The accuracy of simple, feasible alternatives to polysomnography for assessing sleep in intensive care: An observational study.

BACKGROUND: Sleep disturbance is common in intensive care patients. Understanding the accuracy of simple, feasible sleep measurement techniques is essential to informing their possible role in usual clinical care. OBJECTIVE: The aim of the study was to investigate whether sleep monitoring techniques such as actigraphy (ACTG), behavioural assessments, and patient surveys are comparable with polysomnography (PSG) in accurately reporting sleep quantity and quality among conscious, intensive care patients. METHODS: An observational study was conducted in 20 patients admitted to the intensive care unit (ICU) for a minimum duration of 24 h, who underwent concurrent sleep monitoring via PSG, ACTG, nursing-based observations, and self-reported assessment using the Richards-Campbell Sleep Questionnaire. RESULTS: The reported total sleep time (TST) for the 20 participants measured by PSG was 328.2 min (±106 min) compared with ACTG (362.4 min [±62.1 min]; mean difference = 34.22 min [±129 min]). Bland-Altman analysis indicated that PSG and ACTG demonstrated clinical agreement and did not perform differently across a number of sleep variables including TST, awakening, sleep-onset latency, and sleep efficiency. Nursing observations overestimated sleep duration compared to PSG TST (mean difference = 9.95 ± 136.3 min, p > 0.05), and patient-reported TST was underestimated compared to PSG TST (mean difference = -51.81 ± 144.1 7, p > 0.05). CONCLUSIONS: Amongst conscious patients treated in the ICU, sleep characteristics measured by ACTG were similar to those measured by PSG. ACTG may provide a clinically feasible and acceptable proxy approach to sleep monitoring in conscious ICU patients.

Validation of the Decipher genomic classifier in patients receiving salvage radiotherapy without hormone therapy after radical prostatectomy - an ancillary study of the SAKK 09/10 randomized clinical trial.

BACKGROUND: The Decipher genomic classifier (GC) has shown to independently prognosticate outcomes in prostate cancer. The objective of this study was to validate the GC in a randomized phase III trial of dose-escalated salvage radiotherapy (SRT) after radical prostatectomy. PATIENTS AND METHODS: A clinical-grade whole-transcriptome assay was carried out on radical prostatectomy samples obtained from patients enrolled in Swiss Group for Clinical Cancer Research (SAKK) 09/10, a phase III trial of 350 men with biochemical recurrence after radical prostatectomy randomized to 64 Gy versus 70 Gy without concurrent hormonal therapy or pelvic nodal RT. A prespecified statistical plan was developed to assess the impact of the GC on clinical outcomes. The primary endpoint was biochemical progression; secondary endpoints were clinical progression and time to hormone therapy. Multivariable analyses adjusted for age, T-category, Gleason score, postradical prostatectomy persistent prostate-specific antigen (PSA), PSA at randomization, and randomization arm were conducted, accounting for competing risks. RESULTS: The analytic cohort of 226 patients was representative of the overall trial, with a median follow-up of 6.3 years (interquartile range 6.1-7.2 years). The GC (high versus low-intermediate) was independently associated with biochemical progression [subdistribution hazard ratio (sHR) 2.26, 95% confidence interval (CI) 1.42-3.60; P < 0.001], clinical progression (HR 2.29, 95% CI 1.32-3.98; P = 0.003), and use of hormone therapy (sHR 2.99, 95% CI 1.55-5.76; P = 0.001). GC high patients had a 5-year freedom from biochemical progression of 45% versus 71% for GC low-intermediate. Dose escalation did not benefit the overall cohort, nor patients with lower versus higher GC scores. CONCLUSIONS: This study represents the first contemporary randomized controlled trial in patients treated with early SRT without concurrent hormone therapy or pelvic nodal RT that has validated the prognostic utility of the GC. Independent of standard clinicopathologic variables and RT dose, high-GC patients were more than twice as likely than lower-GC patients to experience biochemical and clinical progression and receive of salvage hormone therapy. These data confirm the clinical value of Decipher GC to personalize the use of concurrent systemic therapy in the postoperative salvage setting.

Transcriptional profiling of primary prostate tumor in metastatic hormone-sensitive prostate cancer and association with clinical outcomes: correlative analysis of the E3805 CHAARTED trial.

BACKGROUND: The phase III CHAARTED trial established upfront androgen-deprivation therapy (ADT) plus docetaxel (D) as a standard for metastatic hormone-sensitive prostate cancer (mHSPC) based on meaningful improvement in overall survival (OS). Biological prognostic markers of outcomes and predictors of chemotherapy benefit are undefined. PATIENTS AND METHODS: Whole transcriptomic profiling was performed on primary PC tissue obtained from patients enrolled in CHAARTED prior to systemic therapy. We adopted an a priori analytical plan to test defined RNA signatures and their associations with HSPC clinical phenotypes and outcomes. Multivariable analyses (MVAs) were adjusted for age, Eastern Cooperative Oncology Group status, de novo metastasis presentation, volume of disease, and treatment arm. The primary endpoint was OS; the secondary endpoint was time to castration-resistant PC. RESULTS: The analytic cohort of 160 patients demonstrated marked differences in transcriptional profile compared with localized PC, with a predominance of luminal B (50%) and basal (48%) subtypes, lower androgen receptor activity (AR-A), and high Decipher risk disease. Luminal B subtype was associated with poorer prognosis on ADT alone but benefited significantly from ADT + D [OS: hazard ratio (HR) 0.45; P = 0.007], in contrast to basal subtype which showed no OS benefit (HR 0.85; P = 0.58), even in those with high-volume disease. Higher Decipher risk and lower AR-A were significantly associated with poorer OS in MVA. In addition, higher Decipher risk showed greater improvements in OS with ADT + D (HR 0.41; P = 0.015). CONCLUSION: This study demonstrates the utility of transcriptomic subtyping to guide prognostication in mHSPC and potential selection of patients for chemohormonal therapy, and provides proof of concept for the possibility of biomarker-guided selection of established combination therapies in mHSPC.

The feasibility and reliability of actigraphy to monitor sleep in intensive care patients: an observational study.

BACKGROUND: Sleep amongst intensive care patients is reduced and highly fragmented which may adversely impact on recovery. The current challenge for Intensive Care clinicians is identifying feasible and accurate assessments of sleep that can be widely implemented. The objective of this study was to investigate the feasibility and reliability of a minimally invasive sleep monitoring technique compared to the gold standard, polysomnography, for sleep monitoring. METHODS: Prospective observational study employing a within subject design in adult patients admitted to an Intensive Care Unit. Sleep monitoring was undertaken amongst minimally sedated patients via concurrent polysomnography and actigraphy monitoring over a 24-h duration to assess agreement between the two methods; total sleep time and wake time. RESULTS: We recruited 80 patients who were mechanically ventilated (24%) and non-ventilated (76%) within the intensive care unit. Sleep was found to be highly fragmented, composed of numerous sleep bouts and characterized by abnormal sleep architecture. Actigraphy was found to have a moderate level of overall agreement in identifying sleep and wake states with polysomnography (69.4%; K = 0.386, p < 0.05) in an epoch by epoch analysis, with a moderate level of sensitivity (65.5%) and specificity (76.1%). Monitoring accuracy via actigraphy was improved amongst non-ventilated patients (specificity 83.7%; sensitivity 56.7%). Actigraphy was found to have a moderate correlation with polysomnography reported total sleep time (r = 0.359, p < 0.05) and wakefulness (r = 0.371, p < 0.05). Bland-Altman plots indicated that sleep was underestimated by actigraphy, with wakeful states overestimated. CONCLUSIONS: Actigraphy was easy and safe to use, provided moderate level of agreement with polysomnography in distinguishing between sleep and wakeful states, and may be a reasonable alternative to measure sleep in intensive care patients. Clinical Trial Registration number ACTRN12615000945527 (Registered 9/9/2015).

Reduced rotavirus vaccine efficacy in protein malnourished human-faecal-microbiota-transplanted gnotobiotic pig model is in part attributed to the gut microbiota.

The low efficacy of human rotavirus (HRV) vaccines in low- and middle-income countries (LMIC) remains a major challenge for global health. Protein-calorie malnutrition (kwashiorkor) affects the gut microbiota and compromises immune development, leading to environmental enteropathy, vaccine failures, and increased susceptibility to enteric diseases in young children. Relationship between diet and reduced vaccine efficacy in developing countries is not well established; therefore, we investigated the interconnections between the host-microbiota-nutrition-HRV vaccine using HRV-vaccinated, human infant faecal microbiota (HIFM)-transplanted neonatal gnotobiotic pigs fed with a protein deficient or sufficient diet. The microbiota from faecal, intestinal (duodenum, ileum, jejunum, and colon), and systemic tissue (liver, spleen, and mesenteric lymph node [MLN]) samples was analysed before and after HRV challenge using MiSeq 16S rRNA sequencing. Overall, microbiota from deficient fed HIFM pigs displayed, compared to the sufficient group, significantly higher Shannon index, especially in the faeces and lower intestines; higher level of Proteus and Enterococcus, and lower level of Bifidobacterium, Clostridium, and Streptococcus in the three types of samples collected (P<0.05); and higher unique operational taxonomic units (OTUs), especially in the systemic tissues. Further, the multivariate analysis between microbiota and immunologic data showed that 38 OTUs at the genus level correlated (r2≤0.5 or ≥-0.5; P<0.05) with at least one host immune response parameter (regulatory [Tregs and transforming growth factor-ß], effectors [interferon (IFN)-γ+ CD4+ and CD8+ T cells, IFN-γ and interleukin (IL)-12], and inflammatory [tumour necrosis factor-α, IL-17 and IL-22]) and with opposite trends between diet groups. Differences described above were increased after HRV challenge. We demonstrated that a protein deficient diet affects the composition of the gut microbiota and those changes may further correlate with immune responses induced by HRV and perturbed by the deficient diet. Thus, our findings suggest that the reduced efficacy of HRV vaccine observed in Gn pig model is in part attributed to the altered microbiota composition.

A case of GNE myopathy mimicking hereditary motor neuropathy.

A 36-year-old woman who presented with upper limb distal weakness since the age of 15 years, with gradual progression to the lower limbs, is reported. Hereditary motor neuropathy was initially suspected based on distal weakness and hyporeflexia; however, whole exome sequencing accidentally revealed a compound heterozygous variant in the GNE gene, and ultrasound revealed increased homogeneous echogenicity in the involved muscles, which is characteristic of myopathic changes. Muscle magnetic resonance imaging revealed fatty infiltration in all limb muscles, sparing the triceps brachii, vastus lateralis and vastus medialis. Muscle biopsy revealed intracytoplasmic rimmed vacuole, supporting the diagnosis of GNE myopathy.

Gender difference in clinical and genetic characteristics of Brugada syndrome: SADS-TW BrS registry.

BACKGROUND: Brugada syndrome (BrS) is a heritable sudden cardiac death (SCD) disease with male predominance. Information on gender difference of BrS remains scarce. AIM: To investigate the gender difference of BrS in Han Chinese. DESIGN: We consecutively enrolled 169 BrS patients (153 males and 16 females) from Han Chinese in Taiwan from 1998 to 2017. METHODS: Clinical characteristics, electrocardiographic parameters and SCN5A mutation status were compared between genders. RESULTS: The percentage of family history of SCD in females was slightly higher (31.3% vs. 15%, P = 0.15). Females exhibited longer QTc (457.8 ± 33.0 vs. 429.5 ± 42.1 ms, P < 0.01). Regarding cumulative event occurrence by age, Mantel-Cox test showed females had earlier age of onset of first cardiac events (SCD or syncope) than males (P = 0.049), which was mainly attributed to syncope (P < 0.01). Males with SCD exhibited longer QRS duration (114.2 ± 26.8 vs. 104.8 ± 15.3 ms, P = 0.02) and QTc (442.5 ± 57.4 vs. 422.9 ± 28.8 ms, P = 0.02). Males with syncope exhibited longer PR interval (181.2 ± 33.7 vs. 165.7 ± 27.1 ms, P = 0.01), whereas females with SCD or syncope had a trend towards slower heart rates (69.1 ± 9.6 vs. 82.2 ± 16.3 bpm, P = 0.10) than female with no or mild symptoms. There was no difference in the percentage of SCN5A mutation between genders. CONCLUSION: Gender difference is present in BrS. Females have longer QTc and suffer from syncope earlier than males. Risk of SCD in males is associated with boarder QRS complex and longer QTc, whereas risk of syncope is associated with longer PR interval in males and slower heart rate in females.

Effect of antibiotic, probiotic, and human rotavirus infection on colonisation dynamics of defined commensal microbiota in a gnotobiotic pig model.

We developed a gnotobiotic (Gn) pig model colonised with defined commensal microbiota (DMF) to provide a simplified and controlled system to study the interactions between intestinal commensals, antibiotics (ciprofloxacin, CIP), probiotics (Escherichia coli Nissle 1917, EcN) and virulent human rotavirus (VirHRV). The DMF included seven gut commensal species of porcine origin that mimic the predominant species in the infant gut. Gn piglets were divided into four groups: DMF control (non-treated), DMF+CIP (CIP treated), DMF+CIP+EcN (CIP/EcN treated), DMF+EcN (EcN treated) and inoculated orally with 105 cfu of each DMF strain. The pig gut was successfully colonised by all DMF species and established a simplified bacterial community by post-bacteria colonisation day (PBCD) 14/post-VirHRV challenge day (PCD) 0. Overall, Bifidobacterium adolescentis was commonly observed in faeces in all groups and time points. At PCD0, after six days of CIP treatment (DMF+CIP), we observed significantly decreased aerobic and anaerobic bacteria counts especially in jejunum (P<0.001), where no DMF species were detected in jejunum by T-RFLP. Following HRV challenge, 100% of pigs in DMF+CIP group developed diarrhoea with higher diarrhoea scores and duration as compared to all other groups. However, only 33% of pigs treated with EcN plus CIP developed diarrhoea. EcN treatment also enhanced the bacterial diversity and all seven DMF species were detected with a higher proportion of Bifidobacterium longum in jejunum in the DMF+CIP+EcN group on PBCD14/PCD0. Our results suggest that EcN increased the proportion of B. longum especially in jejunum and mitigated adverse impacts of antibiotic use during acute-infectious diarrhoea. The DMF model with a simplified gut commensal community can further our knowledge of how commensals and probiotics promote intestinal homeostasis and contribute to host health.

Oncoprotein ZNF322A transcriptionally deregulates alpha-adducin, cyclin D1 and p53 to promote tumor growth and metastasis in lung cancer.

This corrects the article DOI: 10.1038/onc.2015.296.

Oncoprotein ZNF322A transcriptionally deregulates alpha-adducin, cyclin D1 and p53 to promote tumor growth and metastasis in lung cancer.

This corrects the article DOI: 10.1038/onc.2015.296.

The upper-limb volumetric changes in breast cancer survivors with axillary web syndrome.

Whether upper-limb swelling is associated with axillary web syndrome (AWS) is unknown. We recruited unilateral breast cancer (BC) patients who were scheduled for surgical intervention and lymph node dissection. The pre-operative assessment and post-operative assessment 3-4 weeks after surgery evaluated the upper-limb circumferential measurements, segmental limb volume, pain scores, grasp, shoulder range of motion (ROM), shoulder muscle power and quality-of-life scores. In the control group, the peri-elbow volume and upper-arm volume were significantly higher post-operatively than pre-operatively. In the AWS group, no significant difference was found. In comparison with the control group, the AWS group had significantly more pain, less active ROM in shoulder abduction and a lower upper-limb volume at 0-10 cm proximal to the lateral epicondyle. The incidence of lymphedema was 9.9% and was not associated with AWS. AWS is a common morbidity of lymph node dissection and causes significant pain and restricted shoulder abduction in the affected limb in BC survivors. This study is the first to investigate post-operative upper-limb volumetric changes in BC survivors with and without AWS. Our findings are of great value for the clinical effect of AWS in BC survivors, for patient education, and for developing diagnostic tools for detecting AWS.

Oncoprotein ZNF322A transcriptionally deregulates alpha-adducin, cyclin D1 and p53 to promote tumor growth and metastasis in lung cancer.

ZNF322A encoding a classical Cys2His2 zinc finger transcription factor was previously revealed as a potential oncogene in lung cancer patients. However, the oncogenic role of ZNF322A and its underlying mechanism in lung tumorigenesis remain elusive. Here we show ZNF322A protein overexpression in 123 Asian and 74 Caucasian lung cancer patients. Multivariate Cox regression analysis indicated that ZNF322A was an independent risk factor for a poor outcome in lung cancer, corroborating the Kaplan-Meier results that patients with ZNF322A protein overexpression had significantly poorer overall survival than other patients. Overexpression of ZNF322A promoted cell proliferation and soft agar growth by prolonging cell cycle in S phase in multiple lung cell lines, including the immortalized lung cell BEAS-2B. In addition, ZNF322A overexpression enhanced cell migration and invasion, whereas knockdown of ZNF322A reduced cell growth, invasion and metastasis abilities in vitro and in vivo. Quantitative proteomic analysis revealed potential ZNF322A-regulated downstream targets, including alpha-adducin (ADD1), cyclin D1 (CCND1), and p53. Using luciferase promoter activity assay combined with site-directed mutagenesis and sequential chromatin immunoprecipitation-PCR assay, we found that ZNF322A could form a complex with c-Jun and cooperatively activate ADD1 and CCND1 but repress p53 gene transcription by recruiting differential chromatin modifiers, such as histone deacetylase 3, in an AP-1 element dependent manner. Reconstitution experiments indicated that CCND1 and p53 were important to ZNF322A-mediated promotion of cell proliferation, whereas ADD1 was necessary for ZNF322A-mediated cell migration and invasion. Our results provide compelling evidence that ZNF322A overexpression transcriptionally dysregulates genes involved in cell growth and motility therefore contributes to lung tumorigenesis and poor prognosis.

Slug is temporally regulated by cyclin E in cell cycle and controls genome stability.

The transcriptional repressor Slug is best known to control epithelial-mesenchymal transition (EMT) and promote cancer invasion/metastasis. In this study, we demonstrate that Slug is temporally regulated during cell cycle progression. At G1/S transition, cyclin E-cyclin-dependent kinase 2 mediates the phosphorylation of Slug at Ser-54 and Ser-104, resulting in its ubiquitylation and degradation. Non-phosphorylatable Slug is markedly stabilized at G1/S transition compared with wild-type Slug and greatly leads to downregulation of DNA synthesis and checkpoint-related proteins, including TOP1, DNA Ligase IV and Rad17, reduces cell proliferation, delays S-phase progression and contributes to genome instability. Our results indicate that Slug has multifaceted roles in cancer progression by controlling both EMT and genome stability.

Combination therapy targeting ectopic ATP synthase and 26S proteasome induces ER stress in breast cancer cells.

F1Fo ATP synthase is present in all organisms and is predominantly located on the inner membrane of mitochondria in eukaryotic cells. The present study demonstrated that ATP synthase and electron transport chain complexes were ectopically expressed on the surface of breast cancer cells and could serve as a potent anticancer target. We investigated the anticancer effects of the ATP synthase inhibitor citreoviridin on breast cancer cells through proteomic approaches and revealed that differentially expressed proteins in cell cycle regulation and in the unfolded protein response were functionally enriched. We showed that citreoviridin triggered PERK-mediated eIF2α phosphorylation, which in turn attenuated general protein synthesis and led to cell cycle arrest in the G0/G1 phase. We further showed that the combination of citreoviridin and the 26S proteasome inhibitor bortezomib could improve the anticancer activity by enhancing ER stress, by ameliorating citreoviridin-caused cyclin D3 compensation, and by contributing to CDK1 deactivation and PCNA downregulation. More interestingly, the combined treatment triggered lethality through unusual non-apoptotic caspase- and autophagy-independent cell death with a cytoplasmic vacuolization phenotype. The results imply that by boosting ER stress, the combination of ATP synthase inhibitor citreoviridin and 26S proteasome inhibitor bortezomib could potentially be an effective therapeutic strategy against breast cancer.

Bacteria killing nanotechnology Bio-Kil effectively reduces bacterial burden in intensive care units.

A contaminated hospital environment has been identified as an important reservoir of pathogens causing healthcare-associated infections. This study is to evaluate the efficacy of bacteria killing nanotechnology Bio-Kil on reducing bacterial counts in an intensive care unit (ICU). Two single-bed rooms (S-19 and S-20) in the ICU were selected from 7 April to 27 May 2011. Ten sets of new textiles (pillow cases, bed sheets, duvet cover, and patient clothing) used by patients in the two single-bed rooms were provided by the sponsors. In the room S-20, the 10 sets of new textiles were washed with Bio-Kil; the room walls, ceiling, and air-conditioning filters were treated with Bio-Kil; and the surfaces of instruments (respirator, telephone, and computer) were covered with Bio-Kil-embedded silicon pads. Room S-19 served as the control. We compared the bacterial count on textiles and environment surfaces as well as air samples between the two rooms. A total of 1,364 samples from 22 different sites in each room were collected. The mean bacterial count on textiles and environmental surfaces in room S-20 was significantly lower than that in room S-19 (10.4 vs 49.6 colony-forming units [CFU]/100 cm(2); P < 0.001). Room S-20 had lower bacterial counts in air samples than room S-19 (33.4-37.6 vs 21.6-25.7 CFU/hour/plate; P < 0.001). The density of microbial isolations was significantly greater among patients admitted to room S-19 than those to room S-20 (9.15 vs 5.88 isolates per 100 patient-days, P < 0.05). Bio-Kil can significantly reduce bacterial burden in the environment of the ICU.

Differential trajectory of functional recovery and determinants for first time stroke survivors by using a LCGA approach: a hospital based analysis over a 1-year period.

BACKGROUND: Functional outcome and the risk factors for stroke survivors have explored in previous study. However, a comprehensive understanding of the patterns and critical risk factors of functional recovery is limited. AIM: To explore the trajectory groups and determinants of functional recovery for ischemic stroke patients during 1 year after stroke. DESIGN: Longitudinal study. SETTING: Inpatient. POPULATION: First-time stroke patients. METHOD: A total of 367 first-time ischemic stroke patients from the Stroke Registry in the Chang Gung Hospital (SRICH) database were analyzed in this study. Study variables comprised demographic and disease characteristics, laboratory data, and functional outcome. The Latent Class Growth Analysis (LCGA) was used to identify various trajectory clusters and multinomial logistic regression was used to identify the predictors of functional recovery. RESULT: Five trajectory clusters of functional recovery were identified using the Barthel Index. Among five clusters of functional recovery, nearly 18% of first-ever ischemic stroke patients maintained functional dependence, whereas 82% of stroke patients demonstrated functional recovery; and the significant recovery time totaled three months after the stroke. Determinants for various trajectory clusters of functional recovery were body mass index and serum albumin level, especially a higher serum albumin concentration predicted a more favorable functional recovery. CONCLUSION: Our findings suggest that diverse functional recovery clusters persisted and serum albumin concentration at admission was a critical assessment factor. CLINICAL REHABILITATION: Such information could be useful for identifying the different rehabilitation needs of varying trajectory groups and for effectively improving functional ability among the ischemic stroke population.

Expression of GALNT2 in human extravillous trophoblasts and its suppressive role in trophoblast invasion.

Extravillus trophoblast (EVT) invasion plays a critical role in placental development. Integrins bind to extracellular matrix (ECM) proteins to mediate EVT cell adhesion, migration, and invasion. Changes in O-glycans on ß1-integrin have been found to regulate cancer cell behavior. We hypothesize that O-glycosyltransferases can regulate EVT invasion through modulating the glycosylation and function of ß1-integrin. Here, we found that the GALNT1 and GALNT2 mRNA were highly expressed in HTR8/SVneo and first trimester EVT cells. Immunohistochemstry and immunofluorescence staining showed that GALNT2 was expressed in subpopulations of EVT cells in deciduas, but not in syncytiotrophoblasts and cytotrophoblasts of placental villi. The percentage of GALNT2-positive EVT cells increased with gestational ages. Overexpression of GALNT2 in HTR8/SVneo cells significantly enhanced cell-collagen IV adhesion, but suppressed cell migration and invasion. Notably, we found that GALNT2 increased the expression of Tn antigen (GalNAc-Ser/Thr) on ß1-integrin as revealed by Vicia Villosa agglutinin (VVA) binding. Furthermore, GALNT2 suppressed the phosphorylation of focal adhesion kinase (FAK), a crucial downstream signaling molecule of ß1-integrin. Our findings suggest that GALNT2 is a critical initiating enzyme of O-glycosylation for regulating EVT invasion.

Resection hip arthroplasty as a feasible surgical procedure for periacetabular tumors of the pelvis.

AIMS: Surgical treatment of periacetabular tumors remains one of the most challenging problems in musculoskeletal oncology. The purpose of this study was to review the clinical and functional outcomes of resection hip arthroplasty and analyze its feasibility. METHODS: This study assesses twenty-seven patients with periacetabular tumors treated by resection hip arthroplasty between 1999 and 2010. The tumors were excised with wide margins and the residual intact femoral head placed underneath the resected ilium. Clinical, functional and oncological outcomes as well as complications were carefully evaluated. RESULTS: The average follow-up time was 55 months (range, 3-118) and the mean surgical time 170 min (range, 120-350) with an average blood loss 1200 ml (range, 600-2200). Six patients died in 6-33 months postoperatively; no other local recurrences or deaths occurred. The 1-year, 5-year, and 10-year disease-free survival rates were 96.3%, 77.8% and 77.8% respectively. The mean limb-length discrepancy was 5 cm (range, 2-7.5) and all patients required custom-made shoes with their heels heightened by 2-5 cm. At the last follow-up, the mean functional score was 75.6%. Twenty patients recovered normal ambulation function with custom-made shoes and seven had to walk with crutches. Wound healing problems were observed in nine patients and deep or superficial infection in none. CONCLUSIONS: Resection hip arthroplasty is recommended as a feasible surgical protocol for periacetabular tumors because it has few complications, good functional results, short surgical time and little blood loss.

Electrophysiological characterization of sodium-activated potassium channels in NG108-15 and NSC-34 motor neuron-like cells.

AIMS: The electrical properties of Na(+) -activated K(+) current (I(K(Na)) ) and its contribution to spike firing has not been characterized in motor neurons. METHODS: We evaluated how activation of voltage-gated K(+) current (I(K) ) at the cellular level could be coupled to Na(+) influx through voltage-gated Na(+) current (I(N) (a) ) in two motor neuron-like cells (NG108-15 and NSC-34 cells). RESULTS: Increasing stimulation frequency altered the amplitudes of both I(Na) and I(K) simultaneously. With changes in stimulation frequency, the kinetics of both I(Na) inactivation and I(K) activation were well correlated at the same cell. Addition of tetrodotoxin or ranolazine reduced the amplitudes of both I(Na) and I(K) simultaneously. Tefluthrin (Tef) increased the amplitudes of both I(Na) and I(K) throughout the voltages ranging from -30 to + 10 mV. In cell-attached recordings, single-channel conductance from a linear current-voltage relation was 94 ± 3 pS (n = 7). Tef (10 µm) enhanced channel activity with no change in single-channel conductance. Tef increased spike firing accompanied by enhanced facilitation of spike-frequency adaptation. Riluzole (10 µm) reversed Tef-stimulated activity of K(Na) channels. In motor neuron-like NSC-34 cells, increasing stimulation frequency altered the kinetics of both I(Na) and I(K) . Modelling studies of motor neurons were simulated to demonstrate that the magnitude of I(K(Na)) modulates AP firing. CONCLUSIONS: There is a direct association of Na(+) and K(Na) channels which can provide the rapid activation of K(Na) channels required to regulate AP firing occurring in motor neurons.