Differential levels of Neurofilament Light protein in cerebrospinal fluid in patients with a wide range of neurodegenerative disorders.

Cerebrospinal fluid (CSF) biomarkers are useful in the diagnosis and the prediction of progression of several neurodegenerative diseases. Among them, CSF neurofilament light (NfL) protein has particular interest, as its levels reflect neuroaxonal degeneration, a common feature in various neurodegenerative diseases. In the present study, we analyzed NfL levels in the CSF of 535 participants of the SPIN (Sant Pau Initiative on Neurodegeneration) cohort including cognitively normal participants, patients with Alzheimer disease (AD), Down syndrome (DS), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). We evaluated the differences in CSF NfL accross groups and its association with other CSF biomarkers and with cognitive scales. All neurogenerative diseases showed increased levels of CSF NfL, with the highest levels in patients with ALS, FTD, CBS and PSP. Furthermore, we found an association of CSF NfL levels with cognitive impairment in patients within the AD and FTD spectrum and with AD pathology in DLB and DS patients. These results have implications for the use of NfL as a marker in neurodegenerative diseases.

The impact of wastewater matrix on the degradation of pharmaceutically active compounds by oxidation processes including ultraviolet radiation and sulfate radicals.

Ultraviolet radiation (UV)-activated peroxydisulfate (PDS) and peroxymonosulfate (PMS) advanced oxidation processes were examined for their capacity to remove nine pharmaceutically active compounds (PhACs) from secondary effluent. The effect of operational parameters (initial oxidant concentration, UV exposure time, pH, common coexisting anions and effluent organic matter (EfOM)) on UV/PDS and UV/PMS treatment efficiency was investigated in a collimated beam device housing a low-pressure mercury UV lamp emitting light at 253.7 nm. Both AOPs achieved high removals (>90%) when applied to pure water. Under otherwise similar conditions the removal percentage fell by 20-30% due to the scavenging of effluent organic matter (EfOM) in secondary effluent. Finally, eliminating EfOM but maintaining the inorganic composition, the radical scavenging effect was reduced and 98.3% and 85.6% average removals were obtained by UV/PDS and UV/PMS, respectively. Increasing pH improved degradation of several PhACs containing amine groups. Higher oxidant dosages created only a significant benefit in UV/PDS. The chloride anion produced a negligible effect on both processes, while higher nitrate concentrations increased removal percentage but did not affect degradation rate constants. Finally and surprisingly, the addition of bicarbonate had the strongest positive impact on the degradation kinetics observed, even stronger than the elimination of EfOM from secondary effluent.

Evolución a largo plazo de la hidrocefalia crónica del adulto idiopática tratada con válvula de derivación ventrículo-peritoneal / Long-term outcomes of adult chronic idiopathic hydrocephalus treated with a ventriculo-peritoneal shunt

Introducción. La hidrocefalia crónica del adulto idiopática (HCAI) es considerada una causa de demencia tratable mediante la implantación de una válvula de derivación ventrículo-peritoneal (VDVP). Nos planteamos estudiar la evolución clínica y funcional de la HCAI tratada con VDVP, así como los factores asociados con una mejor evolución a largo plazo. Sujetos y métodos. Estudio observacional de pacientes con diagnóstico de HCAI probable (según criterios de la Sociedad Japonesa de Neurocirugía) y tratados con VDVP entre 2008 y 2013 en un hospital de tercer nivel español. Se establecieron 4 grupos de respuesta clínica (normalización, mejoría parcial, mejoría dudosa y empeoramiento) y la situación funcional se evaluó mediante la escala de Rankin modificada (ERm). Resultados. Se incluyó a 29 pacientes con una edad media de 73,9 años. El 62,1% eran hombres y el 65,5% presentaban HTA. Se observó una respuesta clínica al menos parcial en el 58 y el 48% al año y al final del seguimiento (seguimiento medio de 37,8 meses), respectivamente. La edad, la frecuencia de HTA y las complicaciones quirúrgicas fueron superiores en el grupo con mala respuesta. Un paciente falleció, el 20,7% presentó complicaciones graves y el 69% era dependiente (ERm ≥ 3) al final del seguimiento. La edad se asoció de manera independiente a peor respuesta clínica al año y una mayor dependencia al final del seguimiento. Conclusión. El beneficio de la VDVP fue parcial y transitorio, con una alta frecuencia de complicaciones y dependencia funcional en el seguimiento a largo plazo, especialmente en los pacientes de mayor edad (AU)

Introduction. Adult chronic idiopathic hydrocephalus (ACIH) is a cause of dementia that can be treated by implanting a ventriculo-peritoneal shunt (VPS). We aim to study clinical and functional outcomes in patients with ACIH corrected with a VPS. Subjects and methods. Observational cohort study of patients diagnosed with probable ACIH (Japan Neurosurgical Society guidelines) and undergoing shunt placement between 2008 and 2013 in a centre of reference for neurosurgery in Spain. Clinical improvement was classified in 4 categories (resolution, partial improvement, equivocal improvement, and no improvement); functional outcome was assessed on the modified Rankin scale (mRS). Results. The study included 29 patients with a mean age of 73.9 years; 62.1% were male and 65.5% had hypertension. Clinical improvement (complete or partial) was observed in 58% after one year and in 48% by the end of the follow-up period (mean follow-up time was 37.8 months). Older age, presence of hypertension, and surgery-related complications were more prevalent in the group responding poorly to treatment. One patient died, 20.7% experienced severe complications, and 69% were dependent (mRS ≥ 3) by the end of the follow-up period. Age at diagnosis was independently associated with poorer clinical response at one year and a higher degree of dependency by the end of follow-up. Conclusion. Symptomatic benefits offered by VPS were partial and transient; treatment was associated with a high complication rate and poor functional outcomes in the long term, especially in the oldest patients (AU)

Long-term outcomes of adult chronic idiopathic hydrocephalus treated with a ventriculo-peritoneal shunt. / Evolución a largo plazo de la hidrocefalia crónica del adulto idiopática tratada con válvula de derivación ventrículo-peritoneal.

INTRODUCTION: Adult chronic idiopathic hydrocephalus (ACIH) is a cause of dementia that can be treated by implanting a ventriculo-peritoneal shunt (VPS). We aim to study clinical and functional outcomes in patients with ACIH corrected with a VPS. SUBJECTS AND METHODS: Observational cohort study of patients diagnosed with probable ACIH (Japan Neurosurgical Society guidelines) and undergoing shunt placement between 2008 and 2013 in a centre of reference for neurosurgery in Spain. Clinical improvement was classified in 4 categories (resolution, partial improvement, equivocal improvement, and no improvement); functional outcome was assessed on the modified Rankin scale (mRS). RESULTS: The study included 29 patients with a mean age of 73.9 years; 62.1% were male and 65.5% had hypertension. Clinical improvement (complete or partial) was observed in 58% after one year and in 48% by the end of the follow-up period (mean follow-up time was 37.8 months). Older age, presence of hypertension, and surgery-related complications were more prevalent in the group responding poorly to treatment. One patient died, 20.7% experienced severe complications, and 69% were dependent (mRS ≥ 3) by the end of the follow-up period. Age at diagnosis was independently associated with poorer clinical response at one year and a higher degree of dependency by the end of follow-up. CONCLUSION: Symptomatic benefits offered by VPS were partial and transient; treatment was associated with a high complication rate and poor functional outcomes in the long term, especially in the oldest patients.

A missense variant in GLP1R gene is associated with the glycaemic response to treatment with gliptins.

Gliptins act by increasing endogenous incretin levels. Glucagon-like peptide-1 receptor (GLP1R) and glucose-dependent insulinotropic peptide receptor (GIPR) are their indirect drug targets. Variants of GLP1R and GIPR have previously been associated with the incretin effect. The aim of the present pilot study was to examine associations of the GLP1R and GIPR gene variants with the glycaemic response to gliptins. A total of 140 consecutive patients with type 2 diabetes were followed-up 6 months after initiation of gliptin treatment. GLP1R rs6923761 (Gly168Ser) and GIPR rs10423928 genotyping was performed using real-time PCR, with subsequent high-resolution melting analysis. The main study outcome was reduction in glycated haemoglobin (HbA1c) after treatment. GLP1R Gly168Ser variant was significantly associated with reduction in HbA1c in an additive model (ß = -0.33, p = 0.011). The mean reduction in HbA1c in Ser/Ser homozygotes was significantly lower compared with Gly-allele carriers [0.12 ± 0.23% vs. 0.80 ± 0.09% (1.3 ± 2.5 mmol/mol vs. 8.7 ± 1.0 mmol/mol); p = 0.008]. In conclusion, GLP1R missense variant was associated with a reduced response to gliptin treatment. The genotype-related effect size of ∼0.7% (8 mmol/mol) is equal to an average effect of gliptin treatment and makes this variant a candidate for use in precision medicine.

Overall adsorption rate of metronidazole, dimetridazole and diatrizoate on activated carbons prepared from coffee residues and almond shells.

This study analyzed the overall adsorption rate of metronidazole, dimetridazole, and diatrizoate on activated carbons prepared from coffee residues and almond shells. It was also elucidated whether the overall adsorption rate was controlled by reaction on the adsorbent surface or by intraparticle diffusion. Experimental data of the pollutant concentration decay curves as a function of contact time were interpreted by kinetics (first- and second-order) and diffusion models, considering external mass transfer, surface and/or pore volume diffusion, and adsorption on an active site. The experimental data were better interpreted by a first-order than second-order kinetic model, and the first-order adsorption rate constant varied linearly with respect to the surface area and total pore volume of the adsorbents. According to the diffusion model, the overall adsorption rate is governed by intraparticle diffusion, and surface diffusion is the main mechanism controlling the intraparticle diffusion, representing >90% of total intraparticle diffusion.

Recurrence of stroke amongst women of reproductive age: impact of and on subsequent pregnancies.

BACKGROUND AND PURPOSE: The risk of recurrence of stroke after pregnancy is poorly known. METHODS: This was an observational study of women younger than 45 years of age with transient ischaemic attack (TIA), cerebral infarction (CI), cerebral venous thrombosis (CVT) or intracerebral hemorrhage (ICH) treated in a stroke unit (January 1996-2011). The clinical data were prospectively collected in a database. Information on reproductive history after stroke was obtained using telephone surveys (2011). The variables were demographic data, vascular risk factors, stroke type, outcomes, medical advice concerning pregnancies after stroke, number of pregnancies after stroke, neurological assessment during pregnancy, antithrombotic treatments during pregnancy/puerperium, fertility treatments administered and information about hemorrhagic/ischaemic stroke recurrence. RESULTS: Overall, 102 women were included: 24 TIA, 64 CI (four large vessel disease, 14 cardioembolic, 12 small vessel disease, 17 undetermined etiology, 17 uncommon etiology), 12 CVT and two ICH. Mean age at the time of first stroke was 35 (±7.5) years. Median follow-up was 7.4 years (range 1-17). Thirty-two pregnancies occurred in 27 patients (previous diagnosis: four TIA, 17 CI, five CVT and one ICH). One woman became pregnant using in vitro fertilization. Only eight pregnancies were followed up by a neurologist. Of 26 pregnancies without previous history of ICH, 18 (62%) underwent preventive antithrombotic treatment. No recurrence of stroke was observed during pregnancy/puerperium. Of the women without pregnancies after the first cerebrovascular event, four CIs and three TIAs were observed. CONCLUSION: The recurrence of stroke after pregnancy is very low, which should be considered when counseling these patients.

Nitroimidazoles adsorption on activated carbon cloth from aqueous solution.

The objective of this study was to analyze the equilibrium and adsorption kinetics of nitroimidazoles on activated carbon cloth (ACC), determining the main interactions responsible for the adsorption process and the diffusion mechanism of these compounds on this material. The influence of the different operational variables, such as ionic strength, pH, temperature, and type of water (ultrapure, surface, and waste), was also studied. The results obtained show that the ACC has a high capacity to adsorb nitroimidazoles in aqueous solution. Electrostatic interactions play an important role at pH<3, which favors the repulsive forces between dimetridazole or metronidazole and the ACC surface. The formation of hydrogen bonds and dispersive interactions play the predominant role at higher pH values. Modifications of the ACC with NH3, K2S2O8, and O3 demonstrated that its surface chemistry plays a predominant role in nitroimidazole adsorption on this material. The adsorption capacity of ACC is considerably high in surface waters and reduced in urban wastewater, due to the levels of alkalinity and dissolved organic matter present in the different types of water. Finally, the results of applying kinetic models revealed that the global adsorption rate of dimetridazole and metronidazole is controlled by intraparticle diffusion.

Pituitary apoplexy in a patient with acute myeloid leukemia and thrombocytopenia.

We describe a 72-year-old woman with a history of acute myeloid leukemia who developed pituitary apoplexy associated with thrombocytopenia secondary to chemotherapy. She presented with new onset severe headache, nausea, vomiting and blurred vision. Initial physical examination was unremarkable. CT scan of the head was initially negative. Upon admission for further work up, She developed a high-grade fever, hypotension and obtundation. Subsequent physical examination revealed bitemporal visual fields defects and decreased visual acuity. Repeat imaging of head revealed a hemorrhagic pituitary mass compressing the optic chiasm. Laboratory results were compatible with the diagnosis of pan-hypopituitary syndrome. She received high dose steroids and was transferred for transnasal sphenoidotomy decompression surgery. The visual defects improved postoperatively. A literature review of Pituitary apoplexy is presented. Pituitary apoplexy secondary to thrombocytopenia has never been reported.

Usefulness of Telfa pads in the histologic assessment of stereotactic-guided breast biopsy specimens.

Stereotactic core-needle biopsies (SCNBs) are being increasingly used for the diagnosis of breast lesions. Focal mammographic calcifications are often considered significant and sampled by SCNB. We compared diagnostic outcomes in breast tissue cut from 59 core biopsy blocks using Telfa pad embedding with those of 48 routinely embedded blocks. Specifically, we addressed the total length of core tissue in the first histologic section, the continuity and average core length in the first section, the frequency with which mammographic calcifications were confirmed histologically, and the number of sections per case needed to assure histologic-mammographic correlation. The first level of Telfa pad-embedded material showed significantly greater aggregate tissue length, more core continuity, and greater average core length. With routine embedding, we missed 3 of 17 radiologic calcific foci. With Telfa pad embedding, we detected all of the 24 calcific foci and consumed 50% fewer slides in doing so. We conclude that Telfa pad embedding of SCNBs of the breast provides an improved, cost-effective approach to diagnosis and histologic-radiologic correlation.

Fine-needle aspiration cytology of idiopathic pancreatic islet cell adenosis.

A 68-yr-old woman was hospitalized because of abdominal pain, an enlarged pancreatic head by CT, and a questionable 4-cm mass in the liver. Fine-needle aspiration (FNA) of the pancreatic head disclosed a highly cellular specimen consisting of clusters of cytologically bland, monotonous, small nuclei and variable but generally sparse cytoplasm. Because of the differentiated monomorphic character of the cell clusters, the postaspiration differential cytopathologic diagnosis included islet cell tumor, acinic cell tumor, carcinoid, lymphoma, and well differentiated ductal adenocarcinoma. Pancreaticoduodenectomy and hepatic biopsy yielded a grossly normal pancreas and a cirrhotic liver. Histologic examination of the pancreas revealed a spotty but extensive spectrum of islet changes ranging from normal to bland hyperplasia, nesidioblastosis, microadenosis, and neuroendocrine microadenomas, all appearing in a light and electron microscopic context of an otherwise normal pancreas. This case highlights the differential diagnostic ambiguities presented by a continuum of pancreatic islet cell proliferations, especially among patients in whom there are no known predisposing factors for such diffuse preneoplastic or neoplastic changes.