An Energy-Efficient Skyline Query for Massively Multidimensional Sensing Data.
Cyber physical systems (CPS) sense the environment based on wireless sensor networks. The sensing data of such systems present the characteristics of massiveness and multi-dimensionality. As one of the major monitoring methods used in in safe production monitoring and disaster early-warning applications, skyline query algorithms are extensively adopted for multiple-objective decision analysis of these sensing data. With the expansion of network sizes, the amount of sensing data increases sharply. Then, how to improve the query efficiency of skyline query algorithms and reduce the transmission energy consumption become pressing and difficult to accomplish issues. Therefore, this paper proposes a new energy-efficient skyline query method for massively multidimensional sensing data. First, the method uses a node cut strategy to dynamically generate filtering tuples with little computational overhead when collecting query results instead of issuing queries with filters. It can judge the domination relationship among different nodes, remove the detected data sets of dominated nodes that are irrelevant to the query, modify the query path dynamically, and reduce the data comparison and computational overhead. The efficient dynamic filter generated by this strategy uses little non-skyline data transmission in the network, and the transmission distance is very short. Second, our method also employs the tuple-cutting strategy inside the node and generates the local cutting tuples by the sub-tree with the node itself as the root node, which will be used to cut the detected data within the nodes of the sub-tree. Therefore, it can further control the non-skyline data uploading. A large number of experimental results show that our method can quickly return an overview of the monitored area and reduce the communication overhead. Additionally, it can shorten the response time and improve the efficiency of the query.


Status of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal carcinomatosis from colorectal cancer.
Peritoneal carcinomatosis (PC) was previously considered an incurable disease with a poor survival outcome. As our understanding of its biology evolved, the paradigm of the management of PC from colorectal cancer (CRC) has changed, including the combination of macroscopic disease control, cytoreductive surgery (CRS), maximal regional chemotherapy to treat residual microscopic disease, and hyperthermic intraperitoneal chemotherapy (HIPEC). As with many surgical innovations, CRS with HIPEC has evolved faster than data to support it, leaving many skeptics and critics. This review highlights the recent evidence of current practice and outcome of CRS with HIPEC. Furthermore, it also summarizes the ongoing clinical trials and potential future progress of this treatment modality.


Optimizing nitroxide biradicals for cross-effect MAS-DNP: the role of g-tensors' distance.
Nitroxide biradicals are common polarizing agents used to enhance the sensitivity of solid-state NMR experiments via Magic Angle Spinning Dynamic Nuclear Polarization (MAS-DNP). These biradicals are used to increase the polarization of protons through the cross-effect mechanism, which requires two unpaired electrons with a Larmor frequency difference greater than that of the protons. From their early conception, the relative orientation of the nitroxide rings has been identified as a critical factor determining their MAS-DNP performance. However, the MAS leads to a complex DNP mechanism with time dependent energy level anti-crossings making it difficult to pinpoint the role of relative g-tensor orientation. In this article, a single parameter called "g-tensors' distance" is introduced to characterize the relative orientation's impact on the MAS-DNP field profiles. It is demonstrated for the first time how the g-tensors' distance determines the nuclear hyperpolarization and depolarization properties of a given biradical. This provides a new critical parameter that paves the way for more efficient bis-nitroxides for MAS-DNP.


Intrinsic and extrinsic heterogeneity in the responses of parent and clonal human colon carcinoma xenografts to photon irradiation.
Responses to photon irradiation of xenografted human colon tumors derived from the heterogeneous DLD-1 line or its derivative A and D subpopulations were determined using excision assay and tumor regrowth delay assays. Differential responses among the three xenografted carcinomas were demonstrated. Clone A tumors treated with up to 17.5 Gy showed no actual regression below pretreatment volume. In contrast, clone D tumors were sensitive to doses as low as 3.5 Gy, and tumor volumes were reduced by 65% with a dose of 17.5 Gy. The responses of DLD-1 tumors were intermediate between the clone A and clone D tumor responses. The survival parameters obtained in the excision assay studies for the DLD-1, clone A, and clone D tumors were, respectively: n = 3.3, 1.4, and 1.0; D0 (Gy) = 2.1, 2.2, and 2.7; and DQ (Gy) = 2.6, 0.6, and 0.0. These data indicate that the DLD-1 tumors were the most resistant, with clone A of intermediate sensitivity, clone D being the most sensitive tumor. In addition to the interclonal diversity among xenograft lines, intraclonal variation was also observed with clone A (but not clone D or DLD-1) tumors. A biphasic survival curve of cells from clone A xenografts irradiated in air-breathing hosts clearly indicated a minority (approximately 3%) subpopulation of hypoxic cells. Similar results indicating a small percentage of hypoxic cells in clone A solid tumors were obtained from the tumor regrowth delay studies. Also, excision assay data from experiments in which the heterografted carcinomas were irradiated under anoxic conditions support the interpretation that clone A tumors contain a small fraction of hypoxic cells. This study indicates that: (a) heterogeneity in vivo to ionizing radiation exists in the DLD-1 system; and (b) intraclonal variation occurs in vivo due to extrinsic (e.g., environmental hypoxia) factors, such that the intrinsic radioresistance of a subpopulation (clone A) of a heterogeneous human tumor can be further increased.


Male Victims of Female-Perpetrated Partner Violence: A Qualitative Analysis of Men's Experiences, the Impact of Violence, and Perceptions of Their Worth.
There has been a recent increase in the amount of research on male victims of female-perpetrated partner violence (PV) but research needs to be conducted to understand how the patterns of abuse persist in these relationships. In the current study, the experiences of 59 male PV victims in the USA, recruited through online advertisements in professional networks and websites (e.g., agencies that specialize in male victims of PV), were explored through a thematic analysis. Analyses suggested that the help seeking process of male PV victims is complex and heterogeneous and can often lead to further negative consequences due to various structural, cultural, social, and organizational factors. The findings also highlight the potential societal issues that male victims perceived as contributing to male victimization and lack of available resources for them. The results are discussed in terms of its implications for agencies, service providers, and general societal attitudes that are relevant to raising awareness about this phenomenon.


Self-rating level of perceived exertion for guiding exercise intensity during a 12-week cardiac rehabilitation programme and the influence of heart rate reducing medication.
To investigate whether self-rating level of perceived exertion can adequately guide exercise intensity during a 12-week cardiac rehabilitation programme. Linear regression analysis using rehabilitation data from two randomised controlled trials. Patients undergoing radiofrequency ablation for atrial fibrillation or following heart valve surgery and participating in exercise-based rehabilitation were included. The 12-week rehabilitation outpatient programme comprised three weekly training sessions, each consisting of 20min aerobic exercise divided into three steps. Patients were asked to base their exercise intensity for each step on a predefined rating of perceived exertion specified in a training diary. Exercise intensity was objectively measured by heart rate during the last 2min for each exercise step. Comparative analysis and linear regression of the rating of perceived exertion and heart rate were performed. A total of 2622 ratings of perceived exertion were collected from 874 training sessions in 97 patients. Heart rate and rating of perceived exertion were associated both across all three exercise steps and individually for each step, with a mean of 6 to7bpm per 1-point difference in the rating of perceived exertion (p<0.001). Adjusting for rate-reducing medication slightly improved the strength of the association. The association between change in the rating of perceived exertion and change in heart rate indicates that a diary-led and self-regulated model using rating of perceived exertion can help guide exercise intensity in everyday clinical practice among patients with heart disease, irrespective if they are taking heart rate-reducing medication.


Genetic variation in codons 167, 198 and 200 of the beta-tubulin gene in whipworms (Trichuris spp.) from a range of domestic animals and wildlife.
A recurrent problem in the control of whipworm (Trichuris spp.) infections in many animal species and man is the relatively low efficacy of treatment with a single application of benzimidazoles (BZs). The presence of single nucleotide polymorphisms (SNPs) in codons 167, 198 and 200 in the beta-tubulin gene has been associated with BZ anthelmintic resistance in intestinal nematodes of veterinary importance. We hypothesized that the low susceptibility to BZ could be related to a natural tolerance or induced resistance caused by BZ-resistant associated SNPs. The aim of the present study was therefore to investigate the presence of these SNPs in the beta-tubulin gene of Trichuris spp. obtained from a range of animals. DNA was extracted from a total of 121 Trichuris spp. adult whipworm specimens obtained from 6 different host species. The number of worms from each host was pig: 31, deer: 21, sheep: 18, mouse: 17, dog: 19 and Arabian camels: 14. A pooled sample of Trichuris eggs from 3 moose was also used. In order to amplify the beta-tubulin fragments which covered codons 167, 198 and 200 of the gene, degenerate primers were designed. The sequences obtained were used to design species specific primers and used to amplify a ~476 bp fragment of the beta-tubulin gene. The PCR products were sequenced, analysed and evaluated. We did not identify SNPs in codons 167, 198 or 200 that led to amino acid substitutions in any of the studied Trichuris spp., but genetic variation expected to be related to species differences was observed. The cluster analysis showed close evolutionary relationship between Trichuris spp. from ruminants and between mouse and dog whereas the pig-derived worms, T. suis, clustered with T. trichiura obtained from Genbank.


A database of the coseismic effects following the 30 October 2016 Norcia earthquake in Central Italy.
We provide a database of the coseismic geological surface effects following the Mw 6.5 Norcia earthquake that hit central Italy on 30 October 2016. This was one of the strongest seismic events to occur in Europe in the past thirty years, causing complex surface ruptures over an area of >400 km2. The database originated from the collaboration of several European teams (Open EMERGEO Working Group; about 130 researchers) coordinated by the Istituto Nazionale di Geofisica e Vulcanologia. The observations were collected by performing detailed field surveys in the epicentral region in order to describe the geometry and kinematics of surface faulting, and subsequently of landslides and other secondary coseismic effects. The resulting database consists of homogeneous georeferenced records identifying 7323 observation points, each of which contains 18 numeric and string fields of relevant information. This database will impact future earthquake studies focused on modelling of the seismic processes in active extensional settings, updating probabilistic estimates of slip distribution, and assessing the hazard of surface faulting.


The treatment of childhood Hodgkin lymphoma: improved survival in a developing country.
To evaluate the clinical characteristics, treatment regimens, and outcome of children with Hodgkin lymphoma in a developing country over a period of 34 years. This paper retrospectively evaluates the treatment and prognosis of 614 children with Hodgkin lymphoma disease between 1971 and 2005. All patients were treated with chemotherapy, and also received radiotherapy. There were 452 males and 162 females with a median age of 8 years (2 to 21); 183 patients had B symptoms. There were 165, 185, 145, and 119 patients in stage I, II, III, and IV, respectively. Histopathologic subtypes were mixed cellularity (344 patients), nodular sclerosis (90), lymphocytic predominance (62), lymphocytic depletion (46), unclassified types (69), and nodular lymphocyte predominant Hodgkin lymphoma (3). Overall (OS) and event-free survival (EFS) rates were 83 and 60%, though OS rates varied according to chemotherapy protocol; age; presence of B symptoms, leukocytosis, anemia, and extranodal involvement; and stage at diagnosis. Over the years, the median age of patients increased, as did the frequency of the nodular sclerosing type of disease. This is one of the largest series in a single center. The increase in the median age and in the frequency of the nodular-sclerosing type are thought to be related to the development status of Turkey. The ABVD protocol yielded the best survival rates and should be used for treatment of patients with Hodgkin lymphoma.


Growth hormone and prolactin response to bromocriptine in patients with Huntington's chorea.
The growth hormone (hGH) and prolactin (hPRL) responses to oral bromocriptine were studied in two groups of patients with Huntington's chorea and in seven healthy control subjects. The patients included six patients who had previously been treated with phenothiazines and six patients who had not received phenothiazine treatment. All medication was stopped 72 hours before the investigation which involved taking blood samples for up to 210 minutes after taking bromocriptine (2.5 mg). Plasma samples were analysed for hGH and hPRL. There was no significant difference in basal hGH concentrations between the patients and control subjects. The hGH response to bromocriptine varied in the individual patients but the concentrations were significantly lower in the patients compared with the controls between 160 and 210 minutes. The basal concentrations of hPRL were also not different, apart from the findings of elevated hPRL concentrations in three patients previously treated with phenothiazines. The patients and control subjects showed a consistent fall in hPRL concentrations after taking bromocriptine. The lower peak hGH response to bromocriptine found in the patients suggests that there may be an alteration of dopaminergic neurones mediating hGH release.


Production and validation of CR-39-based dishes for alpha-particle radiobiological experiments.
The study of radiobiological effects induced in vitro by low fluences of alpha particles would be significantly enhanced if the precise localization of each particle track in the cell monolayer was known. From this perspective, we developed a new method based on tailor-made UV-radiation-cured CR-39, the production of which is described. Its validation both as a petri dish and as solid-state nuclear track detectors is demonstrated. With respect to the demands on solid-state nuclear track detectors in such experiments, these biologically compatible detectors have a controlled micrometric thickness that allows them to be crossed by the alpha particles. In this study, we present a method for obtaining 10-mum-thick CR-39, its chemical characterization, and its properties as a solid-state nuclear track detector under the environmental conditions of radiobiological experiments. The experimental studies performed with 3.5 MeV alpha particles show that their transmitted energy is sufficient enough to cross the entire cellular volume. Under optimal conditions, etched tracks are clearly defined 2 h after etching. Moreover, the UV-radiation-cured CR-39 represents an essentially zero background that is due to the short time between the production and use of the polymer. Under a confocal microscope, this thin solid-state nuclear track detector allows the precise localization of the impact parameter at the subcellular level.


Fructose induces transketolase flux to promote pancreatic cancer growth.
Carbohydrate metabolism via glycolysis and the tricarboxylic acid cycle is pivotal for cancer growth, and increased refined carbohydrate consumption adversely affects cancer survival. Traditionally, glucose and fructose have been considered as interchangeable monosaccharide substrates that are similarly metabolized, and little attention has been given to sugars other than glucose. However, fructose intake has increased dramatically in recent decades and cellular uptake of glucose and fructose uses distinct transporters. Here, we report that fructose provides an alternative substrate to induce pancreatic cancer cell proliferation. Importantly, fructose and glucose metabolism are quite different; in comparison with glucose, fructose induces thiamine-dependent transketolase flux and is preferentially metabolized via the nonoxidative pentose phosphate pathway to synthesize nucleic acids and increase uric acid production. These findings show that cancer cells can readily metabolize fructose to increase proliferation. They have major significance for cancer patients given dietary refined fructose consumption, and indicate that efforts to reduce refined fructose intake or inhibit fructose-mediated actions may disrupt cancer growth.


Return to Basketball After Hip Arthroscopy: Minimum 2-Year Follow-up.
To present minimum 2-year patient-reported outcomes (PROs) and return to sport (RTS) data for a population of basketball players after hip arthroscopy. Data were prospectively collected and retrospectively reviewed for all patients who underwent hip arthroscopy between February 2009 and May 2014. Patients with preoperative and minimum 2-year postoperative PROs, visual analog scale score for pain, and satisfaction, who regularly played basketball within 1 year before surgery, and who attempted to RTS met the inclusion criteria. Exclusion criteria were previous ipsilateral hip surgery or conditions such as fracture, dysplasia, or femoral avascular necrosis. Patients were matched 1:1 to a control group composed of those who did not play any sports before surgery, based on the following matching criteria: age ±5 years, sex, and body mass index ±5. Statistical analysis was performed to determine significant differences in PROs. Conversion to total hip arthroplasty (THA) was considered an endpoint. Thirty-one patients (81.6%) met inclusion criteria with follow-up of 46.8 ± 20.6 months. The mean age was 30.0 ± 12.3, and the mean body mass index was 26.3 ± 6.5. Male patients (64.5%) outnumbered female patients (35.5%). A majority of the players (54.8%) identified themselves as recreational athletes; the remainder competed at the high school, collegiate, amateur, or professional level. There was significant (P < .001) improvement in all PRO measures and visual-analog scale scores from baseline to a minimum 2-year follow-up. At the most recent follow-up, mean patient satisfaction was 8.1 ± 2.1. Twenty-two (78.6%), and 23 patients (82.1%) achieved the patient acceptable symptom state on the modified Harris Hip Score and the Hip Outcomes Score-Sports Specific Subscale. Twenty-one (75.0%) and 17 (60.7%) patients had a minimal clinically important difference on the modified Harris Hip Score and the Hip Outcomes Score-Sports Specific Subscale, respectively. Three patients (9.7%) with an average age of 47.5 (P = .023) converted to THA at a mean of 35.9 ± 7.2 (range 29.66-43.75) months after arthroscopy. At the most recent follow-up, the RTS rate was 83.9%. Subjective ability level was the same or higher in 23 patients (74.2%). Hip arthroscopy in basketball athletes demonstrates a significant increase in PROs, a high RTS rate, and a low risk of complications. Hip arthroscopy may be considered in basketball players <40 years old for whom nonoperative treatment fails and who have a significantly limited level of play. Careful patient selection and counseling should be used when considering hip arthroscopy in basketball players >40 years old because there may be a high rate of conversion to THA. Level III, retrospective comparative study.


[Progressive glomerular sclerosis and renal failure in rat with 7/8 nephrectomy model].
A model of progressive glomerular sclerosis and chronic renal failure was established in 7/8 nephrectomized rats. Three fourths of left kidney of six-week old Sprague Dawley rats were ligated and removed. One week later right kidney was removed. As controls 3/4 nephrectomized rats operated the same manner as 7/8 nephrectomized rats and sham operated rats were used. Remarkable excretion of the protein into the urine and rise in blood pressure were noted in all 7/8 nephrectomized rats. Eight weeks after 7/8 nephrectomy, serum creatinine rose as high as 2.8 +/- 0.3 mg/dl and BUN 260 +/- 65 mg/dl. In contrast, only minor degree of elevation of blood pressure, excretion of protein into the urine and elevation of serum creatinine were noted in 3/4 nephrectomized rats. Morphologically deposition of rat IgG, C3, fibrinogen and albumin were observed mainly on the capillary wall in 7/8 nephrectomized rats. Minor amount of deposition was observed in 3/4 nephrectomized rats. By light microscopy there were remarkable glomerular and tubular lesions in 7/8 nephrectomized rats. Most of the glomeruli showed hypertrophy, 40% of the glomeruli had cellular or fibrocellular crescent, 34% of glomeruli failed into global sclerosis or hyalinosis, tubular atrophy or enlargement and hyaline cast in the lumen and interstitial fibrosis were also noted. By electron microscopy detachment of epithelial and endothelial cells from the GBM, increase in the mesangial matrix, obliteration of the capillary lumen by fibrin, hyaline material were observed. Only minor degree of increase in mesangial matrix and epithelial degenerative lesions were observed and 3% of glomeruli were sclerosed in 3/4 nephrectomized rats. From these results 7/8 nephrectomized rats can serve as useful model for studying the mechanism of glomerular sclerosis or hyalinosis and effect of various drugs on glomerulonephritis.


Recombinant protein production-associated metabolic burden reflects anabolic constraints and reveals similarities to a carbon overfeeding response.
A comparison of the metabolic response of Escherichia coli BL21 (DE3) towards the production of human basic fibroblast growth factor (hFGF-2) or towards carbon overfeeding revealed similarities which point to constraints in anabolic pathways. Contrary to expectations, neither energy generation (e.g., ATP) nor provision of precursor molecules for nucleotides (e.g., uracil) and amino acids (e.g., pyruvate, glutamate) limit host cell and plasmid-encoded functions. Growth inhibition is assumed to occur when hampered anabolic capacities do not match with the ongoing and overwhelming carbon catabolism. Excessive carbon uptake leads to by-product secretion, for example, pyruvate, acetate, glutamate, and energy spillage, for example, accumulation and degradation of adenine nucleotides with concomitant accumulation of extracellular hypoxanthine. The cellular response towards compromised anabolic capacities involves downregulation of cAMP formation, presumably responsible for subsequently better-controlled glucose uptake and resultant accumulation of glucose in the culture medium. Growth inhibition is neglectable under conditions of reduced carbon availability when hampered anabolic capacities also match with catabolic carbon processing. The growth inhibitory effect with accompanying energy spillage, respectively, hypoxanthine secretion and cessation of cAMP formation is not unique to the production of hFGF-2 but observed during the production of other proteins and also during overexpression of genes without transcript translation.


Manipulation of a floating liquid marble using dielectrophoresis.
A liquid marble is a microliter-sized droplet coated with hydrophobic powder. The porous coating prevents the liquid content from being in direct physical contact with its surroundings, making the liquid marble perfectly non-wetting. On the one hand, the non-wetting ability allows the liquid marble to float and move across a liquid surface with little resistance. On the other hand, the porosity enables gas exchange between the liquid marble and its surroundings. These properties allow the liquid marble to serve as a bioreactor platform for important applications such as cell culture. Liquid marbles floating on a free liquid surface prevent evaporation due to the high humidity near the liquid surface. Moving a floating liquid marble allows for stirring and mixing inside the liquid marble. This paper reports a novel technique for manipulating a floating liquid marble using dielectrophoresis. A relatively simple setup can move liquid marbles of various sizes across the water surface at high speeds. We also present an analytical model to model and accurately predict the motion of the floating liquid marble. The technique reported here potentially allows for high-throughput and efficient handling of floating liquid marbles as a digital microfluidics platform.


Hypotension is 100 mm Hg on the battlefield.
Historically, emergency physicians and trauma surgeons have referred to a systolic blood pressure (SBP) of 90 mm Hg as hypotension. Recent evidence from the civilian trauma literature suggests that 110 mm Hg may be more appropriate based on associated acidosis and outcome measures. In this analysis, we sought to determine the relationship between SBP, hypoperfusion, and mortality in the combat casualty. A total of 7,180 US military combat casualties from the Joint Theater Trauma Registry from 2002 to 2009 were analyzed with respect to admission SBP, base deficit, and mortality. Base deficit, as a measure of hypoperfusion, and mortality were plotted against 10-mm Hg increments in admission SBP. By plotting SBP, baseline mortality was less than 2% down to a level of 101 to 110 mm Hg, at which point the slope of the curve increased dramatically to a mortality rate of 45.1% in casualties with an SBP of 60 mm Hg or less but more than 0 mm Hg. A presenting SBP of 0 mm Hg was associated with 100% mortality. The data also established a similar effect for base deficit with a sharp increase in the rate of acidosis, which became manifest at an SBP in the range of 90 to 100 mm Hg. This analysis shows that an SBP of 100 mm Hg or less may be a better and more clinically relevant definition of hypotension and impending hypoperfusion in the combat casualty. One utility of this analysis may be the more expeditious identification of battlefield casualties in need of life-saving interventions such as the need for blood or surgical intervention.


Measurement properties of the EQ-5D-5L compared to the EQ-5D-3L across eight patient groups: a multi-country study.
The aim of this study was to assess the measurement properties of the 5-level classification system of the EQ-5D (5L), in comparison with the 3-level EQ-5D (3L). Participants (n = 3,919) from six countries, including eight patient groups with chronic conditions (cardiovascular disease, respiratory disease, depression, diabetes, liver disease, personality disorders, arthritis, and stroke) and a student cohort, completed the 3L and 5L and, for most participants, also dimension-specific rating scales. The 3L and 5L were compared in terms of feasibility (missing values), redistribution properties, ceiling, discriminatory power, convergent validity, and known-groups validity. Missing values were on average 0.8% for 5L and 1.3% for 3L. In total, 2.9% of responses were inconsistent between 5L and 3L. Redistribution from 3L to 5L using EQ dimension-specific rating scales as reference was validated for all 35 3L-5L-level combinations. For 5L, 683 unique health states were observed versus 124 for 3L. The ceiling was reduced from 20.2% (3L) to 16.0% (5L). Absolute discriminatory power (Shannon index) improved considerably with 5L (mean 1.87 for 5L versus 1.24 for 3L), and relative discriminatory power (Shannon Evenness index) improved slightly (mean 0.81 for 5L versus 0.78 for 3L). Convergent validity with WHO-5 was demonstrated and improved slightly with 5L. Known-groups validity was confirmed for both 5L and 3L. The EQ-5D-5L appears to be a valid extension of the 3-level system which improves upon the measurement properties, reducing the ceiling while improving discriminatory power and establishing convergent and known-groups validity.


TiO2-coated luminescent porous silicon micro-particles as a promising system for nanomedicine.
Porous silicon (pSi) is a sponge-like material obtained by electrochemical etching of a crystalline silicon wafer. Due to quantum confinement effects, this material is photoluminescent and this is a fundamental property from the perspective of bioimaging applications. Limitations in nanomedicine to the use of photoluminescent pSi structures are mainly due to optical quenching in an aqueous environment and to the adverse effects of reactive groups introduced by etching procedures. In this work, we exploited an inorganic TiO2 coating of pSi microparticles by Atomic Layer Deposition (ALD) that resulted in optical stability of pSi particles in a biological buffer (e.g. PBS). The use of a rotary reactor allows deposition of a uniform coating on the particles and enables a fine tuning of its thickness. The ALD parameters were optimized and the photoluminescence (PL) of pSi-TiO2 microparticles was stabilized for more than three months without any significant effect on their morphology. The biocompatibility of the coated microparticles was evaluated by analyzing the release of cytokines and superoxide anion (O2 -) by human dendritic cells, which play an essential role in the regulation of inflammatory and immune responses. We demonstrated that the microparticles per se are unable to significantly damage or stimulate human dendritic cells and therefore are suitable candidates for nanomedicine applications. However, a synergistic effect of the microparticles with bacterial products, which are known to stimulate immune-response, was observed, indicating that a condition unfavorable to the use of inorganic nanomaterials in biological systems is the presence of infection diseases. These results, combined with the proved PL stability in biological buffers, open the way for the use of pSi-TiO2 microparticles as promising materials in nanomedicine, but their ability to increase immune cell activation by other agonists should be considered and even exploited.


Postoperative quantitative assessment of reconstructive tissue status in a cutaneous flap model using spatial frequency domain imaging.
The purpose of this study was to investigate the capabilities of a novel optical wide-field imaging technology known as spatial frequency domain imaging to quantitatively assess reconstructive tissue status. Twenty-two cutaneous pedicle flaps were created on 11 rats based on the inferior epigastric vessels. After baseline measurement, all flaps underwent vascular ischemia, induced by clamping the supporting vessels for 2 hours (either arteriovenous or selective venous occlusions); normal saline was injected into the control flap and hypertonic-hyperoncotic saline solution was injected into the experimental flap. Flaps were monitored for 2 hours after reperfusion. The spatial frequency domain imaging system was used for quantitative assessment of flap status over the duration of the experiment. All flaps demonstrated a significant decline in oxyhemoglobin and tissue oxygen saturation in response to occlusion. Total hemoglobin and deoxyhemoglobin were increased markedly in the selective venous occlusion group. After reperfusion and the administration of solutions, oxyhemoglobin and tissue oxygen saturation in those flaps that survived gradually returned to baseline levels. However, flaps for which oxyhemoglobin and tissue oxygen saturation did not show any signs of recovery appeared to be compromised and eventually became necrotic within 24 to 48 hours in both occlusion groups. Spatial frequency domain imaging technology provides a quantitative, objective method of assessing tissue status. This study demonstrates the potential of this optical technology to assess tissue perfusion in a very precise and quantitative way, enabling wide-field visualization of physiologic parameters. The results of this study suggest that spatial frequency domain imaging may provide a means for prospectively identifying dysfunctional flaps well in advance of failure.


Past recreational physical activity, body size, and all-cause mortality following breast cancer diagnosis: results from the Breast Cancer Family Registry.
Few studies have considered the joint association of body mass index (BMI) and physical activity, two modifiable factors, with all-cause mortality after breast cancer diagnosis. Women diagnosed with invasive breast cancer (n = 4,153) between 1991 and 2000 were enrolled in the Breast Cancer Family Registry through population-based sampling in Northern California, USA; Ontario, Canada; and Melbourne and Sydney, Australia. During a median follow-up of 7.8 years, 725 deaths occurred. Baseline questionnaires assessed moderate and vigorous recreational physical activity and BMI prior to diagnosis. Associations with all-cause mortality were assessed using Cox proportional hazards regression, adjusting for established prognostic factors. Compared with no physical activity, any recreational activity during the 3 years prior to diagnosis was associated with a 34% lower risk of death [hazard ratio (HR) = 0.66, 95% confidence interval (CI): 0.51-0.85] for women with estrogen receptor (ER)-positive tumors, but not those with ER-negative tumors; this association did not appear to differ by race/ethnicity or BMI. Lifetime physical activity was not associated with all-cause mortality. BMI was positively associated with all-cause mortality for women diagnosed at age > or =50 years with ER-positive tumors (compared with normal-weight women, HR for overweight = 1.39, 95% CI: 0.90-2.15; HR for obese = 1.77, 95% CI: 1.11-2.82). BMI associations did not appear to differ by race/ethnicity. Our findings suggest that physical activity and BMI exert independent effects on overall mortality after breast cancer.


Brain calcification because of neurocysticercosis: a vast field to be explored.
Neurocysticercosis is the most common helminthic infection of the central nervous system caused by the larval stage of the pork tapeworm, Taenia solium. Endemic regions include Latin American countries, sub-Saharan Africa, and large regions of Asia, including the Indian subcontinent and is a global health problem. Seizures are the most common manifestation and approximately 30% of adult-onset seizures in endemic regions are attributable to NCC. Calcifications because of neurocysticercosis is the most common finding on imaging in endemic regions and are important seizure foci contributing to the burden of epilepsy. After treatment with antiparasitics for multiple viable parenchymal disease, approximately 38% of cysts that resolved after 6 months of therapy will result in residual calcifications, which represents a significant burden of residual disease. Calcified disease has been referred to as 'inactive disease', but there is accumulating evidence to suggest that calcified granulomas are actually dynamic and substantially contribute to the development and maintenance of seizures. Calcified parenchymal neurocysticercosis contributes significantly to the development and maintenance of seizures in endemic regions. Understanding the pathogenesis of the role of calcified NCC in seizure development and risk factors for development of calcifications after treatment is critical to decreasing the burden of symptomatic disease in endemic regions.


Disentangling causes of seasonal infection prevalence patterns: tropical tadpoles and chytridiomycosis as a model system.
Identifying the factors that affect pathogen prevalence is critical to understanding the effects of wildlife diseases. We aimed to examine drivers of seasonal changes in the prevalence of infection by the amphibian chytrid fungus Batrachochytrium dendrobatidis in tadpoles. Because tadpoles may be important reservoirs for this disease, examining them will aid in understanding how chytridiomycosis affects entire amphibian populations. We hypothesized that temperature is a strong driver of prevalence of Bd in tadpoles, and the accumulation of infection as tadpoles become larger and older also drives prevalence in this system. We studied Litoria rheocola, a tropical rainforest stream frog with seasonal recruitment of annual tadpoles, and surveyed 6 streams in northeastern Queensland, Australia. Comparisons among models relating infection status to stream type, season, their interaction, tadpole age, and water temperature showed that age explained a large portion of the variance in infection status. Across sites and seasons, larger, older tadpoles had increased mean probabilities of infection, indicating that a large component of the variation among individuals was related to age, and thus to cumulative infection risk. Our results indicate that in systems with annual tadpoles, seasonal changes in infection prevalence may be strongly affected by seasonal patterns of tadpole growth and development in addition to stream type, season, and water temperature. These effects may then influence prevalence of infection in terrestrial individuals in species that have relatively frequent contact with water. This reinforces the need to integrate studies of the drivers of pathogen prevalence across all host life history stages.


The relationship between eye-winking tics, frequent eye-blinking and blepharospasm.
A family is reported in which three generations were affected with eye-winking tics and/or blepharospasm. The proband developed eye-winking tics in childhood and then developed excessive blinking progressing to blepharospasm by the age of 21 years. His mother presented with Meige's syndrome and spasmodic torticollis at the age of 59 years; his uncle had blinked excessively from his early forties. His eldest son developed an eye-winking tic with facial grimacing at the age of 8 years, and in another son, a self-limiting period of eye-blinking occurred at the age of 4 years. The recovery cycle of the blink reflex was abnormal in all three generations. Three other children with eye-winking tics have a parent or close relative with frequent eye-blinking or blepharospasm. Five patients with adult-onset blepharospasm or Meige's syndrome are also described who had excessive eye-blinking dating back to childhood. It is suggested that eye-winking tics, frequent blinking and blepharospasm may share common pathophysiological mechanisms; the clinical expression may be age-related.


Automatic classification of foot examination findings using clinical notes and machine learning.
We examine the feasibility of a machine learning approach to identification of foot examination (FE) findings from the unstructured text of clinical reports. A Support Vector Machine (SVM) based system was constructed to process the text of physical examination sections of in- and out-patient clinical notes to identify if the findings of structural, neurological, and vascular components of a FE revealed normal or abnormal findings or were not assessed. The system was tested on 145 randomly selected patients for each FE component using 10-fold cross validation. The accuracy was 80%, 87% and 88% for structural, neurological, and vascular component classifiers, respectively. Our results indicate that using machine learning to identify FE findings from clinical reports is a viable alternative to manual review and warrants further investigation. This application may improve quality and safety by providing inexpensive and scalable methodology for quality and risk factor assessments at the point of care.


Arabidopsis CPL4 is an essential C-terminal domain phosphatase that suppresses xenobiotic stress responses.
Eukaryotic gene expression is both promoted and inhibited by the reversible phosphorylation of the C-terminal domain of RNA polymerase II (pol II CTD). More than 20 Arabidopsis genes encode CTD phosphatase homologs, including four CTD phosphatase-like (CPL) family members. Although in vitro CTD phosphatase activity has been established for some CPLs, none have been shown to be involved in the phosphoregulation of pol II in vivo. Here we report that CPL4 is a CTD phosphatase essential for the viability of Arabidopsis thaliana. Mass spectrometry analysis identified the pol II subunits RPB1, RPB2 and RPB3 in the affinity-purified CPL4 complex. CPL4 dephosphorylates both Ser2- and Ser5-PO(4) of the CTD in vitro, with a preference for Ser2-PO(4). Arabidopsis plants overexpressing CPL4 accumulated hypophosphorylated pol II, whereas RNA interference-mediated silencing of CPL4 promoted hyperphosphorylation of pol II. A D128A mutation in the conserved DXDXT motif of the CPL4 catalytic domain resulted in a dominant negative form of CPL4, the overexpression of which inhibited transgene expression in transient assays. Inhibition was abolished by truncation of the phosphoprotein-binding Breast Cancer 1 C-terminal domain of CPL4, suggesting that both catalytic function and protein-protein interaction are essential for CPL4-mediated regulation of gene expression. We were unable to recover a homozygous cpl4 mutant, probably due to the zygotic lethality of this mutation. The reduction in CPL4 levels in CPL4(RNAi) plants increased transcript levels of a suite of herbicide/xenobiotic-responsive genes and improved herbicide tolerance, thus suggesting an additional role for CPL4 as a negative regulator of the xenobiotic detoxification pathway.


Heme oxygenase-1 expression in the guinea pig cochlea induced by intense noise stimulation.
These results suggest that noise induces free radical formation in the cochlea and that, in the guinea pig, heme oxygenase-1 (HO-1) may play an important role in the recovery from noise trauma in the organ of Corti. Free radicals are involved in noise-induced hearing loss. It has been demonstrated that the induction of HO-1 may protect cells exposed to oxidative challenge. The present study was designed to investigate the effect of intense noise exposure on HO-1 induction. A total of 25 adult guinea pigs (body weight 200-300 g) with a normal Preyers's reflex were used as subjects. Based on preliminary tests, the appropriate intensities and durations of noise were determined that were adequate to induce apparent threshold shifts and lead to various recovery patterns to initial thresholds. The sound was routed through a power amplifier to a speaker, which was positioned directly over the animals in a sound chamber. Auditory brainstem response (ABR) testing, Western blot analysis for HO-1, and immunohistochemical testing were done. Exposure of the guinea pigs to 115 dB SPL octave band noise for 5 h induced HO-1 expression in the organ of Corti. In the organ of Corti, HO-1 expression increased mainly in the outer hair cells. Some expression of HO-1 was observed before and after noise exposure in the supporting cells. HO-1 expression in the organ of Corti was definitely increased in guinea pigs with an intense noise exposure which causes a temporary threshold shift.


Quantification and prognostic value of programmed cell death ligand-1 expression in dogs with diffuse large B-cell lymphoma.
OBJECTIVE To measure programmed cell death ligand-1 (PD-L1) mRNA expression in archived primary nodal diffuse large B-cell lymphoma (DLBCL) specimens of dogs and determine whether that expression was associated with progression-free survival time (PFST). SAMPLE Archived tumoral lymph node specimens from 42 dogs with DLBCL and lymph node specimens from 10 healthy dogs (controls). PROCEDURES Archived tumoral and control lymph node specimens underwent multiplex qPCR analysis with probes and primers against canine PD-L1 and glyceraldehyde 3-phosphate dehydrogenase (housekeeping gene) to determine PD-L1 mRNA expression. The 2-ΔΔCt method was used to calculate the fold change in PD-L1 expression in DLBCL specimens relative to that in control lymph nodes. Kaplan-Meier and Cox proportional hazard analyses were used to evaluate the association of various tumoral and clinical factors with PFST. RESULTS The fold change in PD-L1 mRNA expression in DLBCL specimens relative to control specimens ranged from 0.21 to 7.44. Twenty-one of 42 (50%) DLBCL specimens had a PD-L1-fold change > 1, which suggested PD-L1 was overexpressed in those specimens. Median PFST was 249 days for dogs with DLBCL. The PFST was not associated with PD-L1 mRNA expression but was associated with thrombocytopenia at the time of diagnosis (hazard ratio, 2.56; 95% confidence interval, 1.28 to 5.15). CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that tumoral PD-L1 mRNA expression varied among dogs with DLBCL and that PD-L1 MRNA was overexpressed in half the study population. Therefore, anti-PD-L1 therapies may be clinically beneficial for some dogs with DLBCL.


Impact of food and drinks on urine production: A systematic review.
The impact of food and drinks on body fluid metabolism is of direct clinical relevance but current evidence remains fragmented. Synthesise current evidence on the role of food and drinks in urine production. Systematic review as per PRISMA guidelines using MEDLINE and EMBASE databases (completed October 2019). Studies reporting on the effect of food, food constituents, and drinks on urine production were included. Two authors performed an independent extraction of relevant articles using predetermined data sets and completed quality-of-study indicators. A total of 49 studies were included, of which 21 enroled human subjects, and 28 were clinically relevant animal studies (all of which utilised rodent models). The included studies were determined to be of variable quality. High dietary sodium, as well as wine, spirits, high-caffeine coffee, and caffeinated energy drinks, increased urine production in human studies. Decreased urine production was associated with low dietary sodium and consumption of milk, orange juice, and high-salt/high-sugar drinks. In animal models, a variety of fruits, vegetables, herbs, spices, and honey were associated with increased urine production. Current evidence suggests that although several types of food and drinks may impact body fluid metabolism, the quality of the data is variable. Urine production appears to be influenced by multiple factors including composition (ie, moisture, macronutrients, and electrolytes), metabolite load, and the presence of specific diuresis-promoting substances (eg, caffeine, alcohol) and other bioactive phytochemicals. Future research is needed to support current evidence and the physiologic mechanisms underlying these findings.


Evaluation of distal radial artery cross-sectional internal diameter in neonates and infants by ultrasound and adequate selection of an intra-arterial catheter size.
Radial artery catheterization in neonates, infants, and young children is a common and useful invasive procedure that brings technical placement challenges and potential complications due to the small diameter size of the radial artery in these patients. The aim of this study is to determine appropriate catheter sizes in infants up to 6 months of age. A total of fifty infants undergoing general anesthesia or hospitalized in the neonatal intensive care unit were included. Images of the radial artery diameter were obtained from the infant's wrist using Philips EPIQ Diagnostic Ultrasound System CVX Release 4.0. All images obtained were distal in the forearm, medial to the border of the styloid process of the radius, at the point of maximal impulse of the radial artery, and with the wrist at a 45-degree angle position. We recorded postmenstrual age, chronological age, gender, weight, location, comorbidities, medications, weight, and vital signs of each individual. In this single cohort study of 50 children whose ages ranged from 0 to 6 months chronological age, their radial artery diameters were averaged proportionally to their weight and age. Use of a 22G catheter would result in 100% occlusion of the diameter of the artery in most study subjects. Use of a 24G catheter would result in a range of 75%-99% occlusion depending on weight, postmenstrual age, and chronological age of the infants. In view of these findings, we recommend using US to measure the diameter of the radial artery and choose the most appropriate catheter size before proceeding with US-guidance for radial artery cannulation in infants. This will prevent inappropriate sizing of the catheter and the thrombotic complications this can incur.


Rebamipide may be comparable to H2 receptor antagonist in healing iatrogenic gastric ulcers created by endoscopic mucosal resection: a prospective randomized pilot study.
Endoscopic mucosal resection (EMR) results in the formation of iatrogenic gastric ulcers and the optimal treatments for such ulcers are still unclear. We aimed to evaluate the efficacy of rebamipide in the management of EMR-induced ulcers by comparing it with an H(2) receptor antagonist. After EMR, patients were randomly assigned into either rebamipide or famotidine groups. All patients received a one-week lansoprazole 30 mg q.d. therapy followed by three-week famotidine (20 mg b.i.d.) or rebamipide (100 mg t.i.d.) therapy. Four weeks after the treatments, ulcer sizes, stages, bleeding rates, and ulcer-related symptoms were compared using endoscopy and a questionnaire. A total of 63 patients were enrolled in this study. Finally, 51 patients were analyzed, 26 in rebamipide and 25 in famotidine group. Baseline characteristics were not significantly different between the two groups. Four weeks after EMR, the two groups were comparable in terms of ulcer reduction ratio (P=0.297), and ulcer stage (P=1.000). Moreover, no difference was observed with regard to ulcer-related symptoms, drug compliance, adverse drug event rates, and bleeding rates. Our data suggest that rebamipide is not inferior to famotidine in healing iatrogenic gastric ulcers, and could be a therapeutic option in the treatment of such ulcers.


L-ascorbic acid: A true substrate for HIF prolyl hydroxylase?
L-Ascorbate (L-Asc), but not D-isoascorbate (D-Asc) and N-acetylcysteine (NAC) suppress HIF1 ODD-luc reporter activation induced by various inhibitors of HIF prolyl hydroxylase (PHD). The efficiency of suppression by L-Asc was sensitive to the nature of HIF PHD inhibitor chosen for reporter activation. In particular, the inhibitors developed to compete with alpha-ketoglutarate (αKG), were less sensitive to suppression by the physiological range of L-Asc (40-100 μM) than those having a strong iron chelation motif. Challenging those HIF activators in the reporter system with D-Asc demonstrated that the D-isomer, despite exhibiting the same reducing potency with respect to ferric iron, had almost no effect compared to L-Asc. Similarly, no effect on reporter activation was observed with cell-permeable reducing agent NAC up to 1 mM. Docking of L-Asc and D-Asc acid into the HIF PHD2 crystal structure showed interference of Tyr310 with respect to D-Asc. This suggests that L-Asc is not merely a reducing agent preventing enzyme inactivation. Rather, the overall results identify L-Asc as a co-substrate of HIF PHD that may compete for the binding site of αKG in the enzyme active center. This conclusion is in agreement with the results obtained recently in cell-based systems for TET enzymes and jumonji histone demethylases, where L-Asc has been proposed to act as a co-substrate and not as a reducing agent preventing enzyme inactivation.


Nerve growth factor-independent reduction in choline acetyltransferase activity in PC12 cells expressing mutant presenilin-1.
Mutations in the presenilin genes (PS-1 and PS-2) are linked to early onset familial Alzheimer's disease (AD), but the mechanisms by which these mutations cause the cognitive impairment characteristic of AD are unknown. Basal forebrain cholinergic neurons are involved in learning and memory processes, and reductions in choline acetyl-transferase (ChAT) activity are a characteristic feature of AD brain. We therefore hypothesized that presenilin mutations suppress expression of the cholinergic phenotype. In rat PC12 cells stably transfected with the human PS-1 gene containing the Leu --> Val mutation at codon 286 (L286V), we observed a drastic reduction (>90%) in basal ChAT activity compared with cells transfected with vector alone. By immunocytochemistry, a similar decrease in ChAT protein levels was found in the mutant transfectants. In cells differentiated with nerve growth factor, ChAT activity was again markedly lower in L286V-expressing cells than in control cells. We also observed reductions in ChAT activity in PC12 cells expressing the wild-type human PS-1 gene but to a lesser extent than in L286V-expressing cells. The viability of cells transfected with either the wild-type or the mutant PS-1 gene was not compromised. Our results suggest that PS-1 mutations may contribute to the cognitive impairment in AD by causing a nontoxic suppression of the cholinergic phenotype.


A cross-sectional study of medication-related factors and caries experience in asthmatic children.
The purpose of this study was to examine the relationship between the specific types of medication, length of use, frequency of use, and dosing time of day on the dental caries of children diagnosed with asthma. Using a patient list from a previous study, surveys were mailed to the parents of 179 asthmatic children. The survey itself consisted of a table that asked 4 questions: (1) What combination of asthma medications was used by the subject? (2) How long were the medications used? (3) How often were the medications used? (4) What time of day were the medications used? Of the 179 surveys that were mailed out, 156 were returned. Children who used their medication greater than twice daily were significantly more likely to experience dental disease in both the primary (odds ratio [OR]=2.56, 95% confidence interval [CI]=1.45-6.29) and mixed dentitions (OR=3.56, 95% CI 2.45-5.94). Increased frequency of asthma medication use was associated with increased likelihood of caries experience. The time of day asthma medication was used was associated with increased likelihood of caries experience in children in the primary dentition. Duration of asthma medication use was associated with a decreased likelihood of caries experience in children in the mixed dentition.


Inhibitors of the Transcription Factor STAT3 Decrease Growth and Induce Immune Response Genes in Models of Malignant Pleural Mesothelioma (MPM).
Malignant pleural mesothelioma (MPM) is an aggressive cancer defined by loss-of-function mutations with few therapeutic options. We examined the contribution of the transcription factor Signal transducer and activator of transcription 3 (STAT3) to cell growth and gene expression in preclinical models of MPM. STAT3 is activated in a variety of tumors and is thought to be required for the maintenance of cancer stem cells. Targeting STAT3 using specific small hairpin RNAs (shRNAs) or with the pharmacologic inhibitors atovaquone or pyrimethamine efficiently reduced cell growth in established cell lines and primary-derived lines while showing minimal effects in nontransformed LP9 mesothelial cells. Moreover, atovaquone significantly reduced viability and tumor growth in microfluidic cultures of primary MPM as well as in an in vivo xenotransplant model. Biological changes were linked to modulation of gene expression associated with STAT3 signaling, including cell cycle progression and altered p53 response. Reflecting the role of STAT3 in inducing localized immune suppression, using both atovaquone and pyrimethamine resulted in the modulation of immunoregulatory genes predicted to enhance an immune response, including upregulation of ICOSLG (Inducible T-Cell Costimulator Ligand or B7H2). Thus, our data strongly support a role for STAT3 inhibitors as anti-MPM therapeutics.


Twisted light transmission over 143 km.
Spatial modes of light can potentially carry a vast amount of information, making them promising candidates for both classical and quantum communication. However, the distribution of such modes over large distances remains difficult. Intermodal coupling complicates their use with common fibers, whereas free-space transmission is thought to be strongly influenced by atmospheric turbulence. Here, we show the transmission of orbital angular momentum modes of light over a distance of 143 km between two Canary Islands, which is 50× greater than the maximum distance achieved previously. As a demonstration of the transmission quality, we use superpositions of these modes to encode a short message. At the receiver, an artificial neural network is used for distinguishing between the different twisted light superpositions. The algorithm is able to identify different mode superpositions with an accuracy of more than 80% up to the third mode order and decode the transmitted message with an error rate of 8.33%. Using our data, we estimate that the distribution of orbital angular momentum entanglement over more than 100 km of free space is feasible. Moreover, the quality of our free-space link can be further improved by the use of state-of-the-art adaptive optics systems.


Non-pharmacological management of musculoskeletal disease in primary care.
Musculoskeletal diseases as a group are one of the most common causes of contact in primary care and the most common causes of disability and long-term sick leave in several Western countries. Pain and dysfunction are often present without any specific findings in the musculoskeletal system, and a strictly biomedical approach is often inadequate. Body structure and function interact with personal and environmental factors, affecting the ability to perform activities and participate in society. It is important to meet these needs in primary care, and non-pharmacological principles such as physical activity and patient education with a cognitive approach are cornerstones in a multimodal management model.


Validation of the nurse leadership and organizational culture (N-LOC) questionnaire.
Leadership style and organizational culture have often been studied independently in nursing research despite abundant evidence that the two factors both influence employee outcomes. Moreover, diverse theoretical typology and measuring instruments challenges generalizability of findings. Employees from different cultural, geographical, occupational settings were also reported to have varying interpretation on organizational culture and leadership style underlying constructs. This study aims to validate the Nursing Leadership and Organizational Culture (N-LOC) questionnaire, based on the two commonly used theoretical frameworks: Multifactor Leadership Theory and Competing Values Framework, on its applicability in an Asian hospital setting. All full-time nurses from two distinctive Asian hospitals (H1: n = 295 and H2: n = 1146) were invited to participate in this questionnaire study. Exploratory factor analysis (EFA) was carried out when confirmatory factor analysis (CFA) fit indices were not satisfactory after model refinement to explore the actual underlying construct in sampled population. Part-time and outsourced nurses were excluded. 93 nurses from H1 were randomly selected for test-retest reliability 4 weeks post initial survey. Scale internal consistency, convergent and discriminant validity were also assessed. CFA results indicated that the proposed CVF organizational culture 4-factor structure was applicable to our sample but not the MLQ leadership 3-factor/9-factor structure. EFA revealed a 2-factor leadership style construct for our sample, named Confucius transformational and Laissez-Faire passive leadership. Transformational leadership traits already embedded in Confucius cultural values (self-sacrifice, stresses collective mission, instills pride) did not apply, the new Confucius transformational construct which resembles LMX theory paternalistic leadership style is deemed more suitable in an Asian context. A final 14-item 2-factor leadership and 13-item 4-factor organizational culture construct was yielded with satisfactory fit indices (CFI, TLI > 0.95, RMSEA < 0.08), internal consistency (Cronbach's alpha > 0.7), test-retest reliability (ICC > 0.4) and convergent and discriminant validity. A reliable N-LOC organizational culture and leadership questionnaire (N-LOC) has been validated in an Asian nurse context. Study results demonstrated the importance of scale validation in cross-cultural adaptation, as underlying scale constructs may change with specific cultural and contextual factors. Future studies are encouraged to test the adaptation of this scale in other cultural and occupational settings.


Synthetic-array heterodyne detection: a single-element detector acts as an array.
A simple technique, synthetic-array heterodyne detection, permits an ordinary single-element optical detector to behave as though it were a coherent array. A successful experimental implementation of a synthetic two-pixel array, using a CO(2) laser and a single-element HgCdTe photodiode is reported. A different heterodyne local oscillator frequency is incident upon each resolvable region of the detector surface. Thus different regions are mapped to different heterodyne beat frequencies. One can determine where the photons struck the detector surface even though a single electrical connection to the detector is used. This also prevents the destructive interference that occurs when multiple speckles are imaged (akin to spatial diversity). In coherent lidar this permits a larger field of view. An acousto-optic modulator produces the local oscillator frequencies and can achieve good spatial separation of optical frequencies of the order of a megahertz apart.


Assessment of the upper motor neuron in amyotrophic lateral sclerosis.
Clinical signs of upper motor neuron (UMN) involvement are an important component in supporting the diagnosis of amyotrophic lateral sclerosis (ALS), but are often not easily appreciated in a limb that is concurrently affected by muscle wasting and lower motor neuron degeneration, particularly in the early symptomatic stages of ALS. Whilst recent criteria have been proposed to facilitate improved detection of lower motor neuron impairment through electrophysiological features that have improved diagnostic sensitivity, assessment of upper motor neuron involvement remains essentially clinical. As a result, there is often a significant diagnostic delay that in turn may impact institution of disease-modifying therapy and access to other optimal patient management. Biomarkers of pathological UMN involvement are also required to ensure patients with suspected ALS have timely access to appropriate therapeutic trials. The present review provides an analysis of current and recently developed assessment techniques, including novel imaging and electrophysiological approaches used to study corticomotoneuronal pathology in ALS.


The yeast Rat1 exonuclease promotes transcription termination by RNA polymerase II.
The carboxy-terminal domain (CTD) of the RNA polymerase II (RNApII) largest subunit consists of multiple heptapeptide repeats with the consensus sequence YSPTSPS. Different CTD phosphorylation patterns act as recognition sites for the binding of various messenger RNA processing factors, thereby coupling transcription and mRNA processing. Polyadenylation factors are co-transcriptionally recruited by phosphorylation of CTD serine 2 (ref. 2) and these factors are also required for transcription termination. RNApII transcribes past the poly(A) site, the RNA is cleaved by the polyadenylation machinery, and the RNA downstream of the cleavage site is degraded. Here we show that Rtt103 and the Rat1/Rai1 5' --> 3' exonuclease are localized at 3' ends of protein coding genes. In rat1-1 or rai1Delta cells, RNA 3' to polyadenylation sites is greatly stabilized and termination defects are seen at many genes. These findings support a model in which poly(A) site cleavage and subsequent degradation of the 3'-downstream RNA by Rat1 trigger transcription termination.


Production of carbon monoxide and gaseous hydrocarbons in seawater: relation to dissolved organic carbon.
Carbon monoxide, ethylene, and propylene were produced in illuminated, cell-free distilled water or natural seawater systems to which dissolved organic matter produced by phytoplankton had been added. Methane and the higher saturated gaseous hydrocarbons were not produced. In the dark, little or no carbon monoxide and no hydrocarbons were produced in the distilled water systems; only carbon monoxide was produced in natural seawater, but less was produced than in the light.


Chestnut resistance to the blight disease: insights from transcriptome analysis.
A century ago, Chestnut Blight Disease (CBD) devastated the American chestnut. Backcross breeding has been underway to introgress resistance from Chinese chestnut into surviving American chestnut genotypes. Development of genomic resources for the family Fagaceae, has focused in this project on Castanea mollissima Blume (Chinese chestnut) and Castanea dentata (Marsh.) Borkh (American chestnut) to aid in the backcross breeding effort and in the eventual identification of blight resistance genes through genomic sequencing and map based cloning. A previous study reported partial characterization of the transcriptomes from these two species. Here, further analyses of a larger dataset and assemblies including both 454 and capillary sequences were performed and defense related genes with differential transcript abundance (GDTA) in canker versus healthy stem tissues were identified. Over one and a half million cDNA reads were assembled into 34,800 transcript contigs from American chestnut and 48,335 transcript contigs from Chinese chestnut. Chestnut cDNA showed higher coding sequence similarity to genes in other woody plants than in herbaceous species. The number of genes tagged, the length of coding sequences, and the numbers of tagged members within gene families showed that the cDNA dataset provides a good resource for studying the American and Chinese chestnut transcriptomes. In silico analysis of transcript abundance identified hundreds of GDTA in canker versus healthy stem tissues. A significant number of additional DTA genes involved in the defense-response not reported in a previous study were identified here. These DTA genes belong to various pathways involving cell wall biosynthesis, reactive oxygen species (ROS), salicylic acid (SA), ethylene, jasmonic acid (JA), abscissic acid (ABA), and hormone signalling. DTA genes were also identified in the hypersensitive response and programmed cell death (PCD) pathways. These DTA genes are candidates for host resistance to the chestnut blight fungus, Cryphonectria parasitica. Our data allowed the identification of many genes and gene network candidates for host resistance to the chestnut blight fungus, Cryphonectria parasitica. The similar set of GDTAs in American chestnut and Chinese chestnut suggests that the variation in sensitivity to this pathogen between these species may be the result of different timing and amplitude of the response of the two to the pathogen infection. Resources developed in this study are useful for functional genomics, comparative genomics, resistance breeding and phylogenetics in the Fagaceae.


Tuberculosis-associated HLH in a patient with chronic kidney disease on haemodialysis.
Haemophagocytic lymphohistiocytosis (HLH) is a rare immunological disorder that is accompanied by a high mortality rate when the underlying aetiology is miliary tuberculosis. We report a case of tuberculosis (TB)-associated HLH in a haemodialysis patient, from a TB-endemic region, who missed two sessions of dialysis before developing the primary symptoms of HLH. The patient presented with non-specific findings including pancytopenia, coagulopathy and transaminitis. Computer-tomography imaging and microbiology from bronchoalveolar lavage evidenced miliary tuberculosis. Further testing revealed the TB-associated-HLH characteristic pattern of thrombocytosis, leukopenia, transaminitis, hyperferritinemia and elevated fibrinogen. The patient initially demonstrated improvement after initiation of anti-TB therapy. However, soon thereafter began to paradoxically deteriorate and then expire from apparent tuberculosis-immune reconstitution inflammatory syndrome. This case highlights the importance of early diagnosis and treatment, and consequently of the utility of diagnostic systems such as the HScore in cases of high clinical suspicion.


Twelve Months Post-treatment Results From the Norwegian Version of Improving Access to Psychological Therapies.
Prompt Mental Health Care (PMHC) is the Norwegian version of the England's Improving Access to Psychological Therapies (IAPT). Both programs have been associated with substantial symptom reductions from pre- to post-treatment. The present study extends these findings by investigating symptom levels at 12 months post-treatment, as well as treatment outcome in relation to low- vs. high-intensity treatment forms. A prospective cohort design was used. All participants (n = 1530) were asked to complete the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 questionnaire (GAD-7) at baseline, before each session during treatment, at final treatment, and at 12 months post-treatment. Cohen's d was used as effect size measure. Sensitivity analyses were conducted to examine the impact of the high missing data rates at post-treatment (≈44%) and 12 months post-treatment (≈58%). A large symptom reduction was seen from baseline to 12 months post-treatment for both PHQ (d = -0.98) and GAD (d = -0.94). Improvements observed at post-treatment were largely maintained at 12 months post-treatment (PHQ (Δd = 0.10) and GAD (Δd = 0.09). Recovery rates decreased only slightly from 49.5% at post-treatment to 45.0% at follow-up. Both low- and high-intensity treatment forms were associated with substantial and lasting symptoms reductions (-1.26 ≤ d ≤ -0.73). Sensitivity analyses did not substantially alter the main results. The findings suggest long-lasting effects of the PMHC program and encourage the use of low-intensity treatment forms in PMHC like settings.


Ovarian follicular cysts in dairy cows.
Ovarian follicular cysts are anovulatory follicular structures that occur in 10 to 13% of dairy cows. This review focuses upon the dynamics of cyst growth, development, and persistence as well as on associated endocrine and cellular mechanisms. During the estrous cycle of cows, two to four waves of follicular growth occur. From a cohort of recruited follicles, one is selected for continued growth and dominance while the other undergo atresia and regress. In contrast, cysts have long been thought to be static structures that persist for extended periods. Although cysts can persist for extended periods, most regress over time and are replaced during subsequent follicular waves. The next dominant follicle either ovulates or develops into a new cyst. The recruitment of a cohort of follicles from which a cyst develops and the growth rate of cysts to ovulatory size are similar to ovulatory follicular waves, but the cyst continues to grow for a longer period. The interval between waves of follicular growth is longer for cows with cysts than for cows with normal estrous cycles. Each wave is preceded by a transient increase in circulating FSH. Near the time of cyst development and persistence, the concentration of FSH is not different from that during normal estrous cycles. Serum concentrations of LH and estradiol-17 beta are higher in cows that develop cysts than in cows that do not. Conversely, hypothalamic content of GnRH is lower in cows with cysts. Thus, cysts are dynamic structures, and their development and lifespan are likely associated with altered hypothalamic-hypophysial-ovarian function.


Fluoroquinolone resistance and Clostridium difficile, Germany.
We characterized 670 Clostridium difficile isolates collected from patients in 84 hospitals in Germany in 2008. PCR ribotyping showed high prevalence of ribotype 001 and restricted dissemination of ribotype 027 strains. Fluoroquinolone resistance and associated gyrase mutations were frequent in various ribotypes, but no resistance to metronidazole or vancomycin was noted.


Structural phase transitions in flexible DUT-8(Ni) under high hydrostatic pressure.
The behaviours of the open pore (op) and closed pore (cp) phases of the flexible Ni2(ndc)2(dabco) (ndc - 2,6-naphthalene dicarboxylate, dabco - 1,4-diazabicyclo[2.2.2]octane, DUT-8(Ni)) metal-organic framework under high hydrostatic pressures up to 10 GPa in isopropanol and silicone oil were studied by Raman spectroscopy. Ab initio simulations of vibrational spectra were performed for the open and closed pore phases, which allowed us to disclose the characteristic vibrational modes affected by the structural transitions under pressure. Analysis of theoretical and experimental Raman data suggests that the op-cp transition involves gateway vibrations at 25 and 67 cm-1, corresponding to trampoline/rotational motions of aromatic linkers. The experiments reveal the formation of new distorted cp phases at pressures higher than 2 GPa, which are formed without amorphisation. The transition between the cp phase and the distorted cp phase is reversible. The experiments also reveal the pivotal role of the pressure transmitting medium on the phase transition behaviour.


HIV-1 conserved-element vaccines: relationship between sequence conservation and replicative capacity.
To overcome the problem of HIV-1 variability, candidate vaccine antigens have been designed to be composed of conserved elements of the HIV-1 proteome. Such candidate vaccines could be improved with a better understanding of both HIV-1 evolutionary constraints and the fitness cost of specific mutations. We evaluated the in vitro fitness cost of 23 mutations engineered in the HIV-1 subtype B Gag-p24 Center-of-Tree (COT) protein through fitness competition assays. While some mutations at conserved sites exacted a high fitness cost, as expected under the assumption that the most conserved residue confers the highest fitness, there was no overall strong relationship between sequence conservation and replicative capacity. By comparing sites that have evolved since the beginning of the epidemic to those that have remain unchanged, we found that sites that have evolved over time were more likely to correspond to HLA-associated sites and that their mutation had limited fitness costs. Our data showed no transcendent link between high conservation and high fitness cost, indicating that merely focusing on conserved segments of HIV-1 would not be sufficient for a successful vaccine strategy. Nonetheless, a subset of sites exacted a high fitness cost upon mutation--these sites have been under selective pressure to change since the beginning of the epidemic but have proved virtually nonmutable and could constitute preferred targets for vaccine design.


Floral abundance, richness, and spatial distribution drive urban garden bee communities.
In urban landscapes, gardens provide refuges for bee diversity, but conservation potential may depend on local and landscape features. Foraging and population persistence of bee species, as well as overall pollinator community structure, may be supported by the abundance, richness, and spatial distribution of floral resources. Floral resources strongly differ in urban gardens. Using hand netting and pan traps to survey bees, we examined whether abundance, richness, and spatial distribution of floral resources, as well as ground cover and garden landscape surroundings influence bee abundance, species richness, and diversity on the central coast of California. Differences in floral abundance and spatial distribution, as well as urban cover in the landscape, predicted different bee community variables. Abundance of all bees and of honeybees (Apis mellifera) was lower in sites with more urban land cover surrounding the gardens. Honeybee abundance was higher in sites with patchy floral resources, whereas bee species richness and bee diversity was higher in sites with more clustered floral resources. Surprisingly, bee species richness and bee diversity was lower in sites with very high floral abundance, possibly due to interactions with honeybees. Other studies have documented the importance of floral abundance and landscape surroundings for bees in urban gardens, but this study is the first to document that the spatial arrangement of flowers strongly predicts bee abundance and richness. Based on these findings, it is likely that garden managers may promote bee conservation by managing for floral connectivity and abundance within these ubiquitous urban habitats.


The skeletal impact of cancer therapies.
Both cancer and therapies used in the treatment of cancer can have significant deleterious effects on the skeleton, increasing the risks for both bone loss and fracture development. While advancements in cancer therapies have resulted in enhanced cancer survivorship for patients with many types of malignancies, it is increasingly recognized that efforts to reduce bone loss and limit fractures must be considered for nearly all patients undergoing cancer therapy in order to diminish the anticipated future skeletal consequences. To date, most studies examining the impact of cancer therapies on skeletal outcomes have focused on endocrine-associated cancers of the breast and prostate, with more recent advances in our understanding of bone loss and fracture risk in other malignancies. Pharmacologic efforts to limit the adverse effects of cancer therapies on bone have nearly universally employed anti-resorptive approaches, although studies have frequently relied on surrogate outcomes such as changes in bone mineral density or bone turnover markers, rather than on fractures or other skeletal-related events, as primary study endpoints. Compounding current deficiencies for the provision of optimal care is the recognition that despite clearly written and straightforward society-based guidelines, vulnerable eligible patients are very often neither identified nor provided with appropriate treatments to limit the skeletal impact of their cancer therapies.


A health disparities study of MicroRNA-146a expression in prostate cancer samples derived from African American and European American patients.
Considering the prevalence of prostate cancer all over the world, it is desired to have tools, technologies, and biomarkers which help in early detection of the disease and discriminate different races and ethnic groups. Genetic information from the single gene analysis and genome-wide association studies have identified few biomarkers, however, the drivers of prostate cancer remain unknown in the majority of prostate cancer patients. In those cases where genetic association has been identified, the genes confer only a modest risk of this cancer, hence, making them less relevant for risk counseling and disease management. There is a need for additional biomarkers for diagnosis and prognosis of prostate cancer. MicroRNAs are a class of non-protein coding RNA molecules that are frequently dysregulated in different cancers including prostate cancer and show promise as diagnostic biomarkers and targets for therapy. Here we describe the role of micro RNA 146a (miR-146a) which may serve as a diagnostic and prognostic marker for prostate cancer, as indicated from the data presented in this report. Also, a pilot study indicated differential expression of miR-146a in prostate cancer cell lines and tissues from different racial groups. Reduced expression of miR-146a was observed in African American tumor tissues compared to those from European Whites This report provides a novel insight into understanding the prostate carcinogenesis.


Health status and quality of life in patients with severe hemophilia A: A cross-sectional survey.
Among different groups of hemophiliacs, those suffering from Severe Hemophilia A (SHA) are most vulnerable to the complications of the disease. This study investigated the Health-Related Quality of Life (HR-QoL) among adult patients with SHA. A cross-sectional study was designed to gather demographic and clinical information from adult patients with SHA. Patients with inhibitors were excluded. The remaining were asked to complete the HR-QoL questionnaire after being examined for joint health using the Hemophilia Joint Health Score (HJHS). The HR-QoL and joint conditions were measured in 38 patients. The mean EQ-5D value scores were 0.46 (SD=0.23) while the mean Visual Analogous Scale score was 50 (SD=18.7). The clinical examination of patients indicated that the HJHS were as follows: eight patients had a score of 55-75, 12 patients had a score of 40-55, 7 of them (25-40) and 11 patients had a score of 10-25. The results obtained from this study showed that HRQoL in hemophilia patients was considerably low. Pain, anxiety/depression, and motion limitations were the main causes of the disutility for these patients respectively.


Effects of secondhand smoke on thyroid function.
Growing evidence suggests that the effects of second hand smoke (SHS) exposure contribute to disruptions in thyroid function. Toxic elements contained in cigarette smoke, such as thiocyanate, may be partially responsible for impaired thyroid hormonogenesis. SHS-induced inflammatory stress, namely interleukin 1beta (IL-1beta), impairs thyroid hormonogenesis and iodine uptake; initiates interleukin 6 (IL-6) production from thyroid epithelial cells and stimulates the expression of molecules that exacerbate thyroid autoimmunity. The link between SHS exposure and thyroid autoimmune disease is not well documented and thus, remains to be fully understood. Elevated inflammatory stress and thyroid hormone secretion in response to SHS exposure initiates catabolic processes that alter body composition via lean body mass breakdown; translating to an elevation in resting energy expenditure of approximately 10%. The combination of certain biological factors, such as sex and/or existing thyroid disease may stimulate differential SHS-induced effects on thyroid function. Nevertheless, exposure to SHS disturbs vital human processes via thyroid disruption.


Powered liposuction: an evaluation of currently available instrumentation.
Over the past several years, powered liposuction instruments have become available to the dermatologic surgeon. These instruments all move the cannula forward and backward 2-12 mm with rapidity. This motion simulates the standard human movement of the cannula and facilitates movement through the tissue. Powered liposuction may help to prevent surgeon fatigue and has recently been shown to aid in the efficacy of fat removal. To compare and contrast currently available powered liposuction instruments, to obtain objective engineering data on the instruments, and to compare the instruments when used on actual liposuction cases. Five currently available powered liposuction systems were evaluated by the author. Each instrument was used with a 3 mm dual side port cannula on patients undergoing tumescent liposuction. An independent engineering firm, who collected objective measurements such as weight, stroke force, temperature, and vibration measurements on the instruments, evaluated the units. Noise measurements were obtained. Each of the five systems showed advantages and disadvantages. Important issues were the size and weight of the units, as well as whether they were driven electrically or pneumatically. Stroke force is variable (range 9.5-30 pounds). The noise of the units ranged between 60 and 87 dB. Vibration measurements varied from instrument to instrument. Units produced a variable amount of heat ranging from 77 degrees F to 102 degrees F. Most instruments are autoclavable, and one system is disposable. Build quality and reliability varied with the instrument. Instruments for powered liposuction have emerged in the last 2 years, with each instrument having distinct advantages and disadvantages. This article reviews five currently available powered liposuction instruments and presents objective measurements as well as the author's experience using the instruments.


Fluorescence activation with switchable oxazines.
The identification of operating principles to activate fluorescence under the influence of external stimulations is essential to enable the implementation of imaging strategies requiring the spatiotemporal control of emission. In this context, our laboratories designed mechanisms to switch fluorescence with either light or pH based on the unique photochemical and photophysical properties of either photoresponsive or halochromic oxazines respectively. These heterocycles can be connected covalently to fluorescent chromophores and opened with either light or pH to impose a significant bathochromic shift on the main absorption of the emissive appendage. Such a spectral change allows the selective excitation of the resulting species to activate bright fluorescence with infinite contrast and spatiotemporal control. Indeed, these mechanisms for fluorescence activation enable the acquisition of images with subdiffraction resolution, the selective signaling of cancer cells and the monitoring of translocating species in real time. Thus, our structural designs for fluorescence switching under external control can evolve into invaluable probes for the implementation of bioimaging strategies that would be impossible to perform with conventional fluorophores.


Grapevine leafroll-associated virus 1 occurs as genetically diverse populations.
The genetic diversity of 34 isolates of Grapevine leafroll-associated virus 1 (GLRaV-1) from different wine, table, and ornamental grape cultivars in California, New York, and Washington States in the United States was investigated. Segments of the heat-shock protein 70 homolog (HSP70h) gene, coat protein (CP) gene, coat protein duplicate 2 (CPd2) gene, and open reading frame 9 (p24) were amplified by reverse-transcription polymerase chain reaction, cloned, and sequenced. A pairwise comparison of nucleotide sequences revealed intra- and interisolate sequence diversity, with CPd2 and HSP70h being the most and the least divergent, respectively, among the four genomic regions studied. The normalized values for the ratio of nonsynonymous substitutions per nonsynonymous site to synonymous substitutions per synonymous site indicated different purifying selection pressures acting on each of the four genomic regions, with the CP and CPd2 being subjected to the strongest and weakest functional constraints, respectively. A global phylogenetic analysis of sequences from the four genomic regions revealed segregation of GLRaV-1 isolates into three major clades and a lack of clearly defined clustering by geographical origin. In contrast, only two lineages were apparent when the CP and CPd2 gene sequences were used in phylogenetic analyses. Putative recombination events were revealed among the HSP70h, CP, and p24 sequences. The genetic landscape of GLRaV-1 populations presented in this study provides a foundation for better understanding of the epidemiology of grapevine leafroll disease across grape-growing regions in the United States. In addition, this study will benefit grape clean plant programs across the country in improving the sanitary status of planting materials provided to nurseries and grape growers.


Light Sheet Tomography (LST) for in situ imaging of plant roots.
The production of crops capable of efficient nutrient use is essential for addressing the problem of global food security. The ability of a plant's root system to interact with the soil micro-environment determines how effectively it can extract water and nutrients. In order to assess this ability and develop the fast and cost effective phenotyping techniques which are needed to establish efficient root systems, in situ imaging in soil is required. To date this has not been possible due to the high density of scatterers and absorbers in soil or because other growth substrates do not sufficiently model the heterogeneity of a soil's microenvironment. We present here a new form of light sheet imaging with novel transparent soil containing refractive index matched particles. This imaging method does not rely on fluorescence, but relies solely on scattering from root material. We term this form of imaging Light Sheet Tomography (LST). We have tested LST on a range of materials and plant roots in transparent soil and gel. Due to the low density of root structures, i.e. relatively large spaces between adjacent roots, long-term monitoring of lettuce root development in situ with subsequent quantitative analysis was achieved.


Insulin-Sensitizers, Polycystic Ovary Syndrome and Gynaecological Cancer Risk.
Preclinical, early phase clinical trials and epidemiological evidence support the potential role of insulin-sensitizers in cancer prevention and treatment. Insulin-sensitizers improve the metabolic and hormonal profile in PCOS patients and may also act as anticancer agents, especially in cancers associated with hyperinsulinemia and oestrogen dependent cancers. Several lines of evidence support the protection against cancer exerted by dietary inositol, in particular inositol hexaphosphate. Metformin, thiazolidinediones, and myoinositol postreceptor signaling may exhibit direct inhibitory effects on cancer cell growth. AMPK, the main molecular target of metformin, is emerging as a target for cancer prevention and treatment. PCOS may be correlated to an increased risk for developing ovarian and endometrial cancer (up to threefold). Several studies have demonstrated an increase in mortality rate from ovarian cancer among overweight/obese PCOS women compared with normal weight women. Long-term use of metformin has been associated with lower rates of ovarian cancer. Considering the evidence supporting a higher risk of gynaecological cancer in PCOS women, we discuss the potential use of insulin-sensitizers as a potential tool for chemoprevention, hypothesizing a possible rationale through which insulin-sensitizers may inhibit tumourigenesis.


Cancer chemotherapy with lipid-based nanocarriers.
Nanotechnology has a profound effect on many areas of scientific research. Having grown exponentially, the focus of nanotechnology has been on therapeutic activity, such as cancer treatment. Lipid-based nanocarriers have attracted increasing scientific and commercial attention in the last few years as alternative carriers for the delivery of anticancer drugs. Lipid-based nanocarriers have played significant roles in the formulation of anticancer drugs to improve therapeutics. Shortcomings frequently encountered with anticancer compounds, such as poor solubility, normal tissue toxicity, poor specificity and stability, as well as the high incidence rate of drug resistance, are expected to be overcome through use of lipid-based nanocarriers. In this review, the advantages and methods of using nanocarriers to improve cancer treatment efficiency will be discussed. In addition, types of lipid-based nanocarriers are presented and hotspots in research are highlighted. It is anticipated that, in the near future, lipid-based nanocarriers will be further improved to deliver cytotoxic anticancer compounds in a more efficient, specific and safe manner.


Interleukin-5 Inhibitors for Severe Asthma: Rationale and Future Outlook.
In this review, we outline the pathophysiology of severe asthma and discuss the role of anti-interleukin (IL)-5 inhibitors for the treatment of asthma. Anti-IL-5 treatments have shown efficacy in reducing the rate of severe asthma attacks in eosinophilic asthma. We review the history of the development of these agents, lessons learnt about severe asthma along the way and key clinical trials supporting efficacy of the three anti-IL-5 treatments that are clinically available or undergoing clinical trials in asthma.


Consumption of groundwater as an independent risk factor of Salmonella choleraesuis infection: a case-control study in Taiwan.
Infection with Salmonella enterica serovar Choleraesuis (S. Choleraesuis) in humans can be considered as an endemic disease in certain regions of Taiwan, and the number of cases has increased in recent years. The goal of the case-control study discussed in this article was to identify the possible demographic and environmental risk factors associated with S. Choleraesuis infection in Taiwan. During the period of December 2005 to March 2007, the case-control study was conducted in human patients with Salmonella infection from two medical centers. Structured questionnaires were applied to collect information of relevant risk factors after interviewing 13 culture-confirmed S. Choleraesuis cases and 84 controls with other Salmonella serotype infection. After evaluation by univariate and multivariate statistical models, the results suggested that consumption of groundwater could be an independent risk factor associated with S. Choleraesuis in Taiwan. Therefore, appropriate health education needs to be conducted especially in areas where groundwater is used.


Drug attitude and other predictors of medication adherence in schizophrenia: 12 months of electronic monitoring (MEMS(®)) in the Swedish COAST-study.
The aim was to investigate clinical predictors of adherence to antipsychotics. Medication use was electronically monitored with a Medication Event Monitoring System (MEMS(®)) for 12 months in 112 outpatients with schizophrenia and schizophrenia-like psychosis according to DSM-IV. Symptom burden, insight, psychosocial function (PSP) and side effects were rated at baseline. A comprehensive neuropsychological test battery was administered and a global composite score was calculated. The Drug Attitude Inventory (DAI-10) was filled in. A slightly modified DAI-10 version for informants was distributed as a postal questionnaire. Non-adherence (MEMS(®) adherence ≤0.80) was observed in 27%. In univariate regression models low scores on DAI-10 and DAI-10 informant, higher positive symptom burden, poor function, psychiatric side effects and lack of insight predicted non-adherence. No association was observed with global cognitive function. In multivariate regression models, low patient-rated DAI-10 and PSP scores emerged as predictors of non-adherence. A ROC analysis showed that DAI-10 had a moderate ability to correctly identify non-adherent patients (AUC=0.73, p<0.001). At the most "optimal" cut-off of 4, one-third of the adherent would falsely be identified as non-adherent. A somewhat larger AUC (0.78, p<0.001) was observed when the ROC procedure was applied to the final regression model including DAI-10 and PSP. For the subgroup with informant data, the AUC for the DAI-10 informant version was 0.68 (p=0.021). Non-adherence cannot be properly predicted in the clinical setting on the basis of these instruments alone. The DAI-10 informant questionnaire needs further testing.


Immunocapture-Selected Reaction Monitoring Screening Facilitates the Development of ELISA for the Measurement of Native TEX101 in Biological Fluids.
Monoclonal antibodies that bind the native conformation of proteins are indispensable reagents for the development of immunoassays, production of therapeutic antibodies and delineating protein interaction networks by affinity purification-mass spectrometry. Antibodies generated against short peptides, protein fragments, or even full length recombinant proteins may not bind the native protein form in biological fluids, thus limiting their utility. Here, we report the application of immunocapture coupled with selected reaction monitoring measurements (immunocapture-SRM), in the rapid screening of hybridoma culture supernatants for monoclonal antibodies that bind the native protein conformation. We produced mouse monoclonal antibodies, which detect in human serum or seminal plasma the native form of the human testis-expressed sequence 101 (TEX101) protein-a recently proposed biomarker of male infertility. Pairing of two monoclonal antibodies against unique TEX101 epitopes led to the development of an ELISA for the measurement of TEX101 in seminal plasma (limit of detection: 20 pg/ml) and serum (limit of detection: 40 pg/ml). Measurements of matched seminal plasma samples, obtained from men pre- and post-vasectomy, confirmed the absolute diagnostic specificity and sensitivity of TEX101 for noninvasive identification of physical obstructions in the male reproductive tract. Measurement of male and female serum samples revealed undetectable levels of TEX101 in the systemic circulation of healthy individuals. Immunocapture-SRM screening may facilitate development of monoclonal antibodies and immunoassays against native forms of challenging protein targets.