Comparison of perinatal outcomes for all modes of second stage delivery in obstetric theatres: a retrospective observational study.

OBJECTIVE: To compare rates of vaginal delivery and adverse outcomes of instrumental delivery trials in obstetric theatre compared to primary emergency full dilation caesarean section. DESIGN: Retrospective cohort study. SETTING: University teaching hospital. POPULATION: Women with singleton, non-anomalous, pregnancy undergoing instrumental delivery trial in obstetric theatre. METHODS: Data were collected from consecutive cases during 2014 until 2018 using clinical records. Multivariate regression analysis was used comparing outcomes per first delivery method. MAIN OUTCOME MEASURES: Primary outcome was completion of vaginal delivery between all methods of instrumental delivery. Secondary outcome was a composite of immediate perinatal adverse outcomes for instrumental delivery modes and primary full dilation caesarean section. RESULTS: From 971 deliveries analysed: ventouse delivery was significantly less likely to achieve vaginal delivery compared with Keilland's forceps delivery (odds ratio [OR] 0.42, 95% CI 0.22-0.79). Once confounding factors were adjusted for, adverse outcome rates were less frequent in the Keilland's forceps group than with primary full dilation caesarean section (OR 0.37, 95% CI 0.16-0.81); however, the receiver operating characteristic curve produced from this model demonstrated a low predictive value (AUC 0.64). CONCLUSIONS: Attempting instrumental delivery in delivery suite theatre, as an alternative to primary emergency full dilation caesarean section, is both reasonable and safe. In this study, ventouse delivery performed poorly in comparison with other modes of instrumental delivery. Further research in the form of randomised controlled trials to identify the optimal mode of second stage delivery is paramount. TWEETABLE ABSTRACT: Instrumental delivery trials in theatre are safe but use of ventouse was associated with a higher rate of failure.

Integration of membrane distillation as volume reduction technology for in-land desalination brines management: Pre-treatments and scaling limitations.

Management of in-land reverse osmosis (RO) desalination brines generated from surface brackish waters is a current challenge. Among the different near-Zero and Zero Liquid Discharge (ZLD) alternatives, Membrane Distillation (MD), in which the transport of water is thermally driven, appears as an attractive technology if a residual heat source is available. The aim of this study was to identify the limits of Direct Contact MD (DCMD) pre-treatments such as acidification and aeration, or the combination of both to quantify the scaling reduction potential when treating a RO brine from surface brackish water. Experimental data were used to evaluate the effectiveness of DCMD to achieve the highest concentration factors, depending on the chosen pre-treatment. Additionally, an economic analysis of the operational cost, taking as case study a site where the current management of the brine is the discharge to the sea, was also carried out. Results showed that pre-treatments enhanced MD performance by increasing the concentration factor achieved and highest volume reductions (about 3 times) were reached with the combination of acidification and aeration pre-treatments. Both processes reduced the precipitation potential of CaCO3(s) by reducing the total inorganic carbon (>90%); however, CaSO4·2H2O(s) precipitated. Results also indicated that even if a waste heat source is available, brine disposal into the sea is the cheapest option, while ZLD alternatives were not attractive in the current regulatory framework since their cost was higher than the discharge to the sea. Other options related to the Minimal Liquid Discharge may be more economically attractive.

Coding of COPD Exacerbations and the Implications on Clinical Practice, Audit and Research.

International Classification of Disease 10 (ICD-10) codes record hospital admissions. We aimed to measure the accuracy of COPD exacerbation (ECOPD) codes and examine coding practices for COPD exacerbation.Prospective screening and ICD-10 codes were used to identify potential ECOPD within the DECAF internal validation cohort. Two coding searches were performed. The first search identified patients with an ECOPD discharge code, and a second, broad search was developed to identify all clinically confirmed ECOPD.717 of 1,122 (64%) patients with an ECOPD code had confirmed ECOPD. Common reasons for misclassification in the 405 patients who did not have an ECOPD included: lack of obstructive spirometry to diagnose COPD; and hospital admission due to progressive malignancy, asthma or cardiovascular disease. The broad search identified an additional 297 patients with ECOPD missed by the ECOPD codes. The vast majority of this group had pneumonia complicating ECOPD.ECOPD codes are insufficiently reliable to identify patients with clinically confirmed ECOPD for the purposes of audit or research. Search strategies should include pneumonia codes, specialist review of medical notes and spirometry confirmation of COPD.

The PEARL score predicts 90-day readmission or death after hospitalisation for acute exacerbation of COPD.

BACKGROUND: One in three patients hospitalised due to acute exacerbation of COPD (AECOPD) is readmitted within 90 days. No tool has been developed specifically in this population to predict readmission or death. Clinicians are unable to identify patients at particular risk, yet resources to prevent readmission are allocated based on clinical judgement. METHODS: In participating hospitals, consecutive admissions of patients with AECOPD were identified by screening wards and reviewing coding records. A tool to predict 90-day readmission or death without readmission was developed in two hospitals (the derivation cohort) and validated in: (a) the same hospitals at a later timeframe (internal validation cohort) and (b) four further UK hospitals (external validation cohort). Performance was compared with ADO, BODEX, CODEX, DOSE and LACE scores. RESULTS: Of 2417 patients, 936 were readmitted or died within 90 days of discharge. The five independent variables in the final model were: Previous admissions, eMRCD score, Age, Right-sided heart failure and Left-sided heart failure (PEARL). The PEARL score was consistently discriminative and accurate with a c-statistic of 0.73, 0.68 and 0.70 in the derivation, internal validation and external validation cohorts. Higher PEARL scores were associated with a shorter time to readmission. CONCLUSIONS: The PEARL score is a simple tool that can effectively stratify patients' risk of 90-day readmission or death, which could help guide readmission avoidance strategies within the clinical and research setting. It is superior to other scores that have been used in this population. TRIAL REGISTRATION NUMBER: UKCRN ID 14214.

Validation of the DECAF score to predict hospital mortality in acute exacerbations of COPD.

BACKGROUND: Hospitalisation due to acute exacerbations of COPD (AECOPD) is common, and subsequent mortality high. The DECAF score was derived for accurate prediction of mortality and risk stratification to inform patient care. We aimed to validate the DECAF score, internally and externally, and to compare its performance to other predictive tools. METHODS: The study took place in the two hospitals within the derivation study (internal validation) and in four additional hospitals (external validation) between January 2012 and May 2014. Consecutive admissions were identified by screening admissions and searching coding records. Admission clinical data, including DECAF indices, and mortality were recorded. The prognostic value of DECAF and other scores were assessed by the area under the receiver operator characteristic (AUROC) curve. RESULTS: In the internal and external validation cohorts, 880 and 845 patients were recruited. Mean age was 73.1 (SD 10.3) years, 54.3% were female, and mean (SD) FEV1 45.5 (18.3) per cent predicted. Overall mortality was 7.7%. The DECAF AUROC curve for inhospital mortality was 0.83 (95% CI 0.78 to 0.87) in the internal cohort and 0.82 (95% CI 0.77 to 0.87) in the external cohort, and was superior to other prognostic scores for inhospital or 30-day mortality. CONCLUSIONS: DECAF is a robust predictor of mortality, using indices routinely available on admission. Its generalisability is supported by consistent strong performance; it can identify low-risk patients (DECAF 0-1) potentially suitable for Hospital at Home or early supported discharge services, and high-risk patients (DECAF 3-6) for escalation planning or appropriate early palliation. TRIAL REGISTRATION NUMBER: UKCRN ID 14214.

Techno-economic assessment of decentralized polishing schemes for municipal water reclamation and reuse in the industrial sector in costal semiarid regions: The case of Barcelona (Spain).

This study demonstrates the techno-economic reliability of an innovative fit-for-use treatment train to boost municipal reclaimed water reuse fore industrial uses in the Barcelona Metropolitan Area (BMA). The relatively high conductivity (2090 µS/cm) and hardness (454 mg/L) of reclaimed water in the BMA (e.g. Water Reclamation Plant (WRP) of El Baix Llobregat, Barcelona, Spain), together with the restrictive water quality demands in industrial uses, claims for the implementation of advanced reclamation schemes based on desalination technologies such as reverse osmosis (RO). The study assesses the benefits of two potential pre-treatments of the RO stage: (i) ultrafiltration (UF) or (ii) an innovative high-performance nano-structured polymeric adsorbent (CNM); in which a permeability decline of 5% was observed when CNM was used as a pre-treatment, while a stable permeability of RO was found when was fed by the UF effluent. On the other hand, generic cost curves have been calculated for the technologies evaluated and were applied to estimate capital and operational expenditures (CAPEX and OPEX) for the scale-up in three different industrial sites (e.g., chemical, waste management and electro-coating industries). The economic assessment indicates that the use of municipal reclaimed water is economically competitive in front of the use of tap water in the BMA, providing savings between 0.13 and 0.52 €/m3 for the waste management industry and between 0.49 and 0.98 €/m3 for the electrocoating industry. On the other hand, the use of groundwater in one of the industrial sites and its relatively low cost implied that, although it is necessary a RO, the current cost of water is significantly lower.

Techno-economic evaluation and comparison of PAC-MBR and ozonation-UV revamping for organic micro-pollutants removal from urban reclaimed wastewater.

The presence of sewage-borne Organic Micro-Pollutants (OMP) in Wastewater Treatment Plants (WWTP) effluents represents an increasing concern when water is reclaimed for irrigation or even indirect potable reuse. During eighteen months, an innovative hybrid water reclamation scheme based on a Membrane Biological Reactor (MBR) enhanced with Powder Activated Carbon (PAC) was operated at pilot-scale (70 m3/d) in order to compare it with state-of-the art Wastewater Reclamation System (WWRS) also revamped with a final step of ozonation-UV. Removal of persistent OMP, water quality and treatment costs were evaluated and compared for the different treatment schemes. OMP removal efficiency results for the different schemes concluded that established technologies, such as physico-chemical and filtration systems as well as MBR, do not remove significantly (>15%) the most recalcitrant compounds. The upgrading of these two systems through the addition of ozonation-UV step and PAC dosing allowed improving average recalcitrant OMP removal to 85 ±â€¯2 and 75 ±â€¯5%, respectively. In term of costs, PAC-MBR represents an increase of 37% of costs regarding conventional systems but presents improvements of 50% reduction in space and water quality. On the other hand, ozonation requires up to a 15% increase of foot-print; nevertheless, represents lower costs and lower carbon footprint. Ozonation-UV seems to be the best option for upgrading existing facilities, while PAC-MBR should be considered when space represents a critical limitation and produced water is reused for high water quality purposes.

[Prevalence of human papillomavirus in Spanish women from a population screening program]. / Prevalencia de virus del papiloma humano en mujeres españolas de un programa de cribado poblacionales de riesgo.

OBJECTIVE: The human papillomavirus (HPV), is necessary to cause a woman developing cervical cancer. The aim of the study was to estimate the prevalence of women with HPV infection, covered by the program of prevention and early detection of cervical cancer of Castile and León (Spain). METHODS: Samples of women included in the screening program were analyzed. Including a total of 120,326 cervical swab samples, collected in the period from January 2012 to December 2014. RESULTS: 12,183 HPV positive samples were detected, representing a prevalence of 9.6 ‰, (IC 95% 9.5%-9.8%) in the female population. High-risk HPV were found in higher proportion that HPV low-risk genotypes. HPV prevalence correlates inversely with women age. Coinfections of multiple genotypes were found in one third of screened women population. CONCLUSIONS: Data showed in this study are the first and wider Spanish results from a cervical cancer screening program population non opportunistic based on HPV detection. These results would serve as a reference for future prevalence studies and to evaluate the future impact of HPV vaccination campaigns.

Long-Term Outcomes of Intestinal and Multivisceral Transplantation at a Single Center in Argentina.

BACKGROUND: Intestinal failure (IF) patients received parenteral nutrition (PN) as the only available therapy until intestinal transplantation (ITx) evolved as an accepted treatment. The aim of this article is to report the long-term outcomes of a series of ITx performed in pediatric and adult patients at a single center 9 years after its creation. PATIENTS AND METHODS: This is a retrospective analysis of the ITx performed between May 2006 and January 2015. Diagnoses, pre-ITx mean time on PN, indications for ITx, time on the waiting list for types of ITx, mean total ischemia time, and warm ischemia time, time until PN discontinuation, incidence of acute and chronic rejection, and 5-year actuarial patient survival are reported. RESULTS: A total of 42 patients received ITx; 80% had short gut syndrome (SG); the mean time on PN was 1620 days. The main indication for ITx was lack of central venous access followed by intestinal failure-associated liver disease (IFALD) and catheter-related infectious complications. The mean time on the waiting list was 188 days (standard deviation, ±183 days). ITx were performed in 26 children and 14 adults. In all, 32 procedures were isolated ITx (IITX); 10 were multiorgan Tx (MOT; 3 combined, 7 multivisceral Tx (MVTx), 1 modified MVTx and 2 with kidney); 2 (4.7 %) were retransplantations: 1 IITx, 1 MVTx, and 5 including the right colon. Thirteen patients (31%) received abdominal rectus fascia. All procedures were performed by the same surgical team. Total ischemia time was 7:53 ± 2:04 hours, and warm ischemia time was 40.2 ± 10.5 minutes. The mean length of implanted intestine was 325 ± 63 cm. Bishop-Koop ileostomy was performed in 67% of cases. In all, 16 of 42 Tx required early reoperations. The overall mean follow-up time was 41 ± 35.6 months. The mean time to PN discontinuation after Tx was 68 days (P = .001). The total number of acute cellular rejection (ACR) episodes until the last follow-up was 83; the total number of grafts lost due to ACR was 4; and the total graft lost due to chronic rejection was 3. At the time of writing, the overall 5-year patient survival is 55% (65% for IITx vs 22% for MOT; P = .0001); 60% for pediatric recipients vs 47% for adults (P = NS); 64% when the indication for ITx was SG vs 25% for non-SG (P = .002). CONCLUSIONS: At this center, candidates with SG, in the absence of IFALD requiring IITx, showed the best long-term outcomes, independent of recipient age. A multidisciplinary approach is mandatory for the care of intestinal failure patients, to sustain a rehabilitation and transplantation program over time.

In Vivo and in Vitro Phosphorylation of the Phosphoenolpyruvate Carboxylase from Wheat Seeds during Germination.

Phosphoenolpyruvate carboxylase (PEPC) activity was detected in the aleurone endosperm of wheat (Triticum aestivum cv Chinese Spring) seeds, and specific anti-Sorghum C4 PEPC polyclonal anti-bodies cross-reacted with 103- and 100-kD polypeptides present in dry seeds and seeds that had imbibed; in addition, a new, 108-kD polypeptide was detected 6 h after imbibition. The use of specific anti-phosphorylation-site immunoglobulin G (APS-IgG) identified the presence of a phosphorylation motif equivalent to that found in other plant PEPCs studied so far. The binding of this APS-IgG to the target protein promoted changes in the properties of seed PEPC similar to those produced by phosphorylation, as previously shown for the recombinant Sorghum leaf C4 PEPC. In desalted seed extracts, an endogenous PEPC kinase activity catalyzed a bona fide phosphorylation of the target protein, as deduced from the immunoinhibition of the in vitro phosphorylation reaction by the APS- IgG. In addition, the major, 103-kD PEPC polypeptide was also shown to be radiolabeled in situ 48 h after imbibition in [32P]orthophosphate. The ratio between optimal (pH 8) and suboptimal (pH 7.3 or 7.1) PEPC activity decreased during germination, thereby suggesting a change in catalytic rate related to an in vivo phosphorylation process. These collective data document that the components needed for the regulatory phosphorylation of PEPC are present and functional during germination of wheat seeds.

Evidence for a slow-turnover form of the Ca2+-independent phosphoenolpyruvate carboxylase kinase in the aleurone-endosperm tissue of germinating barley seeds

Phosphoenolpyruvate carboxylase (PEPC) activity was detected in aleurone-endosperm extracts of barley (Hordeum vulgare) seeds during germination, and specific anti-sorghum (Sorghum bicolor) C4 PEPC polyclonal antibodies immunodecorated constitutive 103-kD and inducible 108-kD PEPC polypeptides in western analysis. The 103- and 108-kD polypeptides were radiolabeled in situ after imbibition for up to 1.5 d in 32P-labeled inorganic phosphate. In vitro phosphorylation by a Ca2+-independent PEPC protein kinase (PK) in crude extracts enhanced the enzyme's velocity and decreased its sensitivity to L-malate at suboptimal pH and [PEP]. Isolated aleurone cell protoplasts contained both phosphorylated PEPC and a Ca2+-independent PEPC-PK that was partially purified by affinity chromatography on blue dextran-agarose. This PK activity was present in dry seeds, and PEPC phosphorylation in situ during imbibition was not affected by the cytosolic protein-synthesis inhibitor cycloheximide, by weak acids, or by various pharmacological reagents that had proven to be effective blockers of the light signal transduction chain and PEPC phosphorylation in C4 mesophyll protoplasts. These collective data support the hypothesis that this Ca2+-independent PEPC-PK was formed during maturation of barley seeds and that its presumed underlying signaling elements were no longer operative during germination.

Reversible light activation of the phosphoenolpyruvate carboxylase protein-serine kinase in maize leaves.

C4-leaf phosphoenolpyruvate carboxylase (PEPC; EC 4.1.1.31) undergoes reversible, light-induced increases in its activity-seryl phosphorylation-status in vivo. We now report that the PEPC-protein kinase activity in desalted crude extracts of light-adapted maize leaves is several-fold greater than that from the corresponding dark tissue when in vitro phosphorylation assays are performed with either endogenous or purified dark-form maize PEPC as substrate, both in the absence or presence of okadaic acid, a potent inhibitor of the PEPC type 2A protein phosphatase(s). These and related results indicate that the PEPC protein-serine kinase(s) per se is reversibly light activated in vivo by either covalent modification, protein turnover or, less likely, a tight-binding effector.

Capillary zone electrophoretic separation and determination of imidazolic antifungal drugs.

Capillary zone electrophoresis (CZE) was adapted to the simultaneous determination of a mixture of three imidazolic antifungal drugs. Separation was achieved by using a fused-silica capillary column with an acetic acid-Tris buffer at pH 5.18 and UV detection at 196 nm. Several electrophoretic parameters were investigated: pH and buffer concentration, applied voltage, temperature and injection conditions. The optimized CZE method was applied to the individual determination of ketoconazole, clotrimazole and econazole in pharmaceutical forms, after a previous single extraction step in methanol, with recoveries of 98.00, 99.96 and 99.58% respectively. The antifungal drugs can be determined at a concentration level lower than 1.0 x 10(-7) M.

Influence of the transmission route and disease duration in the histopathology of chronic hepatitis C: a study of 101 patients.

OBJECTIVE: Different studies have demonstrated that factors such as transmission route, disease duration and age at the time of infection can influence the histological evolution of chronic hepatitis by the hepatitis C virus (HCV). The aim of this study was to determine if epidemiological factors such as disease duration and transmission route influence the severity of the histological lesions of patients with chronic hepatitis by HCV. DESIGN: A prospective study. METHODS: The hepatic biopsies of 101 patients diagnosed with chronic hepatitis by HCV were studied. The patients were divided into three groups according to transmission mode: (1) post-transfusional (n = 28), (2) associated with the use of drugs by parenteral route or intravenous drug use (n = 28), and (3) sporadic hepatitis (n = 45). RESULTS: We found more severe forms of hepatopathy in post-transfusional hepatitis and sporadic groups than in the intravenous drug user group of patients. The disease evolution time was significantly higher in patients diagnosed as having chronic active hepatitis with or without cirrhosis (13.8 +/- 9 years) than in patients with chronic persistent hepatitis (8 +/- 4 years), P < 0.01. We found a significant correlation between the evolution time of the infection by HCV and the Histology Activity Index (P < 0.01). The multivariate analysis showed that only the transmission route and the disease evolution time are predictive variables of Histology Activity Index in chronic hepatitis C. CONCLUSION: These results suggest that the post-transfusional and sporadic transmission routes and a greater evolution time of the disease are epidemiological variables that are associated with the presence of more severe histological lesions in chronic hepatitis C.

Voltammetric and spectrophotometric techniques for the determination of the antihypertensive drug Prazosin in urine and formulations.

A sensitive method was developed to determine Prazosin using a nafion modified carbon paste electrode (NMCPE). Prazosin was accumulated at a potential of 750 mV in Britton-Robinson buffer (pH 6.0) and then a negative sweep was made obtaining a cathodic peak close to 0 V. Cyclic voltammetric studies indicated that the process was quasi-reversible, and fundamentally controlled by adsorption. To obtain a good sensitivity, the instrumental and accumulation variables were studied using differential pulse voltammetry (DPV). Adsorptive voltammetric peak currents showed a linear response for Prazosin concentrations in the range between 4.0 x 10(-11) and 4.0 x 10(-8) M with two different slopes, and a detection limit (LOD) of 3.1 x 10(-11)M was obtained. The variation coefficient (CV) for a 8.0 x 10(-10) M solution (n = 10) was 4.08%. A spectrophotometric study of Prazosin was also carried out and two absorption bands were obtained at 246 and 329 nm (pH 1.8). The band at 329 nm was pH-dependent and its height and position changed with the pH values, so this allowed the pK'a determination (7.14 +/- 0.20) using different methods. The detection limit reached by means of UV-spectrophotometry was 0.9 x 10(-7) M, and the variation coefficient for 1.5 x 10(-5) M Prazosin solutions was 1.14% (n = 10). Although the sensitivity of the UV-spectrophotometric method was lower than that obtained using adsorptive stripping-differential pulse voltammetry (AdS-DPV), it could be applied to the determination of Prazosin in Minipres tablets. The voltammetric method was used for the determination of the drug in human urine samples at trace levels with good recoveries.

[Serum levels of vitamin A (retinol), vitamin E (alpha-tocopherol), cholesterol and triglycerides in women with breast cancer. The relationship to some food habits]. / Niveles séricos de vitamina A (retinol), vitamina E (alfa-tocoferol) colesterol y triglicéridos en mujeres con cáncer de mama. Relación con algunos hábitos alimentarios.

The serum levels of vitamin A (retinol), vitamin E (alpha-tocopherol), cholesterol and triglycerides were studied in a group of 40 women who had been diagnosed as having breast cancer, and they were compared to the levels found in a group of 30 healthy women. Our results indicate that the only statistically significant differences found were those involving retinol, with the cancer group showing significantly lower levels (p < 0.05). These parameters have been examined in the context of the frequency of consumption of foods rich in these vitamins and lipids. A higher frequency of consumption of foods rich in the studied vitamins does not appear to cause significant differences in their blood levels. The differences in specific dietary habits have also been analyzed, with both groups showing a high percentage of people who consume skimmed milk and a majority who use olive oil. Nevertheless, the consumption of fruits and vegetables is lower in the cancer group than in the control group.

[Alterations in iron metabolism in chronic anti-HCV positive hepatitis. The relationship with response to interferon treatment]. / Alteraciones del metabolismo del hierro en las hepatitis crónicas anti-VHC positivo. Relación con la respuesta al tratamiento con interferón.

A prospective study in which the existence of iron metabolism alterations (increase in the serum levels of iron and ferritin and the presence of iron in liver tissue) in a group of 53 patients diagnosed with chronic anti-HCV positive hepatitis was performed. The aim of the study was to determine whether these parameters influence the response to interferon treatment. Elevations were observed in the serum levels of iron and/or ferritin in 17 (32%) of the patients. Higher than normal values of serum iron or ferritin in pretreatment analyses were associated with worse therapeutic response. The basal serum levels of iron and ferritin were significantly higher in non responding patients. No relationship was found between the presence of iron in the hepatic parenchyma and response to interferon treatment.

Aß promotes VDAC1 channel dephosphorylation in neuronal lipid rafts. Relevance to the mechanisms of neurotoxicity in Alzheimer's disease.

Voltage-dependent anion channel (VDAC) is a mitochondrial protein abundantly found in neuronal lipid rafts. In these membrane domains, VDAC is associated with a complex of signaling proteins that trigger neuroprotective responses. Loss of lipid raft integrity may result in disruption of multicomplex association and alteration of signaling responses that may ultimately promote VDAC activation. Some data have demonstrated that VDAC at the neuronal membrane may be involved in the mechanisms of amyloid beta (Aß)-induced neurotoxicity, through yet unknown mechanisms. Aß is generated from amyloid precursor protein (APP), and is released to the extracellular space where it may undergo self-aggregation. Aß aggregate deposition in the form of senile plaques may lead to Alzheimer's disease (AD) neuropathology, although other pathological hallmarks (such as hyper-phosphorylated Tau deposition) also participate in this neurodegenerative process. The present study demonstrates that VDAC1 associates with APP and Aß in lipid rafts of neurons. Interaction of VDAC1 with APP was observed in lipid rafts from the frontal and entorhinal cortex of human brains affected by AD at early stages (I-IV/0-B of Braak and Braak). Furthermore, Aß exposure enhanced the dephosphorylation of VDAC1 that correlated with cell death. Both effects were reverted in the presence of tyrosine phosphatase inhibitors. VDAC1 dephosphorylation was corroborated in lipid rafts of AD brains. These results demonstrate that Aß is involved in alterations of the phosphorylation state of VDAC in neuronal lipid rafts. Modulation of this channel may contribute to the development and progression of AD pathology.

Profound bradycardia associated with NIV removal.

A patient with lower-limb onset ALS presented with a one-month history of vasovagal episodes and a one-week history of cough productive of green sputum and lethargy. She was drowsy and in acute on chronic type-two respiratory failure. She responded to non-invasive ventilation, however she suffered recurrent episodes of profound bradycardia on removal of the mask, which gradually resolved over ten days. We have reviewed the literature and offer a potential explanation for these events.