Cortical resting motor threshold difference in asleep-awake craniotomy for motor eloquent gliomas: WHO grading influences motor pathway excitability.

Developing neurophysiological tools to predict WHO tumor grade can empower the treating teams for a better surgical decision-making process. A total of 38 patients with supratentorial diffuse gliomas underwent an asleep-awake-sedated craniotomies for tumor removal with intraoperative neuromonitoring. The resting motor threshold was calculated for different train stimulation paradigms during awake and asleep phases. Receiver operating characteristic analysis and Bayesian regression models were performed to analyze the prediction of tumor grading based on the resting motor threshold differences. Significant positive spearman correlations were observed between resting motor threshold excitability difference and WHO tumor grade for train stimulation paradigms of 5 (R = 0.54, P = 0.00063), 4 (R = 0.49, P = 0.002), 3 (R = 0.51, P = 0.001), and 2 pulses (R = 0.54, P = 0.0007). Kruskal-Wallis analysis of the median revealed a positive significant difference between the median of excitability difference and WHO tumor grade in all paradigms. Receiver operating characteristic analysis showed 3 mA difference as the best predictor of high-grade glioma across different patterns of motor pathway stimulation. Bayesian regression found that an excitability difference above 3 mA would indicate a 75.8% probability of a glioma being high grade. Our results suggest that cortical motor excitability difference between the asleep and awake phases in glioma surgery could correlate with tumor grade.

Two Types of σ-Allenyl Complexes from Reactions of Silylenes and Germylenes with Chromium Fischer Alkynyl(alkoxy)carbenes.

The reactivity of amidinatotetrylenes of the type E(tBu2 bzm)R1 (E=Si, Ge; tBu2 bzm=N,N'-bis(tertbutyl)benzamidinate; R1 =alkyl or aryl) with the chromium Fischer alkynylcarbene complexes [Cr{C(OEt)C2 R2 }(CO)5 ] (R2 =Ph; ferrocenyl, Fc) has been studied. At room temperature, two different reaction pathways have been identified: (a) attack of the amidinatotetrylene to the alkynyl C2 atom (γ-attack), which leads to σ-allenyl complexes in which the original Ccarbene atom maintains its attachment to the Cr(CO)5 and OEt groups (compounds 3 E - R 1 - R 2 ), and (b) attack of the amidinatotetrylene to the Ccarbene atom (α-attack), which ends in σ-allenyl complexes in which the original Ccarbene atom is not attached to the metal atom and has been inserted into an E-N bond of the amidinatotetrylene forming an E-C-N-C-N five-membered ring (compounds 4 E - R 1 - R 2 ). It has been found that compounds 3 E - R 1 - R 2 are thermodynamically less stable than their corresponding 4 E - R 1 - R 2 isomers and that some of the former (E=Ge; R1 =CH2 SiMe3 ) can be transformed into the latter upon heating. At high temperatures (>70 °C) the reactions involving bulky amidinatotetrylenes (R1 =Mes, tBu) end in the carbene-substitution products [Cr{E(tBu2 bzm)R1 }(CO)5 ].

Reversible Carbene Insertion into a Ge-N Bond and Insights into CO and Carbene Substitution Reactions Involving Amidinatogermylenes and Fischer Carbene Complexes.

The formation of the five-membered-ring germylene complexes [M(CO)5 {Ge(tBu2 bzamC(OEt)Me)tBu}] (3M ; M=Cr, W), which occurs readily at room temperature from the germylene Ge(tBu2 bzam)tBu (1tBu ) and Fischer carbenes [M(CO)5 {C(OEt)Me}] (2M ; M=Cr, W), has been found to be reversible. Upon heating at 60 °C, complexes 3M undergo epimerization to an equilibrium mixture of 3M and 3'M . At that temperature, the chromium epimers (but not the tungsten ones) release CO to end in the mixed germylene-Fischer carbene complexes [Cr(CO)4 {C(OEt)Me}{Ge(tBu2 bzam)tBu}] (cis-4Cr and trans-4Cr ). The latter decompose at 120 °C to [Cr(CO)5 {Ge(tBu2 bzam)tBu}] (6Cr ). Because the formation of cis-4Cr and trans-4Cr from 3Cr or 3'Cr requires the presence of free 1tBu and 2Cr in the reaction solutions, the reactions of 1tBu with 2M to give 3M (and 3'M at 60 °C) should be reversible. This proposal has been proven by germylene-exchange crossover reactions in which free 1tBu and [M(CO)5 {Ge(tBu2 bzamC(OEt)Me)CH2 SiMe3 }] (5'M ; M=Cr, W) were formed when complexes 3M were treated at room temperature with the germylene Ge(tBu2 bzam)CH2 SiMe3 (1tmsm ). A clear differential behavior between N-heterocyclic carbenes (NHCs) and amidinatogermylenes (1tBu and 1tmsm ) in their reactivity against group 6 metal Fischer carbene complexes is demonstrated. The higher electron-donor capacity of amidinatogermylenes with respect to NHCs and the bias of the former to get involved in ring expansion processes are responsible for this differential behavior.

Unexpected Zwitterionic Allenyls from Silylenes and a Fischer Alkynylcarbene: A Remarkable Silylene-Promoted Rearrangement.

The silylenes Si(tBu2 bzam)R (tBu2 bzam=N,N'-bis(tertbutyl)benzamidinate; R=mesityl, CH2 SiMe3 ) attack the Ccarbene atom of the Fischer alkynyl(ethoxy)carbene complex [W(CO)5 {C(OEt)C2 Ph}] to give, after a striking rearrangement, zwitterionic σ-allenyl complexes in which the original carbene C atom forms part of the allene C3 fragment and also of a Si-C-N-C-N five-membered ring after insertion into a Si-N bond of the original amidinatosilylene. These remarkable allenyl products, which contain two stereogenic groups, are selectively formed as single diastereomers.

Triazole-Containing [FeFe] Hydrogenase Mimics: Synthesis and Electrocatalytic Behavior.

Through a Cu-catalyzed Huisgen cycloaddition between terminal alkynes and azides (CuAAC) reaction, azide [(µ-SCH2)2N(4-N3C6H4)Fe2(CO)6] has demonstrated to be a robust and versatile reagent able to incorporate the [(µ-SR)2Fe2(CO)6] fragment on a wide range of substrates, ranging from aromatic compounds to nucleosides, metallocenes, or redox and luminescent markers. The [FeIFeI]/[Fe0FeI] and [Fe0FeI]/[Fe0Fe0] reduction potentials of the triazole derivatives prepared are comparable to those of other aminodithiolate (adt) Fe-Fe hydrogenase mimics. The presence of the triazole linker influences the electrochemical behavior of these complexes depending on the strength of the acid employed.

First Insertions of Carbene Ligands into Ge-N and Si-N Bonds.

The insertion of carbene ligands into Ge-N (three examples) and Si-N (one example) bonds has been achieved for the first time by treating Fischer carbene complexes (M=W, Cr) with bulky amidinatotetrylenes (E=Ge, Si). These reactions, which start with a nucleophilic attack of the amidinatotetrylene heavier group 14 atom to the carbene C atom, proceed through a stereoselective insertion of the carbene fragment into an E-N bond of the amidinatotetrylene ENCN four-membered ring, leading to [M(CO)5 L] derivatives in which L belongs to a novel family of tetrylene ligands comprising an ECNCN five-membered ring.

Sequential Reactions of Alkynes on an Iridium(III) Single Site.

Sequential insertion of terminal alkynes on IrIII cyclometalated complexes allow the formation of novel metallapolycycles in a controlled and efficient manner. ortho-Methylarylethynyl derivatives led to an unprecedented cascade combination of three fundamental processes (C-C bond formation, C(sp3 )-H activation, and reductive coupling) on a single IrIII center, in a process compatible with functionalized biomolecules and photoactive substrates. The reaction with tert-butylacetylene led to a [6,5,4]-polycycle that incorporates an iridacyclobutenylidene in its structure. The sequence is a multicomponent reaction in which the metal not only promotes the different steps but also determines their stereoselectivity. This is an elegant example of the synergy between a metal-promoting reaction and a symmetry-defined stereochemistry.

An Entry to Mixed NHC-Fischer Carbene Complexes and Zwitterionic Group 6 Metal Alkenyls.

The addition of NHCs to α,ß-unsaturated Cr(0) and W(0) (Fischer) carbene complexes is strongly dependent on the electrophilicity of the carbene carbon. Electrophilic alkoxy-carbene complexes quantitatively react with NHCs to yield stable zwitterionic (racemic) Cr(0) - and W(0) -alkenyls with total regio- and E-stereoselectivity. Less electrophilic aminocarbenes react with NHCs to promote the displacement of a CO ligand and yield "mixed" NHC/Fischer biscarbenes in a process that is unprecedented in group 6 metal-carbene chemistry. In fact, the compounds prepared, are some of the scarce examples of Fischer bisylidenes reported in the literature. The electrochemistry of the zwitterionic Cr(0) - and W(0) -alkenylcomplexes made, show that these compounds have a strong reductor character, which is demonstrated in their reactions towards [Ph3 C][PF6 ]. The oxidation processes lead to new types of cationic Fischer mono- and biscarbene complexes having a charged NHC fragment in their structures, in a new example of the use of electron-transfer reactions as a method to prepare novel group 6 (Fischer) carbene complexes.

Novel artemisinin derivatives with potential usefulness against liver/colon cancer and viral hepatitis.

Antitumor and antiviral properties of the antimalaria drug artemisinin from Artemisia annua have been reported. Novel artemisinin derivatives (AD1-AD8) have been synthesized and evaluated using in vitro models of liver/colon cancer and viral hepatitis B and C. Cell viability assays after treating human cell lines from hepatoblastoma (HepG2), hepatocarcinoma (SK-HEP-1), and colon adenocarcinoma (LS174T) with AD1-AD8 for a short (6h) and long (72h) period revealed that AD5 combined low acute toxicity together with high antiproliferative effect (IC50=1-5µM). Since iron-mediated activation of peroxide bond is involved in artemisinin antimalarial activity, the effect of iron(II)-glycine sulfate (ferrosanol) and iron(III)-containing protoporphyrin IX (hemin) was investigated. Ferrosanol, but not hemin, enhanced antiproliferative activity of AD5 if the cells were preloaded with AD5, but not if both compouds were added together. Five derivatives (AD1>AD2>AD7>AD3>AD8) were able to inhibit the cytopathic effect of bovine viral diarrhoea virus (BVDV), a surrogate in vitro model of hepatitis C virus (HCV), used here to evaluate the anti-Flaviviridae activity. Moreover, AD1 and AD2 inhibited the release of BVDV-RNA to the culture medium. Co-treatment with hemin or ferrosanol resulted in enhanced anti-Flaviviridae activity of AD1. In HepG2 cells permanently infected with hepatitis B virus (HBV), AD1 and AD4, at non-toxic concentrations for the host cells were able to reduce the release of HBV-DNA to the medium. In conclusion, high pharmacological interest deserving further evaluation in animal models has been identified for novel artemisinin-related drugs potentially useful for the treatment of liver cancer and viral hepatitis B and C.

Bacterial tracheitis: a varied entity.

OBJECTIVE: The objective of the study was to highlight the different presentations of bacterial tracheitis (BT), a potential life-threatening cause of airway obstruction in children. DESIGN: Case series. METHODS: A review of medical records of 4 cases of BT who presented with differing signs and symptoms was performed. RESULTS: Clinical manifestations of 4 patients with BT are presented with corresponding endoscopic appearances of the airway. Two patients were afebrile and nontoxic, and 2 had an elevated white cell count. Three had different degrees of stridor. One had a respiratory arrest. Cultures grew Staphylococcus aureus in 2 and Moraxella catarrhalis in 1 and were mixed in 1 patient. None required intubation. All were successfully treated with antibiotics and bronchoscopic debridement of the membranes. CONCLUSIONS: Bacterial tracheitis needs a high index of suspicion because of its varied presentations. Certain forms have less severe clinical manifestations. These forms also require aggressive management as they can result in airway obstruction from membranes and edema.

Enamel thickness in the Middle Miocene great apes Anoiapithecus, Pierolapithecus and Dryopithecus.

On the basis of industrial computed tomography, relative enamel thickness (RET) is computed in three Middle Miocene (ca 11.9-11.8 Ma) hominoids from Abocador de Can Mata (Vallès-Penedès Basin, Catalonia, Spain): Pierolapithecus catalaunicus from BCV1 and Anoiapithecus brevirostris from C3-Aj, interpreted as stem hominids; and Dryopithecus fontani from C3-Ae of uncertain phylogenetic affinities. Pierolapithecus displays an average RET value of 19.5, Anoiapithecus of 18.6 and Dryopithecus of 10.6. The thick-enamelled condition of Pierolapithecus and Anoiapithecus is also characteristic of afropithecids, including the more derived kenyapithecins from the early Middle Miocene of Eurasia (Griphopithecus and Kenyapithecus). Given the presence of other dentognathic and craniofacial similarities, thick enamel may be interpreted as a symplesiomorphy of the Hominidae (the great ape and human clade), which would have been later independently modified along several lineages. Given the correlation between thick enamel and hard-object feeding, our results suggest that thick enamel might have been the fundamental adaptation that enabled the out-of-Africa dispersal of great-ape ancestors and their subsequent initial radiation throughout Eurasia. The much thinner enamel of Dryopithecus is difficult to interpret given phylogenetic uncertainties, being either a hominine synapomorphy or a convergently developed feature.

Orang-like manual adaptations in the fossil hominoid Hispanopithecus laietanus: first steps towards great ape suspensory behaviours.

Morphological and biometrical analyses of the partial hand IPS18800 of the fossil great ape Hispanopithecus laietanus (=Dryopithecus laietanus), from the Late Miocene (about 9.5Ma) of Can Llobateres (Catalonia, Spain), reveal many similarities with extant orang-utans (Pongo). These similarities are interpreted as adaptations to below-branch suspensory behaviours, including arm-swinging and clambering/postural feeding on slender arboreal supports, due to an orang-like double-locking mechanism. This is confirmed by the long and highly curved phalanges of Hispanopithecus. The short and stout metacarpals with dorsally constricted heads, together with the dorsally extended articular facets on proximal phalanges, indicate the persistence of significant degrees of palmigrady. A powerful grasping capability is indicated by the great development of basal phalangeal tubercles, the marked insertions for the flexors on phalangeal shafts and the large pits for the collateral ligaments. The morphology of the Hispanopithecus long bones of the hand indicates a unique positional repertoire, combining orthogrady with suspensory behaviours and palmigrade quadrupedalism. The retention of powerful grasping and palmigrady suggests that the last common ancestor of hominids might have been more primitive than what can be inferred on the basis of extant taxa, suggesting that pronograde behaviours are compatible with an orthograde bodyplan suitable for climbing and suspension.

Association between within-visit systolic blood pressure variability and development of pre-diabetes and diabetes among overweight/obese individuals.

Short-term blood pressure variability is associated with pre-diabetes/diabetes cross-sectionally, but there are no longitudinal studies evaluating this association. The objective of this study is to evaluate the association between within-visit systolic and diastolic blood pressure variability and development of pre-diabetes/diabetes longitudinally. The study was conducted among eligible participants from the San Juan Overweight Adults Longitudinal Study (SOALS), who completed the 3-year follow-up exam. Participants were Hispanics, 40-65 years of age, and free of diabetes at baseline. Within-visit systolic and diastolic blood pressure variability was defined as the maximum difference between three measures, taken a few minutes apart, of systolic and diastolic blood pressure, respectively. Diabetes progression was defined as development of pre-diabetes/diabetes over the follow-up period. We computed multivariate incidence rate ratios adjusting for baseline age, gender, smoking, physical activity, waist circumference, and hypertension status. Participants with systolic blood pressure variability ≥10 mmHg compared to those with <10 mmHg, showed higher progression to pre-diabetes/diabetes (RR = 1.77, 95% CI: 1.30-2.42). The association persisted among never smokers. Diastolic blood pressure variability ≥10 mmHg (compared to <10 mmHg) did not show an association with diabetes status progression (RR = 1.20, 95% CI: 0.71-2.01). Additional adjustment of baseline glycemia, C-reactive protein, and lipids (reported dyslipidemia or baseline HDL or triglycerides) did not change the estimates. Systolic blood pressure variability may be a novel independent risk factor and an early predictor for diabetes, which can be easily incorporated into a single routine outpatient visit at none to minimal additional cost.

Outbreak of brainstem encephalitis associated with enterovirus-A71 in Catalonia, Spain (2016): a clinical observational study in a children's reference centre in Catalonia.

OBJECTIVES: To describe the characteristics of an outbreak of brainstem encephalitis and encephalomyelitis related to enterovirus (EV) infection in Catalonia (Spain), a setting in which these manifestations were uncommon. METHODS: Clinical and microbiological data were analysed from patients with neurological symptoms associated with EV detection admitted to a reference paediatric hospital between April and June 2016. RESULTS: Fifty-seven patients were included. Median age was 27.7 months (p25-p75 17.1-37.6). Forty-one (72%) were diagnosed with brainstem encephalitis, seven (12%) with aseptic meningitis, six (11%) with encephalitis, and three (5%) with encephalomyelitis (two out of three with cardiopulmonary failure). Fever, lethargy, and myoclonic jerks were the most common symptoms. Age younger than 12 months, higher white-blood-cell count, and higher procalcitonin levels were associated with cardiopulmonary failure. Using a PAN-EV real-time PCR, EV was detected in faeces and/or nasopharyngeal aspirate in all the patients, but it was found in cerebrospinal fluid only in patients with aseptic meningitis. EV was genotyped in 47 out of 57 and EV-A71 was identified in 40 out of 47, being the only EV type found in patients with brainstem symptoms. Most of the detected EV-A71 strains were subgenogroup C1. Intravenous immunoglobulins were used in 34 patients. Eight cases (14%) were admitted to the intensive care unit. All the patients but three, those with encephalomyelitis, showed a good clinical course and had no significant sequelae. No deaths occurred. CONCLUSIONS: The 2016 outbreak of brainstem encephalitis in Catalonia was associated with EV-A71 subgenogroup C1. Despite the clinical manifestations of serious disease, a favourable outcome was observed in the majority of patients.

Relationship of basal and postprandial intraduodenal bile acid concentrations and plasma cholecystokinin levels with abdominal pain in patients with chronic pancreatitis.

Abdominal pain in patients with chronic pancreatitis has been related to an increase in plasma cholecystokinin (CCK) levels. The aim of the study was to disclose the relation of the altered response with the low intraduodenal bile acids levels found in these patients. Twenty patients with chronic pancreatitis were classified into groups I (n = 11) and II (n = 9) according to the presence or absence of pain. Intraduodenal trypsin and bile acids concentrations and plasma CCK levels were measured before and 30, 60, and 90 min after a test meal. Comparisons between values in both groups were carried out. Correlation of intraduodenal trypsin and bile acids with plasma CCK was analyzed. Patients with pain exhibited significantly lower intraduodenal trypsin levels at 30 and 90 min and lower basal and postprandial intraduodenal bile acids levels than patients without pain. In patients with pain, basal and postprandial plasma CCK levels were significantly higher than in patients without pain. A negative correlation was demonstrated between intraduodenal bile acids and plasma CCK. In patients with chronic pancreatitis and pain, a reduction in intraduodenal postprandial trypsin and basal and postprandial bile acids concentrations, as well as an increase in basal and postprandial plasma CCK levels, was encountered. A negative correlation between intraduodenal bile acids and plasma CCK concentrations was detected that may be implicated in the pathogenesis of pain.

[Isolated laryngeal candidiasis. Description of 2 cases and review of the literature]. / Candidiasis laríngea aislada. Descripción de 2 casos y revisión de la literatura.

Infection of the larynx by Candida is rare and usually accompanies lung or disseminated candidiasis. The incidence of isolated laryngeal candidiasis (ILC) is low, although it may be underestimated. We describe 2 patients with ILC confirmed during autopsy: a 45-years-old male with pulmonary fibrosis and a 4-years-old girl with acute myeloblastic leukemia. Hoarseness and dysphagia are the most common symptoms of ILC. The most effective diagnostic technique is laryngoscopy with specimen culture and/or histopathology. Specimens usually show whitish plaques on the larynx. Most ILC patients have some associated disease and/or predisposing factors, with frequent antibiotic treatment prior to the advent of candidiasis. Intravenous amphotericin B provides the most effective therapy, although other antimycotics are also useful. Early diagnosis and initiation of therapy curtail the disease and can prevent systemic dissemination.

[Meningitis due to streptococcus viridans]. / Meningitis producidas por estreptococos viridans.

Viridans Streptococci (VS) may cause meningitis although, in most cases, they are isolated as contaminants in CSF. However VS should not be systematically underestimated as contaminants in CSF without a suitable clinical and analytical evaluation. Meningitis as a result of VS is being diagnosed with increasing frequency, especially in new born babies. Classic predisposition factors and illnesses (traumatism, surgery and infection) have increased, one frequent pathogenic mechanism being rupture of the mucous membrane with subsequent meningitis. VS are normally sensitive to penicillin G. However VS may be resistant to penicillin (low affinity of PBP to penicillin) and cause serious infections, including meningitis. For this reason it is convenient to perform sensitivity tests on VS in vitro in isolation to determine the appropriate therapy.

[Neurologic manifestations of Whipple disease]. / Manifestaciones neurológicas de la enfermedad de Whipple.

Pure neurologic Whipple's disease (WD) may be suspected by same clinical data (dementia-ophthalmoplegia-myoclonus triad, oculomasticatory myorhythmia) with support of MRI. Diagnosis is confirmed by intestinal and/or brain biopsy. Early recognition is critical in a disease that can lead to irreversible neurologic sequelae and that can potentially be cured. Despite therapy, relapses in patients with WD are common, being neurologic recurrence the most frequent and serious. Antibiotics that do not cross the blood-brain barrier are not adequate initial therapy for WD, because they predispose to neurologic relapse. Patients with WD should be treated for one year with antibiotics that cross the blood-brain barrier (such as parenteral penicillin+streptomycin, followed by oral trimethoprim-sulfamethoxazole). CNS relapse is usually resistant to therapy.

[Viridans streptococci isolated from cerebrospinal fluid. Clinical significance of 9 cases]. / Estreptococos viridans aislados del líquido cefalorraquídeo. Significado clínico de 9 casos.

Viridans streptococci (VS) are often isolated from cerebrospinal fluid (CSF). However, the significance of such isolates is poorly understood. In the present study we carry out a retrospective analysis of 9 patients in whom VS were isolated from CSF during a 1-year period at La Paz Hospital. Two patients (22.2%) had meningitis diagnosed through clinical, laboratory and bacteriologic findings. Both patients had predisposition diseases (previous difficult spinal tap, ventriculo-peritoneal shunt). The other isolations were considered as contaminants. Three patients (33.3%) with no VS meningitis had other different serious disease (sepsis without bacteriologic confirmation). VS are isolated with relative frequency from CSF, although they cause meningitis in less than one-quarter of the cases (those who have a predisposition disease). In the other cases, VS are isolated as contaminants of CSF and other disease should be search as cause of patient symptoms.

[Sero-ascitic gradient of albumin: usefulness and diagnostic limitations]. / Gradiente sero-ascítico de albúmina: utilidad y limitaciones diagnósticas.

The serum-ascites albumin (SAA) gradient has been defined as the serum albumin concentration minus the ascitic fluid albumin concentration. The SAA gradient is superior to the exudate-transudate concept to classify ascites, being a exact portal hypertension (PH) marker. An elevated SAA gradient (1.1 g/L or greater) correlates with PH, whereas a low gradient indicates no PH. The SAA gradient correlates well with PH in cirrhotic patients. It is also of particular utility to differentiate between congestive heart failure and malignant ascites without liver metastases (both of them with elevated ascites fluid proteins -AFP-). However, a low SAA gradient do not differentiate between tuberculous and malignant ascites. Consequently, there are still need for tests a cytology, culture for mycobacteria or ascites fluid polymorphonuclear cell count in some cases. The level of AFP, apart from the exudate-transudate concept, has some value for certain cases (a low level of AFP implicates a high risk of spontaneous bacterial peritonitis). The SAA gradient should replace the AFP concentration as the initial test to classify ascites.