Preparation and Characterization of Composites Based on Polylactic Acid and Beeswax with Improved Water Vapor Barrier Properties.
Beeswax and a plasticizer (ATBC) were added to polylactic acid (PLA) films in order to enhance the water vapor barrier properties of the films. Beeswax improved the barrier properties; the water vapor permeability in the composite containing 1% beeswax was 58% lower than that of the neat PLA. Fourier transform infrared spectroscopy and X-ray diffraction analysis revealed that the incorporation of beeswax and ATBC had so little effect on the PLA structure. In addition, the structure of PLA did not vary substantially with the additions. The surfaces of the composites were examined by using field emission scanning electron microscopy. Differential scanning calorimetry results showed that the degree of crystallinity of the PLA films increased with the addition of beeswax and ATBC. However, the tensile strength and elongation at break of the composites containing beeswax were up to approximately 50% lower than those of the neat PLA. Although further study is needed to improve the mechanical properties, the aforementioned results showed that the PLA barrier properties can be improved by the incorporation of a small amount of beeswax and ATBC. The results of this study can be applied for the preparation of PLA composite films with improved barrier properties. Such biodegradable films are extremely useful for applications in the food packaging industry.


A phase II trial of bryostatin-1 administered by weekly 24-hour infusion in recurrent epithelial ovarian carcinoma.
Bryostatin-1 is a macrocyclic lactone whose main mechanism of action is protein kinase C modulation. We investigated its activity as a weekly 24-h infusion in recurrent ovarian carcinoma. In all, 17 patients were recruited and 11 had chemotherapy-resistant disease as defined by disease progression within 4 months of last cytotoxic therapy. All were evaluable for toxicity and 14 for response. There were no disease responses and the main toxicity was myalgia.


[Establishing the method of collagen-gel droplet embedded culture drug sensitivity test with rat tail collagen].
To explore the clinical application of collagen-gel droplet embedded-culture drug sensitivity test (CD-DST) in the malignant tumors. CD-DST was established with rat tail collagen. Three pancreatic cancer cell lines, surgical resection specimens including 15 cases of pancreatic cancer and 10 cases of gastrointestinal cancer were examined using CD-DST. The overall achievement ratio of CD-DST for clinical tumor specimens was 80% (20/25). In vitro chemosensitivities of pancreatic carcinoma cells to 5-FU, gemcitabine and oxaliplatin were lower than those of gastrointestinal carcinoma. CD-DST with rat tail collagen is a valuable chemosensitivity testing method for malignant tumors. It can be used to realize individualized anticancer chemotherapy.


Enteric fever: a changing perspective.
All the cases of enteric fever admitted between 1988-1992 were studied. There was a gradual rise in the number of admitted cases. Central nervous system (CNS) complications like encephalopathy (14.9%), meningitis (8.8%), seizures (8.5%) and cerebellitis (3.4%) were noted more during 1991 and 1992. Other complications like myocarditis (4.6%), hepatitis (9.5%) and gastrointestinal bleeding were noted in increasing numbers during 1991-1992. Multidrug resistant (MDRT) cases were 46.3% in 1991 and 33.5% in 1992. There was a significant difference in the time taken for defervescence (a gradual rise) between the years but between the individual drugs there was no such significant difference. Deaths were noted only in 1991 and 1992 in cases of MDRT with complications. There has been an increase in resistance of S. typhi to commonly used drugs like ampicillin, chloramphenicol and cotrimoxazole. S. typhi resistant to ciprofloxacin was cultured in 2 cases each from 1990-1992. Further, the time taken for defervescence with ciprofloxacin also showed a gradual rise from 3.5 days in 1990 to 6.2 days in 1992. Nevertheless, ciprofloxacin is still the drug of choice for treatment of complicated cases of MDRT.


MR imaging in ovarian cancer.
Magnetic resonance (MR) imaging is increasingly being used in patients with gynaecological disorders due to its high contrast resolution compared to computed tomography (CT) and ultrasound. In women presenting with an adnexal mass, ultrasound remains the primary imaging modality in the detection and characterisation of such lesions. However, in recent years overwhelming evidence has accumulated for the use of MR imaging in patients with indeterminate adnexal masses particularly in younger women and where disease markers are unhelpful. In staging ovarian cancer and for evaluating therapeutic response MR imaging is as accurate as CT but CT remains the imaging modality of choice because it is more widely available and quicker. This article reviews that evidence and outlines a place for the use of MR imaging in ovarian cancer.


A rapid and reproducible on line automated technique to determine endothelial function.
To evaluate clinically a new on line, automated technique to measure flow mediated dilatation (FMD) as a marker of endothelial function. Prospective study. 12 healthy volunteers and 12 patients with significant, angiographically documented coronary artery disease. Brachial arteries were imaged using a standard vascular ultrasound system with a 5-12 MHz linear transducer. Arterial diameter was measured on line (in real time) by connecting the ultrasound system to a personal computer equipped with a frame grabber and artery wall detection software (VIA) specially developed by the authors' group. By using this new technique, FMD was measured following 4.5 minutes of ischaemia of the proximal forearm in all subjects on two separate days. The mean (SD) day to day variability in FMD measurements was 0.90 (0.48)%,which compares very favourably with current methods. The FMD measurement was available within seconds of completing the scan. Personal computer based automated techniques to assess FMD involve image acquisition and recording after which a second (off line) image interpretation session is required. The need for off line analysis makes current methods time consuming and increases the variability of measurement. This on line, automated analysis technique for FMD assessment reduces the variability and greatly increases the speed of measurement. Using this system may mean that fewer patients will be required in clinical trials assessing the effects of interventions on endothelial function. Adopting this method may also facilitate the screening of larger numbers of subjects for endothelial dysfunction.


Thoracic Paravertebral Block versus Epidural Anesthesia Combined with Moderate Sedation for Percutaneous Nephrolithotomy.
To investigate the feasibility of thoracic paravertebral block (TPVB) for percutaneous nephrolithotomy (PCNL) in comparison with epidural anesthesia (EA) combined with moderate sedation. One hundred American Society of Anesthesiologists (ASA) I-II adult patients scheduled for first-stage unilateral PCNL were randomly assigned to receive either TPVB or EA. All patients were given standard sedation and analgesia with propofol and sufentanil. Patient characteristics, surgical outcomes, anesthetic outcomes, and time to first use of a patient-controlled intravenous analgesic (PCIA) device and postoperative consumption of sufentanil in the first 24 h were recorded. Intergroup differences of the parameters were analyzed using an independent t test, Mann-Whitney test, and χ2 test as appropriate. Patients who received TPVB consumed more propofol during ureteroscopy (56.2 ± 28.4 vs. 42.9 ± 27.5 mg, p < 0.05) and more sufentanil during ureteroscopy (9.7 ± 4.8 vs. 3.9 ± 2.7 μg, p < 0.05) and during PCNL (7.0 ± 4.3 vs. 1.9 ± 1.8 μg, p < 0.05) than those who received EA. The volume fluids infused in patients who received TPVB was less than in those who received EA (854 ± 362 vs. 1,320 ± 468 ml, p < 0.05). Time to first PCIA use, postoperative 24-hour consumption of sufentanil, and other parameters were comparable between groups. In this study, TPVB was as effective and safe as EA in providing intraoperative anesthesia and postoperative analgesia for PCNL, although more sedatives and analgesics were used during PCNL in patients who received TPVB.


The effects of corticosteroids on the musculoskeletal system.
The use of corticosteroids, both systemically and locally, is commonplace for the management of numerous rheumatic and inflammatory conditions. The effects of corticosteroids are far-reaching and have both beneficial and potential detrimental effects on the musculoskeletal system. Understanding some of the mechanisms of action and the effects of these medications can allow the orthopaedic nurse to anticipate and prepare for possible untoward consequences.


Driving HIV-1 into a Vulnerable Corner by Taking Advantage of Viral Adaptation and Evolution.
Anti-retroviral therapy (ART) is crucial for controlling human immunodeficiency virus type-1 (HIV-1) infection. Recently, progress in identifying and characterizing highly potent broadly neutralizing antibodies has provided valuable templates for HIV-1 therapy and vaccine design. Nevertheless, HIV-1, like many RNA viruses, exhibits genetically diverse populations known as quasispecies. Evolution of quasispecies can occur rapidly in response to selective pressures, such as that exerted by ART and the immune system. Hence, rapid viral evolution leading to drug resistance and/or immune evasion is a significant barrier to the development of effective HIV-1 treatments and vaccines. Here, we describe our recent investigations into evolutionary pressure exerted by anti-retroviral drugs and monoclonal neutralizing antibodies (NAbs) on HIV-1 envelope sequences. We also discuss sensitivities of HIV-1 escape mutants to maraviroc, a CCR5 inhibitor, and HIV-1 sensitized to NAbs by small-molecule CD4-mimetic compounds. These studies help to develop an understanding of viral evolution and escape from both anti-retroviral drugs and the immune system, and also provide fundamental insights into the combined use of NAbs and entry inhibitors. These findings of the adaptation and evolution of HIV in response to drug and immune pressure will inform the development of more effective antiviral therapeutic strategies.


Prevalence and risk factors for diabetic retinopathy: the Singapore Malay Eye Study.
To describe the prevalence and risk factors of diabetic retinopathy in Asian Malays. Population-based cross-sectional study. Persons with diabetes of Malay ethnicity aged 40 to 80 years in Singapore. Diabetes mellitus was defined as random glucose of 11.1 mmol/l or more, use of diabetic medication, or a physician diagnosis of diabetes. Retinal photographs taken from both eyes were graded for diabetic retinopathy using the modified Airlie House classification system. Any diabetic retinopathy, retinopathy grades, macular edema, or vision-threatening retinopathy. Of the 3261 persons who participated in this study, 757 (23.1%) had diabetes and gradable retinal photographs. In persons with diabetes, the overall prevalence of any retinopathy was 35.0% (95% confidence interval [CI], 28.2-43.4), the overall prevalence of macular edema was 5.7% (95% CI, 3.2-9.9), and the overall prevalence of vision-threatening retinopathy was 9.0% (95% CI, 5.8-13.8). Compared with men, women had significantly higher proportions with more severe diabetic retinopathy, moderate (12% vs. 4%) and severe (3% vs. 0.2%) nonproliferative retinopathy, proliferative retinopathy (7% vs. 2%), and vision-threatening retinopathy (13% vs. 3%). In multiple logistic regression, independent risk factors for any retinopathy were longer diabetes duration (odds ratio [OR], 1.07; 95% CI, 1.04-1.09, per year increase), higher hemoglobin A1(c) (OR, 1.21; 95% CI, 1.10-1.33, per % increase), hypertension (OR, 1.85; 95% CI, 1.04-3.30), and higher pulse pressure (OR, 1.34, 95% CI, 1.19-1.51, per 10-mmHg increase); older age (OR, 0.73; 95% CI, 0.57-0.93, per decade increase) and higher total cholesterol levels (OR, 0.75; 95% CI, 0.63-0.89, per 1-mmol/l increase) were protective of any retinopathy. Vision-threatening retinopathy additionally was associated with previous stroke (OR, 3.74; 95% CI, 1.24-11.26), cardiovascular disease (OR, 2.23; 95% CI, 1.08-4.62), and chronic kidney disease (OR, 4.45; 95% CI, 2.18-9.07). Female gender was not an independent risk factor for diabetic retinopathy after adjusting for metabolic and socioeconomic risk factors. One in 10 Malay adults with diabetes in Singapore has vision-threatening diabetic retinopathy. Risk factors for retinopathy in this population are largely similar to white populations elsewhere, suggesting that control of these risk factors may reduce both the prevalence and impact of retinopathy.


Is Bulpa criteria suitable for the diagnosis of probable invasive pulmonary Aspergillosis in critically ill patients with chronic obstructive pulmonary disease? A comparative study with EORTC/ MSG and ICU criteria.
Three diagnostic criteria have been proposed used for invasive pulmonary aspergillosis (IPA) diagnosis, namely EORTC/ MSG criteria, Bulpa criteria and intensive care unit (ICU) criteria. The Bulpa criteria were proposed to diagnose IPA in chronic obstructive pulmonary disease (COPD) patients specially. Our aim is to verify that whether the Bulpa criteria are the most suitable for diagnosing probable IPA in critically ill COPD patients compared with the other two criteria. We included critically ill COPD patients admitted to the ICU from April 2006 to August 2013. Patients were classified into four populations: population one (n1 = 59) comprised all included patients; population two (n2 = 24) comprised patients with positive mycological findings (both positive cultures and positive serologic tests); population three (n3 = 18) comprised patients with positive lower respiratory tracts (LRTs) isolation; and population four (n4 = 5) comprised proven IPA patients with histopathology. Patients in four groups were diagnosed as probable IPA using three criteria respectively, and the "diagnostic rate" of each criteria were compared with each other. Then, the reasons for differences in "diagnostic rate" were analyzed in population two. Finally, the modified Bulpa criteria were proposed. Bulpa criteria yielded the highest "diagnostic rate" of probable IPA followed by the ICU criteria, while the EORTC/ MSG criteria provided the lowest rates in four populations (the "diagnostic rate" of probable IPA was 33.9%, 16.9% and 6.8% in population one, p = 0.001; 83.3%, 41.7% and 16.7% in population two, p < 0.001; 100%, 55.6% and 22.2% in population three, p < 0.001; 100%, 60% and 20% in population four, p = 0.036). The reasons for the highest "diagnostic rate" by Bulpa criteria were its less strict requirements regarding the doses/courses of steroid use and typical computed tomography (CT) findings. Finally, the modified Bulpa criteria for probable IPA were proposed for critically ill COPD patients admitted to ICU, mainly involving revised interpretations of microbiological findings. Among the existing three criteria, the Bulpa criteria are the most suitable for diagnosing probable IPA in critically ill COPD patients admitted to ICU. A modified criteria maybe proposed for better diagnosis,and its clinical validity need to be verified in future studies.


Role of dorsolateral periaqueductal grey in the coordinated regulation of cardiovascular and respiratory function.
The midbrain periaqueductal grey (PAG) contains four longitudinal columns, referred to as the dorsomedial (dmPAG), dorsolateral (dlPAG), lateral (lPAG) and ventrolateral (vlPAG) subdivisions, which collectively have a pivotal role in integrating behavioural and physiological responses to external stressors as well as other functions. This review is focussed on the dlPAG, which is believed to be an important component of the central mechanisms that generate the defensive response to acute psychological stressors, such as the presence of a predator or other immediate threat. The anatomical connections of the dlPAG are highly specific and distinctly different from those of the other PAG subregions. The chemical properties of the dlPAG are also distinctly different from the other PAG subregions (e.g. there is a very high density of neurons that synthesize nitric oxide in the dlPAG but very few such neurons in the other PAG subregions). Recent functional studies have demonstrated that neurons in the dlPAG exert a powerful control over both sympathetic and respiratory activity, and that the pattern of the evoked respiratory changes is also distinctly different from those evoked from other PAG subregions. These studies also showed that the sympathetic and respiratory changes evoked from the dlPAG are highly correlated, suggesting the possibility that a common population of "command neurons" within this region may generate the sympathetic and respiratory changes that accompany defensive behavioural responses to acute psychological stressors. Finally, although the anatomical connections and functional properties of the dlPAG are distinctly different from the other PAG subregions, they have many similarities with adjacent parts of the superior colliculus, suggesting that the dlPAG and deep layers of the superior colliculus may be part of a common defence system in the midbrain.


Investigating novel biomarkers of immune activation and modulation in the context of sedentary behaviour: a multicentre prospective ischemic stroke cohort study.
Sedentary behaviour is associated with disease, but the molecular mechanisms are not understood. Valid biomarkers with predictive and explanatory properties are required. Therefore, we have investigated traditional and novel biomarkers of inflammation and immune modulation and their association to objectively measured sedentary behaviour in an ischemic stroke population. Patients admitted to hospital with acute ischemic stroke were included in the multicentre Norwegian Cognitive Impairment After Stroke (Nor-COAST) study (n = 815). For this sub-study (n = 257), sedentary behaviour was registered 3 months after stroke using position transition data from the body-worn sensor, ActivPal®. Blood samples were analysed for high sensitive C-reactive protein (hsCRP), the cytokines interleukin-6 (IL-6) and 10 (IL-10), neopterin, tryptophan (Trp), kynurenine (kyn), kynurenic acid (KA), and three B6 vitamers, pyridoxal 5'-phosphate (PLP), pyridoxal (PL), and pyridoxic acid (PA). The kynurenine/tryptophan ratio (KTR) and the pyridoxic acid ratio index (PAr = PA: PL + PLP) were calculated. Of the 815 patients included in the main study, 700 attended the three-month follow-up, and 257 fulfilled the inclusion criteria for this study. Sedentary time was significantly associated with levels of hsCRP, IL-6, neopterin, PAr-index, and KA adjusted for age, sex, waist circumference, and creatinine. In a fully adjusted model including all the significant biomarkers except hsCRP (because of missing values), sedentary time was independently positively associated with the PAr-index and negatively with KA. We did not find an association between sedentary behaviour, IL-10, and KTR. The PAr-index is known to capture several modes of inflammation and has previously shown predictive abilities for future stroke. This novel result indicates that the PAr-index could be a useful biomarker in future studies on sedentary behaviour and disease progression. KA is an important modulator of inflammation, and this finding opens new and exciting pathways to understand the hazards of sedentary behaviour. The study was registered at Clinicaltrials.gov ( NCT02650531 ). First posted 08/01/2016.


Hepatic complications of allogeneic hematopoietic cell transplantation.
Hepatic complications of allogeneic hematopoietic cell transplantation contribute substantially to the overall success of the procedure and represent a major cause of morbidity and mortality. Early hepatic complications consist of the sinusoidal obstruction syndrome, drug toxicities, infections, acute graft-versus-host disease, while late hepatic complications consist of chronic graft-versus host disease, chronic viral hepatitis, and iron overload states. Successful management of the hepatic complications of allogeneic hematopoietic cell transplantation is dependent on several factors. These include the recognition and elimination of any pre-transplant risk factors for these problems and the development of strategies to evaluate and prevent them in both the early and later posttransplant periods. The aims of present review are 1) to identify the early and late hepatic complications of allogeneic hematopoietic cell transplantation, in the chronological order at which they occur, 2) to characterize the diagnostic procedures used to identify them, and finally 3) to present the current therapeutic approaches used to manage these problems.


Efficacy of infliximab on MRI-determined bone oedema in psoriatic arthritis.
Psoriatic arthritis (PsA) is commonly associated with bone pathology, including entheseal new bone formation and osteolysis. On MRI, areas of active clinical involvement are represented by bone oedema and synovitis. To assess the impact of infliximab on bone oedema in PsA as shown by MRI. 18 patients with joint swelling, psoriasis and seronegativity for rheumatoid factor received four infusions of infliximab, 3 mg/kg, in combination with methotrexate. MRI of the affected hand (12 patients) or knee joints (6 patients) was performed before and after treatment. The primary outcome was the assessment of bone oedema and synovitis at 20 weeks as shown by MRI. Secondary outcomes included the American College of Rheumatology (ACR) response criteria, psoriasis skin scores (Psoriasis Area and Severity Index (PASI)) and a quality of life measure (Psoriatic Arthritis Quality of Life (PsAQoL)). At baseline, bone oedema was seen in 50% of patients (seven hands and two knees) in 30% of scanned joints, and this improved or resolved in all cases in the hand joints (p = 0.018) and in one knee joint at 20 weeks. Synovitis was found to be reduced in 90% of cases on MRI. Likewise, a significant improvement in all clinical outcomes, including PASI (p = 0.003) and PsAQoL (p = 0.006) was seen at week 20. 65% (n = 11) of the patients achieved an ACR response, of whom 45% had ACR70 or above and 54% had ACR20 or ACR50. Infliximab treatment is associated with dramatic improvements in MRI-determined bone oedema in PsA in the short term. It remains to be determined whether infliiximib treatment is the cause for prevention of new bone formation, bone fusion or osteolysis in PsA as shown by radiography.


In vitro Evaluation of the Nutritive Value of Trianthema portulacastrum as a Source of Fodder for Ruminants.
Trianthema portulacastrum (common farm weed in tropical countries) contains 21.5 ± 1.2% crude protein, similar to Lucerne with relatively low structural carbohydrate (neutral detergent fibre: 43.6 ± 3.1%). The mineral profile of T. portulacastrum was well above the critical level as far as calcium (0.3%), magnesium (0.2%), iron (50 ppm), copper (8 ppm), zinc (30.0 ppm) and manganese (50 ppm), whereas the phosphorus content at 0.13 ± 0.1 % was below the critical level recommended by McDowell et al. (1983). Degradability studies in rumen stimulation technique (RUSITEC) revealed that nearly half of the dry matter in T. portulacastrum was soluble and degradable, while 69.9% of the nitrogen was insoluble but degradable. The digestible rumen degradable nitrogen and digestible un-degradable nitrogen values were 1.2% and 1.4% respectively, with the total absorbable nitrogen value of 2.5%. This study revealed that supplementation of digestible organic matter to the extent of 14.9% and phosphorus to the extent of 0.2% was suggested as a tool to exploit the full potential nutritive value of T. portulacastrum.


Molecular mechanism of polarized transport.
Mechanisms of generation and maintenance of cell polarity have been investigated using various organisms and cell lines. During and after the establishment of cell polarity, polarized (vesicular) transport as well as cell-cell adhesion is essential. Here, I introduce each molecular step of polarized transport and the molecules involved there. Usually, epithelial cells and neurons are two well-known examples of polarized cells. Thus, I next describe the similarity and difference in polarized transport between these two cell types. Though closely connected, the relationship between cell-cell adhesion and polarized transport remain poorly understood. I will take a few examples indicating the relationship between them. Finally, I will present the future directions in this field.


Old and new insights into the diagnosis of hereditary spherocytosis.
Hereditary spherocytosis (HS) belongs to the group of congenital hemolytic anemias resulting from plasma membrane protein deficiency. When diagnosed too late, HS bares the risk of long-term complications including gall stones and severe anemia. Here, there are discussed advances in HS screening and diagnostics, with a particular focus on methodologies, most of which are available in clinical laboratories worldwide.


The role of interneuron networks in driving human motor cortical plasticity.
The after-effects of repetitive transcranial magnetic stimulation (rTMS) are highly variable between individuals. Because different populations of cortical neurons are stimulated more easily or are more excitable in different people at different times, the variability may not be due to differences between individuals in the plasticity of cortical synapses, but may instead be due to individual differences in the recruitment of cortical neurons. In this study, we examined the effects of rTMS in 56 healthy volunteers. The responses to excitatory and inhibitory theta burst stimulation (TBS) protocols were highly variable between individuals. Surprisingly, the TBS effect was highly correlated with the latency of motor-evoked potentials (MEPs) evoked by TMS pulses that induced an anterior-posterior (AP) directed current across the central sulcus. Finally, we devised a new plasticity protocol using closely timed pairs of oppositely directed TMS current pulses across the central sulcus. Again, the after-effects were related to the latency of MEPs evoked by AP current. Our results are consistent with the idea that variation in response to rTMS plasticity probing protocols is strongly influenced by which interneuron networks are recruited by the TMS pulse.


Formation of hippocampal mHTT aggregates leads to impaired spatial memory, hippocampal activation and adult neurogenesis.
Huntington's disease (HD) is a genetic neurodegenerative disorder characterized by a triad of motor, psychiatric and cognitive deficits with the latter classically attributed to disruption of fronto-striatal circuits. However, emerging evidence suggests that some of the cognitive deficits in HD may have their origin in other structures including the hippocampus. Hippocampal abnormalities have been reported in HD mouse models particularly in terms of performance on the Morris Water Maze. However, in these animals, it is difficult to be certain whether the spatial memory deficits are due to local pathology within this structure or their poor mobility and motivation. Thus, a better model of hippocampal dysfunction in HD is needed especially given that we have previously shown that patients with HD have hippocampal-related problems from the very earliest stages of disease. In this study, our aim was therefore to understand the cellular and behavioural consequences of local overexpression of mutant huntingtin (mHTT) in the hippocampus of adult mice. We found that a targeted injection of a lentivirus, encoding an N-terminal of mHTT with 82 CAG repeats, into the murine hippocampus led to the focal formation of mHTT aggregates, long-term spatial memory impairments with decreased neurogenesis and expression of the immediate early gene c-fos. This study has therefore shown for the first time that local expression of mHTT in the dentate gyrus has deleterious effects, including its neurogenic capacity, with functional behavioural consequences, which fits well with recent data on hippocampal deficits seen in patients with HD.


[Spatial parameters of the automatically reproduced QRS loop of the VCG in healthy subjects].
The findings of the VCG automatic construction in 55 healthy subjects with different axial and positional variants of ECG were analyzed . The applied method of the automatic corrected VCG construction has shown that QRS loop morphology coincides with the classical forms of VCG described before in healthy persons. The data of the automatic calculations of spatial characteristics demonstrated the orientation stability according to the angle--azimuth, max QRSxyz , S/2 QRSxyz and the integral vector-- AQRSxyz , i. e. independence of the azimuth value on the ECG axial and positional variants. The positional and rotational shifts regularly change the azimuth value in the spatial orientation of the initial (0.01"--0.02') and end (0.06") moment vector of depolarization, and the value of the angles of spatial vector elevation max QRSxyz , S/2 QRSxyz , AQRSxyz . In the normal intraventricular conduction, the orientations of max QRSxy , yz , xz are sufficiently informative in order to reveal the integral vector directions. The coincidence of S/2 QRSxy , yz , xz direction with that of AQRSxy , yz , xz in the two-polar loops indicates that S/2 QRSxy , yz , xz should be calculated to determine AQRSxy , yz , xz orientation. Indeed, in case of intraventricular conduction disorders, the AQRSxy , yz , xz calculation alone gives an idea of a resultant vector projection.


Production of mesenchymal tumors in nude mice by Ph1 negative fibroblasts obtained from a Ph 1 positive CML patient: a preliminary report.
An experimental model system is presented for the investigation in humans of the role of hematopoietic stromal elements in the regulation of hematopoiesis as well as in the pathogenesis of myelofibrosis in myeloproliferative disorders. The model is based on the simultaneous application of three experimental techniques: (1) growth of bone-marrow derived fibroblastic colonies in vitro, (2) cytogenetic demonstration of marker chromosomes associated with hematopoietic malignancies, and (3) the transplantation of isolated stromal elements into athymic (nude) mice. Using this model, we describe the induction of mesenchymal tumors in nude mice by Ph1 negative fibroblasts obtained from the bone marrow of a patient with a Ph1 positive chronic myelogenous leukemia. Mesenchymal tumors also were induced in nude mice with bone marrow-derived fibroblasts from a patient with aplastic anemia, who was successfully treated with bone marrow transplantation, and from a normal human volunteer. Morphologic, cytogenetic and electron microscopic studies of bone marrow mesenchymal elements in culture and of tumors induced in nude mice from the CML patient indicate the cells composing the tumor are of human origin and are negative for the Ph1 chromosome. The results provide the first in vivo morphological and cytogenetic support using human materials, of the hypothesized relationship of progenitors of in vitro fibroblastic colonies to marrow stromal elements.


Recurrent Carpal Tunnel Syndrome Associated with Mycobacterium szulgai Infection: A Case Report.
We present the case of an otherwise healthy 77-year-old male retired firefighter and recreational pheasant hunter who presented with recurrent symptoms of carpal tunnel syndrome and tenosynovitis because of Mycobacterium szulgai. He was initially treated unsuccessfully for a presumed seronegative rheumatologic flare, followed by surgical diagnosis and treatment including revision carpal tunnel release with tenosynovectomy, and a secondary debridement and wound closure. His symptoms resolved after several months of multidrug antibiotic therapy with only mild residual median nerve deficit. Nontuberculous Mycobacterium infections of the upper extremity are extremely rare and challenging to diagnose/treat. This report highlights diagnostic and surgical challenges in this rarely reported infection.


Reduced expression of Na(v)1.6 sodium channels and compensation by Na(v)1.2 channels in mice heterozygous for a null mutation in Scn8a.
The voltage-gated sodium channel alpha subunit Na(v)1.6, encoded by the Scn8a gene, accumulates at high density at mature nodes of Ranvier of myelinated axons, replacing the Na(v)1.2 channels found at nodes earlier in development. To investigate this preferential expression of Na(v)1.6 at adult nodes, we examined isoform-specific expression of sodium channels in mice heterozygous for a null mutation in Scn8a. Immunoblots from these +/- mice had 50% of the wild-type level of Na(v)1.6 protein, and their optic-nerve nodes of Ranvier had correspondingly less anti-Na(v)1.6 immunofluorescence. Protein level and nodal immunofluorescence of the Na(v)1.2 alpha subunit increased in Scn8a(+/-) mice, keeping total sodium channel expression approximately constant despite partial loss of Na(v)1.6 channels. The results are consistent with a model in which Na(v)1.6 and Na(v)1.2 compete for binding partners at sites of high channel density, such as nodes of Ranvier. We suggest that Na(v)1.6 channels normally occupy most of the molecular machinery responsible for channel clustering because they have higher binding affinity, and not because they are exclusively recognized by mechanisms for transport and insertion of sodium channels in myelinated axons. The reduced amount of Na(v)1.6 protein in Scn8a(+/-) mice is apparently insufficient to saturate the nodal binding sites, allowing Na(v)1.2 channels to compete more successfully.


Intraoperative post-annuloplasty three-dimensional valve analysis does not predict recurrent ischemic mitral regurgitation.
High ischemic mitral regurgitation (IMR) recurrence rates continue to plague IMR repair with undersized ring annuloplasty. We have previously shown that pre-repair three-dimensional echocardiography (3DE) analysis is highly predictive of IMR recurrence. The objective of this study was to determine the quantitative change in 3DE annular and leaflet tethering parameters immediately after repair and to determine if intraoperative post-repair 3DE parameters would be able to predict IMR recurrence 6 months after repair. Intraoperative pre- and post-repair transesophageal real-time 3DE was performed in 35 patients undergoing undersized ring annuloplasty for IMR. An advanced modeling algorhythm was used to assess 3D annular geometry and regional leaflet tethering. IMR recurrence (≥ grade 2) was assessed with transthoracic echocardiography 6 months after repair. Annuloplasty significantly reduced septolateral diameter, commissural width, annular area, and tethering volume and significantly increased all segmental tethering angles (except A2). Intraoperative post-repair annular geometry and leaflet tethering did not differ significantly between patients with recurrent IMR (n = 9) and patients with non-recurrent IMR (n = 26). No intraoperative post-repair predictors of IMR recurrence could be identified. Undersized ring annuloplasty changes mitral geometry acutely, exacerbates leaflet tethering, and generally fixes IMR acutely, but it does not always fix the delicate underlying chronic problem of continued left ventricular dilatation and remodeling. This may explain why pre-repair 3D valve geometry (which reflects chronic left ventricular remodeling) is highly predictive of recurrent IMR, whereas immediate post-repair 3D valve geometry (which does not completely reflect chronic left ventricular remodeling anymore) is not.


Effects of thyroid hormone replacement on glycated hemoglobin levels in non diabetic subjects with overt hypothyroidism.
Glycated hemoglobin (HbA1c) may not accurately reflect the level of glycemia in conditions of altered erythrocyte turnover. Hypothyroidism is one condition associated with sluggish erythropoesis. To assess changes in HbA1c, independent of changes in plasma glucose after initiation of thyroxine replacement in patients with overt hypothyroidism. In this prospective longitudinal study carried out in a tertiary care centre, adult non-diabetic patients with overt hypothyroidism recruited between March 2012 to August 2013 were rendered euthyroid on thyroxine. They underwent testing for hemoglobin, HbA1c, reticulocyte count, thyroxine, thyrotropin and a standard oral glucose tolerance test, both before and at 3 months after restoration to the euthyroid state. Main outcome assessed was the change in HbA1c independent of the change in glucose parameters. Thirty eight patients (35 female and 3 male) aged 37.8 ± 10.2 years with overt hypothyroidism (thyroxine 12.6 ± 13.4 ng/mL and thyrotropin -98.1 ± 63.7 µIU/mL respectively) were recruited. While HbA1c fell from 5.8 ± 0.7% to 5.6 ± 0.5% (p = 0.009) at 3 months following the correction of hypothyroidism, there were no changes in the fasting and the 2 hr post oral glucose tolerance test glucose (p = 0.67 and 0.56 respectively). The number of patients with dysglycemia diagnosed by HbA1c (i.e HbA1c ≥ 5.7%) fell from 25 (65.78%) to 17 (44.7%) after treatment (p = 0.008). There were 7 (18.4%) patients with HbA1c ≥ 6.5% at baseline, but this fell to just 4 (10.5%) (p < 0.001) after 3 months of euthyroidism. HbA1c is not a reliable diagnostic test for diabetes in the presence of hypothyroidism.


Nanoquinacrine caused apoptosis in oral cancer stem cells by disrupting the interaction between GLI1 and β catenin through activation of GSK3β.
Presences of cancer stem cells (CSCs) in a bulk of cancer cells are responsible for tumor relapse, metastasis and drug resistance in oral cancer. Due to high drug efflux, DNA repair and self-renewable capacity of CSCs, the conventional chemotherapeutic agents are unable to kill the CSCs. CSCs utilizes Hedgehog (HH-GLI), WNT-β catenin signalling for its growth and development. GSK3β negatively regulates both the pathways in CSCs. Here, we have shown that a nano-formulated bioactive small molecule inhibitor Quinacrine (NQC) caused apoptosis in oral cancer stem cells (OCSCs; isolated from different oral cancer cells and oral cancer patient derived primary cells) by down regulating WNT-β catenin and HH-GLI components through activation of GSK3β. NQC activates GSK3β in transcriptional and translational level and reduces β catenin and GLI1 as well as downstream target gene of both the pathways Cyclin D1, C-Myc. The transcription factor activity of both the pathways was also reduced by NQC treatment. GSK3β, β catenin and GLI1 interacts with each other and NQC disrupts the co-localization and interaction between β catenin and GLI1 in OCSCs in a dose dependent manner through activation of GSK3β. Thus, data suggest NQC caused OCSCs death by disrupting the crosstalk between β catenin and GLI1 by activation of GSK3β.


Signs of endothelial inflammation in human heart allografts.
The expression of leucocyte adhesion facilitating molecules on endothelia is a major stimulus for tissue inflammation and cell infiltration. Recently, specific receptor ligands have been identified that mediate cellular adhesion of lymphocytes or monocytes. In the present study, sequential changes in the expression of immune adhesion receptors (LFA-1, CD2) and their ligand molecules (ICAM-1, LFA-3) were studied in heart allografts during rejection. Consecutive endomyocardial biopsies (n = 157; d.3-1013) of 16 heart transplanted patients were studied using monoclonal antibodies and standard immunohistology. In biopsies that showed no rejection, immune adhesion molecules (ICAM-1) were weakly expressed on a few endothelial cells. ICAM-1 was induced on blood vessel and capillary endothelia during rejection. After treatment, expression declined, as did the clearance of infiltrates. Occasionally, ICAM-1 persisted on capillaries compared with class II MHC expression. Weak LFA-3 induction on endothelia was observed in acute rejection, similar to ICAM-1, however LFA-3 expression was more restricted. Infiltrating lymphocytes expressed the adhesion receptor molecules LFA-1 and/or CD2. The variability of expression of ICAM-1 and FA-3 ligand molecules was related to the inflammatory changes in the graft during acute rejection. It is likely that the induction of adhesion ligand molecules in tissue is regulated by systemic and local release of cytokines, and is an initiating step in graft infiltration. The demonstration of immune adhesion-molecule induction in heart graft rejection may also be applicable to inflammatory heart disease in viral myocarditis.


The efficacy of anterior spine exposure by an orthopedic surgeon.
This retrospective study was designed to document the incidence and types of perioperative complications that occurred with anterior spinal fusion surgery performed solely by an orthopedic spine surgeon. This study is contrasted to previous studies that document complications from anterior approaches performed by an orthopedic surgeon with the assistance of a general or a vascular surgeon. Specifically, the procedures included thoracotomies, thoracolumbar retroperitoneal, and lumbosacral approaches. Our sample consisted of 450 patients who underwent anterior spinal fusion between levels T1 and S1, from 1985 to 1997. Patient and surgery characteristics included age, sex, diagnosis, levels of fusion, blood loss, operative time, hospitalization time, complications, American Society of Anesthesiologists state, assessment of risk factors, previous surgery, and surgical approach used. Average follow-up was 41.69 months, with a minimum of 12 months and a maximum of 132 months. Our results indicated that anterior procedures performed solely by our senior orthopedic surgeon had a lower incidence of complications, less blood loss, and shorter operative time than anterior procedures performed by an orthopedic surgeon and a vascular or a general surgeon. Our findings suggest that the anterior spinal exposure is a safe approach that may be performed solely by a spinal surgeon who is knowledgeable and experienced.


Risk Factors for Maternal and Fetal Mortality in Acute Fatty Liver of Pregnancy and New Predictive Models.
Acute fatty liver of pregnancy (AFLP) is a rare but potentially life-threatening hepatic disorder that leads to considerable maternal and fetal mortality. To explore the risk factors for maternal and fetal mortality in AFLP and develop new predictive models, through this retrospective study, we analyzed the demographic characteristics, clinical symptoms, and laboratory findings of 106 patients with AFLP who were admitted to Shandong Provincial Hospital. Risk factors for maternal and fetal mortality were analyzed by univariate and multivariate logistic regression analysis. The new models based on the multivariate logistic regression analysis and the model for end-stage liver disease (MELD) were tested in AFLP. The receiver operating characteristic curve (ROC) was applied to compare the predictive efficiency, sensitivity, and specificity of the two models. Prenatal nausea (p = 0.037), prolonged prothrombin time (p = 0.003), and elevated serum creatinine (p = 0.003) were independent risk factors for maternal mortality. The ROC curve showed that the area under the curve (AUC) of the MELD was 0.948, with a sensitivity of 100% and a specificity of 83.3%. The AUC of the new model for maternal mortality was 0.926, with a sensitivity of 90% and a specificity of 94.8%. Hepatic encephalopathy (p = 0.016) and thrombocytopenia (p = 0.001) were independent risk factors for fetal mortality. Using the ROC curve, the AUC of the MELD was 0.694, yielding a sensitivity of 68.8% and a specificity of 64.4%. The AUC of the new model for fetal mortality was 0.893, yielding a sensitivity of 100% and a specificity of 73.3%. Both the new predictive model for maternal mortality and the MELD showed good predictive efficacy for maternal mortality in patients with AFLP (AUC = 0.926 and 0.948, respectively), and the new predictive model for fetal mortality was superior to the MELD in predicting fetal mortality (AUC = 0.893 and 0.694, respectively). The two new predictive models were more readily available, less expensive, and easier to implement clinically, especially in low-income countries.


DNA-damaging agents induce the RecA-independent homologous recombination functions of integrating conjugative elements of the SXT/R391 family.
Integrating conjugative elements (ICEs) of the SXT/R391 family are major contributors to the spread of antibiotic resistance genes. These elements also catalyze their own diversity by promoting inter-ICE recombination through the action of the RecA-independent homologous recombination system that they encode. Here, we report that expression of this recombination system, which consists of the single-stranded DNA annealing protein Bet and the exonuclease Exo, is induced by DNA-damaging agents via ICE-encoded transcriptional regulators. We show that the bet and exo genes are part of a large polycistronic transcript that contains many conserved ICE genes that are not involved in the main integration/excision and conjugative transfer processes. We show that although the recombination genes are highly transcribed, their translation is subject to additional strong regulatory mechanisms. We also show that an ICE-encoded putative single-stranded DNA binding protein (Ssb) limits hybrid ICE formation. Finally, a thorough in silico analysis reveals that orthologues of Bet and Exo are widely distributed in bacterial strains belonging to very distantly related bacterial species and are carried by various mobile genetic elements. Phylogenetic analyses suggest that the annealing proteins and exonucleases that compose these systems sometimes have different evolutionary origins, underscoring the strong selective pressure to maintain the functionality of these unrelated cooperating proteins.


Decreased nitric oxide products in the urine of patients undergoing cardiac surgery.
Renal vasoconstriction has been blamed as a cause of perioperative renal dysfunction after cardiac surgery. Endothelial function is a critical determinant of vascular tonus, including vasoconstriction. The objective of this study was to establish whether the release of the endothelial vasodilator nitric oxide (NO) or NO products is altered in patients undergoing surgery with cardiopulmonary bypass in 3 different clinical conditions. Observational and randomized prospective study. University hospital. Adults and pediatric patients undergoing elective cardiac surgery with cardiopulmonary bypass. Three groups of patients were studied: group 1, 10 patients undergoing elective coronary artery surgery; group 2, 20 patients undergoing elective coronary artery surgery randomized to 2 hematocrit values during cardiopulmonary bypass, high (27%) and low (23%); and group 3, 10 pediatric patients undergoing surgical repair of noncyanotic cardiac defects. NO products (NO2 + NO3) and cyclic guanosine monophosphate (cGMP) in urine were measured before, during hypo- and normothermic cardiopulmonary bypass, and 1 hour postoperatively. Filtration fraction was calculated. The glomerular filtration rate and effective renal plasma flow were measured with inulin and (131)I-hippuran clearances, respectively. Urinary alpha glutathione s-transferase was measured pre- and postoperatively in groups 1 and 3. NO products, as well as cGMP, decreased significantly during hypo- and normothermic cardiopulmonary bypass in all groups. This was not because of urine dilution or the degree of hemodilution. Age did not appear to alter this response. Filtration fraction decreased during cardiopulmonary bypass. Alpha glutathione s-transferase was normal pre-and postoperatively. Cardiac surgery with cardiopulmonary bypass is associated with a significant decrease of NO products. In the absence of kidney damage, decreased NO products could represent a physiologic response to cardiopulmonary bypass; however, endothelial dysfunction cannot be excluded.


The role of the parietal cortex in multisensory and response integration: evidence from transcranial direct current stimulation (tDCS).
The question of how the brain forms unified representations from multisensory data that are processed in distinct cortical regions is known in the literature as 'the binding problem'. In the last decade, several studies have suggested possible neural mechanisms and brain regions that might be involved in integration processes. One of the brain regions that is implicated with multisensory perception is the posterior parietal cortex (PPC). Evidence from patients with parietal lesions suggests the involvement of the PPC in coherent perception. Here, we investigated the role of the PPC in multisensory feature integration through experimental manipulation of non-invasive brain stimulation with healthy participants using transcranial direct current stimulation (tDCS). In different sessions, healthy participants received anodal, cathodal, or sham stimulation (2 mA, 20 min) over the right PPC while performing an audio-visual event-file task. The results underscore two interesting observations. Firstly, there was a significant difference in integration effects between features from different modalities in the anodal stimulation compared to sham, suggesting interference of the multisensory integration processes during the brain stimulation. And secondly, after anodal stimulation, the unattended feature became more likely to be integrated with the response feature compared to the other conditions, presumably through an interference of attentional processes. Hence, these findings emphasize the role of the right PPC in multisensory integration. Furthermore, from a methodological perspective, tDCS can be used as an experimental tool by creating a temporary, reversible disruption in cognitive processes in order to explore the mechanisms underlying cognitive functions.


Second-order statistics and 'designer' waves for violent free-surface motion around multi-column structures.
Extreme wave-structure interactions are investigated using second-order diffraction theory. The statistics of surface elevation around a multi-column structure are collected using Monte Carlo-type simulations for severe sea states. Within the footprint of a realistic four-column structure, we find that the presence of the structure can give rise to extreme crest elevations greater than twice those at the same return period in the incident wave field. Much of this extra elevation is associated with the excitation of second-order near-trapped modes. A 'designer' incident wave can be defined at each point around the structure for a given sea state as the average input wave to produce extreme crest elevations at a given return period, and we show that this wave can be simply vertically scaled to estimate the response at other return periods.


Modification of the Fiske and SubbaRow method for total phospholipid in serum.
Many of the difficulties encountered in the original Fiske and SubbaRow method for estimating serum phospholid were corrected through the use of vanadium pentoxide, a catalyst used in sample digestion, and through other minor modifications. Results obtained by the modified method agree well with those obtained by three other established phospholipid procedures. The greatly improved speed, simplicity, accuracy, and precision now makes the modified Fiske and SubbaRos method ideal for clinical or research use.


Targeting mitochondria for cardiac protection.
The critical role of mitochondria in cardiomyocyte survival and death has become an exciting field of research in cardiac biology. Indeed, it is accepted that mitochondrial dysfunction plays a crucial role in the pathogenesis of multiple cardiac diseases. Besides the obvious relevance of mitochondria in energy production, calcium homeostasis, and reactive oxygen species (ROS) production, new processes like mitochondrial fusion/fission, phosphorylation and nitrosylation modifications in mitochondrial proteins have been suggested to form part of a cast of key players in cardiac disease. This review describes currently studied drugs and compounds that target mitochondria in the scenario of cardiovascular diseases.


Successful Complete Revascularization With PCI Using Super-Low Volume of Contrast Medium in a Patient With Three-Vessel Disease Including 2 Chronic Total Occlusions With Severe Renal Dysfunction.
The most important factor for preventing contrast-induced nephropathy (CIN) during percutaneous coronary intervention (PCI) in patients with severe renal dysfunction is to minimize the contrast volume. Herein, we report a successful case of complete revascularization after 3 separate PCI procedures using a super-low volume of contrast medium in a patient with 3-vessel disease, including two chronic total occlusions (CTOs). A 70-year-old man having exertional angina despite maximal medical therapy was referred to our hospital. He had severe renal dysfunction (estimated glomerular filtration rate 19 mL/minute/1.73 m2). Coronary angiography, in which a total volume of 15 mL (over 3 injections) of contrast medium was used after hydration with normal saline, demonstrated 2 CTOs in the proximal left circumflex artery (LCX) and the proximal right coronary artery (RCA) as well as focal stenosis in the mid left descending artery (LAD). Because the patient refused coronary artery bypass grafting, we opted for revascularization with PCI, divided into 3 procedures. We made full use of microcatheter tip injection and evaluation with intravascular ultrasound and achieved complete revascularization with a total of 31 mL of contrast medium: 9 mL for RCA, 6 mL for LAD, and 16 mL for LCX, without the occurrence of CIN. Additionally, we present tips for performing PCI using super-low contrast medium.


Transformation of the gas-phase favored O-protomer of p-aminobenzoic acid to its unfavored N-protomer by ion activation in the presence of water vapor: An ion-mobility mass spectrometry study.
An ion-mobility mass spectrometry study showed that the preferred O-protonated form of p-aminobenzoic in the gas phase can be converted to the thermodynamically less favored N-protomer by in-source collision-induced ion activation during the ion transfer process from the atmospheric region to the first vacuum region if the humidity is high in the ion source. Upon the addition of water vapor to the nitrogen gas used to promote the solid analyte to the gas phase under helium-plasma ionization conditions, the intensity of the ion-mobility arrival-time peak for the N-protomer increased dramatically. Evidently, the ion-activation process in the first vacuum region is able to provide the energy required to surmount the barrier to isomerize the O-protomer to the more energetic N-protomer. The transfer of the proton attached to the carbonyl oxygen atom of the O-protomer to the amino group takes place by a water-bridge mechanism. Apparently, the postionization transformations that take place during the transmission of ions from the atmospheric-pressure ion source to the detector, via different physical compartments of low to high vacuum, play an eminent role in determining the population ratios eventually manifested at the detector.


Ozone and temperature trends associated with the 11-year solar cycle.
Evidence is presented which suggests that trends in the ozone concentration and stratospheric temperature, reported between the early 1960's and 1976, are to a large extent due to solar ultraviolet flux variability associated with the 11-year solar cycle. Radiative-convective-photochemical simulations of ozone and temperature variations have been made with a solar ultraviolet flux variability model. Results for temperatures and ozone concentrations, when compared with published data, show good agreement.


Dietary Inflammatory Index and liver status in subjects with different adiposity levels within the PREDIMED trial.
To assess the possible association between a validated Dietary Inflammatory Index (DII) and specific dietary components with suitable non-invasive markers of liver status in overweight and obese subjects within the PREDIMED study. A cross-sectional study encompassing 794 randomized overweight and obese participants (mean ± SD age: 67.0 ± 5.0 y, 55% females) from the PREDIMED (PREvención con DIeta MEDiterránea) trial was conducted. DII is a validated tool evaluating the effect of diet on six inflammatory biomarkers (IL-1b, IL-4, IL-6, IL-10, TNF-α and C-reactive protein). Furthermore, a validated 137-item food-frequency-questionnaire was used to obtain the information about the food intake. In addition, anthropometric measurements and several non-invasive markers of liver status were assessed and the Fatty Liver Index (FLI) score was calculated. A higher DII and lower adherence to Mediterranean diet (MeDiet) were associated with a higher degree of liver damage (FLI > 60) in obese as compared to overweight participants. Furthermore, the DII score was positively associated with relevant non-invasive liver markers (ALT, AST, GGT and FLI) and directly affected FLI values. Interestingly, a positive correlation was observed between liver damage (>50th percentile FLI) and nutrients and foods linked to a pro-inflammatory dietary pattern. This study reinforced the concept that obesity is associated with liver damage and revealed that the consumption of a pro-inflammatory dietary pattern might contribute to obesity and fatty liver disease features. These data suggest that a well-designed precision diet including putative anti-inflammatory components could specifically prevent and ameliorate non-alcoholic fatty liver manifestations in addition to obesity.


Elder hearing aids. Infrared listening device in a geriatric day center.
1. An infrared listening device (IRLD) is a device that changes an auditory signal into infrared light. This signal is delivered to an infrared receiver via light-emitting diodes. The signal is then converted back into auditory energy. 2. Nineteen percent of elders at the Day Care Center for the Elderly who participated in the survey expressed an interest in using an IRLD if it were made available to them. More than half of the clients in this group were successful in using the listening device. 3. The application of an IRLD can add a dimension of independence to the lives of older adults. For those individuals who are unable to operate a conventional hearing aid, an IRLD can offer the benefits of amplification in a form that may be easier to comprehend and operate.


[Erythrodermic lichen planus pemphigoides].
Lichen planus pemphigoides is a clinico-histological subtype of lichen planus in which there are bullous lesions similar to those of bullous pemphigoid. Lichen planus is included among the rare causes of erythroderma. We present a case of erythrodermic lichen planus pemphigoides in a 49-year-old female patient who satisfactorily responded to treatment with cyclosporine. A detailed physical examination and immunofluorescence study are key to the diagnosis of lichen planus pemphigoides.


Which form of environmental enrichment is most effective in rodent models of autism?
Environmental enrichment (EE) is known to produce experience-dependent changes in the brains and behaviors of rodents, and it has therefore been widely used to study neurodevelopmental disorders, including autism. Current studies show significant protocol variation, such as the presence of running wheels, number of cagemates, duration of enrichment, and the age of the animals at the beginning and end of the enrichment interventions. EE has been shown to have prominent positive effects in animal models of idiopathic and syndromic autism, but little is known about the ideal type of EE and the most efficient protocols for reversing autism spectrum disorder (ASD) behaviors modeled in rodents. This review presents evidence that social enrichment is the most effective way to rescue typical behaviors, and that variables such as onset, duration, and type of induction in the ASD model are important for EE success. Understanding which EE protocols are most beneficial for reversing ASD behaviors modeled in rodents opens up possibilities for the potential treatment of neuropsychiatric disorders characterized by behavioral deficits, such as autism.


Electrophysiological evidence for detrimental impact of a reappraisal emotion regulation strategy on subsequent cognitive control in schizophrenia.
In healthy individuals, there is evidence that effective implementation of an emotion regulation strategy has beneficial effects on temporally proximal cognitive control task performance. This effect occurs because both of these processes rely heavily on the prefrontal cortex. Individuals with schizophrenia (SZ) have impairments in both emotion regulation and cognitive control that are driven by structural and functional abnormalities of the prefrontal cortex; however, it is unknown whether emotion regulation attempts fail to benefit subsequently performed cognitive control tasks in people with SZ. The present study examined whether attempts to increase or decrease negative emotion via reappraisal have differential effects on subsequent cognitive control in a sample of outpatients diagnosed with SZ (n = 30) and demographically matched healthy controls (CN; n = 29). Participants completed a combined emotion regulation and cognitive control task in which numerical Stroop trials were presented immediately after unpleasant or neutral images that were either increased via reappraisal, decreased via reappraisal, or passively viewed. The electroencephalogram was recorded while participants performed the reappraisal-Stroop task and event related potentials (ERPs) were used to index emotion regulation effectiveness (late positive potential: LPP) and cognitive control (sustained potential: SP). Both CN and SZ evidenced higher LPP amplitude for unpleasant than neutral stimuli consistent with robust neural response to unpleasant stimuli. Although CN demonstrated neurophysiological evidence of effective use of reappraisal to increase and decrease negative emotion, SZ only showed an effective ability to increase negative emotion via reappraisal. CN displayed enhanced cognitive control following increase trials and impaired cognitive control following decrease trials, as indicated by modulation of SP amplitude. In SZ, increase instructions impaired cognitive control and decrease instructions had no effect on cognitive control. Findings suggest that emotion regulation abnormalities may play an underrecognized role in general cognitive control deficits that occur in SZ. (PsycINFO Database Record


Immunologic Effects of Maraviroc in HIV-Infected Patients with Severe CD4 Lymphopenia Starting Antiretroviral Therapy: A Sub-Study of the CADIRIS Trial.
We aimed to describe the mechanisms of immunological recovery and the effects of blocking CCR5 in patients starting ART with advanced HIV-infection. This was a sub-study of a 48 week double-blind, clinical trial where patients starting ART with CD4+ cell counts <100 cells/uL were randomized to receive maraviroc or a placebo. CD4+ and CD8+ cell maturation phenotypes, expression of PD-1 and CCR5, and activation indices were measured at weeks 0, 4, 12, 24, and 48. The reactivity of CD4+ and CD8+cells with peptides of CMV and MTb, and with Staphylococcal enterotoxin B (SEB) was assessed by intracellular expression of IFNγ, TNFα, and CD40 ligand at weeks 0, 4, and 12 of ART. Forty patients were included in the study (Maraviroc = 22; placebo = 18). Sustained increases in CD8+ cells and in proportions of CCR5+ CD4+ and CD8+ cells were observed in the maraviroc arm. Early increases in the proportions of activated (CD38+, HLA-DR+), PD-1+ CD4+, and CD8+ cells and more matured CD8+ cells, were observed in the maraviroc arm. T cell responses to CMV, MTb, and SEB did not differ by treatment arms. During antiretroviral therapy in advanced HIV infection, maraviroc retains mature, activated CCR5+ cells in circulation without impact on CD4+ T cell recovery or T cell reactivity to antigen or superantigen.


Retinitis Pigmentosa and Other Dystrophies.
Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal degenerations characterized by progressive degeneration of rod and cone cells that affects predominantly peripheral visual fields. Macular edema may cause additional central visual acuity decrease. Cystoid macular edema (CME) is one of the few treatable causes of visual loss in RP. The prevalence of CME in RP has been found to be between 10 and 20% on fluorescein angiography-based studies, and as high as 49% on reports based on optical coherence tomography. Macular edema can manifest at any stage of the disease and may be unilateral or bilateral. It can be found in any genetic form, but is more often associated with RP caused by CRB1 mutations. The origin of macular edema in RP patients still remains poorly understood. Some mechanisms have been suggested, including antiretinal antibodies (retinal, carbonic anhydrase, and enolase antibodies), vitreous traction, retinal pigment epithelium dysfunction, and Müller cell edema. There is no gold standard therapeutic strategy. Drug therapy is the primary treatment. Systemic carbonic anhydrase inhibitors, such as oral acetazolamide or topical dorzolamide, are still the mainstays of initial therapy. If CME is refractory to acetazolamide, intravitreal corticosteroid injections may be a therapeutic option. However, antivascular endothelium growth factor injections have limited effect and should be avoided. Vitrectomy has also been evaluated, but its exact role remains to be determined. The benefits of these therapies are variable among patients. The establishment of therapeutic approaches is limited by our poor understanding of the pathophysiology of CME in patients with RP. Autoimmune retinopathies (AIRs) are a group of rare diseases characterized by acute or subacute progressive vision loss and are thought to be mediated by autoantibodies specific to retinal antigens. The AIRs encompass paraneoplastic syndromes, such as cancer-associated retinopathy and melanoma-associated retinopathy, and a larger group of AIRs that have similar clinical and immunological findings but without underlying malignancy. These diseases may also be complicated by macular edema. RP is one of the most common forms of inherited retinal degeneration. It displays extensive clinical and genetic variations and leads to progressive blindness with variable onset.


Fluvastatin enhances receptor-stimulated intracellular Ca2+ release in human keratinocytes.
We analyzed the effect of isoprenoid depletion by fluvastatin on bradykinin (BK)- and epidermal growth factor (EGF)-mediated Ca2+ mobilization and prostaglandin E2 production, in the human keratinocyte cell line HaCaT. BK and EGF stimulated Ca2+ mobilization in an agonist-dependent manner. The synthesis of prostaglandin E2 paralleled the level of Ca2+ mobilization induced by BK and EGF. Treatment with fluvastatin increased the EGF-promoted but not the BK-promoted Ca2+ mobilization and prostaglandin E2 production in Ca(2+)-containing medium. In the absence of extracellular Ca2+, fluvastatin treatment led to an increase in intracellular Ca2+ release by both agonists. This effect was abolished by depleting the intracellular pool of Ca2+ with thapsigargin. Our findings showed that the intracellular Ca2+ release was dependent on the metabolism of mevalonate and that the Ca2+ mobilization modulated prostaglandin E2 synthesis in human keratinocytes.


A major phosphoprotein of cells infected with pseudorabies virus is phosphorylated by cellular casein kinase II.
Endogenous protein phosphorylation was studied in extracts of hamster fibroblasts infected with pseudorabies virus. The major phosphorylation was detected quite late in infection and involved an acidic protein of Mr 62,000. It was catalysed by an enzyme activity with the properties of cellular casein kinase II. Two-dimensional gel analysis was used to demonstrate that this same protein was also phosphorylated in vivo. The phosphoprotein was detected in mature virions and is most likely viral in origin.


Prevent the blue, be true to you: Authenticity buffers the negative impact of loneliness on alcohol-related problems, physical symptoms, and depressive and anxiety symptoms.
This study investigated authenticity as a moderator of the association between loneliness and depressive symptoms, anxiety, physical symptoms, and alcohol-related problems. It was expected that loneliness and health outcomes would be negatively related and that relationship would be weaker among those higher in authenticity. Significant interactions emerged between authenticity and loneliness for each outcome such that authenticity mitigated the relationship between higher loneliness and negative health outcomes. Results suggest that authenticity may be an underutilized resource for lonely individuals and warrants future investigation. The potential implications are diverse and could be incorporated in college adjustment and health promotion programs.


Prevalence and molecular characterisation of Acanthocephala in pinnipedia of the North and Baltic Seas.
Harbour seals (Phoca vitulina) and grey seals (Halichoerus grypus) are final hosts of acanthocephalans in the German North and Baltic Seas. Parasitic infections in seals can cause pathological changes, which may result in deteriorated health of the host. Common gastrointestinal parasites of harbour and grey seals are acanthocephalans and a number of 275 of 2460 (11.2%) investigated seals from 1996 to 2013 were infected with Corynosoma spp. (Acanthocephala, Polymorphidae). The prevalence showed a wave-like pattern: it increased from 1.2% and 0.4% in 1996 and 1997, respectively, to 23.9% during the second phocine distemper epizootic in 2002 and decreased to 6.2% in 2004. In 2005, prevalence peaked again with 25.0% followed by a decrease to 9.3% in 2009 and an increase to 38.5% in 2012. Statistical analysis revealed that harbour seals originating from the North Sea showed a higher prevalence than grey seals, whereas no significant difference between grey and harbour seals from the Baltic Sea was observed. Furthermore, juvenile pinnipedia from the North Sea were significantly less infected with Corynosoma spp. than seals older than seven month. Molecular species identification as well as phylogenetic relationship analysis among the detected Corynosoma species were achieved by sequencing and comparisons of the ribosomal ITS1-5.8S-ITS2-complex and cytochrome-c-oxidase I gene. Molecular analysis resulted in a newly arranged distribution of Acanthocephala in the North Sea as in contrast to previous studies, C. strumosum could not be confirmed as predominant species. Instead, C. magdaleni and a C. magdaleni isolate (isolate Pv1NS) with an atypical number of longitudinal rows of hooks at the proboscis were detected. Furthermore, morphological and molecular analyses indicate the possible finding of a cryptic species (Candidatus Corynosoma nortmeri sp. nov.).


Stenting for coronary artery spasm.
We evaluated coronary stenting in nine patients with clinically severe, angiographically documented spasm refractory to aggressive pharmacologic management. No patient subsequently developed unstable ischemia requiring hospitalization as a consequence of recurrent spasm within the stent. Mechanisms of therapeutic failure included both persistent spasm and spasm in a different artery in one patient. Restenosis occurred in three patients who subsequently underwent repeat revascularization. In the rare, carefully selected patient, stents may represent an adjunct in the management of focal coronary artery spasm, although currently medical therapy remains the standard initial approach.


Basis set superposition error in MP2 and density-functional theory: a case of methane-nitric oxide association.
A systematic study of basis set superposition error (BSSE) behavior in H(3)C-H[ellipsis (horizontal)][NO] complexes for both -H...N- and -H...O- orientations were carried out using MP2 and density-functional theory with Pople's [6-31G(d,p),6-311++G(nd,nd), where n=1,2,3, and 6-311++G(3df,3pd)] and Dunning's augmented correlation consistent basis sets [aug-cc-pVXZ (X=D and T)]. Corrected and uncorrected counterpoise potential-energy surfaces (PESs) were explored and differences obtained between them indicate that reliable optimizations of these molecular interactions must be carried out in a PES free of BSSE, even in the case of large basis sets and popularly used functionals such as B3LYP. Although all basis used could be always considered within a margin of approximation for representing molecular orbitals and show important values of BSSE, 6-311++G(2d,2p) basis set shows the best results in uncorrected PES with respect to the corrected ones. B3LYP functional produces erratic results: complexes appear repulsive and the intermolecular distances are always large, evidencing the lack of a correct dispersive forces treatment in the original parameterization. According to the MP2 results, the -H...N- interactions appear as slightly more stable than those of the -H...O- orientation.


Application of Low Tube Voltage 70 kV and Advanced Modeled Iterative Reconstruction in the Third-generation Dual-source CT to CT Colonography.
Objective To explore the feasibility of reducing radiation dose of CT colonography (CTC) while preserving image quality using the third-generation dual-source CT at 70 kV tube voltage with advanced modeled iterative reconstruction (ADMIRE). Methods This prospective study consecutively included 53 patients. All patients underwent CTC at 120 kV in supine position with filtered back projection reconstruction and at 70 kV in prone position with ADMIRE with the same scan range. Radiation dose and image quality were compared between these two protocols. Results CT dose index volume,dose-length product,and effective dose of 70 kV were (1.47±0.23)mGy,(68.85±13.82)mGy·cm,and (1.03±0.21)mSv,respectively,which were significantly lower than 120 kV mode [(2.96±0.61)mGy (t=25.356,P=0.000),(136.97±32.77)mGy·cm (t=22.246,P=0.000),and (2.05±0.49)mSv (t=22.293,P=0.000)]. Signal to noise ratio of 70 kV with ADMIRE was 3.60±0.58,which was obviously higher than that of 120 kV as 2.34±0.47 (t=-18.036,P=0.000). Noise of 70 kV with ADMIRE was (11.81±1.93)HU,which was obviously lower than that of 120 kV as (14.39±2.57)HU (t=7.856,P=0.000). The κ value of two radiologists' overall subjective image score was 0.843 (P=0.000). For 2D images,the noise score of 70 kV with ADMIRE was significantly lower (Z=325.000,P=0.000) and the overall image quality was significantly higher (Z=78.000,P=0.001) compared with 120 kV;however,the sharpness had no significant difference. All scores ranged from 4 to 5. For 3D virtual endoscopy,the overall image quality of 70 kV with ADMIRE and 120 kV was not significantly different (Z=4.000,P=0.059),and all scores ranged from 4 to 5. Conclusion CTC at 70 kV tube voltage combined with ADMIRE can remarkably reduce the radiation dose while maintaining imaging quality than 120 kV at third-generation dual-source CT.


Oral vaccination with salmonella simultaneously expressing Yersinia pestis F1 and V antigens protects against bubonic and pneumonic plague.
The gut provides a large area for immunization enabling the development of mucosal and systemic Ab responses. To test whether the protective Ags to Yersinia pestis can be orally delivered, the Y. pestis caf1 operon, encoding the F1-Ag and virulence Ag (V-Ag) were cloned into attenuated Salmonella vaccine vectors. F1-Ag expression was controlled under a promoter from the caf1 operon; two different promoters (P), PtetA in pV3, PphoP in pV4, as well as a chimera of the two in pV55 were tested. F1-Ag was amply expressed; the chimera in the pV55 showed the best V-Ag expression. Oral immunization with Salmonella-F1 elicited elevated secretory (S)-IgA and serum IgG titers, and Salmonella-V-Ag(pV55) elicited much greater S-IgA and serum IgG Ab titers than Salmonella-V-Ag(pV3) or Salmonella-V-Ag(pV4). Hence, a new Salmonella vaccine, Salmonella-(F1+V)Ags, made with a single plasmid containing the caf1 operon and the chimeric promoter for V-Ag allowed the simultaneous expression of F1 capsule and V-Ag. Salmonella-(F1+V)Ags elicited elevated Ab titers similar to their monotypic derivatives. For bubonic plague, mice dosed with Salmonella-(F1+V)Ags and Salmonella-F1-Ag showed similar efficacy (>83% survival) against approximately 1000 LD(50) Y. pestis. For pneumonic plague, immunized mice required immunity to both F1- and V-Ags because the mice vaccinated with Salmonella-(F1+V)Ags protected against 100 LD(50) Y. pestis. These results show that a single Salmonella vaccine can deliver both F1- and V-Ags to effect both systemic and mucosal immune protection against Y. pestis.


Skip metastasis in osteosarcoma.
Skip metastasis is rare in high-grade osteosarcoma and indicates a very poor prognosis. The authors describe two patients who had high-grade osteosarcoma and skip metastasis. MRI detected the skip lesion in both patients, and both lesions were confirmed by histology. The patients were treated with adjuvant chemotherapy and radical surgical resection. Both are alive and free of disease 3 and 6 years from diagnosis.


Sphenostylis stenocarpa (ex. A. Rich.) Harms., a Fading Genetic Resource in a Changing Climate: Prerequisite for Conservation and Sustainability.
The southeastern part of Nigeria is one of the major hotspots of useful plant genetic resources. These endemic species are associated with a rich indigenous knowledge and cultural diversity in relation to their use and conservation. Sphenostylis stenocarpa (ex. A. Rich.) Harms., (African Yam Bean (AYB)), is one such crop within the family of Fabaceae. Its nutritional and eco-friendly characteristics have value in ameliorating malnutrition, hidden hunger and environmental degradation inherent in resource-poor rural and semi-rural communities throughout Africa. However, lack of information from the custodians of this crop is limiting its sustainable development. Therefore, ethnobotanical surveys on the diversity, uses, and constraints limiting the cultivation and use of the crop in southeastern Nigeria were carried out. Five-hundred respondents were randomly selected and data collected through oral interviews and focused group discussion (FGD). Semi-structured questionnaires (SSQ) were also used to elicit information from a spectrum of AYB users comprising community leaders, farmers, market women and consumers in five States. Results showed that the majority of the respondents lacked formal education and were of the age group of 40-50 years, while the female gender dominated with limited access to land and extension officers. Seed coat colour largely determined utilization. Long cooking time, requirement for staking materials, aging of farmers and low market demand were among the major constraints limiting further cultivation and utilization of AYB. In-situ conservation was by hanging dried fruits by the fireside, beside the house, storing in earthenware, calabash gourds, cans and bottles. It is concluded that there is urgent need to scale up conservation through robust linkages between contemporary scientific domains and indigenous peoples in order to harness and incorporate the rich indigenous knowledge in local communities for enhanced scientific knowledge, biodiversity conservation and its sustainable utilization for food security.


A model for integrating independent physicians into accountable care organizations.
The Affordable Care Act encourages the formation of accountable care organizations as a new part of Medicare. Pending forthcoming federal regulations, though, it is unclear precisely how these ACOs will be structured. Although large integrated care systems that directly employ physicians may be most likely to evolve into ACOs, few such integrated systems exist in the United States. This paper demonstrates how Advocate Physician Partners in Illinois could serve as a model for a new kind of accountable care organization, by demonstrating how to organize physicians into partnerships with hospitals to improve care, cut costs, and be held accountable for the results. The partnership has signed its first commercial ACO contract effective January 1, 2011, with the largest insurer in Illinois, Blue Cross Blue Shield. Other commercial contracts are expected to follow. In a health care system still dominated by small, independent physician practices, this may constitute a more viable way to push the broader health care system toward accountable care.


Visual recognition of age class and preference for infantile features: implications for species-specific vs universal cognitive traits in primates.
Despite not knowing the exact age of individuals, humans can estimate their rough age using age-related physical features. Nonhuman primates show some age-related physical features; however, the cognitive traits underlying their recognition of age class have not been revealed. Here, we tested the ability of two species of Old World monkey, Japanese macaques (JM) and Campbell's monkeys (CM), to spontaneously discriminate age classes using visual paired comparison (VPC) tasks based on the two distinct categories of infant and adult images. First, VPCs were conducted in JM subjects using conspecific JM stimuli. When analyzing the side of the first look, JM subjects significantly looked more often at novel images. Based on analyses of total looking durations, JM subjects looked at a novel infant image longer than they looked at a familiar adult image, suggesting the ability to spontaneously discriminate between the two age classes and a preference for infant over adult images. Next, VPCs were tested in CM subjects using heterospecific JM stimuli. CM subjects showed no difference in the side of their first look, but looked at infant JM images longer than they looked at adult images; the fact that CMs were totally naïve to JMs suggested that the attractiveness of infant images transcends species differences. This is the first report of visual age class recognition and a preference for infant over adult images in nonhuman primates. Our results suggest not only species-specific processing for age class recognition but also the evolutionary origins of the instinctive human perception of baby cuteness schema, proposed by the ethologist Konrad Lorenz.


[Vapors: a historical approach].
This paper deals with the historical problem of "les Vapeurs". The word was largely used in ancient times, especially during the 18th century. The philosophical background goes back as far as Plato and Aristotle, but the turning point of the concept was given by a french scientist: B. Pomme. According his hypothesis "the nerves were shrinking because of drying" and the treatment had to be long, prolonged bathing. After being very fashionable, the treatment became obsolete and B. Pomme retired in his home city of Arles. This history of "les vapeurs" is of a great interest, because it shows how scientists are being easily abused by intellectual conceptions and words, only "words without meaning".


Mitigation of soil contaminated with diesel fuel using bioelectrokinetics.
This study investigated the effectiveness of bioelectrokinetics in rehabilitating a silty clayey sand contaminated with diesel fuel using three novel bacterial strains; Acinetobacter calcoaceticus, Sphingobacterium multivorum, and Sinorhizobium, isolated form agriculture land. Three electrokinetic bioremediation cells were used to conduct the tests and a novel electrode configuration technique was used to stabilize pH and water content in the soil specimen. Solar photovoltaic panels were used to generate sustainable energy for the process. The tests were carried out in outdoors for 55 days. Applied voltage, current passing through the electrokinetic cell, and the temperature of the soil specimen were recorded periodically during the test. The pH, water content, and diesel concentration were determined at the end of the tests. Over the test period, the voltage typically increased from zero before sunrise, remained relatively stabilized for about 4 h, and then started to decrease and dropped to zero by sunset. The temperatures in the cells were found to be 5-7 °C higher than the ambient temperature. The innovative electrode configuration succeeded in keeping the pH of soil to remain the same and thereby prevented the development of a pH gradient in the soil, an important development for survival of the bacteria. The diesel degradation in the soil after bioelectrokinetics were 20-30%, compared to 10-12% in the control test. The study was successful in developing environmentally friendly technology employing novel bacterial strains to degrade diesel fuel and utilizing solar panel to produce renewable energy for bioelectrokinetic during the winter season.


Operationalizing legal rights in end-of- life decision-making: A qualitative study.
For a patient's legal right to make end-of-life treatment decisions to be respected, health care practitioners, patients and their substitute decision-makers must know what rights exist and how to assert them (or support others to assert them). Yet very little is known about what enhances or obstructs the operationalization of legal rights from the perspective of patients, family members and substitute decision-makers. To explore barriers and facilitators to the operationalization of rights in end-of-life decision-making from the perspectives of terminally-ill patients and family members and substitute decision-makers of terminally ill patients in Australia. Semi-structured interviews (face to face and telephone) with patients, family or substitute decision-makers experienced in end-of-life decision-making completed between November 2016 and October 2017. A thematic content analysis of interview transcripts. Purposive sampling across three Australian states provided 16 terminally-ill patients and 33 family and/or substitute decision-makers. Barriers and facilitators emerged across three overlapping domains: systemic factors; individual factors, influenced by personal characteristics and decision-making approach; and communication and information. Health care practitioners play a key role in either supporting or excluding patients, family and substitute decision-makers in decision-making. In addition to enhancing legal literacy of community members and health practitioners about end-of-life decision-making, support such as open communication, advocacy and help with engaging with advanced care planning is needed to facilitate people operationalizing their legal rights, powers and duties. Palliative care and other support services should be more widely available to people both within and outside health systems.


[Cooperative program for domestic accidents of children in the department of Doubs. Epidemiological aspects].
This work presents the results of a survey carried out among 818 families in the department of the Doubs. Each family had a child between one and 6 years of age. Its aim was to come as close as possible to exploring morbidity in accidents by questioning parents about the accidents which took place a month before the investigation, and to study the influence of certain psychosocial factors on this pathology, for example the attitude of parents confronted with risks. The annual accident morbidity rate was 1,056 accidents per 1,000 children. In other words, each child has, on the average, one accident per year. Even though no significant difference between town and country has been noted, serious accidents occurred more frequently in rural areas. This may be explained by the way dangerous products are stored (medicines, household cleaning and agricultural products), looser parental surveillance (predominance at games outside home), as well as the fact that children are more often in the kitchen when they are indoors, which is potentially the most dangerous room. Classical notions of disturbing events occurring prior to the accident (divorce, moving, a.s.o.) and children who are "repeat offenders" have also been noticed. The examination of parental attitude in dealing with the possibility of accidents (instructive, lax or repressive) did not allow us to demonstrate in any significant way the influence of these attitudes on accidental morbidity. On the other hand the so-called "instructive" parents are the ones who best put away the poisonous products. There is therefore, an encouraging connection between attitude and behavior.


Right ventricular resynchronization in a patient with repaired tetralogy of Fallot and severe ventricular dysfunction.
Right ventricular (RV) resynchronization therapy (CRT) with stimulation electrode implantation in the latest activation area guided by a high-density electroanatomic activation map was successfully performed in a patient with repaired tetralogy of Fallot (rToF), severe pulmonary regurgitation (PR), and severe dysfunction and dilatation of the right ventricle. An improvement in his clinical condition and intraventricular synchrony was achieved. There is a mechanical-electrical interaction in the right ventricle of patients with rToF; therefore, RV CRT in selected cases may be beneficial. Electroanatomic activation mapping can help achieve maximum clinical benefit by identifying the optimal stimulation site.


Pulsed transcranial photobiomodulation generates distinct beneficial neurocognitive effects compared with continuous wave transcranial light.
Previous research has demonstrated the beneficial effect brought by transcranial photobiomodulation (tPBM). The present study is a further investigation of pulsed transcranial light delivery, from the perspective of wavelength, operation mode, and pulse frequency. A total of 56 healthy young adults (28 males and 28 females) were included in this randomized, sham-controlled experimental study. The wavelength of tPBM was 660 nm and 850 nm, and under each wavelength, subjects were randomly assigned to one of the following four treatments: (1) sham control; (2) continuous-wave (CW) tPBM; (3) pulsed-wave (PW) tPBM (40 Hz); and (4) PW tPBM (100 Hz). The tPBM duration was 8 min and the mean power density was fixed at 250 mW/cm2. Karolinska Sleepiness Scale (KSS) questionnaire, psychomotor vigilance task (PVT), and delayed match-to-sample (DMS) task were completed by subjects before and after the intervention to test whether PW tPBM produced distinct beneficial effects with measures of sleepiness, attention, and memory. 32-channel electroencephalography (EEG) signals were obtained from subjects before, during and after receiving tPBM or sham intervention. Paired sample T test showed that the KSS score, the number of correct responses of PVT, and DMS rate correct score (RCS) of PW tPBM groups improved significantly after intervention (p < 0.05). With regard to EEG analysis, paired one-way repeated ANOVA test showed that during the intervention of PW tPBM, the average power within the Gamma band was higher than the baseline (p < 0.05). Our study presented that PW tPBM could generate better beneficial cognitive effects and change brain electrical activity under certain circumstances.


Strigolactones affect phosphorus acquisition strategies in tomato plants.
Strigolactones (SLs) are plant hormones that modulate morphological, physiological and biochemical changes as part of the acclimation strategies to phosphorus (P) deficiency, but an in-depth description of their effects on tomato P-acquisition strategies under P shortage is missing. Therefore, in this study, we investigate how SLs impact on root exudation and P uptake, in qualitative and quantitative terms over time, in wild-type and SL-depleted tomato plants grown with or without P. Under P shortage, SL-depleted plants were unable to efficiently activate most mechanisms associated with the P starvation response (PSR), except for the up-regulation of P transporters and increased activity of P-solubilizing enzymes. The reduced SL biosynthesis had negative effects also under normal P provision, because plants over-activated high-affinity transporters and enzymatic activities (phytase, acidic phosphatase) to sustain elevated P uptake, at great carbon and nitrogen costs. A shift in the onset of PSR was also highlighted in these plants. We conclude that SLs are master kinetic regulators of the PSR in tomato and that their defective synthesis might lead both to suboptimal nutritional outcomes under P depletion and an unbalanced control of P uptake when P is available.


Salivary gland uptake of 67Ga-citrate following radiation therapy.
Radiogallium uptake in the salivary glands is strongly correlated with prior therapeutic radiation which includes the cervical region. Fifteen of 17 patients with increased salivary gland uptake had such a history. An easily identified characteristic pattern of symmetric localization of 67Ga occurs in the parotid and submandibular regions in these patients. This pattern must not be mistaken for recurrent tumor in the cervical region.


Lineage tracing of human B cells reveals the in vivo landscape of human antibody class switching.
Antibody class switching is a feature of the adaptive immune system which enables diversification of the effector properties of antibodies. Even though class switching is essential for mounting a protective response to pathogens, the in vivo patterns and lineage characteristics of antibody class switching have remained uncharacterized in living humans. Here we comprehensively measured the landscape of antibody class switching in human adult twins using antibody repertoire sequencing. The map identifies how antibodies of every class are created and delineates a two-tiered hierarchy of class switch pathways. Using somatic hypermutations as a molecular clock, we discovered that closely related B cells often switch to the same class, but lose coherence as somatic mutations accumulate. Such correlations between closely related cells exist when purified B cells class switch in vitro, suggesting that class switch recombination is directed toward specific isotypes by a cell-autonomous imprinted state.


Secreted phospholipase A2 of Clonorchis sinensis activates hepatic stellate cells through a pathway involving JNK signalling.
Secreted phospholipase A2 (sPLA2) is a protein secreted by Clonorchis sinensis and is a component of excretory and secretory products (CsESPs). Phospholipase A2 is well known for its role in liver fibrosis and inhibition of tumour cells. The JNK signalling pathway is involved in hepatic stellate cells (HSCs) activation. Blocking JNK activity with SP600125 inhibits HSCs activation. In a previous study, the protein CssPLA2 was expressed in insoluble inclusion bodies. Therefore, it's necessary to express CssPLA2 in water-soluble form and determine whether the enzymatic activity of CssPLA2 or cell signalling pathways is involved in liver fibrosis caused by clonorchiasis. Balb/C mice were given an abdominal injection of MBP-CssPLA2. Liver sections with HE and Masson staining were observed to detect accumulation of collagen. Western blot of mouse liver was done to detect the activation of JNK signalling pathway. In vitro, HSCs were incubated with MBP-CssPLA2 to detect the activation of HSCs as well as the activation of JNK signalling pathway. The mutant of MBP-CssPLA2 without enzymatic activity was constructed and was also incubated with HSCs to check whether activation of the HSCs was related to the enzymatic activity of MBP-CssPLA2. The recombinant protein MBP-CssPLA2 was expressed soluble and of good enzymatic activity. A mutant of CssPLA2, without enzymatic activity, was also constructed. In vivo liver sections of Balb/C mice that were given an abdominal injection of 50 μg/ml MBP-CssPLA2 showed an obvious accumulation of collagen and a clear band of P-JNK1 could be seen by western blot of the liver tissue. In vitro, MBP-CssPLA2, as well as the mutant, was incubated with HSCs and it was proved that activation of HSCs was related to activation of the JNK signalling pathway instead of the enzymatic activity of MBP-CssPLA2. Activation of HSCs by CssPLA2 is related to the activation of the JNK signalling pathway instead of the enzymatic activity of CssPLA2. This finding could provide a promising treatment strategy to interrupt the process of liver fibrosis caused by clonorchiasis.


Electronically Rich N-Substituted Tetrahydroisoquinoline 3-Carboxylic Acid Esters: Concise Synthesis and Conformational Studies.
Recent work in our laboratory has shown that the highly substituted, electronically rich 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (THIQ3CA) scaffold is a key building block for a novel class of promising anticoagulants (Al-Horani et al. J. Med. Chem.2011, 54, 6125-6138). The synthesis of THIQ3CA analogs, especially containing specific, electronically rich substituents, has been a challenge and essentially no efficient methods have been reported in the literature. We describe three complementary, glycine donor-based strategies for high yielding synthesis of highly substituted, electronically rich THIQ3CA esters. Three glycine donors studied herein include hydantoin 1, (±)-Boc-α-phosphonoglycine trimethyl ester 2 and (±)-Z-α-phosphonoglycine trimethyl ester 3. Although the synthesis of THIQ3CA analogs could be achieved using either of the three, an optimal, high yielding approach for the desired THIQ3CA esters was best achieved using 3 in three mild, efficient steps. Using this approach, a focused library of advanced N-arylacyl, N-arylalkyl, and bis-THIQ3CA analogs was synthesized. Variable temperature and solvent-dependent NMR chemical shift studies indicated the presence of two major conformational rotamers in 3:1 proportion for N-arylacyl-THIQ3CA analogs, which were separated by a high kinetic barrier of ~17 kcal/mol. In contrast, N-arylalkyl and bis-THIQ3CA variants displayed no rotamerism, which implicates restricted rotation around the amide bond as the origin for high-barrier conformational interconversion. This phenomenon is of major significance because structure-based drug design typically utilizes only one conformation. Overall, the work presents fundamental studies on the synthesis and conformational properties of highly substituted, electronically rich THIQ3CA analogs.