myelination in the Central Nervous System.

Rapid and effective neural transmission of information requires correct axonal myelination. Modifications in myelination alter axonal capacity to transmit electric impulses and enable pathological conditions. In the CNS, oligodendrocytes (OLs) myelinate axons, a complex process involving various cellular interactions. However, we know little about the mechanisms that orchestrate correct myelination. Here, we demonstrate that OLs express R-Ras1 and R-Ras2. Using female and male mutant mice to delete these proteins, we found that activation of the PI3K/Akt and Erk1/2-MAPK pathways was weaker in mice lacking one or both of these GTPases, suggesting that both proteins coordinate the activity of these two pathways. Loss of R-Ras1 and/or R-Ras2 diminishes the number of OLs in major myelinated CNS tracts and increases the proportion of immature OLs. In R-Ras1-/- and R-Ras2-/--null mice, OLs show aberrant morphologies and fail to differentiate correctly into myelin-forming phenotypes. The smaller OL population and abnormal OL maturation induce severe hypomyelination, with shorter nodes of Ranvier in R-Ras1-/- and/or R-Ras2-/- mice. These defects explain the slower conduction velocity of myelinated axons that we observed in the absence of R-Ras1 and R-Ras2. Together, these results suggest that R-Ras1 and R-Ras2 are upstream elements that regulate the survival and differentiation of progenitors into OLs through the PI3K/Akt and Erk1/2-MAPK pathways for proper myelination.SIGNIFICANCE STATEMENT In this study, we show that R-Ras1 and R-Ras2 play essential roles in regulating myelination in vivo and control fundamental aspects of oligodendrocyte (OL) survival and differentiation through synergistic activation of PI3K/Akt and Erk1/2-MAPK signaling. Mice lacking R-Ras1 and/or R-Ras2 show a diminished OL population with a higher proportion of immature OLs, explaining the observed hypomyelination in main CNS tracts. In vivo electrophysiology recordings demonstrate a slower conduction velocity of nerve impulses in the absence of R-Ras1 and R-Ras2. Therefore, R-Ras1 and R-Ras2 are essential for proper axonal myelination and accurate neural transmission.