The impact of speech-based assistants on the driver's cognitive distraction.
Speech-based interfaces can be a promising alternative and/or addition to visual-manual interfaces since they reduce visual-manual distraction while driving. However, there are also findings indicating that speech-based assistants may be a source of cognitive distraction. The aim of this experiment was to quantify drivers' cognitive distraction while interacting with speech-based assistants. Therefore, 31 participants performed a simulated driving task and a detection response task (DRT). Concurrently they either sent text-messages via speech-based assistants (Siri, Google Assistant, or Alexa) or completed an arithmetic task (OSPAN). In a multifactorial approach, following Strayer et al. (2017), cognitive distraction was then assessed through performance in the DRT, the driving speed, the task completion time and self-report measures. The cognitive distraction associated with speech-based assistants was compared to the OSPAN task and a baseline condition without a secondary task. Participants reacted faster and more accurately to the DRT in the baseline condition compared to the speech conditions. The performance in the speech conditions was significantly better than in the OSPAN task. However, driving speed did not significantly differ between the experimental conditions. Results from the NASA-TLX indicate that speech-based tasks were more demanding than the baseline but less demanding than the OSPAN task. The task completion times revealed significant differences between speech-based assistants. Sending messages took longest with the Google Assistant. Referring to the findings by Strayer et al. (2017), we conclude that nowadays speech-based assistants are associated with a rather moderate than high level of cognitive distraction. Nonetheless, we point towards the need to assess the effects of human-machine interaction via speech-based interfaces due to their potential for cognitive distraction.


Botryoid odontogenic cyst. Report of a case with histologic evidence of multicentric origin.
Histologic examination of an excisionally biopsied botryoid odontogenic cyst (BOC) documented that it was composed of at least 2 separate cysts, the location of which suggested that both originated within the alveolar bone rather than from within the periodontal ligament. These observations provide evidence for a multicentric origin of this example of BOC, and are consistent with a previous suggestion that lateral periodontal cysts of non-inflammatory origin arise from remnants of the dental lamina.


[The influence of bacteria of the Burkholderia cepacia and Pseudomonas aeruginosa complex on cell-mediated immune reactions in experimental animals].
The evidence has been obtained that various species, as well as individual strains having pathogenicity factors, produced different effect on the functional activity of immunocompetent B and T lymphocytes of mice infected intraperitoneally. The injection of live P. aerruginosa PA 103 and B. cepacia 8240 cells resulted in imunosuppression of antibody-forming cells, synthesizing antibodies to heterologous antigens. On the contrary, in the animals infected with B. cepacia 8236 the functional activity of B lymphocytes increased. An increase in the proliferative activity of spleen cells was noted in the presence of T and B mitogens after the infection of mice with P. aeruginosa PA 103 in comparison with B. cepacia 8236 and B. cepacia 8240 which produced a faintly pronounced modulating effect. The pathogenesis mechanisms of infections induced by these microorganisms as well as the development of chronic, persisting forms of the infectious process are discussed.


Diet therapy for minority patients with diabetes.
Diet therapy for minority diabetic patients must be directed to NIDDM, the most prominent form of diabetes in minority populations. Diet programs must be tailored to the cultural framework, and traditional foods with desirable characteristics can be encouraged. To teach patients about diet, educators must use educational techniques appropriate to culture and literacy of the patient and family. Single-concept messages such as "eat less fat" or "eat less food" promote learning and minimize failure. Nutrition information can be divided into sequenced manageable steps that can then be individualized to the patient's setting. No single set of exchange lists will suffice for all minority groups, nor are exchange lists themselves appropriate for all situations. To meet the needs of minority patients, nutrition educators must use a variety of tools and techniques relating to the foods of a particular ethnic group. Sound education strategies and simplified materials for NIDDM patients should also be employed.


Progestin receptors: neuronal integrators of hormonal and environmental stimulation.
Although it originally was believed that neuronal steroid hormone receptors require binding to cognate ligand for activation, more recent evidence suggests that the receptors can be activated indirectly by other compounds, such as neurotransmitters and growth factors, acting through their own membrane receptors and specific intracellular signaling pathways. For example, as is the case with facilitation of sexual behavior by progesterone, facilitation of sexual behavior by D(1)/D(5) dopamine receptor agonists is blocked by disruption of progestin receptors. Therefore, some dopamine agonists facilitate sexual behavior at least in part by a progestin receptor-dependent mechanism, as does progesterone. This "ligand-independent activation" of neuronal progestin receptors is not limited to dopamine agonists; a variety of other compounds, as well as mating stimulation, facilitate sexual receptivity by a progestin receptor-dependent process. Steroid hormone receptors also can be regulated by afferent input in another way. Various neurotransmitters upregulate or downregulate steroid hormone receptors in some neurons. This, in turn, presumably confers greater or decreased sensitivity to the particular factors that can activate the particular steroid receptor in those particular neurons. Therefore, steroid hormones are but one class of factors that can regulate and activate steroid hormone receptors. Some additional factors that activate steroid hormone receptors have been identified, as have some factors that can regulate concentrations of receptors. Relatively little is known at this time about the range of neurotransmitters, humoral factors, and intracellular signaling pathways that are involved.


Development of a short form of the Attitudes to Ageing Questionnaire (AAQ).
The original 24-item Attitudes to Aging Questionnaire (AAQ) is well established as a measure of attitudes to aging, comprising domains of psychosocial loss (PL), physical change (PC), and psychological growth (PG). This paper presents a new 12-item short form Attitudes to Aging Questionnaire (AAQ-SF). The original field trial data used to develop the 24-item AAQ (AAQ-24) were used to compare 6-item, 9-item, and 12-item versions of AAQ-SF (sample 1, n = 2487) and to test the discriminative validity of the selected 12-item AAQ-SF (sample 2, n = 2488). Data from a separate study reporting on the AAQ-24 (sample 3, n = 792) verified the analyses. The 12-item AAQ-SF reported adequate internal consistency in both sample 1 (PL α = .72, PC α = .72, and PG α = .62) and sample 3 (PL α = .68, PC α = .73, and PG α = .61). The AAQ-SF functioned consistently with the profile of the AAQ-24 in that subscales in both formats of this measure discriminate between respondents on key parameters such as depression, subjective health status, and overall quality of life in sample 2. Sample 3 also demonstrated the AAQ-SF can detect the differences in attitudes toward aging between individuals experiencing anxiety and depression and those without psychological symptoms. Confirmatory factor analysis confirmed that the structure of the AAQ-SF mirrors that of the original 24-item AAQ. The AAQ-SF is a robust measure of attitudes toward aging, which can reduce respondent burden when used within longer questionnaire batteries or longitudinal research. Copyright © 2017 John Wiley & Sons, Ltd.


In vitro evolution of molecular cooperation in CATCH, a cooperatively coupled amplification system.
One of the key issues in the investigation of evolution is how complex systems evolved from simple chemical replicators. Theoretical work proposed several models in which complex replicating systems are kinetically stabilized. The development of powerful isothermal amplification technique allows complex nucleic acid based evolving in vitro systems to be set up, which may then serve to verify experimentally current theories of evolution. Recently such a system based on the 3SR (self-sustained sequence replication) reaction has been established to investigate the evolution of cooperation: the trans-cooperatively coupled CATCH (cooperative amplification by cross hybridization). Over four rounds of serial transfer, the cooperatively coupled two species CATCH system evolved into a more complex cooperative four species system, which then was overgrown by CATCH-derived RNA-Z-like hairpin species. In contrast to the classical RNA-Z species, these molecules have complementary loop sequences and self-amplify using a dual mechanism that includes concentration-dependent phases of noncooperative and cooperative amplification. The evolution of a cooperative system, under conditions that were alternately unfavorable and favorable for cooperative amplification, led to a system showing facultative cooperation. This principle of facultative cooperation preserves the complexity of the system investigated and could have general implications for the evolution and stabilization of cooperation under oscillating reaction conditions.


Quantitative Representativeness and Constituency of the Long-Term Agroecosystem Research Network and Analysis of Complementarity with Existing Ecological Networks.
Studies conducted at sites across ecological research networks usually strive to scale their results to larger areas, trying to reach conclusions that are valid throughout larger enclosing regions. Network representativeness and constituency can show how well conditions at sampling locations represent conditions also found elsewhere and can be used to help scale-up results over larger regions. Multivariate statistical methods have been used to design networks and select sites that optimize regional representation, thereby maximizing the value of datasets and research. However, in networks created from already established sites, an immediate challenge is to understand how well existing sites represent the range of environments in the whole area of interest. We performed an analysis to show how well sites in the USDA Long-Term Agroecosystem Research (LTAR) Network represent all agricultural working lands within the conterminous United States (CONUS). Our analysis of 18 LTAR sites, based on 15 climatic and edaphic characteristics, produced maps of representativeness and constituency. Representativeness of the LTAR sites was quantified through an exhaustive pairwise Euclidean distance calculation in multivariate space, between the locations of experiments within each LTAR site and every 1 km cell across the CONUS. Network representativeness is from the perspective of all CONUS locations, but we also considered the perspective from each LTAR site. For every LTAR site, we identified the region that is best represented by that particular site-its constituency-as the set of 1 km grid locations best represented by the environmental drivers at that particular LTAR site. Representativeness shows how well the combination of characteristics at each CONUS location was represented by the LTAR sites' environments, while constituency shows which LTAR site was the closest match for each location. LTAR representativeness was good across most of the CONUS. Representativeness for croplands was higher than for grazinglands, probably because croplands have more specific environmental criteria. Constituencies resemble ecoregions but have their environmental conditions "centered" on those at particular existing LTAR sites. Constituency of LTAR sites can be used to prioritize the locations of experimental research at or even within particular sites, or to identify the extents that can likely be included when generalizing knowledge across larger regions of the CONUS. Sites with a large constituency have generalist environments, while those with smaller constituency areas have more specialized environmental combinations. These "specialist" sites are the best representatives for smaller, more unusual areas. The potential of sharing complementary sites from the Long-Term Ecological Research (LTER) Network and the National Ecological Observatory Network (NEON) to boost representativeness was also explored. LTAR network representativeness would benefit from borrowing several NEON sites and the Sevilleta LTER site. Later network additions must include such specialist sites that are targeted to represent unique missing environments. While this analysis exhaustively considered principal environmental characteristics related to production on working lands, we did not consider the focal agronomic systems under study, or their socio-economic context.


Acetylcholine, GABA and glutamate induce ionic currents in cultured antennal lobe neurons of the honeybee, Apis mellifera.
The honeybee, Apis mellifera, is a valuable model system for the study of olfactory coding and its learning and memory capabilities. In order to understand the synaptic organisation of olfactory information processing, the transmitter receptors of the antennal lobe need to be characterized. Using whole-cell patch-clamp recordings, we analysed the ligand-gated ionic currents of antennal lobe neurons in primary cell culture. Pressure applications of acetylcholine (ACh), gamma-amino butyric acid (GABA) or glutamate induced rapidly activating ionic currents. The ACh-induced current flows through a cation-selective ionotropic receptor with a nicotinic profile. The ACh-induced current is partially blocked by alpha-bungarotoxin. Epibatidine and imidacloprid are partial agonists. Our data indicate the existence of an ionotropic GABA receptor which is permeable to chloride ions and sensitive to picrotoxin (PTX) and the insecticide fipronil. We also identified the existence of a chloride current activated by pressure applications of glutamate. The glutamate-induced current is sensitive to PTX. Thus, within the honeybee antennal lobe, an excitatory cholinergic transmitter system and two inhibitory networks that use GABA or glutamate as their neurotransmitter were identified.


Estrogen biosynthesis in cultured skeletal muscle cells (L6) induced by amino acids.
Previous investigations have indicated upregulation of gene expression in cellular pathways related to the biosynthesis of steroids in response to amino acids (AA) in skeletal muscle cells. This suggests AA as modulators of de novo synthesis of sex steroids for muscle growth and improved functional capacity. The aim of the present study was to investigate if increased availability of amino acids induced biosynthesis of sex steroids in skeletal muscles. Confluent L6 muscle cells were cultured in media with various AA concentrations (0.3 or 9 mM AA or 2.1 mM branched-chain (BCAA) only), following pre-culture in serum-free medium. Sex steroids were quantified by gas chromatography-tandem mass spectrometry (GC-MS/MS). Mevalonate (diphospho-) decarboxylase enzyme (MVD) was quantified by Western blot. The experiments confirmed that estradiol and estrone increased in both L6 cell lysates and in conditioned media at the end of experiments on confluent cells, while progesterone or androgenic steroids were not detected in either cell lysates or culture media. Estradiol (+ 31 ± 3%) and estrone (+ 18 ± 4%) increased significantly in cells cultured at 9 mM AA (p < 0.001 vs. 0.3 mM AA, n = 10). Similarly, MVD protein increased at 9 mM AA (p < 0.001 vs. 0.3 mM AA, n = 17). An addition of BCAA alone to media increased MVD-protein levels to the same extent as all AA (p < 0.01 vs. 0.3 mM AA, n = 3). Female sex steroids and MVD enzyme production increased significantly in response to amino acid availability. The results indicate a role of amino acids as modulators of local muscle estrogen synthesis in muscle cells from rats at feeding.


THE EFFECT OF LOW TO MODERATE PRENATAL ALCOHOL EXPOSURE AND BINGE DRINKING EPISODES ON DRAW-A-PERSON AT AGE 5 YEARS.
This study examined the effects of maternal alcohol consumption and binge drinking during pregnancy on children's Draw-A-Person (DAP) scores. Participants were 1,533 5-year-olds from the Danish National Birth Cohort. Regression analyses revealed an adverse effect of nine or more drinks per week. A drop in mean DAP score of 6.26 (95 % CI: -12.24; -0.39) was observed in the fully adjusted model. A significant interaction between average weekly consumption and binge episodes also was observed. Findings suggest that prenatal exposure to moderate weekly doses of alcohol and binge drinking episodes are associated with lowered scores on the DAP.


Synergistic effect of drug/antibiotic-impregnated micro/nanohybrid mesoporous bioactive glass/calcium phosphate composite bone cement on antibacterial and osteoconductive activities.
Calcium phosphate bone cements (CPC) can be used in minimally invasive surgery because of their injectability, and they can also be used to repair small and irregular bone defects. This study aimed to release the antibiotic gentamicin sulfate (Genta) to reduce tissue inflammation and prevent infection in the early stages of bone recovery. Subsequently, the sustained release of the bone-promoting drug ferulic acid (FA) mimicked the response of osteoprogenitor D1 cells interaction, thereby accelerating the healing process of the overall bone repair. Accordingly, the different particle properties of micro-nano hybrid mesoporous bioactive glass (MBG), namely, micro-sized MBG (mMBG) and nano-sized MBG (nMBG), were explored separately to generate different dose releases in MBG/CPC composite bone cement. Results show that nMBG had better sustained-release ability than mMBG when impregnated with the same dose. When 10 wt% of mMBG hybrid nMBG and composite CPC were used, the amount of MBG slightly shortened the working/setting time and lowered the strength but did not hinder the biocompatibility, injectability, anti-disintegration, and phase transformation of the composite bone cement. Furthermore, compared with 2.5wt%Genta@mMBG/7.5 wt% FA@nMBG/CPC, 5wt.%Genta@mMBG/5wt.%FA@nMBG/CPC exhibited better antibacterial activity, better compressive strength, stronger mineralization of osteoprogenitor cell, and similar 14-day slow-release trend of FA. The MBG/CPC composite bone cement developed can be used in clinical surgery to achieve the synergistic sustained release of antibacterial and osteoconductive activities.


Relationship between lipoprotein(a) and spontaneous recanalization of infarct-related arteries in the early phase of acute myocardial infarction.
Lipoprotein(a) (Lp[a]) is known to inhibit the fibrinolysis system and promote thrombus formation. We retrospectively investigated the influences of Lp(a) on infarct-related artery patency in the early phase of acute myocardial infarction (AMI). In 144 patients with ST-segment elevation, myocardial, coronary angiography (CAG) was performed within 12 h of the onset of symptoms. Subjects were divided into 2 groups according to the thrombolysis in myocardial infarction (TIMI) grade, Group I (TIMI 0-1, n = 94) versus Group II (TIMI 2-3, n = 50). The Gensini score and 0- to 3-vessel disease score estimated the severity and extent of coronary artery disease (CAD), respectively. Lp(a), lipid profile and c-reactive protein (CRP) were measured before any medications including thrombolytics were given. The Lp(a) level was higher in Group I than in Group II. There was a weak correlation between Lp(a) level and Gensini score. By multivariate logistic regression analysis, a Lp(a) level was a predictor of infarct-related artery patency in the early phase of AMI. There were no significant differences in the location of the infarct-related arteries, extent of CAD, time from pain to CAG, number of risk factors, and hs-CRP values between the 2 groups. The Lp(a) level was significantly higher in patients with persistent occlusion compared with those with spontaneous recanalization of infarct-related arteries in the early phase of AMI.


Simultaneous molecular and morphological analysis of braconid relationships (Insecta: Hymenoptera: Braconidae) indicates independent mt-tRNA gene inversions within a single wasp family.
We investigated the phylogeny of the Braconidae (Insecta: Hymenoptera) with a much expanded data set compared with that of previous attempts, employing 16S and 28S rDNA gene fragments, together with a suite of morphological characters, from 74 ingroup taxa. Most notably, parsimony analyses under a range of models recovered the Aphidiinae as sister group to the cyclostomes and the Ichneutinae as sister group to the microgastroids. The cyclostomes were recovered as a natural group only if certain, putatively misplaced genera (Mesostoa, Aspilodemon) were excluded from them. Further, mapping of rearrangement characters onto this phylogeny of the Braconidae indicated parallel inversions of the mt-tRNAD gene, with the two instances of inversion distinguishable by the presence or absence of an additional tRNA gene (tRNAH). This is the first report of a parallel inversion of a mt-tRNA gene and makes the Braconidae the first metazoan family to display both parallel inversions and translocations.


Maturation of synapses and electrical properties of cells in the cochlear nuclei.
Auditory nerve fibers carry impulses from the cochlea to the cochlear nuclei. There the temporal firing patterns of auditory nerve fibers are preserved by some cells and altered by others. The two factors which govern how firing patterns are shaped are (1) the intrinsic electrical properties of cells that determine the size and time course of voltage changes caused by synaptic currents and (2) the synaptic circuitry between cells. The electrical properties of cells were measured by recording the responses to current injected intracellularly into brain slice preparations. The synaptic responses to electrical shocks of the auditory nerve were used to determine the functional properties of synaptic connections. The three distinct types of electrical properties of cells that can be distinguished electrophysiologically in similar preparations of mature tissue, bushy and stellate cells in the ventral cochlear nucleus [(1984) J. Neurosci. 4, 1577-1588] and cells in the dorsal cochlear nucleus [Hirsch and Oertel (1987) (submitted); Oertel et al. (1987) In: Functions of the Auditory System, Editor: S. Hassler. J. Wiley and Sons (in press)] can be differentiated at least as early as 7 days after birth. Young cells, however, have higher input resistances and lower input capacitances than mature cells, and they cannot sustain high firing rates. Bushy and stellate cells in the ventral cochlear nucleus respond to electrical stimulation of the auditory nerve with both excitatory and inhibitory postsynaptic potentials as early as 4 days after birth. The synaptic potentials occur with longer and more variable latencies than in mature cells and synapses fatigue more easily, however. Cells of the dorsal cochlear nucleus also receive both excitatory and inhibitory synaptic inputs 4 days after birth, upon stimulation of the auditory nerve. No systematic changes were detected in these synaptic responses as a function of age but this may have been because the variability in the shape and timing of synaptic responses was large even in mature tissue.


[Some details concerning hospitalism (author's transl)].
The authors discuss problems of hospitalism especially room and skin disinfection. The percentage of disturbed wound healing in clean surgical cases is dealt with.


Rearrest rates among Norwegian drugged drivers compared with drunken drivers.
The rearrest rates among Norwegian drugged (n=1102) and a group of drunken drivers (n=850) (BAC: 0.16-0.19%) apprehended during 1992, were 57% (n=629) and 28% (n=238), respectively, when followed prospectively for 7 years. The most important risk factors for recidivism among drugged drivers were previous arrests for drugged or drunken driving (rearrest rate among previous arrests: 73%, no previous arrest: 42%), multi-drug detection at selection (multi-drug: 62%, single drug: 41%), sex (male: 61%, female: 35%) and age (below 36 years: 60%, 36 years and older: 44%). Most of the recidivist drugged drivers were rearrested during the year of selection (21%), followed by 13, 7 and 6%, retrospectively, during the following years. When followed both retrospectively and prospectively for a period extending from 1984 to 1998, 71% (n=779) and 40% (n=344) of the selected drugged and drunken drivers, respectively, were arrested two or more times.


Expression of C5a in the brain does not exacerbate experimental autoimmune encephalomyelitis.
Complement is implicated in the pathology of neurodegenerative and inflammatory disease in the central nervous system (CNS). Although studies demonstrate that inhibition of complement activation attenuates disease development in the CNS, the specific complement components that contribute to the pathogenesis of CNS diseases remain unclear. To dissect the role of C5a in CNS disease, we developed a transgenic mouse that produces C5a exclusively in the brain using the astrocyte-specific, murine glial fibrillary acidic protein (GFAP) promoter. C5a/GFAP mice develop normally and do not demonstrate any signs of spontaneous inflammation or neurodegeneration with age. Using C5a/GFAP mice, we examined the outcome of the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). To our surprise the onset and severity of myelin oligodendrocyte glycoprotein-induced EAE was essentially identical between C5a/GFAP and control mice. These results demonstrate that C5a, despite it is pro-inflammatory functions, is not critical to the development and progression of EAE.


Transcutaneous electrical acupoint stimulation in adult patients receiving gastrectomy/colorectal resection: A randomized controlled trial.
Acupuncture promotes the recovery of gastrointestinal function and provides analgesia after major abdominal surgery. The effects of transcutaneous electrical acupoint stimulation (TEAS) remain unclear. To explore the potential effects of TEAS on the recovery of gastrointestinal function after gastrectomy and colorectal resection. Patients scheduled for gastrectomy or colorectal resection were randomized at a 2:3:3:2 ratio to receive: (1) TEAS at maximum tolerable current for 30 min immediately prior to anesthesia induction and for the entire duration of surgery, plus two 30-min daily sessions for 3 consecutive days after surgery (perioperative TEAS group); (2) Preoperative and intraoperative TEAS only; (3) Preoperative and postoperative TEAS only; or (4) Sham stimulation. The primary outcome was the time from the end of surgery to the first bowel sound. In total, 441 patients were randomized; 405 patients (58.4 ± 10.2 years of age; 247 males) received the planned surgery. The time to the first bowel sounds did not differ among the four groups (P = 0.90; log-rank test). On postoperative day 1, the rest pain scores differed significantly among the four groups (P = 0.04; Kruskal-Wallis test). Post hoc comparison using the Bonferroni test showed lower pain scores in the perioperative TEAS group (1.4 ± 1.2) than in the sham stimulation group (1.7 ± 1.1; P = 0.04). Surgical complications did not differ among the four groups. TEAS provided analgesic effects in adult patients undergoing major abdominal surgery, and it can be added to clinical practice as a means of accelerating postoperative rehabilitation of these patients.


Comparative performance of warfarin pharmacogenetic algorithms in Chinese patients.
Multiple warfarin pharmacogenetic algorithms have been confirmed to predict warfarin dose more accurately than clinical algorithm or the fixed-dose approach. However, their performance has never been objectively evaluated in patients under low intensity warfarin anticoagulation, which is optimal for prevention of thromboembolism in Asian patients. We sought to compare the performances of 8 eligible pharmacogenetic algorithms in a cohort of Chinese patients (n=282) under low intensity warfarin anticoagulation with target international normalized ratio (INR) ranged from 1.6 to 2.5. The performance of each algorithm was evaluated by calculating the percentage of patients whose predicted dose fell within 20% of their actual therapeutic dose (percentage within 20%), and the mean absolute error (MAE) between each predicted dose and actual stable dose. In the entire cohort, the pharmacogenetic algorithms could predict warfarin dose with the average MAE of 0.87 ± 0.17 mg/day (0.73-1.17 mg/day), and the average percentage within 20% of 43.8% ± 8.1% (29.1% - 52.1%). By pairwise comparison, warfarin dose prediction was significantly more accurate with the algorithms derived from Asian patients (48.6% - 50.0%) than those from Caucasian patients (29.1% - 39.7%; odds ratio [OR]: 1.61-3.36, p ≤ 0.02). Algorithms with additional covariates of INR values or CYP4F2*3 performed better than those without the covariates (adding INR: OR: 1.71 (1.08-2.72), p =0.029; adding CYP4F2*3: OR: 2.67(1.41-5.05), p =0.004). When the patients were stratified according to the dose range, the algorithms from Caucasian and racially mixed populations tended to perform better in higher dose group (≥ 4.5mg/day), and algorithms from Asian populations performed better in intermediate dose group (1.5-4.5mg/day). None of the algorithms performed well in lower dose group (≤ 1.5mg/day). No eligible pharmacogenetic algorithm could perform the best for all dosing range in the Chinese patients under low intensity warfarin anticoagulation. Construction of a refinement pharmacogenetic algorithm integrating 3 genotypes (CYP2C9, VKORC1 and CYP4F2) and INR data should be warranted to improve the warfarin dose prediction in such patients.


Seasonal abundance and potential of Japanese encephalitis virus infection in mosquitoes at the nesting colony of ardeid birds, Thailand.
To investigate the abundance and seasonal dynamics of mosquitoes, and to detect Japanese encephalitis virus (JEV) in these mosquitoes at the nesting colony of ardeid birds. Mosquitoes were collected bimonthly from July 2009 to May 2010 by Centers for Disease Control. Light traps and dry ice, as a source of CO2, were employed to attract mosquitoes. Mosquitoes were first identified, pooled into groups of upto 50 mosquitoes by species, and tested for JEV infection by viral isolation and reverse transcriptase polymerase chain reaction. A total of 20 370 mosquitoes comprising 14 species in five genera were collected. The five most abundant mosquito species collected were Culex tritaeniorhynchus (95.46%), Culex vishnui (2.68%), Culex gelidus (0.72%), Anopheles peditaeniatus (0.58%) and Culex quinquefasciatus (0.22%). Mosquito peak densities were observed in July. All of 416 mosquito pools were negative for JEV. This study provides new information about mosquito species and status of JEV infection in mosquitoes in Thailand. Further study should be done to continue a close survey for the presence of this virus in the ardeid birds.


Altering the concentration of silica tunes the functional properties of collagen-silica composite scaffolds to suit various clinical requirements.
The success of a tissue engineering scaffold depends on a fine balance being achieved between the physicochemical and biological properties. This study attempts to understand the influence of silica concentration on the functional properties of collagen-silica (CS) composite scaffolds for soft tissue engineering applications. Increasing the ratio of silica to collagen (0.25, 0.5, 0.75, 1.0, 1.25, 1.5 and 2.0 w/w) gave a marked advantage in terms of improving the water uptake and compressive modulus of the CS scaffolds, while also enhancing the biological stability and the turnover time. With increase in silica concentration the water uptake and compressive modulus increased concurrently, whereas it was not so for surface porous architecture and biocompatibility which are crucial for cell adhesion and infiltration. Silica:collagen ratio of ≤1 exhibits favourable surface biocompatibility, and any further increase in silica concentration has a detrimental effect.


Impact of a stress coping strategy on perceived stress levels and performance during a simulated cardiopulmonary resuscitation: a randomized controlled trial.
Cardiopulmonary resuscitation (CPR) causes significant stress for the rescuers which may cause deficiencies in attention and increase distractibility. This may lead to misjudgements of priorities and delays in CPR performance, which may further increase mental stress (vicious cycle). This study assessed the impact of a task-focusing strategy on perceived stress levels and performance during a simulated CPR scenario. This prospective, randomized-controlled trial was conducted at the simulator-center of the University Hospital Basel, Switzerland. A total of 124 volunteer medical students were randomized to receive a 10 minute instruction to cope with stress by loudly posing two task-focusing questions ("what is the patient's condition?", "what immediate action is needed?") when feeling overwhelmed by stress (intervention group) or a control group. The primary outcome was the perceived levels of stress and feeling overwhelmed (stress/overload); secondary outcomes were hands-on time, time to start CPR and number of leadership statements. Participants in the intervention group reported significantly less stress/overload levels compared to the control group (mean difference: -0.6 (95% CI -1.3, -0.1), p=0.04). Higher stress/overload was associated with less hands-on time. Leadership statements did not differ between groups, but the number of leadership statements did relate to performance. Hands-on time was longer in the intervention- group, but the difference was not statistically significant (difference 5.5 (95% CI -3.1, 14.2), p=0.2); there were no differences in time to start CPR (difference -1.4 (95% CI -8.4, 5.7), p=0.71). A brief stress-coping strategy moderately decreased perceived stress without significantly affecting performance in a simulated CPR. Further studies should investigate more intense interventions for reducing stress. NCT01645566.


Water movement between myocardial tissue and capillary blood during and after coronary reactive hyperemia as studied by continuous measurement of colloid osmotic pressure of cardiac venous blood.
Colloid osmotic pressure (COP) of blood from the great cardiac vein was continuously measured by the use of a membrane colloid osmometer during reactive hyperemia resulting from temporary occlusion of the anterior descending branch of left coronary artery. The COP increased sharply but transit was concluded that a measurable amount of water moved from the capillary blood into the myocardial tissue and then flowed back slowly into the capillary blood.


The analysis of Survivin promoter (-31G/C) gene variation in oral squamous cell carcinoma risk and prognosis.
Oral squamous cell carcinoma (OSCC) is a malign tumor that associated with smoking and alcohol consumption, eating habits, environmental factors, and genetic susceptibility of the individuals. The Survivin gene, also known as BIRC5, plays important roles in the regulation of the cell cycle and apoptosis. The aim of the present study is to investigate Survivin -31G/C polymorphism in OSCC development and prognosis. A total of 61 patients with oral squamous cell carcinoma and 133 healthy individuals were genotyped by using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism method (PCR-RFLP) to evaluate the role of the Survivin gene promoter region (-31) variation. There were no statistically significant differences in the distribution of Survivin promoter -31 polymorphism genotype and allele frequencies between the cases and controls but we analyzed the clinicopathological characteristics of patients and noticed a significant correlation between the C allele and advanced tumor stage in the patients (p = 0.022). The Survivin (-31) gene polymorphism might be associated with advanced tumor stage in oral squamous cell carcinoma but further studies in a larger population are needed most effective evaluation of the Survivin (-31) gene variation in the OSCC risk and prognosis.


Enzyme-regulated topology of a cyclic peptide brush polymer for tuning assembly.
Norbornenyl cyclic elastin-like peptides were polymerized via ring opening metathesis polymerization (ROMP) to generate thermally responsive brush polymers. The thermally-responsive nature of the materials could be attenuated by the addition of a proteolytic enzyme that causes the cyclic peptide side chains to be linearized.


Proteomics reveals defective peroxisomal fatty acid oxidation during the progression of acute kidney injury and repair.
Acute kidney injury (AKI) is characterized by a rapid decrease in renal function with high mortality and risk of progression to chronic kidney disease (CKD). Ischemia and reperfusion injury (IRI) is one of the major causes of AKI. However, the cellular and molecular responses of the kidney to IRI are complex and not fully understood. Herein, we conducted unbiased proteomics and bioinformatics analyses in an IRI mouse model on days 3, 7, and 21, and validated the results using IRI, unilateral ureteral obstruction (UUO), and biopsies from patients with AKI or CKD. The results indicated an obvious temporal expression profile of differentially expressed proteins and highlighted impaired lipid metabolism during the progression of AKI to CKD. Acyl-coenzyme A oxidase 1 (Acox1), the first rate-limiting enzyme of peroxisomal fatty acid beta-oxidation, was then selected, and its disturbed expression in the two murine models validated the proteomic findings. Accordingly, Acox1 expression was significantly downregulated in renal biopsies from patients with AKI or CKD, and its expression was negatively correlated with kidney injury score. Furthermore, in contrast to the decreased Acox1 expression, lipid droplet accumulation was remarkably increased in these renal tissues, suggesting dysregulation of fatty acid oxidation. In conclusion, our results suggest that defective peroxisomal fatty acid oxidation might be a common pathological feature in the transition from AKI to CKD, and that Acox1 is a promising intervention target for kidney injury and repair.


Organochlorine pesticides and polychlorinated biphenyls in grass, yak muscle, liver, and milk in Ruoergai high altitude prairie, the eastern edge of Qinghai-Tibet Plateau.
In highland pastures, where no agricultural and industrial activities exist, organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) are believed to be mainly coming from water-soil-grass system which is subject to air-water and air-soil exchanges and atmospheric precipitation. Samples of grass and yak muscle, liver, and milk were measured for OCPs and PCBs in the summer and winter of 2011. The total concentrations of HCHs, DDTs, endosulfans, HCB, and PCBs in grass samples were in the range of 0.53-2.45, 1.6-6.0, 1.10-4.38, 0.30-1.24, 0.65-2.04 ng g(-1) dw (dry weight), with the means 1.38, 2.86, 2.06, 0.73, and 1.19 ng g(-1) dw, respectively. The mean concentrations of HCHs and DDTs in yak muscle were 1.65 and 0.55 ng g(-1) fw (fresh weight), respectively; no significant seasonal differences. The average total concentrations of HCHs, DDTs, HCB, endosulfans, and PCBs in yak milk were 4.46, 0.59, 1.00, 0.27, and 0.097 ng g(-1) fat, respectively. Among the POPs investigated, β-HCH and HCB were dominant in yak muscle and liver, whereas β-HCH dominated the yak milk. Consistent with the results of other studies, PCB 153, 138, and 180 were detected in yak milk that is in accordance with the case reported for farmed cow milk in China and other countries. A human health risk was conducted based on the intake of OCPs via consumptions of the yak muscle and milk. Since the daily intake of HCHs and DDTs was lower than WHO or USEPA's acceptable daily intake or minimal risk level, showing that the consumptions of the yak muscle and milk would not pose any immediate risk to local people.


Active View and Passive View in Virtual Reality Have Different Impacts on Memory and Impression.
Virtual reality (VR) through a head-mounted display (HMD) can provide new experiences. However, it remains unclear how the characteristics of HMDs affect users' memory. To use HMDs more effectively and appropriately in several applied fields, including education, it is necessary to clarify what characteristics of HMDs affect users' memory. A head-tracking function mounted on an HMD helps to detect the user's head direction to enable a simulation experience akin to the real world. When we experience a simulation on an HMD, we actively perceive the visual world. In this study, we assessed how active/passive viewing affects users' memory of VR content. We conducted a psychological experiment in which participants watched a movie on an HMD. In the active viewing condition, the presented view changed depending on the participant's head direction. In the passive viewing condition, the presented view was a recorded movie that was shown to the participants in the active viewing condition. All participants took a memory test about the content presented in the movie on the day of viewing and 2 weeks later. The results showed that performance on the memory test in the active viewing condition was significantly lower than that in the passive viewing condition after 2 weeks. This result indicated that active viewing in VR inhibited users' memory compared to passive viewing. The current study contributes to the development of new VR techniques, such as educational learning.


Effect of steam-processing of the Panax ginseng root on its inducible activity on granulocyte-colony stimulating factor secretion in intestinal epithelial cells in vitro.
Panax ginseng root has been used as tonic in traditional Chinese medicine (TCM) and traditional Japanese Kampo medicine. Steam processing of Panax ginseng root is carried out to enhance its nourishing effects on qi. In order to explore the mechanism of these beneficial effects behind the steam processing of the P. ginseng root, we evaluated effectiveness of processing on the granulocyte-colony stimulating factor (G-CSF) secretion in intestinal epithelial cell-like MCE301 cells. We collected P. ginseng root samples in the markets of China and Japan. Fresh or dried samples were steamed for different time lengths and subsequently dried and extracted. MCE301 cells were incubated with the medium containing various P. ginseng root extracts, while the concentration of G-CSF in the medium was measured. We also investigated the active ingredients by size exclusion HPLC. The extracts of fresh P. ginseng hairy root samples steamed for more than 6 h significantly induced G-CSF secretion, and the maximum activity was recorded at a 9-h steaming. The same activity was noted when already dried P. ginseng hairy root samples were steamed. The extracts of fresh P. ginseng hairy root without steam processing and those of fresh P. ginseng root body samples with steam processing exhibited no activities. The active ingredients of steamed P. ginseng hairy root samples were high-molecular-weight compounds with an average molecular weight of 758 kDa, and the activity was mediated by the toll-like receptor (TLR) 9. Our results shed on more light on the mechanism underlying the appearance of immunostimulatory activity of the P. ginseng hairy root induced by steam processing.


Validation of a Method for Quantification of Lutein in Spinach Using High-Performance Liquid Chromatography: Interlaboratory Study.
Lutein is gaining attention as a strong antioxidant contained in foods. It accumulates in the human blood and retina, and is considered to play an important role in the body, especially in the eyes. A method to determine the lutein content of raw spinach (Spinacia oleracea L.) was developed with the aim of its enactment as a Japanese agricultural standard (JAS) measurement method for components beneficial to human health. An interlaboratory study was conducted to evaluate an analytical method for the determination of lutein in spinach. The detection limit and quantification limit of lutein for this method were 0.2 and 0.7 mg/kg, respectively. Twelve participating laboratories independently analyzed test samples (five pairs of blind duplicates) using high-performance liquid chromatography (HPLC). After removal of a few outliers, the repeatability relative standard deviation (RSDr), reproducibility (RSDR), and predicted RSDR of the evaluated method were 3.4-7.5, 4.6-13, and 7.5-8.5%, respectively, in a concentration range from 64.9-150 mg/kg. The HorRat values (RSDR/predicted RSDR) of the lutein concentration were calculated to be 0.61-1.6. The study results indicate the acceptable precision of this method.


MR imaging of the spine at 3.0T with T2-weighted IDEAL fast recovery fast spin-echo technique.
To compare the iterative decomposition of water and fat with echo asymmetry and the least-squares estimation (IDEAL) method with a fat-saturated T2-weighted (T2W) fast recovery fast spin-echo (FRFSE) imaging of the spine. Images acquired at 3.0 Tesla (T) in 35 patients with different spine lesions using fat-saturated T2W FRFSE imaging were compared with T2W IDEAL FRFSE images. Signal-to-noise ratio (SNR)-efficiencies measurements were made in the vertebral bodies and spinal cord in the mid-sagittal plane or nearest to the mid-sagittal plane. Images were scored with the consensus of two experienced radiologists on a four-point grading scale for fat suppression and overall image quality. Statistical analysis of SNR-efficiency, fat suppression and image quality scores was performed with a paired Student's t test and Wilcoxon's signed rank test. Signal-to-noise ratio-efficiency for both vertebral body and spinal cord was higher with T2W IDEAL FRFSE imaging (p < 0.05) than with T2W FRFSE imaging. T2W IDEAL FRFSE demonstrated superior fat suppression (p < 0.01) and image quality (p < 0.01) compared to fat-saturated T2W FRFSE. As compared with fat-saturated T2W FRFSE, IDEAL can provide a higher image quality, higher SNR-efficiency, and consistent, robust and uniform fat suppression. T2W IDEAL FRFSE is a promising technique for MR imaging of the spine at 3.0T.


Maintenance of host leukocytes in peripheral immune compartments following lethal irradiation and bone marrow reconstitution: implications for graft versus host disease.
Bone marrow reconstitution is utilized as a tool for disease treatment and as a research technique to elucidate the function of bone marrow derived cells. Clinically successful engraftment is indicated by the development of a functioning immune repertoire. In research, reconstitution is considered successful if >85% of splenic leukocytes are of donor origins. Previous work suggests that splenic reconstitution may not be indicative of reconstitution in the mucosa. We sought to evaluate mucosal reconstitution in animals following a standard bone marrow eradication and reconstitution technique. Bone marrow was harvested from adult B6.SJL donor mice (CD45.1) and injected via either the retro-orbital or intraperitoneal route into lethally irradiated B6 (CD45.2) adult or neonatal recipients respectively. The expression of CD45 by flow cytometry was used to calculate reconstitution with respect to immune compartment and cell type. In reconstituted adult animals 93.2±1.5% of splenic leukocytes expressed the donor CD45.1 antigen thus meeting the standard definition of reconstitution, however only 58.6±13.6% of intestinal lamina propria lymphocytes and 52.4±16.0% of intestinal intraepithelial lymphocytes were of donor origin, confirming splenic reconstitution fails to represent peripheral immune reconstitution. T-cells in the gastrointestinal tract are the most poorly reconstituted, while B-cells appear to be almost universally replaced by donor cells. The inadequate mucosal reconstitution was not corrected by evaluating later time points or by performing the bone marrow transfer during the neonatal period. This demonstration that substantial host T-cells remain in the intestinal mucosa after a "successful" bone marrow transplantation should cause a re-evaluation of data from research bone marrow chimera experiments, as well as the mechanisms for complications after clinical bone marrow transplantation.


How It Works: The Immunology Underlying Phototherapy.
Phototherapeutic modalities induce apoptosis of keratinocytes and immune cells, impact cytokine production, downregulate the IL-23/Th17 axis, and induce regulatory T cells. As in anti-IL-17 or anti-IL-23 antibody treatment, the dual action of phototherapy on skin and the immune system is likely responsible for sustained resolution of lesions in diseases such as psoriasis. In cutaneous T cell lymphoma, phototherapy may function by causing tumor cell apoptosis and eliminating the neoplastic and inflammatory infiltrate. Further research on phototherapeutic mechanisms will help advance, optimize, and refine dermatologic treatments and may open up novel avenues for treatment strategies in dermatology and beyond.


Bacillus velezensis SQR9 inhibition to fungal denitrification responsible for decreased N2O emissions from acidic soils.
Tropical and subtropical acidic soils are hotspots of global terrestrial nitrous oxide (N2O) emissions, with N2O produced primarily through denitrification. Plant growth-promoting microbes (PGPMs) may effectively mitigate soil N2O emissions from acidic soils, achieved through differential responses of bacterial and fungal denitrification to PGPMs. To test this hypothesis, we conducted a pot experiment and the associated laboratory trials to gain the underlying insights into the PGPM Bacillus velezensis strain SQR9 effects on N2O emissions from acidic soils. SQR9 inoculation significantly reduced soil N2O emissions by 22.6-33.5 %, dependent on inoculation dose, and increased the bacterial AOB, nirK and nosZ genes abundance, facilitating the reduction of N2O to N2 in denitrification. The relative contribution of fungi to the soil denitrification rate was 58.4-77.1 %, suggesting that the N2O emissions derived mainly from fungal denitrification. The SQR9 inoculation significantly inhibited the fungal denitrification and down-regulated fungal nirK gene transcript, dependent on the SQR9 sfp gene, which was necessary for secondary metabolite synthesis. Therefore, our study provides new evidence that decreased N2O emissions from acidic soils can be due to fungal denitrification inhibited by PGPM SQR9 inoculation.


High density culture of mouse-human hybridoma cells using a perfusion culture apparatus with multi-settling zones to separate cells from the culture medium.
Mouse-human hybridoma X87X cells were cultivated using a novel perfusion culture apparatus provided with three-settling zones to separate the cells from the culture medium by gravitational settling. The maximum viable cell density in a serum-free culture medium attained 3.0×10(7) cells/ml, when the specific perfusion rate was set to 2.3 vol day(-1), and monoclonal antibody was continuously produced. These results were almost the same as those in the perfusion culture vessel with one settling zone and revealed that the process with a plurality of settling zones is a promising one for scale-up of a gravitation type of perfusion culture vessel.


Physical activity and screen-based recreation: Prevalences and trends over time among adolescents and barriers to recommended engagement.
Adolescence is a critical time for disengagement from physical activity making young people a priority group for interventions. To determine whether existing initiatives are working in this population segment and help inform future programs, the present study sought to (i) examine prevalences and trends in physical activity and screen-based recreation among Australian adolescents and (ii) identify the barriers to adolescents meeting recommended guidelines. Two cross-sectional representative samples of Western Australian secondary school students aged 12 to 17years were surveyed in 2009-2010 (n=1505) and 2012-2013 (n=1406). Around a quarter (24%) of boys and just 9% of girls reported engaging in the recommended 60min of physical activity per day in 2012-2013. A minority (13% of boys, 17% of girls) adhered to guidelines for time spent engaging in screen-based recreation (≤2h of electronic media use for entertainment). These findings were comparable to 2009-2010 prevalence levels. Multivariable logistic regression analyses conducted on data from the most recent wave found individual-level barriers to be significantly associated with lower odds of meeting physical activity guidelines in both boys (Adj. OR=0.52, 95% CI=0.38, 0.72) and girls (Adj. OR=0.41, 95% CI=0.25, 0.66). The consistently high proportion of adolescents not meeting physical activity recommendations over time suggests that current efforts to increase physical activity may be failing to have an impact on population-level trends in compliance. While initiatives to improve the built environment may reduce barriers at the environmental level, these initiatives risk having little impact on physical activity if individual level barriers remain unaddressed.


The OCT angular sign of Henle fiber layer (HFL) hyperreflectivity (ASHH) and the pathoanatomy of the HFL in macular disease.
The Henle fiber layer (HFL) is comprised of bundles of unmyelinated photoreceptor axons intermingled with outer Müller cell processes. The photoreceptor axons extend from the cell bodies located in the outer nuclear layer and radially project toward the outer plexiform layer, the inner third of which includes the synaptic junctional complexes and the outer two-thirds of which includes the HFL. The oblique path of the HFL provides unique structural and reflectance properties and this radial anatomy is highlighted in many macular disorders including those with macular star exudation and HFL hemorrhage. Recent investigations using multimodal imaging techniques, especially cross sectional and en face optical coherence tomography (OCT), have provided new perspectives regarding HFL disruption in retinal diseases. The aim of this review is to highlight the pathoanatomy and multimodal imaging, especially OCT, associated with HFL disruption that is present in various macular diseases. After describing the current knowledge of the embryology, anatomy, and physiology of the HFL, we review the existing imaging modalities that allow in vivo visualization of the HFL in the healthy and diseased retina. Finally, we report the clinical and imaging findings of acute HFL alteration in various macular disorders, including degenerative, inflammatory, and vascular conditions. Also, we propose a novel and signature OCT biomarker indicative of acute photoreceptor disruption involving the HFL, termed the "angular sign of HFL hyperreflectivity" (ASHH) of macular disease, to unify the pathoanatomy common to these various macular disorders and to provide clarity regarding the underlying pathogenesis.


A prospective evaluation of thiamine and magnesium status in relation to clinicopathological characteristics and 1-year mortality in patients with alcohol withdrawal syndrome.
Alcohol withdrawal syndrome (AWS) is routinely treated with B-vitamins. However, the relationship between thiamine status and outcome is rarely examined. The aim of the present study was to examine the relationship between thiamine and magnesium status in patients with AWS. Patients (n = 127) presenting to the Emergency Department with AWS were recruited to a prospective observational study. Blood samples were drawn to measure whole blood thiamine diphosphate (TDP) and serum magnesium concentrations. Routine biochemistry and haematology assays were also conducted. The Glasgow Modified Alcohol Withdrawal Score (GMAWS) measured severity of AWS. Seizure history and current medications were also recorded. The majority of patients (99%) had whole blood TDP concentration within/above the reference interval (275-675 ng/gHb) and had been prescribed thiamine (70%). In contrast, the majority of patients (60%) had low serum magnesium concentrations (< 0.75 mmol/L) and had not been prescribed magnesium (93%). The majority of patients (66%) had plasma lactate concentrations above 2.0 mmol/L. At 1 year, 13 patients with AWS had died giving a mortality rate of 11%. Male gender (p < 0.05), BMI < 20 kg/m2 (p < 0.01), GMAWS max ≥ 4 (p < 0.05), elevated plasma lactate (p < 0.01), low albumin (p < 0.05) and elevated serum CRP (p < 0.05) were associated with greater 1-year mortality. Also, low serum magnesium at time of recruitment to study and low serum magnesium at next admission were associated with higher 1-year mortality rates, (84% and 100% respectively; both p < 0.05). The prevalence of low circulating thiamine concentrations were rare and it was regularly prescribed in patients with AWS. In contrast, low serum magnesium concentrations were common and not prescribed. Low serum magnesium was associated more severe AWS and increased 1-year mortality.


A comprehensive phylogeny of the genus Kurixalus (Rhacophoridae, Anura) sheds light on the geographical range evolution of frilled swamp treefrogs.
Currently, the genus Kurixalus comprises 14 species distributed in Southern, Southeast and East Asia. Because of their relatively low dispersal capability and intolerance of seawater, this group is ideal for the study of terrestrial range evolution, especially that portion of its range that extends into the island archipelagos of Southern Asia. We assembled a large dataset of mitochondrial and nuclear genes, and estimated phylogeny by maximum likelihood and Bayesian methods, and we explored the history of each species via divergence-time estimation based on fossil-calibrations. A variety of ancestral-area reconstruction strategies were employed to estimate past changes of the species' geographical range, and to evaluate the impact of different abiotic barriers on range evolution. We found that frilled swamp treefrogs probably originated in Taiwan or South Vietnam in the Oligocene. Alternatively, the lineage leading to Kurixalus appendiculatus strongly supports a hypothesis of terrestrial connection between the Indian and Asian continents in the Oligocene. The outcome of both our divergence-time estimates and ancestral-area reconstruction suggests that the divergence between species from Indochina and Taiwan can probably be attributed to the opening of the South China Sea, approximately 33 million years ago. We could not find evidence for dispersal between mainland China and Taiwan Island. Formation of both Mekong and Red River valleys did not have any impact on Kurixalus species diversification. However, coincidence in timing of climate change and availability of plausible dispersal routes from the Oligocene to the middle Miocene, plausibly implied that Kurixalus diversification in Asia resulted from contemporaneous, climate-induced environmental upheaval (Late Oligocene Warming at 29 Ma; Mi-1 glaciation since 24.4-21.5 Ma; Mid-Miocene Climatic Optimum at 14 Ma), which alternatively opened and closed dispersal routes.


Autosomal dominant optic atrophy with OPA1 gene mutations accompanied by auditory neuropathy and other systemic complications in a Japanese cohort.
This study aimed to describe the genetic and clinical characteristics of four Japanese patients with autosomal dominant optic atrophy (DOA) accompanied by auditory neuropathy and other systemic complications (i.e., DOA-plus disease). Four patients from four independent families underwent comprehensive ophthalmic and auditory examinations and were diagnosed with DOA-plus disease. The disease-causing gene variants in the OPA1 gene were identified by direct sequencing. The genetic and clinical data of 48 DOA patients without systemic complications-that is, with simple DOA-were compared to those of DOA-plus patients. DOA-plus patients noticed a decrease in vision before the age of 14 and hearing impairment 3 to 13 years after the development of visual symptoms. Two patients had progressive external ophthalmoplegia, and one patient had vestibular dysfunction and ataxia. The DOA-plus phenotypes accounted for 13.3% (4/30) of the families with the OPA1 gene mutations. Each DOA-plus patient harbored one of the monoallelic mutations in the OPA1 gene: c.1334G>A, p.R445H, c.1618A>C, p.T540P, and c.892A>C, p.S298R. Missense mutations accounted for 100% (4/4) of the DOA-plus families and only 11.5% (3/26) of the families with simple DOA. All the patients with the DOA-plus phenotype carried one of the missense mutations in the OPA1 gene. They all had typical ocular symptoms and signs of DOA in their first or second decade, and other systemic complications-such as auditory neuropathy, vestibular dysfunction, and ataxia-followed the ocular symptoms. We should consider the occurrence of extraocular complications in cases with DOA, especially when they carry the missense mutations in the OPA1 gene.


Primaquine as a Candidate for HHV-8-Associated Primary Effusion Lymphoma and Kaposi's Sarcoma Treatment.
Human Herpesvirus 8 (HHV-8) is associated with three main severe orphan malignancies, Kaposi's sarcoma (KS), multicentric Castleman's disease (MCD), and primary effusion lymphoma (PEL), which present few therapeutic options. We identified the antimalarial primaquine diphosphate (PQ) as a promising therapeutic candidate for HHV-8-associated PEL and KS. Indeed, PQ strongly reduced cell viability through caspase-dependent apoptosis, specifically in HHV-8-infected PEL cells. Reactive oxygen species (ROS)- and endoplasmic reticulum (ER) stress-mediated apoptosis signaling pathways were found to be part of the in vitro cytotoxic effect of PQ. Moreover, PQ treatment had a clinically positive effect in a nonobese diabetic (NOD)/SCID xenograft PEL mouse model, showing a reduction in tumor growth and an improvement in survival. Finally, an exploratory proof-of-concept clinical trial in four patients harboring severe KS was conducted, with the main objectives to assess the efficacy, the safety, and the tolerability of PQ, and which demonstrated a positive efficacy on Kaposi's sarcoma-related lesions and lymphedema.


[Morphological variability of thorny-headed worms of the genus Neoechinorhynchus (Acanthocephala: Neoechinorhynchidae) that parasitize fishes of the Arctic Ocean province in the boundaries of the USSR].
Study of the morphology of 602 specimens of N. rutili (Müller, 1780) and N. crassus Van Cleave, 1919 collected in 10 species of fishes from waterbodies of the Kola Peninsular, the Ob, Yenisei, Lena, Kolyma and Chauna rivers has shown that all absolute specific characters considered (13 in female and 17 in male) have a considerable range of variations due to the modificational individual and age variability. Differences have been revealed in morphometric indexes of some characters in members of the European and Siberian populations of N. rutili that is due to a geographic variability of the species. It has been established that most constant characters of all species studied are the length of the proboscis and its hooks.


Bronchial stump buttressing with an intercostal muscle flap in diabetic patients.
The development of a bronchopleural fistula (BPF) is a devastating complication after lung resection. Diabetic patients exhibit a high propensity for postpneumonectomy complications, particularly BPF. This study evaluated the use of an intercostal muscle flap to reinforce the bronchus in high-risk diabetic patients after pneumonectomy. From February 2002 to December 2005, 70 patients with established diabetes mellitus undergoing pneumonectomy were prospectively enrolled in this study. Patients were randomized to have their bronchial stump reinforced with an intercostal muscle flap or to a conventional resection. A univariable statistical analysis was performed to assess differences in perioperative variables and in outcomes of interest. A multivariable logistic regression analysis was also performed to evaluate the association of BPF development with a number of confounding variables, including intercostal muscle flap usage. Randomization ensured that groups were equally distributed. Mean follow-up was 18 +/- 9.2 months. The group that received an intercostal muscle flap had a lower incidence of BPF development (0% versus 8.8%; p = 0.02) and of empyema (0% versus 7.4%; p = 0.05) compared with the group that received conventional pneumonectomy. The low incidence of BPF and empyema observed in patients who received an intercostal muscle flap suggest that bronchial stump reinforcement with this technique is a highly effective method for the prevention of BPF in high-risk diabetic patients.


Management and closure of the open abdomen after damage control laparotomy for trauma. A systematic review and meta-analysis.
Damage control laparotomy for trauma (DCL) entails immediate control of haemorrhage and contamination, temporary abdominal closure (TAC), a period of physiological stabilisation, then definitive repair of injuries. Although immediate primary fascial closure is desired, fascial retraction and visceral oedema may dictate an alternate approach. Our objectives were to systematically identify and compare methods for restoration of fascial continuity when primary closure is not possible following DCL for trauma, to simplify these into a standardised map, and describe the ideal measures of process and outcome for future studies. Cochrane, OVID (Medline, AMED, Embase, HMIC) and PubMed databases were accessed using terms: (traum*, damage control, abbreviated laparotomy, component separation, fascial traction, mesh closure, planned ventral hernia (PVH), and topical negative pressure (TNP)). Randomised Controlled Trials, Case Series and Cohort Studies reporting TAC and early definitive closure methods in trauma patients undergoing DCL were included. Outcomes were mortality, days to fascial closure, hospital length of stay, abdominal complications and delayed ventral herniation. 26 studies described and compared early definitive closure methods; delayed primary closure (DPC), component separation (CS) and mesh repair (MR), among patients with an open abdomen after DCL for trauma. A three phase map was developed to describe the temporal and sequential attributes of each technique. Significant heterogeneity in nomenclature, terminology, and reporting of outcomes was identified. Estimates for abdominal complications in DPC, MR and CS groups were 17%, 41% and 17% respectively, while estimates for mortality in DPC and MR groups were 6% and 0.5% (data heterogeneity and requirement of fixed and random effects models prevented significance assessment). Estimates for abdominal closure in the MR and DPC groups differed; 6.30 (95% CI=5.10-7.51), and 15.90 (95% CI=9.22-22.58) days respectively. Reporting poverty prevented subgroup estimate generation for ventral hernia and hospital length of stay. Component separation or mesh repair may be valid alternatives to delayed primary closure following a trauma DCL. Comparisons were hampered by the lack of uniform reporting and bias. We propose a new system of standardised nomenclature and reporting for further investigation and management of the post-DCL open abdomen.


PD-1 and PD-L1 Protein Expression Predict Survival in Completely Resected Lung Adenocarcinoma.
We assessed the prognostic value of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in patients with completely resected lung adenocarcinoma. PD-1 and PD-L1 expression was determined using immunohistochemistry in formalin-fixed paraffin-embedded surgical specimens and correlated with the clinicopathologic features and survival of 161 patients with lung adenocarcinoma. PD-1 expression on immune cells was observed in 71 of 159 evaluable tumor samples (45%) and was not significantly associated with the clinicopathologic features. Multivariate analyses identified PD-1 expression as an independent prognostic factor for recurrence (adjusted hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.36-0.95; P = .03) and death (adjusted HR, 0.48; 95% CI, 0.27-0.86; P = 0.01). PD-L1 expression on tumor cells was seen in 59 of 161 cases (37%) and correlated with KRAS mutation status (P = .02) and type of surgery (P = .01). PD-L1 expression was not associated with recurrence-free survival in the patients (adjusted HR, 0.90; 95% CI, 0.55-1.48; P = .68) but correlated with longer overall survival (adjusted HR, 0.54; 95% CI, 0.30-0.97; P = .04). PD-1 and PD-L1 expression was associated with favorable overall survival in patients with completely resected adenocarcinoma of the lung.


Severe cholestasis associated with methyltestosterone: a case report.
We report a 62-yr-old man with severe jaundice and weight loss attributed to methyltestosterone administration. This case is unusual both in the severity of the cholestasis as well as the associated findings that mimicked an underlying malignancy.


Modification of staging and treatment of head and neck cancer by FDG-PET/CT prior to radiotherapy.
Reliable tumor staging is a fundamental pre-requisite for efficient tumor therapy and further prognosis. The aim of this study was to compare head and neck cancer (HNC) staging before and after FDG-PET/CT, evaluating the stage modifications for radiotherapy (RT) planning. A total of 102 patients with untreated primary HNC, who underwent conventional staging and staging including FDG-PET/CT before RT, were enrolled in this retrospective study. Blinded pre-FDG-PET/CT and post-FDG-PET/CT staging data were compared. The impact on patient management was tested by comparing the intention before and after FDG-PET/CT. Significant modifications of T, N, and M stage as well as clinical stage were detected after inclusion of FDG-PET/CT data (p = 0.002, 0.0006, 0.001, 0.03, respectively). Overall, the implementation of FDG-PET/CT led to modification of RT intention decision in 14 patients. FDG-PET/CT demonstrates essential influence on tumor staging in HNC patients scheduled for irradiation. Implementation of FDG-PET/CT in imaging protocol improves selection of candidates for curative and palliative RT and allows further optimization of treatment management and therapy intention.


NOD2-expressing bone marrow-derived cells appear to regulate epithelial innate immunity of the transplanted human small intestine.
Intestinal allograft rejection resembles Crohn's disease clinically and pathologically. An understanding of its mechanism could impact this life-saving procedure, as well as provide insight into the pathophysiology of inflammatory bowel disease. The NOD2 protein has been implicated as a key player in intestinal immune health, as a consequence of the discovery of three polymorphisms linked with Crohn's disease. An investigation was carried out to determine whether epithelial immune function and graft survival were influenced by NOD2 mutations in an intestinal transplant population. The NOD2 genotypes of 34 transplants performed consecutively over the past 3 years were determined. The NOD2 genotypes were related to clinical outcomes and the expression of certain intestinal antimicrobial peptides (AMPs) believed to protect the epithelium. An unexpectedly high percentage of recipients, 35%, possessed NOD2 polymorphisms, while 8.6% of donors had comparable mutations. The likelihood of allograft failure was about 100-fold higher in recipients with mutant NOD2 alleles compared with recipients with wild-type NOD2 loci. Rejection in NOD2 mutant recipients was characterised by decreased expression of certain Paneth cell and enterocyte AMPs, prior to the onset of epithelial injury and inflammation. Crohn's disease-associated polymorphisms in the NOD2 gene in the recipient represent a critical immunological risk factor for intestinal allograft rejection. Compromised epithelial defences precede visible epithelial injury and inflammatory infiltration. The association of impaired epithelial immunity with the recipient's genotype suggests that certain NOD2-expressing cells of haematopoietic origin play a role in the process, perhaps by regulating expression of certain epithelial AMPs within the allograft.


The effect of personalized intelligent digital systems for self-care training on type II diabetes: a systematic review and meta-analysis of clinical trials.
Type 2 diabetes (T2D) is rising worldwide. Self-care prevents diabetic complications. Lack of knowledge is one reason patients fail at self-care. Intelligent digital health (IDH) solutions have a promising role in training self-care behaviors based on patients' needs. This study reviews the effects of RCTs offering individualized self-care training systems for T2D patients. PubMed, Web of Science, Scopus, Cochrane Library, and Science Direct databases were searched. The included RCTs provided data-driven, individualized self-care training advice for T2D patients. Due to the repeated studies measurements, an all-time-points meta-analysis was conducted to analyze the trends over time. The revised Cochrane risk-of-bias tool (RoB 2.0) was used for quality assessment. In total, 22 trials met the inclusion criteria, and 19 studies with 3071 participants were included in the meta-analysis. IDH interventions led to a significant reduction of HbA1c level in the intervention group at short-term (in the third month: SMD = - 0.224 with 95% CI - 0.319 to - 0.129, p value < 0.0; in the sixth month: SMD = - 0.548 with 95% CI - 0.860 to - 0.237, p value < 0.05). The difference in HbA1c reduction between groups varied based on patients' age and technological forms of IDH services delivery. The descriptive results confirmed the impact of M-Health technologies in improving HbA1c levels. IDH systems had significant and small effects on HbA1c reduction in T2D patients. IDH interventions' impact needs long-term RCTs. This review will help diabetic clinicians, self-care training system developers, and researchers interested in using IDH solutions to empower T2D patients.


The restoration of myeloid-derived suppressor cells as functional antigen-presenting cells by NKT cell help and all-trans-retinoic acid treatment.
Myeloid-derived suppressor cells (MDSCs), which accumulate during tumor progression, have been shown to function as important suppressor cells. In a previous study, we showed that immunosuppressive MDSCs could function as immunogenic antigen-presenting cells (APCs) with the help of activated natural killer T (NKT) cells. In the current study, however, we found that MDSCs harvested at a late time point after tumor injection (late MDSCs) were poorly immunogenic even when stimulated with activated NKT cells. As tumor growth progressed, the expression of MHC and costimulatory molecules on MDSCs was gradually down-regulated. Late MDSCs also had innate defects in activation and differentiation mediated by cytokine stimuli. Although late MDSCs treated only with all-trans-retinoic acid (ATRA), a stimulating agent for MDSC differentiation, could not become immunogenic, NKT ligand-loaded, ATRA-treated late MDSCs could be converted into immunogenic APCs to induce incremental immune responses. Furthermore, these effects were mediated by NKT cells secreting IFNγ, and ATRA-mediated increases in glutathione (GSH) levels. Thus, combined treatment with differentiating and activating agents is a prerequisite for the conversion of late MDSCs into immunogenic APCs. Collectively, these results suggest that combined treatments are required for the differentiation and activation of late MDSCs in late stage cancer.


Incidence of fractures and changes over time among the aged in a Finnish municipality: a population-based 12-year follow-up.
The incidence of fractures is high in older populations. The aim of this study was to describe the incidence of different fractures and to analyse the changes in age-adjusted yearly incidences among older persons. A prospective true cohort design. Information about fractures in 482 men and 695 women aged 65 or over living in the municipality of Lieto, south-western Finland, was collected from 1991 until 2002. Poisson's regression model was used to analyse changes in yearly incidences. During 10,040 person years (PY) of follow-up, 307 (26%) persons sustained 425 fractures. The total incidence rate of fractures was 53.4 per 1000 PY (95% confidence intervals: 47.9-59.5) in women, and 24.9 per 1000 PY (20.4-30.4) in men. The age-specific incidence of fractures increased with age in both genders. Rates of hip and wrist fractures tended to be higher in women. 7.2% subjects sustained two or more fractures during follow- up. The majority of fractures resulted from a fall, and only 3.5% were caused by extremely serious accidents. No significant changes in the age-adjusted incidences of all fractures were found in either gender during follow-up. Fractures are common in the aged population, and the incidence of most types of fracture is associated with increasing age. Only a minority of fractures are caused by extremely serious accidents. No significant changes in the age-adjusted yearly incidences of fractures were observed in this aged cohort during a 12-year follow-up.


Pallial expression of Enc1 RNA in postnatal mouse telencephalon.
We analysed the pallial expression pattern of Enc1 (a member of the kelch family of genes) in postnatal mice (P1-P10). At early developmental stages this gene plays a role in the histogenesis of cortical structures [M.C. Hernández, P.J. Andrés-Barquin, S. Martínez, A. Bulfone, J.L.R. Rubenstein, M.A. Israel, Enc1: novel mammalian kelch-related gene specifically expressed in the nervous system encodes an actino-binding protein, J. Neurosci. 17 (1997) 3038-3051]. A restricted expression of Enc1 was found in the mouse pallium, notably within claustroamygdaloid derivatives of the lateral pallium and in some cortical layers in the lateral, dorsal and medial pallium sectors, with distinct regional differences. The strongest cortical expression was found in isocortical layer II and in the piriform cortex, anterior olfactory area and olfactory bulb mitral cells. The lowest signal occurred in the retrosplenial cortex. The subgranular layers V/VI were also positive, particularly layer V, with clearcut areal differences. The hippocampal CA3/CA4 areas and the dentate gyrus were strongly positive. The dorsolateral (core) portion of the claustrum and dorsal endopiriform nucleus were moderately positive, as were the amygdaloid lateral and basolateral nuclei.


Simultaneous detection of enteric bacteria from surface waters by QPCR in comparison with conventional bacterial indicators.
A rapid quantitative polymerase chain reaction (QPCR) method was developed for simultaneous detection of enteric bacteria from surface waters by utilizing a pair of universal primers which targeted four bacteria strains, namely Shigella dysenteriae, Vibrio cholerae, Salmonella typhimurium, and Escherichia coli. It was estimated that the QPCR method had a 94% confidence, and a detection limit as 2.7 E. coli cells per sample in undiluted DNA extracts. The QPCR method was applied for the bacteriological examination of several surface waters in the urban area of Xi'an, China and comparison was made with the conventional bacteria indicators determined by conventional membrane filter (MF) method. As a result, the calibrator cell equivalents (CCE) determined by QPCR was 2.2 to five times of the total coliform CFU, and the characteristics of the bacterial quality of different waters could be well presented by the QPCR results with a higher sensitivity. The coefficient of variation (CV) of data obtained by QPCR was smaller than that by traditional MF method, indicating a more stable analysis result. The QPCR method could thus be used as a supplement of the conventional culture method for more sensitive detection of pathogenic enteric bacteria from water.


[Differential diagnosis of papilledema and macular exudation-the exophytically growing juxtapapillary retinal capillary hemangioma].
In a 38-year-old female patient, who had been treated for acute visual impairment and suspected optic neuritis with no organic evidence in the right eye, an exophytically growing juxtapapillary retinal capillary hemangioma was found. The benign tumor is a rare but important differential diagnosis in cases of papilledema and macular exudation. The treatment is difficult; various therapeutic concepts are discussed.


LC-MS characterized methanolic extract of zanthoxylum armatum possess anti-breast cancer activity through Nrf2-Keap1 pathway: An in-silico, in-vitro and in-vivo evaluation.
Zanthoxylum armatum DC (Rutaceae) containing flavonoids, alkaloids, coumarins, lignans, amides and terpenoid is well-known for its curative properties against various ailments including cancer. In the current research, phytochemicals present in the methanolic extract of Zanthoxylum armatum bark (MeZb) were characterized by LC-MS/MS analysis and chemotherapeutic potential of this extract was determined on DMBA-induced female Sprague Dawley rats. A simple and fast high-performance liquid chromatography-mass spectroscopy (LC-MS/MS) of MeZb was established followed by in-vitro antioxidant assays. This was followed by in-silico docking analysis as well as cytotoxicity assessment. Successively in-vivo study of MeZb was performed in DMBA-induced Sprague Dawley rats possessing breast cancer along with detailed molecular biology studies involving immunofluorescence, RT-qPCR and Western blot analysis. LC-MS/MS investigation revealed the presence of compounds belonging to flavonoid, alkaloid and glycoside groups. MeZb revealed potential antioxidant activity in in-vitro antioxidant assays and strong binding energy of identified compounds was seen from the in-silico study with both HO1 and Keap1 receptor. Furthermore, the antioxidant action of MeZb was proven from the in-vivo analysis of antioxidant marker enzymes (lipid peroxidation, enzymic and non-enzymic antioxidants). This study also revealed upregulation of protective Nrf-2 following downregulation of Keap1 after MeZb treatment with respect to untreated cancerous rats. These results exhibited anti-breast-cancer potential of MeZb through Nrf2-Keap1 pathway which may be due to the flavonoids, alkaloids and glycosides present in it.


Metagenomic and physicochemical analyses reveal microbial community and functional differences between three types of low-temperature Daqu.
Complex microbes of different types of low-temperature Daqu (LTD) play an important role in the formation of flavors and qualities of light-flavor Baijiu during fermentation. However, characterizing the taxonomic and functional diversity of microbiota in three types of LTD (Houhuo, Hongxin, Qingcha) remains a major challenge. The present study combined metagenomic sequencing with culture-based methods and physicochemical analysis to compare the three LTD microbiota and elucidate their function in LFB brewing. The results revealed a high diversity of microbes in LTD, with 1286 genera and 4157 species detected across all studied samples. Bacteria and fungi were the main microbes in LTD, with a bacterial to fungal relative abundance ratio of above 4:1. Bacillus (21.18%) and Bacillus licheniformis (17.45%) were the most abundant microbes in the LTD microbiota at the genus and species levels, respectively. Culture-dependent analysis found the highest abundances of bacteria, fungi, and lactic acid bacteria in Houhuo, while the metagenomic-based microbiota found that the relative abundance of bacteria and fungi were highest in Houhuo and Hongxin among the three types of LTD, respectively. The different production temperatures of LTD had little effect on its microbial variety, but obviously impacted the microbiota structure and metagenomic function of LTD. Although the microbiota of the three types of LTD shared a high commonality, each had specific microbiota and functional metagenomic features, suggesting their different but complementary roles in the LFB fermentation process. The representative dominant microbes in Houhuo were mostly involved in metabolic pathways associated with the production of flavor substances in liquor. In contrast, the enriched microbes in Qingcha and Hongxin were not only capable of producing specific flavor substances but also had a strong ability to degrade macromolecular substances in raw materials, promoting microbial growth. This study has greatly enriched our knowledge of the effect of LTD fermentation temperature on its quality, providing practical and interesting information for future improvement of LTD and light-flavor Baijiu products.


Mini-P1 plasmid replication: the autoregulation-sequestration paradox.
It has been proposed that the initiator protein RepA is rate limiting for mini-P1 plasmid replication, and that the role of the plasmid copy number control locus is to sequester the initiator and thus reduce replication. This proposal appears inconsistent with the observation that RepA is autoregulated, since the protein lost by sequestration should be replenished. A resolution of this autoregulation-sequestration paradox is possible if the sequestered RepA, unavailable for replication, is still available for promoter repression. We demonstrate that RepA binds to the control locus and to the promoter region simultaneously, causing the intervening DNA to loop. DNA looping could provide the requisite mechanism by which RepA bound to the control locus might exert repression.


Factors of cyclone disaster deaths in coastal Bangladesh.
Bangladesh's success in disaster risk management is often evidenced by referencing the reduction of deaths caused by tropical cyclones - the Cyclone Gorky 1991 caused 147,000 deaths, the Cyclone Sidr 2007 caused 4500 deaths and only 6 deaths by the Cyclone Mora in 2017. This raises questions of how deaths occurred by tropical cyclones in the past and what factors still might contribute towards deaths from cyclone hazards? This study answers these questions through face-to-face interviews with 362 residents, field visits and observations across coastal Bangladesh. The findings indicate that there have been improvements in house structures and design, warning responses and evacuation processes to public cyclone shelters and informal cyclone shelter centres. In the past, due to a lack of built infrastructure, strong residential houses and public cyclone shelters, deaths occurred whilst living in fragile houses; attempting to survive through holding trees and floating in storm surges. The top ten factors that may still cause deaths by tropical cyclones include: (1) Living adjacent to the coast without an embankment or lack of embankment, or the failure of an established embankment; (2) the repeat of a 1991-like cyclone; (3) non-evacuation following early warning; (4) poor roads in remote areas to facilitate mass movement; (5) distance to and insufficient number of public cyclone shelters; (6) lack of protective measures for the rising number of elderly and disabled people; (7) community's unawareness; (8) communication failure during the emergency period; (9) failure to evacuate people from remote locations; and (10) Poor radio signal and mobile network issues resulting in no warning information being effectively and timely communicated. This study provides several key recommendations addressing these factors of deaths, to be implemented by individual, community, private sectors, non-government organisations (NGOs) and public sectors across coastal Bangladesh.


Parental work patterns in alternative families: influence on child development.
The increasing return to work by mothers of young children was documented for matching samples of mothers in families representing traditional marriages, single-mother units, social-contract relationships, and communal living groups. No evidence was found of negative effects on children's social, emotional, and cognitive development attributable to maternal absence due to employment.


Evaluating the toxicity of food processing wastes as co-digestion substrates with dairy manure.
Studies have shown that including food waste as a co-digestion substrate in the anaerobic digestion of livestock manure can increase energy production. However, the type and inclusion rate of food waste used for co-digestion need to be carefully considered in order to prevent adverse conditions in the digestion environment. This study determined the effect of increasing the concentration (2%, 5%, 15% and 30%, by volume) of four food-processing wastes (meatball, chicken, cranberry and ice cream processing wastes) on methane production. Anaerobic toxicity assay (ATA) and specific methanogenic activity (SMA) tests were conducted to determine the concentration at which each food waste became toxic to the digestion environment. Decreases in methane production were observed at concentrations above 5% for all four food waste substrates, with up to 99% decreases in methane production at 30% food processing wastes (by volume).


Huntington Disease: Genetics, Prevention, and Therapy Approaches.
Huntington's chorea or Huntington disease (HD) is a late-onset autosomal dominant neurodegenerative disorder caused by a trinucleotide repeat expansion. The multidisciplinary study of HD has been the focus of an international collaborating effort of basic and applied research for several decades. HD was the first human genetic disease mapped using linkage analysis of DNA polymorphisms and became a paradigm for scores of genes mapped in the same manner. Presymptomatic and prenatal testing have been available for HD families in the last 30 years, following genetic counseling and careful bioethical guidelines. Nevertheless, with the cure for the disease still elusive the uptake of predictive testing by at risk individuals is low. Current treatment of HD is mostly symptomatic, but ongoing observational studies, clinical trials and development of new gene silencing technologies have provided hopeful results.


The Croton megalobotrys Müll Arg. traditional medicine in HIV/AIDS management: Documentation of patient use, in vitro activation of latent HIV-1 provirus, and isolation of active phorbol esters.
Current HIV therapies do not act on latent cellular HIV reservoirs; hence they are not curative. While experimental latency reversal agents (LRAs) can promote HIV expression in these cells, thereby exposing them to immune recognition, existing LRAs exhibit limited clinical efficacy and high toxicity. We previously described a traditional 3-step medicinal plant regimen used for HIV/AIDS management in Northern Botswana that inhibits HIV replication in vitro. Here we describe use of one component of the regimen that additionally contains novel phorbol esters possessing HIV latency-reversal properties. We sought to document experiences of traditional medicine users, assess the ability of traditional medicine components to reverse HIV latency in vitro, and identify pure compounds that conferred these activities. Experiences of two HIV-positive traditional medicine users (patients) were documented using qualitative interview techniques. Latency reversal activity was assessed using a cell-based model (J-Lat, clone 9.2). Crude plant extracts were fractionated by open column chromatography and reverse-phase HPLC. Compound structures were elucidated using NMR spectroscopy and mass spectrometry. Patients using the 3-step regimen reported improved health over several years despite no reported use of standard HIV therapies. Crude extracts from Croton megalobotrys Müll Arg. ("Mukungulu"), the third component of the 3-step regimen, induced HIV expression in J-lat cells to levels comparable to the known LRA prostratin. Co-incubation with known LRAs and pharmacological inhibitors indicated that the active agent(s) in C. megalobotrys were likely to be protein kinase C (PKC) activator(s). Consistent with these results, two novel phorbol esters (Namushen 1 and 2) were isolated as abundant components of C. megalobotrys and were sufficient to confer HIV latency reversal in vitro. We have identified novel LRAs of the phorbol ester class from a medicinal plant used in HIV/AIDS management. These data, combined with self-reported health effects and previously-described in vitro anti-HIV activities of this traditional 3-step regimen, support the utility of longitudinal observational studies of patients undergoing this regimen to quantify its effects on plasma viral loads and HIV reservoir size in vivo.


[Coprologic diagnosis of amebiasis : the rectocolitis cell trap and the value of cultures].
The authors give the differential characters of dysenteric amoebae and cells observed in the feaces of patients affected by recto-colitis. In this purpose, they recall the usefullness of cultures for both the presence and the possibility of determination of the Amoebae. In short, they deplore the misappreciation of these advantages.


An evaluation of a new test of reactive agility and its relationship to sprint speed and change of direction speed.
The purpose of this study was to evaluate the reliability and validity of a new test of agility, the reactive agility test (RAT), which included anticipation and decision-making components in response to the movements of a tester. Thirty-eight Australian football players took part in the study, categorized into either a higher performance group (HPG) (n=24) or lower performance group (LPG) (n=14) based on playing level from the previous season. All participants undertook testing of a 10m straight sprint (10mSS), a 8-9m change of direction speed test (CODST), and the RAT. Test-retest and inter-tester reliability testing measures were conducted with the LPG. The intra-class correlation (ICC) of the RAT was 0.870, with no significant (p<0.05) difference between the test results obtained on the first and second test sessions using a t-test. A dependent samples t-test revealed no significant (p<0.05) difference between the test results of two different testers with the same population. The HPG were significantly (p=0.001) superior to those of the LPG on the RAT, with no differences observed on any other variable. The RAT is an acceptably reliable test when considering both test-retest reliability, as well as inter-rater reliability. In addition, the test was valid in distinguishing between players of differing performance level in Australian football, while the 10mSS and CODST were not. This result suggests that traditional closed skill sprint and sprint with direction change tests may not adequately distinguish between players of different levels of competition in Australian football.


Frequent derepression of G6PD and HPRT on the marsupial inactive X chromosome associated with cell proliferation in vitro.
X chromosome dosage compensation in Marsupials is like that in eutherian mammals except that the paternal X chromosome is always inactive, and silence of this chromosome is not well maintained. We previously showed that the unstable inactivation of the paternal G6PD allele is associated with the lack of DNA methylation in the 5' CpG cluster. Even though this CpG island is unmethylated, the paternal allele (marked by an enzyme variant) is at least partially and often severely repressed in most tissues of the opossum, so that factors other than methylation must inactivate the locus. Here we report that when cell cultures are established from these tissues, the silent G6PD locus is depressed. Although often complete, the extent of derepression differs among tissues and within different cell types in the same tissue, and is not accompanied by obvious changes in the pattern of chromosome replication. Studies of the HPRT locus in these cells show that the paternal HPRT allele also derepresses in cultured cells. These observations suggest that without DNA methylation to maintain the silence of the locus, tissue or cell-specific factors act to repress the silent locus, but are unable to maintain inactivity through cell division, or are lost as cells proliferate in culture.


From the Journals.
VENOUS LEG ULCERS AND SQUAMOUS CELL CARCINOMA LEG ULCER MANAGEMENT IN THE COMMUNITY A REAWAKENING OF TRACE-ELEMENT WOUND RESEARCH.


Perceived Benefits of Implantable Cardioverter Defibrillator Implantation among Heart Failure Patients and Its Relation to Quality of Life: A Cross-Sectional Study.
Patients with heart failure (HF) and implantable cardioverter defibrillators (ICDs) may misunderstand the indication of ICDs due to unsatisfactory information. The goal of this study is to evaluate the patient perspective of ICD indication and its relation to quality of life, as well as to identify probable communication gaps between doctors and ICD receivers. A total of 119 patients with HF who were implanted with a single-chamber ICD were evaluated in outpatient clinics. Patients with cardiac resynchronization therapy-defibrillators were not included in the study. In a questionnaire, patients were asked about the indication of the ICD procedure and classified according to the perceived benefits. This study showed that most of the patients (n = 92, 77.3%) believed that ICD was implanted for improvement of heart dysfunction or for symptom relief. According to the perceived benefit groups, physical function, general health, vitality, and role physical scores were significantly lower in the symptom relief group (p < 0.05). Patients with HF and ICD mostly believed that the cardioverter defibrillator implanted for improving heart function or symptom relief. Doctors play a significant role when a patient is first referred for ICD because less-informed patients are more prone to misunderstand the procedure's benefits. Moreover, unfulfilled expectations may lead to loss of confidence in applied therapies and result in poor health outcomes.