Analysis of the university experience of undergraduate students of Education degrees.

The evaluation of the university experience of students is an increasingly frequent field of analysis among the academic community, as they represent one of the most important groups in universities and it is essential to know their opinion and satisfaction with the different services and resources that the university institution makes available to them. In this sense, the two objectives of the study were the following: 1) To analyse the undergraduate university experience of the different groups of students (graduates, students, drop-outs). 2) To identify which aspects of the academic training received predict each of the student groups. To this end, a study was carried out specifically aimed at undergraduate education students at the University of Granada (Spain), distinguishing between graduates, students, and those who had dropped out of their studies. A total of 292 students participated (82 female and 210 male), of whom 123 were graduates, 98 were still students and 71 were drop-outs. After the application of three questionnaires, it was found that the three aforementioned groups of participants coincided in particularly valuing characteristic dimensions of the formal teaching-learning scenario in the university experience. In addition, the linear regression analysis carried out identified the personalised attention factor as having the highest predictive value as regards student type. Thus, the results of the study point to an assessment of academic training focused on the need on the part of all three groups of participants for teacher support and individualised guidance. The study may be useful in providing universities with new data to help improve the teaching performance of Education degree teaching staff concerning students; for example, by encouraging their participation in tutorial action programmes.

Rearrangements involving 11q23.3/KMT2A in adult AML: mutational landscape and prognostic implications - a HARMONY study.

Balanced rearrangements involving the KMT2A gene (KMT2Ar) are recurrent genetic abnormalities in acute myeloid leukemia (AML), but there is lack of consensus regarding the prognostic impact of different fusion partners. Moreover, prognostic implications of gene mutations co-occurring with KMT2Ar are not established. From the HARMONY AML database 205 KMT2Ar adult patients were selected, 185 of whom had mutational information by a panel-based next-generation sequencing analysis. Overall survival (OS) was similar across the different translocations, including t(9;11)(p21.3;q23.3)/KMT2A::MLLT3 (p = 0.756). However, independent prognostic factors for OS in intensively treated patients were age >60 years (HR 2.1, p = 0.001), secondary AML (HR 2.2, p = 0.043), DNMT3A-mut (HR 2.1, p = 0.047) and KRAS-mut (HR 2.0, p = 0.005). In the subset of patients with de novo AML < 60 years, KRAS and TP53 were the prognostically most relevant mutated genes, as patients with a mutation of any of those two genes had a lower complete remission rate (50% vs 86%, p < 0.001) and inferior OS (median 7 vs 30 months, p < 0.001). Allogeneic hematopoietic stem cell transplantation in first complete remission was able to improve OS (p = 0.003). Our study highlights the importance of the mutational patterns in adult KMT2Ar AML and provides new insights into more accurate prognostic stratification of these patients.

Effect of calcium soaps from garlic (Allium sativum) and willow (Salix babylonica) extracts on nematode loads, nutrient intake and digestibility, nitrogen balance and rumen fermentation kinetics in dairy goats.

The objective of this study was to determine the effect of dietary calcium soaps from garlic (Allium sativum) and willow (Salix babylonica) extracts on nematode loads, nutrient intake and digestibility, nitrogen balance and rumen fermentation kinetics in dairy goats. Nine adult non-lactating Saanen goats were grouped into a complete randomized block design with 3 treatments (n = 3) over a period of 28 d. Animals were fed a diet based on alfalfa hay and a concentrate that was supplemented (65 g/kg DM) with calcium soaps of safflower (control), garlic or willow. Intake of dry matter (DM), organic matter (OM) and neutral detergent fiber (NDF) were not affected by dietary calcium soaps. However, the highest digestibility of DM and OM were observed in willow supplemented goats. In vitro gas kinetics and fermentation profile were not affected by diets. Results from fecal egg count indicated a reduction in total count, Haemonchus spp. and Trychostrongylus spp. for both garlic and willow compared to control. Our results suggest that calcium soaps of garlic or willow extracts can be used to reduce gastrointestinal parasites in goats without compromising productive traits or rumen function.

Developmental outcome of electroencephalographic findings in SYNGAP1 encephalopathy.

SYNGAP1 haploinsufficiency results in a developmental and epileptic encephalopathy (DEE) causing generalized epilepsies accompanied by a spectrum of neurodevelopmental symptoms. Concerning interictal epileptiform discharges (IEDs) in electroencephalograms (EEG), potential biomarkers have been postulated, including changes in background activity, fixation-off sensitivity (FOS) or eye closure sensitivity (ECS). In this study we clinically evaluate a new cohort of 36 SYNGAP1-DEE individuals. Standardized questionnaires were employed to collect clinical, electroencephalographic and genetic data. We investigated electroencephalographic findings, focusing on the cortical distribution of interictal abnormalities and their changes with age. Among the 36 SYNGAP1-DEE cases 18 presented variants in the SYNGAP1 gene that had never been previously reported. The mean age of diagnosis was 8 years and 8 months, ranging from 2 to 17 years, with 55.9% being male. All subjects had global neurodevelopmental/language delay and behavioral abnormalities; 83.3% had moderate to profound intellectual disability (ID), 91.7% displayed autistic traits, 73% experienced sleep disorders and 86.1% suffered from epileptic seizures, mainly eyelid myoclonia with absences (55.3%). A total of 63 VEEGs were revised, observing a worsening of certain EEG findings with increasing age. A disorganized background was observed in all age ranges, yet this was more common among older cases. The main IEDs were bilateral synchronous and asynchronous posterior discharges, accounting for ≥50% in all age ranges. Generalized alterations with maximum amplitude in the anterior region showed as the second most frequent IED (≥15% in all age ranges) and were also more common with increasing age. Finally, diffuse fast activity was much more prevalent in cases with 6 years or older. To the best of our knowledge, this is the first study to analyze EEG features across different age groups, revealing an increase in interictal abnormalities over infancy and adolescence. Our findings suggest that SYNGAP1 haploinsufficiency has complex effects in human brain development, some of which might unravel at different developmental stages. Furthermore, they highlight the potential of baseline EEG to identify candidate biomarkers and the importance of natural history studies to develop specialized therapies and clinical trials.

Immune response of the Almaco jack (Seriola rivoliana) against the infestation with Neobenedenia sp. in three cultivated temperatures.

The Almaco jack (Seriola rivoliana) is a marine fish maintained in mariculture systems and frequently infested by monogenean parasites like Neobenedenia sp. Severe infestations can lead to high mortalities and economic losses for farmers. This study evaluated the effects of temperature on the immune response on Almaco jack infested with Neobenedenia sp. We exposed infested fishes at temperatures of 20 °C, 24 °C, and 30 °C for 20 days and took samples of different tissues at the beginning of the experiment, and after 3 and 20 days. The tissues considered were the skin, thymus, cephalic kidney, and spleen to evaluate the relative gene expression of different genes: Hsp70, IgM, IL-1ß, IL-10, and MyD88. Our results showed an increase in IL-1ß gene expression in the skin after 20 days of infestation but no significant effect of temperature on gene expression, despite increases in infestation rates with temperature. Therefore, relative genetic expression was controlled by the number of parasites and the days post-infestation. These results show that the parasite infestation induced a local response in the skin, but that temperature has an indirect effect on the immune system of Almaco jack.

Determinants of Tricuspid Regurgitation Progression and Its Implications for Adequate Management.

BACKGROUND: Tricuspid regurgitation (TR) is associated with an increased mortality. Previous studies have analyzed predictors of TR progression and the clinical impact of baseline TR. However, there is a lack of evidence regarding the natural history of TR: the pattern of change and clinical impact of progression. OBJECTIVES: The authors sought to evaluate predictors of TR progression and assess the prognostic impact of TR progression. METHODS: A total of 1,843 patients with at least moderate TR were prospectively followed up with consecutive echocardiographic studies and/or clinical evaluation. All patients with less than a 2-year follow-up were excluded. Clinical and echocardiographic features, hospitalizations for heart failure, and cardiovascular death and interventions were recorded to assess their impact in TR progression. RESULTS: At a median 2.3-year follow-up, 19% of patients experienced progression. Patients with baseline moderate TR presented a rate progression of 4.9%, 10.1%, and 24.8% 1 year, 2 years, and 3 years, respectively. Older age (HR: 1.03), lower body mass index (HR: 0.95), chronic kidney disease (HR: 1.55), worse NYHA functional class (HR: 1.52), and right ventricle dilation (HR: 1.33) were independently associated with TR progression. TR progression was associated with an increase in chamber dilation as well as a decrease in ventriculoarterial coupling and in left ventricle ejection fraction (P < 0.001). TR progression was associated with an increased cardiovascular mortality and hospitalizations for heart failure (P < 0.001). CONCLUSIONS: Marked individual variability in TR progression hindered accurate follow-up. In addition, TR progression was a determinant for survival regardless of initial TR severity.

NLRP3 inflammasome activation and symptom burden in KRAS-mutated CMML patients is reverted by IL-1 blocking therapy.

Chronic myelomonocytic leukemia (CMML) is frequently associated with mutations in the rat sarcoma gene (RAS), leading to worse prognosis. RAS mutations result in active RAS-GTP proteins, favoring myeloid cell proliferation and survival and inducing the NLRP3 inflammasome together with the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), which promote caspase-1 activation and interleukin (IL)-1ß release. Here, we report, in a cohort of CMML patients with mutations in KRAS, a constitutive activation of the NLRP3 inflammasome in monocytes, evidenced by ASC oligomerization and IL-1ß release, as well as a specific inflammatory cytokine signature. Treatment of a CMML patient with a KRASG12D mutation using the IL-1 receptor blocker anakinra inhibits NLRP3 inflammasome activation, reduces monocyte count, and improves the patient's clinical status, enabling a stem cell transplant. This reveals a basal inflammasome activation in RAS-mutated CMML patients and suggests potential therapeutic applications of NLRP3 and IL-1 blockers.

Endovascular Versus Surgical Treatment for All Comer Patients With Prosthetic Bypass Graft Occlusion: The Multicentre ENSUPRO Study.

OBJECTIVE: Bypass surgery plays a key role in complex lower limb lesions. However, there is a lack of evidence regarding the management of symptomatic prosthetic bypass graft (PBG) occlusion. This study aimed to report outcomes following open, hybrid, or endovascular management of patients presenting with symptomatic PBG occlusion. METHODS: A multicentre, retrospective cohort study was conducted, including patients presenting with PBG occlusion between January 2014 and December 2021 from 18 centres. It assessed the comparative value of treatment strategies, including (1) recanalisation of native vessels, (2) endovascular treatment of the failed PBG, (3) hybrid treatment, and (4) open surgery. The primary outcome measure was amputation free survival (AFS, time to major amputation and or death), whereas all cause mortality, major amputation, PBG re-occlusion, target lesion revascularisation (TLR), and Rutherford category (RC) improvement during follow up were considered as secondary endpoints. RESULTS: Of 260 patients with occluded PBGs, 108 (41.5%) were treated endovascularly (24 [22.2%] by recanalisation of native vessels and 84 [77.7%] by PBG re-opening), 57 (21.9%) underwent hybrid revascularisation, and 58 (22.3%) had surgery. In addition, 27 (10.4%) were treated conservatively and 10 (3.8%) received systemic thrombolysis. With a median follow up of 1.4 (0.6 - 3.0) years, AFS was 95.5%, 76.4%, 45.5%, and 37.1%, respectively in Groups 1 - 4 (p = .007). Older age and non-endovascular treatment (HR 1.05 and 1.70; p < .01 for both) were independent predictors of poor AFS. Endovascular treatment was associated with lower rates of major amputation (p = .04), PBG re-occlusion (p < .001), and TLR (p = .037), and higher RC improvements (p < .001), whereas all cause mortality was comparable between treatment groups (p = .21). CONCLUSION: Endovascular treatment is associated with higher rates of AFS and RC improvement and lower rates of PBG re-occlusion and TLR in patients with PBG occlusion.

Multimodal Imaging Features of the Posterior Segment in Ocular Syphilis and HIV Co-Infection: A Single Center Case Series.

OBJECTIVE: To analyze the frequent multimodal imaging features in posterior syphilitic uveitis. PURPOSE: Syphilis infection has re-emerged as a global health problem. Multimodal imaging approach has been proposed for diagnosis and follow-up; there are not previous reports dedicated to the anatomic and visual outcomes in patients diagnosed with ocular syphilis and concomitant HIV infection. METHODS: All demographic information was recovered; a complete ophthalmological examination and multimodal imaging evaluation (retinal fluorescein angiography (FA), autofluorescence (AF), optical coherence tomography (OCT)) were performed on initial visit and 1 month after antibiotic therapy. RESULTS: 18 eyes of 9 patients were included. The most frequent features observed were: Hyperfluorescence on optic disk on FA, Hyperautofluorescence punctate pattern on AF, Vitritis on SD-OCT. After treatment, there was a functional and anatomical improvement. CONCLUSION: Ocular syphilis represents a diagnostic challenge. Multimodal imaging approach allows identification of structural changes, follow-up and early detection of complications.

Mutational Profile Enables the Identification of a High-Risk Subgroup in Myelodysplastic Syndromes with Isolated Trisomy 8.

Trisomy 8 (+8) is the most frequent trisomy in myelodysplastic syndromes (MDS) and is associated with clinical heterogeneity and intermediate cytogenetic risk when found in isolation. The presence of gene mutations in this group of patients and the prognostic significance has not been extensively analyzed. Targeted deep sequencing was performed in a cohort of 79 MDS patients showing isolated +8. The most frequently mutated genes were: TET2 (38%), STAG2 (34.2%), SRSF2 (29.1%) and RUNX1 (26.6%). The mutational profile identified a high-risk subgroup with mutations in STAG2, SRSF2 and/or RUNX1, resulting in shorter time to acute myeloid leukemia progression (14 months while not reached in patients without these mutations, p < 0.0001) and shorter overall survival (23.7 vs. 46.3 months, p = 0.001). Multivariate analyses revealed the presence of mutations in these genes as an independent prognostic factor in MDS showing +8 isolated (HR: 3.1; p < 0.01). Moreover, 39.5% and 15.4% of patients classified as low/intermediate risk by the IPSS-R and IPSS-M, respectively, were re-stratified as a high-risk subgroup based on the mutational status of STAG2, SRSF2 and RUNX1. Results were validated in an external cohort (n = 2494). In summary, this study validates the prognosis significance of somatic mutations shown in IPSS-M and adds STAG2 as an important mutated gene to consider in this specific subgroup of patients. The mutational profile in isolated +8 MDS patients could, therefore, offer new insights for the correct management of patients with a higher risk of leukemic transformation.

Short-Term Thermal Effect of Continuous Ultrasound from 3 MHz to 1 and 0.5 W/cm2 Applied to Gastrocnemius Muscle.

Continuous ultrasound is recognized for its thermal effect and use in the tissue repair process. However, there is controversy about its dosage and efficacy. This study used infrared thermography, a non-invasive technique, to measure the short-term thermal effect of 3 MHz continuous ultrasound vs. a placebo, referencing the intensity applied. It was a single-blind, randomized clinical trial of 60 healthy volunteers (19-24 years old) divided into three equal groups. Group 1:1 W/cm2 for 5 min; Group 2: 0.5 W/cm2 for 10 min; and Group 3: the placebo for 5 min. The temperature was recorded through five thermographic images per patient: pre- and post-application, 5, 10, and 15 min later. After statistical analysis, a more significant decrease in temperature (p<0.05 ) was observed in the placebo group compared with the remaining groups after the application of continuous ultrasound. Group 1 was the one that generated the highest significant thermal effect (p<0.001), with an increase of 3.05 °C at 15 min, compared with the other two groups. It is concluded that to generate a thermal effect in the muscle, intensities of ≥1 W/cm2 are required, since the dosage maintained a temperature increase for more than 5 min.

Editor's Choice - RANDOMisation Screening for Drug coated or Drug Eluting Device Randomised Trials Among Patients Undergoing Endovascular FemorOPopliteal Procedures (RANDOM-STOP study).

OBJECTIVE: The aim was to assess the proportion of patients undergoing endovascular therapy for femoropopliteal arterial disease (FP) who would be eligible to take part in seven major randomised controlled trials (RCTs) that investigated the efficacy of some of the currently available paclitaxel based (PTX) devices used in this clinical context. Various RCTs have shown a potential clinical benefit from the use of paclitaxel in FP endovascular therapy. Nonetheless, patients enrolled were highly selected and the generalisability of these findings in pragmatic cohorts is unclear. METHODS: Between 1 January and 31 December 2021, all consecutive patients who underwent endovascular procedures for symptomatic FP disease in 16 European centres were retrospectively screened and included in this analysis. The primary outcome measure was individual patient eligibility for inclusion into at least one of the seven RCTs. The reasons for exclusion (clinical and or radiological) as well as in hospital death and morbidity were also reported. RESULTS: A total of 1 567 consecutive patients (959 male, 61%), corresponding to 1 567 lower limbs, were included. Most patients (1 009 patients, 64.39%) were treated for chronic limb threatening ischaemia (CLTI). A total 1 280 patients (81.68%) were not eligible for inclusion in any of the evaluated RCTs. Of them, 741 (47.28%) were excluded for clinical and 1 125 (71.79%) for radiological reasons. CONCLUSION: The analysed RCTs assessing the efficacy or effectiveness of PTX based endovascular therapies do not seem representative of the patient population with FP disease receiving endovascular therapy in routine clinical practice.

Adjusted morbidity groups and survival: a retrospective cohort study of primary care patients with chronic conditions.

BACKGROUND: Chronic conditions are one of the main determinants of frailty, functional disability, loss of quality of life and the number one cause of death worldwide. This study aimed to describe the survival of patients with chronic conditions who were followed up in primary care according to the level of risk by adjusted morbidity groups and to analyse the effects of sex, age, clinician and care factors on survival. METHODS: This was a longitudinal observational study of a retrospective cohort of patients with chronic conditions identified by the adjusted morbidity group stratifier of the electronic medical records in a primary health centre of the Region of Madrid, which has an assigned population of 18,107 inhabitants. The follow-up period was from June 2015 to June 2018. A description of survival according to the Kaplan-Meier method and Cox proportional hazards multivariate regression model was used to analyse the effects of sex, age, clinician and care factors. RESULTS: A total of 9,866 patients with chronic conditions were identified; 77.4% (7,638) had a low risk, 18.1% (1,784) had a medium risk, and 4.5% (444) had a high risk according to the adjusted morbidity groups. A total of 477 patients with chronic conditions died (4.8%). The median survival was 36 months. The factors associated with lower survival were age over 65 years (hazard ratio [HR] = 1.3; 95% confidence interval [CI] = 1.1-1.6), receiving palliative care (HR = 3.4; 95% CI = 2.6-4.5), high versus low risk level (HR = 2.4; 95% CI = 1.60-3.7), five chronic conditions or more (HR = 1.5; 95% CI = 1.2-2), complexity index (HR = 1.01; 95% CI = 1.02-1.04) and polymedication (HR = 2.6; 95% CI = 2.0-3.3). CONCLUSIONS: There was a gradual and significant decrease in the survival of patients with chronic conditions according to their level of risk as defined by adjusted morbidity groups. Other factors, such as older age, receiving palliative care, high number of chronic conditions, complexity, and polymedication, had a negative effect on survival. The adjusted morbidity groups are useful in explaining survival outcomes and may be valuable for clinical practice, resource planning and public health research.

Novel Loss-of-Function KCNA5 Variants in Pulmonary Arterial Hypertension.

Reduced expression and/or activity of Kv1.5 channels (encoded by KCNA5) is a common hallmark in human or experimental pulmonary arterial hypertension (PAH). Likewise, genetic variants in KCNA5 have been found in patients with PAH, but their functional consequences and potential impact on the disease are largely unknown. Herein, this study aimed to characterize the functional consequences of seven KCNA5 variants found in a cohort of patients with PAH. Potassium currents were recorded by patch-clamp technique in HEK293 cells transfected with wild-type or mutant Kv1.5 cDNA. Flow cytometry, Western blot, and confocal microscopy techniques were used for measuring protein expression and cell apoptosis in HEK293 and human pulmonary artery smooth muscle cells. KCNA5 variants (namely, Arg184Pro and Gly384Arg) found in patients with PAH resulted in a clear loss of potassium channel function as assessed by electrophysiological and molecular modeling analyses. The Arg184Pro variant also resulted in a pronounced reduction of Kv1.5 expression. Transfection with Arg184Pro or Gly384Arg variants decreased apoptosis of human pulmonary artery smooth muscle cells compared with the wild-type cells, demonstrating that KCNA5 dysfunction in both variants affects cell viability. Thus, in addition to affecting channel activity, both variants were associated with impaired apoptosis, a crucial process linked to the disease. The estimated prevalence of dysfunctional KCNA5 variants in the PAH population analyzed was around 1%. The data indicate that some KCNA5 variants found in patients with PAH have critical consequences for channel function, supporting the idea that KCNA5 pathogenic variants may be a causative or contributing factor for PAH.

Sigma-1 receptor modulation fine-tunes KV1.5 channels and impacts pulmonary vascular function.

KV1.5 channels are key players in the regulation of vascular tone and atrial excitability and their impairment is associated with cardiovascular diseases including pulmonary arterial hypertension (PAH) and atrial fibrillation (AF). Unfortunately, pharmacological strategies to improve KV1.5 channel function are missing. Herein, we aimed to study whether the chaperone sigma-1 receptor (S1R) is able to regulate these channels and represent a new strategy to enhance their function. By using different electrophysiological and molecular techniques in X. laevis oocytes and HEK293 cells, we demonstrate that S1R physically interacts with KV1.5 channels and regulate their expression and function. S1R induced a bimodal regulation of KV1.5 channel expression/activity, increasing it at low concentrations and decreasing it at high concentrations. Of note, S1R agonists (PRE084 and SKF10047) increased, whereas the S1R antagonist BD1047 decreased, KV1.5 expression and activity. Moreover, PRE084 markedly increased KV1.5 currents in pulmonary artery smooth muscle cells and attenuated vasoconstriction and proliferation in pulmonary arteries. We also show that both KV1.5 channels and S1R, at mRNA and protein levels, are clearly downregulated in samples from PAH and AF patients. Moreover, the expression of both genes showed a positive correlation. Finally, the ability of PRE084 to increase KV1.5 function was preserved under sustained hypoxic conditions, as an in vitro PAH model. Our study provides insight into the key role of S1R in modulating the expression and activity of KV1.5 channels and highlights the potential role of this chaperone as a novel pharmacological target for pathological conditions associated with KV1.5 channel dysfunction.

Validation of Knock-Out Caco-2 TC7 Cells as Models of Enterocytes of Patients with Familial Genetic Hypobetalipoproteinemias.

Abetalipoproteinemia (FHBL-SD1) and chylomicron retention disease (FHBL-SD3) are rare recessive disorders of lipoprotein metabolism due to mutations in MTTP and SAR1B genes, respectively, which lead to defective chylomicron formation and secretion. This results in lipid and fat-soluble vitamin malabsorption, which induces severe neuro-ophthalmic complications. Currently, treatment combines a low-fat diet with high-dose vitamin A and E supplementation but still fails in normalizing serum vitamin E levels and providing complete ophthalmic protection. To explore these persistent complications, we developed two knock-out cell models of FHBL-SD1 and FHBL-SD3 using the CRISPR/Cas9 technique in Caco-2/TC7 cells. DNA sequencing, RNA quantification and Western blotting confirmed the introduction of mutations with protein knock-out in four clones associated with i) impaired lipid droplet formation and ii) defective triglyceride (-57.0 ± 2.6% to -83.9 ± 1.6%) and cholesterol (-35.3 ± 4.4% to -60.6 ± 3.5%) secretion. A significant decrease in α-tocopherol secretion was also observed in these clones (-41.5 ± 3.7% to -97.2 ± 2.8%), even with the pharmaceutical forms of vitamin E: tocopherol-acetate and tocofersolan (α-tocopheryl polyethylene glycol succinate 1000). MTTP silencing led to a more severe phenotype than SAR1B silencing, which is consistent with clinical observations. Our cellular models thus provide an efficient tool to experiment with therapeutic strategies and will allow progress in understanding the mechanisms involved in lipid metabolism.

A novel loss-of-function mutation of the voltage-gated potassium channel Kv10.2 involved in epilepsy and autism.

BACKGROUND: Novel developmental mutations associated with disease are a continuous challenge in medicine. Clinical consequences caused by these mutations include neuron and cognitive alterations that can lead to epilepsy or autism spectrum disorders. Often, it is difficult to identify the physiological defects and the appropriate treatments. RESULTS: We have isolated and cultured primary cells from the skin of a patient with combined epilepsy and autism syndrome. A mutation in the potassium channel protein Kv10.2 was identified. We have characterised the alteration of the mutant channel and found that it causes loss of function (LOF). Primary cells from the skin displayed a very striking growth defect and increased differentiation. In vitro treatment with various carbonic anhydrase inhibitors with various degrees of specificity for potassium channels, (Brinzolamide, Acetazolamide, Retigabine) restored the activation capacity of the mutated channel. Interestingly, the drugs also recovered in vitro the expansion capacity of the mutated skin cells. Furthermore, treatment with Acetazolamide clearly improved the patient regarding epilepsy and cognitive skills. When the treatment was temporarily halted the syndrome worsened again. CONCLUSIONS: By in vitro studying primary cells from the patient and the activation capacity of the mutated protein, we could first, find a readout for the cellular defects and second, test pharmaceutical treatments that proved to be beneficial. The results show the involvement of a novel LOF mutation of a Potassium channel in autism syndrome with epilepsy and the great potential of in vitro cultures of primary cells in personalised medicine of rare diseases.

Ultrasound intima media thickness cut-off values for cranial and extracranial arteries in patients with suspected giant cell arteritis.

Objective: To determine the optimal ultrasound (US) cut-off values for cranial and extracranial arteries intima media thickness (IMT) to discriminate between patients with and without giant cell arteritis (GCA). Methods: Retrospective observational study including patients referred to an US fast-track clinic. All patients underwent bilateral US examination of the cranial and extracranial arteries including the IMT measurement. Clinical confirmation of GCA after 6 months was considered the gold standard for diagnosis. A receiver operating characteristic (ROC) analysis was performed to select the cut-off values on the basis of the best tradeoff values between sensitivity and specificity. Results: A total of 157 patients were included, 47 (29.9%) with clinical confirmation of GCA after 6 months. 41 (87.2%) of patients with GCA had positive US findings (61.7% had cranial and 44.7% extracranial involvement). The best threshold IMT values were 0.44 mm for the common temporal artery; 0.34 mm for the frontal branch; 0.36 mm for the parietal branch; 1.1 mm for the carotid artery and 1 mm for the subclavian and axillary arteries. The areas under the ROC curves were greater for axillary arteries 0.996 (95% CI 0.991-1), for parietal branch 0.991 (95% CI 0.980-1), for subclavian 0.990 (95% CI 0.979-1), for frontal branch 0.989 (95% CI 0.976-1), for common temporal artery 0.984 (95% CI 0.959-1) and for common carotid arteries 0.977 (95% CI 0.961-0.993). Conclusion: IMT cut-off values have been identified for each artery. These proposed IMT cut-off values may help to improve the diagnostic accuracy of US in clinical practice.