[Clinical significance of adhesive properties of leukocytes and blood serum in patients with multiple sclerosis].
Adhesive blood properties have been studied in 100 MS patients with the help of the new method developed on the basis of the leucocyte adherence inhibition (LAI) test, which was based on the calculation of the ratio of adhesive cells to non-adhesive ones. The value obtained was called the Index of Spontaneous Adhesion (ISA), while the respective indicator reflecting the effect of adhesion strengthening under the influence of autoserum, being expressed by 30% and more, was named the Effect of the Adhesion Strengthening (ES-a). Blood samples of 54 donors and 31 patients with other neurological diseases were used as controls. Statistically significant increase of ISA values of MS patients was detected as compared to the group of donors. The highest indices of ISA and ES-a were found in the primarily progressive course and at the stage of MS exacerbation in the remitting course. Correlation between levels of adhesion and clinical features as well as parameters of clinical and humoral immunity are described. A role of membrane and soluble forms of adhesion molecules in initiation and progression of the immunologic process in MS is discussed.


Effect of Number of Tests on the Mechanical Characteristics of Agave sisalana Yarns for Composites Structures: Statistical Approach.
A designer of sustainable biocomposite structures and natural ropes needs to have a high confidence interval (95% CI) for mechanical characteristics data of performance materials, yet qualities for plant-based fibers are very diverse. A comprehensive study of the elements that enhance the performance of biocomposites or sustainable ropes created from vegetable fibers is necessary. The current study included five groups with varying numbers (N) of tests of 20, 40, 60, 80, and 100 on the mechanical characteristics at room temperatures. The purpose of this study was to determine how changing N affects the mechanical properties of sisal yarn. These properties include its strength, Young's modulus, and deformation at rupture. A significance testing program including more than 100 tests was performed. Owing to the heterogeneity of the plant yarn, each group received more than 20 samples at a gauge length (GL) of 100 mm. The tensile strength characteristics of sisal yarns produced a wide range of findings, as is common for natural fibers, necessitating a statistical analysis. Its dispersion was explored and measured using the statistical methods. The Weibull distribution with two parameters and a prediction model with a 95% confidence level for maximum likelihood (ML) and least squares (LS) were used to investigate and quantify its dispersion.


Prenatal diagnosis of anencephaly: spectrum of sonographic appearances and distinction from the amniotic band syndrome.
To document the characteristic sonographic abnormalities of anencephaly and to identify potentially confusing sonographic features, we reviewed 20 cases of anencephaly. All of these cases were diagnosed prenatally with sonography after 14 menstrual weeks in patients who were seen at our institution between 1984 and 1988. In all cases, the correct diagnosis was made on the prenatal sonograms and was confirmed pathologically. The sonographic diagnosis was primarily based on the absence of brain and calvarium superior to the orbits on coronal views of the fetal head. This typical appearance was altered by the presence of echogenic tissue superior to the orbits in nine (45%) of 20 cases. Pathologically, the tissue corresponded to angiomatous stroma (area cerebrovasculosa) and appeared quite sizable on sonograms in four fetuses (20%). It may appear solid or mixed solid and cystic. In one fetus, it appeared brainlike. Despite this appearance, the sonologist should not be dissuaded from the diagnosis of classic anencephaly. Hydramnios occurred in seven (35%) of 20 patients, and oligohydramnios occurred in none of the patients. Anencephaly may be distinguished from the cranial defects associated with the amniotic band syndrome (amputation defects that occur as the sequelae of amniotic disruption) on the basis of the symmetry of the cranial defects (100% of anencephalic fetuses in this series) and the absence of limb, body wall, and spinal abnormalities that typically accompany the amniotic band syndrome. Although there may be minor variations in the sonographic appearance of the cranial defect of anencephalic fetuses (i.e., much or little angiomatous stroma), we conclude that this anomaly can be accurately detected and diagnosed on fetal sonograms obtained after 14 weeks menstrual age and distinguished from the amniotic band syndrome.


Nanocellulose-Based Conductive Membranes for Free-Standing Supercapacitors: A Review.
There is currently strong demand for the development of advanced energy storage devices with inexpensive, flexibility, lightweight, and eco-friendly materials. Cellulose is considered as a suitable material that has the potential to meet the requirements of the advanced energy storage devices. Specifically, nanocellulose has been shown to be an environmentally friendly material that has low density and high specific strength, Young's modulus, and surface-to-volume ratio compared to synthetic materials. Furthermore, it can be isolated from a variety of plants through several simple and rapid methods. Cellulose-based conductive composite membranes can be assembled into supercapacitors to achieve free-standing, lightweight, and flexible energy storage devices. Therefore, they have attracted extensive research interest for the development of small-size wearable devices, implantable sensors, and smart skin. Various conductive materials can be loaded onto nanocellulose substrates to endow or enhance the electrochemical performance of supercapacitors by taking advantage of the high loading capacity of nanocellulose membranes for brittle conductive materials. Several factors can impact the electronic performance of a nanocellulose-based supercapacitor, such as the methods of loading conductive materials and the types of conductive materials, as will be discussed in this review.


A 3D-Printable Polymer-Metal Soft-Magnetic Functional Composite-Development and Characterization.
In this work, a 3D printed polymer-metal soft-magnetic composite was developed and characterized for its material, structural, and functional properties. The material comprises acrylonitrile butadiene styrene (ABS) as the polymer matrix, with up to 40 vol. % stainless steel micropowder as the filler. The composites were rheologically analyzed and 3D printed into tensile and flexural test specimens using a commercial desktop 3D printer. Mechanical characterization revealed a linearly decreasing trend of the ultimate tensile strength (UTS) and a sharp decrease in Young's modulus with increasing filler content. Four-point bending analysis showed a decrease of up to 70% in the flexural strength of the composite and up to a two-factor increase in the secant modulus of elasticity. Magnetic hysteresis characterization revealed retentivities of up to 15.6 mT and coercive forces of up to 4.31 kA/m at an applied magnetic field of 485 kA/m. The composite shows promise as a material for the additive manufacturing of passive magnetic sensors and/or actuators.


hCTLA4-gene modified human bone marrow-derived mesenchymal stem cells as allogeneic seed cells in bone tissue engineering.
Immune rejection of heterogeneic seed cells, even of low antigenicity human bone marrow derived mesenchymal stem cells (hBMMSCs), remains an obstacle for bone tissue engineering. It is still a question how to transfer the gene of human cytotoxic T lymphocyte-associated antigen 4-Ig (CTLA4-Ig), a well-known ligand for CD80/CD86, to hBMMSCs to prolong survival time while not interfering with their osteogenesis in vivo. Our data, for the first time, clearly demonstrate that CTLA4-Ig gene modified hBMMSCs could normally differentiate to osteoblasts in vitro, significantly inhibit immune response in the model of mixed lymphocyte culture, and survive until bone tissue formed in vivo. Thus, CTLA4Ig gene-modified hBMMSCs might be promising seed cells for bone tissue engineering.


CVAS: A Rapid Dysphagia Evaluation Tool.
A simple-to-administer test for dysphagia was developed at our institution. The test can be administered rapidly and easily in the Emergency Department (ED) by a nurse or other qualified medical person, making formal consultation with a speech pathologist for rapid determination of dysphagia unnecessary. Our study shows that the use of the test does not increase the incidence of aspiration pneumonia.


Effect of continuous subcutaneous insulin infusion vs multiple daily insulin injection with glargine as basal insulin: an open parallel long-term study.
Aim of this 1-yr open parallel study was to evaluate the efficacy of two regimens of intensive insulin treatment: continuous s.c. insulin infusion (CSII) and multiple daily insulin injection (MDI) treatment with lispro plus glargine in 48 Type 1 diabetic patients that had been treated with MDI (regular or lispro insulin before each meal plus NPH) for at least 1 yr. Twenty-four patients treated with CSII, receiving lispro at multiple basal infusion rates plus boluses at meal (CSII group), were compared to 24 patients, matched for age, duration of diabetes and metabolic control, treated with MDI with lispro at each meal combined with glargine (glargine group). In the CSII group, compared to traditional MDI treatment, there was a decrease in HbA1c (9.0 +/- 1.3% during traditional MDI vs 8.0 +/- 1.0% during CSII, p<0.001), severe hypoglycaemic episodes (0.42 vs 0.17 per patient/yr, p<0.05), insulin requirement (48 +/- 11.7 vs 35.9 +/- 8.5 U/day, p<0.001). In the glargine group, compared to MDI traditional treatment, there was a decrease in HbA1c (8.6 +/- 1.1 vs 7.9 +/- 1.2%, p<0.001) and severe hypoglycaemic episodes (0.46 vs 0.21 per patient/yr, p<0.05). No significant difference between the CSII group and the glargine group was present in the degree of improvement in HbA1c and severe hypoglycaemic episodes. However, in the CSII group there was a significantly greater reduction in mean amplitude of glycaemic excursions (MAGE) and insulin requirement than in the glargine group. In conclusion, despite a similar improvement in metabolic control, CSII improves blood glucose variability when compared to MDI with glargine as basal insulin.


Blood pressure response to a community-based program and long-term cardiovascular outcome.
The significance in terms of the cardiovascular outcome of different patterns of blood pressure (BP) response to community-based activities has not been previously studied. The aim of our study was to evaluate the relationship between changes of BP observed during a community-based program and long-term rate of cardiovascular disease (CVD) events. A program focused on the prevention of CVDs was implemented in a small city in Argentina over a 6-year period (1997-2003). The program was evaluated using a cohort of 1,526 randomly selected individuals. The population's mean systolic BP (SBP) decreased approximately 5mm Hg, but BP changes were heterogeneous. Eight years after the intervention had stopped, 1,124 individuals of the cohort were surveyed to evaluate incident CVD events. The sample was divided into 3 SBP change categories during the intervention: decrease (< -5mm Hg), no change (-5 to 5mm Hg) and increase (> 5mm Hg). Cox models were used to estimate the hazard ratio (HR) of CVD events for each category adjusted for age, sex, and baseline BP. At the end of the intervention, individuals who had increased their SBP showed an adjusted HR for CVD that was double those whose SBP levels decreased or did not change. An inverse relationship between baseline SBP and ΔSBP was observed: individuals with an increase in BP during the intervention had lower SBP at the beginning of the study. BP increase during the community-based program was an independent predictor of CVD events.


Cytology of non-Hodgkin's malignant lymphomas involving the stomach.
An attempt was made to diagnose cytologically non-Hodgkin's malignant lymphomas (ML) of the stomach on gastric smears in terms of the Kiel classification. This classification represents a more advanced approach for the identification of ML with regard to the cell type specificity, with some functional connotations as compared with previous classifications. The endoscopic brushing cell film studies, when compared with histology of endoscopic biopsies and/or surgical specimens, indicated a high accuracy of cell type identification. Sampling may represent problems in relation to the type of gross lesion. Specific cell types could be recognized in 20 of 25 cases of gastric involvement of ML. Six of nine cases of lymphoplasmacytoid ML revealed diagnostic cells, such as lymphoplasmacytoid cells, plasma cells, lymphocytes, and occasional immunoblasts. Six of seven cases of centrocytic ML had a large number of small cells with indented nuclei, and seven of eight centroblastic-centrocytic ML yielded a mixture of large centroblasts and small centrocytes. In addition to these 24 low-grade ML, one case of unclassifiable high-grade ML was diagnosed. Differential diagnostic problems within ML subtypes and with benign lesions, such as pseudolymphoma of the stomach, as well as malignant tumors and especially diffuse type gastric carcinoma, are taken into consideration.


Prevalence and factors associated with smoking among tobacco growers in southern Brazil.
identify the prevalence and factors associated with smoking in tobacco growers. descriptive, cross-sectional research. Data collection occurred in 2012 through household survey and interviews, including application of a structured instrument and scale Fargeström. there were 100 growers included, average age of 46,9 ± 10,8 years; 90(90%) married; 72(72%) white, average family composition 3,7±1,1 people; median number of children 3(1-3), and the average study time 6±2,5. The prevalence of smoking among tobacco growers was 17%, which had less education (p=0.010) and fewer people in the household (p=0.049). the prevalence of smoking among tobacco growers was higher than the national average, but the nicotine dependence was low, which can facilitate the smoking cessation process. Highlights the need to implement a program to control smoking among tobacco growers.


Effects of the potential lithium-mimetic, ebselen, on impulsivity and emotional processing.
Lithium remains the most effective treatment for bipolar disorder and also has important effects to lower suicidal behaviour, a property that may be linked to its ability to diminish impulsive, aggressive behaviour. The antioxidant drug, ebselen, has been proposed as a possible lithium-mimetic based on its ability in animals to inhibit inositol monophosphatase (IMPase), an action which it shares with lithium. The aim of the study was to determine whether treatment with ebselen altered emotional processing and diminished measures of risk-taking behaviour. We studied 20 healthy participants who were tested on two occasions receiving either ebselen (3600 mg over 24 h) or identical placebo in a double-blind, randomized, cross-over design. Three hours after the final dose of ebselen/placebo, participants completed the Cambridge Gambling Task (CGT) and a task that required the detection of emotional facial expressions (facial emotion recognition task (FERT)). On the CGT, relative to placebo, ebselen reduced delay aversion while on the FERT, it increased the recognition of positive vs negative facial expressions. The study suggests that at the dosage used, ebselen can decrease impulsivity and produce a positive bias in emotional processing. These findings have implications for the possible use of ebselen in the disorders characterized by impulsive behaviour and dysphoric mood.


A Chinese expert consensus on thoracic endovascular aortic repair of type B aortic dissection with a single-branched stent graft for revascularization of the left subclavian artery.
Thoracic endovascular repair (TEVAR) is currently the recommended and most widely used treatment for type B aortic dissection. A major challenge is revascularization of the left subclavian artery in order to extend the landing zone to zone 2 (Ishimaru classification). Various strategies have been used for revascularization, including branched stent graft, fenestrated stent graft, the chimney technique, the parallel technique, and bypass surgery. Single-branched stent graft is one of the most promising strategies, and several products have recently been reported as potential candidates for use with this approach. The Castor single-branched stent graft is the only off-the-shelf product available; this product has been developed through collaboration between Chinese corporations and clinicians. In this Perspective article, clinical experience and data obtained from TEVAR with the Castor single-branched stent graft are summarized by experienced Chinese experts.


A 3-year oral health dose-response study of sodium monofluorophosphate dentifrices with and without zinc citrate: anti-caries results.
A 3-yr clinical trial has been conducted on 3000 12-yr-old children in Lanarkshire, Scotland, with the aim of investigating the effects on oral health of toothpastes containing both sodium monofluorophosphate and zinc citrate, the former being present at fluoride levels of 1000, 1500, and 2500 ppm F. No significant difference in caries increments was found between the group of children using toothpastes incorporating zinc citrate and their counterparts using zinc-free pastes. However, a significant anti-caries dose-response was demonstrated over the SMFP range used. This dose-response was evident for boys and girls and also for the various types of teeth and tooth surfaces.


A Pilot Study of Urinary Exosomes in Alzheimer's Disease.
Exosomes are nano-sized extracellular vesicles secreted by most cell types and abundantly present in body fluids, including blood, saliva, urine, cerebrospinal fluid, and breast milk. Exosomes can spread toxic amyloid-beta (Aβ) and hyperphosphorylated tau between cells, contributing to neuronal loss in Alzheimer's disease (AD). To explore changes in the morphology, number, and pathological protein levels of urinary exosomes in AD patients compared with age-matched healthy subjects. In this study, enzyme-linked immunosorbent assay was used to detect the levels of Aβ1-42 and P-S396-tau (normalized by CD63) in urinary exosomes of AD patients and matched healthy subjects. We used transmission electron microscopy and nanoparticle tracking analysis to observe the exosomes. We found that the levels of Aβ1-42 and P-S396-tau in the urinary exosomes of AD patients were higher than those of matched healthy controls. Exosomes taken from AD patients were more numerous. The differences in levels of Aβ1-42 and P-S396-tau and the quantity of urinary exosomes between AD patients and healthy controls may provide a basis for early diagnosis of AD.


Effects of the Synthetic Neurosteroid: 3β-Methoxypregnenolone (MAP4343) on Behavioral and Physiological Alterations Provoked by Chronic Psychosocial Stress in Tree Shrews.
Most currently available active antidepressant drugs are selective serotonin/noradrenaline reuptake inhibitors. However, as their clinical efficacy is not immediate, long-term administration is often accompanied by substantial side effects, and numerous patients remain non- or partial responders. We have recently found that the synthetic neurosteroid derivative 3β-methoxypregnenolone, which binds to the microtubule-associated protein-2, can provide a novel therapeutic approach in experimental model of depressive disorders in rats. To further validate the antidepressant-like efficacy of 3β-methoxypregnenolone, we investigated effects of a longer treatment (4-week oral administration; 50mg/kg/d) in a nonrodent species, the tree shrew, exposed to psychosocial stress that elicits close-to-human alterations observed in patients with depressive disorders. During the experimental period, physiological parameters were registered, including core body temperature and electroencephalogram, while animals were videotaped to analyze their avoidance behavior. Morning urine samples were collected for measurements of cortisol and noradrenaline levels. We found that treatment with 3β-methoxypregnenolone abolished stress-triggered avoidance behavior and prevented hormone hypersecretion, hypothermia, and sleep disturbances, further suggesting its antidepressant-like efficacy. Comparative treatment with fluoxetine also prevented some of the physiological alterations, while the hypersecretion of cortisol and sleep disturbances were not or partially restored by fluoxetine, suggesting a better efficacy of 3β-methoxypregnenolone. Alpha-tubulin isoforms were measured in hippocampi: we found that 3β-methoxypregnenolone reversed the specific decrease in acetylation of α-tubulin induced by psychosocial stress, while it did not modify the psychosocial stress-elicited reduction of tyrosinated α-tubulin. Taken together, these data strongly suggest a potent antidepressant-like effect of 3β-methoxypregnenolone on translational parameters.


Health promotion. Applying COPC to incontinence.
This article explores the application of the community oriented primary care (COPC) model to primary care. The authors describe how the health needs of the population were assessed and met.


Impact of reperfusion strategy on outcomes in very elderly patients with acute myocardial infarction.
The best reperfusion strategy for patients of advanced age (either primary-angioplasty or thrombolysis) after a ST-segment elevation myocardial infarction (STEMI) remains controversial. Aim of the study was to test differences in morbidity and mortality regarding the reperfusion strategy adopted. From 2007-2012, 182 patients ≥85 year-old with STEMI were admitted to the coronary care unit of two tertiary centers. Data regarding baseline characteristics, clinical presentation, reperfusion strategy adopted and outcomes were retrospectively reviewed. The relation between the type of reperfusion therapy and outcomes was evaluated. Median age was 86.8±6.9 years (range 85-96). Most patients (54.4%) were woman. Anterior wall STEMI was the main electrocardiographic location (45.1%). A conservative treatment was seen in 64 patients (35.2%), thrombolysis in 41 (22.5%) and primary-angioplasty in the remaining 77 patients (42.3%). A total of 56 patients died (30.8%). The mortality rate in the thrombolysis group (21.9%) was similar than that found in the primary-angioplasty group (15.6%) (P=0.45). No difference was found in a subgroup analysis of high risk patients (i.e. anterior wall STEMI, Killip class ≥2). Morbidity rates were also similar between both therapeutic groups (thrombolisys 58.5% vs. primary-angioplasty 46.7%, P=0.22). Morbidity and mortality rates were much higher among those patients treated conservatively than that found in patients who received any of the reperfusion strategies (54.6% vs. 17.8%, P<0.0001 and 79.7% vs. 50.8%, P<0.0001, respectively). Mortality and morbidity among very elderly patients with STEMI are extremely high. No differences were found between primary-angioplasty and fibrinolysis with regard to outcomes. A conservative treatment was associated with a worse prognosis.


Granular cell tumor of the scrotum in a child with Noonan syndrome.
Granular cell tumor is a rare neoplasm thought to be of neural origin, composed of cells with distinctive granular cytoplasm. Granular cell tumors most often arise on the tongue, but can occur at any body site, and therefore initial presentation to dermatologists is common. We report a granular cell tumor of the scrotum in a child with Noonan syndrome, known to have a mutation in the PTPN11 gene. No previous reports of granular cell tumor of the scrotum in a child are found. The tumor is usually benign; however, it can have a high local recurrence rate (variable between 2% and 50% dependent on whether initial excision is complete and on the occurrence of an infiltrative growth pattern) and therefore long-term follow-up is necessary. This case highlights the occurrence of granular cell tumor, a diagnosis not to be missed by the dermatologist. In addition, we postulate the possible role of PTPN11 mutations in the development of granular cell tumor.


Evaluation of nano-magnetic fluid on malignant glioma cells.
The temperature variation rule of nano-magnetic fluid in the specific magnetic field and the effect on the treatment of malignant glioma were examined. The temperature variation of nano-magnetic fluid in the specific magnetic field was investigated by heating in vitro, and cell morphology was observed through optical microscopy and electron microscopy. MTT detection also was used to detect the effect of Fe3O4 nanometer magnetic fluid hyperthermia (MFH) on the proliferation of human U251 glioma cell line. The Fe3O4 nano MFH experiment was used to detect the inhibition rate of the tumor volume in nude mice with tumors. The results of the experiment showed that the heating ability of magnetic fluid was positively correlated with its concentration at the same intensity of the magnetic field. The results also indicated the prominent inhibitory effect of nanometer MFH on the proliferation of glioma cells, which was a dose-dependent relationship with nanometer magnetic fluid concentration. The hyperthermia experiment of nude mice with tumors displayed a significant inhibiting effect of Fe3O4 nanometer magnetic fluid in glioma volume. These results explain that iron (II, III) oxide (Fe3O4) nanometer MFH can inhibit the proliferation of U251 glioma cells, and has an obvious inhibitory effect on glioma volume, which plays a certain role in the treatment of brain glioma.


3-Dimensional nano-fibre scaffold for ex vivo expansion of cord blood haematopoietic stem cells.
Cord blood (CB) haematopoietic stem cell (HSC) is an alternative source of HSC transplantation. The limited cell number greatly restricts their clinic-scale therapeutic applications. The objective of this study was an ex vivo expansion of CB HSCs in a new three-dimensional polycaprolactone nano-scaffold coated with fibronectin (FN). First, we isolated CB CD34+ cells and cultured 10 days in presence of growth factors. The evaluation was performed by qRT-PCR, flow cytometry and clonogenicity. 3D PCL nano-scaffold coated with FN produced significantly higher total nucleated cells and CD34+ cells (p < .05) and also had significantly higher homing and self-renewality genes than 2D cell culture and before expansion (p < .05). The expression of CXCR-4, VLA-4, VLA-5 and LFA-1, and also HOXB-4, HOXA-9, BMI-1 and hTERT genes was higher in 3D than 2D. The CD13, CD14, CD33, CD34 and CD45 markers were significantly higher and CD2, CD3 and CD19 markers were significantly lower in 3D scaffold than 2D cell culture (p < .05). The type and number of colonies in 2D culture were lower than 3D culture medium (p > .05). 3D PCL nano-scaffold coated with FN could better keep specifications homing and self renewality of CB HSCs after expansion.


[Diagnosis and treatment of biatrial myxomas of the heart].
Of the multiple myxomas of the heart (MH) the bilateral myxomas were revealed in 57.1%. Of 4 patients before the operation the correct diagnosis was established only in one. Meticulous data on clinical signs, diagnosis and surgical treatment peculiarities of patients with bilateral MH were adduced. Morphological peculiarities of the tumor were analyzed. Special attention was paid to the necessity of clinical and surgical guard toward revelation of undiagnosed tumors, the choice of optimal approaches to the heart cavities while performing radical operation. Basing on results of histological studying of operational specimen it was established that MH is originated from transformed vessels of interatrial septum.


Analyzing Excitation-Energy Transfer Based on the Time-Dependent Density Functional Theory in Real Time.
Excitation-energy transfer is a key step in processes such as photosynthesis that convert light into other forms of energy. Time-dependent density functional theory (DFT) in real time is ideal for the first-principles simulation of such processes due to its computational efficiency. We here demonstrate how real-time DFT can be used for analyzing excitation-energy transfer from first-principles. We discuss several measures of energy transfer that are based solely on the time-dependent density, are well founded in the DFT framework, allow for intuitive understanding and visualization, and reproduce important limiting cases of an analytical model. We demonstrate their usefulness in calculations for model systems, both with static nuclei and in the context of DFT-based Ehrenfest dynamics.


Delayed periprosthetic seroma in a male Poland syndrome patient: A case report.
Custom-made implant is an accepted treatment option for treatment of chest deformity in Poland syndrome. Unlike the raised concerns and awareness for the long-term consequences of breast implants, the long-term complications of customized implants for special purposes like Poland syndrome has not been reported in the literature. A 44-year-old male with Poland syndrome presented to our institution complaining of a large bulge and fluctuation on the right chest wall. This occurred after 14 years from the initial implant surgery for correction of chest wall deformity. Upon failure of resolution by multiple aspirations, workup was carried out under suspicion of implant associated malignancy. Total Capsulectomy and implant removal was done. Histology revealed chronic inflammation with fibrosis. Implant-associated malignancy was not found. He is being followed up with no signs of recurrence. For rare cases of implant insertion such as Poland syndrome, awareness of delayed complications and workups based on suspicion of implant-associated malignancy is needed. Surgeon awareness and patient education is required.


Structural properties determining low K+ affinity of the selectivity filter in the TWIK1 K+ channel.
Canonical K+ channels are tetrameric and highly K+-selective, whereas two-pore-domain K+ (K2P) channels form dimers, but with a similar pore architecture. A two-pore-domain potassium channel TWIK1 (KCNK1 or K2P1) allows permeation of Na+ and other monovalent ions, resulting mainly from the presence of Thr-118 in the P1 domain. However, the mechanistic basis for this reduced selectivity is unclear. Using ion-exchange-induced difference IR spectroscopy, we analyzed WT TWIK1 and T118I (highly K+-selective) and L228F (substitution in the P2 domain) TWIK1 variants and found that in the presence of K+ ions, WT and both variants exhibit an amide-I band at 1680 cm-1 This band corresponds to interactions of the backbone carbonyls in the selectivity filter with K+, a feature very similar to that of the canonical K+ channel KcsA. Computational analysis indicated that the relatively high frequency for the amide-I band is well explained by impairment of hydrogen bond formation with water molecules. Moreover, concentration-dependent spectral changes indicated that the K+ affinity of the WT selectivity filter was much lower than those of the variants. Furthermore, only the variants displayed a higher frequency shift of the 1680-cm-1 band upon changes from K+ to Rb+ or Cs+ conditions. High-speed atomic force microscopy disclosed that TWIK1's surface morphology largely does not change in K+ and Na+ solutions. Our results reveal the local conformational changes of the TWIK1 selectivity filter and suggest that the amide-I bands may be useful "molecular fingerprints" for assessing the properties of other K+ channels.


Heart rate variability in children with obstructive sleep apnea.
Adults with obstructive sleep apnea syndrome (OSAS) display substantial heart rate changes associated with obstructive events, and recent reports suggest similar heart rate changes in children with OSAS. These rate changes could assist screening of young patients for OSAS. Six-hour polysomnographic recordings were obtained from seven children with OSAS (mean age: 4.5 years; apnea index: 19.5 +/- 5.1) and from seven primary snorers without OSAS who served as controls (mean age: 4.7; apnea index: 0). Scatterplots of each cardiac R-R interval against the preceding interval (Poincaré plots) were used to assess beat-to-beat cardiac variability at different heart rates. Beat-to-beat variation at slow rates was significantly increased in children with OSAS relative to controls, while variation at fast and intermediate heart rates was significantly reduced in these children. We conclude that OSAS alters beat-to-beat variation in characteristic fashions in children, that the variability changes occur at all heart rates but are most significant at slow heart rates, and that these heart rate patterns could assist in screening of suspected cases of OSAS.


Clinical and laboratory evaluation of the effect of cephradine on patients with ear, nose and throat infections.
27 patients with ear, nose and throat infections have been treated with cephradine orally. Ten patients received 250 mg and 17 patients 500 mg every 6 h during 10 days. 26 patients were cured. One patient failed to respond to treatment but reinfection could not be excluded. Determination of plasma concentrations showed that cephradine was well absorbed. The drug showed no severe adverse effects. Cephradine is a good replacement in patients with allergy to penicillins. It is also suitable when broad-spectrum therapy is needed.


The selective inhibition of nitric oxide production in the avian macrophage cell line HD11.
The production of reactive nitrogen, nitric oxide (NO), has previously been demonstrated to be a major mechanism by which the innate immune system defends against microbial invasion. The induction of many antimicrobial mechanisms is regulated by numerous components during the transduction of the signal from the cell surface to the cell nucleus where response genes are upregulated. Toll-like cell surface receptor activation often leads to sequential modulation of protein tyrosine kinases (PTK), mitogen activated protein kinases (MAPK), degradation of I kappa B (IkappaB) regulatory molecules which, in turn, release the nuclear factor-kappa B (NF-kappaB) family proteins for translocation into the nucleus and subsequent gene transcription. The purpose of this study was to investigate components of the upstream signal transduction pathway induced by bacterial and viral-like stimulation of NO for antimicrobial defense by the transformed chicken macrophage cell line, HD11. We quantified the production of nitrite by chicken macrophages after exposure to selective pharmacological inhibitors of specific signal transduction components prior to stimulation by polyinosinic polycytidylic acid (poly I:C), formalin-fixed Enterococcus gallinarum (EG) or formalin-fixed Klebsiella pneumoniae (KP). We found that NO production induced by dsRNA or bacteria was reduced in a dose dependent manner by specific inhibitors of PTK, p38 MAPK, IkappaB, and NF-kappaB. Inhibition efficacy varied dependent on stimulation by bacterial or viral-like ligands. In general, NO production induced by bacterial stimulation was most effectively reduced by inhibition of p38 MAPK and least effectively reduced by inhibition of IkappaB. NF-kappaB and IkappaB inhibition affected NO production induced by dsRNA more than that induced by bacterial stimulation.


Cerebral venous thrombosis: a diagnostic and treatment update.
Cerebral venous thrombosis (CVT) is still a significant diagnostic and therapeutic challenge, due to its high variability of clinical manifestations and its lack of a clear therapeutic consensus. A search of the medical literature was made through PubMed using the conjoined terms of CVT and epidemiology (428 results), pathophysiology (504 results), aetiology (2714 results), diagnosis (2802 results), treatment (2173 results) and outcome (648 results). Original and review publications deemed to be useful for this review were selected. Classical and historical works on CVT were also included. The present paper reviews the fundamental aspects of the epidemiology, pathophysiology and aetiology of CVT. There is a comparison of the most common initial clinical manifestations along with a description of the most important neuroradiological studies needed to establish a diagnosis, all based on multiple published series. Moreover, in order to serve as an important tool in both clinical practice and continuing research, there is also an analysis of recent evidence on treatment and prognosis. CVT represents approximately 0.5% of all stroke cases worldwide. Headache, focal deficits and seizures are the most frequent initial clinical manifestations, representing 89%, 50%, and 35% of appearances, respectively. Magnetic resonance imaging (MRI) in combination with magnetic resonance venography has proved to have the highest sensitivity and specificity in establishing a diagnosis. An equal alternative to MRI is computed tomography venography due to similar diagnostic results. Pharmacological treatment with heparin is widely accepted today. Recurrence and mortality rates of CVT are 2.8 per 100 cases and 10%, respectively, despite of anticoagulation treatment.


Death preparation among the ethnic Chinese well-elderly in Singapore: an exploratory study.
Death preparation is an important process as it can help the elderly to achieve ego integrity at the last stage of their lives. This study aims to explore how the ethnic Chinese elderly in Singapore approach issues related to death and dying, and to identify factors that influence death preparation. Descriptive surveys with semi-structured interview questions were used. Eight ethnic Chinese older adults, recruited through purposive sampling, were interviewed. Additionally, 4 adults with a deceased parent were also interviewed to validate and complement the earlier identified themes. Results show that the current generation of Chinese elderly in Singapore do not seem to be averse to talking about issues related to death, and those who find it unnecessary to prepare for death seem to be associated with, among other factors, lesser financial assets and a strong belief in filial piety. With increasing affluence and dissolving traditions, it will be beneficial to draw the attention of the current generation of mature adults on early preparation at the final stage of the lifespan.


[A case of cervical intramedullary neurenteric cyst].
A case of cervical intramedullary neurenteric cyst was reported. A 12-year-old girl was admitted with severe pain over the nape and shoulders, and weakness of all extremities. At the age of 4 years, she had suffered from the nape pain and paraparesis which, however, cleared later spontaneously. Neurological examination revealed evidences of presumptive cervical intramedullary lesion, and myelography showed a complete block at the third cervical level accordingly. Surgical exploration through C3-C5 laminectomy disclosed an intramedullary cyst situated within the right half of the cord. The cyst was removed except for its upper and lower apices. Excellent clinical results followed the operation. The cyst was composed of collagen fibers with an inner epithelial lining, which consisted of single or pseudostratified layer of columnar, cuboidal or squamous cells. Cells were ciliated at some parts. The base of the epithelial cells rested upon the basement membrane. Nuclei were positioned near the base of the cells, to present a row. The cytoplasm in the majority of cells contained abundant mucin positive to PAS staining. Pathological diagnosis of neurenteric cyst was made on the basis of these histological findings. Usually intraspinal neurenteric cyst is located in the subarachnoid space and ventrally to the spinal cord. Neurenteric cyst appears histologically similar to ependymal cyst, though, in the latter the epithelial cells seldom contain mucin, and only in scanty amount, if any present. Embryogenesis during the third week of embryonic life was discussed in relation to the development of neurenteric cyst.


Particles of all sizes provoke inflammatory responses in vivo.
The aim of this study was to investigate whether all sizes of wear particles are capable of provoking inflammatory responses and whether there are different responses among different particle sizes. The knees of 40 female Balb/c mice were injected with polystyrene particles of three different diameters, 0.5 microm, 2.0 microm, and 75 microm, using a 0.1% vol/vol concentration. Seven days after particle injection, assessment of the synovial microcirculation using intravital microscopy, and histologic examination, were done. All the mice injected with polystyrene particles had enhanced leukocyte-endothelial cell interactions and histologic scores regardless of particle size when compared with control animals injected with sterile phosphate buffered saline. Polystyrene particles 0.5 microm in size provoked stronger membrane thickening and increased leukocyte-endothelial cell interactions than 75-microm particles. The fraction of rolling leukocytes was enhanced in the 2.0-microm particle group when compared with the 75-microm particle group. These results indicate that polystyrene particles of all sizes (0.5 microm, 2.0 microm, and 75 microm) are capable of inducing an inflammatory response. Small particles (0.5 microm, 2.0 microm) seem to provoke a stronger inflammatory response than larger particles (75 microm) in conditions with equal particle volume.


Importance of γ-secretase in the regulation of liver X receptor and cellular lipid metabolism.
Presenilins (PS) are the catalytic components of γ-secretase complexes that mediate intramembrane proteolysis. Mutations in the PS genes are a major cause of familial early-onset Alzheimer disease and affect the cleavage of the amyloid precursor protein, thereby altering the production of the amyloid β-peptide. However, multiple additional protein substrates have been identified, suggesting pleiotropic functions of γ-secretase. Here, we demonstrate that inhibition of γ-secretase causes dysregulation of cellular lipid homeostasis, including up-regulation of liver X receptors, and complex changes in the cellular lipid composition. Genetic and pharmacological inhibition of γsecretase leads to strong accumulation of cytoplasmic lipid droplets, associated with increased levels of acylglycerols, but lowered cholesteryl esters. Furthermore, accumulation of lipid droplets was augmented by increasing levels of amyloid precursor protein C-terminal fragments, indicating a critical involvement of this γ-secretase substrate. Together, these data provide a mechanism that functionally connects γ-secretase activity to cellular lipid metabolism. These effects were also observed in human astrocytic cells, indicating an important function of γ-secretase in cells critical for lipid homeostasis in the brain.


[The epidemiology of heat disorders].
Recently, the number of deaths from heat stroke has been increasing. On the whole, such deaths are more prevalent among males in the age groups of 0 to 4, 15 to 19, 50 to 54, and 80. Such deaths are rare among young females, but its number gradually increases with aging, and peaks in the age group of 80 to 84. Recently, the proportion of people aged 65 or above has significantly increased among those who die from heat stroke. Heat disorders are frequently induced by outdoor sports, such as baseball, mountain-climbing, and long-distance running competitions, although it has reportedly occurred also during indoor sports as well.


Leucine-rich repeat kinase 2 (LRRK2): a key player in the pathogenesis of Parkinson's disease.
Parkinson's disease (PD) is the most common neurodegenerative movement disorder, with a prevalence of more than 1% after the age of 65 years. Mutations in the gene encoding leucine-rich repeat kinase-2 (LRRK2) have recently been linked to autosomal dominant, late-onset PD that is clinically indistinguishable from typical, idiopathic disease. LRRK2 is a multidomain protein containing several protein interaction motifs as well as dual enzymatic domains of GTPase and protein kinase activities. Disease-associated mutations are found throughout the multidomain structure of the protein. LRRK2, however, is unique among the PD-causing genes, because a missense mutation, G2019S, is a frequent determinant of not only familial but also sporadic PD. Thus, LRRK2 has emerged as a promising therapeutic target for combating PD. In this Mini-Review, we look at the current state of knowledge regarding the domain structure, amino acid substitutions, and potential functional roles of LRRK2.


Immune responses to small nuclear ribonucleoproteins: antigen-dependent distinct B cell epitope spreading patterns in mice immunized with recombinant polypeptides of small nuclear ribonucleoproteins.
Complex patterns of autoantibody reactivities with the small nuclear ribonucleoproteins (snRNPs) are observed in systemic lupus erythematosus. To investigate the role of individual snRNP components in the initiation and diversification of anti-snRNP Ab responses, we immunized A/J mice with recombinant Smith D (SmD), Smith B (SmB), and A ribonucleoprotein (A-RNP) with alum as adjuvant. Sera at different time points after initial immunizations were analyzed by Western blot and immunoprecipitation assays. In SmD-immunized mice, specific Abs to A-RNP and SmB were generated by 2 mo postimmunization, in addition to the detection of cross-reactive Abs between the immunogen and other snRNPs. Whereas Abs reactive with the immunogen decreased by 5 mo, Abs capable of immunoprecipitating A-RNP and SmB increased. In SmB-immunized mice, specific Abs to A-RNP were readily detectable, in addition to cross-reactive Abs. In contrast, A-RNP-immunized mice had only cross-reactive Abs to SmB without detectable Abs to SmD. However, in these mice, specific Abs to the 70-kDa protein were generated. Abs, which precipitated the native snRNP particle, were generated in all three groups of the immunized mice. Our results show that different initiating Ags from the same multiprotein antigenic complex induce distinct patterns of epitope spreading to proteins within that complex. These data have significant implications for the mechanisms of autoantibody diversification in systemic lupus erythematosus.


Thallium-rich rust scales in drinkable water distribution systems: A case study from northern Tuscany, Italy.
Following the detection of a severe thallium contamination of the drinkable water from the public distribution system of Valdicastello Carducci-Pietrasanta (northern Tuscany, Italy), and the identification of the source of contamination in the Molini di Sant'Anna spring (average Tl content≈15μgL-1), the replacement of the contaminated water with a virtually Tl-free one (Tl<0.10μgL-1) caused an increase in Tl concentration in the drinkable water. This suggested that the pipeline interior had become a secondary source of Tl contamination, promoting its mineralogical and geochemical study. Rust scales samples taken from several pipeline segments, as well as leaching products obtained from these samples, were investigated through scanning electron microscopy, X-ray fluorescence chemical analyses, inductively coupled plasma - mass spectrometry, X-ray diffraction, and X-ray absorption spectroscopy. Thallium-rich rust scales (up to 5.3wt% Tl) have been found only in pipeline samples taken downstream the water treatment plant, whereas the sample taken upstream contains much less Tl (~90μgg-1). The Tl-rich nature of such scales is related to the occurrence of nano- and micro-spherules of Tl2O3 and less abundant nanocrystalline μm-sized encrustations of TlCl. Leaching experiments on Tl-rich rust scales indicate that a fraction of the available Tl is easily dissolved in tap water; X-ray absorption spectroscopy suggests that monovalent thallium occurs in water equilibrated with the rust scales, probably related to the dissolution of TlCl encrustations. Therefore, Tl dissolved as Tl+ only in the water from the Molini di Sant'Anna spring was partially removed through oxidative precipitation of Tl2O3 and precipitation of TlCl. This highlights the critical role played by the addition of chlorine-based oxidants in water treatment plants that could favour the deposition of Tl-rich coatings within the pipelines, giving rise to unexpected secondary sources of contamination.


Development of a UHPLC-MS/MS method for the quantitation of bioactive compounds in Phyllanthus species and its herbal formulations.
Phyllanthus species are extensively used in traditional medicines for the treatment of hepatic diseases due to their bioactive hypophyllanthin and phyllanthin. This work describes the development and validation of an ultra high performance liquid chromatography with tandem mass spectrometry method in polarity switching multiple reaction monitoring mode for the simultaneous detection and quantitation of 23 compounds using ultra-performance liquid chromatography coupled with electrospray-hybrid triple quadrupole-linear ion trap mass spectrometer. The validated parameters showed good linearity (R2 ≥ 0.996), limit of detection (0.05-1.62 ng/mL), limit of quantitation (0.15-4.95 ng/mL), precisions (intra-day: RSD ≤ 2.11%), (inter-day: RSD ≤ 2.91%), stability (RSD ≤ 2.56%) and overall recovery (98.22-104.48%; RSD ≤ 2.93%). The validated method was successfully applied in ethanolic extracts of P. amarus, P. niruri, P. emblica, P. fraternus, fractions of P. amarus and their herbal formulations for quantitation. The maximum content of hypophyllanthin (29.40 mg/g) and phyllanthin (56.60 mg/g) was detected in ethyl acetate fraction of P. amarus. The total content of 23 compounds was abundant in the ethanolic extract of P. emblica fruit. Principal component analysis was used to differentiate the selected Phyllanthus species and their herbal formulations. The results indicated that the present method could be used for quality control of Phyllanthus species and its herbal formulations.


Efficacy of Vedolizumab in a Nationwide Cohort of Elderly Inflammatory Bowel Disease Patients.
The elderly inflammatory bowel disease (IBD) population has historically been under-represented in clinical trials, and data on the efficacy of biologic medications in elderly IBD patients are generally lacking. Our study aims to evaluate the efficacy of vedolizumab (VDZ) among elderly IBD patients and compare it with younger IBD patients in a nationwide population-based cohort of IBD patients. We conducted a retrospective cohort study of patients within the US national Veterans Affairs Healthcare System (VAHS). Patients were stratified into 2 groups based on age at the time of starting VDZ (60 years of age and older or younger than 60 years of age) with outcomes compared between the 2 groups. The primary outcome was steroid-free remission during the 6- to 12-month period after starting VDZ therapy among those patients who were on steroids when VDZ was started. There were 568 patients treated with VDZ, of whom 56.7% had Crohn's disease and 43.3% had ulcerative colitis. Among them, 316 patients were on steroids when VDZ was started. The percentage of patients who were on VDZ and off steroids during the 6- to 12-month period after VDZ initiation was 46.8% and 40.1% for the younger and elderly groups, respectively (P = 0.2374). Rates of hospitalization for an IBD-related reason within 1 year of VDZ start among the whole cohort were nearly identical in the younger and elderly groups (11.2% vs 11.3%, P = 0.9737). Rates of surgery for an IBD-related reason within 1 year of VDZ start were also similar between the young and elderly (3.9% vs 3.9%, P = 0.9851). In a nationwide real-world retrospective cohort study of elderly IBD patients, we found that the efficacy of VDZ was similar among younger and older IBD patients and comparable with the published data in clinical trials.


Acute effects of ethanol on hippocampal long-term potentiation and long-term depression are mediated by different mechanisms.
To determine potential mechanisms contributing to ethanol-induced cognitive impairment, we examined acute effects of ethanol on hippocampal N-methyl-d-aspartate receptors and forms of synaptic plasticity thought to underlie memory processing. In the CA1 region of rat hippocampal slices, ethanol partially inhibited N-methyl-d-aspartate receptor-mediated synaptic responses at concentrations up to 180 mM. The block of synaptic N-methyl-d-aspartate receptors by 60mM ethanol occluded the effects of 10 microM ifenprodil, an agent that has relative selectivity for N-methyl-D-aspartate receptors expressing NR1 and NR2B subunits. Ethanol did not occlude the effects of a low concentration of 2-amino-5-phosphonovalerate, an antagonist with less N-methyl-d-aspartate receptor subtype selectivity. Recent studies indicate that ifenprodil and other NR2B-selective antagonists inhibit N-methyl-D-aspartate receptor-dependent long-term depression but not long-term potentiation. We found that ethanol reversibly inhibited long-term depression in a manner consistent with its effects on synaptic N-methyl-D-aspartate receptors. Ethanol also inhibited the induction of N-methyl-D-aspartate receptor-dependent long-term potentiation, but the actions on long-term potentiation were complex and largely irreversible over the time course of our experiments. Furthermore, ethanol inhibited a form of long-term potentiation induced by very high frequency stimulation that does not depend on N-methyl-D-aspartate receptor activation. The effects of ethanol on both forms of long-term potentiation, but not on long-term depression, were at least partially reversed by block of GABA type A receptors with picrotoxin. These results indicate that pharmacologically relevant concentrations of ethanol exert preferential effects on a subtype of synaptic N-methyl-D-aspartate receptors in the CA1 hippocampal region. Inhibition of synaptic N-methyl-D-aspartate receptors appears to contribute strongly to ethanol-mediated long-term depression inhibition, but effects on long-term potentiation are complex, involving, at least partially, changes in GABAergic transmission.


The Sugar Kinase That Is Necessary for the Catabolism of Rhamnose in Rhizobium leguminosarum Directly Interacts with the ABC Transporter Necessary for Rhamnose Transport.
Rhamnose catabolism in Rhizobium leguminosarum was found to be necessary for the ability of the organism to compete for nodule occupancy. Characterization of the locus necessary for the catabolism of rhamnose showed that the transport of rhamnose was dependent upon a carbohydrate uptake transporter 2 (CUT2) ABC transporter encoded by rhaSTPQ and on the presence of RhaK, a protein known to have sugar kinase activity. A linker-scanning mutagenesis analysis of rhaK showed that the kinase and transport activities of RhaK could be separated genetically. More specifically, two pentapeptide insertions defined by the alleles rhaK72 and rhaK73 were able to uncouple the transport and kinase activities of RhaK, such that the kinase activity was retained, but cells carrying these alleles did not have measurable rhamnose transport rates. These linker-scanning alleles were localized to the C terminus and N terminus of RhaK, respectively. Taken together, the data led to the hypothesis that RhaK might interact either directly or indirectly with the ABC transporter defined by rhaSTPQ. In this work, we show that both N- and C-terminal fragments of RhaK are capable of interacting with the N-terminal fragment of the ABC protein RhaT using a 2-hybrid system. Moreover, if RhaK fragments carrying either the rhaK72 or rhaK73 allele were used, this interaction was abolished. Phylogenetic and bioinformatic analysis of the RhaK fragments suggested that a conserved region in the N terminus of RhaK may represent a putative binding domain. Alanine-scanning mutagenesis of this region followed by 2-hybrid analysis revealed that a substitution of any of the conserved residues greatly affected the interaction between RhaT and RhaK fragments, suggesting that the sugar kinase RhaK and the ABC protein RhaT interact directly. ABC transporters involved in the transport of carbohydrates help define the overall physiological fitness of bacteria. The two largest groups of transporters are the carbohydrate uptake transporter classes 1 and 2 (CUT1 and CUT2, respectively). This work provides the first evidence that a kinase that is necessary for the catabolism of a sugar can directly interact with a domain from the ABC protein that is necessary for its transport.


Molecular cloning and transcriptional regulation of the Aspergillus nidulans xlnD gene encoding a beta-xylosidase.
The xlnD gene encoding the 85-kDa beta-xylosidase was cloned from Aspergillus nidulans. The deduced primary structure of the protein exhibits considerable similarity to the primary structures of the Aspergillus niger and Trichoderma reesei beta-xylosidases and some similarity to the primary structures of the class 3 beta-glucosidases. xlnD is regulated at the transcriptional level; it is induced by xylan and D-xylose and is repressed by D-glucose. Glucose repression is mediated by the product of the creA gene. Although several binding sites for the pH regulatory protein PacC were found in the upstream regulatory region, it was not clear from a Northern analysis whether PacC is involved in transcriptional regulation of xlnD.


Experimental demonstration of emittance compensation with velocity bunching.
In this Letter we report the first experiments aimed at the simultaneous demonstration of the emittance compensation process and velocity bunching in a high brightness electron source, the SPARC photoinjector in INFN-LNF. While a maximum compression ratio up to a factor 14 has been observed, in a particular case of interest a compression factor of 3, yielding a slice current of 120 A with less than 2 microm slice emittance, has been measured. This technique may be crucial in achieving high brightness beams in photoinjectors aiming at optimized performance of short wavelength single-pass free electron lasers or other advanced applications in laser-plasma accelerators.


[Surveillance of schistosomiasis in Hubei Province in 2014].
To analyze the surveillance results of schistosomiasis and understand the transmission situation in Hubei Province in 2014. According to the Scheme of Schistosomiasis Surveillance in Hubei Province (the 2009 edition), 207 endemic sites were selected, where the schistosome infections of residents and livestock, and the distribution of Oncomelania hupensis snails were investigated. In the 207 sites, there were 27 sites without positive results of the blood tests and 129 sites without positive results of the stool tests. The infection rates of residents and cattle were 0.17% and 0, respectively. The density of living snails was 0.339 3 snails/0.1m2, the rate of living snails was 10.12%, and the infection rate of snails was 0. The infection rate of residents in the inner embankment type was 0.22%, higher than the rates in the other types. In different age groups, the infection rate in the 50-59 years age group was higher than the rates in other age groups. The infection rates of residents in farmer and fisherman were higher than those in the other occupation groups. The infection rate of floating people was 0, and no acute schistosomiasis patients were found. The endemic situation of schistosomiasis has decreased obviously in Hubei Province, and the whole province has achieved the criteria for transmission control of schistosomiasis.


Skeletal muscle mass and body fat in relation to successful ageing of older adults: The multi-national MEDIS study.
The determinants that promote successful ageing still remain unknown. The aim of the present work was to evaluate the role of skeletal muscle mass and body fat percentage (BF%), in the level of successful ageing. during 2005-2011, 2663 older (aged 65-100 years) from 21 Mediterranean islands and the rural Mani region (Peloponnesus) of Greece were voluntarily enrolled in the study. Appendicular skeletal muscle mass (ASM), skeletal muscle mass index (SMI) and BF% were calculated using population formulas. Dietary habits, energy intake, expenditure and energy balance were derived throughout standard procedures. A successful ageing index ranging from 0 to 10 was used. The mean ASM mass was 24±6.0kg, the SMI was 0.84±0.21 and the BF% was 44%. Females had lower SMI and higher BF% in comparison with males, respectively [(SMI: 0.66±0.09 vs. 1.03±0.11; BF%: 51% vs. 34%, (p<0.001)]. High successful agers had better rates in ASM (p=0.01), SMI (p<0.001) and BF% (p<0.001), compared with the medium and low successful ones. Changes in SMI [b-coefficient (95% CI):2.14 (1.57 to 2.71)] were positively associated with successful ageing, while changes in BF% [b-coefficient (95% CI): -0.04 (-0.05 to -0.03)] were inversely associated with successful ageing. Results from sensitivity analysis showed that the effects of variations on body composition were consistent, less pronounced in the positive energy balance group and more pronounced among the oldest old. Body composition changes seem to be associated with lower quality of life in the older adults, as measured through successful ageing.


[Myocardial infarct following embolism in a newborn].
A case of myocardial infarction in a newborn, most probably consecutive to air embolism, is described. The acute episode occurred immediately after the removal of a venous umbilical catheter. The infant survived, without clinical evidence of cardiac impairment 14 months later. However, he developed signs of a spastic cerebral palsy.


Deciphering the Clinical Presentations in LMNA-Related Lipodystrophy: Report of 115 cases and a Systematic Review.
Lipodystrophy syndromes are a heterogeneous group of rare genetic or acquired disorders characterized by generalized or partial loss of adipose tissue. LMNA-related lipodystrophy syndromes are classified based on the severity and distribution of adipose tissue loss. We aimed to annotate all clinical and metabolic features of patients with lipodystrophy syndromes carrying pathogenic LMNA variants and assess potential genotype-phenotype relationships. We retrospectively reviewed and analyzed all our cases (n=115) and all published cases (n=379) curated from 94 studies in the literature. The study included 494 patients. The most common variants in our study, R482Q and R482W, were associated with similar metabolic characteristics and complications though those with the R482W variant were younger (33 (24) years vs 44 (25) years, p<0.001), had an earlier diabetes diagnosis, (27 (18) vs 40 (17) years, p<0.001) and had lower BMI levels (24 (5) kg/m2 vs 25 (4) kg/m2, p=0.037). Dyslipidemia was the earliest biochemical evidence described in 83% of all patients at a median age of 26 (10) years, while diabetes was reported in 61% of cases. Among 39 patients with an episode of acute pancreatitis, the median age at acute pancreatitis diagnosis was 20 (17) years. Patients who were reported to have diabetes had 3.2 times, while those with hypertriglyceridemia had 12.0 times, the odds of having pancreatitis compared to those who did not. This study reports the largest number of patients with LMNA-related lipodystrophy syndromes to date. Our report helps to quantify the prevalence of the known and rare complications associated with different phenotypes and serves as a comprehensive catalog of all known cases.


Imatinib mesylate in the treatment of chronic myelogenous leukemia.
Imatinib mesylate binds to the inactive conformation of BCR-ABL tyrosine kinase, suppressing the Philadelphia chromosome-positive clone in chronic myelogenous leukemia (CML). Clinical studies of imatinib have yielded impressive results in the treatment of all phases of CML. With the higher rates of complete cytogenetic response with imatinib, molecular monitoring of disease has become mandatory in assessing response and determining prognosis. The practical aspects of the treatment of CML with imatinib are discussed. The emergence of imatinib resistance, albeit in a small percentage of patients, has prompted an evaluation of innovative treatment strategies.


Non-dermatophytes in onychomycosis of the toenails.
A multicentre trial for the treatment of dermatophyte onychomycosis of the toenails with terbinafine was carried out in Australia and New Zealand. Between eight and 12 nail samples were obtained from each of the 118 patients in the 48-week trial, and each sample was investigated by direct microscopy and culture for dermatophyte and non-dermatophyte fungi. Patients were randomized to treatment with terbinafine at 250 mg/day or placebo for the first 12 weeks of the study, then non-responders were offered a 12-week course of terbinafine from week 28. All patients had a dermatophyte infection. In 42 patients (36%) microscopy and mycological culture identified dermatophytes alone. In the remaining 76 patients (64%), a non-dermatophyte mould or yeast was also isolated at some stage during the trial, but in only three patients did the same non-dermatophyte persist in two or more successive nail specimens. The presence of a fungal contaminant in addition to a dermatophyte had no apparent effect on the efficacy of treatment with terbinafine. We conclude that non-dermatophyte moulds and yeasts are generally found as contaminating organisms in dermatophyte onychomycosis, secondary to the dermatophytes, and that they do not influence the outcome of treatment.


Bow hunter syndrome due to severe stenosis of the left subclavian artery with a thoracic aortic aneurysm.
Bow hunter syndrome is a rare condition characterized by repetitive syncope, which is reflected in brain stem ischaemia due to vertebral compression induced by head rotation. We herein report a rare presentation of bow hunter syndrome due to severe stenosis of the left subclavian artery with a thoracic aortic aneurysm. Disease, hypoplasia of the vertebral artery, or degenerative bone disease as well as congenital foraminal narrowing can be causative. However, to our knowledge, this is the first report describing bow hunter syndrome due to severe stenosis of the left subclavian artery. Computed tomography angiography performed with the symptom induced by head rotation demonstrated obstruction of vertebral arteries. The patient underwent successful open-chest surgery and subclavian artery construction, and postural dizziness was resolved. This report may be helpful when treating similar cases.


Clinical use of C-reactive protein for cardiovascular disease.
Recent evidence supports an association between elevation of inflammatory markers, such as C-reactive protein, and subsequent cardiovascular disease risk. The American Heart Association released guidelines in 2003 to help clinicians know when to use such markers. Because inflammatory markers are associated with diabetes, obesity, and hypertension, knowledge of the role of such markers is extremely important for prevention and chronic disease management. Newer studies published after the guidelines, and another recent review provide further documentation of the growing role of inflammation in cardiovascular risk. Based on the available literature, this article reviews the new guidelines, more recent evidence since the guidelines, and forms recommendations for primary care clinical practice.


[Differential diagnosis of obstruction--clinical aspects of obstructive lung diseases].
The term obstructive lung disease is applied to a group of diseases of different nosology and pathogenesis with the common feature of a characteristic disturbance of the respiratory function consisting in increased resistance of air flow with dyspnoea as the leading clinical symptom. With regard to a differentiated therapy, it is necessary to distinguish precisely between the entities chronic bronchitis, bronchial asthma, emphysema. Meticulous anamnesis, careful clinical examination, basic lung function tests, x-ray examination, electrocardiographic and laboratory examinations, and eventually bronchologic and allergologic methods are sufficient in outpatient and general internal hospital care for a reliable classification and differentiation from a broad spectrum of causes of obstructive symptomatology located outside from the airways.


Comparative proteomics analysis of placenta from pregnant women with intrahepatic cholestasis of pregnancy.
Intrahepatic cholestasis of pregnancy (ICP) usually occurs in the third trimester and associated with increased risks in fetal complications. Currently, the exact cause of this disease is unknown. In this study we aim to investigate the potential proteins in placenta, which may participate in the molecular mechanisms of ICP-related fetal complications using iTRAQ-based proteomics approach. The iTRAQ analysis combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to separate differentially expressed placental proteins from 4 pregnant women with ICP and 4 healthy pregnant women. Bioinformatics analysis was used to find the relative processes that these differentially expressed proteins were involved in. Three apoptosis related proteins ERp29, PRDX6 and MPO that resulted from iTRAQ-based proteomics were further verified in placenta by Western blotting and immunohistochemistry. Placental apoptosis was also detected by TUNEL assay. Proteomics results showed there were 38 differentially expressed proteins from pregnant women with ICP and healthy pregnant women, 29 were upregulated and 9 were downregulated in placenta from pregnant women with ICP. Bioinformatics analysis showed most of the identified proteins was functionally related to specific cell processes, including apoptosis, oxidative stress, lipid metabolism. The expression levels of ERp29, PRDX6 and MPO were consistent with the proteomics data. The apoptosis index in placenta from ICP patients was significantly increased. This preliminary work provides a better understanding of the proteomic alterations of placenta from pregnant women with ICP and may provide us some new insights into the pathophysiology and potential novel treatment targets for ICP.


Deciphering the heterogeneity in DNA methylation patterns during stem cell differentiation and reprogramming.
Human induced pluripotent stem cells (iPSCs) have a wide range of applications throughout the fields of basic research, disease modeling and drug screening. Epigenetic instable iPSCs with aberrant DNA methylation may divide and differentiate into cancer cells. Unfortunately, little effort has been taken to compare the epigenetic variation in iPSCs with that in differentiated cells. Here, we developed an analytical procedure to decipher the DNA methylation heterogeneity of mixed cells and further exploited it to quantitatively assess the DNA methylation variation in the methylomes of adipose-derived stem cells (ADS), mature adipocytes differentiated from ADS cells (ADS-adipose) and iPSCs reprogrammed from ADS cells (ADS-iPSCs). We observed that the degree of DNA methylation variation varies across distinct genomic regions with promoter and 5'UTR regions exhibiting low methylation variation and Satellite showing high methylation variation. Compared with differentiated cells, ADS-iPSCs possess globally decreased methylation variation, in particular in repetitive elements. Interestingly, DNA methylation variation decreases in promoter regions during differentiation but increases during reprogramming. Methylation variation in promoter regions is negatively correlated with gene expression. In addition, genes showing a bipolar methylation pattern, with both completely methylated and completely unmethylated reads, are related to the carbohydrate metabolic process, cellular development, cellular growth, proliferation, etc. This study delivers a way to detect cell-subset specific methylation genes in a mixed cell population and provides a better understanding of methylation dynamics during stem cell differentiation and reprogramming.


Phylogenetic study of SIVcpz MT145 virus based on proteome and genome analysis.
Molecular phylogenetic studies were performed by the alignment of protein/nucleotide sequences of human/simian immunodeficiency virus (HIV/SIV), followed by the construction of phylograms according to maximum likelihood method. We aimed to investigate the evolutionary relationship of the recombinant SIVcpzMT145, to other well-known SIVcpz and HIV-1 viruses. Expectedly, MT145 follows the rule of feasible recombination occurrence in SIVcpz clade as to it consists several recombinations in different genome sites including gag, Pol, and Env region. Phylograms indicated that in Pol gene, MT145 is more related to GAB1 and CAM13 SIVs; while in Env gene, it has a closed relationship to GAB2 SIV. Moreover, MT145 differs from other SIVcpzPtt strains in the Env V3 loop having the QIGPAMT motif (same as HIV-1N), instead of usual QIGPGMT motif in these strains. Data indicated that the Env proteins contain considerable amino acid sequence diversification. Overall, this study suggests that, parts of the Gag and especially Vpu/Env gene sequences of SIVcpzMT145 were derived from an unknown SIVcpz lineage ancestral to HIV-1 group M/MB66.


Force transmission through the wrist during performance of push-ups on a hyperextended and a neutral wrist.
Cross-sectional cohort. Push-ups are used ubiquitously to evaluate and strengthen the upper body. They are usually performed in 1 of 2 main ways: with the wrist in hyperextension and with the wrist in a neutral position. The purpose of our study was to compare the dynamic forces in the wrist during the 2 push-up styles. Fourteen volunteers performed push-ups in 2 different patterns: on a hyperextended wrist and a neutral wrist (NW). Two force plates and a motion capture system were used to measure the ground reaction forces (GRFs) and the kinematics of the upper extremity during push-ups. Kinematic and kinetic analyses were performed using Matlab software (Mathworks, Natick, MA). The GRF vector was distributed differently during the different types of push-ups. For both methods, the total GRF carried by the upper dominant extremity was larger than those of the nondominant extremity. In the NW configuration, the GRF vector was more uniform throughout the push-up in the vertical direction. The horizontal distance between the capitate bone location and the GRF origin was smaller in hyperextension. The forces traveled more dorsally over a wider area and more ulnarly in the hyperextended wrist. Forces are transmitted differently through the wrist in the 2 methods. Push-ups on an NW are likely safer because ligaments may be preferentially loaded in hyperextension. Further study may delineate the differences in the anatomic location of force transmission and the long-term clinical effect on the wrist. This study supports the performance of push-ups on a wrist in neutral flexion extension; both to enable patients after surgery or injury to strengthen the upper body and prevent injury and long-term wear in the wrist. The knowledge gained from this study may assist in outlining guidelines for push-up performance. Diagnostic level 2a.


[Diffuse interstitial pneumopathy related to tungsten carbide, confirmed by bronchoalveolar lavage, and responding to corticotherapy].
The authors report a case of severe diffuse interstitial hard metal lung disease responding to corticosteroid therapy. They point out that the course of this disease may be regressive and emphasise that analysis of broncho-alveolar washings showed no abnormality in the differential cell count. Mineralogical study of the same material confirmed exposure.


Circular RNAs as Diagnostic and Prognostic Indicators of Colorectal Cancer: A Pooled Analysis of Individual Studies.
Background: Circular RNAs (circRNAs) have proven as a special subset of endogenous RNAs that are implicated in the tumorigenesis of various cancers. This study sought to evaluate the role of circRNAs in the diagnosis and prognosis of colorectal cancer (CRC). Methods: The online databases were searched for collecting relevant studies on circRNAs as diagnostic and prognostic biomarkers of CRC. Two researchers independently screened literature, extracted data, and evaluated the bias and risks of included studies. The diagnostic and prognostic indicators were merged and analyzed using STATA 12.0 software, and sources of heterogeneity were traced by the sensitivity analysis and the meta-regression test. Results: A total of 29 articles representing 2639 CRC patients were included. The pooled sensitivity, specificity, and area under the curve (AUC) of circRNAs in differentiating CRC from non-tumor control were 0.75 (95% CI: 0.69-0.80) and 0.74 (95% CI: 0.69-0.78) and 0.81, respectively. The survival analysis showed that up-regulations of up-regulated circRNAs were significantly related to dismal survival in CRC patients (HR = 2.38, p < 0.001). A stratified analysis showed that the comprehensive diagnostic value of up-regualted circRNAs in CRC was higher than that of down-regualted circRNAs (AUC: 0.83 vs. 0.77; Z test, p < 0.05). The efficacy of tissue-derived circRNAs in the diagnosis of CRC was equal to that of plasma/serum-derived ones (AUC: 0.81 vs. 0.82; Z test, p > 0.05). Conclusion: Abnormally expressed circRNAs as auxiliary biomarkers present underlying value in the diagnosis and prognosis prediction of CRC.


[Self aggressive-behaviours in prison].
Suicide among prisoners is a relatively well documented public health issue. On the other hand, data about self-aggressive behaviours in prisons are scarce, despite the fact that this problem seems to be highly prevalent. We conducted a retrospective study over a fifteen months period in a remand prison situated in the French speaking area of Switzerland. During this time period, 161 self-aggressive behaviours were recorded, corresponding to 80 inmates. The most frequent acts were self-cuttings and self-mutilations, followed by strangulations. All these patients were male and their mean age was 25. Some of these behaviours (ingesting cutting objects and sewing of the lips) were specific to some ethno-cultural groups. Copycat behaviours play a significant role in closed communities such as prisons. These results underline the necessity of taking into account self-aggressive behaviours in penitentiary institutions.


Traumatic distal pancreatic transection: beware of the horses.
Blunt pancreatic trauma is rare; however, if missed, it can lead to devastating consequences such as fistula, pancreatitis, and pseudocyst. Blunt trauma accounts for 30% of all pancreatic injuries. High-speed motor vehicle collisions make up the greatest proportion of blunt pancreatic trauma, whereas other causes could be easily overlooked because of being so rare. In this case report we present a case of full-thickness transection of pancreatic tail after being kicked by a horse. The injury was timely identified and successfully treated by completing transection with a stapler. Considering that delay in diagnosis leads to a morbidity rate of 20%, physicians must have high level of suspicion and knowledge of invasive and noninvasive modalities to ensure early detection of pancreatic trauma and a positive outcome.


Ameliorating effect of black tea extract on cadmium chloride-induced alteration of serum lipid profile and liver histopathology in rats.
Cadmium is one among the most environmental pollutants that affects many organs like kidney, liver and testis. The present study was aimed to assess the simultaneous effects of black tea extracts (BTE) on cadmium chloride induced alterations in lipid profile and liver histology. Adult rats were divided into four groups (n=6/group), group I (normal saline), group II (CdCl2, 1.0 mg/kg, b.wt; i.p), group III (black tea extract, 2.5 gm tea leaf/dl of water that is 2.5% of aqueous BTE) and group IV (cadmium chloride + BTE). Cadmium chloride intoxicated rats showed significant increase in serum total cholesterol, triglycerides, and low density lipoprotein-cholesterol and there is a significant decrease in the serum high density lipoprotein-cholesterol. In the liver, cadmium chloride showed changes in normal architecture, swollen hepatocytes, kupffer cells hyperplasia, dilation and congestion of central vein. Oral administration of black tea extracts with cadmium chloride significantly improves lipid profile and liver architecture as compared to the cadmium chloride group. The results indicate that BTE is beneficial in preventing cadmium-induced lipid alterations and hepatocellular damage.


Motor expertise interacts with physical enactment to enhance action memory.
Previous research on action memory showed the advantage for performing the action in memorising the action phrases. We tested if performing the action would help participants with or without motor expertise to memorise the novel action poses. Thirty novel action poses performed by an expert were photographed to constitute memory and interference stimuli. Eighty college students observed to remember the randomly displayed stimuli; however, half were asked to perform the displayed stimuli. Both free-recall and recognition tests were administered immediately and 24 h after the memory task. The results showed that acting was better than observing for memorising the novel action poses, which not only promoted the absolute retention but also alleviated the retention loss caused by interference. Motor expertise enhanced the overall memory performance by promoting a deeper motor encoding. Based on our results, novices should act with (rather than just observe) the model to learn novel motor skills.


Serum interferon in first psychotic attack.
A group of 34 physically healthy young patients, aged 18-27 years at their first psychotic attack, before neuroleptic treatment and admission, were tested simultaneously with 24 age- and sex-matched controls for levels of serum interferon. No statistically significant differences were found between patients and controls. Therefore, no correlation between acute viral infection and schizophrenia was demonstrated.


Acquired cold urticaria: Clinical features, particular phenotypes, and disease course in a tertiary care center cohort.
Data about special phenotypes, natural course, and prognostic variables of patients with acquired cold urticaria (ACU) are scarce. We sought to describe the clinical features and disease course of patients with ACU, with special attention paid to particular phenotypes, and to examine possible parameters that could predict the evolution of the disease. This study was a retrospective chart review of 74 patients with ACU who visited a tertiary referral center of urticaria between 2005 and 2015. Fourteen patients (18.9%) presented with life-threatening reactions after cold exposure, and 21 (28.4%) showed negative results after cold stimulation tests (classified as atypical ACU). Nineteen patients (25.7%) achieved complete symptoms resolution at the end of the surveillance period and had no subsequent recurrences. Higher rates of atypical ACU along with a lower likelihood of achieving complete symptom resolution was observed in patients who had an onset of symptoms during childhood (P < .05). In patients with atypical ACU, shorter disease duration and lower doses of antihistamines required for achieving disease control were detected (P < .05). Age at disease onset, symptom severity, and cold urticaria threshold values were found to be related to disease evolution (P < .05). This study was limited by its retrospective nature. The knowledge of the clinical predictors of the disease evolution along with the clinical features of ACU phenotypes would allow for the establishment of an early and proper therapeutic strategy.


Relation between zinc content in saliva and blood in healthy human adults.
Measurements were made of zinc levels in saliva, whole blood and plasma as well as copper levels in plasma by atomic absorption spectrophotometry. The mean zinc concentration (in ppm) was 0.478 (n = 136) in resting mixed saliva, 0.046 (n = 36) in parotid saliva, 6.41 (n = 145) in whole blood and 0.87 (n = 145) in plasma. The whole blood zinc levels were significantly lower in females than in males (P less than 0.001). Females and blood donors (males) had a significantly (P less than 0.001) higher Cu:Zn ratio than males (non-donors). It would thus appear, first, that the local effect of salivary zinc cannot be assessed simply from the concentration of zinc in stimulated parotid saliva since about nine-tenths of the zinc in resting mixed saliva is derived from other sources and, second, that the Cu:Zn in plasma is the most eligible variable for detecting sub-clinical Zn deficiency.


The Incidence of Gastric Adenocarcinoma Among Patients With Gastric Intestinal Metaplasia: A Long-term Cohort Study.
Gastric intestinal metaplasia (IM) has been known as a premalignant condition, but estimates of its cancer risk vary widely. We aimed to analyze cancer risk of gastric IM by a long-term cohort study. We conducted a hospital-based study that included all patients with gastric IM between 1992 and 2010, and the development of gastric adenocarcinoma was evaluated until July 2011. Patients developing gastric cancer ≤180 days after the index diagnosis of IM were excluded. The incidence rate, the cumulative incidence, and the standardized incidence ratio (SIR) of gastric cancer were determined, and hazard ratios (HRs) of risk factors were calculated. We identified 7059 patients with a median follow-up duration of 5.1 years, and 81 patients developed gastric adenocarcinoma during the study period. The 5-, 10-, and 15-year cumulative incidences of gastric cancer were 0.9% [95% confidence interval (CI), 0.6-1.1), 2.0% (95% CI, 1.5-2.6), and 3.0% (95% CI, 2.0-4.0), respectively. On multivariate analysis, older age (eg, 75 y and above; HR=7.4; 95% CI, 2.8-19.6), low-grade dysplasia (HR=4.0; 95% CI, 2.1-7.9), and high-grade dysplasia (HR=18.8; 95% CI, 9.0-39.5) were independent risk factors. As compared with the risk in the general population, the SIR of gastric cancer among patients with gastric IM was 2.5 (95% CI, 2.0-3.1). However, the SIR was only 2.0 (95% CI, 1.5-2.6) in the nondysplasia subgroup, but was up to 35.2 (95% CI, 15.2-69.4) in the high-grade dysplasia subgroup. Gastric IM is an important risk factor for gastric cancer, but surveillance should be arranged only for those at an especially high risk.


Injection laryngoplasty through a transoral approach using the Guedel oral airway.
Injection laryngoplasty has gained popularity as a treatment modality for glottal insufficiency. Several approaches have been described, specifically transcutaneous, transoral and transnasal. The authors describe a novel technique performed successfully on three subjects, namely endoscopic injection laryngoplasty using the modified Guedel oral airway. There was marked improvement in dysphonia, maximum phonation time and closed quotient in all three subjects with a decrease in the Voice Handicap Index-10 score. This new approach is a viable approach for the treatment of glottal insufficiency.


Genome Sequence of Euphorbia mosaic virus from Passionfruit and Euphorbia heterophylla in Florida.
Euphorbia mosaic virus (EuMV) was found in a symptomatic passionfruit (Passiflora edulis) plant from Homestead, Florida, USA, as well as in the symptomatic weed Euphorbia heterophylla This is the first identification of EuMV in Florida and the United States and the first report of a natural infection of passionfruit by EuMV.


[Principles and stakes of gene therapy].
As the human genome sequencing expands and the molecular bases of diseases are better understood, the tools that allow gene packaging and transfer are available. Transferring a therapeutical gene becomes a reality and indeed more than 100 clinical protocols are currently exploring a variety of applications, from the inherited genetic diseases such as cystic fibrosis to the acquired ones such as cancer. Herein, we describe the different gene transfer strategies applied to animals and humans and we present the advantages and limitations of the currently available vectors which, today, represent the limiting factor for efficient gene therapy.


Free will and the Genome Project.
...I want to argue that the Human Genome Project itself poses no special problem for human freedom, understood in relation to the philosophical issue of free will versus determinism. It seems to pose a problem only if one muddles the interpretation of the issue or of the project that is supposed to bear on it. There is a need for conceptual clarification to point this out, perhaps, but I see no need for "research" in the sense that implies original investigation. However, I also want to probe a bit deeper to identify a distinct set of philosophical worries about freedom that seem to have been misplaced onto the standard issue, the issue of freedom versus determinism, in this discussion and elsewhere. After arguing that the genome project has no real bearing on free will versus determinism, I shall attempt to identify the threat it poses to freedom partly by detaching it from this standard version of the free will question. I shall argue that the worrisome forms of genetic influence that the project might uncover do not really presuppose determinism. But what they do presuppose -- some form of internal or psychological constraint on behavior -- suggests an alternative version of the free will question as the source of popular fears about scientific explanation of human behavior. What is under threat on this version of the question is the Aristotelian notion of character formation and self-control.


Quantitative proton magnetic resonance spectroscopy of the human cervical spinal cord at 3 Tesla.
Cervical spinal cord spectroscopy has the potential to add metabolic information to spinal cord MRI and improve the clinical evaluation and research investigation of spinal cord diseases, such as multiple sclerosis (MS) and intraspinal tumors. However, in vivo proton MR spectroscopy ((1)H-MRS) of the spinal cord is difficult to perform due to magnetic field inhomogeneities, physiological movements, and the size of the anatomical region of interest (ROI). For these reasons, few spinal cord (1)H-MRS studies have been undertaken and two preliminary studies on a 3T system were only recently presented as abstracts. In this work we demonstrate the feasibility of cervical spinal cord quantitative (1)H-MRS on a clinical 3T system, propose a study protocol, and report quantification results obtained from healthy volunteers. The main metabolite concentration ratios obtained in 10 healthy subjects, as provided by LCModel, were as follows: total N-acetyl aspartate/creatine (tNAA/Cr) 1.4 +/- 0.3, choline/creatine (Cho/Cr) 0.5 +/- 0.1, and myoinositol/creatine (mI/Cr) 1.7 +/- 0.2. A significant difference was found between spinal cord tNAA, Cr, Cho, and mI concentration ratios and brainstem concentrations previously acquired on the same system.


Effect of intracrystalline water on longitudinal sound velocity in tetragonal hen-egg-white lysozyme crystals.
Longitudinal sound velocity of tetragonal hen-egg-white (HEW) lysozyme crystals was measured during air drying by ultrasonic pulseecho method. The sound velocity increases with exposure to open air and approaches a constant value. The maximum value is approximately 2900 m/s that is about 1.6 times as much as that of original one before drying. In addition, the sound velocity clearly recovers to original one after immersing the dried crystal in solution. Therefore, the sound velocity in tetragonal HEW lysozyme crystals can be reversibly changed due to dehydration and rehydration. These changes in sound velocity are discussed in the light of water-mediated intramolecular and intermolecular interactions in the crystals.


Plasmacytoma of the Skull-base: A Rare Tumor.
Plasmacytoma of the skull-base is a rare entity. Differential diagnosis includes chordoma, osteosarcoma, carcinoma nasopharynx, meningioma, metastatic carcinoma, lymphoma, and multiple myeloma. Accurate and precise diagnosis is extremely important for plasmacytoma of the skull-base as its treatment and prognosis is different from other skull-base lesions. A 41-year-old man presented with concerns of headache, diplopia, and left eye strabismus. A magnetic resonance image (MRI) of his brain showed a large expansile mass measuring 51 mm involving the clivus and central skull-base. Trans-sphenoidal tumor decompression was done. A biopsy confirmed the plasmacytoma. A positron emission tomography-computed tomography (PET-CT) scan showed a single 2-(18F) fluoro-D-glucose (FDG) avid lesion at the skull-base. The results of all other relevant investigations such as hemoglobin, renal function test, serum calcium, serum protein immunoelectrophoresis, serum quantitative immunoglobulin, bone marrow biopsy, serum lactate dehydrogenase, and beta-2 microglobulin levels were within normal limits. He was treated with radical radiotherapy. He developed complete clinical response after radiotherapy.


Breaking boundaries-coagulation and fibrinolysis at the neurovascular interface.
Blood proteins at the neurovascular unit (NVU) are emerging as important molecular determinants of communication between the brain and the immune system. Over the past two decades, roles for the plasminogen activation (PA)/plasmin system in fibrinolysis have been extended from peripheral dissolution of blood clots to the regulation of central nervous system (CNS) functions in physiology and disease. In this review, we discuss how fibrin and its proteolytic degradation affect neuroinflammatory, degenerative and repair processes. In particular, we focus on novel functions of fibrin-the final product of the coagulation cascade and the main substrate of plasmin-in the activation of immune responses and trafficking of immune cells into the brain. We also comment on the suitability of the coagulation and fibrinolytic systems as potential biomarkers and drug targets in diseases, such as multiple sclerosis (MS), Alzheimer's disease (AD) and stroke. Studying coagulation and fibrinolysis as major molecular pathways that regulate cellular functions at the NVU has the potential to lead to the development of novel strategies for the detection and treatment of neurologic diseases.


Psoriasis: Striving for Potential Biomarkers.
Psoriasis is a chronic disease that is caused by multiple factors and is identified by itchiness, unpleasant, red, or white scaly patches on the skin, particularly on regularly chafed body regions such as the lateral areas of the limbs. Reports suggest that globally around 2%-3% of the population suffers from psoriasis. In this review, we have discussed the clinical classification of psoriasis and also the ideal characteristics of the biomarkers. An overview regarding the discovery of the biomarker and method for validating the study has been discussed. A growing body of research suggests a link to certain other systemic symptoms such as cardiovascular disorder, metabolic syndrome, and few other comorbidities such as hypertension and nonalcoholic fatty liver disease. Natural killer (NK) cells are lymphocyte cells that concentrate on the destruction of virally infected and malignant cells; these tend to produce a wide range of inflammatory cytokines, some of which are associated with the etiology of psoriasis. Detailed information on the molecular pathogenesis of psoriasis in which interleukin (IL)-17, IL-23, tumor necrosis factor-α (TNF-α), and CCL20 play a very significant role in the development of psoriasis. In this review, we have discussed an overview of the recent state of the biomarkers available for the diagnosis and treatment of psoriasis by emphasizing on the available biomarkers such as epigenomic, transcriptomic, glycomic, and metabolomic. The most recent advancements in molecular-targeted therapy utilizing biologics and oral systemic therapy (methotrexate, apremilast) enable to adequately treat the most serious psoriatic symptoms and also the studies have validated the efficacy of biologic therapy such as TNF-α antagonist (infliximab, adalimumab), IL-23 antagonist (guselkumab, risankizumab), and IL-17 antagonist (secukinumab, ixekizumab). Finally, an overview about the technological opportunities as well as various challenges has been discussed.


[Tattoos and permanent make-up: background and complications].
Tattoos and permanent make-up have enjoyed great popularity during recent years. However, a careful consideration of the risks is made only rarely before each procedure. Above all the undefined pigment compositions create unforeseeable health and appearance problems. The family physician should be familiar with the techniques, materials, as well as the possible risks of tattoos and permanent make-up when advising patients. Medical complications include, among other things, infections, allergies, keloid and granuloma formation.


Bioaccumulation-based silver nanoparticle toxicity in Daphnia magna and maternal impacts.
In the present study, we tested whether bioaccumulation in specific tissues of Daphnia magna could explain silver nanoparticle (AgNP) toxicity. Daphnids were exposed to different concentrations of well-suspended AgNPs and AgNO3 . The accumulations of Ag in the whole body, gut, and nongut tissues, as well as the mortality of daphnids, were recorded over a period of 7 d. Regression analysis showed a higher degree of positive correlation between the concentration of Ag in the nongut tissues than gut tissues and the mortality of daphnids. The results strongly suggested that the toxicity of AgNPs could be better explained in terms of bioaccumulation of AgNPs in the nongut tissues. We further tested the maternal transfer of AgNPs in daphnids into the next generation using radioactive tracers, which were able to detect as low as 1.0 to 3.2% of total accumulated Ag transferred to the neonates. The AgNPs significantly affected the reproduction process during the first 2 broods after exposure, whereas AgNO3 only had significant effects on the first brood. It is possible that AgNPs have longer adverse effects than AgNO3 on the reproduction of Daphnia. The present study identified the sensitive site of AgNP toxic action in daphnids and documented the extent of maternal transfer and the significant influence of AgNPs on the reproduction of daphnids. Environ Toxicol Chem 2017;36:3359-3366. © 2017 SETAC.