Safety education of pedestrians for injury prevention.
Each year about one million people die and about 10 million are seriously injured on the world's roads. Educational measures to teach pedestrians how to cope with the traffic environment are considered to be an essential component of any prevention strategy, and pedestrian education has been recommended in many countries. However, as resources available for road safety are limited, a key question concerns the relative effectiveness of different prevention strategies. To quantify the effectiveness of pedestrian safety education programmes in preventing pedestrian-motor vehicle collisions. We searched the Injuries Group specialised register, Cochrane Controlled Trials Register, TRANSPORT, MEDLINE, EMBASE, ERIC, PSYCHLIT, SPECTR, and the WHO database on the Internet. We checked reference lists of relevant reviews and papers and contacted experts in the field. Most database searching was conducted in 1999. Randomised controlled trials of safety education programmes for pedestrians of all ages. One reviewer screened records. Two reviewers independently extracted data and assessed methodological quality of trials. Because of differences in the types of interventions and outcome measures used in the trials, meta-analyses were not carried out. We found 15 randomised-controlled trials of pedestrian safety education programmes, conducted between 1976 and 1997. Methodological quality of the included trials was generally poor. Allocation concealment was adequate in three trials, outcome assessment was blinded in eight, and in most of the studies large numbers of participants were lost to follow-up. Study participants were children in 14 studies and institutionalised adults in one. Eight studies involved the direct education of participants, seven used parents as educators. No trials were conducted in a developing country and there were none of pedestrian safety training in the elderly. None of the included trials assessed the effect of pedestrian safety education on the occurrence of pedestrian injury but six trials assessed the effect on observed behaviour. Some of these trials showed evidence of behavioural change following pedestrian safety education but it is difficult to predict what effect this might have on pedestrian injury risk. Pedestrian safety education can result in improvement in children's knowledge and can change observed road crossing behaviour but whether this reduces the risk of pedestrian motor vehicle collision and injury occurrence is unknown. There is evidence that changes in safety knowledge and observed behaviour decline with time suggesting that safety education must be repeated at regular intervals.


Prognostic accuracy of the serum lactate level, the SOFA score and the qSOFA score for mortality among adults with Sepsis.
Sepsis is a common critical condition caused by the body's overwhelming response to certain infective agents. Many biomarkers, including the serum lactate level, have been used for sepsis diagnosis and guiding treatment. Recently, the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) recommended the Sequential Organ Failure Assessment (SOFA) and the quick SOFA (qSOFA) rather than lactate for screening sepsis and assess prognosis. Here, we aim to explore and compare the prognostic accuracy of the lactate level, the SOFA score and the qSOFA score for mortality in septic patients using the public Medical Information Mart for Intensive Care III database (MIMIC III). The baseline characteristics, laboratory test results and outcomes for sepsis patients were retrieved from MIMIC III. Survival was analysed by the Kaplan-Meier method. Univariate and multivariate analysis was performed to identify predictors of prognosis. Receiver operating characteristic curve (ROC) analysis was conducted to compare lactate with SOFA and qSOFA scores. A total of 3713 cases were initially identified. The analysis cohort included 1865 patients. The 24-h average lactate levels and the worst scores during the first 24 h of ICU admission were collected. Patients in the higher lactate group had higher mortality than those in the lower lactate group. Lactate was an independent predictor of sepsis prognosis. The AUROC of lactate (AUROC, 0.664 [95% CI, 0.639-0.689]) was significantly higher than that of qSOFA (AUROC, 0.547 [95% CI, 0.521-0.574]), and it was similar to the AUROC of SOFA (AUROC, 0.686 [95% CI, 0.661-0.710]). But the timing of lactate relative to SOFA and qSOFA scores was inconsistent. Lactate is an independent prognostic predictor of mortality for patients with sepsis. It has superior discriminative power to qSOFA, and shows discriminative ability similar to that of SOFA.


Diagnostic utility of PETCT in thyroid malignancies: an update.
The primary clinical application of (18)F FDG PET/CT ((18)Fluorine labeled flurodeoxyglucose positron emission tomography/computed tomography) in differentiated thyroid carcinoma is in the identification of active disease in thyroglobulin (Tg) positive (>10 ng/ml), whole body iodine scan negative patients. The impact of FDG PET/CT in diagnosis, surveillance, cure, and progression-free survival of differentiated thyroid carcinoma patients remains to be seen. Five main indications of FDG PET/CT in thyroid cancer have been recommended by revised American thyroid association guidelines 2009. This review aims to provide a complete picture of PET imaging in thyroid malignancies and enumerates each indication with literature review. This review also highlights recent advances in targeted molecular imaging. Currently differentiated thyroid cancer is best imaged using conventional single photon emission computed tomography-based radioiodine tracers ((123)I/(131)I). Although the utility of FDG PET in well differentiated thyroid cancer patients who are iodine negative but with raised Tg is well established, evidence is emerging on the advantages of FDG PET/CT in other histological types of thyroid malignancy, such as Hurthle cell, medullary, and the anaplastic malignancies. Novel PET radiotracers, such as (124)Iodine ((124)I), (18)F-DOPA (3,4-dihydroxy-L-phenylalanine), and (68)Ga-DOTA peptides are revolutionizing the way thyroid malignancies are imaged. Newer concepts on targeted molecular imaging and theranostics are ushering in new possibilities for imaging and treating thyroid cancer.


Expression of brachyury in hemangioblastoma: potential use in differential diagnosis.
Hemangioblastoma (HBL) accounts for up to 2.5% of all intracranial tumors. It may occur as a sporadic entity or as a part of Von Hippel-Lindau syndrome. Patients with Von Hippel-Lindau syndrome are also at an increased risk of developing clear cell renal cell carcinoma (CCRCC). The distinction of HBL from CCRCC metastatic to the central nervous system (CNS) or from other histologic mimics can be challenging at times when based solely on hematoxylin and eosin-stained sections. In the present study we evaluated the potential use of the immunohistochemical evaluation of brachyury protein in the differential diagnosis of these lesions. Archival tissues from 22 HBLs, 16 primary CCRCCs, 8 CCRCCs metastatic to the CNS, and 4 angiomatous and 4 clear cell meningiomas were retrieved from our surgical pathology files and submitted to the immunohistochemical procedures against brachyury. Cases showing nuclear and/or cytoplasmic staining were considered to be positive for brachyury. Positive cytoplasmic staining was evidenced in the stromal cells of 20 of the 22 HBLs. In most cases, >50% of the neoplastic cells were labeled, with strong or moderate intensity of staining. No nuclear or cytoplasmic staining for brachyury was observed in any of the primary renal or metastatic CCRCCs, nor in either of the meningioma types. Thus, brachyury cytoplasmic staining was demonstrated to be highly specific for HBL (specificity, 100%) and represented a sensible (sensitivity, 91%) method, with high positive (100%) and negative (89%) predictive values and high diagnostic accuracy (95%) in the differential diagnosis between HBL and CCRCC metastatic to the CNS or meningioma. On the basis of our findings we propose the use of brachyury as an additional helpful immunohistochemical marker to resolve the differential diagnosis of HBL toward histologic mimics.


Twin- or single-screw extrusion of raw soybeans and preconditioned soybean meal and corn as individual ingredients or as corn-soybean product blends in diets for weanling swine.
Two 28-d experiments were conducted to evaluate the effects of extrusion of ground yellow corn, solvent-extracted soybean meal (SBM), and cracked whole soybeans (CWS) individually or as corn-soybean product blends on growth performance of weanling pigs. For Exp. 1, ground corn, SBM, and the corn-SBM blend were extruded at 137.5°C, 131.5°C, and 135.0°C, respectively, in a twin-screw extruder. Transit time was 60 s. Water was injected at 125 gmin during extrusion. The 5 treatments were the corn-SBM control diet and the diets with extruded (EX) corn + SBM, EX-SBM + corn, EX-corn + EX-SBM, and the EX-blend of corn-SBM. Ninety crossbred pigs with an initial average BW of 5.98 kg were allotted to 9 treatment replications with a barrow and gilt per pen. For Exp. 2, ground corn was preconditioned with water (10.0% of corn weight), and SBM was preconditioned with water and soybean oil (each at 20.0% of SBM weight) before extrusion. Raw CWS were not preconditioned. The corn, SBM, CWS, corn-SBM blend, and corn-CWS blend were extruded at 113.0°C, 132.0°C, 132.0°C, 88.0°C, and 102°C, respectively, with a single-screw extruder. Transit time was 30 s. The 8 isocaloric treatments were the corn-SBM control diet and the diets with EX-corn + SBM, EX-SBM + corn, EX-corn + EX-SBM, the EX-blend of corn-SBM, EX-CWS + corn, EX-CWS + EX-corn, and the EX-blend of corn-CWS. A total of 296 crossbred pigs with an initial average BW of 6.56 kg were allotted to 10 treatment replications. Sex and pigs per pen (3 or 4) were equalized within replication. Results for both experiments indicate that single- or twin-screw extrusion of ground corn or SBM as individual ingredients or as corn-SBM blends in diets for weanling pigs did not improve 28-d growth performance. However, for Exp. 2 weanling pigs fed the diets with EX-CWS + corn and EX-CWS + EX-corn had greater ( < 0.01) ADG and G:F, respectively, than pigs fed the corn-SBM control diet. The extrusion temperature of 102°C for the corn-CWS blend did not inactivate adequate protease inhibitors in CWS, and pigs fed that diet had poor growth performance. In conclusion, single-screw extrusion of CWS (132°C for 30 s) in diets for weanling pigs improved growth performance compared with pigs fed the corn-SBM control diet. However, twin- or single-screw extrusion of ground yellow corn or solvent-extracted SBM as individual ingredients or as corn-SBM blends in diets for weanling pigs did not improve growth performance compared with pigs fed the corn-SBM control diets.


[STT-arthrodesis versus radial shortening osteotomy for Kienböck's disease].
Thirteen patients treated by STT fusion for Kienböck's disease (five stage 3 a, seven stage 3 b, and one stage 4) and 36 patients treated by radial shortening osteotomy (20 stage 3 a, 16 stage 3 b) were checked after 26 and 83 months average. The active range of motion and grip strength were compared by means of the Cooney score, discomfort and pain by the DASH score. X-rays were compared for the bone structure of the lunate and development or progress of carpal collapse. After STT fusion the active over-all range of motion decreased by about 10 degrees, grip strength improved slightly by approximately 10 %, pain and discomfort improved well. Consolidation of the lunate was seen in ten of thirteen patients. The patients treated with radial shortening osteotomy could all improve their range of motion by about 10 degrees and the grip strength by about 20 %, whereas discomfort and pain persisted in some cases. X-rays showed consolidation of the lunate in cases of eleven patients stage 3 a and twelve patients stage 3 b. Radiological results were not always corresponding to the clinical results and the patients' subjective estimation. A group of eight patients could be followed up after more than ten years; all of them showed excellent results. This may indicate the long-term result for those patients who benefit from radius shortening with early pain relief. We recommend both procedures for stage 3 a and 3 b and suggest to decide from case to case, according to the needs of the patient. Ulna minus variance or the patient's wish to restore full active range of motion indicate radial shortening.


Short-term association between road traffic noise and healthcare demand generated by Parkinson's disease in Madrid, Spain.
To analyse whether there is a short-term association between road traffic noise in the city of Madrid and Parkinson's disease (PD)-related demand for healthcare. Time-series analysis (2008-2009) using variables of analysis linked to emergency and daily PD-related demand for healthcare (ICD-10: G20-G21), namely, PD-hospital admissions (HAs), PD-outpatient visits (OVs) and PD-emergency medical calls in Madrid. The noise pollution measurements used were Leqd, equivalent sound level for the daytime hours (from 8 a.m. to 10 p.m.), and Leqn, equivalent sound level for night time hours (from 10 p.m. to 8 a.m.) in dB(A). We controlled for temperature, pollution, trends and seasons, and used the Poisson regression model to calculate relative risk (RR). The association between Leqd and HAs was found to be linear. Leqd and Leqn at lag 0.1 and temperature at lags 1 and 5 were the only environmental variables associated with increased PD-related healthcare demand. The RR (lag 0) for Leqd and HA was 1.07 (1.04-1.09), the RR (lag 0) for Leqd and OV was 1.28 (1.12-1.45), and the RR (lags 0.1) for Leqn and emergency medical calls was 1.46 (1.06-2.01). The above results indicate that road traffic noise is a risk factor for PD exacerbation. Measures to reduce noise-exposure levels could result in a lower PD-related healthcare demand.


Early menopausal changes in bone mass and sex steroids.
Eighty-four healthy perimenopausal and early postmenopausal women were divided into four groups: group A, those with slightly irregular menstrual periods and plasma FSH below 40 mIU/ml; group B, those with irregular periods and FSH above 40 mIU/ml; group C, those whose last menstrual period was within 1 yr of study; and, group D, those whose last menstrual period was between 12 and 55 months before the study. Plasma concentrations of estrone and estradiol progressively decreased in groups B, C and D compared to those in A in parallel with a decrease in the production rates, and FSH and LH were significantly increased. There was little change in the concentration of androstenedione or testosterone. Vertebral bone mass was significantly decreased in groups B, C, and D compared to that in A, and radial bone mass was decreased in group D. There was a significantly positive correlation between plasma estrone and estradiol and bone mass at both the radius and vertebra. Increased bone remodeling was suggested by increases in serum calcium and bone gla protein. These data suggest that bone loss, at least from the spine, may begin before menses cease and is correlated with decreases in estrogen production and increases in bone remodeling.


Cancers after stem cell transplantation in children: a cost of cure?
There have been many advances in the field of stem cell transplantation over the past few years. Newer preparative regimens and better supportive care measures are allowing more children to survive and lead long lives after stem cell transplantation. We are only now beginning to see what the cost of this success may be in regard to the long-term effects of this treatment. Most long-term follow up studies have been reported in the adult literature and there is very little information on the pediatric population. Children who undergo stem cell transplantation will have a long period of observation in which new and different complications can occur. This article looks at the current literature on secondary malignancies and lymphoproliferative disorders after stem cell transplantation in children, with particular focus on risk factors, possible strategies for prevention, and treatment.


Arterial hypertension and neurofibromatosis: renal artery stenosis and coarctation of abdominal aorta.
A 10-year-old girl had arterial hypertension, generalized neurofibromatosis, coarctation of the abdominal aorta and multiple stenoses at the origin of each renal artery. After resection of the stenotic areas and reimplantation of the renal arteries in the aorta, her arterial pressure decreased substantially. However, hypertension recurred and radiologic follow-up 4 1/2 years later showed distinct progression of the coarctation and renewed stenosis of all renal arteries at their origin. The stenotic areas showed eccentric intimal proliferation, frequently bulging into the lumen, with small nodular aggregates of smooth muscle cells and proliferation of fibrous tissue containing spindle-shaped nuclei in a palisading pattern. Hypertension associated with neurofibromatotic vascular disease has been described in 47 other patients in the literature. These patients have been young (mean age, 14 years) and predominantly male. In contrast to fibromuscular dysplasia, in which 95% of all stenoses are found in the distal two thirds of the renal arteries, in vascular neurofibromatosis more than 50% of the stenoses are found at the origin.


Dynamics of Plasmodium falciparum alleles in children with normal haemoglobin and with sickle cell trait in western Uganda.
We describe the diversity of Plasmodium falciparum populations in western Uganda and assess the role that asymptomatic malaria carriers with sickle cell trait (HbAS) may be playing on the Plasmodium population structure. We genotyped P. falciparum in 291 samples using merozoite surface protein (MSP) 1 and 2 loci. Extensive genetic diversity was detected among symptomatic children in Mbarara (20 MSP1 alleles; 31 MSP2 alleles) and Kagando, Kasese (19 MSP1 alleles; 30 MSP2 alleles). Multiplicity of infection (MOI) was significantly higher in Kagando, Kasese than in Mbarara, with 2.7 and 2.1 genotypes/PCR positive sample with MSP2 marker, respectively. Similar strains were circulating in the two sites; however, a few strains specific to individual sites were observed. Prevalence of HbAS was 36% (12/33) among asymptomatic children in Kisinga sub-county, Kasese. In asymptomatic children, MOI was age-dependent and higher in HbAS carriers than HbAA, suggesting that HbAS carriers harbour a wider range of P. falciparum genotypes. Sickle cell trait may influence rapid acquisition of premunition by creating a reservoir of variant parasite strains in the host. The high level of genetic diversity demonstrated here shows that even in areas with low or seasonal transmission, high levels of parasite polymorphism can occur.


Association of Prior Vaccination With Influenza Vaccine Effectiveness in Children Receiving Live Attenuated or Inactivated Vaccine.
Some studies have reported negative effects of prior-season influenza vaccination. Prior-season influenza vaccination effects on vaccine effectiveness (VE) in children are not well understood. To assess the association of prior-season influenza vaccination with subsequent VE in children aged 2 to 17 years. This multiseason, test-negative case-control study was conducted in outpatient clinics at 4 US sites among children aged 2 to 17 years with a medically attended febrile acute respiratory illness. Participants were recruited during the 2013-2014, 2014-2015, and 2015-2016 seasons when influenza circulated locally. Cases were children with influenza confirmed by reverse-transcription polymerase chain reaction. Test-negative control individuals were children with negative test results for influenza. Vaccination history, including influenza vaccine type received in the enrollment season (live attenuated influenza vaccine [LAIV], inactivated influenza vaccine [IIV], or no vaccine) and season before enrollment (LAIV, IIV, or no vaccine), determined from medical records and immunization registries. LAIV and IIV effectiveness by influenza type and subtype (influenza A[H1N1]pdm09, influenza A[H3N2], or influenza B), estimated as 100 × (1 - odds ratio) in a logistic regression model with adjustment for potential confounders. Prior season vaccination associations were assessed with an interaction term. Of 3369 children (1749 [52%] male; median age, 6.6 years [range, 2-17 years]) included in the analysis, 772 (23%) had a positive test result for influenza and 1674 (50%) were vaccinated in the enrollment season. Among LAIV recipients, VE against influenza A(H3N2) was higher among children vaccinated in both the enrollment and 1 prior season (50.3% [95% CI, 17.0% to 70.2%]) than among those without 1 prior season vaccination (-82.4% [95% CI, -267.5% to 9.5%], interaction P < .001). The effectiveness of LAIV against influenza A(H1N1)pdm09 was not associated with prior season vaccination among those with prior season vaccination (47.5% [95% CI, 11.4% to 68.9%]) and among those without prior season vaccination (7.8% [95% CI, -101.9% to 57.9%]) (interaction P = .37). Prior season vaccination was not associated with effectiveness of IIV against influenza A(H3N2) (38.7% [95% CI, 6.8% to 59.6%] among those with prior-season vaccination and 23.2% [95% CI, -38.3% to 57.4%] among those without prior-season vaccination, interaction P = .16) or with effectiveness of IIV against influenza A[H1N1]pdm09 (72.4% [95% CI, 56.0% to 82.7%] among those with prior season vaccination and 67.5% [95% CI, 32.1% to 84.4%] among those without prior season vaccination, interaction P = .93). Residual protection from prior season vaccination only (no vaccination in the enrollment season) was observed for influenza B (LAIV: 60.0% [95% CI, 36.8% to 74.7%]; IIV: 60.0% [36.9% to 74.6%]). Similar results were observed in analyses that included repeated vaccination in 2 and 3 prior seasons. Influenza VE varied by influenza type and subtype and vaccine type, but prior-season vaccination was not associated with reduced VE. These findings support current recommendations for annual influenza vaccination of children.


Optofluidic light modulator integrated in lab-on-a-chip.
Microfluidic lenses are relevant optical components for sensing application in lab-on-a-chip devices, guaranteeing a robust alignment of the elements, a high level of compactness and tunable optical properties. In this work we describe an innovative integrated in-plane microfluidic lens. The device shows both an optimized shape capable of reducing spherical aberrations and periodically tunable optical properties. Indeed through the combination of the lens with a droplet generator module, we have been able to obtain an integrated optofluidic modulator capable of both on-demand on/off switching and periodic modulation of light. The device possesses a simple 3D geometry, which has been realized by exploiting the 3D capability of the femtosecond laser micromachining fabrication technique.


Molecular mechanisms underlying the inhibitory effects of bovine lactoferrin on osteosarcoma.
Osteosarcoma (OS) is one the most common primary malignancies of the bone in children and young adults with high metastasis. The use of non-toxic naturally derived compounds is one of present strategies in OS therapy to reduce secondary effects and chemo-resistance. Lactoferrin (LF), a transferrin protein derived from milk, currently appears to be an anticancer agent. However, its suppressive effects on OS have not been fully investigated. Therefore, we aimed to examine the molecular mechanism underlying the inhibitory effects of bovine LF (bLF) on OS. OS cell lines (NOS1, U2OS, MG63, and 143B) and an osteoblastic (ST2) were treated with bLF. Effects of bLF on OS-cell proliferation and migration were examined by proliferation and wound-healing assays. Expression levels of low-density-lipoprotein-receptor-related protein 1 (LRP1) and cytokines including interleukin-1 beta (IL-1β), IL-6, and receptor-activator of nuclear factor kappa-Β ligand (RANKL) were measured using western blotting. Osteoclast formation was examined by co-culture of 143B, ST2, and bone marrow cells. We found that bLF down-regulated IL-1β, IL-6, and RANKL expression and suppressed phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 in 143B cells; bLF also drastically suppressed 143B-activated RANKL production in ST2 cells. This may have contributed to the reduction in the number of differentiated osteoclasts. Taken together, these data reveal that bLF down-regulates NF-κB to attenuate proliferation, migration, and bone resorption in OS and the OS-microenvironment. This study provides new findings and the precise underlying mechanisms of the inhibitory effects of bLF on OS. bLF can be a possible therapeutic agent for OS patients.


Cutaneous immune-related adverse events among Taiwanese cancer patients receiving immune checkpoint inhibitors link to a survival benefit.
Cutaneous immune-related adverse events are common in cancer patients receiving immunotherapies but seldom studied in a comprehensive way of collecting all cancer types with comparisons between different immune-oncology drugs and correlation to patient survival. In this retrospective cohort study, we recruited 468 cancer patients receiving immunotherapies in a tertiary referral center in Taiwan and try to determine real-world incidence of cutaneous immune-related adverse events and their associations with the survival rates. Among them, 128 patients (27.4%) had cutaneous immune-related adverse events, with maculopapular eruption (10.6%) and pruritus (10.1%) most frequently identified in the monotherapy group. The incidence of these cutaneous immune-related adverse events was highest in patients receiving pembrolizumab (34.1%, P < .0001). Concurrent usage of molecular-targeted therapy with immunotherapy was associated with a higher incidence (57.8%, P < .0001). The Kaplan-Meier plot and log-rank test showed that patients with any type of immune-related cutaneous adverse events had longer survival time than those without (P < .0001). In conclusion, having either type of cutaneous immune-related adverse event in cancer patients receiving immunotherapies was correlated with a longer overall survival. Prompt diagnosis and suitable treatment are important.


[Protoplast fusion in Bacillus cereus].
Polyethyleneglycol induced fusion of Bacillus cereus protoplasts and its genetic consequences have been investigated. The technique used allows the transfer of a small plasmid pBC16 between Bacillus cereus cells. Fusion has resulted in isolation of hybrid cells having acquired TcR phenotype (harbouring pBC16) with high frequencies (10(-2)-10(-3)). However, the genetic instability of hybrid cells and segregation effects have influenced dramatically the final results of plasmid transfer. Nevertheless, the fusion of protoplasts proves to be useful in construction of BAcillus cereus strains inheriting plasmid determinants.


I will never be too embarrassed to discuss a patient's sexuality.
It was my first week on placement in a busy general medical ward. My mentor asked me to admit a patient with a urinary tract infection and constipation who had just come from A&E.


Description of a symptomless cystic fibrosis L346P/M348K compound heterozygous Cypriot individual.
During the past few years we have been testing the hypothesis that Cyprus may have been spared many severe cystic fibrosis (CF) cases but not cystic fibrosis transmembrane conductance regulator (CFTR) mutations. We have been analysing by molecular methods patients with atypical mild phenotypes where CF enters the differential diagnosis. With this approach we identified a mutation, L346P, which in association with the severe mutation delta F508 or 1677delTA, confers a mild and atypical presentation. Recently, we identified another entirely symptomless 48-year-old individual, with genotype L346P/M348K. The fact that M348K was initially identified in a severely affected Italian patient strengthens the hypothesis that L346P, a putative mild mutation, is dominant over severe ones. One other explanation is that M348K is not a causative defect but a rare polymorphism. These findings have important implications for genetic counselling, especially when the counselling is sought by concerned couples for prenatal diagnostic purposes.


EMaGer: A Wearable Full-Circumference HD-EMG Sensor and Data Augmentation Method for Robust Hand Gesture Recognition.
This work presents EMaGer, a new 360° 64-channel high-density electromyography (HD-EMG) bracelet combined with an original data augmentation method for improved robustness in gesture recognition. By leveraging homogeneous electrode density and powerful deep learning techniques, the sensor is capable of rotation invariance around the arm axis, thus increasing gesture recognition robustness to electrode movement and inter-session evaluation. The system is made of a 4x16 electrode array covering the full circumference of the limb, and uses a sampling frequency of 1 kHz and a 16-bit resolution. The sensor's uniform and adjustable geometry paired with an array barrel shifting data augmentation (ABSDA) technique allows a convolutional neural network to maintain a 76.98% inter-session classification accuracy for a 6 gestures dataset, from a baseline intra-session accuracy of 93.75%. High inter-session classification accuracy decreases the training burden for users of EMG control systems such as myoelectric prostheses by minimizing calibration requirements. The same methods applied with different state-of-the-art sensors are demonstrated to be less effective. Thus, this work evidences the importance of co-designing the EMG sensor system with the gesture inference algorithms to leverage synergistic properties and solve state-of-the-art challenges.Clinical relevance- This paper establishes a method that alleviates clinical manipulations in setting up and calibrating myoelectric prosthetic devices.


Association between neuroimaging findings and neurological sequelae in patients with congenital cytomegalovirus infection.
Congenital cytomegalovirus (CMV) infection is an important cause of disability. There is little evidence on the prognostic value of lesions identified in neuroimaging studies. The study aimed to assess the severity of lesions detected with brain MRI and transfontanellar ultrasound and their relationship with long-term neurological deficits. We performed a retrospective, analytical, observational study of 36 patients with congenital CMV infection. Neuroimaging studies were reviewed and classified according to the modified Noyola' scale. Imaging findings were compared with neurological alterations in the patients' most recent follow-up evaluation at the paediatric neurology department. Thirty-six patients were studied (transfontanellar ultrasound: 30; brain MRI: 29). Twenty of 30 patients showed ultrasound abnormalities; of these, 11 showed alterations on brain MR images (P = .04) and 10 had neurological impairment (P = .008). Transfontanellar ultrasound had a sensitivity of 83.3%, 90% CI: 58-100 and a specificity of 44.4%, 90% CI: 18.7-70.2 for predicting neurological sequelae. Brain MRI displayed abnormalities in 20 of 29 patients, of whom 16 had neurological impairment (P < .001). MRI had a sensitivity of 94%, 95% CI: 80-100 and a specificity of 66.6%, 95% CI: 36-97.5 for predicting neurological sequelae. Modified Noyola' scale values > 2 were correlated with psychomotor retardation (P < .001). Our findings validate previous studies reporting a statistical significant correlation between the extension of neuroimaging lesions and severity of neurological deficits.


Beverages Consumption and Oral Health in the Aging Population: A Systematic Review.
Little study has yet been made of the effect of different beverages on oral health outcomes in the aging population. The purpose of this systematic review is to evaluate the association between different beverages, including alcohol intake, coffee, milk, tea, and sugary drinks, and a cluster of oral health outcomes, including periodontal disease, oral dysbiosis, and tooth loss in older adults. The literature was screened from the inception up to May 2021 using six different electronic databases. Two independent researchers assessed the eligibility of 1308 retrieved articles regarding inclusion criteria; only 12 fitted the eligibility requirements, representing 16 beverage entries. A minimum age of 60 was the inclusion criterion. No exclusion criteria were applied to outcomes assessment tools, recruiting facilities (hospital or community), general health status, country, and study type (longitudinal or cross-sectional). The consumption of alcoholic beverages was expressed as alcohol intake in all eligible studies, thereby replacing alcoholic beverages in the analysis. The quality of evidence was judged as moderate for alcohol and low or very low for beverages. In regard to oral health in the elderly, the review identified information on alcohol (56.25%), followed by coffee (18.75%), milk (12.50%), tea (6.25%), and sugary drinks (6.25%). Alcohol, sugary drinks, and coffee were found to be related to tooth loss. Periodontal disease was inversely related to coffee and milk, but fostered by alcohol consumption. In one article, tea but not coffee seemed to improve oral microbiota. In summary, alcohol seems to be a driver for tooth loss and periodontal disease in the aging population. However, more research is needed to gain a more solid knowledge in this research area. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, PROSPERO, Identifier: CRD42021256386.


Structure-specific DNA endonuclease Mus81/Eme1 generates DNA damage caused by Chk1 inactivation.
The DNA-damage checkpoint kinase Chk1 is essential in higher eukaryotes due to its role in maintaining genome stability in proliferating cells. CHK1 gene deletion is embryonically lethal, and Chk1 inhibition in replicating cells causes cell-cycle defects that eventually lead to perturbed replication and replication-fork collapse, thus generating endogenous DNA damage. What is the cause of replication-fork collapse when Chk1 is inactivated, however, remains poorly understood. Here, we show that generation of DNA double-strand breaks at replication forks when Chk1 activity is compromised relies on the DNA endonuclease complex Mus81/Eme1. Importantly, we show that Mus81/Eme1-dependent DNA damage--rather than a global increase in replication-fork stalling--is the cause of incomplete replication in Chk1-deficient cells. Consequently, Mus81/Eme1 depletion alleviates the S-phase progression defects associated with Chk1 deficiency, thereby increasing cell survival. Chk1-mediated protection of replication forks from Mus81/Eme1 even under otherwise unchallenged conditions is therefore vital to prevent uncontrolled fork collapse and ensure proper S-phase progression in human cells.


Intercondylar roof impingement after anatomic double-bundle anterior cruciate ligament reconstruction in patients with knee hyperextension.
Although an anatomically placed graft in anterior cruciate ligament (ACL) reconstruction is reported to have a low risk of roof impingement, which may cause deterioration of the graft or an extension deficit, the incidence of roof impingement by these grafts has not been evaluated in hyperextensible knees. To evaluate the incidence of roof impingement by the native ACL in hyperextensible knees and to examine the risk of roof impingement by anatomic placement of the ACL graft in hyperextensible knees. Controlled laboratory study. Twelve patients were selected for a hyperextensible knee group (group A), defined as having hyperextension of the knee of greater than 10°. Twelve patients were recruited to a normal extension knee group (group B) with normal extension of the knee of less than 5° of hyperextension. Magnetic resonance imaging (MRI) scans of the knee positioned in 30° of flexion and full extension were acquired from all patients. The shape of the native ACL at full extension was compared between the groups. A 3-dimensional (3D) bone model was created from the acquired 2D MRI scans. A virtual anatomic double-bundle ACL reconstruction in each patient and a virtual anatomic single-bundle reconstruction in the patients in group A were performed using the 3D MRI bone models. The volume of the overlap between the graft and roof was calculated to evaluate graft impingement in each instance. The MRI scans showed posterior bowing of the native ACL in the group A knees. The simulated double-bundle ACL reconstruction showed that the overlapped volume was significantly greater in patients in group A than in patients in group B (P < .05). However, the overlap of the simulated single-bundle ACL reconstruction was significantly less than for the double-bundle ACL reconstruction (P < .05). To reduce the risk of roof impingement by the graft, single-bundle ACL reconstruction with the graft placed at the center of the footprint might be the better method for patients with a hyperextensible knee than an anatomic double-bundle ACL reconstruction. It is recommended that surgeons cautiously consider roof impingement after anatomic double-bundle ACL reconstruction in patients with a hyperextensible knee.


Association between Toxoplasma gondii infection and thyroid dysfunction: a case-control seroprevalence study.
The association between Toxoplasma gondii infection and thyroid disease has been poorly studied. Therefore, we sought to determine the association between T. gondii seropositivity and thyroid dysfunction. We performed an age- and gender-matched case-control study of 176 patients suffering from hypothyroidism (n = 161) or hyperthyroidism (n = 15) and 528 control subjects without these diseases in a public hospital in Durango City, Mexico. Anti-Toxoplasma IgG antibodies were determined in sera from cases and controls using a commercially available enzyme-linked immunoassay. Anti-T. gondii IgG antibodies were found in 11 (6.3%) of 176 patients suffering from thyroid dysfunction and in 48 (9.1%) of 528 control subjects (OR = 0.66; 95% CI: 0.33-1.31; P = 0.23). Stratification by two groups of age (50 years and younger, and 51 year and older) showed that the youngest group of patients with thyroid dysfunction had a significantly lower seroprevalence of T. gondii infection than its age- and gender-matched control group (1/83: 1.2% vs 23/257: 8.6%; OR = 0.12; 95% CI: 0.01-0.93; P = 0.01). This stratification also showed that the youngest group of patients with hypothyroidism had a significantly lower seroprevalence of T. gondii infection than its age- and gender matched control group (0/75: 0% vs 21/233: 9.0%; P = 0.003). Our results suggest that thyroid dysfunction is not associated with seropositivity to T. gondii in general; however, in young (50 years or less) patients, a negative association between infection and thyroid dysfunction and hypothyroidism was found. Further research to confirm this negative association is needed.


Development of Biopolymer and Conducting Polymer-Based Optical Sensors for Heavy Metal Ion Detection.
Great efforts have been devoted to the invention of environmental sensors as the amount of water pollution has increased in recent decades. Chitosan, cellulose and nanocrystalline cellulose are examples of biopolymers that have been intensively studied due to their potential applications, particularly as sensors. Furthermore, the rapid use of conducting polymer materials as a sensing layer in environmental monitoring has also been developed. Thus, the incorporation of biopolymer and conducting polymer materials with various methods has shown promising potential with sensitively and selectively toward heavy metal ions. In this feature paper, selected recent and updated investigations are reviewed on biopolymer and conducting polymer-based materials in sensors aimed at the detection of heavy metal ions by optical methods. This review intends to provide sufficient evidence of the potential of polymer-based materials as sensing layers, and future outlooks are considered in developing surface plasmon resonance as an excellent and valid sensor for heavy metal ion detection.


Papular mucinosis. A clinicopathologic study of four patients.
Four patients with papular mucinosis were studied. Each patient had clinically characteristic cutaneous lesions, increased dermal deposition of mucin, and a serum monoclonal lgG paraprotein. One patient had sclerodermoid features consistent with the scleromyxedema variant of papular mucinosis. Associated findings in the patients included pachydermoperiostosis (one case), adenocarcinoma of the stomach (one case), carcinoma of the pancreas (one case), bizarre neurologic symptoms (one case), and emphysema (two cases). Autopsies were performed in two cases and no increased mucin deposition was observed in internal organs. Immunofluorescence microscopic study of involved skin showed no immunoreactant deposition in the three patients studied. Our observations support the hypothesis that papular mucinosis is a disorder of skin fibroblasts without internal organ involvement.


A volume of intersection approach for on-the-fly system matrix calculation in 3D PET image reconstruction.
The aim of this study is the evaluation of on-the-fly volume of intersection computation for system's geometry modelling in 3D PET image reconstruction. For this purpose we propose a simple geometrical model in which the cubic image voxels on the given Cartesian grid are approximated with spheres and the rectangular tubes of response (ToRs) are approximated with cylinders. The model was integrated into a fully 3D list-mode PET reconstruction for performance evaluation. In our model the volume of intersection between a voxel and the ToR is only a function of the impact parameter (the distance between voxel centre to ToR axis) but is independent of the relative orientation of voxel and ToR. This substantially reduces the computational complexity of the system matrix calculation. Based on phantom measurements it was determined that adjusting the diameters of the spherical voxel size and the ToR in such a way that the actual voxel and ToR volumes are conserved leads to the best compromise between high spatial resolution, low noise, and suppression of Gibbs artefacts in the reconstructed images. Phantom as well as clinical datasets from two different PET systems (Siemens ECAT HR(+) and Philips Ingenuity-TF PET/MR) were processed using the developed and the respective vendor-provided (line of intersection related) reconstruction algorithms. A comparison of the reconstructed images demonstrated very good performance of the new approach. The evaluation showed the respective vendor-provided reconstruction algorithms to possess 34-41% lower resolution compared to the developed one while exhibiting comparable noise levels. Contrary to explicit point spread function modelling our model has a simple straight-forward implementation and it should be easy to integrate into existing reconstruction software, making it competitive to other existing resolution recovery techniques.


Recovery from arterial growth delay reduces penetrance of cardiovascular defects in mice deleted for the DiGeorge syndrome region.
Chromosome 22q11.2 heterozygous deletions cause the most common deletion syndrome, including the DiGeorge syndrome phenotype. Using a mouse model of this deletion (named Df1) we show that the aortic arch patterning defects that occur in heterozygously deleted mice (Df1/+) are associated with a differentiation impairment of vascular smooth muscle in the 4th pharyngeal arch arteries (PAAs) during early embryogenesis. Using molecular markers for neural crest, endothelial cells and vascular smooth muscle, we show that cardiac neural crest migration into the 4th arch and initial formation of the 4th PAAs are apparently normal in Df1/+ embryos, but affected vessels are growth-impaired and do not acquire vascular smooth muscle. As in humans, not all deleted mice present with cardiovascular defects at birth. However, we found, unexpectedly, that all Df1/+ embryos have abnormally small 4th PAAs during early embryogenesis. Many embryos later overcome this early defect, coincident with the appearance of vascular smooth muscle differentiation, and develop normally. Embryos born with aortic arch patterning defects probably represent a more severely affected group that fails to attain sufficient 4th PAA growth for normal remodelling of the PAA system. Our data indicate that Df1/+ embryos are able to overcome a localized arterial growth impairment and thereby reduce the penetrance of birth defects.


Needle-wire-guided breast tumor excision.
Complete resection of large-size tumors can be easily approachable developing needle-guide tumour excision, in the context of Oncoplastic Conservative Breast Surgery. Needles are used as markers showing optimal excision margins, especially at conflicting points.


Intracranial pressure monitoring by flaccid-cuff catheter in an animal model.
Several methods of monitoring intracranial pressure (ICP) are in current use, each with its own advantages and disadvantages. The intraventricular line has been most useful because of the ability to withdraw cerebrospinal fluid to assist in control of elevated ICP. However, masses within the brain or generalized increased ICP may compress the lateral ventricle, making insertion of the catheter difficult or impossible. The intracerebral wick records hydrostatic changes too slowly to be used clinically. Swollen cerebral tissue may occlude the subarachnoid bolt thereby dampening the recorded pressure, and epidural monitors may give falsely high recordings because of irregularities of dura or bone. The authors have developed a flaccid-cuff catheter which has proven in animals to be an effective ICP monitor. There are several advantages, such as easy insertion into the centrum semiovale, rapid response to acute pressure changes, and continued sensitivity for periods of up to 3 weeks. The flaccid catheter cuff has no tension so that the pressure across the membrane is equal to zero, simplifying calibration. This type of cuff is necessary for maximum sensitivity to interstitial, brain-tissue, and gross ICP changes. The flaccid-cuff catheter may prove to be useful in a variety of situations such as after closed head trauma or intracranial surgery to assess elevated ICP caused by edema or evolving hematoma.


Focal nodular hyperplasia of the liver in children: review of follow-up and outcome.
The authors used a conservative approach to treat focal nodular hyperplasia of the liver (FNH) and were interested in the long-term results of different therapeutic approaches in order to establish the most appropriate treatment. A review of the literature was conducted, and 31 pediatric case reports were identified in which follow-up and outcome data were noted. Tumor resection was performed in 18 cases (58%), operative biopsy alone in nine (29%), vascular ligation in two, and embolization of hepatic arteries in two. The outcome appears to be good for both groups of patients, ie, those with observation alone and those with resection. More information is to be collected regarding the new procedures (embolization and ligation). This is a retrospective analysis, and data from future international prospective studies are needed.


Prevention of diabetes, hepatic injury, and colon cancer with dehydroepiandrosterone.
The levels of dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) peak in human in their twenties, then decrease gradually with age. The physiological importance of DHEA was not clear until recent research reports showing that DHEA has beneficial effects on preventing diabetes, malignancy, inflammation, osteoporosis, and collagen disease. We summarize our results concerning diabetes, hepatitis, and colon cancer. In 1982, Coleman et al. [Diabetes 31 (1982) 830] reported that DHEA decreased hyperglycemia in diabetic db/db mice, which become insulin resistant. We measured hepatic gluconeogenic enzymes in an attempt to elucidate the mechanical mechanism of DHEA action. The activity and gene expression of hepatic gluconeogenic enzyme such as glucose-6-phosphatase (G6Pase) was increased in db/db mice despite hyperinsulinemia compared to control db/+m mice. DHEA, like troglitazone, decreased these levels in db/db mice. We also showed that DHEA improved the insulin resistance caused by aging or obesity using the glucose clamp technique in another animal model. In humans, the serum DHEA concentration was shown to be associated with hyperinsulinemia in diabetes. It also became clear that DHEA increased insulin secretion in old-aged db/db mice. DHEA increases not only insulin sensitivity due to the effects in the liver and muscle, but also insulin secretion. As an effect of DHEA on T-cell mediated hepatitis induced by concanavalin A (ConA), DHEA reduced hepatic injury by inhibiting several inflammatory mediators and apoptosis. As an effect of DHEA on carcinogenesis, DHEA would be a potential chemopreventative agent against colon cancer because it decreases the number of azoxymethane (AOM) induced aberrant crypt foci, which is a possible precursor to adenoma and cancer in a murine model.Thus, since DHEA has many beneficial effects experimentally, we should consider administration of DHEA in the future, and common mechanisms among these actions of DHEA should be elucidated in further studies.


Cationic pathway of pH regulation in larvae of Anopheles gambiae.
Anopheles gambiae larvae (Diptera: Culicidae) live in freshwater with low Na(+) concentrations yet they use Na(+) for alkalinization of the alimentary canal, for electrophoretic amino acid uptake and for nerve function. The metabolic pathway by which larvae accomplish these functions has anionic and cationic components that interact and allow the larva to conserve Na(+) while excreting H(+) and HCO(3)(-). The anionic pathway consists of a metabolic CO(2) diffusion process, carbonic anhydrase and Cl(-)/HCO(3)(-) exchangers; it provides weak HCO(3)(-) and weaker CO(3)(2-) anions to the lumen. The cationic pathway consists of H(+) V-ATPases and Na(+)/H(+) antiporters (NHAs), Na(+)/K(+) P-ATPases and Na(+)/H(+) exchangers (NHEs) along with several (Na(+) or K(+)):amino acid(+/-) symporters, a.k.a. nutrient amino acid transporters (NATs). This paper considers the cationic pathway, which provides the strong Na(+) or K(+) cations that alkalinize the lumen in anterior midgut then removes them and restores a lower pH in posterior midgut. A key member of the cationic pathway is a Na(+)/H(+) antiporter, which was cloned recently from Anopheles gambiae larvae, localized strategically in plasma membranes of the alimentary canal and named AgNHA1 based upon its phylogeny. A phylogenetic comparison of all cloned NHAs and NHEs revealed that AgNHA1 is the first metazoan NHA to be cloned and localized and that it is in the same clade as electrophoretic prokaryotic NHAs that are driven by the electrogenic H(+) F-ATPase. Like prokaryotic NHAs, AgNHA1 is thought to be electrophoretic and to be driven by the electrogenic H(+) V-ATPase. Both AgNHA1 and alkalophilic bacterial NHAs face highly alkaline environments; to alkalinize the larva mosquito midgut lumen, AgNHA1, like the bacterial NHAs, would have to move nH(+) inwardly and Na(+) outwardly. Perhaps the alkaline environment that led to the evolution of electrophoretic prokaryotic NHAs also led to the evolution of an electrophoretic AgNHA1 in mosquito larvae. In support of this hypothesis, antibodies to both AgNHA1 and H(+) V-ATPase label the same membranes in An. gambiae larvae. The localization of H(+) V-ATPase together with (Na(+) or K(+)):amino acid(+/-) symporter, AgNAT8, on the same apical membrane in posterior midgut cells constitutes the functional equivalent of an NHE that lowers the pH in the posterior midgut lumen. All NATs characterized to date are Na(+) or K(+) symporters so the deduction is likely to have wide application. The deduced colocalization of H(+) V-ATPase, AgNHA1 and AgNAT8, on this membrane forms a pathway for local cycling of H(+) and Na(+) in posterior midgut. The local H(+) cycle would prevent unchecked acidification of the lumen while the local Na(+) cycle would regulate pH and support Na(+):amino acid(+/-) symport. Meanwhile, a long-range Na(+) cycle first transfers Na(+) from the blood to gastric caeca and anterior midgut lumen where it initiates alkalinization and then returns Na(+) from the rectal lumen to the blood, where it prevents loss of Na(+) during H(+) and HCO(3)(-) excretion. The localization of H(+) V-ATPase and Na(+)/K(+)-ATPase in An. gambiae larvae parallels that reported for Aedes aegypti larvae. The deduced colocalization of the two ATPases along with NHA and NAT in the alimentary canal constitutes a cationic pathway for Na(+)-conserving midgut alkalinization and de-alkalinization which has never been reported before.


Amyloid-β assessed by florbetapir F 18 PET and 18-month cognitive decline: a multicenter study.
Florbetapir F 18 PET can image amyloid-β (Aβ) aggregates in the brains of living subjects. We prospectively evaluated the prognostic utility of detecting Aβ pathology using florbetapir PET in subjects at risk for progressive cognitive decline. A total of 151 subjects who previously participated in a multicenter florbetapir PET imaging study were recruited for longitudinal assessment. Subjects included 51 with recently diagnosed mild cognitive impairment (MCI), 69 cognitively normal controls (CN), and 31 with clinically diagnosed Alzheimer disease dementia (AD). PET images were visually scored as positive (Aβ+) or negative (Aβ-) for pathologic levels of β-amyloid aggregation, blind to diagnostic classification. Cerebral to cerebellar standardized uptake value ratios (SUVr) were determined from the baseline PET images. Subjects were followed for 18 months to evaluate changes in cognition and diagnostic status. Analysis of covariance and correlation analyses were conducted to evaluate the association between baseline PET amyloid status and subsequent cognitive decline. In both MCI and CN, baseline Aβ+ scans were associated with greater clinical worsening on the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog (p < 0.01) and Clinical Dementia Rating-sum of boxes (CDR-SB) (p < 0.02). In MCI Aβ+ scans were also associated with greater decline in memory, Digit Symbol Substitution (DSS), and Mini-Mental State Examination (MMSE) (p < 0.05). In MCI, higher baseline SUVr similarly correlated with greater subsequent decline on the ADAS-Cog (p < 0.01), CDR-SB (p < 0.03), a memory measure, DSS, and MMSE (p < 0.05). Aβ+ MCI tended to convert to AD dementia at a higher rate than Aβ- subjects (p < 0.10). Florbetapir PET may help identify individuals at increased risk for progressive cognitive decline.


Morphological and molecular characterization of Labronema montanum sp. n. (Dorylaimida, Dorylaimidae) from Spain.
A new species of the genus Labronema, collected in a natural mountain habitat of the southern Iberian Peninsula, in Spain, is studied, including its morphological and morphometric characterization, SEM observations, and D2-D3 28S-rRNA sequences. Labronema montanum sp. n. is distinguishable by its 1.56 to 2.08 mm long body, with lip region being offset by constriction and 19 to 24 µm broad, odontostyle 21 to 29 µm long, neck 417 to 551 µm long, pharyngeal expansion 205 to 272 µm long, the presence of three cardiac lobes at the pharyngo-intestinal junction, a long and tripartite uterus, longitudinal vulva (V = 57-60), a short and rounded caudal region (19-35 µm, c = 56-86, c = 0.5-0.8), spicules 65 to 76 µm long, and 20 to 25 nearly contiguous ventromedian supplements with hiatus. A new species of the genus Labronema, collected in a natural mountain habitat of the southern Iberian Peninsula, in Spain, is studied, including its morphological and morphometric characterization, SEM observations, and D2-D3 28S-rRNA sequences. Labronema montanum sp. n. is distinguishable by its 1.56 to 2.08 mm long body, with lip region being offset by constriction and 19 to 24 µm broad, odontostyle 21 to 29 µm long, neck 417 to 551 µm long, pharyngeal expansion 205 to 272 µm long, the presence of three cardiac lobes at the pharyngo-intestinal junction, a long and tripartite uterus, longitudinal vulva (V = 57-60), a short and rounded caudal region (19–35 µm, c = 56-86, c = 0.5-0.8), spicules 65 to 76 µm long, and 20 to 25 nearly contiguous ventromedian supplements with hiatus.


Neural substrates of impulsive decision making modulated by modafinil in alcohol-dependent patients.
Impulsive decision making is a hallmark of frequently occurring addiction disorders including alcohol dependence (AD). Therefore, ameliorating impulsive decision making is a promising target for the treatment of AD. Previous studies have shown that modafinil enhances cognitive control functions in various psychiatric disorders. However, the effects of modafinil on delay discounting and its underlying neural correlates have not been investigated as yet. The aim of the current study was to investigate the effects of modafinil on neural correlates of impulsive decision making in abstinent AD patients and healthy control (HC) subjects. A randomized, double-blind, placebo-controlled, within-subjects cross-over study using functional magnetic resonance imaging (fMRI) was conducted in 14 AD patients and 16 HC subjects. All subjects participated in two fMRI sessions in which they either received a single dose of placebo or 200 mg of modafinil 2 h before the session. During fMRI, subjects completed a delay-discounting task to measure impulsive decision making. Modafinil improved impulsive decision making in AD pateints, which was accompanied by enhanced recruitment of frontoparietal regions and reduced activation of the ventromedial prefrontal cortex. Moreover, modafinil-induced enhancement of functional connectivity between the superior frontal gyrus and ventral striatum was specifically associated with improvement in impulsive decision making. These findings indicate that modafinil can improve impulsive decision making in AD patients through an enhanced coupling of prefrontal control regions and brain regions coding the subjective value of rewards. Therefore, the current study supports the implementation of modafinil in future clinical trials for AD.


Macrophage (Drp1) Dynamin-Related Protein 1 Accelerates Intimal Thickening After Vascular Injury.
Mitochondria consistently change their morphology in a process regulated by proteins, including Drp1 (dynamin-related protein 1), a protein promoting mitochondrial fission. Drp1 is involved in the mechanisms underlying various cardiovascular diseases, such as myocardial ischemia/reperfusion injury, heart failure, and pulmonary arterial hypertension. However, its role in macrophages, which promote various vascular diseases, is poorly understood. We therefore tested our hypothesis that macrophage Drp1 promotes vascular remodeling after injury. To explore the selective role of macrophage Drp1, we created macrophage-selective Drp1-deficient mice and performed femoral arterial wire injury. In these mice, intimal thickening and negative remodeling were attenuated at 4 weeks after injury when compared with control mice. Deletion of macrophage Drp1 also attenuated the macrophage accumulation and cell proliferation in the injured arteries. Gain- and loss-of-function experiments using cultured macrophages indicated that Drp1 induces the expression of molecules associated with inflammatory macrophages. Morphologically, mitochondrial fission was induced in inflammatory macrophages, whereas mitochondrial fusion was induced in less inflammatory/reparative macrophages. Pharmacological inhibition or knockdown of Drp1 decreased the mitochondrial reactive oxygen species and chemotactic activity in cultured macrophages. Co-culture experiments of macrophages with vascular smooth muscle cells indicated that deletion of macrophage Drp1 suppresses growth and migration of vascular smooth muscle cells induced by macrophage-derived soluble factors. Macrophage Drp1 accelerates intimal thickening after vascular injury by promoting macrophage-mediated inflammation. Macrophage Drp1 may be a potential therapeutic target of vascular diseases.


Prediction of (Non)Participation of Older People in Digital Health Research: Exergame Intervention Study.
The use of digital technologies is increasing in health care. However, studies evaluating digital health technologies can be characterized by selective nonparticipation of older people, although older people represent one of the main user groups of health care. We examined whether and how participation in an exergame intervention study was associated with age, gender, and heart failure (HF) symptom severity. A subset of data from the HF-Wii study was used. The data came from patients with HF in institutional settings in Germany, Italy, the Netherlands, and Sweden. Selective nonparticipation was examined as resulting from two processes: (non)recruitment and self-selection. Baseline information on age, gender, and New York Heart Association Functional Classification of 1632 patients with HF were the predictor variables. These patients were screened for HF-Wii study participation. Reasons for nonparticipation were evaluated. Of the 1632 screened patients, 71% did not participate. The nonrecruitment rate was 21%, and based on the eligible sample, the refusal rate was 61%. Higher age was associated with lower probability of participation; it increased both the probabilities of not being recruited and declining to participate. More severe symptoms increased the likelihood of nonrecruitment. Gender had no effect. The most common reasons for nonrecruitment and self-selection were related to physical limitations and lack of time, respectively. Results indicate that selective nonparticipation takes place in digital health research and that it is associated with age and symptom severity. Gender effects cannot be proven. Such systematic selection can lead to biased research results that inappropriately inform research, policy, and practice. ClinicalTrial.gov NCT01785121, https://clinicaltrials.gov/ct2/show/NCT01785121.


Progenitor cells from the adult mouse brain acquire a neuronal phenotype in response to beta-amyloid.
Neurospheres from adult mouse subventricular zone (SVZ) were grown in suspension cultures for 12-15 days. Neurospheres consisted mainly of neural precursor cells (NPCs) immunoreactive for nestin and also contained nestin-negative precursors. We used these neurospheres to determine the effects of synthetic beta-amyloid fragments (both betaAP(1-42) and betaAP(25-35)) on NPC proliferation, differentiation and survival. We show that neurospheres exposed to 25 microM betaAP(25-35) or betaAP(1-42) for 24 h (a toxic condition for mature neurons) did not undergo apoptosis. Instead, betaAP(25-35) orientated nestin-negative precursors towards nestin-positive NPCs and turned nestin-positive NPCs into neuroblasts. Intracerebroventricular infusion of full-length betaAP(1-42) increased the population of PSA-NCAM-positive cells in the SVZ, without affecting proliferation. We conclude that betaAP influences the fate of progenitor cells, driving their differentiation towards a neuronal lineage.


Nuclear cardiology, Part II: Scintigraphic evaluation of cardiac function.
Different methods are currently available to assess cardiac function, especially left ventricular ejection fraction, using either planar or tomographic imaging, first-pass or equilibrium techniques, and blood-pool or myocardial perfusion agents. This is the second article of a four-part series on nuclear cardiology. In this article the authors review the most widely used radiopharmaceuticals and methodologies.


Using white blood cell counts to predict metabolic syndrome in the elderly: A combined cross-sectional and longitudinal study.
Metabolic syndrome (MetS) has an important implication from a preventive medicine perspective as early recognition and intervention will reduce associated mortality and morbidity. To better identify patients at risk for developing MetS and cardiovascular disease, we conduct a combined cross-sectional and longitudinal study to shed light on the elevated white blood cell (WBC) level in elderly. A total of 10,463 subjects were eligible for analysis. In the first stage of study, subjects were enrolled in the cross-sectional study to find out not only the correlation between WBC and MetS but also the optimal cut-off value of WBC with higher chances to have MetS. In the second stage of current study, subjects with MetS at baseline were excluded from the same study group, and performed a median 6.8-year longitudinal study to validate the optimal cut-off value of WBC predicting MetS. WBC is significantly higher in the group with than without MetS in both genders. All MetS components were associated with WBC in multivariate analysis except diastolic blood pressure and fasting plasma glucose. In the longitudinal study, WBC showed to be a good predictor of MetS in both genders. WBC is a good marker to identify the high risk subjects having MetS in the current status or in the future. Elderly with a higher WBC and without any underlying chronic diseases should receive more attention on the potential to develop MetS.


Bone densitometry as an indicator of percentage tibia ash in broiler chicks fed varying dietary calcium and phosphorus levels.
The relative sensitivity of tibia bone mineral content (BMC) and density (BMD), percentage ash (ash), and shear force as indicators for dietary Ca and P was compared in 3-wk-old broiler chicks. One hundred eight 7-d-old chicks were grouped by weight into 6 blocks of 3 cages each with 6 birds per cage. Three corn-soybean meal-based diets were randomly assigned to cages within each block. The diets were low P, medium P, and adequate P and were formulated to contain 4.0, 5.1, and 7.8 g of total P/kg feed, respectively; and 5.1, 6.7, and 10.0 g of Ca/kg feed, respectively. The chicks were fed the experimental diets for 14 d. On d 22, chicks were killed, and tibiae were removed from 3 birds/cage. Weight gain, feed intake, feed efficiency, BMC, BMD, shear force, and ash were determined. The BMC and BMD were determined using dual energy x-ray absorptiometry. Correlations among the various bone status variables and dietary Ca and P were determined. Growth performance criteria and ash increased linearly, and BMC and BMD increased linearly and quadratically as dietary concentrations of Ca and P increased. The correlation coefficient between dietary Ca and BMC, BMD, shear force, or ash was 0.89, 0.91, 0.50, or 0.89, respectively; and between dietary P and BMC, BMD, shear force, or ash was 0.88, 0.91, 0.48, or 0.89, respectively. The correlation coefficient between ash and BMC, BMD, or shear force was 0.92, 0.93, or 0.67, respectively. The correlation coefficients for linear regression between shear force and BMC or BMD was 0.56. The regression model for predicting percentage ash using BMD was as follows: percentage ash = 24 + (240 x BMD) with an r2 of 86%. It is concluded that in broiler chicks, tibia ash, BMC, and BMD may be more sensitive than shear force as indicators of dietary Ca and P concentrations and that BMD as measured by dual energy x-ray absorptiometry may be used to predict percentage of tibia ash.


Direct brainstem recording of auditory evoked potentials during vestibular schwannoma resection: nuclear BAEP recording. Technical note and preliminary results.
The usefulness of intraoperative monitoring in cerebellopontine angle surgery should be improved by obtaining faster and stronger brainstem auditory evoked potential (BAEP) responses. A new technique of direct recording at the brainstem has been developed, which is applicable to all tumor sizes. By placing a retractor with electrodes attached to its tip at the cerebellomedullary junction, the authors have recorded BAEP amplitudes that are 10 times greater than those recorded using the conventional technique. Only small sampling numbers (64-256 recordings) are required and are obtained in 5 to 15 seconds. The technique has been applied successfully in 34 patients who underwent vestibular schwannoma resections. It has also been tested in patients with intrameatal-extrameatal meningiomas and in those with vascular compressive disorders; there have been no false results. The advantages of this new technique are: 1) identification of BAEP components is easier and faster; 2) reliable BAEP responses are obtained in some cases in which conventional BAEP responses are lost or severely deformed; and 3) BAEP response deterioration and improvement are recognized earlier than would occur using the conventional technique. This last advantage provides the surgeon with a useful warning at a stage of surgery at which BAEP changes are still temporary and can be reversed. This method is different from other trials of intradural BAEP recordings in three respects: its use is not limited to particular tumor sizes; there is no interference with the surgical process; and, most important, the obtained responses correlate well with those of conventional BAEP responses, probably because the recording site is in the vicinity of the anterior cochlear nucleus. In conclusion, the chances of useful monitoring feedback with adequate adaptation of the microsurgical strategy are improved considerably.


Small molecule inhibitors of histone arginine methyltransferases: homology modeling, molecular docking, binding mode analysis, and biological evaluations.
The screening of the inhibition capabilities of dye-like small molecules from a focused library against both human PRMT1 and Aspergillus nidulans RmtA is reported as well as molecular modeling studies (homology modeling, molecular docking, and 3-D QSAR) of the catalytic domain of the PRMT1 fungal homologue RmtA. The good correlation between computational and biological results makes RmtA a reliable tool for screening arginine methyltransferase inhibitors. In addition, the binding mode analyses of tested derivatives reveal the crucial role of two regions, the pocket formed by Ile12, His13, Met16, and Thr49 and the SAM cisteinic binding site subsite. These regions should be taken into account in the design of novel PRMT inhibitors.


Contact-Force Catheters: Efficacy Versus Safety? Case Report of 2 Atrioesophageal Fistulae.
Contact-force (CF) catheters appear to be more effective compared to standard ablation catheters for complex radiofrequency ablation including atrial fibrillation (AF) ablation when optimal CF >10 g is achieved. Some have suggested that this technology could also improve procedural safety. We report 2 cases of atrioesophageal fistulae (AEF), a rare but catastrophic complication of AF ablation. These are to our knowledge the first cases of AEF described after using CF catheters.


QUANTITATION OF TRANSPLANTATION IMMUNITY. I. METHOD.
A technique for in vivo quantitation of transplantation immunity has been presented. Known numbers of H(3)-thymidine-labeled lymphoid cells were injected intravenously into isologous or homologous recipients. The total radioactivity in host spleens was counted at different time intervals. The rate of isotope disappearance from the spleen was exponential to 0.5 per cent of the dose or less. In isologous recipients, the calculated half-life of labeled cells was 82 hours; in homologous recipients it was 40 hours; and in presensitized homologous hosts it was 18 hours. The technique is a highly reproducible, precise, and sensitive measure of transplantation immunity.


Hormonal contraception and HIV: the methods have confused the message.
To examine different scenarios through which confounding by condom use may lead to inaccurate conclusions about the effect of hormonal contraception on HIV acquisition in women. Scenario analyses were conducted to evaluate the impact of coarse adjustment for condom use and condom misreporting on adjusted relative risk estimates for HIV acquisition in injectable hormonal contraception (IHC) users vs. nonusers. Analyses crudely accounting for condom use through a binary variable result in biased hormonal contraception-related risk estimates if condoms are used during follow-up periods in which any unprotected sex is reported and condom use differs by hormonal contraception use. We found that over-reporting of condom use is plausible in at least one recent study, as demonstrated by high pregnancy rates given, reported IHC and condom use. Over-reporting of condom use also biases estimates, typically leading to underestimation of IHC-related risk if over-reporting is the same among IHC and non-hormonal contraception users, and overestimation of IHC-related risk if condom misreporting is differential by IHC use. The impact of misreported condom use is most pronounced in study populations with high condom uptake. Discrepant findings in hormonal contraception-HIV-related research may result from inadequate measurement or adjustment for confounding by condom use. Future studies should precisely account for condom use in statistical analyses. Studies should aim to quantify the degree of condom use misreporting, by comparing reported condom use to pregnancy, HIV or other sexually transmitted infection rates, and if possible, testing stored genital swabs for prostate-specific antigen or Y chromosome.


A hematopoietic contribution to microhemorrhage formation during antiviral CD8 T cell-initiated blood-brain barrier disruption.
The extent to which susceptibility to brain hemorrhage is derived from blood-derived factors or stromal tissue remains largely unknown. We have developed an inducible model of CD8 T cell-initiated blood-brain barrier (BBB) disruption using a variation of the Theiler's murine encephalomyelitis virus (TMEV) model of multiple sclerosis. This peptide-induced fatal syndrome (PIFS) model results in severe central nervous system (CNS) vascular permeability and death in the C57BL/6 mouse strain, but not in the 129 SvIm mouse strain, despite the two strains' having indistinguishable CD8 T-cell responses. Therefore, we hypothesize that hematopoietic factors contribute to susceptibility to brain hemorrhage, CNS vascular permeability and death following induction of PIFS. PIFS was induced by intravenous injection of VP2121-130 peptide at 7 days post-TMEV infection. We then investigated brain inflammation, astrocyte activation, vascular permeability, functional deficit and microhemorrhage formation using T2*-weighted magnetic resonance imaging (MRI) in C57BL/6 and 129 SvIm mice. To investigate the contribution of hematopoietic cells in this model, hemorrhage-resistant 129 SvIm mice were reconstituted with C57BL/6 or autologous 129 SvIm bone marrow. Gadolinium-enhanced, T1-weighted MRI was used to visualize the extent of CNS vascular permeability after bone marrow transfer. C57BL/6 and 129 SvIm mice had similar inflammation in the CNS during acute infection. After administration of VP2121-130 peptide, however, C57BL/6 mice had increased astrocyte activation, CNS vascular permeability, microhemorrhage formation and functional deficits compared to 129 SvIm mice. The 129 SvIm mice reconstituted with C57BL/6 but not autologous bone marrow had increased microhemorrhage formation as measured by T2*-weighted MRI, exhibited a profound increase in CNS vascular permeability as measured by three-dimensional volumetric analysis of gadolinium-enhanced, T1-weighted MRI, and became moribund in this model system. C57BL/6 mice are highly susceptible to microhemorrhage formation, severe CNS vascular permeability and morbidity compared to the 129 SvIm mouse. This susceptibility is transferable with the bone marrow compartment, demonstrating that hematopoietic factors are responsible for the onset of brain microhemorrhage and vascular permeability in immune-mediated fatal BBB disruption.


[Relationships between Myers-Briggs Type Indicator (MBTI) psychological type and marital satisfaction, divorce proneness, positive affect, and conflict regulation in clinic couples].
The purpose of the study was to investigate the relationships between the Myers-Briggs Type Indicator (MBTI) psychological type and marital satisfaction, divorce proneness, positive affect, and conflict regulation in couple visiting a clinic. Couples (n=62) who visited "M" couple clinic participated in the study. Data were collected from March to June 2009 using the Marital Satisfaction Scale, Marital Status Inventory, Positive Affect Inventory, and Conflict Regulation Inventory. The couples showed no significant differences in marital satisfaction, positive affect, and conflict regulation according to similarities between spouses in MBTI types. However, they showed significant differences in divorce proneness of husband according to a similarity in the Sensing/Intuition indicator. They also showed significant differences in divorce proneness, positive affect, and conflict regulation between the couples for ISTJ (Introversion, Sensing, Thinking, Judging) or ESTJ (Extraversion, Sensing, Thinking, Judging) types compared to other couples. When nurses counsel couples, they should understand that differences in psychological type between spouses affects their marital relationship. In addition, nurses should educate couples on the characteristics of each type according to the couple's types and help them to understand each other, especially for couples where one spouse is the ISTJ/ESTJ type. These interventions will improve marital satisfaction and prevent the divorce in these couples.


The Impact on Work Patterns of Implementing the Save Sight Keratoconus Registry in the Hospital Setting.
The adoption of clinical registries has the potential to improve outcomes, while reducing the costs of health care. We sought to evaluate the changes in workflow that occurred with implementation of the Save Sight Keratoconus Registry (SSKR) in corneal clinics. A prospective time-motion study and a clinician survey were conducted. The timing of clinic consultations was recorded before and after implementation of the SSKR. The activities were assigned into 3 main categories: 1) direct patient care (eg, talking to, examining), 2) indirect patient care (record keeping), and 3) indirect patient care (reading). Overall, there was no change in average time spent per patient with or without the SSKR; 12.3 (5.3 SD) versus 12.1 (5.3 SD) minutes, respectively, P = 0.84. There was no change in time spent providing direct care with or without the SSKR; 5.4 (2.8 SD) versus 5.9 (2.8 SD) minutes, respectively, P = 0.51. Within direct patient care, there was no impact with or without the SSKR on the time spent examining (1.9 [1.0 SD] vs. 1.9 [1.4 SD] minutes, respectively, P = 0.58) or talking to patients (3.5 [2.3 SD] vs. 4.1 [2.3 SD] minutes, respectively, P = 0.21). Indirect care time was unchanged overall for record keeping (3.2 [2.2 SD] vs. 4.6 [2.9 SD], respectively, P = 0.16) and reading tasks (3.1 [1.8 SD] vs. 2.0 [1.3 SD], respectively, P = 0.09). The SSKR was implemented into clinical practice without affecting the total consultation time, time spent directly interacting with patients, or use of patient records. Our findings support that registries requiring data entry could be widely adopted into routine clinical practice.


Risk of Guillain-Barré syndrome after seasonal influenza vaccination and influenza health-care encounters: a self-controlled study.
The possible risk of Guillain-Barré syndrome from influenza vaccines remains a potential obstacle to achieving high vaccination coverage. However, influenza infection might also be associated with Guillain-Barré syndrome. We aimed to assess the risk of Guillain-Barré syndrome after seasonal influenza vaccination and after influenza-coded health-care encounters. We used the self-controlled risk interval design and linked universal health-care system databases from Ontario, Canada, with data obtained between 1993 and 2011. We used physician billing claims for influenza vaccination and influenza-coded health-care encounters to ascertain exposures. Using fixed-effects conditional Poisson regression, we estimated the relative incidence of hospitalisation for primary-coded Guillain-Barré syndrome during the risk interval compared with the control interval. We identified 2831 incident admissions for Guillain-Barré syndrome; 330 received an influenza vaccine and 109 had an influenza-coded health-care encounter within 42 weeks before hospitalisation. The risk of Guillain-Barré syndrome within 6 weeks of vaccination was 52% higher than in the control interval of 9-42 weeks (relative incidence 1·52; 95% CI 1·17-1·99), with the greatest risk during weeks 2-4 after vaccination. The risk of Guillain-Barré syndrome within 6 weeks of an influenza-coded health-care encounter was greater than for vaccination (15·81; 10·28-24·32). The attributable risks were 1·03 Guillain-Barré syndrome admissions per million vaccinations, compared with 17·2 Guillain-Barré syndrome admissions per million influenza-coded health-care encounters. The relative and attributable risks of Guillain-Barré syndrome after seasonal influenza vaccination are lower than those after influenza illness. Patients considering immunisation should be fully informed of the risks of Guillain-Barré syndrome from both influenza vaccines and influenza illness. Canadian Institutes of Health Research.


Air- and bone-conduction brainstem auditory evoked potentials and flash visual evoked potentials in cats.
To document normal values for air- and bone-conducted brainstem auditory evoked potentials (BAEP) and for flash visual evoked potentials (VEP) in cats. 10 mixed-breed cats (5 males) with normal physical, neurologic, otoscopic, and funduscopic examination results. BAEP in response to air- and bone-conducted click stimuli and VEP in response to flash stimuli were recorded to document species normative data. Mean and SD values were calculated for amplitudes and latencies of 4 peaks in the BAEP in response to air- and bone-conducted stimuli, and for latencies to 5 peaks and the 4 associated peak-to-peak amplitudes in the VEP. BAEP peak latencies increased and peak amplitudes decreased with decreasing stimulus intensity. Latencies were shorter for bone-conducted stimuli owing to the shorter transit time to the cochlea through bone, compared with air, but there were no differences for interpeak latencies. The BAEP and VEP recordings were similar to those reported for cats in other reports and were similar to those seen in other species. Normative data will permit performance of noninvasive electrodiagnostic evaluation of feline auditory and visual systems.


Prevention of familial cardiovascular disease by screening for family history and lipids in youths.
We analyzed medical family history information from 51,053 families of high school students in Utah and Texas and cholesterol measurements from 853 youths and 1618 adults in Utah families with cardiovascular disease (CVD) to assess the utility of different approaches to risk-factor evaluation for youths. The major question addressed was in which youths should blood cholesterol be tested? Applying National Cholesterol Education Program recommendations suggested that 36% in Utah and 38% in Texas be tested. Heterozygous familial hypercholesterolemia (hFH) is the best documented and most serious cholesterol disorder readily diagnosed in youths. In Utah families ascertained for CVD in adults, blood cholesterol levels among youths were significantly bimodal with hFH present in 84% of youths in the upper cholesterol mode. Blood cholesterol levels in adults from the same families were less bimodal with hFH present in 38% of adults in the upper mode. More overlap existed between high and normal modes in adults than in youths. Data from this study suggest that family histories and cholesterol concentrations obtained from high school students may meet the needs of cholesterol screening, education, and follow-up in a controlled and cost-effective setting.


Highly efficient endosomal labeling of progenitor and stem cells with large magnetic particles allows magnetic resonance imaging of single cells.
Tracking transplanted stem cells using magnetic resonance imaging (MRI) could offer biologic insight into homing and engraftment. Ultrasmall dextran-coated iron oxide particles have previously been developed for uptake into cells to allow MRI tracking. We describe a new application of much larger, micron-scale, iron oxide magnetic particles with enhanced MR susceptibility, which enables detection of single cells at resolutions that can be achieved in vivo. In addition, these larger particles possess a fluorophore for histologic confirmation of cell distribution. We demonstrate highly efficient, nontoxic, endosomal uptake of these particles into hematopoietic CD34+ cells and mesenchymal stem cells documented by confocal and electron microscopy. Labeled cells retain biologic activity with preservation of colony-forming ability and differentiation capacity. MRI studies could detect labeled CD34+ cells and mesenchymal stem cells (MSCs) at single cell resolution. This appears to be a promising tool for serial noninvasive monitoring of in vivo cell homing and localization using MRI.


The Role of Reactive Oxygen Species in the Pathogenesis of Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease: A Mini Review.
Neurodegenerative diseases affect not only the life quality of aging populations, but also their life spans. All forms of neurodegenerative diseases have a massive impact on the elderly. The major threat of these brain diseases includes progressive loss of memory, Alzheimer's disease (AD), impairments in the movement, Parkinson's disease (PD), and the inability to walk, talk, and think, Huntington's disease (HD). Oxidative stress and mitochondrial dysfunction are highlighted as a central feature of brain degenerative diseases. Oxidative stress, a condition that occurs due to imbalance in oxidant and antioxidant status, has been known to play a vital role in the pathophysiology of neurodegenerative diseases including AD, PD, and HD. A large number of studies have utilized oxidative stress biomarkers to investigate the severity of these neurodegenerative diseases and medications are available, but these only treat the symptoms. In traditional medicine, a large number of medicinal plants have been used to treat the symptoms of these neurodegenerative diseases. Extensive studies scientifically validated the beneficial effect of natural products against neurodegenerative diseases using suitable animal models. This short review focuses the role of oxidative stress in the pathogenesis of AD, PD, and HD and the protective efficacy of natural products against these diseases.


Gastrin inhibits secretin-induced ductal secretion by interaction with specific receptors on rat cholangiocytes.
We assessed the effect of gastrin on ductal secretion in normal and bile duct-ligated (BDL) rats. The effect of gastrin on ductal secretion was examined in the presence of proglumide, a specific antagonist for gastrin receptor (GR). We isolated pure cholangiocytes from normal and BDL rats and assessed gastrin effects on secretin receptor (SR) gene expression and intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels. We examined the presence of GR mRNA in cholangiocytes by reverse transcription polymerase chain reaction (RT-PCR). In normal or BDL rats, gastrin produced no changes in spontaneous bile secretion. Simultaneous infusion of gastrin inhibited secretin-induced choleresis and bicarbonate output in BDL rats. In the presence of proglumide gastrin did not inhibit secretin-induced choleresis in BDL rats. Gastrin decreased in cholangiocytes from BDL rats 1) SR gene expression and 2) secretin-induced cAMP levels. With the use of RT-PCR, GR mRNA was detected in cholangiocytes. Similar to what is shown for secretin and somatostatin, we propose that the opposing effects of secretin and gastrin on cholangiocyte secretory activity regulate ductal secretion in rats.


Drug-drug interactions between oral antiepileptics and oral anticancer drugs: implications to clinicians.
Existing research has suggested that there can be potential drug-drug interaction (DDI) between antiepileptic drugs (AED) and anticancer drugs (ACD). However, information on the prevalence of patients on concurrent oral AED and oral ACD is limited. A retrospective study was conducted at the National Cancer Centre Singapore. Prevalence was calculated by identifying prescriptions with both oral AED and oral ACD from the outpatient prescription database over three years. Prevalence and physicians' prescribing patterns were evaluated. Co-prescription was defined as medications that were prescribed by the same physician on the same day. Potentially interacting combinations were further detected using an existing database, OncoRx (www.onco-informatics.com). 42,810 prescriptions that contained at least one oral ACD were identified from the database. The number and prevalence of prescriptions that had a combination of oral ACD and AED were 274 and 0.64%, respectively, with the majority (82.8%) of the AED-oral ACD pairs being co-prescribed. Per patient, the average number of exposure days to the AED-oral ACD pair was 19.5 days annually. Fifty-one (18.6%) prescriptions were identified as containing potentially interacting AED-oral ACD pairs. There is a relatively low prevalence of AED-oral ACD combined exposure in the population we sampled; however, the combined exposure is long enough to produce clinically important DDI effects.


Update on intensive motor training in spinocerebellar ataxia: time to move a step forward?
Some evidence suggests that high-intensity motor training slows down the severity of spinocerebellar ataxia. However, whether all patients might benefit from these activities, and by which activity, and the underlying mechanisms remain unclear. We provide an update on the effect and limitations of different training programmes in patients with spinocerebellar ataxias. Overall, data converge of the finding that intensive training is still based either on conventional rehabilitation protocols or whole-body controlled videogames ("exergames"). Notwithstanding the limitations, short-term improvement is observed, which tends to be lost once the training is stopped. Exergames and virtual reality can ameliorate balance, coordination, and walking abilities, whereas the efficacy of adapted physical activity, gym, and postural exercises depends on the disease duration and severity. In conclusion, although a disease-modifying effect has not been demonstrated, constant, individually tailored, high-intensity motor training might be effective in patients with degenerative ataxia, even in those with severe disease. These approaches may enhance the remaining cerebellar circuitries or plastically induce compensatory networks. Further research is required to identify predictors of training success, such as the type and severity of ataxia and the level of residual functioning.


Gap junctions in the rabbit sinoatrial node.
In comparison to the cellular basis of pacemaking, the electrical interactions mediating synchronization and conduction in the sinoatrial node are poorly understood. Therefore, we have taken a combined immunohistochemical and electrophysiological approach to characterize gap junctions in the nodal area. We report that the pacemaker myocytes in the center of the rabbit sinoatrial node express the gap junction proteins connexin (Cx)40 and Cx46. In the periphery of the node, strands of pacemaker myocytes expressing Cx43 intermingle with strands expressing Cx40 and Cx46. Biophysical properties of gap junctions in isolated pairs of pacemaker myocytes were recorded under dual voltage clamp with the use of the perforated-patch method. Macroscopic junctional conductance ranged between 0.6 and 25 nS with a mean value of 7.5 nS. The junctional conductance did not show a pronounced sensitivity to the transjunctional potential difference. Single-channel recordings from pairs of pacemaker myocytes revealed populations of single-channel conductances at 133, 202, and 241 pS. With these single-channel conductances, the observed average macroscopic junctional conductance, 7.5 nS, would require only 30-60 open gap junction channels.


Past Pain Experience and Experimentally induced Pain Perception.
Many intercurrent factors may be involved in the modulation of the pain message and its expression, such as the previous experience of pain built along the life. In this study, we aimed to determine whether susceptibility to experimentally induced pain is differentially influenced by the individual previous painful experience in subjects with schizophrenia (SC) major depression (MD), and controls (C). The SC (30), MD (32) and C (30) groups participated in experimental pain tests (application of pressure and induction of ischemia) after a semi-structured interview to make an inventory of the previous painful experiences, and the evaluation of anxiety either with autonomic (heart rate, blood pressure) or psychological (Hospital Anxiety Depression scale HAD) measures, and catastrophism. The reported pain intensities, severities, duration, of the previous pain events, and the number of previous painful events were equivalent in the three groups, except for the number of painful events experimented before the last six months which was lower in the MD group. Experimental pain sensitivity was influenced by the diagnosis, the HAD scores or the number and intensities of previous lived painful events. The lack of a past experience of pain was comparable for the different groups, suggesting that psychiatric disorders do not affect the experience of pain associated with daily life or past events. For each subject, the reported previous experience of pain influences the present feeling of pain.


Current and experimental antibody-based therapeutics: insights, breakthroughs, setbacks and future directions.
The premise of targeted therapy was born from an intimate understanding of the unique biological pathways and endpoints which are implicated in the development of different disease states and conditions. In addition, the identification of the most appropriate drugs to use for targeted drug therapy has aided in growing interest of the pharmaceutical industry to allocate more resources to monoclonal antibody (mAb) therapeutics. This being the case, it is important to understand antibody based therapeutics, some of the currently Food and Drug Administration (FDA)-approved mAbs in different disease states, as well as the future direction of mAb therapies. In this article, we will provide a critical overview, and discuss a selection of antibody based therapeutics, including their bioengineered structural and functional elements. Furthermore, a segment of the currently FDA-approved mAb antibody therapies, those in research, or in investigation for disease states and conditions ranging from autoimmune disease, inflammatory response, immunosuppression, cancer, including antibody-drug conjugates, immunotherapy, and exciting prospects for antiplatelet and antithrombotic monoclonal antibody therapeutics will be reviewed. Finally, we will discuss our predictions and aspirations for the future directions of mAb-based therapeutic interventions.


A randomized controlled trial of acupuncture for osteoarthritis of the knee: effects of patient-provider communication.
There is conflicting evidence on the efficacy of traditional Chinese acupuncture (TCA), and the role of placebo effects elicited by acupuncturists' behavior has not been elucidated. We conducted a 3-month randomized clinical trial in patients with knee osteoarthritis to compare the efficacy of TCA with sham acupuncture and to examine the effects of acupuncturists' communication styles. Acupuncturists were trained to interact in 1 of 2 communication styles: high or neutral expectations. Patients were randomized to 1 of 3 style groups, waiting list, high, or neutral, and nested within style, TCA or sham acupuncture twice a week over 6 weeks. Sham acupuncture was performed in nonmeridian points with shallow needles and minimal stimulation. Primary outcome measures were Joint-Specific Multidimensional Assessment of Pain (J-MAP), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and satisfaction scores. Patients (n = 455) received treatment (TCA or sham) and 72 controls were included. No statistically significant differences were observed between TCA or sham acupuncture, but both groups had significant reductions in J-MAP (-1.1, -1.0, and -0.1, respectively; P < 0.001) and WOMAC pain (-13.7, -14, and -1.7, respectively; P < 0.001) compared with the waiting group. Statistically significant differences were observed in J-MAP pain reduction and satisfaction, favoring the high expectations group. In the TCA and sham groups, 52% and 43%, respectively, thought they had received TCA (κ = 0.05), suggesting successful blinding. TCA was not superior to sham acupuncture. However, acupuncturists' styles had significant effects on pain reduction and satisfaction, suggesting that the analgesic benefits of acupuncture can be partially mediated through placebo effects related to the acupuncturist's behavior.