Different sleep patterns during the COVID-19 pandemic: association with mood, exercise and light exposure.
The aim was to evaluate the sleep-wake cycle pattern, mood, perceived stress and some behaviors, such as physical exercise and exposure to natural light of college students during the COVID-19 pandemic. This is a cross-sectional study conducted between June and August 2020 using an electronic form provided by Google. The sample consisted of undergraduate students aged between 18 and 30 years old and residents of the northeast region of Brazil. The students generally had sleepiness and poor sleep quality, high levels of anxiety, mild to moderate depressive symptoms and moderate perceived stress. Some of these aspects were worse in women. The college students showed three sleep patterns: one group had good sleep quality without excessive daytime sleepiness; another group had poor sleep quality, but no excessive daytime sleepiness; and a third group had high daytime sleepiness, and less expressive sleep quality impairment. Greater exposure to sunlight and practicing physical exercise predominated in individuals with better sleep quality, suggesting that they are protective factors. In addition, excessive daytime sleepiness and poor sleep quality were separately associated with higher anxiety, depression and stress perception levels, proving to be important aspects for care in order to favor mental health during the pandemic. In conclusion, it is suggested that the COVID-19 pandemic affected the sleep of college students in a heterogeneous way. The differentiated sleep patterns are associated with exposure to natural light and exercising.


Maternal organophosphate flame retardant exposure alters the developing mesencephalic dopamine system in fetal rat.
Organophosphate flame retardants (OPFRs) have become the predominant substitution for legacy brominated flame retardants but there is concern about their potential developmental neurotoxicity (DNT). OPFRs readily dissociate from the fireproofed substrate to the environment, and they (or their metabolites) have been detected in diverse matrices including air, water, soil, and biota, including human urine and breastmilk. Given this ubiquitous contamination, it becomes increasingly important to understand the potential effects of OPFRs on the developing nervous system. We have previously shown that maternal exposure to OPFRs results in neuroendocrine disruption, alterations to developmental metabolism of serotonin (5-HT) and axonal extension in male fetal rats, and potentiates adult anxiety-like behaviors. The development of the serotonin and dopamine systems occur in parallel and interact, therefore, we first sought to enhance our prior 5-HT work by first examining the ascending 5-HT system on embryonic day 14 using whole mount clearing of fetal heads and 3-dimensional (3D) brain imaging. We also investigated the effects of maternal OPFR exposure on the development of the mesocortical dopamine system in the same animals through 2-dimensional and 3D analysis following immunohistochemistry for tyrosine hydroxylase (TH). Maternal OPFR exposure induced morphological changes to the putative ventral tegmental area and substantia nigra in both sexes and reduced the overall volume of this structure in males, whereas 5-HT nuclei were unchanged. Additionally, dopaminergic axogenesis was disrupted in OPFR exposed animals, as the dorsoventral spread of ventral telencephalic TH afferents were greater at embryonic day 14, while sparing 5-HT fibers. These results indicate maternal exposure to OPFRs alters the development trajectory of the embryonic dopaminergic system and adds to growing evidence of OPFR DNT.


[Accidental hypothermia in the elderly].
Accidental hypothermia is unintended body core temperature of 35 degrees C or below, a known hazard to elderly people in temperate and cold climates. We present two old patients with severe hypothermia and a review of the literature focusing on risk factors, clinical presentation, and the treatment of hypothermia in the elderly. Two patients, aged 90 and 102 years, with body core temperature < 28 degrees C were successfully treated at Ullevål University Hospital, Oslo, Norway with slow active external rewarming and a low stress strategy as recommended in the geriatric literature. Successful treatment with more rapid rewarming and use of internal rewarming like peritoneal lavage has also been published. The prognosis of elderly victims of hypothermia is known to be worse than for younger individuals. Epidemiological data are scanty. The most important risk factors are connected to ageing itself and to the morbidity often found in elderly hypothermia victims. Treatment is based on experience from few cases, minor prospective studies mainly on rewarming of younger patients and clinical experience from younger patients. There is a need for more knowledge and experience of treating elderly hypothermia victims.


Syringing as a method of cell dispersal. I. Effect on intermediate and superficial squamous cells.
Mechanical shear in the form of syringing was applied to human gynecologic cytology specimens in an effort to disperse cell clumps. The percentage of single squamous cells achieved with the optimum conditions is generally 70 to 100 per cent. Syringing with a constant pressure device produces a high yield of single squamous cells without the concurrent high cell loss as often observed using enzymatic or chemical procedures. Data presented demonstrate that the slide preparation and clump evaluation procedures used for this study yield reliable and reproducible data. Studies varying stroke number and plunger pressure were completed and conditions for maximum dispersal were established.


Oral cancer cells differ from normal oral epithelial cells in tissue like organization and in response to lycopene treatment: an organotypic cell culture study.
We established distinctive monolayer and organotypic cell culture techniques to assess possible differences in cross-talk and spatial and structural organization of oral cancer cells compared with normal oral cells and also to evaluate possible differential responses of the cells to carotenoids. In monolayers, we investigated the effect of lycopene on the proliferation of an established oral cancer cell line, KB-1, and compared it with a primary cell line obtained from normal oral mucosa. Lycopene exerted a significant inhibitory effect on KB-1 cell proliferation inducing a dose-dependent downregulation of proliferating cell nuclear antigen (PCNA) associated with upregulation of connexin-43 (Cx-43) expression, whereas in the normal oral mucosal cells lycopene did not affect either PCNA expression, which was very low, or the expression of Cx-43, which was basically very high. Lycopene significantly inhibited the formation of colonies induced by the carcinogen 3-methylcholanthrene (MCA) on normal oral cells and almost completely abrogated the hyperplastic effect induced by MCA. KB-1 cells and normal oral epithelial cells in the organotypic cell culture method differed in their stratification and intercellular adhesion patterns as well as in the expression profile of cytokeratins, vimentin, and Cx-43. Lycopene induced Cx-43 expression in KB-1 cells grown by the organotypic raft method, similar to KB-1 cells grown as monolayers. We conclude that lycopene is a promising chemopreventive, pro-differentiating, and anticarcinogenic agent. No adverse effects of lycopene were detected in normal cells cultured in either monolayer or organotypic systems.


Polychlorinated Biphenyl and Organochlorine Pesticide Concentrations in Maternal Mid-Pregnancy Serum Samples: Association with Autism Spectrum Disorder and Intellectual Disability.
Polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) are neurodevelopmental toxicants, but few studies have examined associations with autism spectrum disorder (ASD). We aimed to determine whether prenatal exposure to PCBs and OCPs influences offspring risk of ASD and intellectual disability without autism (ID). We conducted a population-based case-control study among Southern California births, including children with ASD (n = 545) meeting Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV-TR) criteria and ID (n = 181), as well as general population (GP) controls (n = 418). Concentrations of 11 PCB congeners and 2 OCPs measured in banked second-trimester serum samples were compared between the diagnostic groups. Logistic regression was used to calculate crude and adjusted odds ratios (AOR) for associations with ASD, and separately for ID, compared with GP controls, by quartiles of analyte concentrations in primary analyses. Geometric mean levels of several PCB congeners were higher in the ASD group than in the ID and GP groups. ASD risk was elevated for a number of PCB congeners, particularly for the highest vs. lowest quartile of PCB138/158 (AOR = 1.79; 95% CI: 1.10, 2.71) and PCB153 (AOR = 1.82; 95% CI: 1.10, 3.02), and for highest deciles of other congeners in secondary analyses. PCB138/158 was also associated with increased ID (AOR = 2.41; 95% CI: 1.18, 4.91), though no trend was suggested. OCPs were not associated with increased risk of ASD in primary analyses, whereas nonmonotonic increases in risk of ID were found with p,p´-DDE. Our results suggest higher levels of some organochlorine compounds during pregnancy are associated with ASD and ID. Citation: Lyall K, Croen LA, Sjödin A, Yoshida CK, Zerbo O, Kharrazi M, Windham GC. 2017. Polychlorinated biphenyl and organochlorine pesticide concentrations in maternal mid-pregnancy serum samples: association with autism spectrum disorder and intellectual disability. Environ Health Perspect 125:474-480; http://dx.doi.org/10.1289/EHP277.


Protective, repairing and fibrinolytic effects of rivaroxaban on vascular endothelium.
Rivaroxaban, a direct inhibitor of activated factor X (FXa), is the only new oral anticoagulant approved for secondary prevention after acute coronary syndrome. Our objective was to identify the possible molecular mechanisms of rivaroxaban that contribute to endothelial function. Cell viability and growth of human umbilical vein endothelial cells (HUVEC) were registered. Gene expression studies comparing the effects of rivaroxaban and FXa were conducted by a selective RNA array and confirmed by protein quantification. Wound-healing experiments on HUVEC, platelet adhesion, enzymatic activity, and cell-based assays for fibrin formation were performed with rivaroxaban. Rivaroxaban (50 nM) only altered (>2 fold change) the expression of matrix metallopeptidase 2 and urokinase plasminogen activator (u-PA), but counteracted the FXa (9 nM)-induced upregulation of several pro-inflammatory genes (P < 0.05) and FXa-enhanced platelet adhesion over HUVEC. Rivaroxaban increased u-PA protein expression in HUVEC supernatants and enhanced u-PA activity (up to 4 IU ng-1 of u-PA). Rivaroxaban (1 nM-1 μM) showed a significant and dose-dependent positive effect on HUVEC growth that was inhibited by BC-11-hydroxibromide, an inhibitor of u-PA. Healing properties after a wound on HUVEC cultures, and fibrinolytic properties were also shown by rivaroxaban. Both effects were reversed by BC-11-hydroxibromide. Rivaroxaban enhanced viability, growth and migration of HUVEC, mainly by u-PA activation and upregulation, which also participate in the rivaroxaban-induced fibrinolytic activity at endothelial level. Rivaroxaban also protected from the pro-inflammatory effects of FXa on HUVEC. Altogether may improve endothelial functionality and could contribute to the cardiovascular benefits of rivaroxaban.


[Telomerase reverse transcriptase (TERT) promoter mutations in the tumors of human endocrine organs: Biological and prognostic value].
The analysis of the data available in the literature has shown that telomerase reverse transcriptase TERT promoter may serve as promising markers of malignancy, aggressive disease course, and poor prognosis for malignant tumors of endocrine organs. Considering the established association of mutations with tumors having a poor prognosis (high-grade and anaplastic carcinoma of the thyroid), it is reasonable to perform prognostic-value investigations in a group of low-grade thyroid carcinomas that may occasionally recur and may be resistant to radioactive iodine therapy, i.e. can demonstrate a poor course and prognosis. TERT promoter mutations may be a specific marker of the clinically aggressive forms of adrenocortical carcinoma, but the determination of its diagnostic value calls for additional investigations that will have the larger number cases and establish the association with clinical features and survival rates.


The neuropathic postural tachycardia syndrome.
The postural tachycardia syndrome is a common disorder that is characterized by chronic orthostatic symptoms and a dramatic increase in heart rate on standing, but that does not involve orthostatic hypotension. Several lines of evidence indicate that this disorder may result from sympathetic denervation of the legs. We measured norepinephrine spillover (the rate of entry of norepinephrine into the venous circulation) in the arms and legs both before and in response to exposure to three stimuli (the cold pressor test, sodium nitroprusside infusion, and tyramine infusion) in 10 patients with the postural tachycardia syndrome and in 8 age- and sex-matched normal subjects. At base line, the mean (+/-SD) plasma norepinephrine concentration in the femoral vein was lower in the patients with the postural tachycardia syndrome than in the normal subjects (135+/-30 vs. 215+/-55 pg per milliliter [0.80+/-0.18 vs. 1.27+/-0.32 nmol per liter], P=0.001). Norepinephrine spillover in the arms increased to a similar extent in the two groups in response to each of the three stimuli, but the increases in the legs were smaller in the patients with the postural tachycardia syndrome than in the normal subjects (0.001+/-0.09 vs. 0.12+/-0.12 ng per minute per deciliter of tissue [0.006+/-0.53 vs. 0.71+/-0.71 nmol per minute per deciliter] with the cold pressor test, P=0.02; 0.02+/-0.07 vs. 0.23+/-0.17 ng per minute per deciliter [0.12+/-0.41 vs. 1.36+/-1.00 nmol per minute per deciliter] with nitroprusside infusion, P=0.01; and 0.008+/-0.09 vs. 0.19+/-0.25 ng per minute per deciliter [0.05+/-0.53 vs. 1.12+/-1.47 nmol per minute per deciliter] with tyramine infusion, P=0.04). The neuropathic postural tachycardia syndrome results from partial sympathetic denervation, especially in the legs.


Headache: pregnancy and breastfeeding. Recommendations of the Spanish Society of Neurology's Headache Study Group.
Headache is one of the most common neurological complaints, and is most frequent during reproductive age. As a result, we are routinely faced with pregnant or breastfeeding women with this symptom in clinical practice. It is important to know which pharmacological choices are the safest, which should not be used, and when we should suspect secondary headache. To this end, the Spanish Society of Neurology's Headache Study Group has prepared a series of consensus recommendations on the diagnostic and therapeutic algorithms that should be followed during pregnancy and breastfeeding. This guide was prepared by a group of young neurologists with special interest and experience in headache, in collaboration with the Group's Executive Committee. Recommendations focus on which drugs should be used for the most frequent primary headaches, both during the acute phase and for prevention. The second part addresses when secondary headache should be suspected and which diagnostic tests should be performed in the event of possible secondary headache during pregnancy and breastfeeding. We hope this guide will be practical and useful in daily clinical practice and that it will help update and improve understanding of headache management during pregnancy and breastfeeding, enabling physicians to more confidently treat these patients.


Academic Emergency Medicine Faculty Experiences with Racial and Sexual Orientation Discrimination.
Despite the increasing diversity of individuals entering medicine, physicians from racial and sexual minority groups continue to experience bias and discrimination in the workplace. The objective of this study was to determine the current experiences and perceptions of discrimination on the basis of race and sexual orientation among academic emergency medicine (EM) faculty. We conducted a cross-sectional survey of a convenience sample of EM faculty across six programs. Survey items included the Overt Gender Discrimination at Work (OGDW) Scale adapted for race and sexual orientation, and the frequency and source of experienced and observed discrimination. Group comparisons were made using t-tests or chi-square analyses, and relationships between race or sexual orientation, and we evaluated physicians' experiences using correlation analyses. A total of 141 out of 352 (40.1%) subjects completed at least a portion of the survey. Non-White physicians reported higher mean racial OGDW scores than their White counterparts (13.4 vs 8.6; 95% confidence interval (CI) for difference, -7.7 - -2.9). Non-White EM faculty were also more likely to report having experienced discriminatory treatment based on race than were White EM faculty (48.0% vs 12.6%; CI for difference, 16.6% - 54.2%), although both groups were equally likely to report having observed race-based discrimination of another physician. EM faculty who identified as sexual minorities reported higher mean sexual minority OGDW scores than their heterosexual counterparts (11.1 vs 7.1; 95% CI for difference, -7.3 - -0.6). There were no significant differences between sexual minority and heterosexual faculty in their reports of experiencing or observing discrimination based on sexual orientation. EM faculty from racial and sexual minority groups perceived more discrimination based on race or sexual orientation in their workplace than their majority counterparts. EM faculty regardless of race or sexual orientation were similar in their observations of discriminatory treatment of another physician based on race or sexual orientation.


Supraciliary hema implant in combined deep sclerectomy and phacoemulsification: one year results.
We present the combined surgery of non-penetrating deep sclerectomy with insertion of the implant in the supraciliary space as an effective and safe surgery for patients with both cataract and primary open angle glaucoma. This study included 20 eyes of 16 patients who were followed up during 12 months. We found a significant intraocular pressure reduction, changing from a preoperative mean of 23 ± 5 mmHg to a postoperative mean of 18 ± 3 mmHg (p<0.002). Similarly, a significant reduction in the number of glaucoma drugs needed was observed, varying from 2.5 ± 0.9 drops per patient to 0.7 ± 0.9 (p<0.0002) at the end of the study. We also report a significant improvement in best-corrected visual acuity, from 5/10 ± 2/10 to 8/10 ± 2/10 (p<0.006), one year after the combined surgery. The only intraoperative complication observed was the microperforation of the trabeculo-descemetic membrane (TDM) and postoperative complications were iris incarceration, seidel test positivity and microhyphema. All these complications resolved successfully.


2'-Deoxy-5-propynyluridine: a nucleoside with two conformations in the asymmetric unit.
The title compound, 1-(2-deoxy-beta-D-erythro-pentofuranosyl)-5-(prop-1-ynyl)pyrimidin-2,4(1H,3H)-dione, C(12)H(14)N(2)O(5), shows two conformations in the crystalline state: conformer 1 adopts a C2'-endo (close to (2)E; S-type) sugar pucker and an anti nucleobase orientation [chi = -134.04 (19) degrees], while conformer 2 shows an S sugar pucker (twisted C2'-endo-C3'-exo), which is accompanied by a different anti base orientation [chi = -162.79 (17) degrees]. Both molecules show a +sc (gauche, gauche) conformation at the exocyclic C4'-C5' bond and a coplanar orientation of the propynyl group with respect to the pyrimidine ring. The extended structure is a three-dimensional hydrogen-bond network involving intermolecular N-H...O and O-H...O hydrogen bonds. Only O atoms function as H-atom acceptor sites.


Biophysical characterization of antimicrobial peptides activity: from in vitro to ex vivo techniques.
Antimicrobial peptides (AMPs) are evolutionarily conserved components of the innate immune defense system of many living organisms varying from prokaryotes to eukaryotes, including humans. Due to their broad-spectrum activity and low level of induced resistance, these short aminoacid sequences represent a novel class of potential antimicrobial agents. Besides the development of anti-bacterial drugs, AMPs constitute ideal molecular models for the design of molecules with wide-ranging nanomedical applications, such as anti-tumorigenic agents and pharmacological tools to cure channelopaties. Several techniques are currently used to shed light on the mechanisms of action of AMPs, ranging from the characterization of the interaction between peptides and biomimetic membranes and/or intracellular targets, to the study of AMPs effects on pathogens, living cells and tissues. Comprehensive and multiscale studies are crucial to design new AMPs and to identify molecules that can boost their activity. In this minireview we summarize the most recent achievements in AMP-characterization, with a special emphasis on the integration of biophysical approaches, which can synergistically help to bridge the gap between in vitro and ex vivo investigations.


Widespread high grade prostatic intraepithelial neoplasia on biopsy predicts the risk of prostate cancer: a 12 months analysis after three consecutive prostate biopsies.
To evaluate the risk of prostate cancer (PCa) on a third prostate biopsy in a group of patients with two consecutive diagnoses of high grade intraepithelial neoplasia (HGPIN). From November 2004 to December 2007, patients referred to our clinic with a PSA ! 4 ng/ml or an abnormal digital rectal examination (DRE) were scheduled for trans-rectal ultrasound (TRUS) guided 12-core prostate biopsy. Patients with HGPIN underwent a second prostate biopsy, and if the results of such procedure yielded a second diagnosis of HGPIN, we proposed a third 12-core needle biopsy regardless of PSA value. Crude and adjusted logistic regressions were used to assess predictors of PCa on the third biopsy. A total of 650 patients underwent 12 cores transrectal ultrasound prostatic biopsy in the study period. Of 147 (22%) men with a diagnosis of HGPIN, 117 underwent a second prostatic biopsy after six months and 43 a third biopsy after other six months. After the third biopsy, 19 patients (34%) still showed HGPIN, 15 (35%) were diagnosed with PCa and 9 (21%) presented with chronic prostatitis. Widespread HGPIN on a second biopsy was significantly associated with PCa on further biopsy (!2 = 4.04, p = 0.04). Moreover, the presence of widespread HGPIN significantly predicted the risk of PCa on crude and adjusted logistic regressions. Widespread HGPIN on second biopsy is associated with the presence of PCa on a third biopsy. Nonetheless, the relationship between HGPIN and PCa remains complex and further studies are needed to confirm our findings.


Applying family analyses to electronic health records to facilitate genetic research.
Pedigree analysis is a longstanding and powerful approach to gain insight into the underlying genetic factors in human health, but identifying, recruiting and genotyping families can be difficult, time consuming and costly. Development of high throughput methods to identify families and foster downstream analyses are necessary. This paper describes simple methods that allowed us to identify 173 368 family pedigrees with high probability using basic demographic data available in most electronic health records (EHRs). We further developed and validate a novel statistical method that uses EHR data to identify families more likely to have a major genetic component to their diseases risk. Lastly, we showed that incorporating EHR-linked family data into genetic association testing may provide added power for genetic mapping without additional recruitment or genotyping. The totality of these results suggests that EHR-linked families can enable classical genetic analyses in a high-throughput manner. Pseudocode is provided as supplementary information. firstname.lastname@example.com. Supplementary data are available at Bioinformatics online.


Amino acid precursors of Myxococcus xanthus antibiotic TA.
The production of Myxococcus xanthus antibiotic TA was stimulated by addition of alanine, serine and glycine to Casitone medium. These three amino acids served as the major biosynthetic precursors of the antibiotic. Alanine and serine were incorporated via acetate. In Casitone medium supplemented with alanine and serine, 29 to 30 of the 34 carbon atoms of antibiotic TA were derived from these two amino acids. Both carbon atoms of glycine were incorporated into antibiotic TA by a mechanism not involving acetate as an intermediate. Antibiotic TA was split into two fragments by alkaline hydrolysis followed by periodate oxidation. Radioactive alanine was incorporated into both fragments, whereas glycine was incorporated only into the smaller, polar fragment.


Neurosurgical treatment of status epilepticus.
The purpose of this study was to report the cases of five patients with status epilepticus who were treated successfully with neurosurgery. Five children presented with refractory status epilepticus, including complex partial status epilepticus, epilepsia partialis continua and "status gelasticus." Multiple medical therapies had failed to control the seizures, and focal resection was performed. Seizures were fully controlled in four patients, and in one patient seizure frequency was reduced by more than 90%. Refractory status epilepticus is associated with a high mortality rate and by definition does not respond well to medical treatment, even optimal medical treatment. Neurosurgical treatment should be considered as another therapeutic option once medical management has failed, and neurosurgery should not necessarily be a last resort.


Location In Vivo of the Innervation Zone in the Human Medial Gastrocnemius Using Imposed Contractions: A Comparison of the Usefulness of the M-Wave and H-Reflex.
The anatomical territory where the neuromuscular junctions are grouped corresponds to the innervation zone (IZ). This can be located in-vivo using high-density electromyography and voluntary muscle contractions. However, in patients with motor impairment, the use of contractions imposed by electrical stimulation (ES) could be an alternative. The present study has two aims: Firstly, to describe the location of the IZ in-vivo of the medial gastrocnemius (MG) using imposed contractions by ES. Secondly, to compare the usefulness of M-waves and H-reflexes to localize the IZs. Twenty-four volunteers participated (age: 21.2 ± 1.5 years). ES was elicited in the tibial nerve to obtain M-waves and H-reflexes in the MG. The evaluators used these responses to localize the IZs relative to anatomical landmarks. M-wave and H-reflex IZ frequency identification were compared. The IZs of the MG were mostly located in the cephalocaudal direction, at 39.7% of the leg length and 34% of the knee's condylar width. The IZs were most frequently identified in the M-wave (83.33%, 22/24) compared to the H-reflex (8.33%, 2/24) (p > 0.001). Imposed contractions revealed that the IZ of the MG is located at 39.7% of the leg length. To locate the IZs of the MG muscle, the M-wave is more useful than the H-reflex.


Comparative study of zopiclone and pentobarbitone as hypnotics.
The safety and efficacy of zopiclone (7.5 mg) and pentobarbitone (100 mg) were compared in 60 adult outpatients suffering from insomnia. The patients were randomly assigned to one of the two treatment groups, and the medication was taken at bedtime for 16 days. Zopiclone and pentobarbitone, compared with placebo, improved sleep onset, duration of sleep, number of night time awakenings, and quality of sleep. Zopiclone was superior to pentobarbitone with regard to sleep quality, judgement of therapy, and condition in the morning. Side effects were reported in each treatment group, but were less frequent in the zopiclone group (p less than 0.005). Zopiclone is a useful drug for the treatment of sleep disturbances, not only because of its efficacy, but also because of its tolerability.


A novel and easy chemical-clock synthesis of nanocrystalline iron-cobalt bearing layered double hydroxides.
A novel synthesis of cobalt-iron layered double hydroxide (LDH) with interlayer chlorides was investigated. The method consists in mixing concentrated solutions of hexaamminecobalt(III) trichloride with ferrous chloride at room temperature and in anoxic conditions. Four initial Fe/Co atomic ratios have been tried out (0.12, 0.6, 1.2 and 1.8). Neither heating nor addition of alkali was employed for adjusting the pH and precipitating the metal hydroxides. Still, each mixture led to the spontaneous precipitation of a LDH-rich solid having a crystal-chemistry that depended on the initial solution Fe/Co. These LDHs phases were carefully characterized by mean of X-ray diffraction, (57)Fe Mössbauer spectrometry, transmission electron microscopy and chemical analysis (total dissolution and phenanthroline method). Solution Eh and pH were also monitored during the synthesis. Increasing initial Fe/Co ratio impacted the dynamic of the observed stepwise reaction and the composition of the resulting product. Once the two solutions are mixed, a spontaneous and abrupt color change occurs after an induction time which depends on the starting Fe/Co ratio. This makes the overall process acting as a chemical clock. This spontaneous generation of CoFe-LDH arises from the interplay between redox chemistries of iron and cobalt-ammonium complexes.


Design of microarray experiments for genetical genomics studies.
Microarray experiments have been used recently in genetical genomics studies, as an additional tool to understand the genetic mechanisms governing variation in complex traits, such as for estimating heritabilities of mRNA transcript abundances, for mapping expression quantitative trait loci, and for inferring regulatory networks controlling gene expression. Several articles on the design of microarray experiments discuss situations in which treatment effects are assumed fixed and without any structure. In the case of two-color microarray platforms, several authors have studied reference and circular designs. Here, we discuss the optimal design of microarray experiments whose goals refer to specific genetic questions. Some examples are used to illustrate the choice of a design for comparing fixed, structured treatments, such as genotypic groups. Experiments targeting single genes or chromosomic regions (such as with transgene research) or multiple epistatic loci (such as within a selective phenotyping context) are discussed. In addition, microarray experiments in which treatments refer to families or to subjects (within family structures or complex pedigrees) are presented. In these cases treatments are more appropriately considered to be random effects, with specific covariance structures, in which the genetic goals relate to the estimation of genetic variances and the heritability of transcriptional abundances.


Effect of dietary bacteriophage supplementation on internal organs, fecal excretion, and ileal immune response in laying hens challenged by Salmonella Enteritidis.
With the current researches on replacing antibiotics with different dietary interventions, bacteriophages (BP) are potential antimicrobial intervention because of their ability to affect specific bacteria. A study was conducted to evaluate the role of BP against Salmonella enterica serovar Enteritidis (SE) on SE internal organs colonization and ileum immune response in laying hens. Hens were challenged both orally and intracloacally with 108 cfu/mL cells of nalidixic acid resistant Salmonella Enteritidis (SENAR). Thirty-two Single Comb White Leghorns were randomly allocated to 4 dietary treatments: 1) unchallenged control (negative control; T1), 2) SENAR challenged control (positive control; T2), 3) SENAR challenged + 0.1% BP (T3), and 4) SENAR challenged + 0.2% BP (T4). The number of SENAR in the ceca was significantly reduced by 0.2% BP supplementation (P < 0.05) at 7 d post infection (dpi). The respective number of SENAR was reduced from 2.9 log cfu/gm in T2 and T3 to 2.0 log cfu/gm in T4. There was no significant effect of T3 on reduction of numbers of cecal SENAR. A significant reduction of SENAR was observed in the liver with gall bladder (LGB) from 0.75 in T2 to 0.18 log cfu/gm in T4. In the spleen, T4 significantly reduced (P < 0.05) SENAR to 0.56 log cfu/gm compared to T2 and T3 (0.94 log cfu/gm). There was no significant effect of T3 in reduction of prevalence of spleen SENAR. By supplementing 0.2% BP (T4), the SENAR in the ovary was reduced to 0 log cfu/gm. There was a significant reduction (P < 0.05) in fecal SENAR at 6 dpi by T4 (0.71 log cfu/gm) compared to the positive control (1.57 log cfu/gm). The expression of interferon (IFN)-Γ, interleukin (IL)-6, and IL-10 was significantly increased in the ileum by SENAR challenge compared to the negative control. This study suggests that apart from commonly used prebiotics or probiotics, BP are pathogen-specific and can be used as one of the dietary strategies to reduce SE colonization and induce immune modulation in laying hens.


The End of the World As We Have Known It? An Introduction to Collapsology.
Human-induced climate change is fast becoming a climate emergency as we near an irreversible point of no return. In our anthropocentric quest to have dominion over all the earth, we are putting all of life at risk, including human life and civilization. The introduction of collapsology serves as a reality check for better understanding the severity and urgency of the present crisis. Moreover, because of the deleterious effects of environmental racism and classism, there can be no climate justice without racial justice as well. It is hoped that in the end there will emerge a more informed pastoral theology and, by extension, a more informed pastoral and spiritual care, guided by the findings of climate science.


Reduction of splenic immunosuppressive cells and enhancement of anti-tumor immunity by synergy of fish oil and selenium yeast.
Growing evidence has shown that regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) abnormally increase in cancer cachectic patients. Suppressions of Tregs and MDSCs may enhance anti-tumor immunity for cancer patients. Fish oil and selenium have been known to have many biological activities such as anti-inflammation and anti-oxidation. Whether fish oil and/or selenium have an additional effect on population of immunosuppressive cells in tumor-bearing hosts remained elusive and controversial. To gain insights into their roles on anti-tumor immunity, we studied the fish oil- and/or selenium-mediated tumor suppression and immunity on lung carcinoma, whereof cachexia develops. Advancement of cachexia in a murine lung cancer model manifested with such indicative symptoms as weight loss, chronic inflammation and disturbed immune functionality. The elevation of Tregs and MDSCs in spleens of tumor-bearing mice was positively correlated with tumor burdens. Consumption of either fish oil or selenium had little or no effect on the levels of Tregs and MDSCs. However, consumption of both fish oil and selenium together presented a synergistic effect--the population of Tregs and MDSCs decreased as opposed to increase of anti-tumor immunity when both fish oil and selenium were supplemented simultaneously, whereby losses of body weight and muscle/fat mass were alleviated significantly.


Living conditions, quality of life, adherence and treatment outcome in Greenlandic HIV patients.
Despite a high level of sexually transmitted infections, HIV incidence has remained quite stable in Greenland with 5-6 new cases per year (approximately 10 per 100,000). However, disease control is suboptimal and mortality is relatively high. The aim of the present study was to determine associations between adherence to treatment and treatment outcome, living conditions and quality of life among HIV patients in Greenland. Cross-sectional questionnaire-based cohort study of HIV patients in Greenland during 2008-2009. Data regarding treatment, viral load, CD4 count, etc. were obtained from a central HIV-database. Forty-six persons, 17 women and 29 men, of the 60 registered HIV-positive patients (77%) were included. Eighty percent were heterosexually infected and 17% by men having sex with men (MSM) activity. Median age at the time of diagnosis was 48 years (range 20-63). Eighty-nine percent received highly active antiretroviral therapy (HAART). Sixty-seven percent were adherent as defined by a combination of adherence to appointments and to treatment. Ninety-seven percent of adherent and 17% non-adherent patients on HAART had HIV-RNA less than 200 copies per ml (RR=24.2, p<0.0001). Poor adherence was associated with younger age (<50 years) (adjusted RR=7.95, p=0.005) and living in remote areas with no direct contact with skilled personnel (adjusted RR=6.75, p=0.01). Unsafe sex was also more frequent among non-adherent patients (RR=4.12, p=0.026), but due to few answers this topic was not included in the multivariate model. The HIV population in Greenland is peculiar since most patients are heterosexually infected and middle-aged at diagnosis. A relatively poor adherence and consequently inferior treatment outcome is related to young age and living in remote areas.


Application of a pH-sensitive fluoroprobe (C-SNARF-4) for pH microenvironment analysis in Pseudomonas aeruginosa biofilms.
An important feature of microbial biofilms is the development of four-dimensional physical and chemical gradients in space and time. There is need for novel approaches to probe these so-called microenvironments to determine their effect on biofilm-specific processes. In this study, we describe the use of seminaphthorhodafluor-4F 5-(and-6) carboxylic acid (C-SNARF-4) for pH microenvironment analysis in Pseudomonas aeruginosa biofilms. C-SNARF-4 is a fluorescent ratiometric probe that allows pH quantification independent of probe concentration and/or laser intensity. By confocal scanning laser microscopy, C-SNARF-4 revealed pH heterogeneity throughout the biofilm in both the x,y and x,z planes, with values ranging from pH 5.6 (within the biofilm) to pH 7.0 (bulk fluid). pH values were typically remarkably different than those just a few micrometers away. Although this probe has been successfully used in a number of eukaryotic systems, problems have been reported which describe spectral emission changes as a result of macromolecular interactions with the fluorophore. To assess how the biofilm environment may influence fluorescent properties of the dye, fluorescence of C-SNARF-4 was quantified via spectrofluorometry while the probe was suspended in various concentrations of representative biofilm matrix components (i.e., proteins, polysaccharides, and bacterial cells) and growth medium. Surprisingly, our data demonstrate that few changes in emission spectra occur as a result of matrix interactions below pH 7. These studies suggest that C-SNARF-4 can be used as a reliable indicator of pH microenvironments, which may help elucidate their influence on the medical and geobiological roles of natural biofilms.


Absence behavior as traffic crash predictor in bus drivers.
Various indicators of health have been shown to be associated with traffic crash involvement. As general health is also related to absence from work, the latter variable may be more strongly related to crashes, especially for professional drivers. Bus driver absence from work was analyzed in association with their crash records. Two British samples and one Swedish sample were used. One of the British samples yielded fair correlations between crash record and absence, while for the other the effect was restricted to the first three months of driving. The Swedish data had effects in the expected direction but these were not significant. The use of an indirect, overall measurement of health, may be a viable method for predicting the traffic crash involvement for professional drivers, although replications are needed in larger samples and other populations. The use of absence records for the identification of at risk drivers would seem to be a simple and useful method for companies with major fleets, and it also shows the importance of promoting employee health and well being at work as a potential method of reducing the cost, not only of absenteeism, but also of crashes in company vehicles.


H∞ based control of a DC/DC buck converter feeding a constant power load in uncertain DC microgrid system.
DC microgrids are gaining more and more popularity and are becoming a more viable alternative to AC microgrids (MGs) due to their advantages in terms of simpler power converter stages, flexible control algorithms and the absence of synchronization and reactive power. However, DC-MGs are prone to instability issues associated with the presence of nonlinear loads such as constant power loads (CPL) known by their incremental negative impedance (INI), which may lead to voltage collapse of the main DC Bus. In this paper, H∞-based controller of a source side buck converter is designed to avoid the instability issues caused by the load-side converter acting as a CPL. Besides, the proposed controller allows a perfect rejection of all perturbations that may arise from parameter variations, input voltage and CPL current fluctuations. The design process of H∞-based controller is based on the Golver Doyle Optimization Algorithm (GDOA), which requires an augmented system extracted from the small-signal model of the DC/DC converter including the mathematical model of parameter variations and overall external perturbations. The H∞ based controller involves the use of weight functions in order to get the desired performances. The proposed controller is easy to implement and lead to reducing the implementation cost and avoid the use of current measurement that may have some disadvantages. The derived controller is validated by simulation performed in Psim software and experimental setup.


Genetic Labeling of Nuclei-Specific Thalamocortical Neurons Reveals Putative Sensory-Modality Specific Genes.
The thalamus is a central brain structure with topographically ordered long-range axonal projections that convey sensory information to the cortex via distinct nuclei. Although there is an increasing knowledge about genes important for thalamocortical (TC) development, the identification of genetic landmarks of the distinct thalamic nuclei during the embryonic development has not been addressed systematically. Indeed, a more comprehensive understanding of how the axons from the individual nuclei find their way and connect to their corresponding cortical area is called for. Here, we used a genetic dual labeling strategy in mice to purify distinct principal sensory thalamic neurons. Subsequent genome-wide transcriptome profiling revealed genes specifically expressed in each nucleus during embryonic development. Analysis of regulatory regions of the identified genes revealed key transcription factors and networks that likely underlie the specification of individual sensory-modality TC connections. Finally, the importance of correct axon targeting for the specific sensory-modality population transcriptome was evidenced in a Sema6A mutant, in which visual TC axons are derailed at embryonic life. In sum, our data determined the developmental transcriptional profile of the TC neurons that will eventually support sensory processing.


Familial progressive sensorineural deafness is mainly due to the mtDNA A1555G mutation and is enhanced by treatment of aminoglycosides.
Hearing loss involves both genetic and environmental factors. A mutation (A1555G) in the mtDNA has been associated with aminoglycoside-induced and nonsyndromic sensorineural deafness. The pathological significance of this mutation in Caucasoid families has not been established, and its relationship with antibiotic treatment is not well understood. We studied 70 Spanish families with sensorineural deafness (36 congenital and 34 late onset) for the mtDNA A1555G mutation. The A1555G mutation was found in 19 families with maternally transmitted deafness but not in the other 51 families or in 200 control subjects. In 12 families all the patients with the A1555G mutation who received aminoglycosides became deaf, representing 30.3% of the deaf patients in these families. None of the deaf patients from seven other families received aminoglycosides. Overall, only 17.7% of the patients with deafness and the A1555G mutation had been treated with aminoglycosides. The age at onset of deafness was lower (median age 5 years, range 1-52 years) in those treated with aminoglycosides than in those who did not receive antibiotics (median age 20 years, range 1-65 years) (P < .001). The mtDNA of these families belongs to haplotypes common in Europeans. These data indicate that the A1555G mutation accounts for a large proportion of the Spanish families with late-onset sensorineural deafness, that the A1555G mutation has an age-dependent penetrance for deafness (enhanced by treatment with aminoglycosides), and that mtDNA backgrounds probably do not play a major role in disease expression.


Imaging the distribution of transient viscosity after the 2016 Mw 7.1 Kumamoto earthquake.
The deformation of mantle and crustal rocks in response to stress plays a crucial role in the distribution of seismic and volcanic hazards, controlling tectonic processes ranging from continental drift to earthquake triggering. However, the spatial variation of these dynamic properties is poorly understood as they are difficult to measure. We exploited the large stress perturbation incurred by the 2016 earthquake sequence in Kumamoto, Japan, to directly image localized and distributed deformation. The earthquakes illuminated distinct regions of low effective viscosity in the lower crust, notably beneath the Mount Aso and Mount Kuju volcanoes, surrounded by larger-scale variations of viscosity across the back-arc. This study demonstrates a new potential for geodesy to directly probe rock rheology in situ across many spatial and temporal scales.


qRT-PCR analysis of CEACAM5, KLK6, SLC35D3, MUC2 and POSTN in colon cancer lymph nodes-An improved method for assessment of tumor stage and prognosis.
One fourth of colorectal cancer patients having curative surgery will relapse of which the majority will die. Lymph node (LN) metastasis is the single most important prognostic factor and a key factor when deciding on postoperative treatment. Presently, LN metastases are identified by histopathological examination, a subjective method analyzing only a small LN volume and giving no information on tumor aggressiveness. To better identify patients at risk of relapse we constructed a qRT-PCR test, ColoNode, that determines levels of CEACAM5, KLK6, SLC35D3, MUC2 and POSTN mRNAs. Combined these biomarkers estimate the tumor cell load and aggressiveness allocating patients to risk categories with low (0, -1), medium (1), high (2) and very high (3) risk of recurrence. Here we present result of a prospective, national multicenter study including 196 colon cancer patients from 8 hospitals. On average, 21 LNs/patient, totally 4698 LNs, were examined by both histopathology and ColoNode. At 3-year follow-up, 36 patients had died from colon cancer or lived with recurrence. ColoNode identified all patients that were identified by histopathology and in addition 9 patients who were undetected by histopathology. Thus, 25% of the patients who recurred were identified by ColoNode only. Multivariate Cox regression analysis proved ColoNode (1, 2, 3 vs 0, -1) as a highly significant risk factor with HR 4.24 [95% confidence interval, 1.42-12.69, P = .01], while pTN-stage (III vs I/II) lost its univariate significance. In conclusion, ColoNode surpassed histopathology by identifying a significantly larger number of patients with future relapse and will be a valuable tool for decisions on postoperative treatment.


Teen peer educators and diabetes knowledge of low-income fifth grade students.
The current study was designed to evaluate a unique adolescent peer type 2 diabetes mellitus (Type 2 DM) prevention training program for fifth grade children. Peer educators were 22 high school students who participated in the Elementary Institute of Science's Commission on Science that Matters, a year-long program promoting active participation in the health and environmental sciences. Peer education was delivered in the form of a two hour health fair. A knowledge survey was given to fifth grade students in the classroom before the health fair began and then again in the classroom after the health fair. Fifth grade students were able to correctly identify Type 1 DM (23 vs. 40%; P < .01), Type 2 DM (21 vs. 52%; P < .001), and the signs of diabetes (10 vs. 39%; P < .001) after the health fair. This approach could be inexpensively integrated into any community-based health promotion with children and adolescents.


In situ STM imaging of bis-3-sodiumsulfopropyl-disulfide molecules adsorbed on copper film electrodeposited on Pt(111) single crystal electrode.
The adsorption of bis-3-sodiumsulfopropyldi-sulfide (SPS) on metal electrodes in chloride-containing media has been intensively studied to unveil its accelerating effect on Cu electrodeposition. Molecular resolution scanning tunneling microscopy (STM) imaging technique was used in this study to explore the adsorption and decomposition of SPS molecules concurring with the electrodeposition of copper on an ordered Pt(111) electrode in 0.1 M HClO(4) + 1 mM Cu(ClO(4))(2) + 1 mM KCl. Depending on the potential of Pt(111), SPS molecules could react, adsorb, and decompose at chloride-capped Cu films. A submonolayer of Cu adatoms classified as the underpotential deposition (UPD) layer at 0.4 V (vs Ag/AgCl) was completely displaced by SPS molecules, possibly occurring via RSSR (SPS) + Cl-Cu-Pt → RS(-)-Pt(+) + RS(-) (MPS) + Cu(2+) + Cl(-), where MPS is 3-mercaptopropanesulfonate. By contrast, at 0.2 V, where a full monolayer of Cu was presumed to be deposited, SPS molecules were adsorbed in local (4 × 4) structures at the lower ends of step ledges. Bulk Cu deposition driven by a small overpotential (η < 50 mV) proceeded slowly to yield an atomically smooth Cu deposit at the very beginning (<5 layers). On a bilayer Cu deposit, the chloride adlayer was still adsorbed to afford SPS admolecules arranged in a unique 1D striped phase. SPS molecules could decompose into MPS upon further Cu deposition, as a (2 × 2)-MPS structure was observed with prolonged in situ STM imaging. It was possible to visualize either SPS admolecules in the upper plane or chloride adlayer sitting underneath upon switching the imaging conditions. Overall, this study established a MPS molecular film adsorbed to the chloride adlayer sitting atop the Cu deposit.


3D optical nanoscopy with excited state saturation at liquid helium temperatures.
We present a 3D fluorescence nanoscopy method operating at cryogenic temperatures, based on optical saturation of the excited state of individual molecules. Using a focused laser beam structured with a zero-intensity central region surrounded by intensity gradients in the three space directions, we achieve a sub-30 nm 3D optical resolution. Moreover, the analysis of the fluorescence scanning images of single molecules reveals the 3D orientation of their transition dipole with an accuracy of a few degrees. This method provides a valuable tool for locating neighboring molecules with overlapping optical transitions in order to study their interactions.


Sustainable polyelectrolyte multilayer surfaces: possible matrix for salt/dye separation.
The development of a sustainable membrane surface based on chitosan/poly(acrylic acid) (CHI/PAA) multilayers suitable for applications in analytical separations is reported here. Bilayers are constructed on polyamide microfiltration membranes at a pH combination of 3/3 (CHI pH/PAA pH) through a layer by layer approach. A 12.5 bilayer yielded a thickness of 400 nm. Low pressure (10 psi) filtrations through a 5.5 bilayered membrane exhibited high flux (7 m(3) m(-2) day(-1)) and selectivity (NaCl/reactive black 5 (RB5) selectivity >8000). The selectivity and flux observed here are the highest reported to date for low pressure filtrations through membranes. The increase in flux with increasing feed salt concentration is correlated with morphological transformations. Salt content above 7500 ppm causes some perturbation of surface layers. The presence of RB5, a model dye in the feed, restores the surface to maintain sustainability. A skin layer as thin as 50 nm imparts a large separation window. An RB5 feed concentration of 500 ppm results in 98.64% rejection with a flux of 25.79 m(3) m(-2) day(-1). The increase in flux with feed dye concentration supports the plasticizing action of RB5. The transport studies with large feed dye concentrations indicate that at a dye concentration of 500 ppm, the linear growing region (pre-exponential, 5.5 bilayer) itself provides a separation window similar to that of 100 ppm. At the same time, 1000 ppm requires a 9.5 bilayer that falls in the nonlinear growing region. Scanning electron microscopy images show the increase in porosity with respect to feed dye. Interesting morphologies that show the sustainable nature of the membrane surfaces along with the transport data of RB5 are presented.


Wallerian degeneration in central nervous system: dynamic associations between diffusion indices and their underlying pathology.
Although diffusion tensor imaging has been used to monitor Wallerian degeneration, the exact relationship between the evolution of diffusion indices and its underlying pathology, especially in central nervous system, remains largely unknown. Here we aimed to address this question using a cat Wallerian degeneration model of corticospinal tract. Twenty-five domestic mature Felis catus were included in the present study. The evolution of diffusion indices, including mean diffusivity (MD), fractional anisotropy (FA), primary (λ1) and transverse eigenvalues (λ23) of the degenerated corticospinal tract, were observed at baseline (before modeling) and at 2, 4, 6, 8, 10, 15, 20, 25, 30, 45 and 60 days after modeling in 4 cats. Pathological examinations were performed at eight time points mentioned above. Wallerian degeneration can be detected as early as the 2nd day after modeling by both diffusion tensor imaging and pathology. According to the evolution of diffusion indices, Wallerian degeneration can be classified into 2 stages. During the early stage (within 8 days after modeling), progressive disintegration of axons and myelin sheaths underlies the decreases in FA and λ1 and the increase in λ23. However, during the late stage (after 8 days), the gradual increases in FA, MD and λ1 and the unchanged λ23 seem to be a comprehensive reflection of the pathological processes including microglia activation, myelin clearance, and astrocytosis. Our findings help the understanding of the altered diffusion indices in the context of pathology and suggest that diffusion tensor imaging has the potential to monitor the processes of Wallerian degeneration in the central nervous system in vivo after acute damage.


Unique diversity of acanthothoracid placoderms (basal jawed vertebrates) in the Early Devonian of the Prague Basin, Czech Republic: A new look at Radotina and Holopetalichthys.
The taxonomy of Early Devonian placoderm material from the Lochkovian and Pragian of the Prague basin, previously attributed to the genera Radotina and Holopetalichthys, is revised. The Pragian species Radotina tesselata Gross 1958 shares detailed similarities with the holotype of the Lochkovian Radotina kosorensis Gross 1950, which is also the holotype of the genus; the assignation of both species to Radotina is supported. However, the Lochkovian material previously attributed to Radotina kosorensis also contains two unrecognised taxa, distinguishable from Radotina at the generic level: these are here named Tlamaspis and Sudaspis. The disputed genus Holopetalichthys, synonymised with Radotina by some previous authors, is shown to be valid. Furthermore, whereas Radotina, Tlamaspis and Sudaspis can all be assigned to the group Acanthothoracii, on the basis of several features including possession of a projecting prenasal region of the endocranium, Holopetalichthys lacks such a region and is probably not an acanthothoracid. Skull roof patterns and other aspects of morphology vary greatly between these taxa. Radotina has a substantially tesselated skull roof, whereas the skull roofs of Tlamaspis and Holopetalichthys appear to lack tesserae altogether. Tlamaspis has an extremely elongated facial region and appears to lack a premedian plate. Sudaspis has a long prenasal region, but unlike Tlamaspis the postnasal face is not elongated. Past descriptions of the braincase of 'Radotina' and the skull roofs of 'Radotina' and 'Holopetalichthys' incorporate data from more than one taxon, giving rise to spurious characterisations including an apparently extreme degree of skull roof variability. These descriptions should all be disregarded.


Nonfamilial Hypertrophic Cardiomyopathy: Prevalence, Natural History, and Clinical Implications.
Yield of causative variants in hypertrophic cardiomyopathy (HCM) is increased in some probands, suggesting different clinical subgroups of disease occur. We hypothesized that a negative family history and no sarcomere mutations represent a nonfamilial subgroup of HCM. We sought to determine the prevalence, natural history, and potential clinical implications of this nonfamilial subgroup of HCM. Four hundred and thirteen unrelated probands with HCM seen in a specialized HCM center between 2002 and 2015 and genetic testing performed were included in this retrospective cohort study. There were 251 (61%) probands with no reported family history of HCM, including 166 (40% of total) probands with no sarcomere mutation, that is, nonfamilial HCM. Quantified family pedigree data revealed no difference in mean number of first-degree relatives screened between nonfamilial and sarcomere-positive groups. Adjusted predictors of nonfamilial status were older age (odds ratio, 1.04; 95% confidence interval, 1.02-1.06; P=0.0001), male sex (odds ratio, 1.96; 95% confidence interval, 1.11-3.45; P=0.02), hypertension (odds ratio, 2.80; 95% confidence interval, 1.57-5.00; P=0.0005), and nonasymmetric septal morphology (odds ratio, 3.41; 95% confidence interval, 1.64-7.08; P=0.001). They had a less severe clinical course with greater event-free survival from major cardiac events (P=0.04) compared with sarcomere-positive HCM probands. Genotype prediction scores showed good performance in identifying genotype-positive patients (area under the curve, 0.71-0.75) and, in combination with pedigree characteristics, were further improved. Approximately 40% of HCM probands have a nonfamilial subtype, with later onset and less severe clinical course. We propose a revised clinical pathway for management, highlighting the role of genetic testing, a detailed pedigree, and refined clinical surveillance recommendations for family members.


Decomposition of fluorophosphoryl diazide: a joint experimental and theoretical study.
The photolytic and thermal decomposition of fluorophosphoryl diazide, FP(O)(N3)2, was studied using matrix isolation spectroscopy. Upon ArF laser photolysis (λ = 193 nm), FPO and a new geminal azido nitrene FP(O)(N3)N were identified using matrix IR spectroscopy. The nitrene shows a triplet ground state with the zero-field parameters |D/hc| = 1.566 cm(-1) and |E/hc| = 0.005 cm(-1). Further decomposition of the nitrene into FPO was observed under an irradiation of λ > 335 nm. In contrast, no nitrene but only FPO was identified after flash vacuum pyrolysis of the diazide. To reveal the decomposition mechanism, quantum chemical calculations on the potential energy surface (PES) of the diazide using DFT methods were performed. On the singlet PES four conformers of the nitrene were predicted. The two conformers (syn and anti) showing intramolecular Nnitrene···Nα,azide interactions are much lower in energy (ca. 40 kJ mol(-1), B3LYP/6-311+G(3df)) than the other two exhibiting Nnitrene···O interactions. syn/anti refers to the relative orientation of the P[double bond, length as m-dash]O bond and the N3 group. The interconversion of these species and the decomposition into FPO via a novel three-membered ring diazo intermediate cyclo-FP(O)N2 were computationally explored. The calculated low dissociation barrier of 45 kJ mol(-1) (B3LYP/6-311+G(3df)) of this cyclic intermediate rationalizes why it could not be detected in our experiments.


Can Dexmedetomidine Influence Recovery Profiles from General Anesthesia in Nasal Surgery?
Objectives Dexmedetomidine has sympatholytic, sedative, anesthetic, and analgesic effects, as well as vasoconstrictive effects, which may help prevent hypotension under general anesthesia. This meta-analysis aimed to perform a systematic review of the literature and investigate the effect of dexmedetomidine on perioperative morbidity following nasal surgery and its adverse effects. Data Sources MEDLINE, SCOPUS, and the Cochrane database. Review Methods Two authors independently searched the databases from their inception to March 2017. Studies were selected that compared perioperative dexmedetomidine administration (dexmedetomidine groups) with a placebo or remifentanil (control groups) with regard to intraoperative morbidity, including surgical time, bleeding amount, hypotension, and bradycardia during operation, and postoperative morbidity, such as emergence agitation, nausea and vomiting, and sedation after operation. Results Surgical time, intraoperative blood loss, dose of inhaled anesthetic gas, dose of fentanyl, postoperative pain, and incidence of emergence agitation were significantly lower in the dexmedetomidine group versus the placebo group. In contrast, there were no significant differences in intraoperative hemodynamic stability and postoperative residual sedation and nausea and vomiting between groups. Additionally, compared with remifentanil (a currently widely used agent), dexmedetomidine was superior in view of postoperative pain and intraoperative blood pressure control. Conclusion This meta-analysis shows that the systemic administration of dexmedetomidine can decrease surgical time, intraoperative blood loss, and doses of intraoperative inhaled anesthetic gas and fentanyl as compared with placebo. It can also decrease postoperative pain and incidence of the emergence agitation. Due to the small number of studies, further clinical trials are needed to confirm these results.


Hospital Quality Factors Influencing the Mobility of Patients for Radical Prostate Cancer Radiation Therapy: A National Population-Based Study.
To investigate whether patients requiring radiation treatment are prepared to travel to alternative more distant centers in response to hospital choice policies, and the factors that influence this mobility. We present the results of a national cohort study using administrative hospital data for all 44,363 men who were diagnosed with prostate cancer and underwent radical radiation therapy in the English National Health Service between 2010 and 2014. Using geographic information systems, we investigated the extent to which men choose to travel beyond ("bypass") their nearest radiation therapy center, and we used conditional logistic regression to estimate the effect of hospital and patient characteristics on this mobility. In all, 20.7% of men (n=9161) bypassed their nearest radiation therapy center. Travel time had a very strong impact on where patients moved to for their treatment, but its effect was smaller for men who were younger, more affluent, and from rural areas (P for interaction always <.001). Men were prepared to travel further to hospitals that offered hypofractionated prostate radiation therapy as their standard schedule (odds ratio 3.19, P<.001), to large-scale radiation therapy units (odds ratio 1.56, P<.001), and to hospitals that were early adopters of intensity modulated radiation therapy (odds ratio 1.37, P<.001). Men with prostate cancer are prepared to bypass their nearest radiation therapy centers. They are more likely to travel to larger established centers and those that offer innovative technology and more convenient radiation therapy schedules. Indicators that accurately reflect the quality of radiation therapy delivered are needed to guide patients' choices for radiation therapy treatment. In their absence, patient mobility may negatively affect the efficiency and capacity of a regional or national radiation therapy service and offer perverse incentives for technology adoption.


Comparison of different protocols for vestibular rehabilitation in patients with peripheral vestibular disorders.
To compare the therapeutic efficacy of two protocols for vestibular rehabilitation in several vestibular disordes. Twenty patients with chronic peripheral disorders of both genders (prevalence of females, with 60% of the sample) and mean age of 55 years and 9 months participated in this study. Group 1 carried out exercices based on stimulation of vertical and horizontal vestibulocular reflex, and Group 2 carried out exercices based on a protocol of personalized vestibular rehabilitation. Data analysis considered the complaint manifested during anamnesis and the clinical evolution of the patient during the execution of the exercises. The results obtained from the application of the Dizziness Handicap Inventory questionnaire (DHI) and the dizziness visual analog scale (VAS), both before and after vestibular rehabilitation, were also considered in the analysis. Differences were found in the values obtained in VAS and DHI (physical and functional scales and total score), in both groups. However, the comparison of the groups after rehabilitation showed that Group 2 obtained better scores than Group 1, both in VAS and DHI (functional scale and total value). Vestibular rehabilitation allowed significant improvement in otoneurological clinical profile and in self-perception of dizziness, regardless the therapeutic method used. Personalized vestibular rehabilitation was more efficient than the vestibulocular reflex stimulation protocol in improving quality of life of individuals with chronic periferal disorders.


The QualiRede intervention: improving the performance of care continuum in HIV, congenital syphilis, and hepatitis C in health regions.
Care continuum models have supported recent strategies against sexually transmitted diseases, such as HIV and Hepatitis C (HCV). HIV, HCV, and congenital syphilis care continuum models were developed, including all stages of care, from promotion/prevention to clinical control/cure. The models supported the intervention QualiRede, developed by a University-Brazilian National Health System (SUS) partnership focused on managers and other professionals from six priority health regions in São Paulo and Santa Catarina. Indicators were selected for each stage of the care continuum from the SUS information systems and from the Qualiaids and QualiAB facility's process evaluation questionnaires. The indicators acted as the technical basis of two workshops with professionals and managers in each region: the first one to identify problems and to create a Regional Technical Group; and the second one to design action plans for improving regional performance. The indicators are available at www.qualirede.org. The workshops took place in the regions of Alto Tietê, Baixada Santista, Grande ABC, and Registro (São Paulo) and of Foz do Rio Itajaí (Santa Catarina), which resulted in regional action plans in São Paulo, but not in Santa Catarina. A lack of awareness was observed regarding the new HIV and HCV protocols, as well as an incipient use of indicators in routine practices. Improving the performance of the care continuum requires appropriation of performance indicators and coordination of care flows at local, regional, and state levels of management.


Genetic analysis of coagulation properties, curd firming modeling, milk yield, composition, and acidity in Sarda dairy sheep.
Sheep milk is an important source of food, especially in Mediterranean countries, and is used in large part for cheese production. Milk technological traits are important for the sheep dairy industry, but research is lacking into the genetic variation of such traits. Therefore the aim of this study was to estimate the heritability of traditional milk coagulation properties and curd firmness modeled on time t (CFt) parameters, and their genetic relationships with test-day milk yield, composition (fat, protein, and casein content), and acidity in Sarda dairy sheep. Milk samples from 1,121 Sarda ewes from 23 flocks were analyzed for 5 traditional coagulation properties by lactodynamographic tests conducted for up to 60min: rennet coagulation time (min), curd-firming time (k20, min), and 3measures of curd firmness (a30, a45, and a60, mm). The 240 curd firmness observations (1 every 15 s) from each milk sample were recorded, and 4 parameters for each individual sample equation were estimated: rennet coagulation time estimated from the equation (RCTeq), the asymptotic potential curd firmness (CFP), the curd firming instant rate constant (kCF), and the syneresis instant rate constant (kSR). Two other derived traits were also calculated (CFmax, the maximum curd firmness value; and tmax, the attainment time). Multivariate analyses using Bayesian methodology were performed to estimate the genetic relationships of milk coagulation properties and CFt with the other traits; statistical inference was based on the marginal posterior distributions of the parameters of concern. The marginal posterior distribution of heritability estimates of milk yield (0.16±0.07) and composition (0.21±0.11 to 0.28±0.10) of Sarda ewes was similar to those often obtained for bovine species. The heritability of rennet coagulation time as a single point trait was also similar to that frequently obtained for cow milk (0.19±0.09), whereas the same trait calculated as an individual equation parameter exhibited larger genetic variation and a higher heritability estimate (0.32±0.11). The other curd firming and syneresis traits, whether as traditional single point observations or as individual equation parameters and derived traits, were characterized by heritability estimates lower than for coagulation time and for the corresponding bovine milk traits (0.06 to 0.14). Phenotypic and additive genetic correlations among the 11 technological traits contribute to describing the interdependencies and meanings of different traits. The additive genetic relationships of these technological traits with the single test-day milk yield and composition were variable and showed milk yield to have unfavorable effects on all measures of curd firmness (a30, a45, a60, CFP, and CFmax) and tmax, but favorable effects on both instant rate constants (kCF and kSR). Milk fat content had a positive effect on curd firmness traits, especially on those obtained from CFt equations, whereas the negative effects on both coagulation time traits were attributed to the milk protein and casein contents. Finally, in view of the estimated heritabilities and additive genetic correlations, enhancement of technological traits of sheep milk through selective breeding could be feasible in this population.


[Activation of neurohormonal system as an independent mechanism of heart remodeling in patients with chronic obstructive pulmonary disease].
To evaluate the contribution of activation of cytokines and renin-angiotensin-aldosterone system to heart remodeling in patients with chronic obstructive pulmonary disease in the course of a 2 year study and to estimate its relation to severe pulmonary hypertension. 117 patients with COPD underwent measurement of TNFα, IL-6 levels and renin levels, spirometry and echocardiography (mean pressure in pulmonary artery, MPPA)). The data obtainedwere compared with the degree of remodeling of right and left ventricles. After 2 years 30 and 33 of the 63 patients were referred to groups with aggressive and moderate remodeling of the right ventricle respectively. Regressive analysis was used to detect predictors of aggressive remodeling. Initial remodeling severity and rate showed stronger correlation with TNFα, IL-6 levels and renin levels than with MPPA. Multifactor analysis demonstrated that renin activity and creatinine level were the most reliable predictors of remodeling (p = 0.041 and 0.049 respectively). Neurohormonal and imunno-inflammatory changes stimulate remodeling of right and left heart chambers. They independently affect myocardium and their influence is only partly mediated through exacerbation of pulmonary hypertension.


Construction and validation of a robust prognostic model based on immune features in sepsis.
Sepsis, with life-threatening organ failure, is caused by the uncontrolled host response to infection. Immune response plays an important role in the pathophysiology of sepsis. Immune-related genes (IRGs) are promising novel biomarkers that have been used to construct the diagnostic and prognostic model. However, an IRG prognostic model used to predict the 28-day mortality in sepsis was still limited. Therefore, the study aimed to develop a prognostic model based on IRGs to identify patients with high risk and predict the 28-day mortality in sepsis. Then, we further explore the circulating immune cell and immunosuppression state in sepsis. The differentially expressed genes (DEGs), differentially expressed immune-related genes (DEIRGs), and differentially expressed transcription factors (DETFs) were obtained from the GEO, ImmPort, and Cistrome databases. Then, the TFs-DEIRGs regulatory network and prognostic prediction model were constructed by Cox regression analysis and Pearson correlation analysis. The external datasets also validated the reliability of the prognostic model. Based on the prognostic DEIRGs, we developed a nomogram and conducted an independent prognosis analysis to explore the relationship between DEIRGs in the prognostic model and clinical features in sepsis. Besides, we further evaluate the circulating immune cells state in sepsis. A total of seven datasets were included in our study. Among them, GSE65682 was identified as a discovery cohort. The results of GSEA showed that there is a significant correlation between sepsis and immune response. Then, based on a P value <0.01, 69 prognostic DEIRGs were obtained and the potential molecular mechanisms of DEIRGs were also clarified. According to multivariate Cox regression analysis, 22 DEIRGs were further identified to construct the prognostic model and identify patients with high risk. The Kaplan-Meier survival analysis showed that high-risk groups have higher 28-day mortality than low-risk groups (P=1.105e-13). The AUC value was 0.879 which symbolized that the prognostic model had a better accuracy to predict the 28-day mortality. The external datasets also prove that the prognostic model had an excellent prediction value. Furthermore, the results of correlation analysis showed that patients with Mars1 might have higher risk scores than Mars2-4 (P=0.002). According to the previous study, Mars1 endotype was characterized by immunoparalysis. Thus, the sepsis patients in high-risk groups might exist the immunosuppression. Between the high-risk and low-risk groups, circulating immune cells types were significantly different, and risk score was significantly negatively correlated with naive CD4+ T cells (P=0.019), activated NK cells (P=0.0045), monocytes (P=0.0134), and M1 macrophages (P=0.0002). Our study provides a robust prognostic model based on 22 DEIRGs which can predict 28-day mortality and immunosuppression status in sepsis. The higher risk score was positively associated with 28-day mortality and the development of immunosuppression. IRGs are a promising biomarker that might facilitate personalized treatments for sepsis.


Surgical wound infection in a developing country-Papua New Guinea.
The results are presented of a survey of surgical wound infection in the Port Moresby General Hospital. The rate of infection in operations where it was anticipated that there was not a high probability of infection was 10 per cent. This is discussed in terms of world figures. It is concluded that the infection rate is reasonable under the circumstances which apply in such countries. Reference is made to particular factors of importance in preventing wound infection.


Integrating context-aware public displays into a mobile hospital information system.
Hospitals are convenient settings for deployment of ubiquitous computing technology. Not only are they technology-rich environments, but their workers experience a high level of mobility resulting in information infrastructures with artifacts distributed throughout the premises. Hospital information systems (HISs) that provide access to electronic patient records are a step in the direction of providing accurate and timely information to hospital staff in support of adequate decision-making. This has motivated the introduction of mobile computing technology in hospitals based on designs which respond to their particular conditions and demands. Among those conditions is the fact that worker mobility does not exclude the need for having shared information artifacts particular locations. In this paper, we extend a handheld-based mobile HIS with ubiquitous computing technology and describe how public displays are integrated with handheld and the services offered by these devices. Public displays become aware of the presence of physicians and nurses in their vicinity and adapt to provide users with personalized, relevant information. An agent-based architecture allows the integration of proactive components that offer information relevant to the case at hand, either from medical guidelines or previous similar cases.


Biological assays for two mycotoxins produced by Fusarium tricinctum.
A survey was made to detect microorganisms useful for assaying butenolide [4-acetamido-4-hydroxy-2-butenoic acid gamma-lactone] and T-2 toxin [4beta, 15-diacetoxy-8alpha-(3-methylbutyryloxy)-12,13-epoxytricothec -9-en-3alpha-ol]. These mycotoxins produced by strains of Fusarium tricinctum have been implicated in mycotoxicosis of livestock. Although butenolide proved to be a very weak antibiotic, assay discs containing 100 mug of this toxin inhibited Sprillum serpens NRRL B-2052, Vibrio tyrogenus NRRL B-1033, and Xanthomonas campestris NRRL B-1459. T-2 toxin had no effect on 54 bacterial strains but inhibited 6 of 11 fungi. Growth of Rhodotorula rubra NRRL Y-7222 and Penicillium digitatum NRRL 1202 was retarded by assay discs containing 4 mug of T-2 toxin. Solutions with less than 1 mug of T-2 per ml toxin were readily detected by a pea seed germination test. Germination was reduced more than 50% when seeds imbibed solutions of 0.5 mug of T-2 toxin per ml. Butenolide had no effect on pea seed germination at concentrations as high as 200 mug/ml.


Physician's information customizer (PIC): using a shareable user model to filter the medical literature.
The practice of medicine is information-intensive. From reviewing the literature to formulating therapeutic plans, each physician handles information differently. Yet rarely does a representation of the user's information needs and preferences--a user model--get incorporated into information management tools, even though we might reasonably expect better acceptance and effectiveness if the tools' presentation and processing were customized to the user. We developed the Physician's Information Customizer (PIC), which generates a shareable user model that can be used in any medical information-management application. PIC elicits the stable, long-term attributes of a physician through simple questions about her specialty, research focus, areas of interest, patient characteristics (e.g., ages), and practice locale. To show the utility of this user model in customizing a medical informatics application, PIC custom-filters and ranks articles from Medline, using the user model to determine what would be most interesting to the user. Preliminary evaluation on all 99 unselected articles from a recent issue of six prominent medical journals shows that PIC ranks 66% of the articles as the user would. This demonstrates the feasibility of using easily acquired physician attributes to develop a user model that can successfully filter articles of interest from a large undifferentiated collection. Further testing and development is required to optimize the custom filter and to determine which characteristics should be included in the shareable user model and which should be obtained by individual applications.


Local Electric Field Facilitates High-Performance Li-Ion Batteries.
By scrutinizing the energy storage process in Li-ion batteries, tuning Li-ion migration behavior by atomic level tailoring will unlock great potential for pursuing higher electrochemical performance. Vacancy, which can effectively modulate the electrical ordering on the nanoscale, even in tiny concentrations, will provide tempting opportunities for manipulating Li-ion migratory behavior. Herein, taking CuGeO3 as a model, oxygen vacancies obtained by reducing the thickness dimension down to the atomic scale are introduced in this work. As the Li-ion storage progresses, the imbalanced charge distribution emerging around the oxygen vacancies could induce a local built-in electric field, which will accelerate the ions' migration rate by Coulomb forces and thus have benefits for high-rate performance. Furthermore, the thus-obtained CuGeO3 ultrathin nanosheets (CGOUNs)/graphene van der Waals heterojunctions are used as anodes in Li-ion batteries, which deliver a reversible specific capacity of 1295 mAh g-1 at 100 mA g-1, with improved rate capability and cycling performance compared to their bulk counterpart. Our findings build a clear connection between the atomic/defect/electronic structure and intrinsic properties for designing high-efficiency electrode materials.


Moxifloxacine plus amoxicillin and ranitidine bismuth citrate or esomeprazole triple therapies for Helicobacter pylori infection.
Up to 20% of patients, or even more, will fail to obtain eradication after a standard triple therapy. The aim of this study is to evaluate the efficacy of moxifloxacine-containing regimens in the first-line treatment of Helicobacter pylori. One hundred and twenty H. pylori-positive patients were randomized into four groups to receive one of the following 14-day treatments: ranitidine bismuth citrate (RBC) 400 mg b.d. plus amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. (RAC group, n = 30); RBC 400 mg b.d. plus moxifloxacine 400 mg o.d. and amoxicillin 1,000 mg b.d. (RAM group, n = 30); esomeprazole 40 mg b.d. plus amoxicillin 1,000 mg b.d. plus clarithromycin 500 mg b.d. (EAC group, n = 30); and esomeprazole 40 mg b.d. plus amoxicillin 1,000 mg b.d. plus moxifloxacine 400 mg o.d. (EAM group, n = 30). Eradication was assessed by (13)C urea breath test 8 weeks after therapy. Per-protocol and intention-to-treat eradication was achieved in 23 out of 30 patients (76.7%, 95% confidence interval [CI]: 61-92) in the RAC group, in 20 patients (66.7%, 95% CI: 49-84) in the RAM group, in 16 patients in the EAM group (53.3%, 95% CI: 34-71), and in 19 patients in the EAC group (63.3%, 95% CI: 54-72). Mild or moderate side-effects were significantly more common in the EAM group (70%) compared to the RAC (36.6%), RAM (43.3%), and EAC (56.6%) groups (P = 0.03). From our results, we conclude that moxifloxacine-containing triple therapies have neither eradication nor compliance advantages over standard triple therapies. Further studies with new antibiotic associations are needed for the better eradication of H. pylori in developing regions of the world.


Carbon input by roots into the soil: Quantification of rhizodeposition from root to ecosystem scale.
Despite its fundamental role for carbon (C) and nutrient cycling, rhizodeposition remains 'the hidden half of the hidden half': it is highly dynamic and rhizodeposits are rapidly incorporated into microorganisms, soil organic matter, and decomposed to CO2 . Therefore, rhizodeposition is rarely quantified and remains the most uncertain part of the soil C cycle and of C fluxes in terrestrial ecosystems. This review synthesizes and generalizes the literature on C inputs by rhizodeposition under crops and grasslands (281 data sets). The allocation dynamics of assimilated C (after 13 C-CO2 or 14 C-CO2 labeling of plants) were quantified within shoots, shoot respiration, roots, net rhizodeposition (i.e., C remaining in soil for longer periods), root-derived CO2 , and microorganisms. Partitioning of C pools and fluxes were used to extrapolate belowground C inputs via rhizodeposition to ecosystem level. Allocation from shoots to roots reaches a maximum within the first day after C assimilation. Annual crops retained more C (45% of assimilated 13 C or 14 C) in shoots than grasses (34%), mainly perennials, and allocated 1.5 times less C belowground. For crops, belowground C allocation was maximal during the first 1-2 months of growth and decreased very fast thereafter. For grasses, it peaked after 2-4 months and remained very high within the second year causing much longer allocation periods. Despite higher belowground C allocation by grasses (33%) than crops (21%), its distribution between various belowground pools remains very similar. Hence, the total C allocated belowground depends on the plant species, but its further fate is species independent. This review demonstrates that C partitioning can be used in various approaches, e.g., root sampling, CO2 flux measurements, to assess rhizodeposits' pools and fluxes at pot, plot, field and ecosystem scale and so, to close the most uncertain gap of the terrestrial C cycle.


Microarray-based characterisation of a Panton-Valentine leukocidin-positive community-acquired strain of methicillin-resistant Staphylococcus aureus.
Recent years have witnessed the emergence of novel methicillin-resistant Staphylococcus aureus (MRSA) strains that produce the potent toxin Panton-Valentine leukocidin (PVL). PVL-positive strains can cause complicated skin infections or necrotising pneumonia with high mortality, and these strains have the potential for epidemic spread in the community. In 2004-2005, two case clusters and two isolated cases were observed in eastern Saxony and southern Brandenburg. These were the first known infections with PVL-positive community-acquired MRSA (caMRSA) in this part of Germany. The isolates belonged to agr type III, spa type 44 or spa type 131, and showed a SmaI macrorestriction pattern that corresponded to caMRSA of clonal group ST80. The isolates were susceptible to levofloxacin, macrolides, clindamycin, gentamicin and vancomycin. Most isolates showed resistance to tetracycline and fusidic acid because of the presence of the tetK and far1 genes. A novel plasmid (designated pUB102) harbouring far1, tetK and blaZ was characterised and partially sequenced. Microarray analysis revealed that the caMRSA isolates harboured genes encoding several bi-component toxins (lukF/S-PVL, lukD/E, lukS/F plus hlgA, and another putative leukocidin homologue). Neither tst1 nor genes for enterotoxins A-Y were detected, but the isolates harboured several staphylococcal enterotoxin-like toxin genes (set genes), as well as genes encoding an epidermal cell differentiation inhibitor (edinB) and exfoliative toxin D (etD). Comparative analysis of other isolates from Australia, Germany, Switzerland and the UK showed that these isolates were representative of a widespread clone of caMRSA.


Kinetic modelling of lactate utilization and butyrate production by key human colonic bacterial species.
Butyrate is the preferred energy source for colonocytes and has an important role in gut health; in contrast, accumulation of high concentrations of lactate is detrimental to gut health. The major butyrate-producing bacterial species in the human colon belong to the Firmicutes. Eubacterium hallii and a new species, Anaerostipes coli SS2/1, members of clostridial cluster XIVa, are able to utilize lactate and acetate via the butyryl CoA : acetate CoA transferase route, the main metabolic pathway for butyrate synthesis in the human colon. Here we provide a mathematical model to analyse the production of butyrate by lactate-utilizing bacteria from the human colon. The model is an aggregated representation of the fermentation pathway. The parameters of the model were estimated using total least squares and maximum likelihood, based on in vitro experimental data with E. hallii L2-7 and A. coli SS2/1. The findings of the mathematical model adequately match those from the bacterial batch culture experiments. Such an in silico approach should provide insight into carbohydrate fermentation and short-chain fatty acid cross-feeding by dominant species of the human colonic microbiota.


Serial block-face scanning electron microscopy of erythrocytes protruding through the human placental syncytiotrophoblast.
The syncytiotrophoblast forms a continuous barrier between the maternal and fetal circulations. Here we present a serial block-face scanning electron microscopy (SBFSEM) study, based on a single image stack, showing pooling of fetal blood underneath a region of stretched syncytiotrophoblast that has become detached from the basement membrane. Erythrocytes are protruding from discrete holes in the syncytiotrophoblast suggesting that, under specific circumstances, the syncytiotrophoblast may be permeable to fetal cells. This observation represents a pathological process but it poses questions about the physical properties and permeability of the syncytiotrophoblast and may represent an early stage in the formation of fibrin deposits in areas of syncytial denudation. This study also illustrates how the 3D images generated by SBFSEM allow the interpretation of structures that could not be understood from a single histological section.


Body mass index, prostate cancer-specific mortality, and biochemical recurrence: a systematic review and meta-analysis.
Increasing evidence suggested obesity, measured by body mass index (BMI), was associated with prostate cancer-specific mortality, and its impact on biochemical recurrence was also inconclusive. We systematically searched MEDLINE, EMBASE, and bibliographies of retrieved studies up to January 5, 2010. We used random-effects meta-analysis to assess the relative risks (RR) of prostate cancer-specific mortality and biochemical recurrence associated with a 5 kg/m(2) increase in BMI. Among the six population-based cohort studies in 1,263,483 initially cancer-free men, 6,817 prostate cancer deaths occurred; a 5 kg/m(2) increase in BMI was associated with 15% (RR: 1.15, 95% confidence interval (CI): 1.06-1.25, P < 0.01) higher risk of dying of prostate cancer. In the six postdiagnosis survival studies on 18,203 patients with 932 prostate cancer deaths, a 5 kg/m(2) increase in BMI was associated with 20% higher prostate cancer-specific mortality (RR: 1.20, 95% CI: 0.99-1.46, P = 0.06). In the sixteen studies which followed 26,479 prostate cancer patients after primary treatment, a 5 kg/m(2) increase in BMI was significantly associated with 21% increased risk of biochemical recurrence (RR: 1.21, 95% CI: 1.11-1.31 P < 0.01). Elevated BMI is associated with risk of prostate cancer-specific mortality in prospective cohort studies and biochemical recurrence in prostate cancer patients. Its association with prostate cancer-specific mortality in diagnosed patients needs to be further evaluated.


Longitudinal effects of violent victimization during adolescence on adverse outcomes in adulthood: a focus on prosocial attachments.
To assess how prosocial attachments to school and family may diminish the effects of violent victimization during adolescence on adverse outcomes in adulthood. We analyzed secondary data on 13,555 participants from waves 1 (1994-1995) and 3 (2001-2002) of the National Longitudinal Study of Adolescent Health, a nationally representative sample of US high school and middle school students. Adverse outcomes in adulthood included offending, alcohol problems, drug use, risky sexual behavior, violent victimization, depression, low self-esteem, suicidality, hospitalizations, sexually transmitted infections, extreme weight control, and obesity. Analyses were conducted separately for males and females. Our multivariate regression analyses demonstrated that adolescent victimization is a significant predictor of a host of problems in adulthood. Nevertheless, attachment to school and to family meaningfully reduced the effect of victimization on nearly every adult outcome we assessed. Strong attachments to school and family in adolescence can reduce the long-term harms of violence on the lives of young persons. Incorporating this insight into regular clinical assessment could yield significant behavioral, health, and psychoemotional benefits for victims of violence.


Cerebral Malaria Treated with Artemisinin in the Intensive Care Unit: A Case Report.
Malaria is a parasitic disease that is starting to be encountered in intensive care units (ICU) worldwide, owing to increasing globalisation. Severe malaria caused by Plasmodium falciparum, is characterised by cerebral malaria, acute renal failure, hypoglycaemia, severe anaemia, splenomegaly and alveolar oedema. We present the case of a 25-yr old male patient who presented to the Emergency Department of Uludag University in Bursa, Turkey in the winter of 2014 with complaints of fever for three days. His medical history revealed a 14-month stay in Tanzania. Staining of blood smears revealed characteristic gametocytes in accordance with P. falciparum infection. The day after admission, he had an epileptic seizure after which his Glasgow Coma Scale was 6, so he was intubated and transferred to the ICU. A computerized tomography scan revealed findings of cerebral oedema. Intravenous mannitol was administered for 6 days. Intravenous artemisinin was continued for 10 days. Due to refractory fevers, anti-malarial treatment was switched to quinine and doxycycline on the 14th day and on the 16th day the fevers ceased. This case emphasizes that cerebral malaria should be suspected in cases of seizures accompanying malaria, and treatment should be initiated in the ICU. Furthermore, resistance of P. falciparum to artemisinin should be in mind when a response to therapy is lacking.


Characterization of the selective inhibition of the delta subclass of opioid binding sites by alcohols.
We recently reported that ethanol and other aliphatic alcohols exert a selective inhibition on the binding of enkephalins to delta opioid binding sites. We report here a more detailed investigation of the characteristics of this inhibition. Opioid binding sites of the kappa subtype are similar to mu opioid binding sites in their relative insensitivity to inhibition by aliphatic alcohols. Scatchard analysis of saturation data of enkephalin binding showed that inhibition is the result of a decrease in affinity. Results of kinetic experiments demonstrated that the inhibition can be entirely accounted for by an increase in the dissociation rate of the ligand-receptor complex. The presence of sodium ions in the incubation medium and raising the temperature of incubation exacerbate the inhibitory effectiveness of alcohols. The order of potency among structural isomers of alcohols for inhibition of delta receptor binding is as follows: straight-chain primary greater than isoprimary greater than secondary greater than tertiary. The order of inhibitory potency of the aliphatic alcohols tested correlates well with their ability to disorder the cell membrane lipid bilayer. It is suggested that this is a probable mechanism by which alcohols inhibit binding to delta opioid binding sites.


[A bioluminescent method of determining antibiotic sensitivity of microbial cells in septic blood].
A bioluminescence assay for rapid (5-7 h) determination of susceptibility to antibiotics was applied to samples of septic blood and optimized. The method comprises hemolysis of blood, reduction of osmolarity by adding concentrated nutritive media, and further incubation of the samples in the presence or absence of therapeutic doses of the antibiotic examined. Growth of bacteria is estimated by the level of bacterial ATP in the sample, which is determined by a bioluminescence assay. Hemolysis and further incubation of samples in nutrition media reduced the concentration of nonbacterial ATP to a level that did not interfere with the determination of bacterial ATP. There was a positive correlation between the levels of resistance to antibiotics determined by the bioluminescence assay and standard plate counts.


[Preference and trends of treatment for diabetic retinopathy in Korea and Japan].
The difference in preferences and trends of treatment in each country are important to plan an international interventional clinical study in eastern Asia. Accordingly, we compared the preferences and trends in treatment of diabetic retinopathy in Korea and Japan. We obtained answers to questionnaires (49 questions) from 91 ophthalmologists of the Korean Retina Society and 120 ophthalmologists of the Japanese Society of Ophthalmic Diabetology in June/July, 2012. Some of the questions were modified from The Preferences and Trends (PAT) survey of American Society of Retina Specialists. The first choice for a patient with vision of 20/25, clinically significant diabetic macular edema and clear evidence of intraretinal fluid on spectral domain OCT were intravitreal anti-vascular endothelial growth factor agent (31%) in Korea and sub-Tenon steroid (22%) in Japan. The management for a patient with refractory neovascular glaucoma who has closed angle and persistent intraocular pressure elevation (>50 mmHg) were glaucoma drainage implant surgery (74%) in Korea and trabeculectomy (57%) in Japan. There were differences in preferences and trends of treatment for diabetic retinopathy between Korea and Japan. The differences need to be considered when planning international clinical studies.