Comparison of Continuous Intracortical and Scalp Electroencephalography in Comatose Patients with Acute Brain Injury.

BACKGROUND: Depth electroencephalography (dEEG) is a recent invasive monitoring technique used in patients with acute brain injury. This study aimed to describe in detail the clinical manifestations of nonconvulsive seizures (NCSzs) with and without a surface EEG correlate, analyze their long-standing effects, and provide data that contribute to understanding the significance of certain scalp EEG patterns observed in critically ill patients. METHODS: We prospectively enrolled a cohort of 33 adults with severe acute brain injury admitted to the neurological intensive care unit. All of them underwent multimodal invasive monitoring, including dEEG. All patients were scanned on a 3T magnetic resonance imaging scanner at 6 months after hospital discharge, and mesial temporal atrophy (MTA) was calculated using a visual scale. RESULTS: In 21 (65.6%) of 32 study participants, highly epileptiform intracortical patterns were observed. A total of 11 (34.3%) patients had electrographic or electroclinical seizures in the dEEG, of whom 8 had both spontaneous and stimulus-induced (SI) seizures, and 3 patients had only spontaneous intracortical seizures. An unequivocal ictal scalp correlate was observed in only 3 (27.2%) of the 11 study participants. SI-NCSzs occurred during nursing care, medical procedures, and family visits. Subtle clinical manifestations, such as restlessness, purposeless stereotyped movements of the upper limbs, ventilation disturbances, jerks, head movements, hyperextension posturing, chewing, and oroalimentary automatisms, occurred during intracortical electroclinical seizures. MTA was detected in 18 (81.8%) of the 22 patients. There were no statistically significant differences between patients with MTA with and without seizures or status epilepticus. CONCLUSIONS: Most NCSzs in critically ill comatose patients remain undetectable on scalp EEG. SI-NCSzs frequently occur during nursing care, medical procedures, and family visits. Semiology of NCSzs included ictal minor signs and subtle symptoms, such as breathing pattern changes manifested as patient-ventilator dyssynchrony.

A cost-effectiveness analysis of empagliflozin for heart failure patients across the full spectrum of ejection fraction in Spain: combined results of the EMPEROR-Preserved and EMPEROR-Reduced trials.

BACKGROUND: Heart failure (HF) is a chronic condition with considerable clinical burden for patients and economic burden for healthcare systems. Treatment for HF is typically based on ejection fraction (EF) phenotype. The cost-effectiveness of empagliflozin + standard of care (SoC) compared to SoC has been examined for HF phenotypes below or above 40% EF separately, but not across the full spectrum of EF in Spain. METHODS: The results of two preexisting, validated, and published phenotype-specific Markov cohort models were combined using a population-weighted approach, reflecting the incidence of each phenotype in the total HF population in Spain. A probabilistic sensitivity analysis was performed by sampling each model's probabilistic results. RESULTS: Empagliflozin + SoC compared to SoC resulted in increased life-years (LYs) (6.48 vs. 6.35), quality-adjusted LYs (QALYs) (4.80 vs. 4.63), and healthcare costs (€19,090 vs. €18,246), over a lifetime time horizon for the combined HF population in Spain. The incremental cost-effectiveness ratio (ICER) was €5,089/QALY. All subgroup, scenario, and probabilistic ICERs were consistently below €10,000/QALY. CONCLUSIONS: Empagliflozin is the first treatment with established efficacy and cost-effectiveness for HF patients across EF from the perspective of healthcare payers in Spain. Empagliflozin also proved to be cost-effective for all subgroups of patients included in the analysis.

Effectiveness and Safety of Teriflunomide in Relapsing-Remitting Multiple Sclerosis and Improvements in Quality of Life: Results from the Real-World TERICARE Study.

INTRODUCTION: Teriflunomide is a once-daily oral immunomodulator approved for relapsing forms of multiple sclerosis (MS) or relapsing-remitting multiple sclerosis (RRMS; depending on the local label), based on extensive evidence from clinical trials and a real-world setting on efficacy, tolerability and patient-reported benefits. The TERICARE study assessed the impact of teriflunomide treatment over 2 years on health-related quality of life (HRQoL) and some of the most common and disabling symptoms of MS, such as fatigue and depression. METHODS: This prospective observational study in Spain included RRMS patients treated with teriflunomide for ≤ 4 weeks. The following patient-reported outcomes (PROs) were collected at baseline and every 6 months for 2 years: the 29-item Multiple Sclerosis Impact Scale version 2 (MSIS-29), the 21-item Modified Fatigue Impact Scale (MFIS-21), the Beck Depression Inventory (BDI-II), the Short Form (SF)-Qualiveen and the Treatment Satisfaction Questionnaire for Medication v1.4 (TSQM). Annualised relapse rate (ARR), disability progression according to the Expanded Disability Status Scale (EDSS), and no evidence of disease activity (NEDA-3) were also assessed. RESULTS: A total of 325 patients were analysed. Patients had a mean (SD) age of 43.2 years (10.4), a mean baseline EDSS score of 1.75 (1.5), a mean number of relapses in the past 2 years of 1.5 (0.7), and 64% had received prior disease-modifying therapy (DMT). Patients showed significant improvements in the psychological domain of MSIS-29 from 35.9 (26.6) at baseline to 29.4 (25.5) at 18 months (p = 0.004) and 29.0 (24.6) at 24 months (p = 0.002). Levels of fatigue and depression were also reduced. After 2 years of treatment with teriflunomide, ARR was reduced to 0.17 (95% CI 0.14-0.21) from the baseline of 0.42 (95% CI 0.38-0.48), representing a 60.1% reduction. Mean EDSS scores remained stable during the study, and 79.9% of patients showed no disability progression. 54.7% of patients achieved NEDA-3 in the first 12 months, which increased to 61.4% during months 12-24. Patients reported increased satisfaction with treatment over the course of the study, regardless of whether they were DMT naive or not. CONCLUSION: Teriflunomide improves psychological aspects of HRQoL and maintains low levels of fatigue and depression. Treatment with teriflunomide over 2 years is effective in reducing ARR and disability progression.

Highly Sensitive Temperature Sensor Based on Vernier Effect Using a Sturdy Double-cavity Fiber Fabry-Perot Interferometer.

Temperature measuring is a daily procedure carried out worldwide in practically all environments of human activity, but it takes particular relevance in industrial, scientific, medical, and food processing and production areas. The characteristics and performance of the temperature sensors required for such a large universe of applications have opened the opportunity for a comprehensive range of technologies and architectures capable of fulfilling the sensitivity, resolution, dynamic range, and response time demanded. In this work, a highly sensitive fiber optic temperature sensor based on a double-cavity Fabry-Perot interferometer (DCFPI) is proposed and demonstrated. Taking advantage of the Vernier effect, we demonstrate that it is possible to improve the temperature sensitivity exhibited by the polymer-capped fiber Fabry-Perot interferometer (PCFPI) up to 39.8 nm/°C. The DCFPI is sturdy, reconfigured, and simple to fabricate, consisting of a semi-spherical polymer cap added to the surface of the ferrule of a commercial single-mode fiber connector (SMF FC/PC) placed in front of a mirror at a proper distance. The length of the air cavity (Lair) was adjusted to equal the thickness of the polymer cap (Lpol) plus a distance δ to generate the most convenient Vernier effect spectrum. The DCFPI was packaged in a machined, movable mount that allows the adjustment of the air cavity length easily but also protects the polymer cap and simplifies the manipulation of the sensor head.

Bispectral index monitoring to detect delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

PURPOSE: Evaluate the bispectral index (BIS) monitoring to detect delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). MATERIALS AND METHODS: A single-center prospective study in patients with aSAH. BIS monitoring was recorded during 25-120 min in two periods, within the initial 72 h (BIS1) and between days 4 and 6 (BIS2) from admission. The median for each exported BIS parameter was analyzed. Transcranial Doppler (TCD) sonography was simultaneously performed with BIS1 (TCD1) and BIS2 (TCD2) monitoring. A multivariate logistic regression model was built to identify the variables associated with DCI. RESULTS: Sixty-four patients were included and 16 (25%) developed DCI. During BIS2 monitoring, significant differences were found in BIS value (left, p = 0.01; right, p = 0.009), 95% spectral edge frequency (left and right, p = 0.04), and total power (left and right, p = 0.04). In multivariable analysis, vasospasm on TCD2 (OR 42.8 [95% CI 3.1-573]; p = 0.005), a median BIS2 value <85 in one or both sides (OR 6.2 [95% CI 1.28-30]; p = 0.023), and age (OR 1.08 [95% CI 1.00-1.17]; p = 0.04) were associated with the development of DCI. CONCLUSIONS: BIS value is the most useful BIS parameter for detecting DCI after aSAH. Pending further validation, BIS monitoring might be even more accurate than TCD.

Comportamiento de la amoxicilina en agua mediante métodos de solvatación implícita y explícita

El comportamiento molecular de la amoxicilina en agua fue explorado con solvatación implícita y explícita mediante dos estrategias que combinan diferentes técnicas de simulación molecular para evaluar el alcance de estos procedimientos. Con estas dos estrategias de cálculo computacional, la conformación molecular de la amoxicilina fue determinada en fase acuosa. En la primera estrategia se utilizó el generador de conformaciones Ballon-v1.8.2 y la estabilidad de las conformaciones en agua fue evaluada utilizando la energía libre de solvatación determinada con el método de solvatación implícita SMD. En la segunda estrategia, con la dinámica molecular tipo NVT fue evaluado el arreglo espacial de esta molécula en agua y, además, la interacción molecular entre la amoxicilina y el agua fue evaluada en esta simulación. Los resultados obtenidos muestran que la conformación de la amoxicilina más estable en fase acuosa es la plegada. Además, los valores de energías de solvatación de -121,42 y -14,58 kJ/mol obtenidos con solvatación implícita y dinámica molecular sugieren que esta molécula tiene una alta afinidad por el agua. Las funciones distribución radial y espacial sugieren que se forman 3 capas de solvatación alrededor de la amoxicilina y que esta molécula tiene una región altamente hidrofílica. Finalmente, la estrategia usando dinámica molecular permite obtener mejores conformaciones en equilibrio que la estrategia de simulación usando el generador de conformaciones Ballon-v1.8.2.

The molecular behavior of amoxicillin in water was explored with implicit and explicit solvation using two strategies that combine different molecular simulation techniques to assess the scope of these procedures. With these two computational calculation strategies, the molecular conformation of amoxicillin was determined in aqueous phase. In the first strategy, the conformation generator Ballon-v1.8.2 was used and the stability of the conformations in water was evaluated using the solvation free energy determined with the SMD implicit solvation method. In the second strategy, with NVT-type molecular dynamics, the spatial arrangement of this molecule in water was evaluated and, in addition, the molecular interaction between amoxicillin and water was evaluated in this simulation. The results obtained show that the most stable conformation of amoxicillin in the aqueous phase is the folded one. In addition, the solvation energy values of -121.42 and -14.58 kJ/mol obtained with implicit solvation and molecular dynamics suggest that this molecule has a high affinity for water. The radial and spatial distribution functions suggest that 3 solvation shells form around amoxicillin and that this molecule has a highly hydrophilic region. Finally, the strategy using molecular dynamics allows to obtain better equilibrium conformations than the simulation strategy using the Ballon-v1.8.2 conformation generator.

O comportamento da amoxicilina em água foi analisado com solvatação implícita e explícita mediante duas estratégias que combinam diferentes técnicas de simulação molecular para avaliar o escopo destes procedimentos. Com estas duas estratégias de cálculo computacional, a conformação molecular da amoxicilina foi determinada em fase aquosa. Na primeira estratégia, utilizou-se o gerador de conformação do software Ballon-v1.8.2 e avaliou-se a estabilidade das conformações em água a partir da energia livre de solvatação determinada pelo método de solvatação implícita SMD. Na segunda estratégia, avaliou-se o arranjo espacial da amoxicilina e sua interação com a água através de simulações de dinâmica molecular NVT. Os resultados obtidos mostram que a conformação dobrada é a mais estável em fase aquosa. Ademais, os valores de energía de solvatação de -121,42 e -14,58 kJ/mol obtidos com solvatação implícita e dinâmica molecular sugerem que esta molécula possui alta afinidade pela água. As funções de distribuição radial e espacial sugerem que se formam 3 camadas de solvatação ao redor da amoxicilina e que esta molécula possui uma região altamente hidrofílica. Finalmente, a estratégia usando dinâmica molecular permite obter melhores conformações de equilíbrio do que a estratégia de simulação usando o gerador de conformação do software Ballon-v1.8.2.

Typical absence status epilepticus in older people: syndromic delineation.

Objective We describe the clinical, electroencephalograph^ and neuroimaging findings of older patients with typical absence status epilepticus (ASE). Methods This investigation was a retrospective analysis of prospectively collected consecutive patients between January 2011 and October 2021. All patients ≥60 years with impairment of awareness and continuous generalized, rhythmic, synchronous and symmetric epileptiform discharges and normal background on video-electroencephalogram (vEEG) were included. Results Six patients were identified with a diagnosis of typical ASE. The mean age was 67 years. Five could be classified as idiopathic generalized epilepsy (IGE) though two had been erroneously categorized as cryptogenic focal epilepsy (FE). In one, the episode of ASE was thought to represent the beginning of late-onset IGE (de novo late-onset typical ASE). In all cases, ASE was controlled within the first 24 hours. Significance Typical ASE is a rare cause of confusion in the elderly population requiring urgent vEEG evaluation. It most frequently represents reactivation of a previous IGE, in effect related to patients with epilepsy with onset in childhood or adolescence, not previously diagnosed or treated, representing rather the debut of (de novo) late-onset IGE.

A prospective evaluation of phrenic nerve injury after lung transplantation: Incidence, risk factors, and analysis of the surgical procedure.

BACKGROUND: Phrenic nerve injury (PNI) is a complication of lung transplantation related to the surgical procedure and associated with increased morbidity. However, the incidence and risk factors, specifically regarding surgical techniques, have not been adequately studied. METHODS: We conducted a prospective single-center study over 4-years, in recipients of lung transplantation with a normal pretransplant phrenic nerve conduction study (PNCS). Diaphragm ultrasound and PNCS were performed in the first 21 postoperative days and PNI was defined when both tests were abnormal. Patients were followed up until hospital discharge. The association between transplant characteristics and PNI was analyzed by using logistic regression models. RESULTS: Two hundred eleven lung grafts implanted in 127 patients were included in the study. After lung transplantation, PNI was diagnosed in 43.3% of the subjects and 29% of the operated hemithorax. Regression logistic model showed that the variables related to PNI were female gender (p = 0.02), bilateral lung transplantation (BLT) (p = 0.001), right lung graft (p = 0.003), clamshell incision (p = 0.01), mediastinal adhesions (p = 0.002), longer operative time (p = 0.003), intraoperative extracorporeal support (p = 0.02), and blood transfusion (p = 0.003). Conversely, age >61 years (p = 0.008) and higher thoracic diameter (p = 0.04) were protective factors. The use of electrocautery, cardiac mechanical retractors, and diaphragmatic traction was not associated with PNI. Morbidity was increased without any difference in mortality. CONCLUSIONS: PNI is a frequent complication after lung transplantation, associated with higher morbidity. Mainly risk factors were age, BLT, female gender, and variables related to surgical difficulties. Lung graft in the right hemithorax and mediastinal adhesiolysis were the most relevant technical variables.

Vitamin D Status in Hospitalized Patients with SARS-CoV-2 Infection.

BACKGROUND: The role of vitamin D status in COVID-19 patients is a matter of debate. OBJECTIVES: To assess serum 25-hydroxyvitamin D (25OHD) levels in hospitalized patients with COVID-19 and to analyze the possible influence of vitamin D status on disease severity. METHODS: Retrospective case-control study of 216 COVID-19 patients and 197 population-based controls. Serum 25OHD levels were measured in both groups. The association of serum 25OHD levels with COVID-19 severity (admission to the intensive care unit, requirements for mechanical ventilation, or mortality) was also evaluated. RESULTS: Of the 216 patients, 19 were on vitamin D supplements and were analyzed separately. In COVID-19 patients, mean ±â€…standard deviation 25OHD levels were 13.8 ±â€…7.2 ng/mL, compared with 20.9 ±â€…7.4 ng/mL in controls (P < .0001). 25OHD values were lower in men than in women. Vitamin D deficiency was found in 82.2% of COVID-19 cases and 47.2% of population-based controls (P < .0001). 25OHD inversely correlates with serum ferritin (P = .013) and D-dimer levels (P = .027). Vitamin D-deficient COVID-19 patients had a greater prevalence of hypertension and cardiovascular diseases, raised serum ferritin and troponin levels, as well as a longer length of hospital stay than those with serum 25OHD levels ≥20 ng/mL. No causal relationship was found between vitamin D deficiency and COVID-19 severity as a combined endpoint or as its separate components. CONCLUSIONS: 25OHD levels are lower in hospitalized COVID-19 patients than in population-based controls and these patients had a higher prevalence of deficiency. We did not find any relationship between vitamin D concentrations or vitamin deficiency and the severity of the disease.

Intracortical focal non-convulsive status epilepticus causing cerebral hypoxia and intracranial hypertension.

We describe the pathophysiological consequences and long-term neurological outcome of a patient with acute brain injury (ABI) in whom intracortical electroencephalography (iEEG) captured an episode of prolonged focal non-convulsive status epilepticus (NCSE) that remained undetectable on scalp electroencephalography. A 53-year-old right-handed woman was admitted to hospital due to a large frontal left intraparenchymal hematoma. Over two and a half days, we captured recurrent non-convulsive electrographic and electroclinical seizures compatible with the diagnosis of intracortical focal NCSE. The patient remained sedated and a burst-suppression pattern was obtained. We also performed invasive brain multimodality monitoring including iEEG and measurements of intracranial pressure (ICP), partial brain tissue oxygenation (PbtO2) and brain temperature. During non-convulsive electrographic and electroclinical seizures, the values of PbtO2 decreased and those of ICP increased. Six months later, brain MRI revealed encephalomalacia localized to the left paramedial fronto-basal region. The neuropsychological assessment carried out one year after the injury showed scores below average in verbal learning memory, motor dexterity and executive functions. In summary, iEEG is a feasible innovative invasive technique that may be used to record non-convulsive electrographic and electroclinical seizures which remain invisible on the surface. Intracortical focal NCSE causes metabolic changes such as reduced brain oxygenation and an increase in ICP that can further damage previously compromised brain tissue.

14-Electron Rh and Ir silylphosphine complexes and their catalytic activity in alkene functionalization with hydrosilanes.

Herein we report an experimental and computational study of a family of four coordinated 14-electron complexes of Rh(iii) devoid of agostic interactions. The complexes [X-Rh(κ3(P,Si,Si)PhP(o-C6H4CH2SiiPr2)2], where X = Cl (Rh-1), Br (Rh-2), I (Rh-3), OTf (Rh-4), Cl·GaCl3 (Rh-5); derive from a bis(silyl)-o-tolylphosphine with isopropyl substituents on the Si atoms. All five complexes display a sawhorse geometry around Rh and exhibit similar spectroscopic and structural properties. The catalytic activity of these complexes and [Cl-Ir(κ3(P,Si,Si)PhP(o-C6H4CH2SiiPr2)2], Ir-1, in styrene and aliphatic alkene functionalizations with hydrosilanes is disclosed. We show that Rh-1 catalyzes effectively the dehydrogenative silylation of styrene with Et3SiH in toluene while it leads to hydrosilylation products in acetonitrile. Rh-1 is an excellent catalyst in the sequential isomerization/hydrosilylation of terminal and remote aliphatic alkenes with Et3SiH including hexene isomers, leading efficiently and selectively to the terminal anti-Markonikov hydrosilylation product in all cases. With aliphatic alkenes, no hydrogenation products are observed. Conversely, catalysis of the same hexene isomers by Ir-1 renders allyl silanes, the tandem isomerization/dehydrogenative silylation products. A mechanistic proposal is made to explain the catalysis with these M(iii) complexes.

Effectiveness of direct-acting antiviral drugs against hepatitis C virus: predictive factors of response to the treatment.

Background/Aims. Despite the high efficacy and safety of direct-acting antivirals against hepatitis C virus shown in clinical trials, treatment failures continue to occur. Our aim was to establish the effectiveness of these drugs in routine clinical practice, as well as to determine factors that could influence the response to the treatment.Matherials/methods. Single-center, observational, retrospective study. Clinical, virological and pharmacotherapeutic variables were registered at baseline. Adverse drug reactions that occurred were recorded until week 24 of follow-up. Achievement of sustained virologic response was also recorded. Univariate and multivariate analysis were done to determine factors of response.Results. A total of 333 treatment regimens corresponding to 330 different patients were evaluated. Sustained virologic response rate was 94.6% [95%CI: 91.6-96.6%]. 67.9% of the patients experienced adverse drugs reactions (92.2% were grade 1). The univariate analysis identified a higher baseline of platelets, albumin and total cholesterol as predictive factors of sustained virologic response (p < 0.05). Presence of diabetes and complications related to liver disease (splenomegaly, portal hypertension, portal hypertensive gastropathy), body mass index ≥30, greater liver fibrosis, receiving simeprevir and higher baseline levels of glucose, aspartate-aminotransferase, alanine-aminotransferase and alkaline-phosphatase, have been identified as predictive factors of non-response (p < 0.05). The multivariate analysis detected the following independent factors of non-response: body mass index ≥30 and presence of complications related to liver disease.Conclusion. The effectiveness and safety of direct-acting antivirals against hepatitis C virus have been maintained in routine clinical practice. Further research on predictive factors of response is required in order to develop more reliable and reproducible predictive models.

Vitamin D Status in Hospitalized Patients with SARS-CoV-2 Infection.

BACKGROUND: The role of vitamin D status in COVID-19 patients is a matter of debate. OBJECTIVES: To assess serum 25-hydroxyvitamin D (25OHD) levels in hospitalized patients with COVID-19 and to analyze the possible influence of vitamin D status on disease severity. METHODS: Retrospective case-control study of 216 COVID-19 patients and 197 population-based controls. Serum 25OHD levels were measured in both groups. The association of serum 25OHD levels with COVID-19 severity (admission to the intensive care unit, requirements for mechanical ventilation, or mortality) was also evaluated. RESULTS: Of the 216 patients, 19 were on vitamin D supplements and were analyzed separately. In COVID-19 patients, mean ±â€…standard deviation 25OHD levels were 13.8 ±â€…7.2 ng/mL, compared with 20.9 ±â€…7.4 ng/mL in controls (P < .0001). 25OHD values were lower in men than in women. Vitamin D deficiency was found in 82.2% of COVID-19 cases and 47.2% of population-based controls (P < .0001). 25OHD inversely correlates with serum ferritin (P = .013) and D-dimer levels (P = .027). Vitamin D-deficient COVID-19 patients had a greater prevalence of hypertension and cardiovascular diseases, raised serum ferritin and troponin levels, as well as a longer length of hospital stay than those with serum 25OHD levels ≥20 ng/mL. No causal relationship was found between vitamin D deficiency and COVID-19 severity as a combined endpoint or as its separate components. CONCLUSIONS: 25OHD levels are lower in hospitalized COVID-19 patients than in population-based controls and these patients had a higher prevalence of deficiency. We did not find any relationship between vitamin D concentrations or vitamin deficiency and the severity of the disease.

Lingual epilepsia partialis continua: a detailed video-EEG and neuroimaging study.

Motor epilepsia partialis continua (EPC) is a frequent and widely described variant of simple focal motor status epilepticus. However, lingual EPC is an unusual epileptic condition. We present a case of lingual EPC secondary to low-grade glioma in which the EEG and neuroimaging features were particularly remarkable. The video-EEG showed lateralized periodic discharges with superimposed rhythmic activity and frequent recurrent focal epileptic seizures. Moreover, brain magnetic resonance imaging showed a right temporo-insular cortico-subcortical lesion which was hyperintense on FLAIR, suggestive of low-grade glioma. In addition, diffusion-weighted imaging and arterial spin labelling series showed restricted diffusion in the right temporo-insular and parietal cortex and increased cerebral flow, respectively. All these findings are in keeping with changes related to persistent focal status epilepticus. Finally, we review the literature and discuss the differential diagnosis of this rare epileptic entity. [Published with video sequence].

New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab.

Overview: We assessed the role of age and disease activity as new factors contributing to establish the risk of progressive multifocal leucoencephalopathy in multiple sclerosis patients treated with natalizumab in 36 University Hospitals in Europe. We performed the study in 1,307 multiple sclerosis patients (70.8% anti-John Cunninghan virus positive antibodies) treated with natalizumab for a median time of 3.28 years. Epidemiological, clinical, and laboratory variables were collected. Lipid-specific IgM oligoclonal band status was available in 277 patients. Factors associated with progressive multifocal leucoencephalopathy onset were explored by uni- and multivariate logistic regression. Results: Thirty-five patients developed progressive multifocal leucoencephalopathy. The multivariate analysis identified anti-John Cunninghan virus antibody indices and relapse rate as the best predictors for the onset of this serious opportunistic infection in the whole cohort. They allowed to stratify progressive multifocal leucoencephalopathy risk before natalizumab initiation in individual patients [area under the curve (AUC) = 0.85]. The risk ranged from <1/3,300 in patients with anti-John Cunninghan virus antibody indices <0.9 and relapse rate >0.5, to 1/50 in the opposite case. In patients with lipid-specific IgM oligoclonal bands assessment, age at natalizumab onset, anti-John Cunninghan virus antibody indices, and lipid-specific IgM oligoclonal band status predicted progressive multifocal leucoencephalopathy risk (AUC = 0.92). The absence of lipid-specific IgM oligoclonal bands was the best individual predictor (OR = 40.94). The individual risk ranged from <1/10,000 in patients younger than 45 years at natalizumab initiation, who showed anti John Cunningham virus antibody indices <0.9 and lipid-specific IgM oligoclonal bands to 1/33 in the opposite case. Conclusions: In a perspective of personalized medicine, disease activity, anti-lipid specific IgM oligoclonal bands, anti Jonh Cunninghan virus antibody levels, and age can help tailor natalizumab therapy in multiple sclerosis patients, as predictors of progressive multifocal leucoencephalopathy.

Epilepsia partialis continua and cortical motor control: insights into physiology.

Motor epilepsia partialis continua is a widely described variant of simple focal motor status epilepticus. However, few studies have addressed associated pathophysiological anomalies that may help us understand the cortical organization, basic functioning and control of voluntary movement. We describe the clinical, video-EEG and neuroimaging findings from two cases of motor epilepsia partialis continua that support the hypothesis of the coexistence of both classic body and complex motor map models in the cortical organization of voluntary movement in humans. [Published with video sequence].

Bi- and tridentate stannylphosphines and their coordination to low-valent platinum.

Semirigid bifunctional tin-substituted o-tolylphosphines of general formulae [Ph2P(o-C6H4CH2)SnR3] (R = Ph, 1; R = Me, 2) and [{Ph2P(o-C6H4CH2)}2SnPh2] (3) were synthesized and isolated in good yields. The new compounds were fully characterized by single-crystal X-ray diffraction and multinuclear solution NMR spectroscopic techniques. The observed J(119Sn,31P) values in solution NMR spectroscopy as well as the PSn distances in the solid state and DFT calculations (B3LYP) on compounds 1 and 3 do not support the existence of intramolecular P → Sn bond interactions in either of the three compounds. 1 and 2 reacted with stoichiometric amounts of tristriphenylphosphine platinum(0) [Pt(PPh3)3] under toluene refluxing conditions leading to formation of Pt(ii) distorted square-planar complexes [Ph2P(o-C6H4CH2)Pt(SnR3)(PPh3)], (R = Ph, 4; R = Me, 5), each bearing a five-membered carbometallated ring resulting from Pt coordination to P and the benzylic C sp3 atom of the ligand architecture rather than from activation of the terminal Sn-C carbon bonds of the phenyl or methyl substituents which would have rendered six-membered rings. Additionally, the fragment SnR3 also binds to the metal centre disposing cis to the cyclometalated carbon atom and to the single remaining PPh3. This carbometallation takes place affecting the integrity of the ligand skeleton. NBO calculations show the Sn fragment coordinates to the metal as X-type stannyl, SnR3. The analogous reaction of [Pt(PPh3)3] towards the stannyldiphosphine 3 leads to the quantitative formation of complex [(Ph2P-o-C6H4CH2)Pt(Ph2P-o-C6H4CH2SnPh3)], 6, which exhibits five- and six-membered metallacycles at the expense of the ligand frame. All compounds were characterized exhaustively by solution spectroscopic measurements and by single crystal X-ray diffraction analysis. DFT computations corroborate the higher stability of the observed products over those resulting from preservation of the ligand backbone.

Differential Expression of the apsXRS System by Antimicrobial Peptide LL-37 in Commensal and Clinical Staphylococcus epidermidis Isolates.

The three-component apsXRS system senses and responds to cationic antimicrobial peptides (CAMPs), which induces the expression of the dlt operon and the genes mprF and vrafG, modifying the surface net charge in Staphylococcus epidermidis, resulting in the repulsion of CAMPs. The apsXRS system has been only studied in the S. epidermidis 1457 strain, and there are no studies of prevalence and level of expression of apsXRS in commensal and clinical isolates. From 60 isolates, those selected from commensal healthy skin (n = 20), commensal healthy conjunctive (n = 10), and clinical ocular infection (n = 30) presented the apsX, apsR, and apsS genes in their genomes. Constitutive expression of apsX, apsR, and apsS genes was determined by RT-qPCR in all isolates. It was found that expression of apsX, apsR, and apsS was 3.3-5.9-fold higher in commensal isolates stimulated with LL-37 (15 µg/mL) than in clinical isolates. Similarly, expression of the dlt operon and the genes mprF, and vraFG was 8-10-fold higher in commensal isolates than in clinical. However, LL-37 did not increase the addition of lysine in the phospholipids of the cytoplasmic membrane in any of the isolates. Mutations in the apsS loop region, apsR, and their promoter sequence were not found. These results demonstrated that apsXRS system is essential in all isolates for its constitutive expression; however, LL-37 caused an increase of apsXRS expression in commensal isolates, suggesting that S. epidermidis isolates do not respond in the same way to the presence of LL-37.