Seismocardiography-Based Cardiac Computed Tomography Gating Using Patient-Specific Template Identification and Detection.
To more accurately trigger cardiac computed tomography angiography (CTA) than electrocardiography (ECG) alone, a sub-system is proposed as an intermediate step toward fusing ECG with seismocardiography (SCG). Accurate prediction of quiescent phases is crucial to prospectively gating CTA, which is susceptible to cardiac motion and, thus, can affect the diagnostic quality of images. The key innovation of this sub-system is that it identifies the SCG waveform corresponding to heart sounds and determines their phases within the cardiac cycles. Furthermore, this relationship is modeled as a linear function with respect to heart rate. For this paper, B-mode echocardiography is used as the gold standard for identifying the quiescent phases. We analyzed synchronous ECG, SCG, and echocardiography data acquired from seven healthy subjects (mean age: 31; age range: 22-48; males: 4) and 11 cardiac patients (mean age: 56; age range: 31-78; males: 6). On average, the proposed algorithm was able to successfully identify 79% of the SCG waveforms in systole and 68% in diastole. The simulated results show that SCG-based prediction produced less average phase error than that of ECG. It was found that the accuracy of ECG-based gating is more susceptible to increases in heart rate variability, while SCG-based gating is susceptible to high cycle to cycle variability in morphology. This pilot work of prediction using SCG waveforms enriches the framework of a comprehensive system with multiple modalities that could potentially, in real time, improve the image quality of CTA.


Calcium efflux from squid axons under constant sodium electrochemical gradient.
The effect of varying Nao and Nai on Ca efflux while maintaining the ratio Nao/Nai constant was explored in squid giant axons dialyzed with and without ATP. In the absence of ATP, the Ca efflux increased 3.4 +/- 0.2-fold when the Nao/Nai concentrations were reduced from 440/80 to 110/20 mM. In the presence of ATP a similar change did not have an appreciable effect. The inhibition of Ca efflux produced by Nai was studied in the presence and in the absence of ATP. In the absence of ATP, inhibition is very marked and is reminiscent of a unimolecular noncompetitive reaction (inactivation constant [KI] of 34 +/- 5 mM of Nai) whereas in the presence of ATP, the slight inhibition observed indicates that ATP probably increases the KI to 200mM. From the inhibition of the Ca efflux produced by Nai in the presence or absence of ATP a curve describing the dependence of Nai of the ATP-promoted fraction of Ca efflux was constructed. The effect of Nao on the Ca efflux was studied as a function of [Na]i: at low Nai, an activation constant (KA) of 41 mM for Nao was obtained either in the presence of in the absence of ATP. As the intracellular Na is increased in the presence of ATP, Nai seems to have no effect on the apparent half-activation constant. However, in the absence of ATP, the KA for activation increases along a sigmoid curve reaching a value of 112 mM at 100 mM Nai. It is concluded that the Ca efflux system uses the energy of the Na electrochemical gradient. The action of Nai appears to be such that the interaction of a single Na+ is sufficient to block Ca extrusion whereas several Naps externally are necessary to activate Ca extrusion.


Rectal metastasis of prostate cancer: about a case.
Prostate adenocarcinomas present a high risk of metastasis. We report a case of an atypical prostate cancer metastasis. A male patient presented a prostatic adenocarcinoma treated by surgery. A biological recurrence was discovered during the follow-up by an increased rate of Prostate Specific Antigen (PSA) and was treated by hormonotherapy. Several months later, there was a re-increase of the PSA rate. The CT scan showed a radiation proctitis aspect. An intermittent hormonotherapy was decided. Six months later, he presented abdominal pain. Examinations were performed and showed a rectal carcinosarcoma with prostate origins. A surgical management was realised. The outcomes were an early recurrence. A symptomatic treatment was decided. There are not any rectal localisations reported in the literature. Only loco-regional invasions of the rectum are described and no histological modification of metastasis compared to the primitive tumor has been reported. So, we report a metastasis of a prostate adenocarcinoma which transformed into a carcinosarcoma. Adenocarcinoma; Carcinosarcoma; Metastasis; Prostate; Rectal neoplasm.


Vitamin D deficiency and depression in adults: systematic review and meta-analysis.
There is conflicting evidence about the relationship between vitamin D deficiency and depression, and a systematic assessment of the literature has not been available. To determine the relationship, if any, between vitamin D deficiency and depression. A systematic review and meta-analysis of observational studies and randomised controlled trials was conducted. One case-control study, ten cross-sectional studies and three cohort studies with a total of 31 424 participants were analysed. Lower vitamin D levels were found in people with depression compared with controls (SMD = 0.60, 95% CI 0.23-0.97) and there was an increased odds ratio of depression for the lowest v. highest vitamin D categories in the cross-sectional studies (OR = 1.31, 95% CI 1.0-1.71). The cohort studies showed a significantly increased hazard ratio of depression for the lowest v. highest vitamin D categories (HR = 2.21, 95% CI 1.40-3.49). Our analyses are consistent with the hypothesis that low vitamin D concentration is associated with depression, and highlight the need for randomised controlled trials of vitamin D for the prevention and treatment of depression to determine whether this association is causal.


Medicinal plants used in treatment and management of cancer in Kakamega County, Kenya.
Traditional medicine plays a critical role in treatment of chronic debilitating and life threatening conditions and diseases. Cancer is one such condition whose therapeutic intervention is commonly through inexpensive traditional herbal remedies. Increasingly industrialised societies are developing drugs and chemotherapeutics from these traditional herbal plants. Plant biogeography determines the abundance and availability of medicinal plants which in turn determine their use by local communities. The present study was carried out in Kakamega County of Kenya to identify and document medicinal plants used for treatment and management of cancer states by communities living adjacent to Kakamega Tropical rainforest of Kakamega County, Kenya. An ethnobotanical survey was done using semi-structured questionnaires administered to 32 randomly selected herbalists from Kakamega County. Sixty five (65) plants of 59 genera and 32 families were identified as candidates in therapeutic intervention against cancer states. Most commonly cited plant species were Spathodea campanulata P. Beauv. ssp. nilotica (Seem), Microglossa pyrifolia (Lam.) Kuntze, Harungana madagascariensis Lam. ex poir, Prunus africana (Hook. f.) kalkman, Cyphostemma serpens (A. Rich), Catharanthus roseus (L.) G. Don and Aloe volkensii Engl. The following were documented for the first time; Aeschynomene abyssinica (A. Rich.) Vatke, Synsepalum cerasiferum (welw.) T. D penn., Albizia coriaria Welw. ex Oliv., Aloe volkensii Engl. Bridelia micrantha (Hochst.) Baill, Croton macrostachyus Delile, Cyphostemma serpens (A. Rich), Dicliptera laxata C.B. Clarke, Ekebergia capensis Sparrm., Gardenia volkensii K. schum. ssp. volkensii, Glycine wightii (wight & Arn.), Ocimum gratissimum Suave, Olea hotcsh spp. hochstetteri, Pavetta abyssinica Fresen., Phyllanthus fischeri Pax, Psydrax schimperiana (A. Rich), Rhus vulgaris Meikle, Senna didymobotyra (Fresen.) Irwin and Barneby, Solanecio nandensis (S. Moore) C. Jeffrey, Solanum mauritianum Scop, Spathodea campanulata P. Beauv. ssp. nilotica (Seem), Spermacoce princea (K. Schum.) Verdc., Tabernaemontana stapfiana Britten, Tragia brevipes Pax and Zanthoxylum gilletii (De Wild.) P.G.Waterman. The most frequently used plant parts were fresh or dried leaves and stem barks. Administration to patients was almost exclusively oral, with the exceptions being topical application especially for breast cancer and skin sarcomas. This study identified diverse medicinal plants used in therapeutic and management intervention against cancer by communities living adjacent to Kakamega Tropical Rainforest. The primary mode of administration was oral.


Toppar: an interactive browser for viewing association study results.
Data integration and visualization help geneticists make sense of large amounts of data. To help facilitate interpretation of genetic association data we developed Toppar, a customizable visualization tool that stores results from association studies and enables browsing over multiple results, by combining features from existing tools and linking to appropriate external databases. Detailed information on Toppar's features and functionality are on our website http://mccarthy.well.ox.ac.uk/toppar/docs along with instructions on how to download, install and run Toppar. Our online version of Toppar is accessible from the website and can be test-driven using Firefox, Safari or Chrome on sub-sets of publicly available genome-wide association study anthropometric waist and body mass index data (Locke et al., 2015; Shungin et al., 2015) from the Genetic Investigation of ANthropometric Traits consortium. email@example.com.


The mediation effect of individual eating behaviours on the relationship between socioeconomic status and dietary quality in children: the Korean National Health and Nutrition Examination Survey.
Although it has been suggested that socioeconomic status is associated with dietary quality, the possible mediation effects of eating behaviours on dietary quality are unclear. Thus, we investigated the causal chain by which socioeconomic status influences the quality of the diets consumed by children through their eating behaviours using data from the Korean National Health and Nutrition Examination Survey. The study focused on persons from 2 to 18 years of age who completed the 24-h dietary recall survey (n = 3158). Using causal mediation analysis, we assessed the relationship between socioeconomic status and poor dietary quality in children and examined the mediation effects of eating behaviours. Socioeconomic indicators included household income, parental education, and parental occupation. Dietary quality was defined by the number of key nutrients, protein, calcium, phosphorous, iron, vitamin A, vitamin B1, vitamin B2, niacin, and vitamin C, consumed at insufficient levels. In the present study, more than half the children did not consume the recommended amounts of vitamin A, vitamin C, iron, and calcium. Eating breakfast had a significant impact on poor dietary quality regardless of socioeconomic indicators. On the other hand, children from lower-middle-income households consumed insufficient amounts of more nutrients than their counterparts regardless of eating behaviours. Through the mediation model, we found that lower-middle household incomes were associated with poor dietary quality, but that dietary quality was significantly mediated by eating breakfast. We found that poor dietary quality among children in lower-income households was partially explained by their being less likely to eat breakfast, but that eating breakfast did not entirely mediate these effects. Thus, to reduce differences in dietary quality among children, those who are economically vulnerable must be prioritized.


Bioinformatic identification of cassava miRNAs differentially expressed in response to infection by Xanthomonas axonopodis pv. manihotis.
microRNAs (miRNAs) are short RNA molecules that control gene expression by silencing complementary mRNA. They play a crucial role in stress response in plants, including biotic stress. Some miRNAs are known to respond to bacterial infection in Arabidopsis thaliana but it is currently unknown whether these responses are conserved in other plants and whether novel species-specific miRNAs could have a role in defense. This work addresses the role of miRNAs in the Manihot esculenta (cassava)-Xanthomonas axonopodis pv. manihotis (Xam) interaction. Next-generation sequencing was used for analyzing small RNA libraries from cassava tissue infected and non-infected with Xam. A full repertoire of cassava miRNAs was characterized, which included 56 conserved families and 12 novel cassava-specific families. Endogenous targets were predicted in the cassava genome for many miRNA families. Some miRNA families' expression was increased in response to bacterial infection, including miRNAs known to mediate defense by targeting auxin-responding factors as well as some cassava-specific miRNAs. Some bacteria-repressed miRNAs included families involved in copper regulation as well as families targeting disease resistance genes. Putative transcription factor binding sites (TFBS) were identified in the MIRNA genes promoter region and compared to promoter regions in miRNA target genes and protein coding genes, revealing differences between MIRNA gene transcriptional regulation and other genes. Taken together these results suggest that miRNAs in cassava play a role in defense against Xam, and that the mechanism is similar to what's known in Arabidopsis and involves some of the same families.


Genetic variants in CYP and GST genes, smoking and risk for head and neck cancers: a gene-environment interaction hospital-based case-control study among Canadian Caucasians.
The evidence for genetic polymorphisms in genes encoding cytochrome P450 (CYP) and glutathione S-transferase (GST) enzymes as risk factors for squamous cell carcinomas of the head and neck (SCCHN) in Caucasians is conflicting. Furthermore, the interactive effects with smoking have not been documented. We estimated the effects of five single nucleotide polymorphisms and two copy number variants associated with CYP and GST genes, as well as their interactive effects with smoking, on SCCHN risk among Caucasians from a case-control study conducted in Montreal, Canada. The study involved 389 incident SCCHN cases and 429 controls, frequency-matched by age and sex, recruited from four main hospitals between 2005 and 2013. Life-course-based interviews collected information on tobacco smoking history and other risk behaviors. DNA was isolated from oral exfoliated cells and genotyped for genetic variants. Unconditional logistic regression models estimated odds ratios (OR) and 95% confidence intervals (CI) for main, joint effect, stratum-specific and interaction estimates among non-, moderate and heavy smokers. Carriers of GSTP1 105Val (versus non-carriers) had a lower risk of SCCHN (OR = 0.71, 95% CI: 0.53, 0.95), which was observed for heavy smokers (OR = 0.59, 95% CI: 0.36, 0.95) and non-smokers alike (OR = 0.49, 95% CI: 0.24, 0.98). The decreased risk associations were also conserved among human papillomavirus negative individuals. There was no evidence for statistical interaction with smoking on additive or multiplicative scales for any of the variants analyzed. Of CYP and GST polymorphisms detected in Canadian Caucasians, only GSTP1 105Val was associated with a decreased risk for SCCHN.


Electrophysiological correlates of the composite face illusion: disentangling perceptual and decisional components of holistic face processing in the human brain.
When the bottom halves of two faces differ, people's behavioral judgment of the identical top halves of those faces is impaired: they report that the top halves are different, and/or take more time than usual to provide a response. This behavioral measure is known as the composite face effect (CFE) and has traditionally been taken as evidence that faces are perceived holistically. Recently, however, it has been claimed that this effect is driven almost entirely by decisional, rather than perceptual, factors (Richler, Gauthier, Wenger, & Palmeri, 2008). To disentangle the contribution of perceptual and decisional brain processes, we aimed to obtain an event-related potential (ERP) measure of the CFE at a stage of face encoding (Jacques & Rossion, 2009) in the absence of a behavioral CFE effect. Sixteen participants performed a go/no-go task in an oddball paradigm, lifting a finger of their right or left hand when the top half of a face changed identity. This change of identity of the top of the face was associated with an increased ERP signal on occipito-temporal electrode sites at the N170 face-sensitive component (∼160 ms), the later decisional P3b component, and the lateralized readiness potential (LRP) starting at ∼350 ms. The N170 effect was observed equally early when only the unattended bottom part of the face changed, indicating that an identity change was perceived across the whole face in this condition. Importantly, there was no behavioral response bias for the bottom change trials, and no evidence of decisional biases from electrophysiological data (no P3b and LRP deflection in no-go trials). These data show that an early CFE can be measured in ERPs in the absence of any decisional response bias, indicating that the CFE reflects primarily the visual perception of the whole face.


Iron isotope fractionation during microbial dissimilatory iron oxide reduction in simulated Archaean seawater.
The largest Fe isotope excursion yet measured in marine sedimentary rocks occurs in shales, carbonates, and banded iron formations of Neoarchaean and Paleoproterozoic age. The results of field and laboratory studies suggest a potential role for microbial dissimilatory iron reduction (DIR) in producing this excursion. However, most experimental studies of Fe isotope fractionation during DIR have been conducted in simple geochemical systems, using pure Fe(III) oxide substrates that are not direct analogues to phases likely to have been present in Precambrian marine environments. In this study, Fe isotope fractionation was investigated during microbial reduction of an amorphous Fe(III) oxide-silica coprecipitate in anoxic, high-silica, low-sulphate artificial Archaean seawater at 30 °C to determine if such conditions alter the extent of reduction or isotopic fractionations relative to those observed in simple systems. The Fe(III)-Si coprecipitate was highly reducible (c. 80% reduction) in the presence of excess acetate. The coprecipitate did not undergo phase conversion (e.g. to green rust, magnetite or siderite) during reduction. Iron isotope fractionations suggest that rapid and near-complete isotope exchange took place among all Fe(II) and Fe(III) components, in contrast to previous work on goethite and hematite, where exchange was limited to the outer few atom layers of the substrate. Large quantities of low-δ(56)Fe Fe(II) (aqueous and solid phase) were produced during reduction of the Fe(III)-Si coprecipitate. These findings shed new light on DIR as a mechanism for producing Fe isotope variations observed in Neoarchaean and Paleoproterozoic marine sedimentary rocks.


The physician assistant: Shifting the Paradigm of European medical practice?
Physician Assistants are medical care providers working under supervision and/or in collaboration with a medical doctor. The Physician Assistant profession has its origin in the United States, but in the last decade has also reached other nations to overcome medical staffing issues. With little summarized literature available, the aim of this study is to portray the Physician Assistant movement in Europe. A literature search was conducted in Academic Search Premier, CINAHL, ERIC and MEDLINE databases. In addition, European PA educational programs, professional associations, and local experts on the PA profession were queried. Currently, in Europe there are three countries in which physician assistants are trained and are working. The educational models of physician assistant training in the United Kingdom, Germany and the Netherlands differ, as do the degrees offered by the training institutions. There is scant literature about physician assistant training and practice in Europe available in the common scientific databases. The paucity of literature makes it difficult for an outsider to observe the developments and to value the impact of a new profession on national health systems. Further high-quality research is needed to adequately characterize physician assistant education and implementation across Europe.


Detrimental Effects of Helium Ion Irradiation on Cognitive Performance and Cortical Levels of MAP-2 in B6D2F1 Mice.
The space radiation environment includes helium (⁴He) ions that may impact brain function. As little is known about the effects of exposures to ⁴He ions on the brain, we assessed the behavioral and cognitive performance of C57BL/6J × DBA2/J F1 (B6D2F1) mice three months following irradiation with ⁴He ions (250 MeV/n; linear energy transfer (LET) = 1.6 keV/μm; 0, 21, 42 or 168 cGy). Sham-irradiated mice and mice irradiated with 21 or 168 cGy showed novel object recognition, but mice irradiated with 42 cGy did not. In the passive avoidance test, mice received a slight foot shock in a dark compartment, and latency to re-enter that compartment was assessed 24 h later. Sham-irradiated mice and mice irradiated with 21 or 42 cGy showed a higher latency on Day 2 than Day 1, but the latency to enter the dark compartment in mice irradiated with 168 cGy was comparable on both days. ⁴He ion irradiation, at 42 and 168 cGy, reduced the levels of the dendritic marker microtubule-associated protein-2 (MAP-2) in the cortex. There was an effect of radiation on apolipoprotein E (apoE) levels in the hippocampus and cortex, with higher apoE levels in mice irradiated at 42 cGy than 168 cGy and a trend towards higher apoE levels in mice irradiated at 21 than 168 cGy. In addition, in the hippocampus, there was a trend towards a negative correlation between MAP-2 and apoE levels. While reduced levels of MAP-2 in the cortex might have contributed to the altered performance in the passive avoidance test, it does not seem sufficient to do so. The higher hippocampal and cortical apoE levels in mice irradiated at 42 than 168 cGy might have served as a compensatory protective response preserving their passive avoidance memory. Thus, there were no alterations in behavioral performance in the open filed or depressive-like behavior in the forced swim test, while cognitive impairments were seen in the object recognition and passive avoidance tests, but not in the contextual or cued fear conditioning tests. Taken together, the results indicate that some aspects of cognitive performance are altered in male mice exposed to ⁴He ions, but that the response is task-dependent. Furthermore, the sensitive doses can vary within each task in a non-linear fashion. This highlights the importance of assessing the cognitive and behavioral effects of charged particle exposure with a variety of assays and at multiple doses, given the possibility that lower doses may be more damaging due to the absence of induced compensatory mechanisms at higher doses.


Red blood cell Na+,K+-ATPase in men with newly diagnosed or previously treated essential hypertension.
Alterations of cellular function of Na+,K+-adenosine triphosphatase (ATPase; Na+-K+ pump) have been implicated in the pathophysiology of essential hypertension. Therefore, this aspect of red blood cell (RBC) Na metabolism was studied in black men with newly diagnosed, untreated essential hypertension (NEH) and a normotensive control group. RBC Na content, Na+-K+ pump number (ouabain binding sites), and pump activity were measured. No statistically significant differences were found between the two groups for any of these three parameters. However, a group of previously treated essential hypertensive subjects (PEH) who had been withdrawn from therapy in the preceding 6 weeks were also studied. This group differed significantly from the NEH subjects in regard to all RBC Na+-K+ pump parameters. Their RBC Na content (10.27 +/- 3.23 vs 7.77 +/- 2.52 mmol Na/LRBC; p = 0.006) was higher, and their Na+-K+ pump activity (166 +/- 50 vs 221 +/- 87 nmol inorganic phosphate/mg membrane protein/hr; p = 0.03) and Na+-K+ pump number (213 +/- 40 vs 284 +/- 85 binding sites/RBC; p = 0.001) were lower compared with those in NEH subjects. Although the PEH subjects were older and somewhat less hypertensive than their NEH counterparts, these factors were not found to influence the Na+-K+ pump parameters. These results indicate that chronic diuretic therapy of patients with essential hypertension is associated with a reduced number of RBC Na+-K+ pumps. Since RBCs are not considered target cells for diuretics, the effects of these drugs on RBC electrolyte metabolism may occur at the time of erythropoiesis by the production of RBCs with fewer Na+-K+ pumps.(ABSTRACT TRUNCATED AT 250 WORDS)


Genetic markers of comorbid depression and alcoholism in women.
Alcohol dependence (AD) is often accompanied by comorbid depression. Recent clinical evidence supports the benefit of subtype-specific pharmacotherapy in treating the population of alcohol-dependent subjects with comorbid major depressive disorder (MDD). However, in many alcohol-dependent subjects, depression is a reactive response to chronic alcohol use and withdrawal and abates with a period of abstinence. Genetic markers may distinguish alcohol-dependent subjects with MDD not tied chronologically and etiologically to their alcohol consumption. In this work, we investigated the association of adenylyl cyclase genes (ADCY1-9), which are implicated in both AD and mood disorders, with alcoholism and comorbid depression. Subjects from Vienna, Austria (n = 323) were genotyped, and single nucleotide polymorphisms (1,152) encompassing the genetic locations of the 9 ADCY genes were examined. The Vienna cohort contained alcohol-dependent subjects differentiated using the Lesch Alcoholism Typology. In this typology, subjects are segregated into 4 types. Type III alcoholism is distinguished by co-occurrence of symptoms of depression and by affecting predominantly females. We identified 4 haplotypes associated with the phenotype of Type III alcoholism in females. One haplotype was in a genomic area in proximity to ADCY2, but actually within a lincRNA gene, 2 haplotypes were within ADCY5, and 1 haplotype was within the coding region of ADCY8. Three of the 4 haplotypes contributed independently to Type III alcoholism and together generated a positive predictive value of 72% and a negative predictive value of 78% for distinguishing women with a Lesch Type III diagnosis versus women designated as Type I or II alcoholics. Polymorphisms in ADCY8 and ADCY5 and within a lincRNA are associated with an alcohol-dependent phenotype in females, which is distinguished by comorbid signs of depression. Each of these genetic locations can rationally contribute to the polygenic etiology of the alcoholism/depression phenotype, and the use of these genetic markers may aid in choosing appropriate and beneficial treatment strategies.


Health related quality of life before and after laparoscopic radical prostatectomy.
The viability of laparoscopic radical prostatectomy (LRP) as a surgical treatment for prostate cancer depends on oncological and health related quality of life (HRQOL) outcomes. We present a prospective assessment of HRQOL in 122 patients before and after LRP using the validated Expanded Prostate Cancer Index Composite (EPIC) questionnaire. EPIC data were collected preoperatively, and at 3, 6 and 12 months after LRP, and all were normalized to patient preoperative baseline responses. Using traditional single question responses, 93.4% of patients were continent (0 to 1 pads) at postoperative month 12. Of previously potent men who underwent bilateral nerve sparing 78.9% reported engaging in sexual intercourse within postoperative year 1. However, EPIC domain scores provided a more comprehensive assessment of functional outcomes. For the urinary incontinence subdomain, the majority of functional recovery was achieved by postoperative month 6, reaching a 74% return to baseline on average. In contrast, recovery of the sexual function subdomain continued throughout postoperative year 1 (to a mean of 64%). Recovery of sexual function was not significantly affected by age or preoperative potency status, although the extent of nerve sparing was a significant predictor of outcome (mean recovery to 75% of baseline for bilateral vs 36% for no nerve sparing at 12 months, p = 0.005). Nerve sparing LRP provides satisfactory first year HRQOL outcomes when assessed with a validated instrument. The time course and extent of functional recovery documented in this prospective study may prove useful for patient counseling before LRP.


Lipid-Associated Macrophages Control Metabolic Homeostasis in a Trem2-Dependent Manner.
Immune cells residing in white adipose tissue have been highlighted as important factors contributing to the pathogenesis of metabolic diseases, but the molecular regulators that drive adipose tissue immune cell remodeling during obesity remain largely unknown. Using index and transcriptional single-cell sorting, we comprehensively map all adipose tissue immune populations in both mice and humans during obesity. We describe a novel and conserved Trem2+ lipid-associated macrophage (LAM) subset and identify markers, spatial localization, origin, and functional pathways associated with these cells. Genetic ablation of Trem2 in mice globally inhibits the downstream molecular LAM program, leading to adipocyte hypertrophy as well as systemic hypercholesterolemia, body fat accumulation, and glucose intolerance. These findings identify Trem2 signaling as a major pathway by which macrophages respond to loss of tissue-level lipid homeostasis, highlighting Trem2 as a key sensor of metabolic pathologies across multiple tissues and a potential therapeutic target in metabolic diseases.


Memantine in moderate-to-severe Alzheimer's disease.
Overstimulation of the N-methyl-D-aspartate (NMDA) receptor by glutamate is implicated in neurodegenerative disorders. Accordingly, we investigated memantine, an NMDA antagonist, for the treatment of Alzheimer's disease. Patients with moderate-to-severe Alzheimer's disease were randomly assigned to receive placebo or 20 mg of memantine daily for 28 weeks. The primary efficacy variables were the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus) and the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory modified for severe dementia (ADCS-ADLsev). The secondary efficacy end points included the Severe Impairment Battery and other measures of cognition, function, and behavior. Treatment differences between base line and the end point were assessed. Missing observations were imputed by using the most recent previous observation (the last observation carried forward). The results were also analyzed with only the observed values included, without replacing the missing values (observed-cases analysis). Two hundred fifty-two patients (67 percent women; mean age, 76 years) from 32 U.S. centers were enrolled. Of these, 181 (72 percent) completed the study and were evaluated at week 28. Seventy-one patients discontinued treatment prematurely (42 taking placebo and 29 taking memantine). Patients receiving memantine had a better outcome than those receiving placebo, according to the results of the CIBIC-Plus (P=0.06 with the last observation carried forward, P=0.03 for observed cases), the ADCS-ADLsev (P=0.02 with the last observation carried forward, P=0.003 for observed cases), and the Severe Impairment Battery (P<0.001 with the last observation carried forward, P=0.002 for observed cases). Memantine was not associated with a significant frequency of adverse events. Antiglutamatergic treatment reduced clinical deterioration in moderate-to-severe Alzheimer's disease, a phase associated with distress for patients and burden on caregivers, for which other treatments are not available.


The role of turtles as coral reef macroherbivores.
Herbivory is widely accepted as a vital function on coral reefs. To date, the majority of studies examining herbivory in coral reef environments have focused on the roles of fishes and/or urchins, with relatively few studies considering the potential role of macroherbivores in reef processes. Here, we introduce evidence that highlights the potential role of marine turtles as herbivores on coral reefs. While conducting experimental habitat manipulations to assess the roles of herbivorous reef fishes we observed green turtles (Chelonia mydas) and hawksbill turtles (Eretmochelys imbricata) showing responses that were remarkably similar to those of herbivorous fishes. Reducing the sediment load of the epilithic algal matrix on a coral reef resulted in a forty-fold increase in grazing by green turtles. Hawksbill turtles were also observed to browse transplanted thalli of the macroalga Sargassum swartzii in a coral reef environment. These responses not only show strong parallels to herbivorous reef fishes, but also highlight that marine turtles actively, and intentionally, remove algae from coral reefs. When considering the size and potential historical abundance of marine turtles we suggest that these potentially valuable herbivores may have been lost from many coral reefs before their true importance was understood.


Phenotypic analyses and mutation screening of the SLC26A4 and FOXI1 genes in 101 Taiwanese families with bilateral nonsyndromic enlarged vestibular aqueduct (DFNB4) or Pendred syndrome.
Recessive mutations in the SLC26A4 gene are responsible for nonsyndromic enlarged vestibular aqueduct (EVA) and Pendred syndrome. However, in some affected families, only 1 or 0 mutated allele can be identified, as well as no clear correlation between SLC26A4 genotypes and clinical phenotypes, hampering the accuracy of genetic counseling. To elucidate the genetic composition of nonsyndromic EVA and Pendred syndrome, we screened related genomic fragments, including the SLC26A4 coding regions, the SLC26A4 promoter and the FOXI1 transcription factor gene, in 101 Taiwanese families, and analyzed their phenotypic and genotypic results. Mutation screening in the SLC26A4 coding regions by direct sequencing and quantitative polymerase chain reaction detected 2 mutations in 63 (62%) families, 1 mutation in 24 (24%) families and no mutation in 14 (14%) families. The radiological findings, the presence of goiters and the audiological results were not different among probands (i.e. index cases of the families) with different SLC26A4 genotypes. Specifically, probands heterozygous for SLC26A4 mutations demonstrated clinical features indistinguishable from those of probands with 2 mutated alleles, implicating that there might be undetected mutations. However, except for a variant (c.-2554G>A of SLC26A4) with possible pathological consequences, no definite mutation was detected after extensive screening in the SLC26A4 promoter and FOXI1. In other words, in most Taiwanese families nonsyndromic EVA or Pendred syndrome might not result from aberrance in the transcriptional control of SLC26A4 by FOXI1. Meanwhile, exploration of undetected mutations in the SLC26A4 noncoding regions revealed 9 divergent haplotypes among the 21 no-mutation-detected SLC26A4 alleles of the c.919-2A>G heterozygotes, indicating that there might be no common and predominant mutations in the SLC26A4 introns.


Challenges and improvement needs in the care of patients with central diabetes insipidus.
Central diabetes insipidus (CDI) is a rare condition, with significant impact on patient health and well-being. It is a chronic condition which usually requires meticulous long-term care. It can affect both children and adults. There is limited literature considering the needs and challenges inherent in providing high quality care to patients with CDI, across the care pathway. This paper seeks to address this gap by providing a unique and well-rounded understanding of clinical and healthcare systems-related challenges. It draws on insights from the literature, from direct clinical experience contributed by five clinicians as co-authors (providing insights from France, Ireland, Italy, Spain and the United Kingdom), and from patient perspectives provided through interviews with patient representatives from three patient organisations. We identify clinical challenges related to the diagnosis of CDI, including differentiating between other similar conditions and determining the underlying aetiology. Treatment is challenging, given the need to tailor medication to each patient's needs and ongoing management is required to ensure that patients continue to respond adequately to treatment. Ongoing support is required when patients switch between formulations. We also identify healthcare systems challenges related to limited awareness of CDI amongst primary care physicians and general paediatricians, and the need for highly skilled specialist care and appropriate workforce capacity. There is also a significant need for raising awareness and for the education of both healthcare professionals and patients about different aspects of CDI, with the aim of supporting improved care and effective patient engagement with healthcare professionals. We reflect on this information and highlight improvement opportunities. These relate to developing guidance to support patients, carers, primary care physicians and general paediatricians to identify clinical features earlier, and to consider CDI as a possible diagnosis when a patient presents with suggestive symptoms.


An automated microreactor for semi-continuous biosensor measurements.
Living bacteria or yeast cells are frequently used as bioreporters for the detection of specific chemical analytes or conditions of sample toxicity. In particular, bacteria or yeast equipped with synthetic gene circuitry that allows the production of a reliable non-cognate signal (e.g., fluorescent protein or bioluminescence) in response to a defined target make robust and flexible analytical platforms. We report here how bacterial cells expressing a fluorescence reporter ("bactosensors"), which are mostly used for batch sample analysis, can be deployed for automated semi-continuous target analysis in a single concise biochip. Escherichia coli-based bactosensor cells were continuously grown in a 13 or 50 nanoliter-volume reactor on a two-layered polydimethylsiloxane-on-glass microfluidic chip. Physiologically active cells were directed from the nl-reactor to a dedicated sample exposure area, where they were concentrated and reacted in 40 minutes with the target chemical by localized emission of the fluorescent reporter signal. We demonstrate the functioning of the bactosensor-chip by the automated detection of 50 μgarsenite-As l(-1) in water on consecutive days and after a one-week constant operation. Best induction of the bactosensors of 6-9-fold to 50 μg l(-1) was found at an apparent dilution rate of 0.12 h(-1) in the 50 nl microreactor. The bactosensor chip principle could be widely applicable to construct automated monitoring devices for a variety of targets in different environments.


Applying a structured innovation process to interventional radiology: a single-center experience.
To determine the feasibility and efficacy of applying an established innovation process to an active academic interventional radiology (IR) practice. The Stanford Biodesign Medical Technology Innovation Process was used as the innovation template. Over a 4-month period, seven IR faculty and four IR fellow physicians recorded observations. These observations were converted into need statements. One particular need relating to gastrostomy tubes was diligently screened and was the subject of a single formal brainstorming session. Investigators collected 82 observations, 34 by faculty and 48 by fellows. The categories that generated the most observations were enteral feeding (n = 9, 11%), biopsy (n = 8, 10%), chest tubes (n = 6, 7%), chemoembolization and radioembolization (n = 6, 7%), and biliary interventions (n = 5, 6%). The output from the screening on the gastrostomy tube need was a specification sheet that served as a guidance document for the subsequent brainstorming session. The brainstorming session produced 10 concepts under three separate categories. This formalized innovation process generated numerous observations and ultimately 10 concepts to potentially to solve a significant clinical need, suggesting that a structured process can help guide an IR practice interested in medical innovation.


Prevention and Control of Seasonal Influenza with Vaccines.
This report updates the 2015-16 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines (Grohskopf LA, Sokolow LZ, Olsen SJ, Bresee JS, Broder KR, Karron RA. Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices, United States, 2015-16 influenza season. MMWR Morb Mortal Wkly Rep 2015;64:818-25). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. For the 2016-17 influenza season, inactivated influenza vaccines (IIVs) will be available in both trivalent (IIV3) and quadrivalent (IIV4) formulations. Recombinant influenza vaccine (RIV) will be available in a trivalent formulation (RIV3). In light of concerns regarding low effectiveness against influenza A(H1N1)pdm09 in the United States during the 2013-14 and 2015-16 seasons, for the 2016-17 season, ACIP makes the interim recommendation that live attenuated influenza vaccine (LAIV4) should not be used. Vaccine virus strains included in the 2016-17 U.S. trivalent influenza vaccines will be an A/California/7/2009 (H1N1)-like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008-like virus (Victoria lineage). Quadrivalent vaccines will include an additional influenza B virus strain, a B/Phuket/3073/2013-like virus (Yamagata lineage).Recommendations for use of different vaccine types and specific populations are discussed. A licensed, age-appropriate vaccine should be used. No preferential recommendation is made for one influenza vaccine product over another for persons for whom more than one licensed, recommended product is otherwise appropriate. This information is intended for vaccination providers, immunization program personnel, and public health personnel. Information in this report reflects discussions during public meetings of ACIP held on October 21, 2015; February 24, 2016; and June 22, 2016. These recommendations apply to all licensed influenza vaccines used within Food and Drug Administration-licensed indications, including those licensed after the publication date of this report. Updates and other information are available at CDC's influenza website (http://www.cdc.gov/flu). Vaccination and health care providers should check CDC's influenza website periodically for additional information.


Maternal bipolar disorder increased low birthweight and preterm births: a nationwide population-based study.
To investigate pregnancy outcomes, including low birthweight, preterm births, and small-for-gestational-age (SGA) among women with bipolar disorder, schizophrenia compared with women with no history of mental illness using nationwide population-based data. This study linked the Taiwan National Health Insurance Research Dataset with the national birth certificate registry. A total of 528,398 singleton births between 2001 and 2003 were included; 337 were diagnosed with bipolar disorder. Multivariate logistic regression analyses were carried out to examine the relationship between maternal bipolar disorder, schizophrenia and the odds of low birthweight, preterm births, and SGA, after adjusting for characteristics of infant, mother and father. It shows that pregnant women with bipolar disorder were more likely to have LBW infants (9.8% vs. 5.7%), preterm births (14.2% vs. 6.9%) and SGA (22.3% vs. 15.7%) than pregnant women with no history of mental illness. The adjusted odds of low birthweight for women with bipolar disorder was 1.66 times (95% CI, 1.16-2.38) that of women with no history of mental illness. In terms of preterm births and SGA, the adjusted odds ratios were 2.08 (95% CI, 1.53-2.83) and 1.47 (95% CI, 1.14-1.91) respectively, for women with bipolar disorder, compared to their counterparts with no history of mental illness. We conclude that women with bipolar disorder had increased risk of low birthweight, preterm births, and SGA than women without a history of mental illness. More active monitoring and early intervention to counter potential adverse pregnancy outcomes for pregnant women with bipolar disorder should be initiated.


Differential gene expression following early renal ischemia/reperfusion.
Acute renal failure from ischemia/reperfusion injury is associated with tubule cell apoptosis, the molecular mechanisms of which remain under active investigation. The purpose of this study was to identify apoptosis-related genes that are differentially expressed in the early periods following renal ischemia. Mice underwent unilateral renal artery clamping for 45 minutes and were sacrificed at 0, 3, 12, or 24 hours of reperfusion. Tubule cell apoptosis was confirmed by DNA laddering and terminal deoxynucleotidyl transferase-mediated uridine triphosphate nick end labeling (TUNEL) assay. We employed cDNA microarrays to define global changes in renal gene expression. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry were used as confirmatory tools. By microarray analysis, we identified consistent patterns of altered gene expression, including transcription factors, growth factors, signal transduction molecules, and apoptotic factors. Prominent among the last category included FADD, DAXX, BAD, BAK, and p53. Up-regulation of these proapoptotic genes was confirmed by semiquantitative RT-PCR and immunohistochemistry. The results indicate that apoptosis may represent an important mechanism for the early loss of tubule cells following ischemia/reperfusion injury. Both the death receptor-dependent (FADD-DAXX) and mitochondrial (BAD-BAK) pathways are activated. The results also provide a molecular basis for the previous findings that significant intrarenal mechanisms exist to enable tubule cell repair and regeneration, as evidenced by the up-regulation of genes such as growth, proliferation, transcription, and cytoskeletal factors.


Transcriptional analysis of the Azospirillum brasilense indole-3-pyruvate decarboxylase gene and identification of a cis-acting sequence involved in auxin responsive expression.
Expression of the Azospirillum brasilense ipdC gene, encoding an indole-3-pyruvate decarboxylase, a key enzyme in the production of indole-3-acetic acid (IAA) in this bacterium, is upregulated by IAA. Here, we demonstrate that the ipdC gene is the promoter proximal gene in a bicistronic operon. Database searches revealed that the second gene of this operon, named iaaC, is well conserved evolutionarily and that the encoded protein is homologous to the Escherichia coli protein SCRP-27A, the zebrafish protein ES1, and the human protein KNP-I/GT335 (HES1), all of unknown function and belonging to the DJ-1/PfpI superfamily. In addition to this operon structure, iaaC is also transcribed monocistronically. Mutation analysis of the latter gene indicated that the encoded protein is involved in controlling IAA biosynthesis but not ipdC expression. Besides being upregulated by IAA, expression of the ipdC-iaaC operon is pH dependent and maximal at acidic pH. The ipdC promoter was studied using a combination of deletion analyses and site-directed mutagenesis. A dyadic sequence (ATTGTTTC(GAAT)GAAACAAT), centered at -48 was demonstrated to be responsible for the IAA inducibility. This bacterial auxin-responsive element does not control the pH-dependent expression of ipdC-iaaC.


Herpes simplex virus IgG Fc receptors induced using recombinant adenovirus vectors expressing glycoproteins E and I.
Evidence has been presented that herpes simplex virus (HSV) immunoglobulin (IgG) Fc receptors are composed of a complex of two glycoproteins, gE and gI. In previous studies, cells infected with HSV-1 mutants lacking either gE or gI bound lower levels of soluble IgG than cells infected with wild-type viruses suggesting that both gE and gI were required for IgG binding. We have reevaluated the Fc receptor activity of these mutants using a more sensitive assay involving IgG-coated erythrocytes and have found that cells infected with a gE- mutant HSV-1 did not bind IgG-coated erythrocytes whereas cells infected with a gI- mutant retained some Fc binding activity. To further study HSV-induced Fc receptors recombinant adenovirus vectors expressing gE or gI were constructed. Cells expressing gE alone bound both soluble IgG and IgG-coated red cells, although the binding was consistently lower than that observed with HSV-infected cells or cells expressing both gE and gI. Cells expressing only gI were unable to bind either soluble IgG or IgG-coated erythrocytes. These results support the conclusion that both gE and gI are required for full Fc receptor activity, although gE alone can bind IgG to a lesser extent.


Day treatment and psychotropic drugs in the aftercare of schizophrenic patients. A Veterans Administration cooperative study.
Schizophrenic patients referred for day treatment at the time of discharge from ten hospitals were randomly assigned to receive day treatment plus drugs or to receive drugs alone. They were tested before assignment and at 6, 12, 18, and 24 months on social functioning, symptoms, and attitudes. Community tenure and costs were also measured. The ten day centers were described on process variables every six months for the four years of the study. Some centers were found to be effective in treating chronic schizophrenic patients and others were not. All centers improved the patients' social functioning. Six of the centers were found to significantly delay relapse, reduce sumptoms, and change some attitudes. Costs for patients in these centers were not significantly different from the group receiving only drugs. More professional staff hours, group therapy, and a high patient turnover treatment philosophy were associated with poor-result centers. More occupational therapy and a sustained nonthreatening environment were more characteristic of successful outcome centers.


Artistic edge and corner enhancing smoothing.
Two important visual properties of paintings and painting-like images are the absence of texture details and the increased sharpness of edges as compared to photographic images. Painting-like artistic effects can be achieved from photographic images by filters that smooth out texture details, while preserving or enhancing edges and corners. However, not all edge preserving smoothers are suitable for this purpose. We present a simple nonlinear local operator that generalizes both the well known Kuwahara filter and the more general class of filters known in the literature as "criterion and value filter structure." This class of operators suffers from intrinsic theoretical limitations which give rise to a dramatic instability in presence of noise, especially on shadowed areas. Such limitations are discussed in the paper and overcome by the proposed operator. A large variety of experimental results shows that the output of the proposed operator is visually similar to a painting. Comparisons with existing techniques on a large set of natural images highlight conditions on which traditional edge preserving smoothers fail, whereas our approach produces good results. In particular, unlike many other well established approaches, the proposed operator is robust to degradations of the input image such as blurring and noise contamination.


Pedicled Transplantation of Axially Vascularized Bone Constructs in a Critical Size Femoral Defect.
Axial vascularization represents a mandatory requirement for clinically applied larger scale vascularized bone grafts. The aim of this study was to combine the arteriovenous (AV) loop model in the rat with a critically sized femoral bone defect and to successfully transplant axially vascularized bone constructs into the defect. In Groups A and C, an AV loop together with a clinically approved hydroxyapatite and beta-tricalcium phosphate (HA/β-TCP) matrix, mesenchymal stem cells, and recombinant human bone morphogenetic protein 2 were implanted into a newly designed porous titanium chamber with an integrated osteosynthesis plate in the thighs of rats, whereas in Groups B and D, the same matrix composition without AV loop and, in Group E, only the HA/β-TCP matrix were implanted. After 6 weeks, the constructs were transplanted into a 10 mm femoral defect created in the same leg, in Groups A and C, under preservation of the AV loop pedicle. Group F served as a control group with an empty chamber. Ten days (Groups A and B) and 12 weeks (Groups C-F) after transplantation, the femora together with the constructs were explanted and investigated using computed tomography (CT), micro-CT, X-ray, histology, and real-time polymerase chain reaction (RT-PCR). Ten days after transplantation, Group A showed a maintained vascular supply leading to increased vascularization, cell survival in the scaffold center, and bone generation compared to Group B. After 12 weeks, there was no difference detectable among all groups regarding total vessel number, although Group C, using the AV loop, still showed increased vascularization of the construct center compared to Groups D and E. In Group C, there was still enhanced bone generation detectable compared to the other groups and increased bony fusion rate at the proximal femoral stump. This study shows the combination of the AV loop model in the rat with a critically sized femoral defect. By maintenance of the vascular supply, the constructs initially showed increased vascularization, leading to increased bone formation and bony fusion in the long term.


Hypoxaemia in patients with hyperleukocytosis: true or spurious, and clinical implications.
It has been suggested that in asymptomatic patients with leukaemias and very high white blood cell counts, the apparent hypoxaemia found using routine blood gas analysis is spurious, the result of excessive O2 metabolism by leukocytes. Pulse oximetry has been suggested as a means of overcoming the shortcomings of blood gas analysis in the assessment of these patients. We present the findings of two patients with extremely high white cell counts, which show that the hypoxaemia found is in fact true hypoxaemia, even in asymptomatic patients, and that met-haemoglobinaemia may be at least in part responsible for the low PaO2. We also showed that pulse oximetry was completely unreliable in our patients due to the elevated met-haemoglobin levels. We recommend that all patients with markedly elevated white cell counts should undergo blood gas analysis with no delay between sampling and processing and that patients with low PaO2 should undergo urgent cytoreduction.


Active surveillance for early-stage prostate cancer: review of the current literature.
The natural history of prostate cancer is remarkably heterogeneous and, at this time, not completely understood. The widespread adoption and application of prostate-specific antigen (PSA) screening has led to a dramatic shift toward the diagnosis of low-volume, nonpalpable, early-stage tumors. Autopsy and early observational studies have shown that approximately 1 in 3 men aged >50 years has histologic evidence of prostate cancer, with a significant portion of tumors being small and possibly clinically insignificant. Utilizing the power of improved contemporary risk stratification schema to better identify patients with a low risk of cancer progression, several centers are gaining considerable experience with active surveillance and delayed, selective, and curative therapy. A literature review was performed to evaluate the rationale behind active surveillance for prostate cancer and to describe the early experiences from surveillance protocols. It appears that a limited number of men on active surveillance have required treatment, with the majority of such men having good outcomes after delayed selective intervention for progressive disease. The best candidates for active surveillance are being defined, as are predictors of active treatment. The psychosocial ramifications of surveillance for prostate cancer can be profound and future needs and unmet goals will be discussed.


Graphene-based wearable sensors.
The human body is a "delicate machine" full of sensors such as the fingers, nose, and mouth. In addition, numerous physiological signals are being created every moment, which can reflect the condition of the body. The quality and the quantity of the physiological signals are important for diagnoses and the execution of therapies. Due to the incompact interface between the sensors and the skin, the signals obtained by commercial rigid sensors do not bond well with the body; this decreases the quality of the signal. To increase the quantity of the data, it is important to detect physiological signals in real time during daily life. In recent years, there has been an obvious trend of applying graphene devices with excellent performance (flexibility, biocompatibility, and electronic characters) in wearable systems. In this review, we will first provide an introduction about the different methods of synthesis of graphene, and then techniques for graphene patterning will be outlined. Moreover, wearable graphene sensors to detect mechanical, electrophysiological, fluid, and gas signals will be introduced. Finally, the challenges and prospects of wearable graphene devices will be discussed. Wearable graphene sensors can improve the quality and quantity of the physiological signals and have great potential for health-care and telemedicine in the future.


Combinations of paclitaxel and etoposide in the treatment of lung cancer.
Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and etoposide are two chemotherapy agents with broad cytotoxic activity but different mechanisms of action and resistance. Previous in vitro studies of their combined cytotoxicity have yielded conflicting results. We evaluated the effects of drug scheduling in cell growth inhibition in lung and breast human cancer cell lines. A clonogenic assay with either simultaneous or sequential 24-hour incubation of paclitaxel and etoposide was used to assess growth inhibition, and the combination index was used to evaluate drug interactions. In these studies, including the A549 human lung cancer cell line, mild antagonism (combination index, > 1) was observed with concurrent exposure of paclitaxel and etoposide, but synergism (combination index, < 1) was observed when the drugs were incubated sequentially. In view of the wide range of antitumor activity of both paclitaxel and etoposide, and the potential importance and clinical impact of optimizing drug doses and schedules, we recently completed a phase I study with the following objectives: (1) to determine the maximum tolerated dose of paclitaxel given intravenously on day 10 after 10 days of oral etoposide and (2) to investigate the toxicity profile of this combination of agents. Three consecutive cohorts consisting of a total of 29 patients with various measurable or assessable tumors were treated with paclitaxel by intravenous infusion over 3 hours after receiving 10 days of etoposide 50 mg orally twice daily. Conclusions for this clinical study were that the combination was feasible and tolerable and had demonstrated antitumor activity in a group of mostly pretreated patients. The recommended doses for phase II studies were etoposide 50 mg twice daily for 10 days followed by paclitaxel 150 mg/m2 intravenously over 3 hours. A phase II study in patients with extensive small cell lung cancer, with appropriate translational studies, has been initiated.


The impact of the joint commission for accreditation of healthcare organizations pain initiative on perioperative opiate consumption and recovery room length of stay.
The enhanced organizational emphasis on the management of pain in hospitalized patients mandated by the Joint Commission for Accreditation of Health Care Organizations (JCAHO) pain initiative precipitated a number of changes by the perioperative services at our facility. In October 2002, a numeric pain scale became mandatory in our postanesthesia care unit (PACU). Response to analgesia in the PACU was recorded using this scale. In addition, an acceptable pain score was required for discharge from the PACU. We evaluated the effects of these changes in the pain management of 1082 patients undergoing general, orthopedic, neurosurgical, urologic, and gynecologic surgeries. We detected an overall increase in the average consumption of opiates (morphine equivalents) in 2002 compared with 2000 (46.6 +/- 20.4 mg versus 40.4 +/- 13.2 mg, P <0.001). This increase was most significant in the PACU (10.5 +/- 10.4 mg versus 6.5 +/- 7.3 mg, P <0.001 between the 2 periods, respectively). This increase in opiate use was not associated with an increased length of stay, an increase in the requirement for naloxone, or an increase in treatment for postoperative nausea and vomiting. We conclude that the increase in opiate use, which could be explained by compliance with the JCAHO pain initiative, was not associated with additional opiate-induced morbidity in the immediate postoperative period.


Sleep in the intensive care unit - nurses' documentation and patients' perspectives.
Inability to sleep is one of the most distressing factors for patients in the intensive care unit (ICU). Sleep is perceived as light and awakenings are numerous. Nurses' documentations of sleep are narrow, mainly concentrating on the quantity and general quality. Nurses should diversely evaluate, document and promote sleep to provide patient centered care. To investigate the content of nurses' documentation about the sleep of ICU patients, patients' own perceptions of sleep, and the correspondence of the two. Nurses' documentations (n = 90) were analysed retrospectively with quantitative content analysis. A cross-sectional survey of patients' (n = 114) perspectives was collected with the five-item Richards-Campbell Sleep Questionnaire (RCSQ), on a visual analogue scale from 0 (the poorest quality sleep) to 100 (optimum sleep). The data was analysed statistically. Correspondence was tested with cross-tabulation. Nurses documented sleep quantity for 71% and quality for 27% of patients, along with the needs assessment, used interventions and their effect on sleep. Patients' perspectives varied widely. Sleep depth was rated the lowest and falling asleep highest of the RCSQ sleep domains. Age of the patients correlated positively with general quality of sleep, sleep depth and falling asleep. Nurses' documentations and patients' perceptions correlated in over half of the cases. Nurses' documentation of ICU patients' sleep is not systematic or comprehensive and corresponds only partially with patients' own perception. The sleep of non-intubated patients is light and awakenings are frequent. Documentation of ICU patients' sleep should include the whole nursing process, i.e. needs assessment, interventions used, and evaluation of sleep and the effects of the interventions, along with patients' own perspective to promote patient-centered care. Evaluation and documentation of patients' sleep must include patients' own perception to be comprehensive. Nurses' documentation should include all elements of nursing process.


White matter integrity and executive abilities in individuals with phenylketonuria.
Previous studies have revealed white matter abnormalities in the brains of individuals with phenylketonuria (PKU), but the microstructural nature of these abnormalities and their relationship to phenylalanine (Phe) levels and cognitive outcomes are poorly understood. In the current study, the microstructural integrity of white matter in 29 individuals with early-treated PKU and 12 healthy controls was examined using two complementary diffusion tensor imaging (DTI) approaches: region-of-interest (ROI) based analysis and voxel-wise tract based spatial statistics (TBSS) analysis. Relationships among DTI, executive abilities, and Phe level findings were explored. DTI revealed widespread lowering of mean diffusivity (MD) in the white matter of the PKU group in comparison with the control group. Executive abilities were also poorer for individuals with PKU than controls. Within the PKU group, lower MD was associated with higher Phe level and poorer executive abilities. These findings are the first to demonstrate the interplay among microstructural white matter integrity, executive abilities, and Phe control in individuals with PKU.


Reprint of mutation of the fucose-specific beta1,3 N-acetylglucosaminyltransferase LFNG results in abnormal formation of the spine.
Notch signaling is an evolutionarily conserved mechanism that determines cell fate in a variety of contexts during development. This is achieved through different modes of action that are context dependent. One mode involves boundary formation between two groups of cells. With this mode of action, Notch signaling is central to vertebrate evolution as it drives the segmentation of paraxial mesoderm in the formation of somites, which are the precursors of the vertebra. In this case, boundary formation facilitates a mesenchymal to epithelial transition, leading to the creation of a somite. In addition, the boundary establishes a signaling center that patterns the somite, a feature that directly impacts on vertebral column formation. Studies in Xenopus, zebrafish, chicken and mouse have established the importance of Notch signaling in somitogenesis, and indeed in mouse how perturbations in somitogenesis affect vertebral column formation. Spondylocostal dysostosis is a congenital disorder characterized by formation of abnormal vertebrae. Here, mutation in Notch pathway genes demonstrates that Notch signaling is also required for normal somite formation and vertebral column development in humans; of particular interest here is mutation of the LUNATIC FRINGE (LFNG) gene, which causes SCD type 3. LUNATIC FRINGE encodes for a fucose-specific beta1,3-N-acetylglucosaminyltransferase, which modifies Notch receptors and alters Notch signaling activity. This review will focus on Notch glycolsylation, and the role of LUNATIC FRINGE in somite formation and vertebral column development in mice and humans.


Synthesis and properties of 2'-O-methyl-2-thiouridine and oligoribonucleotides containing 2'-O-methyl-2-thiouridine.
A new method for the synthesis of 2'-O-methyl-2-thiouridine (s2Um) found in thermophilic bacterial tRNA was developed. Structural properties of s2Um and s2Um(p)U were studied by using 1H NMR spectroscopy. A modified nonaribonucleotide (RNA*: 5'-CGUUs2UmUUGC-3') was synthesized to study the base-recognition ability of s2Um in formation of RNA-RNA and RNA DNA duplexes. The UV melting experiments revealed that RNA*-RNA and RNA*-DNA duplexes having an s2U-A base pair are more stable than those having a U-A base pair. On the contrary, the thermal stability of RNA*-RNA and RNA*-DNA duplexes having an s2U-G wobble base pair was much lower than that of the unmodified duplexes having a natural U-G base pair. It is concluded that s2Um has higher selectivity toward A over G than unmodified U.


Griseofulvin potentiates antitumorigenesis effects of nocodazole through induction of apoptosis and G2/M cell cycle arrest in human colorectal cancer cells.
In this study, we demonstrate that apoptosis and G2/M cell cycle arrest were easily induced by treatment with the oral-antifungal agent, griseofulvin (GF). The mechanisms of GF-induced G2/M arrest were characterized as (a) induction of abnormal mitotic spindle formation, (b) elevation of cyclin B1/cdc2 kinase activity and (c) down-regulation of myt-1 protein expression. On the other hand, caspase 3 activation, Bcl-2 hyperphosphorylation and inhibition of the normal function of Bcl-2 associated with Bax were demonstrated to be the mechanisms of GF-induced apoptosis. DNA fragmentation and flow cytometry analyses demonstrated that combined treatment of GF with the cancer chemotherapeutic agent, nocodazole (ND), strongly potentiates the apoptotic effect and arrest of the G2/M cell cycle in 5 types of human cancer cells, but not in normal human keratinocytes (#76 KhGH). The combined treatment of GF and ND triggered the polymerization of purified tubulin in HT 29 but not in #76 KhGH cells. To further confirm these observations, the therapeutic efficacy was further examined in vivo by treating athymic mice bearing COLO 205 tumor xenografts, with GF (50 mg/kg), ND (5 mg/kg) or GF + ND. Combined treatment of GF and ND significantly enhanced the effect of ND, and led to cessation of tumor growth. These results suggest that chemotherapeutic agents (such as ND) administered in the presence of GF might provide a novel therapy for colorectal cancer.


The Predicaments of People Whose Suicide was Captured on Film.
Although suicide is commonly linked with mental disorder, the notion that suicide may occur in response to predicaments has been the subject of much recent study and attention. A predicament in this context refers to an uncomfortable situation from which escape is difficult. We aimed to examine the predicaments of people whose suicide was captured on film and displayed on the public record. The authors' extensive private library and the web were explored for examples of suicide on film. The authors viewed the films and associated records, and extracted and listed details of the suicides. Six individual cases and two groups (totalling 2200 plus individuals) were identified. The individual cases were Thich Quang Duc (1963), Christine Chubbuck (1974), Budd Dwyer (1987), Daniel Victor Jones (1998), Michael Marin (2012) and Jordon Romero (2012). The two groups were the Japanese Kamikaze pilots of 1944/1995, and those who jumped from the burning "Twin Towers" on September 11, 2001. One of the six individuals has evidence of a mental disorder, and all (individual and group cases) were in potent social/environmental predicaments. Both psychological autopsies and our clinical experience suggest that suicide is often associated with mental disorder. Nevertheless, social/environmental predicaments may lead to suicide. This study suggests that individuals whose suicide is captured on film are often seeking public exposure of their fatal act.


The management of cryptogenic fibrosing alveolitis in three regions of the United Kingdom.
The case notes of 200 patients with cryptogenic fibrosing alveolitis, from three regions in the United Kingdom, were reviewed, in order to determine how physicians manage this uncommon condition. In the majority of cases (119), the diagnosis was based solely on clinical grounds, with no attempt at histological confirmation of the diagnosis. Transbronchial biopsy was attempted in 66 patients, but was unhelpful in confirming a diagnosis of pulmonary fibrosis in 30% of these patients. Thirty five patients underwent bronchoalveolar lavage, and 15 had an open lung biopsy. Of the 132 patients treated, 110 received prednisolone alone, and the rest a combination of other immunosuppressive agents. The doses and duration of therapy varied considerably. These results suggest that, in the late 1980s, there were wide variations of practice in the management of cryptogenic fibrosing alveolitis in the United Kingdom. This is likely to reflect a paucity of information on the optimum management of this uncommon condition.


Effects of heat shock proteins (Mr 70,000) on protein and DNA synthesis at elevated temperatures in vitro.
The protective effect of Mr 70,000 heat shock protein (HSP-70) during thermotolerance has been previously observed. However, it is not known what cellular processes or components may be protected by this protein during the tolerance state. In the studies reported here, the protective effects of purified HSP-70, the nonspecific heat-stable proteins fetuin and trypsin inhibitor (ovomucoid), and other proteins and agents such as bovine serum albumin, D2O, or glycerol on protein and DNA synthesis during heating were investigated in vitro. In vitro protein synthesis at 30, 40, and 42 degrees C was measured by globin mRNA translation. Protein synthesis was inhibited 40 to 70% when incubated for 60 min at 40 and 42 degrees C. However, protein synthesis was protected when either fetuin or ovomucoid was present during protein synthesis at elevated temperatures. The protection was concentration dependent. The HSP-70 purified from Chinese hamster (HA-1) cells was also able to confer protection to the translation system, but at much lower concentrations than either fetuin or ovomucoid. Other proteins, such as bovine serum albumin, or other agents, such as D2O or glycerol which are known protectors of cellular survival during heating, did not protect the translation system. Similar experiments were performed with DNA synthesis in vitro. Purified DNA polymerase alpha was added to the activated calf thymus DNA in an in vitro replication system. A temperature of 46 degrees C for 60 min inhibited replication by 40%. Addition of heat-stable proteins, purified HSP-70, bovine serum albumin, D2O, or glycerol did not confer protection to the replication system. These studies provide new evidence that HSP-70 may confer protection to a component of the protein synthesis machinery during thermotolerance.


Spicae aetheroleum in uncomplicated acute bronchitis: a double-blind, randomised clinical trial.
The trial aimed to evaluate the efficacy and safety of Spicae aetheroleum (Spicae ae.), a phytomedicine obtained by steam distillation of the flowering tops of Lavandula latifolia, as compared to placebo in adult patients with acute bronchitis. Patients with uncomplicated acute bronchitis (bronchitis severity score [BSS] ≥ 5 score points) were randomly assigned to treatment with Spicae ae. or placebo in a double-blind, parallel-group design. No additional treatment was admitted. The primary objective was the mean difference of a defined total BSS of 25% between the Spicae ae. and the placebo group after 7 days of full medication dose. Secondary endpoints included the BSS at day 10, additional signs and symptoms of bronchitis, quality of life (QoL) and safety. The mean decrease in BSS at day 7 and day 10 was significant with 4.79 vs. 3.20 (p < 0.005 for a 25% difference) and 6.47 vs. 4.32 (p < 0.009 for a 25% difference) score points respectively in the Spicae ae. (n = 119) vs. placebo group (n = 110). Accordingly, most additional signs and symptoms of acute bronchitis as well as the patients' QoL improved significantly with Spicae ae. as compared to placebo. In all, 258 patients were eligible for safety analysis. The treatment with Spicae ae. was well tolerated; no serious adverse events occurred. The defined objectives both for the primary and secondary endpoints have been met. The results of this study provide evidence that Spicae ae. is well tolerated, effective and superior to placebo in the symptomatic treatment of uncomplicated acute bronchitis in adult patients.


Direct retroperitoneal pelvic packing versus pelvic angiography: A comparison of two management protocols for haemodynamically unstable pelvic fractures.
To evaluate the outcomes of haemodynamically unstable cases of pelvic ring injury treated with a protocol focused on either direct retroperitoneal pelvic packing or early pelvic angiography and embolisation. A retrospective review of a prospectively collected database in an academic level I trauma centre, treating matched haemodynamically unstable cases of pelvic fracture with either pelvic packing (PACK group, n=20) or early pelvic angiography (ANGIO group, n=20). Physiological markers of haemorrhage, time to intervention, transfusion requirements, complications and early mortality were recorded. The PACK group underwent operative packing at a median of 45min from admission; the median time to angiography in the ANGIO group was 130min. The PACK group, but not the ANGIO group, demonstrated a significant decrease in blood transfusions over the next 24h post intervention. In the ANGIO group, ten people required embolisation and six died, two from acute haemorrhage; in the PACK group, three people required embolisation; four died, none due to uncontrolled haemorrhage. Pelvic packing is as effective as pelvic angiography for stabilising haemodynamically unstable casualties with pelvic fractures, decreases need for pelvic embolisation and post-procedure blood transfusions, and may reduce early mortality due to exsanguination from pelvic haemorrhage.


In vivo evaluation of blue-light attenuation with tinted and untinted intraocular lenses.
To evaluate blue-light attenuation in eyes with a tinted intraocular lens (IOL) or an untinted IOL. Department of Ophthalmology, University Hospital of Crete, Crete, Greece. Comparative case series. Patients had lens extraction and implantation of an Acrysof Natural tinted or Tecnis ZA9003 or Softec III untinted acrylic IOL. The luminance ratio of green (530 nm) and blue (465 nm) light (green:blue ratio) required for isoluminant perception was determined by heterochromatic flicker photometry. Patients were tested preoperatively and 20 days postoperatively. The parafoveal measure of the green:blue ratio, expressed in decibels, is proportional to the blue-light attenuation by the lens. Twenty-two patients received the tinted IOL and 21 the untinted IOL. Preoperatively, age was strongly linearly correlated with the green:blue ratio (r = 0.59, P < .001). The mean postoperative decrease in the green:blue ratio was greater in the untinted IOL group (P = .003). Postoperatively, the tinted IOL group had a significantly higher green:blue ratio than the untinted IOL group (P < .001). In the tinted IOL group, the green:blue ratio was linearly related to IOL dioptric power. Less blue light reached the retina with tinted IOLs than with untinted IOLs. The absorption properties of tinted IOLs seemed to resemble those of the aging human crystalline lens, while untinted IOLs resembled the lower levels of blue-light attenuation of younger lenses. Thus, tinted IOLs may protect against the presumed blue-light hazard. No author has a financial or proprietary interest in any material or method mentioned.


[Influence of acupuncture and moxibustion on QOL of the elderly living in nursing home and care house].
To clarify the influence of acupuncture therapy on the quality of life (QOL) of the elderly, the acupuncture and moxibustion were performed on 35 elderly subjects (8 men and 27 women) with a mean age 79.1 living in nursing homes and elderly care houses. The acu-points were chosen according to their symptoms. Changes in pain and other complaints, body condition, appetite, sleep, bowel movement and activity of daily living (ADL) were evaluated by questionnaires. A total of 38 symptoms were reported. A high rate of improvement was seen in pain and stiffness. For example, there was 86% improvement in low back pain, 84% in knee joint pain and 82% in shoulder stiffness. Concerning body conditions, decrease of fatigue, relaxed of feeling, improvement in appetite, sleep and bowel movement were observed. Furthermore, gait and ADL were also improved. These results suggested that acupuncture and moxibustion are useful to improve QOL in the elderly.


Standardization of diagnostic biomarker concentrations in urine: the hematuria caveat.
Sensitive and specific urinary biomarkers can improve patient outcomes in many diseases through informing early diagnosis. Unfortunately, to date, the accuracy and translation of diagnostic urinary biomarkers into clinical practice has been disappointing. We believe this may be due to inappropriate standardization of diagnostic urinary biomarkers. Our objective was therefore to characterize the effects of standardizing urinary levels of IL-6, IL-8, and VEGF using the commonly applied standards namely urinary creatinine, osmolarity and protein. First, we report results based on the biomarker levels measured in 120 hematuric patients, 80 with pathologically confirmed bladder cancer, 27 with confounding pathologies and 13 in whom no underlying cause for their hematuria was identified, designated "no diagnosis". Protein levels were related to final diagnostic categories (p = 0.022, ANOVA). Osmolarity (mean = 529 mOsm; median = 528 mOsm) was normally distributed, while creatinine (mean = 10163 µmol/l, median = 9350 µmol/l) and protein (0.3297, 0.1155 mg/ml) distributions were not. When we compared AUROCs for IL-6, IL-8 and VEGF levels, we found that protein standardized levels consistently resulted in the lowest AUROCs. The latter suggests that protein standardization attenuates the "true" differences in biomarker levels across controls and bladder cancer samples. Second, in 72 hematuric patients; 48 bladder cancer and 24 controls, in whom urine samples had been collected on recruitment and at follow-up (median = 11 (1 to 20 months)), we demonstrate that protein levels were approximately 24% lower at follow-up (Bland Altman plots). There was an association between differences in individual biomarkers and differences in protein levels over time, particularly in control patients. Collectively, our findings identify caveats intrinsic to the common practice of protein standardization in biomarker discovery studies conducted on urine, particularly in patients with hematuria.


Relationship between menopausal symptoms and sexual dysfunction among married Turkish women in 40-65 age group.
This was a cross-sectional study to analyse the relationship between menopausal symptoms and sexual dysfunction among 229 married Turkish women in the 40-65 age group. The study was carried out at a menopause clinic of a state hospital between 1 October and 31 December 2010. Data were collected with Personal Characteristics Form, Menopause Rating Scale (MRS) and the Arizona Sexual Experience Scale (ASEX). The average age of the women was 52.33 (SD = 4.80) years. The average MRS total score was 20.13(SD = 9.20). The ASEX mean score was 19.97 (SD = 5.44). It was determined that there is a positive meaningful relationship between ASEX mean score, MRS total mean score and the sub-score of women. From the results obtained from this study, it can be said that women have differing levels of menopausal symptoms, and as the severity of menopausal symptoms increases, there is an increase in sexual dysfunction.


Locally acquired mosquito-transmitted malaria: a guide for investigations in the United States.
Recent outbreaks of locally acquired mosquito-transmitted malaria in the United States demonstrate the continued risk for reintroduction of the disease. Since 1957, when CDC's Malaria Branch started conducting malaria surveillance, 63 outbreaks have occurred, constituting 156 cases (annual range: 1-32) that were a result of locally acquired mosquitoborne transmission. This report describes the steps that should be taken to 1) investigate a case that might have been acquired locally, 2) prevent a small focus of malaria cases from becoming a source of sustained transmission, and 3) inform clinicians regarding the process of an investigation so they can effectively address concerns and questions from patients. Although these locally acquired mosquito-transmitted outbreaks frequently involve only a limited number of infected persons, they frequently raise concerns in the community and require substantial public health resources. For example, as a result of the most recent local outbreak of eight malaria cases in Florida in 2003, reverse 911 telephone calls (a community notification system) were made to approximately 300,000 residents; insect repellent, postcards, flyers, and posters in multiple languages were distributed; public announcements were made through the media and to schools and homeless shelters; and notifications were sent to local hospitals and physicians to inform residents of that community. When a local health department investigates a potential locally acquired mosquito-transmitted case, the systematic inquiry should include epidemiologic, environmental, and laboratory components. Local and state health departments inquiring about the proper approach to investigate and control a potential locally acquired case frequently request urgent assistance and tools from CDC. This report provides a starting point for such investigations to local and state health departments by providing them with the tools necessary to initiate an investigation.


Delayed extrusion of embolic coils into the airway after embolization of an external carotid artery pseudoaneurysm.
Carotid blowout syndrome (CBS) is a known devastating complication of head and neck surgery. The risk of developing CBS increases in the setting of radiation therapy, wound breakdown, or tumor recurrence. Traditionally, the treatment of choice for CBS is surgical ligation of the bleeding artery; however, recently, endovascular occlusion has become a more common option. If a pseudoaneurysm is present, treatment consists of trapping with endovascular coils or occlusion with a liquid embolic agent. Delayed migration of embolization coils into the airway causing acute respiratory distress is a rare occurrence. This report presents a case of a 57-year-old woman who presented to her otolaryngologist after experiencing an episode of acute respiratory distress which resolved when she expectorated embolization coil material from her tracheostomy tube. Three months prior to the episode she underwent coil embolization of an external carotid artery pseudoaneurysm for life-threatening hemorrhage.


Reoperation rate after surgery for lumbar herniated intervertebral disc disease: nationwide cohort study.
Retrospective cohort study using national health insurance data. To provide a longitudinal reoperation rate after surgery for lumbar herniated intervertebral disc (HIVD) disease, and to compare the reoperation rates of surgical methods. Herniated intervertebral disc disease is the most common cause of lumbar spinal surgery. Despite improved surgical techniques and instrumentation, reoperation cannot be avoided. The reoperation rates were in the range of 6% to 24% in previous studies. A population-based study is less subject to bias; hence, a nationwide longitudinal analysis was warranted. A national health insurance database was used to identify a cohort of patients who underwent first surgery for herniated intervertebral disc disease in 2003 and 18,590 patients were selected. Individual patients were followed for at least 5 years through their encrypted unique resident registration number. The primary endpoint was any type of second lumbar surgery. After adjusting for confounding factors, 5 surgical methods (fusion, laminectomy, open discectomy, endoscopic discectomy, and nucleolysis [including mechanical nucleus decompression]) were compared. Open discectomy was used as the reference method. Open discectomy was the most common procedure (68.9%) followed by endoscopic discectomy (16.1%), laminectomy (7.9%), fusion (3.9%), and nucleolysis (3.2%). The cumulative reoperation rate was 5.4% at 3 months, 7.4% at 1 year, 9% at 2 years, 10.5% at 3 years, 12.1% at 4 years, and 13.4% at 5 years. The reoperation rates were 18.6%, 14.7%, 13.8%, 12.4%, and 11.8% after laminectomy, nucleolysis, open discectomy, endoscopic discectomy, and fusion, respectively. Compared with open discectomy, the reoperation rate was higher after laminectomy at 3 months, whereas the other surgical methods had similar rates. The cumulative reoperation rate after 5 years was 13.4% and half of the reoperations occurred during the first postoperative year. With the exception of laminectomy, the reoperation rates of the other procedures were not different from that of open discectomy.


Cost and cost-effectiveness of computerized vs. in-person motivational interventions in the criminal justice system.
Although substance use is common among probationers in the United States, treatment initiation remains an ongoing problem. Among the explanations for low treatment initiation are that probationers are insufficiently motivated to seek treatment, and that probation staff have insufficient training and resources to use evidence-based strategies such as motivational interviewing. A web-based intervention based on motivational enhancement principles may address some of the challenges of initiating treatment but has not been tested to date in probation settings. The current study evaluated the cost-effectiveness of a computerized intervention, Motivational Assessment Program to Initiate Treatment (MAPIT), relative to face-to-face Motivational Interviewing (MI) and supervision as usual (SAU), delivered at the outset of probation. The intervention took place in probation departments in two U.S. cities. The baseline sample comprised 316 participants (MAPIT = 104, MI = 103, and SAU = 109), 90% (n = 285) of whom completed the 6-month follow-up. Costs were estimated from study records and time logs kept by interventionists. The effectiveness outcome was self-reported initiation into any treatment (formal or informal) within 2 and 6 months of the baseline interview. The cost-effectiveness analysis involved assessing dominance and computing incremental cost-effectiveness ratios and cost-effectiveness acceptability curves. Implementation costs were used in the base case of the cost-effectiveness analysis, which excludes both a hypothetical license fee to recoup development costs and startup costs. An intent-to-treat approach was taken. MAPIT cost $79.37 per participant, which was ~$55 lower than the MI cost of $134.27 per participant. Appointment reminders comprised a large proportion of the cost of the MAPIT and MI intervention arms. In the base case, relative to SAU, MAPIT cost $6.70 per percentage point increase in the probability of initiating treatment. If a decision-maker is willing to pay $15 or more to improve the probability of initiating treatment by 1%, estimates suggest she can be 70% confident that MAPIT is good value relative to SAU at the 2-month follow-up and 90% confident that MAPIT is good value at the 6-month follow-up. Web-based MAPIT may be good value compared to in-person delivered alternatives. This conclusion is qualified because the results are not robust to narrowing the outcome to initiating formal treatment only. Further work should explore ways to improve access to efficacious treatment in probation settings.


Negative absolute temperature for motional degrees of freedom.
Absolute temperature is usually bound to be positive. Under special conditions, however, negative temperatures-in which high-energy states are more occupied than low-energy states-are also possible. Such states have been demonstrated in localized systems with finite, discrete spectra. Here, we prepared a negative temperature state for motional degrees of freedom. By tailoring the Bose-Hubbard Hamiltonian, we created an attractively interacting ensemble of ultracold bosons at negative temperature that is stable against collapse for arbitrary atom numbers. The quasimomentum distribution develops sharp peaks at the upper band edge, revealing thermal equilibrium and bosonic coherence over several lattice sites. Negative temperatures imply negative pressures and open up new parameter regimes for cold atoms, enabling fundamentally new many-body states.


Bee venom attenuates neuroinflammatory events and extends survival in amyotrophic lateral sclerosis models.
Amyotrophic lateral sclerosis (ALS) is a disease affecting the central nervous system that is either sporadic or familial origin and causing the death of motor neurons. One of the genetic factors contributing to the etiology of ALS is mutant SOD1 (mtSOD1), which induces vulnerability of motor neurons through protein misfolding, mitochondrial dysfunction, oxidative damage, cytoskeletal abnormalities, defective axonal transport, glutamate excitotoxicity, inadequate growth factor signaling, and neuroinflammation. Bee venom has been used in the practice of Oriental medicine and evidence from the literature indicates that BV plays an anti-inflammatory or anti-nociceptive role against inflammatory reactions associated with arthritis and other inflammatory diseases. The purpose of the present study was to determine whether bee venom suppresses motor neuron loss and microglial cell activation in hSOD1G93A mutant mice. Bee venom (BV) was bilaterally injected (subcutaneously) into a 14-week-old (98 day old) male hSOD1G93A animal model at the Zusanli (ST36) acupoint, which is known to mediate an anti-inflammatory effect. For measurement of motor activity, rotarod test was performed and survival statistics were analyzed by Kaplan-Meier survival curves. The effects of BV treatment on anti-neuroinflammation of hSOD1G93A mice were assessed via immunoreactions using Iba 1 as a microglia marker and TNF-α antibody. Activation of ERK, Akt, p38 MAP Kinase (MAPK), and caspase 3 proteins was evaluated by western blotting. BV-treated mutant hSOD1 transgenic mice showed a decrease in the expression levels of microglia marker and phospho-p38 MAPK in the spinal cord and brainstem. Interestingly, treatment of BV in symptomatic ALS animals improved motor activity and the median survival of the BV-treated group (139 ± 3.5 days) was 18% greater than control group (117 ± 3.1 days). Furthermore, we found that BV suppressed caspase-3 activity and blocked the defects of mitochondrial structure and cristae morphology in the lumbar spinal cord of hSOD1G93A mice at the symptomatic stage. From these findings, our research suggests BV could be a potential therapeutic agent for anti-neuroinflammatory effects in an animal model of ALS.


Sodium Excretion and Cardiovascular Structure and Function in the Nonhypertensive Population: The Korean Genome and Epidemiology Study.
The effect of sodium intake on the cardiovascular system remains controversial. The purpose of this study is to investigate the relation between sodium intake and cardiovascular structure and function in the nonhypertensive population. We performed a cross-sectional analysis in 1,586 nonhypertensive subjects who participated in the Korean Genome Epidemiology Study (2007-2008). Sodium intake was assessed by estimating the 24-hour urinary sodium excretion from a spot urine sample. Changes in cardiovascular structure and function were assessed by using tissue Doppler echocardiography, the carotid intima-media thickness (CIMT), and the brachial-ankle pulse wave velocity (baPWV). Systolic and diastolic blood pressures increased with increasing tertiles of estimated 24-hour urinary sodium excretion. In multivariate analyses adjusting for covariates, there were stepwise decreases in the baPWV (P = 0.003) and CIMT (P = 0.001) values as the estimated 24-hour urinary sodium excretion increased, whereas no significant differences in left ventricular (LV) structural and functional parameters were observed across the tertiles of estimated 24-hour urinary sodium excretion. Multiple linear regression analyses revealed that the estimated 24-hour urinary sodium excretion was independently and inversely associated with baPWV (P < 0.001) and CIMT (P = 0.001), but not with LV parameters. In the nonhypertensive population, urinary sodium excretion was inversely related to baPWV and CIMT. However, there were no associations between urinary sodium excretion and LV structure or function.


Phylogenetic affiliation and quantification of psychrophilic sulfate-reducing isolates in marine Arctic sediments.
Thirteen psychrophilic sulfate-reducing isolates from two permanently cold fjords of the Arctic island Spitsbergen (Hornsund and Storfjord) were phylogenetically analyzed. They all belonged to the delta subclass of Proteobacteria and were widely distributed within this group, indicating that psychrophily is a polyphyletic property. A new 16S rRNA-directed oligonucleotide probe was designed against the largest coherent cluster of these isolates. The new probe, as well as a set of available probes, was applied in rRNA slot blot hybridization to investigate the composition of the sulfate-reducing bacterial community in the sediments. rRNA related to the new cluster of incompletely oxidizing, psychrophilic isolates made up 1.4 to 20.9% of eubacterial rRNA at Storfjord and 0.6 to 3. 5% of eubacterial rRNA at Hornsund. This group was the second-most-abundant group of sulfate reducers at these sites. Denaturing gradient gel electrophoresis and hybridization analysis showed bands identical to those produced by our isolates. The data indicate that the psychrophilic isolates are quantitatively important in Svalbard sediments.


Vaginal Uterosacral Ligament Suspension: A Retrospective Cohort of Absorbable and Permanent Suture Groups.
The aim of this study was to compare anatomic results after vaginal uterosacral ligament suspension with absorbable versus permanent suture. We performed a retrospective cohort study of women who underwent vaginal uterosacral ligament suspension, from 2006 to 2015. We compared 2 groups: (1) absorbable suspension suture and (2) permanent suspension suture (even if accompanied by absorbable suture). Our primary outcome was composite anatomic failure defined as (1) recurrent prolapse in any compartment past the hymen or (2) retreatment for prolapse. Continuous variables were analyzed using the Student t test or Mann-Whitney U test, and categorical variables were analyzed using χ or Fisher exact test. Multivariable logistic regression analysis was performed to control for confounders. P < 0.05 was considered significant. Of the 242 patients with medium-term follow-up (3 months to 2 years after surgery), 188 underwent vaginal uterosacral ligament suspension with only absorbable suture, and 54 underwent suspension with permanent suture. Compared with the absorbable suture cohort, the permanent suture cohort was more likely to have had advanced preoperative prolapse (P = 0.01), less likely to have had a prior hysterectomy (P = 0.01), and less likely to have undergone a concomitant posterior colporrhaphy/perineoplasty (P < 0.01). Overall, there were no differences in composite anatomic failure between the absorbable and permanent suture groups (17.0% vs 20.4%, P = 0.41). In multivariable logistic regression analyses, when controlling for covariates, there remained no difference in composite anatomic failure between permanent and absorbable suture groups. Completion of vaginal uterosacral ligament suspension using only absorbable suture affords similar anatomic outcomes in the medium term as compared with suspension with additional permanent suture.