Multicenter external validation of prediction models for clinical outcomes after spinal fusion for lumbar degenerative disease.

BACKGROUND: Clinical prediction models (CPM), such as the SCOAP-CERTAIN tool, can be utilized to enhance decision-making for lumbar spinal fusion surgery by providing quantitative estimates of outcomes, aiding surgeons in assessing potential benefits and risks for each individual patient. External validation is crucial in CPM to assess generalizability beyond the initial dataset. This ensures performance in diverse populations, reliability and real-world applicability of the results. Therefore, we externally validated the tool for predictability of improvement in oswestry disability index (ODI), back and leg pain (BP, LP). METHODS: Prospective and retrospective data from multicenter registry was obtained. As outcome measure minimum clinically important change was chosen for ODI with ≥ 15-point and ≥ 2-point reduction for numeric rating scales (NRS) for BP and LP 12 months after lumbar fusion for degenerative disease. We externally validate this tool by calculating discrimination and calibration metrics such as intercept, slope, Brier Score, expected/observed ratio, Hosmer-Lemeshow (HL), AUC, sensitivity and specificity. RESULTS: We included 1115 patients, average age 60.8 ± 12.5 years. For 12-month ODI, area-under-the-curve (AUC) was 0.70, the calibration intercept and slope were 1.01 and 0.84, respectively. For NRS BP, AUC was 0.72, with calibration intercept of 0.97 and slope of 0.87. For NRS LP, AUC was 0.70, with calibration intercept of 0.04 and slope of 0.72. Sensitivity ranged from 0.63 to 0.96, while specificity ranged from 0.15 to 0.68. Lack of fit was found for all three models based on HL testing. CONCLUSIONS: Utilizing data from a multinational registry, we externally validate the SCOAP-CERTAIN prediction tool. The model demonstrated fair discrimination and calibration of predicted probabilities, necessitating caution in applying it in clinical practice. We suggest that future CPMs focus on predicting longer-term prognosis for this patient population, emphasizing the significance of robust calibration and thorough reporting.

TREATMENT OF SEVERE HYPERTRIGLYCERIDEMIA THROUGH THERAPEUTIC PLASMA EXCHANGE IN PATIENTS WITH ACUTE PANCREATITIS OR AT RISK OF DEVELOPING IT. / TRATAMIENTO DE LA HIPERTRIGLICERIDEMIA GRAVE MEDIANTE RECAMBIO PLASMÁTICO TERAPÉUTICO EN PACIENTES CON PANCREATITIS AGUDA O EN RIESGO DE PADECERLA.

INTRODUCTION AND OBJECTIVES: TPE drastically reduces serum triglyceride (sTG), but its role in the treatment of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) or at risk of developing it, is not well established. The objectives were to assess the effectiveness and safety of TPE in the treatment of severe HTG (sHTG), as well as to evaluate the severity of HTG-AP treated with TPE. MATERIALS AND METHODS: Observational-retrospective-single-center study, in which a descriptive analysis of sHTG treated with TPE was conducted, with the aim of treating HTG-AP or preventing its recurrence. TPE was performed if sTG≥ 1000 mg/dL after 24 hours of admission. RESULTS: 42 TPE were performed to treat 35 sHTG in 23 patients: 29 HTG-AP, and 6 sHTG with previous HTG-AP. Among the patients, 37% (13/55) were women, with 37±14 years-old, 74.3% had normal BMI (25/35), 34% (12/35) were drinking >40 g/alcohol/day and 54% (19/35) were diabetics. TPE significantly reduced the baseline sTG (4425±2782 mg/dL vs. 709±353 mg/dL, p<0.001) in a single session, achieving a mean percentage reduction of 79±13%; 20% (7/35) of sHTG cases required two TPE sessions to reduce sTG to <1000 mg/dL. Adverse effects were reported in 4/42 TPE sessions (9,5%). sHTG-AP was observed in 3% of cases (1/29), and there were no deaths. sTG at 24 hours of admission showed no relation with the severity of APs. CONCLUSION: The treatment of sHTG with TPE, with the aim of treating HTG-AP or preventing its recurrence, reduces sTG quickly and safety.

Anterior Approach for Pediatric Supracondylar Humerus Fractures: A Systematic Review. / Abordaje Anterior para Fracturas Supracondíleas de Húmero Pediátrica: Revisión Sistemática.

Background and Purpose Open reduction is rarely performed in pediatric supracondylar humerus fractures. However, clear evidence is lacking regarding the optimal open approach to achieve satisfactory results. The anterior approach provides direct visualization of the fracture and excellent exposure to neurovascular structures, although its utilization is less common. The objective of this study was to review the indications, outcomes, and complications associated with the anterior approach for open reduction of these fractures. Methods Our protocol was registered at PROSPERO: CRD42023446923. MEDLINE/PubMed, Embase, Web of Science, Clinicaltrials.gov, and Cochrane Library were searched from database inception to search date (December 2023) and screened in duplicate for relevant studies. Data were collected regarding patient demographics, indications for open reduction, Flynn's functional and cosmetic outcomes, and complications. Study quality was assessed using the Methodological Index for Non-Randomized Studies Criteria. Results A total of 19 studies involving 483 patients were included. One study was classified as Level 2 evidence, ten as Level 3, and eight as Level 4. The mean MINORS score was 13.05 ± 3.47. The primary indication for open reduction was failed closed reduction, observed in 46% of patients. 97.7% and 98.6% of patients achieved Flynn's functional and cosmetic satisfactory results, respectively. The postsurgical neurovascular injury rate was 1.4%. One patient required reintervention. Conclusion The anterior approach is safe and effective for managing pediatric supracondylar humerus fractures requiring open reduction. Level of Evidence: Systematic review of Level 2-4 evidence studies.

Bidirectional modulation of synaptic transmission by insulin-like growth factor-I.

Insulin-like growth factor-I (IGF-I) plays a key role in the modulation of synaptic plasticity and is an essential factor in learning and memory processes. However, during aging, IGF-I levels are decreased, and the effect of this decrease in the induction of synaptic plasticity remains unknown. Here we show that the induction of N-methyl-D-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP) at layer 2/3 pyramidal neurons (PNs) of the mouse barrel cortex is favored or prevented by IGF-I (10 nM) or IGF-I (7 nM), respectively, when IGF-I is applied 1 h before the induction of Hebbian LTP. Analyzing the cellular basis of this bidirectional control of synaptic plasticity, we observed that while 10 nM IGF-I generates LTP (LTPIGF-I) of the post-synaptic potentials (PSPs) by inducing long-term depression (LTD) of the inhibitory post-synaptic currents (IPSCs), 7 nM IGF-I generates LTD of the PSPs (LTDIGF-I) by inducing LTD of the excitatory post-synaptic currents (EPSCs). This bidirectional effect of IGF-I is supported by the observation of IGF-IR immunoreactivity at both excitatory and inhibitory synapses. Therefore, IGF-I controls the induction of Hebbian NMDAR-dependent plasticity depending on its concentration, revealing novel cellular mechanisms of IGF-I on synaptic plasticity and in the learning and memory machinery of the brain.

Effect of early vs. delayed extubation on functional outcome among patients with acute ischemic stroke treated with endovascular thrombectomy under general anesthesia: the prospective, randomized controlled EDESTROKE trial study protocol.

BACKGROUND: Recent meta-analyses and randomized studies have shown that among patients with acute ischemic stroke undergoing endovascular thrombectomy, general anesthesia with mechanical ventilation is associated with better functional status compared to local anesthesia and sedation, and they recommend its use. But once the procedure is completed, when is the optimal moment for extubation? Currently, there are no guidelines recommending the optimal moment for extubation. Prolonged mechanical ventilation time could potentially be linked to increased complications such as pneumonia or disturbances in cerebral blood flow due to the vasodilatation produced by most anesthetic drugs. However, premature extubation in a patient who has suffered a stroke could led to complications such as agitation, disorientation, abolished reflexes, sudden fluctuations in blood pressure, alterations in cerebral blood flow, respiratory distress, bronchial aspiration, and the need for reintubation. We therefore designed a randomized study hypothesizing that early compared with delayed extubation is associated with a better functional outcome 3 months after endovascular thrombectomy treatment under general anesthesia for acute ischemic stroke. METHODS: This investigator-initiated, single-center, prospective, parallel, evaluated blinded, superiority, randomized controlled trial will include 178 patients with a proximal occlusion of the anterior circulation treated with successful endovascular thrombectomy (TICI 2b-3) under general anesthesia. Patients will be randomly allocated to receive early (< 6 h) or delayed (6-12 h) extubation after the procedure. The primary outcome measure is functional independence (mRS of 0-2) at 90 days, measured with the modified Rankin Score (mRS), ranging from 0 (no symptoms) to 6 (death). DISCUSSION: This will be the first trial to compare the effect of mechanical ventilation duration (early vs delayed extubation) after satisfactory endovascular thrombectomy for acute ischemic stroke under general anesthesia. TRIAL REGISTRATION: The study protocol was approved April 11, 2023, by the by the Santiago-Lugo Research Ethics Committee (CEI-SL), number 2023/127, and was registered into the clinicaltrials.gov clinical trials registry with No. NCT05847309. Informed consent is required. Participant recruitment begins on April 18, 2023. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences.

External validation of three diabetes prediction scores in a Spanish cohort: does adding high risk for depression improve the validation of the FINDRISC score (FINDRISC-MOOD)?

OBJECTIVES: To evaluate the external validity of the FINDRISC, DESIR and ADA risk scores for the prediction of diabetes in a Spanish population aged >45 years and to test the possible improvement of FINDRISC by adding a new variable of high risk of depression when Patient Health Questionnaire-9 (PHQ-9) questionnaire score ≥10 (FINDRISC-MOOD). DESIGN: Prospective population-based cohort study. SETTING: 10 primary healthcare centres in the north of the city of Madrid (Spain). PARTICIPANTS: A total of 1242 participants without a history of diabetes and with 2-hour oral glucose tolerance test (OGTT) plasma glucose <200 mg/dL (<11.1 mmol/L) were followed up for 7.3 years (median) using their electronic health records (EHRs) and telephone contact. PRIMARY AND SECONDARY OUTCOME MEASURES: Diabetes risk scores (FINDRISC, DESIR, ADA), PHQ-9 questionnaire and 2-hour-OGTT were measured at baseline. Incident diabetes was defined as treatment for diabetes, fasting plasma glucose ≥126 mg/dL (≥7.0 mmol/L), new EHR diagnosis or self-reported diagnosis. External validation was performed according to optimal cut-off, sensitivity, specificity and Youden Index. Comparison between diabetes risk scores, including FINDRISC-MOOD (original FINDRISC score plus five points if PHQ-9 ≥10), was measured by area under the receiver operating characteristic curve (AUROC). RESULTS: During follow-up, 104 (8.4%; 95% CI, 6.8 to 9.9) participants developed diabetes and 185 had a PHQ-9 score ≥10. The AUROC values were 0.70 (95% CI, 0.67 to 0.72) for FINDRISC-MOOD and 0.68 (95% CI, 0.65 to 0.71) for the original FINDRISC. The AUROCs for DESIR and ADA were 0.66 (95% CI, 0.63 to 0.68) and 0.66 (95% CI, 0.63 to 0.69), respectively. There were no significant differences in AUROC between FINDRISC-MOOD and the other scores. CONCLUSIONS: The results of FINDRISC-MOOD were like those of the other risk scores and do not allow it to be recommended for clinical use.

Shaping the curve from the microscopic transsphenoidal to the endoscopic endonasal approach for the sellar region.

OBJECTIVE: This study aimed to investigate the limitations, barriers, and complications in the early transition from the microscopic transsphenoidal approach (MTA) to the endonasal endoscopic approach (EEA) to the skull base in our institution. METHODS: Technical challenges, as well as clinical features and complications, were compared between MTA, EEA, and mixed cases during the early surgical curve. RESULTS: The period from the early learning curve was 1 year until the EEA protocol was used routinely. A total of 34 patients registered a resection using a transsphenoidal approach. Eighteen patients underwent EEA, 11 underwent MTA, and five underwent a mixed endonasal and microscopic approach. Non-significant differences were found in endocrine outcomes between the three groups. Patients with unchanged or improved visual function were higher in the EEA group (p = 0.147). Non-significant differences were found in terms of the extent of resection (EOR) between groups (p = 0.369). Only 1 (2.9%) patient in the whole series developed a post-operative CSF leaking that resolved with medical management, belonging to the EEA group (5.5%). CONCLUSIONS: The early phase of the learning curve did not affect our series significantly in terms of the EOR, endocrine status, and visual outcomes.

OBJETIVO: Investigar las limitaciones, las barreras y las complicaciones en la transición del abordaje transesfenoidal microscópico (ATM) al abordaje endonasal endoscópico (AEE) para la base del cráneo en nuestra institución. MÉTODO: Se compararon las características clínicas y las complicaciones entre ATM, AEE y casos mixtos durante la curva quirúrgica temprana. RESULTADOS: El periodo desde la curva de aprendizaje inicial fue de 1 año hasta que se utilizó el protocolo AEE de forma sistemática. Un total de 34 pacientes tuvieron una resección por vía transesfenoidal. A 18 pacientes se les realizó AEE, a 11 ATM y a 5 abordaje mixto endonasal y microscópico. Se encontraron diferencias no significativas en los resultados endocrinos entre los tres grupos. Los pacientes con función visual sin cambios o mejorada fueron más en el grupo AEE (p = 0.147). No se encontraron diferencias significativas respecto a la extensión de la resección (p = 0.369). Solo 1 (2.9%) paciente desarrolló una fístula de líquido cefalorraquídeo que se resolvió con manejo médico, perteneciente al grupo AEE (5.5%). CONCLUSIONES: La fase inicial de la curva de aprendizaje no afectó significativamente a nuestra serie en términos de extensión de la resección, estado endocrino y resultados visuales.

Testing and Diagnosis of Clostridioides difficile Infection in Special Scenarios: A Systematic Review.

INTRODUCTION: Clostridioides difficile infection (CDI) is a clinical and laboratory diagnosis. Populations at higher risk of developing disease require a high clinical index of suspicion for laboratory testing to avoid incorrect assumptions of colonization. Common risk factors include recent antibiotic use, elderly (>65 years old), and immunocompromised patients. C. difficile assays should be ordered in an algorithm approach to diagnose an infection rather than colonization. Screening tests are widely available in hospital systems, but novel molecular testing may aid in diagnosis in patients with inconclusive or discordant antigen and toxin test results.  Methods: Data was extracted from PubMed, Scopus, and Cumulative Index of Nursing and Allied Health Literature (CINAHL) databases based on the keywords "clostridioides difficile", "toxin assay", and "toxic megacolon". The data extracted is based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A total of 27 reports were included in this systematic review. RESULTS: Testing patients with a significant gastrointestinal surgical history, hypogammaglobulinemia, inflammatory bowel disease, intensive care unit, and immunocompromised patients for CDI is highly recommended. Diarrhea in these subsets of patients requires correlation of clinical context and an understanding of assay results to avoid over- and under-treating. CONCLUSION: CDI should be considered in all patients with traditional risk factors. Heightened clinical suspicion of CDI is required in patients with hypogammaglobulinemia, transplant recipients, patients with gastrointestinal surgical history, and inflammatory bowel disease. Testing should be limited to patients with clinical manifestations of CDI to ensure a high pretest probability for test interpretation. Healthcare workers should adhere to testing algorithms to optimize yield in the appropriate clinical context. Diagnostic assays should follow a sequential, stepwise approach to categorize the toxin expression status of the bacteria accurately.

A Male Patient Presents With Isolated Abducens Nerve Palsy: An Atypical Presentation of Ocular Myasthenia Gravis.

Myasthenia gravis is an autoimmune disease of the neuromuscular junction caused by autoantibodies directed against the acetylcholine receptors. It presents with skeletal muscle weakness, often initially presenting with ocular symptoms such as ptosis and diplopia. When myasthenia gravis is isolated to only ocular symptoms, it is referred to as ocular myasthenia gravis (OMG). Here, we present an atypical initial presentation of OMG in a 68-year-old male patient presenting with isolated abducens nerve palsy at the initial onset. With this case report, we highlight the importance of a thorough history and clinical assessment necessary for a timely diagnosis of OMG in patients who present with isolated abducens nerve palsy.

Sourdough Yeast Strains Exhibit Thermal Tolerance, High Fermentative Performance, and a Distinctive Aromatic Profile in Beer Wort.

The increasing popularity of home brewing and the fast evolution of craft beer companies have fuelled the interest in novel yeasts as the main actors diversifying the beer portfolio. Here, we have characterized the thermal tolerance and brewing-related features of two sourdough (SD) isolates of Saccharomyces cerevisiae, SDy01 and SDy02, at different temperatures, 20 and 37 °C, comparing them with commercial brew strains, AaB and kNB. The SD strains exhibited tolerance to the main brewing-related stress conditions and increased growth rates and lower lag phases than the reference beer strains at both temperatures. Consistent with this, SDy01 and SDy02 displayed higher fermentative activity in terms of sugar rate depletion and the release of metabolic by-products. Moreover, SDy01 and SDy02 brewing at 20 °C increased their total amount of volatile compounds (VOCs), in particular, their esters and carboxyl compounds, as compared to the reference AaB strain. In contrast, fermentation at 37 °C resulted in a drastic reduction in the number of VOCs in wort fermented with SD yeast, especially in its level of esters. In conclusion, our results stress the high fermentative performance of SD strains in beer wort and their ability to provide a complex and specific aromatic profile at a wide range of temperatures.

Bioprospecting of sourdough microbial species from artisan bakeries in the city of Valencia.

This work describes the characterization of an artisanal sourdough set of bakeries located in the city of Valencia. Culture-dependent and -independent analyses detected Fructilactobacillus sanfranciscensis, Saccharomyces cerevisiae and Kazachstania humilis as dominant species. Nevertheless, specific technological parameters, including backslopping temperature, dough yield, or the addition of salt affected microbial counting, LAB/Yeast ratio, and gassing performance, favouring the appearance of several species of Lactobacillus sp., Limosilactobacillus pontis or Torulaspora delbrueckii as additional players. Sourdough leavening activity was affected positively by yeast counts and negatively by the presence of salt. In addition, the predominance of a particular yeast species appeared to impact the dynamics of CO2 release. Seven important flavour-active compounds (ethyl acetate, 1-hexanol, 2-penthylfuran, 3-ethyl-2-methyl-1,3-hexadiene, 2-octen-1-ol, nonanal and 1-nonanol) were detected in all samples and together with 3-methyl butanol and hexyl acetate represented more than the 53% of volatile abundancy in nine of the ten sourdoughs analysed. Even so, the specific microbial composition of each sample influenced the volatile profile. For example, the occurrence of K. humilis or S. cerevisiae as dominant yeast influenced the composition of major alcohol species, while F. sanfranciscensis and L. pontis positively correlated with aldehydes and octanoic acid content. In addition, relevant correlations could be also found among different technological parameters and between these, volatile compounds and microbial species. Overall, our study emphasises on how differences in technological parameters generate biodiversity in a relatively small set of artisan sourdoughs providing opportunities for excellence and quality baking products.

Balancing Act: A Comprehensive Review of Vestibular Evaluation in Cochlear Implants.

Cochlear implantation, a transformative intervention for individuals with profound hearing loss, has evolved significantly over the years. However, its impact on the vestibular system, responsible for balance and spatial orientation, remains a subject of ongoing research and clinical consideration. This narrative review highlights key aspects of vestibular evaluation in patients undergoing cochlear implantation. Preoperative vestibular assessment is crucial to establish baseline vestibular function and identify any pre-existing balance issues. Various tests, including caloric, rotational chair, vestibular-evoked myogenic potential, and video head impulse tests, play a vital role in evaluating vestibular function. The goal is to assess the risk of vestibular disturbances arising from the surgery, guide surgical planning, and detect pre-existing alterations that could be totally or partially compensated. While some patients experience minimal vestibular disruptions, others may encounter transient or persistent balance issues following cochlear implant surgery. Postoperative vestibular testing allows for the early detection of such disturbances, enabling timely interventions like vestibular rehabilitation and evaluating changes produced due to surgical complications or changes in the patient's prior conditions. Challenges in vestibular evaluation include individual variability in patient responses, the proximity of the cochlea to the vestibular system, and the need to tailor testing protocols to individual needs. Further research is essential to refine testing protocols, minimize vestibular disturbances, and improve outcomes for cochlear implant candidates. A multidisciplinary approach involving otolaryngologists, audiologists, and physical therapists is integral to comprehensive patient care in this context. In conclusion, vestibular evaluation in patients undergoing cochlear implantation is critical for optimizing surgical planning, managing postoperative issues, and enhancing the overall quality of life for individuals embarking on the journey of restored hearing.

Cytotoxicity and concentration of silver ions released from dressings in the treatment of infected wounds: a systematic review.

Introduction: Silver-releasing dressings are used in the treatment of infected wounds. Despite their widespread use, neither the amount of silver released nor the potential in vivo toxicity is known. The aim of this study was to evaluate the cytotoxic effects and the amount of silver released from commercially available dressings with infected wounds. Methods: The review was conducted according to the PRISMA statement. The Web of Science, PubMed, Embase, Scopus, and CINAHL databases were searched for studies from 2002 through December 2022. The criteria were as follows: population (human patients with infected wounds); intervention (commercial dressings with clinical silver authorized for use in humans); and outcomes (concentrations of silver ions released into tissues and plasma). Any study based on silver-free dressings, experimental dressings, or dressings not for clinical use in humans should be excluded. According to the type of study, systematic reviews, experimental, quasi-experimental, and observational studies in English, Spanish, or Portuguese were considered. The quality of the selected studies was assessed using the JBI critical appraisal tools. Studies that assessed at least 65% of the included items were included. Data were extracted independently by two reviewers. Results: 740 articles were found and five were finally selected (all of them quasi-experimental). Heterogeneity was found in terms of study design, application of silver dressings, and methods of assessment, which limited the comparability between studies. Conclusion: In vivo comparative studies of clinical dressings for control of infection lack a standardized methodology that allows observation of all the variables of silver performance at local and systemic levels, as well as evaluation of its cytotoxicity. It cannot be concluded whether the assessed concentrations of released silver in commercial dressings for the topical treatment of infected wounds are cytotoxic to skin cells. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022351041, PROSPERO [CRD42022351041].

Economic evaluation of high tibial osteotomy: Closing wedge is more cost-effective than open wedge technique when analysing the KOOS-12 improvement.

PURPOSE: The purpose of this study was to compare the cost-effectiveness of two techniques for performing a knee valgus osteotomy: opening wedge high tibial osteotomy (OW-HTO) vs closing wedge high tibial osteotomy (CW-HTO). METHODS: In this economic evaluation study, a cost-effectiveness analysis from the perspective of the Spanish public healthcare system was performed, comparing OW-HTO with CW-HTO. All patients with medial knee osteoarthritis who underwent one of these procedures between 2018 and 2020 in our institution were included. The cost analysis included operating room, implant, graft and hospital admission costs. Functional outcomes (KOOS-12, Tegner activity scale, pain and satisfaction) and radiological outcomes (hip-knee-ankle angle, medial proximal tibial angle, tibial slope and patellar height) were analysed. The cost-effectiveness ratio was obtained by calculating the cost of improving the minimal clinically important difference (MCID) of KOOS-12 for each procedure. All costs are expressed in 2020 euros. RESULTS: Fifty-one patients met the inclusion criteria (27 OW-HTO and 24 CW-HTO). Good to excellent functional outcomes, significant pain reduction (>6 points) and high patient satisfaction (>9/10) were observed in both groups. Both techniques yielded excellent radiological outcomes. N.s. differences in functional or radiological outcomes improvements between both procedures were found. However, the OW-HTO group presented a higher total cost than the CW-HTO group (4612.1 ± 765.6€ vs. 1827.1 ± 701.9€; p < 0.001). The cost-effectiveness ratio was 818.1 ± 46.8 €/MCID for the CW-HTO procedure and 2414.3 ± 115.2 €/MCID for the OW-HTO procedure (p = 0.025). CONCLUSION: The CW-HTO procedure presented a cost-effectiveness ratio almost three times lower than the OW-HTO procedure. Both techniques allowed to achieve of good to excellent functional outcomes, significant pain reduction and high patient satisfaction while correcting the varus limb malalignment and the metaphyseal tibial varus in patients with medial compartment osteoarthritis. LEVEL OF EVIDENCE: Level III; economic study.

Consensus document for lipid profile testing and reporting in Spanish clinical laboratories: what parameters should a basic lipid profile include?

Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports.

Altered calcium signaling in Bergmann glia contributes to spinocerebellar ataxia type-1 in a mouse model of SCA1.

Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease caused by an abnormal expansion of glutamine (Q) encoding CAG repeats in the ATAXIN1 (ATXN1) gene and characterized by progressive cerebellar ataxia, dysarthria, and eventual deterioration of bulbar functions. SCA1 shows severe degeneration of cerebellar Purkinje cells (PCs) and activation of Bergmann glia (BG), a type of cerebellar astroglia closely associated with PCs. Combining electrophysiological recordings, calcium imaging techniques, and chemogenetic approaches, we have investigated the electrical intrinsic and synaptic properties of PCs and the physiological properties of BG in SCA1 mouse model expressing mutant ATXN1 only in PCs. PCs of SCA1 mice displayed lower spontaneous firing rate and larger slow afterhyperpolarization currents (sIAHP) than wildtype mice, whereas the properties of the synaptic inputs were unaffected. BG of SCA1 mice showed higher calcium hyperactivity and gliotransmission, manifested by higher frequency of NMDAR-mediated slow inward currents (SICs) in PC. Preventing the BG calcium hyperexcitability of SCA1 mice by loading BG with the calcium chelator BAPTA restored sIAHP and spontaneous firing rate of PCs to similar levels of wildtype mice. Moreover, mimicking the BG hyperactivity by activating BG expressing Gq-DREADDs in wildtype mice reproduced the SCA1 pathological phenotype of PCs, i.e., enhancement of sIAHP and decrease of spontaneous firing rate. These results indicate that the intrinsic electrical properties of PCs, but not their synaptic properties, were altered in SCA1 mice and that these alterations were associated with the hyperexcitability of BG. Moreover, preventing BG hyperexcitability in SCA1 mice and promoting BG hyperexcitability in wildtype mice prevented and mimicked, respectively, the pathological electrophysiological phenotype of PCs. Therefore, BG plays a relevant role in the dysfunction of the electrical intrinsic properties of PCs in SCA1 mice, suggesting that they may serve as potential targets for therapeutic approaches to treat the spinocerebellar ataxia type 1.

Consensus document for lipid profile determination and reporting in Spanish clinical laboratories. What parameters should be included in a basic lipid profile?

Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports.

Semi-supervised learning for industrial fault detection and diagnosis: A systemic review.

The automation of Fault Detection and Diagnosis (FDD) is a central task for many industries today. A myriad of methods are in use, although the most recent leading contenders are data-driven approaches and especially Machine Learning (ML) methods. ML algorithms fall into two main categories: supervised and unsupervised methods, depending on whether or not the instances are labeled with the expected outputs. However, a new approach called Semi-Supervised Learning (SSL) has recently emerged that uses a few labeled instances together with other unlabeled instances for the training process. This new approach can significantly improve the accuracy of conventional ML models for industrial environments where labeled data are scarce. SSL has been tested as a promising solution over the past few years for several FDD problems, although there have been no systemic reviews of this sort of approach up until the present review. In this study, an attempt to organize the existing literature on SSL for FDD using the taxonomy of van Engelen & Hoos is reported. The most and the least frequently used SSL algorithms are identified and considered in terms of different fault detection tasks and their most common dataset structure. Moreover, a set of best practices are proposed in the conclusions of this work for implementation under real industrial conditions, so as to avoid some of the most common faults.

Adaptive laboratory evolution for acetic acid-tolerance matches sourdough challenges with yeast phenotypes.

Acetic acid tolerance of Saccharomyces cerevisiae is an important trait in sourdough fermentation processes, where the accumulation of acid by the growth of lactic acid bacteria reduces the yeast metabolic activity. In this work, we have carried out adaptive laboratory evolution (ALE) experiments in two sourdough isolates of S. cerevisiae exposed to acetic acid, or alternatively to acetic acid and myriocin, an inhibitor of sphingolipid biosynthesis that sped-up the evolutionary adaptation. Evolution approaches resulted in acetic tolerance, and surprisingly, increased lactic susceptibility. Four evolved clones, one from each parental strain and evolutionary scheme, were selected on the basis of their potential for CO2 production in sourdough conditions. Among them, two showed phenotypic instability characterized by strong lactic sensitivity after several rounds of growth under unstressed conditions, while two others, displayed increased constitutive acetic tolerance with no loss of growth in lactic medium. Genome sequencing and ploidy level analysis of all strains revealed aneuploidies, which could account for phenotypic heterogeneity. In addition, copy number variations (CNVs), affecting specially to genes involved in ion transport or flocculation, and single nucleotide polymorphisms (SNPs) were identified. Mutations in several genes, ARG82, KEX1, CTK1, SPT20, IRA2, ASG1 or GIS4, were confirmed as involved in acetic and/or lactic tolerance, and new determinants of these phenotypes, MSN5 and PSP2, identified.

Family Planning in Fertile-Age Patients With Multiple Sclerosis (MS) (ConPlanEM Study): Delphi Consensus Statements.

Family planning is essential for establishing Multiple Sclerosis (MS) prognosis, treatment decision, and disease monitoring. We aimed to generate an expert consensus addressing recommendations for family planning in MS patients of childbearing age. Initially, a committee comprising seven neurologists, experts in the MS field, identified the topics to be addressed. Then, the committee elaborated on different evidence-based preliminary statements. Next, using the Delphi methodology, a panel of neurologists manifested their level of agreement on the different statements using a Likert-type scale. Consensus was reached when ⩾70% of respondents expressed an agreement or disagreement using a five-point scale. Consensus was achieved on 47 out of 63 recommendations after three rounds of evaluations. The panel considered it essential to address family planning in all patients of childbearing age. There was also consensus that treatment should not be delayed due to the patient's desire for pregnancy. Additionally, in highly active patients, planning the pregnancy in the medium to long term using depletory drugs such as cladribine or alemtuzumab might represent a useful strategy. However, risks of adverse effects on the fetus due to drug-associated secondary autoimmunity should be addressed when alemtuzumab is considered. Moreover, the maintenance of natalizumab during pregnancy in very active patients reached expert consensus. Also, the panel supported the use of certain disease-modifying treatment (DMT) during lactation in selected cases. Our results identified specific areas of pregnancy planning in MS patients, where different treatment strategies might be considered to facilitate a safe and successful pregnancy while maintaining clinical and radiological stability.