Dynamic oscillatory signatures of central neuropathic pain in spinal cord injury

Central Neuropathic Pain (CNP) is believed to be accompanied by increased activation of the sensory and motor cortices. Our knowledge on this interaction is based mainly on fMRI studies, but there is little direct evidence on how these changes manifest in terms of dynamic neuronal activity. This study reports on the presence of transient EEG based measures of brain activity during motor imagery in spinal cord injured patients with CNP. We analyse dynamic EEG responses during imaginary movements of arms and legs in 3 groups of 10 volunteers each, comprising able-bodied people, paraplegic patients with CNP (lower abdomen and legs) and paraplegic patients without CNP. Paraplegic patients with CNP had increased event-related desynchronisation in the theta, alpha and beta bands (16-24 Hz) during imagination of movement of both non-painful (arms) and painful limbs (legs). Compared to patients with CNP, paraplegics with no pain showed a much reduced power in relaxed state and reduced event-related desynchronisation during imagination of movement. Understanding these complex dynamic, frequency-specific activations in CNP in the absence of nociceptive stimuli could inform the design of interventional therapies for patients suffering from CNP and possibly further understanding of the mechanisms involved

Alopecia in a Viable Phospholipase C Delta 1 and Phospholipase C Delta 3 Double Mutant

BACKGROUND: Inositol 1,4,5trisphosphate (IP(3)) and diacylglycerol (DAG) are important intracellular signalling molecules in various tissues. They are generated by the phospholipase C family of enzymes, of which phospholipase C delta (PLCD) forms one class. Studies with functional inactivation of Plcd isozyme encoding genes in mice have revealed that loss of both Plcd1 and Plcd3 causes early embryonic death. Inactivation of Plcd1 alone causes loss of hair (alopecia), whereas inactivation of Plcd3 alone has no apparent phenotypic effect. To investigate a possible synergy of Plcd1 and Plcd3 in postnatal mice, novel mutations of these genes compatible with life after birth need to be found. METHODOLOGY/PRINCIPAL FINDINGS: We characterise a novel mouse mutant with a spontaneously arisen mutation in Plcd3 (Plcd3(mNab)) that resulted from the insertion of an intracisternal A particle (IAP) into intron 2 of the Plcd3 gene. This mutation leads to the predominant expression of a truncated PLCD3 protein lacking the N-terminal PH domain. C3H mice that carry one or two mutant Plcd3(mNab) alleles are phenotypically normal. However, the presence of one Plcd3(mNab) allele exacerbates the alopecia caused by the loss of functional Plcd1 in Del(9)olt1Pas mutant mice with respect to the number of hair follicles affected and the body region involved. Mice double homozygous for both the Del(9)olt1Pas and the Plcd3(mNab) mutations survive for several weeks and exhibit total alopecia associated with fragile hair shafts showing altered expression of some structural genes and shortened phases of proliferation in hair follicle matrix cells. CONCLUSIONS/SIGNIFICANCE: The Plcd3(mNab) mutation is a novel hypomorphic mutation of Plcd3. Our investigations suggest that Plcd1 and Plcd3 have synergistic effects on the murine hair follicle in specific regions of the body surface

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Apoptosis and disease: a life or death decision

Conference and Workshop on Apoptosis and Diseas

Effective delivery of pharmaceutical palliative care : challenges in the community pharmacy setting

edication, particularly analgesia, is an important component of palliative care. However, timely access to medication, particularly opioids, can become problematic for patients receiving palliative care in the community setting. In Scotland in 2009, NHS Greater Glasgow & Clyde Health Board (NHS GG&C), in partnership with Macmillan Cancer Support, established a programme to improve the local provision of pharmaceutical palliative care services with the appointment of Macmillan Pharmacist Facilitators. Researchers at the University of Strathclyde were commissioned to support the development and evaluation of this new service. We report the findings of this initial investigation into the provision of current palliative care services and outline an evidence-based action plan to support service improvement. Qualitative data were gathered using focus group interviews. Three key themes were identified: medication supply, communication, and education and training. The study findings have been used to develop an evidence-based action plan for the Macmillan Pharmacist Facilitators. This program of work is due for completion by December 2012

Similar survival on automated peritoneal dialysis and continuous ambulatory peritoneal dialysis in a large prospective cohort

BACKGROUND AND OBJECTIVES: Automated peritoneal dialysis (APD) is increasingly used in comparison with continuous ambulatory peritoneal dialysis (CAPD). Although APD is expected to improve survival, convincing evidence of major advantages is lacking. The objective was to investigate whether overall mortality and technique failure of incident dialysis patients treated with APD are different from those treated with CAPD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients on APD or CAPD at 3 mo after start of dialysis were selected from a prospective multicenter cohort study in incident dialysis patients (NECOSAD). Overall mortality was studied with an intention-to-treat design; the event was death. Technique failure was studied with an as-treated design; the event was a switch of dialysis modality. Hazard ratios (HRs) were calculated with a follow-up of 5 yr. The HRs were adjusted for gender, age, primary kidney disease, comorbidity, residual GFR, urine production and plasma albumin at 3 mo after inclusion. RESULTS: Eighty-seven APD and 562 CAPD patients were included. In the intention-to-treat analysis 154 CAPD and 21 APD patients died. The crude HR for overall mortality was 0.98 (95% CI: 0.62-1.54), the adjusted HR was 1.09. In the as-treated analysis 238 CAPD and 34 APD patients switched therapy, whereas 91 CAPD and 7 APD patients died. The crude HR for technique failure was 0.92 (95% CI: 0.64-1.31) and did not change after adjustment. CONCLUSIONS: No difference was found in overall mortality and technique failure for APD compared with CAPD in incident dialysis patient

Performance of the Cockcroft-Gault, MDRD, and New CKD-EPI Formulas in Relation to GFR, Age, and Body Size

Background and objectives: We compared the estimations of Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations to a gold standard GFR measurement using 125I-iothalamate, within strata of GFR, gender, age, body weight, and body mass index (BMI)

TIME COURSE OF PERITONEAL FUNCTION IN AUTOMATED AND CONTINUOUS PERITONEAL DIALYSIS

Background and Objectives: In automated peritoneal dialysis (APD), a patient's peritoneal membrane is more intensively exposed to fresh dialysate than it is in continuous ambulatory peritoneal dialysis (CAPD). Our aim was to study, in incident peritoneal dialysis (PD) patients, the influence of APD-compared with that of CAPD-on peritoneal transport over 4 years. Design, Setting, Participants, and Measurements: Patients were included if at least 2 annual standard permeability analyses (SPAs) performed with 3.86% glucose were available while the patient was using the same modality with which they had started PD (APD or CAPD). Patients were followed until their first modality switch. Differences in the pattern of SPA outcomes over time were tested using repeated-measures models adjusted for age, sex, comorbidity, primary kidney disease, and year of PD start. Results: The 59 CAPD patients enrolled were older than the 47 APD patients enrolled (mean age: 58 +/- 14 years vs 49 +/- 14 years; p 0.19) or fluid transport (p > 0.13) were observed. Similarly, free water transport (p = 0.43) and small-pore transport (p = 0.31) were not different between the modalities. Over time, patients on APD showed a faster decline in effective lymphatic absorption rate (ELAR: p = 0.02) and in transcapillary ultrafiltration (TCUF: p = 0.07, adjusted p = 0.05). Further adjustment did not change the results. Conclusions: Compared with patients starting on CAPD, those starting on APD experienced a faster decline in ELAR and TCUF. Other transport parameters were not different over time between the groups. Perit Dial Int 2012; 32(6): 605-611 www.PDIConnect.com epub ahead of print: 02 Apr 2012 doi: 10.3747/pdi.2011.0016

LOW ENDOPHTHALMITIS RATES AFTER INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTIONS IN AN OPERATION ROOM: A Retrospective Multicenter Study.

PURPOSE To evaluate the rate of presumed endophthalmitis (EO) after intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections in three European hospitals performed in an operation room (OR) under sterile conditions. METHODS A retrospective multicenter study between 2003 and 2016 at three European sites, City Hospital Triemli Zurich, Switzerland (CHT), Zealand University Hospital Roskilde, Denmark (ZUH) and University Clinic Bern, Switzerland (UCB). Intravitreal injection (IVI) database of each department was reviewed. All anti-vascular endothelial growth factor injections were performed using a standardized sterile technique in an operation room. Injection protocols were similar between the three sites. No preinjection antibiotics were given. Postoperative antibiotics varied among sites. RESULTS A total of 134,701 intravitreal injections were performed at the 3 sites between 2003 and 2016. Ten cases of presumed endophthalmitis were documented: 4 in 50,721 at CHT (95% CI: 0.0071-0.0087%), 2 in 44,666 at ZUH (95% CI: 0.0039-0.0051%), and 4 in 39,314 at UCB (95% CI: 0.0092-0.011%). This results in one case in 13,470 intravitreal injections and a combined incidence of 0.0074% per injection (95% CI: 0.0070-0.0078%). Positive cultures were found in 4 out of 10 presumed endophthalmitis cases. CONCLUSION The standardized sterile technique in an operation room with laminar airflow showed very low rates of endophthalmitis at three European sites