Magnetic resonance temperature imaging.
Continuous, real-time, 3D temperature mapping during a hyperthermic procedure may provide (i) enhanced safety by visualizing temperature maps in and around the treated region, (ii) improved efficiency by adapting local energy deposition with feedback coupling algorithms and (iii) therapy end-points based on the accumulated thermal dose. Non-invasive mapping of temperature changes can be achieved with MRI and may be based on temperature dependent MRI parameters. The excellent linearity of the temperature dependency of the proton resonance frequency (PRF) and its near-independence with respect to tissue type make the PRF-based methods the preferred choice for many applications, in particular at mid- to-high field strength (> or =0.5 T). The PRF methods employ RF-spoiled gradient echo imaging methods and incorporate fat suppression techniques for most organs. A standard deviation of less than 1 degrees C, for a temporal resolution below 1 s and a spatial resolution of approximately 2 mm is feasible for immobile tissues. Special attention is paid to methods for reducing artifacts in MR temperature mapping caused by intra-scan and inter-scan motion and motion and temperature-induced susceptibility effects in mobile tissues. Real-time image processing and visualization techniques, together with accelerated MRI acquisition techniques, are described because of their potential for therapy guidance.


Application of microwave superheating for the synthesis of TiO2 rods.
A simple microwave irradiation method for the large-scale synthesis of submicrometer-sized TiO2 rods at normal atmospheric pressure and the boiling temperature of the solvent is demonstrated. It is emphasized that only 1-3 min of microwave irradiation is adequate to react tetra-isopropyl orthotitanate with ethylene glycol to produce rods of titanium glycolate [TG] with diameters of approximately 0.4 microm and lengths up to 5 microm. The as-formed TG rods, followed by calcination under air for 2 h, fabricated anatase (500 degrees C) and rutile (900 degrees C) titania without changing their rod-shaped morphology. The crystallinity, structure, morphology, and thermal analysis are carried out by several techniques. A mechanism based on microwave superheating phenomena is presented with the support of previous reports and several control experiments.


[Gamma-2-free amalgams: effect of technic (trituration) on physical properties].
The goal of investigation was to find the physical data, viz. changes of volume, pressure resistance after 1 and 24 hours, creep value of gamma-2-free amalgams (dispersion type), to compare the values to each other and to those of conventional amalgams. On the whole, gamma-2-free amalgams are superior to the conventional products. The pressure resistance after 1 hour is considerably higher, and the creep values are significantly lower. Furthermore, it could be proven that a mixing unit of high RPM was able to improve the quality still more. The best results were found with Amalcap non-gamma 2 and Dispersalloy evenly, both premeasured in capsules and triturated in the Silamat unit. Similar data were found with Dispersalloy tablets, mixed in the Diomat II unit at 3000 RPM. Before clinical long-range examinations can be obtained, judgment of quality cannot be passed.


Direct-Access Online Care for the Management of Atopic Dermatitis: A Randomized Clinical Trial Examining Patient Quality of Life.
Atopic dermatitis (AD) is a chronic disease requiring regular follow-up. To increase access to dermatological care, online management of AD is being studied. However, a critical knowledge gap exists in determining AD patients' quality of life in direct-to-patient online models. In this study, we examined quality of life in AD patients managed through a direct-access online model. We randomized 156 patients to receiving care through a direct-access online platform or in person. Patients were seen for six visits over 12 months. At each visit, the patients completed Dermatology Life Quality Index/Children's Dermatology Life Quality Index (DLQI/CDLQI), and Short Form (SF-12). Between baseline and 12 months, the mean (standard deviation, SD) within-group difference in DLQI score in the online group was 4.1 (±2.3); for the in-person group, the within-group difference was 4.8 (±2.7). The mean (SD) within-group difference in CDLQI score in the online group was 4.7 (±2.8); for the in-person group, the within-group difference was 4.9 (±3.1). The mean (SD) within-group difference in physical component score (PCS) and mental component score (MCS) SF-12 scores in the online group was 6.5 (±3.8) and 8.6 (±4.3); for the in-person group, it was 6.8 (±3.2) and 9.1(±3.8), respectively. The difference in the change in DLQI, CDLQI, SF-12 PCS, and SF-12 MCS scores between the two groups was 0.72 (95% confidence interval [90% CI], -0.97 to 2.41), 0.23 (90% CI, -2.21 to 2.67), 0.34 (90% CI, -1.16 to 1.84), and 0.51 (90% CI, -1.11 to 2.13), respectively. All differences were contained within their equivalence margins. Adult and pediatric AD patients receiving direct-access online care had equivalent quality of life outcomes as those see in person. The direct-access online model has the potential to increase access to care for patients with chronic skin diseases.


Polymer catenanes via a supramolecularly templated ATRP initiator.
Synthesis of polymer catenanes via a living radical polymerization and supramolecular template approach are demonstrated. The ring closure was performed via atom transfer radical cross coupling (ATRC) to obtain polymer catenanes from the linear polymer metal complex precursor.


Cell proliferation indexes: a biomarker in solid tumors.
Clinical studies have shown that carcinogenesis is linked to the development of proliferative abnormalities. Proliferative activity has been found to have prognostic significance in a variety of human tumors. Because proliferative abnormalities can precede the occurrence of morphological abnormalities, their measurement could also serve as useful biomarkers for chemoprevention trials. The variety of techniques for measuring cell proliferation in routine sections include mitosis counting, AgNORs, DNA precursor uptake (bromodeoxyuridine), and immunohistochemical detection of cell cycle proteins (PCNA, Ki-67/MIB-1). It is essential that the virtues and limitations of these methods be examined to ensure collection of meaningful clinical data.


X-linked mental retardation, microcephaly, and growth delay associated with hereditary bullous dystrophy macular type: report of a second family.
We report on 2 patients with mental retardation and bullous dystrophy, macular type. The observation of the condition in a male and his maternal uncle is consistent with recessive X-linkage. Due to the rarity of the condition, nosologic definition was difficult before the birth of the propositus. The clinical picture in the two patients described, characterized by mental retardation, dwarfism, microcephaly, alopecia, bullous dystrophy macular type, hypogenitalism, is very much like the one observed in the patients, all males, belonging to the only other family reported to date. The recent localization of the bullous dystrophy gene in the Xq24-qter segment opens the possibility of prenatal diagnosis.


Linezolid for the treatment of children with bacteremia or nosocomial pneumonia caused by resistant gram-positive bacterial pathogens.
Nosocomial infections, particularly hospital-acquired pneumonia (HAP) and bacteremia, are an increasing concern in pediatric hospitals and pediatric intensive care units. Gram-positive pathogens are a leading cause of these infections in children. Linezolid is well-tolerated and as effective as vancomycin in the treatment of these infections in adults. To evaluate the clinical effectiveness and safety of iv/oral linezolid and iv vancomycin in children with resistant Gram-positive HAP or bacteremia. Hospitalized children <12 years of age were randomized 2:1 to linezolid or vancomycin. Patients received linezolid 10 mg/kg iv every 8 h with the option to change treatment to oral linezolid suspension 10 mg/kg every 8 h or iv vancomycin 10 to 15 mg/kg every 6 to 24 h. Clinical response was evaluated at follow-up. Results from an analysis of patients with HAP or bacteremia are presented. Thirty-nine patients (linezolid, 23; vancomycin, 16) with HAP and 113 patients with bacteremia (linezolid, 81; vancomycin, 32) were included in the intent-to-treat group. Clinical cure rates for clinically evaluable patients with HAP did not differ between treatment groups (linezolid, 90.0% and vancomycin, 100%; P = 0.305). No significant difference was seen in clinical cure rates in the clinically evaluable population between the linezolid and vancomycin groups for patients with catheter-related bacteremia (84.8 and 80.0%, respectively; P = 0.716) or patients with bacteremia of unknown source (79.2 and 69.2%, respectively; P = 0.501). In this subset fewer linezolid-treated patients had drug-related adverse events than did vancomycin-treated patients (19.4% vs. 28.3%; P = 0.230). Similar percentages of patients with laboratory abnormalities, including selected hematologic parameters, were seen in both treatment groups. Intravenous/oral linezolid was well-tolerated and as effective as vancomycin in treating children with resistant Gram-positive HAP or bacteremia.


Food restriction normalizes somatic growth and diabetes in adrenalectomized ob/ob mice.
Carcass composition was determined in intact and adrenalectomized (ADX) ob/ob mice after 6 wk of food restriction from weaning (21 days). Diets (2.6 or 3.2 g/day) led to reduced weight gain in intact ob/ob mice, but fat deposition was still greater, and lean growth was less than isocalorically fed lean mice. When diet was combined with ADX, obese mice fed 3.2 g/day had rates of fat-free body growth equal to ad libitum-fed lean mice but still gained more weight and deposited more fat. With 2.6 g/day, however, body weight gain, fat deposition, fat-free body growth, and protein deposition were all similar to intact lean mice receiving the same diet. Neither diet nor diet combined with ADX improved the defective thermoregulation of obese mice tested at 23 degrees C, 8 degrees C, or in response to food deprivation or food ingestion. Together, diet and adrenalectomy reduced blood glucose and insulin levels in ob/ob mice, and with the 2.6 g/day diet, the values of each were the same as littermate lean controls. The present results indicate that adrenal glucocorticoids are necessary for maintaining elevated fat deposition at the expense of lean body growth in dieted ob/ob mice, whereas hyperphagia, defective thermoregulation, energy efficiency, and diabetes are still expressed after surgery.


Hybrid quantum-classical simulations of magic angle spinning dynamic nuclear polarization in very large spin systems.
Solid-state nuclear magnetic resonance can be enhanced using unpaired electron spins with a method known as dynamic nuclear polarization (DNP). Fundamentally, DNP involves ensembles of thousands of spins, a scale that is difficult to match computationally. This scale prevents us from gaining a complete understanding of the spin dynamics and applying simulations to design sample formulations. We recently developed an ab initio model capable of calculating DNP enhancements in systems of up to ∼1000 nuclei; however, this scale is insufficient to accurately simulate the dependence of DNP enhancements on radical concentration or magic angle spinning (MAS) frequency. We build on this work by using ab initio simulations to train a hybrid model that makes use of a rate matrix to treat nuclear spin diffusion. We show that this model can reproduce the MAS rate and concentration dependence of DNP enhancements and build-up time constants. We then apply it to predict the DNP enhancements in core-shell metal-organic-framework nanoparticles and reveal new insights into the composition of the particles' shells.


[Salt fluoridation and dental caries: state of the question].
Objective: Dental caries remains a public health problem, particularly among socially deprived populations. In some developing countries, salt fluoridation programmes have been recently developed, but the use of fluoridated salt is limited worldwide and the level of evidence for its efficacy remains debated. Method: A literature review was conducted to identify epidemiological or clinical studies that have evaluated the effect of salt fluoridation on dental caries experiences in children. Results: After a literature search, 22 references were selected reporting data on the preventive effect of salt fluoridation programmes in Europe (Hungary, Switzerland, France, Germany) and South and Central America (Colombia, Mexico, Jamaica...). Data were mainly obtained from descriptive or retrospective epidemiological studies. The results indicate that, in the absence of topical fluoride support, salt fluoridation leads to a significant reduction in caries indexes among treated children compared to a control group. In a context of widespread use of fluoridated toothpastes, the additional effect achieved by salt fluoridation is limited. The prevalence of fluorosis is not markedly increased with fluoridated salt, but side effects were not always evaluated. Conclusion: Today, a salt fluoridation programme could be useful in areas in which fluoridated toothpastes are not widely used. The communication policy promoting the consumption of fluoridated salt is crucial to ensure the effectiveness of such a programme.


Advances in tracheal reconstruction.
A recent revival of global interest for reconstruction of long-segment tracheal defects, which represents one of the most interesting and complex problems in head and neck and thoracic reconstructive surgery, has been witnessed. The trachea functions as a conduit for air, and its subunits including the epithelial layer, hyaline cartilage, and segmental blood supply make it particularly challenging to reconstruct. A myriad of attempts at replacing the trachea have been described. These along with the anatomy, indications, and approaches including microsurgical tracheal reconstruction will be reviewed. Novel techniques such as tissue-engineering approaches will also be discussed. Multiple attempts at replacing the trachea with synthetic scaffolds have been met with failure. The main lesson learned from such failures is that the trachea must not be treated as a "simple tube." Understanding the anatomy, developmental biology, physiology, and diseases affecting the trachea are required for solving this problem.


PSMD7 downregulation suppresses lung cancer progression by regulating the p53 pathway.
Lung cancer is the second most common cancer in both men and women. The deubiquitinase PSMD7, as a core component of the 26S proteasome, is critical for the degradation of ubiquitinated proteins in the proteasome. Currently, PSMD7 expression and its roles in the progression of lung cancer remain largely unknown. In this study, we assessed PSMD7 expression and investigated the underlying molecular events by which PSMD7 regulates tumor progression in non-small cell lung cancer (NSCLC). The results showed that PSMD7 is more highly expressed in NSCLC tissues than in adjacent noncancerous tissues. PSMD7 expression was also closely associated with lymph node invasion and the laterality of the tumor in lung adenocarcinoma (LUAD). A high PSMD7 level predicted poor overall survival (OS) and disease-free survival (DFS) in LUAD patients, and PSMD7 knockdown significantly reduced cell proliferation and induced G0/G1-phase cell cycle arrest, cell senescence and apoptosis. PSMD7 knockdown inhibited expression of a set of proteins regulating cell cycle progression. Depletion of PSMD7 increased p53 levels and induced p21 and puma expression in a p53-dependent manner. Importantly, knockdown of PSMD7 markedly inhibited LUAD tumor growth in a xenograft mouse model. Taken together, these findings indicate that PSMD7 may serve as a valuable prognostic indicator and potential therapeutic target in LUAD.


Single-pulse magneto-optic microscopy: a new tool for studying optically induced magnetization reversals.
We have developed a femtosecond magneto-optical imaging system that allows measurements of permanent magnetic effects that are initiated by a single excitation pulse. The system combines a subpicosecond temporal resolution and a high spatial resolution. We demonstrate the system in an experiment that studies the laser-induced magnetization reversal in ferromagnetic thin films.


Antitumor activity in RAS-driven tumors by blocking AKT and MEK.
KRAS is the most commonly mutated oncogene in human tumors. KRAS-mutant cells may exhibit resistance to the allosteric MEK1/2 inhibitor selumetinib (AZD6244; ARRY-142886) and allosteric AKT inhibitors (such as MK-2206), the combination of which may overcome resistance to both monotherapies. We conducted a dose/schedule-finding study evaluating MK-2206 and selumetinib in patients with advanced treatment-refractory solid tumors. Recommended dosing schedules were defined as MK-2206 at 135 mg weekly and selumetinib at 100 mg once daily. Grade 3 rash was the most common dose-limiting toxicity (DLT); other DLTs included grade 4 lipase increase, grade 3 stomatitis, diarrhea, and fatigue, and grade 3 and grade 2 retinal pigment epithelium detachment. There were no meaningful pharmacokinetic drug-drug interactions. Clinical antitumor activity included RECIST 1.0-confirmed partial responses in non-small cell lung cancer and low-grade ovarian carcinoma. Responses in KRAS-mutant cancers were generally durable. Clinical cotargeting of MEK and AKT signaling may be an important therapeutic strategy in KRAS-driven human malignancies (Trial NCT number NCT01021748).


Synthesis of novel camphor-derived bifunctional thiourea organocatalysts.
Synthesis and catalyst performance of 2,3- (types and ) and 2,8-disubstituted (type ) thiourea bifunctional organocatalysts was attempted. The synthesis of catalyst of type has, so far, not been realized, while catalysts of type , i.e., the 2,3-exo- and the 2-endo-3-exo-thiourea catalysts, were prepared in six steps starting from (+)-camphor. The catalysts of type were prepared from (+)-camphor in eight steps. All the potential catalysts as well as most of the intermediate products were carefully structurally characterized. The thiourea bifunctional organocatalysts were tested in a model reaction of Michael addition of dimethyl malonate to trans-β-nitrostyrene.


Prefrontal hemodynamics during forward and backward walking, with and without a cognitive task, in people with multiple sclerosis.
Hemodynamics in the prefrontal cortex (PFC) while walking forward and backward, with and without an additional cognitive task (motor single-task [ST] and motor cognitive dual-task [DT]) have not been studied in people with multiple sclerosis (pwMS). To investigate the PFC hemodynamics during forward and as well as backward walking, with and without a cognitive task, in pwMS and healthy controls. Observational case-control study. Sheba Multiple Sclerosis Center, Tel-Hashomer, Israel. Eighteen pwMS (36.1±11.7 years, 66.6% female) and 17 healthy controls (37.5±13.8 years, 76.5% female). Each subject completed four walking trials: ST forward walking, DT forward walking, ST backward walking, DT backward walking. PFC activity for all trials was recorded using functional near-infrared spectroscopy (fNIRS). The PFC was subdivided in the frontal eye field (FEF), frontopolar cortex (FPC) and the dorsolateral PFC (DLPFC). The relative oxygenated hemoglobin (HbO) concentration was higher during the DT forward walking in all PFC subareas compared with the ST forward walking for both groups. The relative HbO concentration was higher during ST backward walking compared with ST forward walking in pwMS (DLPFC, FEF) and the healthy controls (FEF, FPC), specifically during the initial part of the trial. ST backward walking and DT forward walking impact the hemodynamics at the PFC, although, the difference between pwMS and healthy adults requires further clarification. Future RCT's are encouraged to examine the impact of an intervention program based on DT forward and backward walking on PFC activity in pwMS. Backward walking increases activity in the PFC region in pwMS. Similarly, when performing a cognitive task while walking forward.


Multiple Prescription Drug Abuse and Salt Craving in a Psychotic Patient: A Case Report From a Teaching Hospital in Jordan.
Diuretics and laxative abuse as a means of purging is common in patients with bulimia nervosa and there may be an underestimation of the true prevalence of diuretic abuse, as some are also available without prescription. A 28-year-old woman presented with tetany due to hypocalcemia, hypokalemia and hypomagnesemia. She had a history of laxative and diuretic abuse, and salt craving. Psychiatric evaluation revealed a disturbed social history with masked depression that necessitated treatment. Multiple prescription drug abuse and salt/salty food addiction usually reflects a personality of addiction, which leads to harmful use and dependence.


The nuclear factor (erythroid-derived 2)-like 2 (NRF2) antioxidant response promotes melanocyte viability and reduces toxicity of the vitiligo-inducing phenol monobenzone.
Vitiligo, characterised by progressive melanocyte death, can be initiated by exposure to vitiligo-inducing phenols (VIPs). VIPs generate oxidative stress in melanocytes and activate the master antioxidant regulator NRF2. While NRF2-regulated antioxidants are reported to protect melanocytes from oxidative stress, the role of NRF2 in the melanocyte response to monobenzone, a clinically relevant VIP, has not been characterised. We hypothesised that activation of NRF2 may protect melanocytes from monobenzone-induced toxicity. We observed that knockdown of NRF2 or NRF2-regulated antioxidants NQO1 and PRDX6 reduced melanocyte viability, but not viability of keratinocytes and fibroblasts, suggesting that melanocytes were preferentially dependent upon NRF2 activity for growth compared to other cutaneous cells. Furthermore, melanocytes activated the NRF2 response following monobenzone exposure and constitutive NRF2 activation reduced monobenzone toxicity, supporting NRF2's role in the melanocyte stress response. In contrast, melanocytes from individuals with vitiligo (vitiligo melanocytes) did not activate the NRF2 response as efficiently. Dimethyl fumarate-mediated NRF2 activation protected normal and vitiligo melanocytes against monobenzone-induced toxicity. Given the contribution of oxidant-antioxidant imbalance in vitiligo, modulation of this pathway may be of therapeutic interest.


Low-frequency electric cortical stimulation has an inhibitory effect on epileptic focus in mesial temporal lobe epilepsy.
This study was conducted to investigate the effect of low-frequency electric cortical stimulation on epileptic focus in humans. We stimulated the epileptic focus in a patient with medically intractable mesial temporal lobe epilepsy (MTLE) by means of subdural electrodes and evaluated the change in the number of interictal epileptiform discharges. We used biphasic electric current of 0.3-ms duration presented at 0.9-Hz frequency for 250 s, comparing stimulus intensity of 7.5, 2, and 0.5 mA. Interictal epileptiform discharges at the ictal focus occurred less frequently after the stimulation with the intensity of 0.5 mA. With the intensity of 7.5 mA and 2.0 mA, however, habitual auras were elicited by the stimulation, and afterdischarges were seen on the cortical EEG. Low-frequency, low-intensity electric cortical stimulation could produce inhibitory effects on epileptic activity. At the same time, however, a caution for possible induction of EEG seizures is needed, even when applying low-frequency electric stimulation.


Copper Affects Composition and Functioning of Microbial Communities in Marine Biofilms at Environmentally Relevant Concentrations.
Copper (Cu) pollution in coastal areas is a worldwide threat for aquatic communities. This study aims to demonstrate the usefulness of the DNA metabarcoding analysis in order to describe the ecotoxicological effect of Cu at environmental concentrations on marine periphyton. Additionally, the study investigates if Cu-induced changes in community structure co-occurs with changes in community functioning (i.e., photosynthesis and community tolerance to Cu). Periphyton was exposed for 18 days to five Cu concentrations, between 0.01 and 10 μM, in a semi-static test. Diversity and community structure of prokaryotic and eukaryotic organisms were assessed by 16S and 18S amplicon sequencing, respectively. Community function was studied as impacts on algal biomass and photosynthetic activity. Additionally, we studied Pollution-Induced Community Tolerance (PICT) using photosynthesis as the endpoint. Sequencing results detected an average of 9,504 and 1,242 OTUs for 16S and 18S, respectively, reflecting the high biodiversity of marine periphytic biofilms. Eukaryotes represent the most Cu-sensitive kingdom, where effects were seen already at concentrations as low as 0.01 μM. The structure of the prokaryotic part of the community was impacted at slightly higher concentrations (0.06 μM), which is still in the range of the Cu concentrations observed in the area (0.08 μM). The current environmental quality standard for Cu of 0.07 μM therefore does not seem to be sufficiently protective for periphyton. Cu exposure resulted in a more Cu-tolerant community, which was accompanied by a reduced total algal biomass, increased relative abundance of diatoms and a reduction of photosynthetic activity. Cu exposure changed the network of associations between taxa in the communities. A total of 23 taxa, including taxa within Proteobacteria, Bacteroidetes, Stramenopiles, and Hacrobia, were identified as being particularly sensitive to Cu. DNA metabarcoding is presented as a sensitive tool for community-level ecotoxicological studies that allows to observe impacts simultaneously on a multitude of pro- and eukaryotic taxa, and therefore to identify particularly sensitive, non-cultivable taxa.


Retinal circulatory changes associated with interferon-induced retinopathy in patients with hepatitis C.
To evaluate the effect of interferon (IFN) therapy on retinal microcirculation. Thirty-six patients with chronic hepatitis C who were treated with high-dose IFN were included in this prospective study. The changes in vessel diameter and blood velocity were measured, and the retinal blood flow (RBF) and wall shear rate (WSR) were calculated in the retinal arteries before and 2, 4, 8, 16, and 24 weeks after IFN therapy by using laser Doppler velocimetry. Retinal blood velocity, RBF, and WSR significantly (P < 0.0001) increased in all patients, as early as 2 weeks after IFN therapy. The increase in RBF was independently correlated with a decrease in the red blood cell count. In 22 (61%) of the 36 patients asymptomatic retinopathy developed during treatment. In patients with retinopathy, the blood velocity and WSR increased, but the vessel diameter did not change, whereas the vessel diameter increased but the blood velocity and WSR did not change in patients without retinopathy 2 weeks after IFN therapy. Multiple logistic regression analysis showed that patient age and the change in WSR at week 2 were risk factors for the development of IFN-induced retinopathy. RBF increases in association with IFN therapy in patients with chronic hepatitis C. In addition, the increased WSR in patients with retinopathy indicates that retinal vascular endothelial dysfunction may be associated with IFN-induced retinopathy, because wall shear stress should be constant under physiologic conditions.


Formal Synthesis of Ecteinascidin 743 from N-Cbz-l-tyrosine.
A formal total synthesis of ecteinascidin 743 and lurbinectedin is achieved. Key features involve a Pictet-Spengler cyclization coupling of the tetrahydroisoquinoline and phenylalaninol moieties prepared by a common route with high yield and selectivity, a Parikh-Doering oxidation with good chemoselectivity and functionality tolerance, and a light-mediated A-ring elaboration of pentacyclic methoxyquinone substrates. By the approach, the known advanced intermediate (4-step conversion to Et-743) can be obtained conveniently in 21 total steps from N-Cbz-l-tyrosine.


Health-related quality of life in patients with osteoporosis in the absence of vertebral fracture: a systematic review.
To review whether osteoporosis in the absence of vertebral fracture (VFX) affects health-related quality of life (HRQoL), a systematic search of the main literature databases for HRQoL in patients with osteoporosis without VFX was undertaken. This was undertaken. This identified 1,327 articles as potentially relevant to the review. After screening of abstracts and reviewing 168 articles in detail, 27 were considered relevant. HRQoL data were extracted and collated into tables and, where possible, were converted into normative scores and further analysed. Data relating to the associations between HRQoL and bone mineral density (BMD) were also collated. Of the 27 articles included, only 5 directly compared osteoporosis without VFX with a control group (BMD T-score > -1.0, without VFX). Extracted raw data from 21 articles demonstrated that patients with osteoporosis without VFX had clinically relevant reductions in role physical, general health, vitality, mental health domains and the mental component summary score, using SF36. Using Qualeffo-41, pain and physical function were worse in these patients. Also, HRQoL was related to upper femur, but not lumbar spine BMD. HRQoL data in patients with osteoporosis without VFX are limited and variable but suggest that HRQoL is adversely affected by osteoporosis in the absence of VFX. The association of lower BMD and worse HRQoL suggests that more attention should be paid to HRQoL in those without VFX. Future studies are needed to investigate HRQoL in patients with osteoporosis in the absence of fracture, controlling for co-morbidities and social and economic status.


Modulation of CD14 expression on human granulocytes by a bacterial product "Cantastim" derived from Pseudomonas aeruginosa.
Pathophysiological effects of infection with Gram-negative bacteria depend on recognition by host cells of LPS, a major component of the outer membrane of these microorganisms. CD14 is an immunological marker and also the receptor for LPS on phagocytic cells. The aim of the present study was to investigate the capacity of a bacterial immunomodulator, named Cantastim, which is used as a therapeutical agent in neoplasic diseases and chronic infections, to modulate the CD14 expression on human granulocytes. Our preliminary results showed that Cantastim can not influence the expression of CD14 on granulocytes obtained from healthy donors, but on the other hand Cantastim was able in vitro and in vivo to down-regulate the expression of this marker on granulocytes from a patient with neoplasic disease.


Oxidative stress and frailty: A systematic review and synthesis of the best evidence.
Oxidative stress (OS) is associated with accelerated aging. Previous studies have suggested a possible relationship between OS and frailty but this association remains unclear. We conducted a systematic review to investigate potential interactions between OS and frailty. A systematic literature search of original reports providing data on 'OS and antioxidant' parameters and frailty was carried out across major electronic databases from inception until May 2016. Cross-sectional/case control and longitudinal studies reporting data on the association between frailty and anti-oxidants-OS biomarkers were considered for inclusion. Results were summarized with a synthesis based on the best evidence. From 1856 hits, 8 studies (cross-sectional/case control) were included (N=6349; mean age of 75±12years; 56.4% females). Overall, there were 588 (=9.3%) frail, 3036 pre-frail (=47.8%), 40 (=0.6%) pre-frail/robust, and 2685 (=42.3%) robust subjects. Six cross-sectional/case control studies demonstrated that frailty was associated with an increase in peripheral OS biomarkers, including lipoprotein phospholipase A2 (1 study), isoprostanes (2 studies), malonaldehyde (2 studies), 8-hydroxy-20-deoxyguanosine (2 studies), derivate of reactive oxygen metabolites (2 studies), oxidized glutathione/glutathione (1 study), 4-hydroxy-2,3-nonenal (1 study), and protein carbonylation levels (1 study). In addition, preliminary evidence points to lower anti-oxidant parameters (vitamin C, E, α-tocopherol, biological anti-oxidant potential, total thiol levels) in frailty. Frailty and pre-frailty appear to be associated with higher OS and possibly lower anti-oxidant parameters. However, due to the cross-sectional design, it is not possible to disentangle the directionality of the relationships observed. Thus, future high-quality and in particular longitudinal research is required to confirm or refute these relationships and to further elucidate pathophysiological mechanisms.


SHP-1- and phosphotyrosine-independent inhibitory signaling by a killer cell Ig-like receptor cytoplasmic domain in human NK cells.
Killer cell Ig-like receptors (KIR) are MHC class I-binding immunoreceptors that can suppress activation of human NK cells through recruitment of the Src homology 2-containing protein tyrosine phosphatase-1 (SHP-1) to two immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in their cytoplasmic domains. KIR2DL4 (2DL4; CD158d) is a structurally distinct member of the KIR family, which is expressed on most, if not all, human NK cells. 2DL4 contains only one ITIM in its cytoplasmic domain and an arginine in its transmembrane region, suggesting both inhibitory and activating functions. While 2DL4 can activate IFN-gamma production, dependent upon the transmembrane arginine, the function of the single ITIM of 2DL4 remains unknown. In this study, tandem ITIMs of KIR3DL1 (3DL1) and the single ITIM of 2DL4 were directly compared in functional and biochemical assays. Using a retroviral transduction method, we show in human NK cell lines that 1) the single ITIM of 2DL4 efficiently inhibits natural cytotoxicity responses; 2) the phosphorylated single ITIM recruits SHP-2 protein tyrosine phosphatase, but not SHP-1 in NK cells; 3) expression of dominant-negative SHP-1 does not block the ability of 2DL4 to inhibit natural cytotoxicity; 4) surprisingly, mutation of the tyrosine within the single ITIM does not completely abolish inhibitory function; and 5) this correlates with weak SHP-2 binding to the mutant ITIM of 2DL4 in NK cells and a corresponding nonphosphorylated ITIM peptide in vitro. These results reveal new aspects of the KIR-inhibitory pathway in human NK cells, which are SHP-1 and phosphotyrosine independent.


Sphingosine-1-phosphate receptor 2.
Sphingosine-1-phosphate (S1P) is a potent bioactive sphingolipid involved in cell proliferation, angiogenesis, inflammation and malignant transformation among other functions. S1P acts either directly on intracellular targets or activates G protein-coupled receptors, specifically five S1P receptors (S1PRs). The identified S1PRs differ in cellular and tissue distribution, and each is coupled to specific G proteins, which mediate unique functions. Here, we describe functional characteristics of all five receptors, emphasizing S1PR2, which is critical in the immune, nervous, metabolic, cardiovascular, musculoskeletal, and renal systems. This review also describes the role of this receptor in tumor growth and metastasis and suggests potential therapeutic avenues that exploit S1PR2.


Role of Autophagy in the Maintenance of Stemness in Adult Stem Cells: A Disease-Relevant Mechanism of Action.
Autophagy is an intracellular scavenging mechanism induced to eliminate damaged, denatured, or senescent macromolecular substances and organelles in the body. The regulation of autophagy plays essential roles in the processes of cellular homeostasis and senescence. Dysregulated autophagy is a common feature of several human diseases, including cancers and neurodegenerative disorders. The initiation and development of these disorders have been shown to be associated with the maintenance of disease-specific stem cell compartments. In this review, we summarize recent advances in our understanding of the role of autophagy in the maintenance of stemness. Specifically, we focus on the intersection between autophagy and adult stem cells in the initiation and progression of specific diseases. Accordingly, this review highlights the role of autophagy in stemness maintenance from the perspective of disease-associated mechanisms, which may be fundamental to our understanding of the pathogeneses of human diseases and the development of effective therapies.


[The relationship between expressed emotion and daily life functioning of families who take care of the schizophrenics members].
The relationship between Expressed Emotion (EE) and daily life functioning of families who took care of the schizophrenics members was analyzed, to make clear the conceptual substance and psycho-social background of EE, and to get the practical guideline how to offer the effective family support programs. The research was conducted at 3 psychiatric hospitals in Chiba. 72 out of 93 cases were followed up after 9 months, and 64 cases were respondents of the inquiry at the discharge which was conducted to get the information of daily life functioning of families. In the inquiry, we used Family Support Behavior Scale (FSB), representing the family support function as a caretaker, and Disfunction in the Ordinary Family Life Scale (DFL), representing the disfunction of the family life function for a caretaker as a subject who realized his/her own self. The results were as followings. DFL had relatively strong correlation to EE. And a distinctive feature of EE subscales' distribution was observed among 4 groups divided by the median of FSB and DFL. That is, "Critical Comments (CC)" and "Hostility (H)" were high in the "loFSB-hiDFL" group in which both family functions did not operate effectively. "Emotional Over-Involvement (EOI)" was extremely high and CC was moderately high in the "hiFSB-hiDFL" group which had the difficulty only in the ordinary family life function. And the relapse rate of both groups, particularly of "loFSB-hiDFL" was high up to 61.5% after the follow-up period. So far, it was suggested that the disfunction of the ordinary family life was closely related to the whole substance of EE scales, which were the congeries of family factors to predict the relapse, and which had not the internal consistency of the scale. Adding the disfunction of family support to that, had the appearance of EE sub-scales changed, and made the family environment severely related to the relapse.


Ligand binding to the Fe(III)-protoporphyrin IX complex of phosphodiesterase from Escherichia coli (Ec DOS) markedly enhances catalysis of cyclic di-GMP: roles of Met95, Arg97, and Phe113 of the putative heme distal side in catalytic regulation and ligand binding.
Phosphodiesterase (Ec DOS) from Escherichia coli is a gas-sensor enzyme in which binding of gas molecules, such as O(2), CO, and NO, to the Fe(II)-protoporphyrin IX complex in the sensor domain stimulates phosphodiesterase activity toward cyclic-di-GMP. In this study, we report that external axial ligands, such as cyanide or imidazole, bind to Fe(III)-protoporphyrin IX in the sensor domain and induce a 10- to 11-fold increase (from 8.1 up to 86 min(-1)) in catalysis, which is more substantial than that (6.3 to 7.2-fold) observed for other gas-stimulated Fe(II) heme-bound enzymes. Catalytic activity (50 min(-1)) of the heme-free mutant, H77A, was comparable to that of the ligand-stimulated enzymes. Accordingly, we propose that the heme at the sensor domain inhibits catalysis and that ligand binding to the heme iron complex releases this catalytic suppression. Furthermore, mutations of Met95, Arg97, and Phe113 at the putative heme distal side suppressed the ligand effects on catalysis. The rate constants (19,000 x 10(-5) microM(-1)min(-1)) for cyanide binding to the M95A and M95L mutants of the full-length enzyme were 633-fold higher than that to wild-type Ec DOS (30 x 10(-5) microM(-1)min(-1)). The absorption spectrum of the F113Y mutant suggests that the Tyr O(-) group directly coordinates to the Fe(III) complex and that the cyanide binding rate to the mutant is very slow, compared with those of the wild-type and other mutant proteins. We observed a similar trend in the binding behavior of imidazole to full-length mutant enzymes. Therefore, while Met95 and Phe113 are not direct axial ligands for the Fe(III) complex, catalytic, spectroscopic, and ligand binding evidence suggests that these residues are located in the vicinity of the heme.


A psychotherapist engages in behaviour therapy.
The article reviews clinical findings that led an experienced psychotherapist to favour behaviour therapy over psychotherapy for patients who have anxiety disorders involving avoidance of specific situations or avoidance of specific activities. It is maintained that anxiety disorders are best treated through psychotherapy when they are demonstrably connected to disturbances in interpersonal relations. Three basic procedures in behaviour therapy are described: desensitization, direct exposure, and cognitive restructuring. Transference patterns in each of these procedures are delineated. A fourth procedure, "clinical bargaining," helps patients relinquish avoidances by experimenting with new behaviours outside the consulting room. Selected aspects of transferase and counter-transference in clinical bargaining are discussed. In dealing with single patients, it is recommended that clinicians separate the non directive position of the psychotherapist from the directive role of the behaviour therapist, since these two roles are largely irreconcilable.


Dynamics of acute respiratory distress syndrome development due to smoke inhalation injury: Implications for prolonged field care.
Smoke inhalation injury (SII) causes 30% to 40% mortality and will increase as a cause of death during prolonged field care. We used a combat relevant model of acute respiratory distress syndrome due to SII to study temporal changes in ventilation-perfusion (V/Q) matching, computed tomography (CT) scan data, and histopathology and hypothesized that SII leads to increase in shunt (Qshunt), V/Q mismatch, lung consolidation, and diffuse alveolar damage. Swine received severe SII and airway pressure release ventilation (APRV, n = 6), or conventional ARDSNet mechanical ventilation (MV) (CMV, n = 8). A control group without injury received volume controlled MV (CTRL, n = 6), The multiple inert gas elimination technique and CT were performed at baseline (BL), 0.5 hours, 1 hours, 2 hours, 24 hours, and 48 hours after injury. Diffuse alveolar damage scoring was performed post mortem. Significance at p less than 0.05: APRV versus CTRL; CMV versus CTRL; APRV versus CMV*; denotes changes versus BL. (1) SII caused increases in Qshunt more so in APRV than CMV group. Qshunt did not change in CTRL. (2) PaO2-to-FIO2 ratio (PFR) was lower in APRV versus CTRL at 2 hours (375 ± 62‡ vs. 549 ± 40) and 24 hours (126 ± 34‡* vs. 445 ± 5) and 48 hours (120 ± 41‡& vs. 430 ± 13). In CMV animals, PFR was lower versus CTRL and BL at 24 hours (238 ± 33) and 48 hours (98 ± 27). Qshunt correlated with PFR (r = 0.75, p < 0.0001, APRV and (r = 0.65, p < 0.0001, CMV). CT showed decrease in normally aerated lung, while poorly and nonaerated lung increased. Smoke inhalation injury leads to early development of shunt, V/Q mismatch, lung consolidation, and diffuse alveolar damage. These data substantiate the need for new point of injury interventions in the prolonged field care setting. Animal research.


Does chemical composition have an influence on the fate of intraperitoneal gallstone in rat?
Perforation and spillage of gallstones is a common occurrence in laparoscopic cholecystectomies. The long-term complications of these stones remains controversial. Experimental studies have been carried out to elucidate the outcome of intraperitoneal gallstones, but the chemical composition of these stones has not been considered in previous studies. In this study, we investigated the local effects of intraperitoneal gallstones in rats with respect to their chemical composition. Bile and gallstones were taken from human cholecystectomy specimens, and sent for bacteriologic and chemical analysis. Twenty cholesterol and 10 pigment stones were placed in the abdominal cavity of rats. Long-term local effects of gallstones were determined at the end of 3 months with macroscopic and microscopic examination. The fragments of two pigment stones were infected by Staphylococcus aureus. Five (17%) cholesterol stones were found free in the abdominal cavity, and 25 stones (83%) were wrapped with adjacent structures. Granuloma formation was found around 4 pigment stones (13% of all stones, 40% of pigment stones; p = 0.0077). We observed large granulomas and cutaneous fistula formation in two rats with infected pigment stones placed in the abdominal cavity. Histhopathologic examination also showed significantly severe inflammatory reactions secondary to pigment stones (p<0.001). In conclusion our findings revealed that chemical composition has a significant influence on the fate of intraabdominal gallstones, and infection may aggravate local reactions and complications. Based on our findings, laparoscopic retrieval of spilled stones whenever possible seems to be useful to prevent subsequent infectious complications and inflammatory reactions. Patients with retained intraperitoneal pigment stones after laparoscopic cholecystectomy must be followed up closely.


[Development of gene therapy for hemophilia: current states and future perspectives].
Hemophilia is congenital hemorrhagic disease due to genetic abnormality of blood coagulation factor VIII or factor IX. Hemophilia appears suitable for gene therapy because it is caused by a single gene abnormality, and therapeutic coagulation factor levels vary across a broad range. Since the success of gene therapy eliminates the need for regular administration of factor concentrates, the development has been met with great expectation from patients and their families. In fact, several clinical trials using adeno-associated virus (AAV) vectors have been started in Western countries, and long-term therapeutic effect could be obtained by single injection. More recently, the modifications of therapeutic gene and AAV serotypes have further improved therapeutic effects, and it appears to have reached the level of "cure". However, gene therapy using AAV vectors presents difficulties such as the existence of anti AAV capsid neutralizing antibody and hepatic injury due to cellular immunity with CD8+ T cells. Thus, it is essential to develop technologies adapted to a wide range of hemophilia patients, and to observe long-term safety and therapeutic effect after the gene therapy.


Ultrastructure of a novel eurytele nematocyst of Carybdea alata Reynaud (Cubozoa, Cnidaria).
The ultrastructural characteristics of nematocysts from the cubozoan Carybdea alata Reynaud, 1830 (Hawaiian box jellyfish) were examined using light, scanning and transmission electron microscopy. We reclassified the predominant nematocyst in C. alata tentacles as a heterotrichous microbasic eurytele, based on spine, tubule and capsule measurements. These nematocysts exhibited a prominent and singular stylet, herein referred to as the lancet. Discharged nematocysts from fixed tentacle preparations displayed the following structures: a smooth shaft base, lamellae, a hemicircumferential fissure demarking the proximal end of a stratified lancet, and a gradually tapering tubule densely covered with large triangularly shaped spines. The lancet remained partially adjoined to the shaft base in a hinge-like fashion in rapidly fixed, whole-tentacle preparations. In contrast, this structure was not observed in discharged nematocyst preparations which involved multiple transfer steps prior to fixation. Various approaches were designed to detect this structure in the absence of fixative. Detached lancets were located in proximity to discharged tubules in undisturbed coverslip preparations of fresh tentacles. In addition, examination of embedded nematocysts from fresh tentacles laid on polyacrylamide gels revealed still-attached lancets. To examine the function of this structure in prey capture, Artemia sp. laden tentacles were prepared for scanning electron microscopy. While carapace exteriors exhibited structures proximal to the lancet, i.e., the nematocyst capsule and shaft base, neither tubule nor lancet structures were visible. Taken together, the morphological data suggested a series of events involved in the discharge of a novel eurytele from C. alata.


Circadian rhythms, diet, and neuronal excitability.
Many aspects of normal biological function are governed by circadian rhythms, including metabolism, ingestive behaviors, and sleep-wake cycles. Certain pathological processes as well are also affected by the circadian rhythms. For example, it is well known that seizure occurrence can be influenced by the sleep-wake cycle. The ketogenic diet (KD) is a high-fat, low-carbohydrate diet with proven efficacy in the treatment of intractable epilepsies. While the mechanisms underlying the clinical effects of the KD remain unclear, there are emerging links between circadian rhythms and KD action. Such factors should be considered when planning and administering the KD to patients.


HIV/HBV coinfection in children and antiviral therapy.
Small cohort studies from countries where both HIV and HBV are endemic demonstrate prevalence rates of chronic hepatitis B in HIV-infected children of between 1 and 49%. While data on coinfected children are limited, results from studies in adults with HIV/HBV coinfection raise the concern that coinfected children may be at a higher risk of liver disease, hepatic fibrosis and cirrhosis. With the scale-up of combination antiretroviral therapy worldwide, of which lamivudine is included in most first-line regimens, coinfected children treated with lamivudine risk development of HBV resistance mutations. This article summarizes the current literature relevant to HIV/HBV coinfection in children, the options for treatment and highlights priorities for future research.


Facile radical trifluoromethylation of lithium enolates.
[reaction: see text] Highly basic lithium enolates are shown to be applicable to radical trifluoromethylation. The reaction is extremely fast, and the minimum reaction time is approximately 1 s.


Gender, culture, and suicidal behavior: a feminist critique of theories and research.
Suicide research has developed historically from philosophical roots in logical positivism and structural determinism. Thus, much suicide research has been based on assumptions of cause-and-effect relationships, reductionistic analysis, and the individual as the primary unit of analysis. In counterpoint, six guiding themes define feminist research (Worell & Etaugh, 1994). The present manuscript traces these six themes, illustrating them with suicide research projects. By challenging scientific tradition, focusing on women, considering power, recognizing gender constructs, maintaining awareness of the power of language, and promoting active, practical applications, researchers can combine traditional and alternative methodologies to make suicide research more robust.


Genetic evaluation using random regression models with different covariance functions for test-day milk yield in an admixture population of Thailand goats.
The objectives of this study were to compare covariance functions (CF) and estimate the heritability of milk yield from test-day records among exotic (Saanen, Anglo-Nubian, Toggenburg and Alpine) and crossbred goats (Thai native and exotic breed), using a random regression model. A total of 1472 records of test-day milk yield were used, collected from 112 does between 2003 and 2006. CF of the study were Wilmink function, second- and third-order Legendre polynomials, and linear splines 4 knots located at 5, 25, 90 and 155 days in milk (SP25-90) and 5, 35, 95 and 155 of days in milk (SP35-95). Variance components were estimated by restricted maximum likelihood method (REML). Goodness of fit, Akaike information criterion (AIC), percentage of squared bias (PSB), mean square error (MSE), and empirical correlation (RHO) between the observed and predicted values were used to compare models. The results showed that CF had an impact on (co)variance estimation in random regression models (RRM). The RRM with splines 4 knots located at 5, 25, 90 and 155 of days in milk had the lowest AIC, PSB and MSE, and the highest RHO. The heritability estimated throughout lactation obtained with this model ranged from 0.13 to 0.23.


New methodology for the thermal characterization of thermoelectric liquids.
A new and accurate method for the thermal characterization of thermoelectric liquids is proposed. The experiment is based on a self-generated voltage due to the Seebeck effect. This voltage is provided by the sample when one of its two faces is thermally excited using a modulated laser. The sample used is tetradodecylammonium nitrate salt/1-octanol mixture, with high Seebeck coefficient. The thermal properties of the used sample (thermal diffusivity, effusivity, and conductivity) are found and compared to those obtained by other photothermal techniques. In addition to this, a study of the electrolyte thermal parameters with the variation of tetradodecylammonium nitrate concentration was also carried out. This new method is promising due to its accuracy and its simplicity.


Validation of the Children's Intrinsic Needs Satisfaction Scale among Canadian youth: psychometric properties, criterion-related validity and multitrait multimethod confirmatory factor analysis.
Based on self-determination theory, the Children's Intrinsic Needs Satisfaction Scale (CINSS) measures autonomy, competence and relatedness at school, home and with peers. The factor structure and criterion-related validity of the CINSS in the Canadian youth population are tested using data from the Canadian Student Tobacco, Alcohol and Drugs Survey (CSTADS). Data from the 2014/2015 CSTADS were analyzed for evidence of convergent and discriminant validity and for method variance. A multitrait multimethod (MTMM) confirmatory factor analysis (CFA) was conducted to account for the conceptual structure of the measure. Criterion-related validity was demonstrated through correlations between related constructs, prosocial behaviours and behavioural problems, and the CINSS subscale scores. Mean differences on CINSS subscale scores between those who reported and did not report being bullied or bullying others were also examined. Correlation analyses demonstrated that, in general, correlations were higher between concept/context item pairs and lowest between items measuring different concepts and contexts. Cronbach's alpha for concept and context subscales were high: α = 0.77 for autonomy, α = 0.85 for competence and α = 0.79 for relatedness. A MTMM CFA demonstrated that the model fit the data well, with no modifications. Criterion-related validity was demonstrated through correlations between CINSS subscales and related concepts or mean differences on CINSS subscales between groups. The CINSS demonstrates good internal consistency, factorial validity and criterion-related validity in this sample of Canadian students. The measurement of positive mental health among Canadian youth is central to surveillance efforts which will help inform mental health promotion activities across Canada.


[Euthanasia as a topic in criminal literature. Two examples].
Euthanasia is the main theme in the crime novels. The sisterhood by the American author Michael Palmer, published in 1982 and Morfindoktoren nekter seg skyldig (The morphine doctor denies his guilt) by the Norwegian author Waldemar Brøgger, published in 1958. In spite of differences between these two novels in time and space, they show many similarities. In this article the two novels, both of which have physicians as the main characters, are compared. Biographic information on the authors confirms the hypothesis of a close relationship between authors and their heroes in the criminal literature. The criminal literature has many points of connection in the medicine. These two examples show how even important and difficult medical ethical issues can be a subject for a crime novel.


Evaluation of plant resistance inducers on different winter soft wheat cultivars against Septoria leaf blotch.
Septoria tritici blotch (STB) caused by Mycosphaerella graminicola (anamorph: Zymoseptoria tritici) is one of the most devastating foliar diseases on bread wheat (Triticum aestivum L.). Because of the emergence of fungal strains highly resistant to mainly used fungicides and the deleterious impacts of these fungicides on the environment, development of alternative control strategies to protect wheat crops against STB is needed. The induction of plant resistance by elicitors is likely to be a helpful alternative. Our study aims at characterizing the efficiency of potential resistance inducers towards STB in three bread wheat cultivars differing in their resistance levels to the pathogen: Alixan (susceptible), Premio (moderately resistant) and Altigo (resistant). These cultivars were inoculated under controlled and semi-controlled conditions with the pathogenic M. graminicolo strain T01193 in order to assess the protective effect of three potential resistance inducers against the disease. Moreover, the direct antifungal effect bf these products was evaluated in vitro at different concentrations in order to verify their potential biocide activity. Furthermore, cytological analyses were performed in order to determine the effects of these products on the fungal infection process and to compare these effects among the three wheat cultivars. Finally, reactive oxygen species metabolism was investigated in the three cultivars during their interaction with T01193 by measuring peroxidase activity.


Emerging viruses in transplantation: there is more to infection after transplant than CMV and EBV.
Transplant physicians and surgeons are familiar with the risks, clinical behavior, and management of cytomegalovirus in transplant recipients. Donor-transmitted viral infections are uncommon but in recent years have brought to light the clinical manifestations of rabies, West Nile virus, and lymphocytic choriomeningitis virus in the early posttransplant period. Later posttransplant, infection with viruses circulating in the community can occur with a number of pathogens, including some vaccine-preventable illnesses such as measles and mumps. Recent advances in molecular microbiology have made it possible to diagnose a growing number of community-acquired viral pathogens infecting transplant recipients. This article reviews some of the emerging and reemerging viral pathogens infecting solid organ and hematopoietic stem-cell recipients, including adenovirus, bocavirus, coronavirus, human herpesvirus-6, lymphocytic choriomeningitis virus, measles, mumps, metapneumovirus, parainfluenza, rotavirus, respiratory syncytial virus, and West Nile virus.


Enhancement of thermal response of normal and malignant tissues by Corynebacterium parvum.
Further studies were carried out on the combined effects of Corynebacterium parvum and hyperthermia on animal tissues and cultured Chinese hamster ovary cells. Experimental animals were C3Hf/Sed mice derived from our defined flora mouse colony. Tumors were eighth-generation isotransplants of a spontaneous fibrosarcoma, FSa-II. Hyperthermia was given by immersing the mouse foot or culture flasks in the constant temperature water bath. Present experiments include thermal enhancement of C. parvum at different temperatures, effect of the agent on the kinetics of thermal resistance, and the mechanism of the thermal enhancement. The thermal enhancement by C. parvum was independent of temperature in a range between 42.5 and 46.5 degrees, and it increased with decreasing temperature. The analysis of the Arrhenius plot suggested a comparable activation energy for combined treatments and for heat alone between 42.5 and 46.5 degrees. The thermal resistance developed very rapidly in both normal and tumor tissues. Systemic administration of C. parvum failed to modify the kinetics of thermal resistance. Several experiments were attempted in order to disclose the mechanism. A single injection of C. parvum-induced macrophages failed to enhance thermal response of the mouse foot, while 3 daily injections of the macrophages enhanced the response, indicating that the enhancement by C. parvum is at least partly attributed to the C. parvum-induced macrophages. Whole-body irradiation of 6 Gy and/or administration of anti-mouse T-cell serum and histamine failed to inhibit the C. parvum enhancement of thermal response. No thermal enhancement was observed for Chinese hamster ovary cells treated at 43.0 degrees in vitro with C. parvum or thiomersalate , a preservative supplemented in C. parvum, although cytotoxic effect was shown at a high concentration of thiomersalate .


Decreased Insulin Sensitivity in Telomerase-Immortalized Mesenchymal Stem Cells Affects Efficacy and Outcome of Adipogenic Differentiation in vitro.
Modern biomedical science still experiences a significant need for easy and reliable sources of human cells. They are used to investigate pathological processes underlying disease, conduct pharmacological studies, and eventually applied as a therapeutic product in regenerative medicine. For decades, the pool of adult mesenchymal stem/stromal cells (MSCs) remains a promising source of stem and progenitor cells. Their isolation is more feasible than most other stem cells from human donors, yet they have a fair share of drawbacks. They include significant variability between donors, loss of potency, and transformation during long-term culture, which may impact the efficacy and reproducibility of research. One possible solution is a derivation of immortalized MSCs lines which receive a broader use in many medical and biological studies. In the present work, we demonstrated that in the most widely spread commercially available hTERT-immortalized MSCs cell line ASC52telo, sensitivity to hormonal stimuli was reduced, affecting their differentiation efficacy. Furthermore, we found that immortalized MSCs have impaired insulin-dependent and cAMP-dependent signaling, which impairs their adipogenic, but not osteogenic or chondrogenic, potential under experimental conditions. Our findings indicate that hTERT-immortalized MSCs may present a suboptimal choice for studies involving modeling or investigation of hormonal sensitivity.


MicroRNA transport: a new way in cell communication.
MicroRNAs (miRNAs) can efficiently regulate gene expression by targeting mRNA to cause mRNA cleavage or translational repression. Growing evidence indicates that miRNAs exist not only in cells but also in a variety of body fluids, which stimulates substantial interest in the transport mechanism and regulating process of extracellular miRNAs. This article reviews the basic biogenesis of miRNAs in detail to explore the origin of extracellular miRNAs. Different miRNA transporters have been summarized (e.g., exosomes, microvesicles, apoptosis bodies, and RNA-binding proteins). In addition, we discuss the regulators affecting miRNA transport (e.g., ATP and ceramide) and the selection mechanism for different miRNA transporters. Studies about miRNA transporters and the transport mechanism are new and developing. With the progress of the research, new functions of extracellular miRNAs may be uncovered in the future.


Secure key distribution based on chaos synchronization of VCSELs subject to symmetric random-polarization optical injection.
We propose and numerically demonstrate a secure key distribution scheme based on the dynamic chaos synchronization of two external cavity vertical-cavity surface-emitting lasers (VCSELs) subject to symmetric random-polarization injections. By exchanging the random parameters that control the polarization angles of the driving injection, Alice and Bob can identify the time slots in which high-quality private chaos synchronization is achieved and independently generate a shared key from the synchronized polarization difference signals of their local VCSELs. The results show that Gb/s key distribution with a low bit error ratio can be achieved, and the shared key can pass all NIST tests, which guarantee the randomness of the key. In the proposed scheme, the exchange messages do not contain any information about the key generation, which affords a high-level of security for key distribution.


A redox-driven multicomponent molecular shuttle.
A multicomponent [2]rotaxane designed to operate as a molecular shuttle driven by light energy has been constructed, and its properties have been investigated. The system is composed of (1) a light-fueled power station, capable of using the photon energy to create a charge-separated state, and (2) a mechanical switch, capable of utilizing such a photochemically generated driving force to bring about controllable molecular shuttling motions. The light-fueled power station is, in turn, a dyad comprising (i) a pi-electron-accepting fullerene (C60) component and (ii) a light-harvesting porphyrin (P) unit which acts as an electron donor in the excited state. The mechanical switch is a redox-active bistable [2]rotaxane moiety that consists of (i) a tetrathiafulvalene (TTF) unit as an efficient pi-electron-donor station, (ii) a dioxynaphthalene (DNP) unit as a second pi-electron-rich station, and (iii) a tetracationic cyclobis(paraquat-p-phenylene) (CBPQT4+) pi-electron-acceptor cyclophane, which encapsulates the better pi-electron-donating TTF station. Diethylene glycol spacers were conveniently introduced between the electroactive components in the dumbbell-shaped thread to facilitate the template-directed synthesis of the [2]rotaxane. A modular synthetic approach was undertaken for the overall synthesis of this multicomponent bistable [2]rotaxane, beginning with the syntheses of the P-C60 dyad unit and the two-station TTF-DNP-based [2]rotaxane separately, using conventional synthetic methodologies. These two components were finally stitched together by an esterification to afford the target rotaxane. Its structure was characterized by 1H NMR spectroscopy and mass spectrometry as well as by UV-vis-NIR absorption spectroscopy and voltammetry. The observations reflect remarkable electronic interactions between the various units, pointing to the existence of folded conformations in solution. The redox-driven shuttling process of the CBPQT4+ ring between the two competitive electron-rich recognition units, namely, TTF and DNP, was investigated by electrochemistry and spectroelectrochemistry as a means to verify its operational behavior prior to the photophysical studies related to light-driven operation. The oxidation process of the TTF unit is dramatically hampered in the rotaxane, thereby reducing the efficiency of the shuttling motion. These results confirm that, as the structural complexity increases, the overall function of the system no longer depends simply on its "primary" structure but also on higher-level effects which are reminiscent of the secondary and tertiary structures of biomolecules.


Structural studies of the exopolysaccharide from Lactobacillus plantarum C88 using NMR spectroscopy and the program CASPER.
Some lactic acid bacteria, such as those of the Lactobacillus genus, have the ability to produce exopolysaccharides (EPSs) that confer favorable physicochemical properties to food and/or beneficial physiological effects on human health. In particular, the EPS of Lactobacillus plantarum C88 has recently demonstrated in vitro antioxidant activity and, herein, its structure has been investigated using NMR spectroscopy and the computer program CASPER (Computer Assisted Spectrum Evaluation of Regular polysaccharides). The pentasaccharide repeating unit of the O-deacetylated EPS consists of a trisaccharide backbone, →4)-α-D-Galp-(1→2)-α-D-Glcp-(1→3)-β-D-Glcp-(1→, with terminal D-Glc and D-Gal residues (1.0 and 0.8 equiv per repeating unit, respectively) extending from O3 and O6, respectively, of the →4)-α-D-Galp-(1→ residue. In the native EPS an O-acetyl group is present, 0.85 equiv per repeating unit, at O2 of the α-linked galactose residue; thus the repeating unit of the EPS has the following structure: →4)[β-D-Glcp-(1→3)][β-D-Galp-(1→6)]α-D-Galp2Ac-(1→2)-α-D-Glcp-(1→3)-β-D-Glcp-(1→. These structural features, and the chain length (∼10(3) repeating units on average, determined in a previous study), are expected to play an important role in defining the physicochemical properties of the polymer.


Addressing the Challenges of Conducting Research in Developing Countries.
To explore the unique challenges that occur when conducting research in developing countries so the reader can consider approaches for providing ethically and culturally appropriate research strategies applicable for the context of the host country. This article presents an overview of the challenges, which are organized based on the phases of the research period: pre-enrollment, enrollment, and post-enrollment. At each stage, examples of adaptation to meet the challenges are presented and recommendations are posited. Strategies for research should protect the rights of the most vulnerable and disadvantaged populations while balancing the needs of society at large, provide culturally relevant ethical informed consent while balancing institutional review board requirements, and conduct research in a culturally appropriate manner for the host country while balancing the principles of ethical research established by developed countries. Researchers are implored to focus on the ethical and cultural appropriateness of each aspect of the study process to afford the highest level of research credibility and validity.


Bioavailability and feasibility of subcutaneous 5-fluorouracil.
Continuous intravenous (i.v.) infusion of 5-fluorouracil (5-FU) has been shown to be superior to bolus regimens in terms of response rates and toxicity. However, a continuous infusion is more expensive and prone to complications such as thromboembolism and infections. A way to circumvent these problems would be to administer 5-FU subcutaneously (s.c.). To assess feasibility and bioavailability of s.c. 5-FU, eight patients with advanced cancer received 250 mg 5-FU as an infusion over 90 min either intravenously (i.v.) or s.c. into the abdominal wall. The mean +/- s.d. bioavailability of s.c. 5-FU was 0.89 +/- 0.23. The interpatient variability for the area under the plasma concentration-time curve was 48% for the s.c. and 36% for the i.v. infusion. No local side effects were observed. To test the local tolerance of a more prolonged administration three patients received 930-1,000 mg m-2 5-FU by 24-h continuous s.c. infusion. The steady-state plasma levels were comparable to i.v. infusion. One patient developed a painless skin pigmentation at the s.c. infusion site. However, the same reaction was observed at the forearm after i.v. infusion. We conclude that at the dose studied s.c. 5-FU has an almost complete bioavailability and is well tolerated. Further work will show, whether prolonged s.c. infusion can be used as a safe and economical alternative to i.v. infusion.


Endothelial cells assemble into a 3-dimensional prevascular network in a bone tissue engineering construct.
To engineer tissues with clinically relevant dimensions, one must overcome the challenge of rapidly creating functional blood vessels to supply cells with oxygen and nutrients and to remove waste products. We tested the hypothesis that endothelial cells, cocultured with osteoprogenitor cells, can organize into a prevascular network in vitro. When cultured in a spheroid coculture model with human mesenchymal stem cells, human umbilical vein endothelial cells (HUVECs) form a 3-dimensional prevascular network within 10 days of in vitro culture. The formation of the prevascular network was promoted by seeding 2% or fewer HUVECs. Moreover, the addition of endothelial cells resulted in a 4-fold upregulation of the osteogenic marker alkaline phosphatase. The addition of mouse embryonic fibroblasts did not result in stabilization of the prevascular network. Upon implantation, the prevascular network developed further and structures including lumen could be seen regularly. However, anastomosis with the host vasculature was limited. We conclude that endothelial cells are able to form a 3-dimensional (3D) prevascular network in vitro in a bone tissue engineering setting. This finding is a strong indication that in vitro prevascularization is a promising strategy to improve implant vascularization in bone tissue engineering.


Respiratory coupling between prefrontal cortex and hippocampus of rats anaesthetized with urethane in theta and non-theta states.
Respiratory modulation of forebrain activity, long considered hard to reliably separate from breathing artefacts, has been firmly established in recent years using a variety of advanced techniques. Respiratory-related oscillation (RRO) is derived from rhythmic nasal airflow in the olfactory bulb (OB) and is conveyed to higher order brain networks, including the prefrontal cortex (PFC) and hippocampus (HC), where it may potentially contribute to communication between these structures by synchronizing their activities at the respiratory rate. RRO was shown to change with sleep-wake states; it is strongest in quiet waking, somewhat less in active waking, characterized with theta activity in the HC, and absent in sleep. The goal of this study was to test RRO synchronization between PFC and HC under urethane anaesthesia where theta and non-theta states spontaneously alternate. We found that in theta states, PFC-HC coherences significantly correlated with OB-HC but not with OB-PFC, even though RRO was stronger in PFC than in HC. In non-theta states, PFC-HC synchrony correlated with coherences connecting OB to either PFC or HC. Thus, similar to freely behaving rats, PFC-HC synchrony at RRO was primarily dependent on the response of HC to the common rhythmic drive, but only in theta state. The findings help outlining the value and the limits of applications in which urethane-anaesthetized rats can be used for modelling the neural mechanisms of RRO in behaving animals.


Oral Cancer Knowledge, Attitudes and Practices: A Survey of Undergraduate Medical Students in Himachal Pradesh, India.
Oral cancer is the sixth most common cancer among Indian males and the third most common cancer among Indian females. Early detection of oral cancers makes them more amenable to treatment and allows the greatest chance of cure. Lack of awareness among the health care providers is the most significant factor in delaying diagnosis and treatment of oral cancer. So the aim of the study was to assess the knowledge, attitude and practices of oral cancer among undergraduate medical students in Indira Gandhi Medical College, Shimla, India. A cross-sectional questionnaire study was conducted among 186 undergraduate medical students between the third to fifth years in Indira Gandhi Medical College, Shimla. The questionnaire consisted of 15 questions, five each on knowledge, attitudes and practices. The data were analysed by Statistical Package for the Social Sciences version 16. Test used were t-test, Chi-square and ANOVA. The response rate of the study was 96.5%. The mean knowledge percent of the sample was good. Mean knowledge percent was higher in females than males. Higher percentage of students in 5(th) year (internship) had excellent knowledge. The knowledge and practices about risk factors was not satisfactory. One hundred and twenty four (66.6%) of the subjects disagreed/strongly disagreed that their knowledge regarding the prevention and detection of oral cancer is current adequate. One hundred and seventy six and (94.6%) agreed/strongly agreed that there is need for additional training/information regarding oral cancer. It can be concluded that though the mean knowledge of the population was good but the knowledge and practices about risk factors had to be reinforced among these students so that they can help the patients in tobacco and alcohol cessation and contribute in prevention of oral cancers.


[Quantitative evaluation method of the informational value of initial symptoms based on Bayesian theory].
In accordance with Article 25-2 of the Pharmacists Act, pharmacists provide patients with information about the initial symptoms of adverse drug reactions for detecting and preventing those reactions. Thus far, however, there have been no reports quantitatively evaluating the usefulness of such information. We present a theory of information evaluation using posterior probability (PP), positive likelihood ratio (LR(+)) and incidence of nonspecific initial symptoms (NIS)-a measure of general symptoms without anything come to mind. First, we calculated using the data from the clinical trials. For liver damage caused by loxoprofen sodium hydrate, the LR(+) was as high as 27.9 in the presence of rash, but the PP was 0.002067, which means there were only 2 liver damage cases among 1000 rash cases. Calculated in the same way for voriconazole, the LR(+) was 5 and the PP was 0.2 (1 liver damage case among 5 rash cases). This suggests that information about rash as an initial symptom of liver damage is useful for patients taking voriconazole. However, the PP was greatly reduced when it was calculated by considering NIS. Since patients cannot distinguish initial symptom of side effect from mere change in body condition, the calculation considering NIS is realistic. Therefore, it is necessary to study in order to raise the value of the information service of the pharmacist. Our study demonstrates how PP and NIS, our new effective measure, allow a quantitative evaluation of the usefulness of information about initial symptoms.


Effects of chronic beta-adrenoceptor antagonism on plasma catecholamines and blood pressure in hypertension.
Plasma catecholamines were measured before and after treatment with beta-adrenoceptor antagonists in 17 hypertensive patients. Chronic treatment with beta-adrenoceptor antagonists caused substantial reductions in heart rate and intra-arterial blood pressure recorded continuously during ambulation. Before treatment, a quantitative relationship was observed between plasma norepinephrine and blood pressure and heart rate during a variety of activities; a similar relationship was also observed after chronic treatment five of six patients, suggesting that plasma norepinephrine remains an index of sympathetic activity despite the influence of beta-adrenoceptor antagonism. After treatment, plasma norepinephrine tended to be higher at any level of blood pressure, although not significantly so. Chronic treatment caused no significant change in mean resting plasma levels of norepinephrine and epinephrine. During exercise, plasma norepinephrine and epinephrine levels were significantly elevated above control after acute but not after chronic treatment. These observations do not support the hypothesis that beta-adrenoceptor antagonist drugs lower blood pressure in hypertensive man through a sympatholytic mechanism in he central nervous system or at peripheral presynaptic receptors.


Healthcare price transparency in North America and Europe.
Healthcare price transparency is an effort to inform patient decision-making, but also to decrease prices and their variation across healthcare systems for equivalent medical services. The initiative is meaningful only for medical services that are shoppable-such as imaging examinations-for which patients incur out-of-pocket costs. Therefore, several countries in which patients commonly share a portion of their healthcare costs have been implementing mandates to improve healthcare price transparency. However, the provisional implementation has many issues, especially in the United States, including provider non-compliance and limited accessibility of price transparency tools by the general public. Many of the existing tools are not user-friendly, are difficult to navigate, focus on charges and health plan negotiated rates rather than patients' out-of-pocket costs, and disclose prices on the service level instead of per episode of care. As such, the disclosed amounts are often not reliable. Many price transparency tools also lack valid and measurable quality metrics, which can result in a selection of high-cost care as a proxy for high-value care, as well as an increase in healthcare prices when providers want to imply they offer high-quality care. Nevertheless, the impact of the initiatives on patients' decision-making and healthcare costs remains unclear. While transparency initiatives are patient-centric, efforts should be made to increase patient engagement, provide accurate patient-specific out-of-pocket cost information, compare available treatment and provider alternatives, and couple price information with quality metrics to enable making fully informed decisions.


Wendan decoction for dyslipidemia: Protocol for a systematic review and meta-analysis.
Dyslipidemia is one of the most popular metabolic diseases and an important risk factor for arteriosclerotic cardiovascular diseases. In China, Wendan decoction (WDD) has been widely used to treat hyperlipidemia. However, no systematic review has been found. In order to evaluate the efficacy and safety of WDD in the treatment of dyslipidemia, a meta-analysis and systematic evaluation are conducted. The randomized controlled trials (RCTs) evaluating the effectiveness and safety of WDD in the treatment of dyslipidemia will be enrolled. Data are mainly from 4 English databases (Pubmed, Embase, Cochrane Library, and Web of science) and 4 Chinese databases (Wanfang, CBM, CNKI, and VIP Database). The enrollment of RCTs is from the starting date of database establishment till December 15, 2018. Low density lipoprotein cholesterol is considered as the main outcome, while the serum concentrations of total cholesterol, triglyceride, high density lipoprotein cholesterol, apolipoprotein A, and apolipoprotein B are regarded as the secondary outcome. Safety indicators include liver enzyme, fasting blood glucose, and kidney function. The work such as selection of literature, data collection, quality evaluation of included literature, and assessment of publication bias will be conducted by 2 independent researchers. Meta-analysis will be performed by RevMan 5.0 software. This study will provide high-quality evidence for the treatment of dyslipidemia with WDD in terms of effectiveness and safety. The results of the study will help us determine whether WDD can effectively treat hyperlipidemia. PROSPERO CRD 42018114957.


Orthotopic liver transplantation totally corrects factor IX deficiency in hemophilia B.
Orthotopic liver transplantation has been performed for a growing range of liver-based inborn errors of metabolism. Previous authors have documented that liver transplantation can reverse the coagulation defect of hemophilia A. In this article we report total correction of factor IX deficiency in a patient with hemophilia B and blood product-related liver disease. Intraoperative bleeding was not excessive, and the donor liver produced normal amounts of factor IX immediately.


Coumarins from the bark of Juglans mandshurica exhibited anti-hepatoma activities via inducing apoptosis.
Hepatocellular carcinoma (HCC), the most common type of liver cancer, has high morbidity and mortality rates, and its prognosis is poor. The treatment options of HCC are limited by the lack of effective chemotherapy. Therefore, looking for effective drugs with little toxicity is very urgent. The aim of this study was to search for small molecule targeting on liver cancer from Juglans mandshurica, which has been used to treat cancers for a long time in China. Under the guide of anti-hepatoma activity, a new coumarin (1), together with eight reported analogs (2‒9), was isolated from the 75% EtOH extract. The structures of these compounds were determined by 1D and 2D NMR experiments. The absolute configuration of 1 was established by comparison of experimental and calculated electronic circular dichroism (ECD) spectra. The in vitro cytotoxicity experiments on two liver cancer cell lines (HepG2 and Hep3B) showed that compounds 2 and 5 had moderate antitumor activities on both cell lines. And further studies of antitumor mechanisms by the observation of morphological changes and Western blot analyses exhibited that induction of apoptosis might be a possible way that inhibited cell growth.


Chronotype Variability and Patterns of Light Exposure of a Large Cohort of United States Residents.
Chronotype (i.e., disposition for activity early or late in the day) has traditionally been measured with questionnaires. A few studies with small sample sizes have also been conducted using actigraphy devices. In the present study, analysis was conducted of the daily pattern of activity of 1887 United States residents who wore actigraphy devices for a whole week. The devices also recorded the participants' exposure to light. As determined by cosinor analysis, the mean pattern of ambulatory activity exhibited robust 24-hour oscillation with a peak at 14:48. On average, participants went to sleep 2 minutes before midnight and woke up at 07:43. The distribution of chronotypes (defined as the midpoint of sleep) had a mean of 03:50, and 95% of all chronotypes were between 01:00 and 07:00. The mean duration of exposure to bright daylight was 3.57 hours per day. Duration of daily exposure to bright light was moderately but significantly correlated with chronotype (r = -0.18). The acrophase of the rhythm of exposure to bright light was significantly correlated with chronotype (r = 0.27) and with the acrophase of the activity rhythm (r = 0.36). Chronotype did not vary with the seasons, but exposure to bright light was longer in summer and spring than in winter and fall. These results confirmed chronotype findings from actigraphic studies with smaller sample sizes, endorsed their equivalence to the results of questionnaire studies, and confirmed and extended previous observations that urban dwellers have limited daily exposure to sunlight.


[Nonsurgical treatment of post-catheterization femoral pseudoaneurysm].
Iatrogenic femoral pseudoaneurysms have traditionally been treated surgically. Since 1991, many non surgical methods have been developed: ultrasound guided compression repair, embolization, covered stenting and recently thrombin injection.


[Focus on biological agents in rheumatoid arthritis: newer treatments and therapeutic strategies].
Tumour necrosis factor (TNF)-alpha and interleukin (IL)-1 are major regulators of inflammation. TNFalpha inhibitors have been shown to be effective in treating some inflammatory diseases such as rheumatoid arthritis. TNFalpha inhibitors include soluble receptor antagonists (etanercept) and monoclonal antibodies (infliximab, adalimumab). IL-1 inhibitors (anakinra) were also developed, used in therapeutics and licensed in France. TNFalpha inhibitors can be added to background regimens of methotrexate in second-line treatments. Etanercept and adalimumab can be administered alone, especially to patients who have experienced methotrexate toxicity or who do not show clinical and/or radiological improvement. The use of these new agents may optimise rheumatoid arthritis treatment and delay disease progression, particularly when first-line treatments are disappointing. This paper reviews recent data on biological therapies for rheumatoid arthritis: tolerance and their ability to modify the course of disease and prevent radiological damage.


[Metastatic Atypical Meningioma of the Lung;Report of a Case].
A 56-years-old woman, who had undergone a complete resection for atypical meningioma (grade 2 of World Health Organization classification)8 years before was admitted to our hospital to treat a mass on the right middle lobe detected by chest X-ray. The mass was resected successfully by video-assisted thoracoscopic surgery and pathological diagnosis of the tumor was a metastatic atypical meningioma. We experienced a rare case of extracranial pulmonary metastasis of meningioma. Grade 2 meningioma is thought to have malignant potential of local recurrence and extracranial metastasis compared to grade 1 meningioma, so long-term observation may be necessary after resection of atypical meningioma.


Increasing referrals and donations using the Transplant Center Development Model.
Although transplantation centers directly benefit from organ and tissue donation, they continue to yield low organ and tissue referral and donation rates. Our medical center and organ procurement organization developed a model to increase referral and donation rates. This model, called the Transplant Center Development Model, facilitates the donation process, specializes staff education, and promotes administrative involvement. After it was was implemented at our medical center in 1991, the referral and donation rates from 1988 to 1990 were compared with those from 1991 to 1993. The results showed that after implementation of the model, the organ referral mean increased 47%; the organ donation mean, 50%; and the tissue donation mean, 117%. These findings suggest that this model may be a valuable tool in transplant center development.


NIR Irradiation Based on Low-Power LED Drive Module Design for Fat Reduction.
In this study, we designed a low-power visible ray (V) drive module based on a light-emitting diode (LED) to initiate fat reduction using light source irradiation. A chemical phantom of muscle and fat was fabricated, and the performance of the proposed LED drive module was tested using this chemical phantom. The LED light source could reduce fat by irradiating the skin 4-5 cm deep. The device exhibits a negative feedback and parallel amplification to maintain a stable circuit based on low-power consumption. Muscles have a high-water content and low impedance, whereas fats have a low water content and significant salt content. Therefore, fat exhibits high impedance. Chemical phantoms were fabricated according to these impedance values, and the fat reduction effect using the LED circuits was analyzed. When the fat phantom was irradiated by the light source, the fat impedance lowered, and we confirmed that fat reduction could be obtained. This study is expected to be applicable to family medicine and weight management health care.


Rates of apoptosis and proliferation vary with caloric intake and may influence incidence of spontaneous hepatoma in C57BL/6 x C3H F1 mice.
Although the dysregulation of physiological signals and mechanisms controlling cell proliferation has been a major focus in cancer research, recent evidence suggests that explicit evaluation of apoptosis or physiological cell death may be equally important in understanding multistage carcinogenesis. Dietary restriction of rodents is well known to reproducibly retard development of spontaneous and chemically induced tumors. We reasoned that the decrease in metabolic and hormonal trophic factors induced with this intervention could promote selective cell deletion via apoptosis. To pursue this possibility, we quantified the spontaneous apoptotic rate in liver sections from diet-restricted (DR) and ad libitum-fed (AL) 12-month-old male C57BL/6 x C3H F1 mice, a murine strain known to develop a high incidence of spontaneous liver tumors by 18 months of age. The identification of hepatocyte apoptotic bodies was facilitated by in situ end-labeling immunohistochemistry. The basal rate of proliferation of hepatocytes was quantified utilizing proliferating cell nuclear antigen immunohistochemistry. The incidence of apoptotic bodies and total proliferating cell nuclear antigen-positive cells was enumerated in 14 mice/group by scoring 50,000 random hepatocytes/liver and expressed as the mean incidence/100 cells. When the comparison was made between diet groups, the apoptotic rate was significantly higher in the DR mice relative to the AL mice, while the proliferation rate was significantly lower (P < 0.01 and P < 0.05, respectively). The increase in spontaneous level of apoptosis and the decrease in proliferation rate in livers of DR mice were associated with a significantly lower rate of spontaneous hepatoma over a 36-month period. In summary, the results suggest that caloric intake may modulate the basal turnover rates of cell death and proliferation in a direction consistent with a cancer-protective effect in the DR mice and a cancer-promoting effect in AL mice.


Q-switching near-infrared multiwavelength generation by intracavity tungsten-oxide-induced four-wave mixing in an erbium-doped fiber laser.
We report on the generation of a stable multiwavelength Q-switched erbium-doped fiber laser based on tungsten oxide nanoparticles (WO3 NPs) combined with an intracavity comb filter for the first time, to the best of our knowledge. The prepared WO3-PVA thin film has a modulation depth and saturable intensity of 20% and 100 MW/cm2, respectively. A spectrum of up to 15 peaks with a channel spacing of 0.48 nm has been obtained. In the Q-switching regime, a minimum pulse width of 4.24 μs and a maximum repetition rate of 52.49 kHz were achieved at a maximum pump power of 300 mW. The dual effect of WO3 NPs in saturable absorption and high optical nonlinearity has induced pulsed and four-wave mixing effects. Therefore, the intrinsic advantages of WO3 nanomaterial provide a promising source for the realization of a stable multiwavelength fiber laser.


Annihilation of photochemical reactivity of photo-alignment layer.
The gas-polymer and liquid-polymer interfacial reactions of photosensitive polyimide can annihilate photo-reactive carbon-carbon double bonds, which remain after photo-alignment process. The annihilation processes dramatically affect voltage holding ratio and reorientation of photo-active functional groups. Photochemical dimerizations were identified using UV-visible and FT-IR spectroscopy. Polyimide films containing cinnamate groups were irradiated by linear polarized ultra violet (LPUV) light. Schadt et al. claims that the photo-alignment results from the anisotropy depletion of the cinnamate side chains as a consequence of the (2+2) cycloaddition reactions. The photo-aligned polyimide induces the orientation of nematic liquid crystals perpendicular to the polarization axis. However, the un-reacted photo-sensitive functional groups generate problems such as image sticking and reduced contrast ratio. Voltage holding ratio and photo-fading observed from photo-alignment layer can be dramatically improved by annihilation process of remnant photoreactive groups.


Should gratitude be a requirement for access to live organ donation?
Gratitude is both expected and problematic in live organ donation. Are there grounds to require it, and to forbid access to live donor transplantation to a recipient who fails to signal that he feels any form of gratitude? Recipient gratitude is not currently required for organ donation, but it is expected and may be a moral requirement. Despite this, we argue that making it a condition for live organ transplantation would be unjustified. It would constitute a problematic and disproportionate punishment for perceived immoral behaviour on the part of the recipient. It would also bar the donor from positive aspects of organ donation that remain even in the absence of recipient gratitude. A potential recipient's lack of gratitude should be explored as a possible symptom of other morally problematic issues and integrated into the information provided to the potential donor. Recognition of the donor's gift and gratitude for it may also need to be expressed in part by others. This last aspect is relevant even in cases where the recipient feels and expresses gratitude.


Mandibular molar with five root canals.
The purpose of this study was to demonstrate the importance of knowledge of the internal anatomy of root canals for the success of endodontic treatment. Lack of knowledge of anatomic variations and their characteristics in different teeth has been pointed out as one of the main causes of endodontic therapy failure. In this report, the authors describe the endodontic treatment of a mandibular first molar with five root canals, evaluate the rate of occurrence of this number of canals, and discuss the importance of their identification and treatment.


Three- to eight-month-old infants' catching under monocular and binocular vision.
We report a cross-sectional and a longitudinal experiment that examined developmental changes in the relative contribution of monocular and binocular variables in the guidance of interceptive arm movements. Three- to eight-month-old infants were observed while presented with differently sized balls that approached frontally with a constant velocity under both monocular and binocular viewing conditions. Movement onset indicated that with age infants increasingly came to rely on binocular variables in controlling the timing of the interceptive arm movements. That is, from 7 to 8 months of age movement onset was independent from object size under binocular but not under monocular viewing. In contrast, binocular viewing enhanced the spatial accuracy of the interceptive arm movements at all ages. We concluded that attunement to binocular information is a key process in infants' gaining adaptive control of goal-directed arm movements. However, interceptive arm movements entail the formation of multiple on-line couplings between optic and movement variables, each of which appears to develop at its own pace.