A non-supervised training program for Carkhuff's discrimination and communication skills and its effects upon the reactions of others during brief interactions.
Used Carkhuff's Indices of Communication and Discrimination along with other measures to assess the level of communication and discrimination skills at various stages of communication training. Ss were 14 male and 9 female students in a psychology of adjustment class. Results indicated that: (a) treatment and control groups did not differ in communication skills before they went through training; (b) the treatment group offered higher levels of communication skill after it had completed training than did the control group before it began training; (c) the control group offered levels of communication skill equal to those of the treatment group once the control group also had completed training. A similar pattern was found for discrimination skill. The effects of training cannot be dismissed as paper-and-pencil artifacts because others who were ignorant of the growth conditions concept reacted differently in brief unstructured interactions to those who had completed training.


Interpretation as comparison.
Analytic subjectivity may not be the problem it seems. What is crucial for patients is not that analysts possess the objective truth, but that patients see a truth for themselves. How they accomplish this may depend on the analyst's showing them a view of themselves that differs from their own and can be compared to it. Each aspect of experience is defined by its relation to another reference point. I propose that the interpretive process is a medium for knowing one's mind in relation to that of another. This has implications for issues of analytic authority and autonomy.


Negative pressure wound therapy limits downgrowth in percutaneous devices.
Maintenance of a soft tissue seal around percutaneous devices is challenged by the downgrowth of periprosthetic tissues-a gateway to potential infection. As negative pressure wound therapy (NPWT) is used clinically to facilitate healing of complex soft tissue pathologies, it was hypothesized that NPWT could limit downgrowth of periprosthetic tissues. To test this hypothesis, 20 hairless guinea pigs were randomly assigned into four groups (n = 5/group). Using a One-Stage (Groups 1 and 3) or a Two-Stage (Groups 2 and 4) surgical procedure, each animal was implanted with a titanium-alloy subdermal device porous-coated with commercially pure, medical grade titanium. Each subdermal device had a smooth titanium-alloy percutaneous post. The One-Stage procedure encompassed insertion of a fully assembled device during a single surgery. The Two-Stage procedure involved the implantation of a subdermal device during the first surgery, and then three weeks later, insertion of a percutaneous post. Groups 1 and 2 served as untreated controls and Groups 3 and 4 received NPWT. Four weeks postimplantation of the post, the devices and surrounding tissues were harvested, and histologically evaluated for downgrowth. Within the untreated control groups, the Two-Stage surgical procedure significantly decreased downgrowth (p = 0.027) when compared with the One-Stage procedure. Independent of the surgical procedures performed, NPWT significantly limited downgrowth (p ≤ 0.05) when compared with the untreated controls.


Two-stage response adaptive randomization designs for multi-arm trials with binary outcome.
In recent years, adaptive randomization methods have gained significant popularity in clinical research and trial design due to their ability to provide both efficiency and flexibility in adjusting the statistical procedures of ongoing clinical trials. For a study to compare multiple treatments, a multi-arm two-stage design could be utilized to select the best treatment from the first stage and further compare that treatment with control in the second stage. The traditional design used equal randomization in both stages. To better utilize the interim results from the first stage, we propose to develop response adaptive randomization two-stage designs for a multi-arm clinical trial with binary outcome. Two allocation methods are considered: (1) an optimal allocation based on a sequential design; (2) the play-the-winner rule. Optimal multi-arm two-stage designs are obtained under three criteria: minimizing the expected number of failures, minimizing the average expected sample size, and minimizing the expected sample size under the null hypothesis. Simulation studies show that the proposed adaptive design based on the play-the-winner rule has good performance. A phase II trial for patients with pancreas adenocarcinoma and a germline BRCA/PALB2 mutation was used to illustrate the application of the proposed response adaptive randomization designs.


Concomitant overdosing of other drugs in patients with paracetamol poisoning.
Paracetamol is frequently involved in intended self-poisoning, and concomitant overdosing of other drugs is commonly reported. The purpose of the study was to investigate further concomitant drug overdose in patients with paracetamol poisoning and to evaluate its effects on the outcome of the paracetamol intoxication. Six hundred and seventy-one consecutive patients admitted with paracetamol poisoning were studied and concomitant drug intake was recorded. The relative risk of hepatic encephalopathy, death or liver transplantation, hepatic dysfunction, liver cell damage, and renal dysfunction associated with concomitant overdosing of other drugs was evaluated by multivariate analysis. Concomitant drug overdose was found in 207 patients (31%, 95% confidence interval [CI] 27, 34%). Concomitant overdosing of benzodiazepines (99 cases), opioid analgesics (38 cases), acetylsalicylic acid (33 cases), and NSAID (32 cases) predominated. Concomitant benzodiazepine overdose was an independent risk factor in the development of hepatic encephalopathy (odds ratio [OR] 1.91; CI 1.00, 3.65) and renal dysfunction (OR 1.81; CI 1.00, 3.22). Concomitant overdosing of opioid analgesics was a protective factor in the development of hepatic encephalopathy (OR 0.26; CI 0.07, 0.96). Concomitant acetylsalicylic acid overdose was a risk factor in the development of hepatic encephalopathy (OR 4.87; CI 1.52, 15.7) and death or liver transplantation (OR 6.04; CI 1.69, 21.6). A tendency towards a more favourable outcome was observed in patients with concomitant NSAID overdose. Concomitant overdosing of benzodiazepines or analgesics is frequent in patients admitted with paracetamol poisoning. Concomitant benzodiazepine or acetylsalicylic acid overdose was associated with more severe toxicity, whereas concomitant overdosing of opioid analgesics was associated with less toxicity.


Occlusal plane analysis using the Broadrick flag.
The determination of the occlusal plane can have a profound effect on the short- and long-term success of a restorative case. The fewer posterior interferences that result from the reconstruction means fewer problems for patients with their teeth, muscles, and temporomandibular joints. Proper utilization of the Broadrick flag on a semi-adjustable articulator will allow the dentist or laboratory technician to easily determine the ideal plane for each case. As mentioned earlier, the use of Monson's theory is only a starting point for the analysis. Patients come in different shapes and sizes and sometimes have mandibular incisors that are not positioned ideally. With a little experience and training, dentists can make the Broadrick flag an integral part of their practice. The Broadrick flag now has been adapted to several articulator systems, including Hanau (all models), Denar, Jensen (Artex--under development), and Kavo (Protar).


Similarity and diversity in visual cortex: is there a unifying theory of cortical computation?
The cerebral cortex, with its conserved 6-layer structure, has inspired many unifying models of function. However, recent comparative studies of primary visual cortex have revealed considerable structural diversity, raising doubts about the possibility of an all-encompassing theory. This review examines similarities and differences in V1 across mammals. Gross laminar interconnections are relatively conserved. Major functional response classes are found universally or nearly universally. Orientation and spatial frequency tuning bandwidths are quite similar despite an enormous range of visual resolution across species, and orientation tuning is contrast-invariant. Nevertheless, there is considerable diversity in the abundance of different cell classes, laminar organization, functional architecture, and functional connectivity. Orientation-selective responses arise in different layers in different species. Some mammals have elaborate columnar architecture like orientation maps and ocular dominance bands, but others lack this organization with no apparent impact on single cell properties. Finally, local functional connectivity varies according to map structure: similar cells are connected in smooth map regions but dissimilar cells are linked in animals without maps. If there is a single structure/function relation for cortex, it must accommodate significant variations in cortical circuitry. Alternatively, natural selection may craft unique circuits that function differently in each species.


Nurses, indirect trauma, and prevention.
To begin examining the nature of vicarious or indirect trauma and to discuss risk factors and prevention strategies. Despite the fact that many nurses are traumatized indirectly, few recognize the insidious development of such trauma. The dynamics of indirect trauma are relevant to nursing as are risk factors and prevention strategies. Brief review of the literature (1974-1997) on vicarious trauma, compassion fatigue, secondary traumatic stress disorder, and traumatic countertransference using short vignettes for illustration. Nurses who are informed about vicarious trauma and who actively maintain a balanced personal and professional life are in the best position to bring themselves and their clients through the many hazards of trauma work. The implications of vicarious or indirect trauma for nurses and clients are serious and complex requiring thoughtful analysis and research to clarify its effects.


Elderly people and responses to COVID-19 in 27 Countries.
Amongst the most robust consensus related to the COVID-19 disease is that the elderly are by far the most vulnerable population group. Hence, public authorities target older people in order to convince them to comply with preventive measures. However, we still know little about older people's attitudes and compliance toward these measures. In this research, I aim to improve our understanding of elderly people's responses to the pandemic using data from 27 countries. Results are surprising and quite troubling. Elderly people's response is substantially similar to their fellow citizens in their 50's and 60's. This research (i) provides the first thorough description of the most vulnerable population's attitudes and compliance in a comparative perspective (ii) suggest that governments' strategies toward elderly people are far from successful and (iii) shows that methodologically, we should be more cautious in treating age as having a linear effect on COVID-19 related outcomes.


The release of beta-thromboglobulin and platelet factor 4 during extracorporeal circulation for open heart surgery.
Cardiopulmonary bypass is extremely damaging to platelets and it causes a quantitative and qualitative alteration in their functions. We evaluated the release of two platelet-specific proteins, beta-thromboglobulin (beta TG) and platelet factor 4 (PF4), in patients who underwent extracorporeal circulation for open heart surgery. A parallel release (basal value beta TG: 119.6 ng/ml, PF4 30 ng/ml) was present for both proteins in a time dependent fashion until the end of extracorporeal circulation. High average levels were observed in patients in whom the bypass was stopped after about 1 h (beta TG 1606 ng/ml, PF4 745 ng/ml) and similarly in those in whom the bypass was stopped after about 2 h (beta TG 1540 ng/ml, PF 4754 ng/ml). No correlation was found either between the level of PF4 and the additional heparin administered after the initial standard dose (r = 0.29, P greater than 0.10) and between the level of PF4 and the amount of heparin consumed during the bypass (r = 0.05, P greater than 0.5).


Statistical binning enables an accurate coalescent-based estimation of the avian tree.
Gene tree incongruence arising from incomplete lineage sorting (ILS) can reduce the accuracy of concatenation-based estimations of species trees. Although coalescent-based species tree estimation methods can have good accuracy in the presence of ILS, they are sensitive to gene tree estimation error. We propose a pipeline that uses bootstrapping to evaluate whether two genes are likely to have the same tree, then it groups genes into sets using a graph-theoretic optimization and estimates a tree on each subset using concatenation, and finally produces an estimated species tree from these trees using the preferred coalescent-based method. Statistical binning improves the accuracy of MP-EST, a popular coalescent-based method, and we use it to produce the first genome-scale coalescent-based avian tree of life.


Bio-inspired aptamers decorated gold nanoparticles enable visualized detection of malathion.
Biosensors always respond to the targets of interest in a specific manner, employing biological or bio-mimic recognition elements such as antibodies and aptamers. Inspired by target recognition in nature, an aptamer-mediated, gold nanoparticle-based sensing approach is developed in this work for effective determination of malathion. The sensing system consists of negatively charged aptamer probes, and polycationic proteins, protamine, as well as exceptional colorimetric nanoprobes, barely gold nanoparticles (AuNPs). Protamine molecules bound to aptamer probes hinder the aggregation of AuNPs, while no such inhibition is maintained when aptamer-specific malathion is introduced into the solution, thus leading to the solution colour change from red to blue observable by the naked eye. The assay is accomplished via a mix-and-measure step within 40 min with a detection limit as low as 1.48 μg/L (3σ/s rule). The assay method also exhibits high selectivity and good applicability for the quantification of malathion in tap water with recovery rates of 98.9%-109.4%. Additionally, the good detection accuracy is also confirmed by the high-performance liquid chromatography method. Therefore, the non-enzymatic, label- and device-free characteristics make it a robust tool for malathion assay in agricultural, environmental, and medical fields.


Ferrocene derived carbon nanotubes and their application as electrochemical double layer capacitor electrodes.
We report on the synthesis of carbon nanotubes (CNTs) by direct thermal decomposition of ferrocene (Fe(C5H5)2). Our studies indicate that presence of a small amount of sulfur along with the ferrocene in the decomposition process strongly affects the quality of the CNTs produced and is crucial for obtaining thin diameter nanotubes. Raman spectroscopic investigations suggest that the atomic ratio of sulfur to the total iron plus sulfur content of approximately 0.09 yields CNTs with highly crystalline structure having diameters ranging from 0.85 nm to 1.75 nm. Electrochemical double layer capacitor electrodes fabricated from these CNTs show impressive energy storage properties, capable of delivering a maximum power density of approximately 27 KW/kg and energy density of approximately 2.12 Wh/Kg.


Thermoplasmonic-Triggered Release of Loads from DNA-Modified Hydrogel Microcapsules Functionalized with Au Nanoparticles or Au Nanorods.
Microcapsules consisting of hydrogel shells cross-linked by glucosamine-boronate ester complexes and duplex nucleic acids, loaded with dyes or drugs and functionalized with Au nanoparticles (Au NPs) or Au nanorods (Au NRs), are developed. Irradiation of Au NPs or Au NRs results in the thermoplasmonic heating of the microcapsules, and the dissociation of the nucleic acid cross-linkers. The separation of duplex nucleic acid cross-linkers leads to low-stiffness hydrogel shells, allowing the release of loads. Switching off the light-induced plasmonic heating results in the regeneration of stiff hydrogel shells protecting the microcapsules, leading to the blockage of release processes. The thermoplasmonic release of tetramethylrhodamine-dextran, Texas Red-dextran, doxorubicin-dextran (DOX-D), or camptothecin-carboxymethylcellulose (CPT-CMC) from the microcapsules is introduced. By loading the microcapsules with two different drugs (DOX-D and CPT-CMC), the light-controlled dose release is demonstrated. Cellular experiments show efficient permeation of Au NPs/DOX-D or Au NRs/DOX-D microcapsules into MDA-MB-231 cancer cells and inefficient uptake by MCF-10A epithelial breast cells. Cytotoxicity experiments reveal selective thermoplasmon-induced cytotoxicity of the microcapsules toward MDA-MB-231 cancer cells as compared to MCF-10A cells. Also, selective cytotoxicity towards MDA-MB-231 cancer cells upon irradiation of the Au NPs- and Au NRs-functionalized microcapsules at λ = 532 or 910 nm is demonstrated.


Systemic inflammation-based scores and mortality for all causes in HIV-infected patients: a MASTER cohort study.
Two biomarkers, the neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR), have been shown to be indicative of systemic inflammation and predictive of mortality in general population. We aimed to assess the association of NLR and PLR, with risk of death in HIV-infected subjects when also taking account of HIV-related factors. We conducted a multicenter Italian cohort study from 2000 to 2012 including HIV-infected subjects naïve at antiretroviral treatment. The associations of NLR and PLR with all-cause mortality were tested by univariate and multivariate analyses using both time independent and dependent Cox proportional hazard models. We also fitted models with a cubic-spline for PLR and NLR to evaluate the possible non-linear relationship between biomarkers values and risk of death. Eight-thousand and two hundred thirty patients (73.1% males) with a mean age of 38.4 years (SD 10.1) were enrolled. During a median follow-up of 3.9 years, 539 patients died. PLR < 100 and ≥ 200, as compared to PLR of 100-200, and NLR ≥ 2, as compared to < 2, were associated with risk of death at both univariate and multivariate analyses. Using multivariate models with restricted cubic-splines, we found a linear relationship of increasing risk of death with increasing values for NRL over 1.1, and an U-shape curve for PLR, with higher mortality risk for values higher or lower than 120. Our data suggest that NLR and PLR can reflect the severity of the underlying systemic disturbance of the inflammatory process and coagulation leading to augmented mortality in HIV positive subjects.


Diurnal fatigue patterns, sleep timing, and mental health outcomes among healthy postpartum women.
Postpartum women have frequently interrupted sleep, report high levels of fatigue, and may experience circadian rhythm disruptions. They are also susceptible to mood impairments, anxiety, and stress. The current study explored associations between maternal postpartum daily fatigue patterns, which should vary according to circadian influences and mental health. Seventy-one primiparous, healthy mothers completed multiple daily self-reports of fatigue during postpartum Weeks 2 and 12 and were categorized at each week as having either a rhythmic or random fatigue pattern during the daytime. Wrist actigraphy data were used to calculate sleep midpoints. Surveys assessed chronotype, mood, anxiety, and stress. At postpartum Week 2, there were no differences in mental health measures between fatigue groups. At postpartum Week 12, higher overall fatigue levels were associated with increased anxiety, stress, and mood disruption. However, overall fatigue levels did not differ between fatigue groups. Women with a rhythmic fatigue pattern reported significantly less stress and more vigor than women with a random fatigue pattern. An earlier sleep midpoint was associated with a rhythmic fatigue pattern during postpartum Week 12. These data suggest that, despite similar average daily fatigue levels, having a rhythmic daily pattern of fatigue may be advantageous for mental health outcomes among postpartum women.


Cardiovascular Collapse in COVID-19 Infection: The Role of Venoarterial Extracorporeal Membrane Oxygenation (VA-ECMO).
Coronavirus Disease 2019 (COVID-19) has been associated with cardiovascular complications, including acute cardiac injury, heart failure, and cardiogenic shock (CS). The role of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in the event of COVID-19-associated cardiovascular collapse has not been established. We reviewed the existing literature surrounding the role of VA-ECMO in the treatment of coronavirus-related cardiovascular collapse. COVID-19 is associated with a higher incidence of cardiovascular complications compared with previous coronavirus outbreaks (Severe Acute Respiratory Syndrome Coronavirus and Middle East Respiratory Syndrome Coronavirus). We found only 1 case report from China in which COVID-19-associated fulminant myocarditis and CS were successfully rescued using VA-ECMO as a bridge to recovery. We identified potential clinical scenarios (cardiac injury, myocardial infarction with and without obstructive coronary artery disease, viral myocarditis, and decompensated heart failure) leading to CS and risk factors for poor/uncertain benefit (age, sepsis, mixed/predominantly vasodilatory shock, prothrombotic state or coagulopathy, severe acute respiratory distress syndrome, multiorgan failure, or high-risk prognostic scores) specific to using VA-ECMO as a bridge to recovery in COVID-19 infection. Additional considerations and proposed recommendations specific to the COVID-19 pandemic were formulated with guidance from published data and expert consensus. A small subset of patients with cardiovascular complications from COVID-19 infection may progress to refractory CS. While accepting that resource scarcity may be the overwhelming concern for healthcare systems during this pandemic, VA-ECMO can be considered in highly selected cases of refractory CS and echocardiographic evidence of biventricular failure. The decision to initiate this therapy should take into consideration the availability of resources, perceived benefit, and risks of transmitting disease.


MRI-Cavernosography: A New Diagnostic Tool for Erectile Dysfunction Due to Venous Leakage: A Diagnostic Chance.
Erectile dysfunction caused by venous leakage is a vascular disease in which blood fails to accumulate in the corpora cavernosa due to the abrupt drainage of blood from the penis secondary to an abnormal venous network that affects 1 to 2% of men under 25 years old and about 10 to 20% over 60 years old, who do not raise a sufficient erection for penetrative sex. The study of the venous leak and its characterization in young patients with erectile dysfunction represent a diagnostic challenge, and imaging remains the best way to diagnose this condition. In the article, it is described the methods of execution and the diagnostic role of the cavernous MRI in the study of vasogenic erectile dysfunction from the venous leak, proposing it as a good alternative to the cavernous CT, considering the satisfactory results in terms of diagnostic interpretation, the absence of ionizing radiation, the higher soft tissue resolution of the imaging method and the lower administration of contrast agent.


Primary laryngeal cancer-derived miR-193b induces interleukin-10-expression monocytes.
The pathogenesis of laryngeal cancer (LC) is unclear. Published data indicate that micro RNAs (miRNA) play an important role in the pathogenesis of cancer. This study aims to elucidate the role of miR-193b in the tumor tolerance of LC. High levels of miR-193b were detected in LC cells as well as in the culture supernatant. Interleukin (IL)-10-expressing Mos were detected in the LC tissue-derived single cells. Treating naïve Mos with a miR-193b induced expression of IL-10 in the Mos. Culturing the IL-10(+) Mos with effector CD8(+) T cells resulted in the suppression of CD8(+) T-cell activities.


Treatment of intra-oral injection phobia: a randomized delayed intervention controlled trial among Norwegian 10- to 16-year-olds.
To evaluate the effect of five sessions of cognitive behavioural therapy (CBT) for 10- to 16-year-olds with intra-oral injection phobia. This was a randomized delayed intervention controlled trial in 67 patients, fulfilling the DSM-5 criteria for specific phobia. All patients received the same CBT performed by dentists specially trained in CBT. The patients were randomly assigned to either an immediate treatment group (ITG) (34 patients) or a waitlist-control group (WCG) (33 patients). The WCG was put on a waitlist for 5 weeks. After treatment, all patients were combined for post-treatment analyses. Assessments including the psychometric self-report scales Intra-oral injection fear scale (IOIF-s), Children's Fear Survey Schedule-Dental Subscale (CFSS-DS), Injection Phobia Scale for children (IS-c) and Mutilation Questionnaire for children (MQ-c) and a behavioural avoidance test (BAT) followed by a questionnaire on cognitions during the BAT, occurred pre-, post-treatment/waitlist and at a 1-year follow-up. CBT had a significant effect compared to no treatment (WCG). After treatment, the scores on the psychometric self-report scales were significantly reduced and higher levels in the BAT were achieved. The results were maintained at 1-year follow-up. Of the 67 patients, 70.1% received intra-oral injections during CBT treatment, whereas 69.4% of those completing the CBT, in need for further dental treatment, managed to receive the necessary intra-oral injections at their regular dentist. The 10- to 16-year-olds diagnosed with intra-oral injection phobia benefitted positively on CBT performed by specially trained dentists.


Down-regulated expression of aquaporin-4 in the cerebellum after status epilepticus.
Status epilepticus (SE) is a common neurological condition associated with high rates of mortality and permanent brain injury. SE usually leads to neuronal death which may be accompanied by edema, epileptogenesis and learning impairment. Aquaporin-4 (AQP4), is a transmembrane water channel protein in the neuropil of the central nervous system that has an important role in water transport in the brain; AQP4 expression is altered in many pathological conditions such as changes in the blood- brain barrier and/or astrocytic activation, including seizures. AQP4 was shown to be downregulated in the piriform cortex and the hippocampus after SE. Although it is normally expressed at a high level in the cerebellum, little is known about AQP4 levels in the cerebellum following SE. We addressed this in the present study in a mouse model of pilocarpine-induced SE. We found that AQP4 expression was reduced from 3 h to 3 days after SE, with the levels recovering on day 7. Moreover, mice in the acute post-SE stages exhibited impaired motor coordination and learning. These results indicate that cerebellar damage following SE involves changes in AQP4 expression.


Skin and environmental contamination with vancomycin-resistant Enterococci in patients receiving oral metronidazole or oral vancomycin treatment for Clostridium difficile-associated disease.
Oral metronidazole has been recommended for treatment of mild-to-moderate Clostridium difficile-associated disease (CDAD), in part because of concern that use of vancomycin may be more likely to promote colonization and transmission of vancomycin-resistant enterococci (VRE). The objective of our study was to compare the frequency of skin and environmental VRE contamination associated with metronidazole treatment for CDAD with such frequency associated with vancomycin treatment for CDAD. Prospective, observational study. This study was performed at the Cleveland Veterans Affairs Medical Center (Cleveland, OH). For patients with CDAD who had concurrent VRE colonization, stool, skin, and environmental samples were cultured for VRE before, during, and up to 3 weeks after therapy with metronidazole or vancomycin. The proportions of skin and environmental contamination were compared before and after resolution of diarrhea and during treatment with metronidazole or vancomycin. Of the 34 patients, 17 were treated with vancomycin and 17 were treated with metronidazole. The proportion of environmental cultures that were positive for VRE was significantly higher during resolution of diarrhea than it was after resolution of diarrhea (38% vs 28%; P=.025), whereas the proportion of skin cultures positive was not different during and after resolution of diarrhea (78% vs 71%; P=.60). There were no differences between patients who received metronidazole and patients who received vancomycin in the proportions of skin culture results (73% vs 77%; P=.80) or environmental culture results (37% vs 32%; P=.359) that were positive for VRE. Eleven patients (32%) had chronic fecal incontinence, and 28 (82%) had incontinence at least once during their CDAD episode. In VRE-colonized patients with CDAD who experienced frequent fecal incontinence, skin and environmental VRE contamination was common during and after resolution of diarrhea. The frequency of VRE contamination was similar between patients treated with metronidazole and patients treated with vancomycin.


Starvation and the clinicopathologic abnormalities associated with starved dogs: a review of 152 cases.
The objectives of this retrospective study were to identify the most common clinicopathologic abnormalities in starved dogs, assess the time required for those abnormalities to resolve, and determine whether clinicopathologic abnormalities recorded at time of intake to the hospital influenced time to regain weight. Records of 152 very underweight or emaciated dogs seized by the American Society for the Prevention of Cruelty to Animals (ASPCA) Humane Law Enforcement (HLE) division were reviewed. Dogs were classified as emaciated if the admission body weight was estimated to be ≥ 30% below the anticipated ideal body weight and classified as very underweight if the admission weight was estimated to be 20-29% below the anticipated ideal body weight. An initial minimum database was obtained on each animal, and when possible, clinicopathologic abnormalities were serially assessed. The most common initial abnormalities, present in ≥ 25% of dogs, were hypoalbuminemia, thrombocytosis, anemia, elevated blood urea nitrogen (BUN), elevated BUN/creatinine ratio, and hypocalcemia. Mean time to gain 20% of admission body weight was similar for the abnormalities studied. Although there was some evidence that dogs with anemia and/or hypoalbuminemia required more days to gain weight, future studies are required for confirmation.


Incongruence between mtDNA phylogeny and morphologial and ecological characters in loaches of the genus Lefua (Balitoridae, Cypriniformes).
To elucidate the phylogenetic position of Lefua loaches from Aichi and Shizuoka Prefectures of Honshu Island, Japan, we determined their nucleotide sequences for the mitochondrial D-loop region and compared these to sequences from four other Lefua species: L. costata, L. nikkonis, L. echigonia, and L. sp. Loaches identified as L. sp. on the basis of morphology comprised a clade (the L. sp. Tokai population) that grouped together with L. echigonia; hence, the processes involved in evolution within the genus Lefua were unclear. We performed randomly amplified polymorphic DNA (RAPD) analyses to obtain genetic information on nuclear DNA. The RAPD patterns of the L. sp. Tokai population differed from those of the local L. echigonia and L. sp. populations. The L. sp. Tokai population was similar to L. echigonia with regard to mitochondrial DNA but differed from L. echigonia and L. sp. with respect to nuclear DNA; this indicated that the evolutionary background of the L. sp. Tokai population was unique. We suggest that introgression of mitochondria occurred from L. echigonia to the L. sp. Tokai population, and speculate on the process of evolution of the latter population of Lefua. As with six L. echigonia populations and two L. sp. populations, we regard the L. sp. Tokai population as an evolutionary significant unit (ESU) that qualifies for protection as an endangered loach.


Optimization of Centrifugal Pump Characteristic Dimensions for Mechanical Circulatory Support Devices.
The application of artificial mechanical pumps as heart assist devices impose power and size limitations on the pumping mechanism, and therefore requires careful optimization of pump characteristics. Typically new pumps are designed by relying on the performance of other previously designed pumps of known performance using concepts of fluid dynamic similarity. Such data are readily available for industrial pumps, which operate in Reynolds numbers region of 10. Heart assist pumps operate in Reynolds numbers of 10. There are few data available for the design of centrifugal pumps in this characteristic range. This article develops specific speed versus specific diameter graphs suitable for the design and optimization of these smaller centrifugal pumps concentrating in dimensions suitable for ventricular assist devices (VADs) and mechanical circulatory support (MCS) devices. A combination of experimental and numerical techniques was used to measure and analyze the performance of 100 optimized pumps designed for this application. The data are presented in the traditional Cordier diagram of nondimensional specific speed versus specific diameter. Using these data, nine efficient designs were selected to be manufactured and tested in different operating conditions of flow, pressure, and rotational speed. The nondimensional results presented in this article enable preliminary design of centrifugal pumps for VADs and MCS devices.


[New findings about Priessnitz from the unknown Vinzenz Priessnitz Familien-Wasserbuch from 1847].
The large scope of therapies that Priessnitz used for his cure treatments in Gräfenberg completely fell into oblivion. More than 50 different applications of water, partly created by Priessnitz, dietary therapy for every patient, a lot of physical exercise, air as well as sun baths, improvement of fitness, and a regular life style were included in Priessnitz' treatments. He treated a variety of indications, not only chronic but also severe acute ones. The Vinzenz Priessnitz'sche Familien-Wasserbuch is a real treasury of forgotten facts about the genius who was the first to rediscover and remodel hydrotherapy before Kneipp.


Simple Bulk Readout of Digital Nucleic Acid Quantification Assays.
Digital assays are powerful methods that enable detection of rare cells and counting of individual nucleic acid molecules. However, digital assays are still not routinely applied, due to the cost and specific equipment associated with commercially available methods. Here we present a simplified method for readout of digital droplet assays using a conventional real-time PCR instrument to measure bulk fluorescence of droplet-based digital assays. We characterize the performance of the bulk readout assay using synthetic droplet mixtures and a droplet digital multiple displacement amplification (MDA) assay. Quantitative MDA particularly benefits from a digital reaction format, but our new method applies to any digital assay. For established digital assay protocols such as digital PCR, this method serves to speed up and simplify assay readout. Our bulk readout methodology brings the advantages of partitioned assays without the need for specialized readout instrumentation. The principal limitations of the bulk readout methodology are reduced dynamic range compared with droplet-counting platforms and the need for a standard sample, although the requirements for this standard are less demanding than for a conventional real-time experiment. Quantitative whole genome amplification (WGA) is used to test for contaminants in WGA reactions and is the most sensitive way to detect the presence of DNA fragments with unknown sequences, giving the method great promise in diverse application areas including pharmaceutical quality control and astrobiology.


Bisphenol A (BPA) and its potential role in the pathogenesis of the polycystic ovary syndrome (PCOS).
Polycystic ovary syndrome (PCOS) is the most common and the most heterogeneous endocrine disorder in premenopausal women. Apart from signs of hyperandrogenism such as acne, hirsutism and hair loss, women with PCOS usually present with menstrual irregularities and fertility problems.Additionally, they are often characterized by impaired glucose tolerance, which usually leads to the development of type 2 diabetes mellitus (T2DM). This review article describes current and novel approach to the pathomechanisms of PCOS and the potential role of an endocrine disrupting chemical ("endocrine disruptor" - ED) - bisphenol A (BPA), which is commonly used as a plasticizer and due to its molecular structure can interact with estrogen receptors (ERs). Recent observations point to the higher levels of BPA in biological fluids of women with PCOS and its role in the pathogenesis of hyperandrogenism and hyperinsulinemia. It seems that mother's exposure to BPA during pregnancy may also lead to the development of PCOS in the female offspring.


A practical protocol for comprehensive evaluation of sulfur-fumigation of Gastrodia Rhizoma using metabolome and health risk assessment analysis.
Gastrodia Rhizoma is one of the most heavily sulfur-fumigated edible and medical herbs in the marketplace. We developed a practical protocol using an ultra-performance liquid chromatography coupled with quadrupole time-of-flight-MSE (UPLC/QTOF-MSE)-based metabolome and health risk assessment model to identify characteristic sulfur-fumigated markers, dissect chemical transformation mechanisms, and control the quality of sulfur-fumigated Gastrodia Rhizoma. Two sulfur-containing p-hydroxybenzyl products, one sulfur-containing disaccharide, one glycolipid, and two phospholipids were selected and identified as markers based on multivariate statistical analysis. In particular, the sulfur-containing markers p-hydroxybenzyl hydrogen sulfite and trace p-mercaptobenzyl hydrogen sulfate were positively correlated with the active major phenolics. Moreover, a practical index the time of the minimum content was useful for evaluating the extent of the sulfur-fumigation under different weight ratios of the sulfur to herbal materials (1:20, 1:40, and 1:80). Ultimately, the 1:40 ratio within 1h of sulfur-fumigation was considered as safe and efficient for herb quality preservation under the maximum residue limit of 750mg/kg. This study shows that the practical protocol-based discriminated markers and practical limits can be applied to quality assurance of sulfur-fumigation and non-fumigation Gastrodia Rhizoma and other edible or medical materials.


Exercise-induced proteinuria in well-trained athletes.
We studied the rate of urinary excretion of albumin, alpha 1-microglobulin (as an indicator of the renal tubular involvement), sodium, potassium, and creatinine in the basal state (overnight urine collection) and after physical exercise (training session) in 10 professional cyclists, to verify whether protein excretion is increased even in well-trained athletes after physical effort. In addition, we wanted to understand whether the origin of exercise-induced proteinuria was glomerular, tubular, or both. Compared with the basal state (overnight collection), exercise significantly (P less than 0.01) increased the excretion rate of albumin (4.2 +/- 2.6 micrograms/min vs 18.1 +/- 10.6 micrograms/min, mean +/- SD), Na, and K, and also the urinary volume. Creatinine output was not affected by exercise. The mean (+/- SD) overnight excretion rate of albumin by athletes was quite similar to that found for 91 healthy nonathletes at rest (4.6 +/- 2.7 micrograms/min). The mean exercise-related excretion of alpha 1-microglobulin by the athletes significantly exceeded the overnight value (6.6 vs 0.3 mg/L, P = 0.037). Our study indicates that (a) albuminuria furnishes the greater contribution to the increase in exercise-induced proteinuria; (b) the exercise proteinuria is both glomerular and tubular in origin, and is reversible; (c) the enhanced protein requirement of athletes may in part be due to the recurrent excretion of proteins in the urine after physical effort.


Novel intracellular functions of apolipoproteins: the ApoO protein family as constituents of the Mitofilin/MINOS complex determines cristae morphology in mitochondria.
Mitochondria exist in a highly dynamic network that is constantly altered by fusion and fission events depending on various factors such as cellular bioenergetic state and cell cycle. Next to this dynamic nature of the organelle, its cristae membrane also undergoes drastic morphological changes upon physiological or pathological alterations. The Mitofilin/mitochondrial inner membrane organizing system (MINOS) complex was recently reported to ensure mitochondrial architecture and crista junction integrity. Several subunits of this complex are linked to a diverse set of neurological human disorders. Recently, two apolipoproteins, ApoO (APOO) and ApoO-like (APOOL) were suggested to represent constituents of the mammalian Mitofilin/MINOS complex. APOOL was shown to bind the mitochondrial phospholipid cardiolipin (CL) and to interact physically with this complex. In this review we highlight the current view on the mammalian Mitofilin/MINOS complex and focus on APOOL and the role of CL in determining cristae morphology. We will discuss possible functions of the Mitofilin/MINOS complex on lipid transport, on assembly of respiratory supercomplexes, on F1FO-ATP synthase organization, on contact site formation, and on trapping CL within the cristae subcompartment.


Biology of Vampyressa pusilla (Wagner) in Rio de Janeiro State, southeastern Brazil (Mammalia, Chiroptera, Phyllostomidae).
Vampyressa pusilla is widespread in Rio de Janeiro State, southeastern Brazil. It occurs in forested areas, and is absent from urban and open habitats. This species occurs mainly in altitudes up to 1,300 m a.s.l. Vampyressa pusilla was captured during the whole night, from 18 minutes before sunset to 759 minutes after sunset. Captures peaked in the first two hours of the night. Reproductive activity was seasonal, pregnant females were observed in January, February, April, August, October, November and December and lactating females from November to January and in March.


Condom use and associated factors among men who have sex with men in Togo, West Africa.
In 2011, the prevalence of HIV among men who have sex with men (MSM) in Togo was estimated at 19.6% compared to 3.4% in the general population. This study aimed to describe condom use and associated factors among MSM in Togo. In 2011, a cross-sectional survey was conducted using the snowball sampling method among MSM in Togo. This study enrolled MSM aged 18 years and above who reported having sexual contact with other men within the last 30 days. A standardized survey form was used for data collection, and multivariate analyses were performed. A total of 724 MSM were included in this study. The median age was 25 years [22-28], 90.3% had at least a secondary school level. The sexual practices during the last sexual encounter with another man included: insertive anal sex (62.2%), receptive anal sex (56.6%), oral sex (33.8%) and oral-anal sex (8.6%). A condom was used during the last insertive and receptive anal encounters in 78.4% and 81.2% of the time, respectively. In multivariate analysis, condom use was positively associated with previous participation in HIV/STD prevention activities (aOR=1.72; 95% CI=[1.09-2.71]), with the consideration of the last sexual partner as a casual one (aOR=1.87; 95% CI=[1.24-2.82]) and with having at least a secondary school level (aOR=2.40; 95% CI=[1.22-4.69]). One out of five MSM did not use a condom during the last anal encounter with another man. HIV prevention programs in Africa should develop specific interventions targeting MSM to reduce the incidence of HIV in this hidden population.


Asymptomatic omental granuloma following spillage of gallstones during laparoscopic cholecystectomy protects patients and influences surgeons' decisions: a review.
Spillage of gallstones in the peritoneal cavity during laparoscopic cholecystectomy (LC) occurs at rates varying from 5.7% to 16%. These gallstones often cannot be retrieved and can cause early and late abscesses at rates ranging from 0.08% to 1.4%. The case of an 86-year-old woman with colon cancer is described because during an elective right hemicolectomy a granuloma of the omentum with retained gallstones from LC performed 8 years earlier was unexpectedly found. Importantly, the gallstones were found high up in the abdominal cavity. Moreover, this report reaffirms the excellent response of the peritoneal cavity defence mechanisms for protecting patients against gallstones through asymptomatic omental granuloma. Current data indicate that every effort should be made to retrieve spilled gallstones, but routine conversion to an open cholecystectomy is not recommended. Identifying factors that impair host defence mechanisms should help surgeons' decision-making.


Postoperative Complication and Reoperation Rates Following Resection of Soft Tissue vs. Bone Malignancies Based on Anatomic Location in the Inpatient Setting.
Surgical excisions of upper and lower extremity malignancies are increasing annually, due in part to the rising incidence of sarcomas. The purpose of this study is to compare readmissions, reoperation rate, and complications following surgical excision of soft/connective tissue vs bone malignancies of the upper and lower extremities. The Nationwide Readmissions Database (NRD) was queried from 2016-2017 to conduct a retrospective analysis of 16,435 patients diagnosed with malignant neoplasms of the long bone (ULLB, n = 1,433) and soft tissue (ULST, n = 2,049) of the upper limb and malignant neoplasms of the long bone (LLLB, n = 5,422) and soft tissue (LLST, n = 7,531) of the lower limb. Patients who underwent surgical excision of their neoplasms were included. Binomial multivariate logistic regression was used to compare complications, nonelective readmission rates, and reoperation rates between the two groups at 30 and 90 days. Average age of the ULST group was 61.88, with 36% female. Average age of the ULLB group was 44.97, with 41.90% female. Average age of the LLST group was 60.96, with 46.90% female. Average age of the LLLB group was 43.09, with 42.60% female. The ULST group had lower odds of readmission within 30 days (p=0.263), which became significant within 90 days of surgery (p=0.045). The LLST group had significantly higher odds of infection, reoperation within 30 to 90 days of the index surgery compared to the LLLB group (p < 0.0001). The LLST group had significantly lower odds of readmission within 30 (p=0.04) and 90 days (p=0.015) of the index surgery. Patients in the ULST group had significantly lower odds of 90-day readmission compared to the ULLB group. There were also significantly lower odds of 30- and 90-day readmission in the LLST group compared to the LLLB group. However, the LLST group had significantly higher odds of infection and reoperation within 30 and 90 days compared to the LLLB group.


Protein interactions at Sp1-like sites in the TGF alpha promoter as visualized by in vivo genomic footprinting.
Transcription from the rat TGF alpha promoter initiates at two predominant sites (-188 and -58) in a G+C-rich region that does not contain TATA or CAAT motifs. Previous studies using transfected reporter constructs implicated the transcription factor Sp1 in active expression from the promoter, particularly from the -58 site (Chen et al., 1992; Shin et al., 1992). In the present report we have examined the functionality of two adjacent clusters of Sp1-like recognition sites that are located in the upstream portion of the promoter from -300 to -273. A double-stranded oligonucleotide, which spanned this region and contained the putative Sp1 elements, demonstrated similar gel-mobility shifts in the presence of both crude HeLa cells nuclear extract and pure Sp1 protein. Mutations that simultaneously altered several of the overlapping Sp1 elements significantly reduced the gel-mobility shift activity of this oligonucleotide probe and, when introduced into the promoter templates, inhibited transcription in vitro from the proximal -188 start site. To confirm the binding of protein to these sites in cells, we carried out an in vivo genomic footprinting analysis of this portion of the TGF alpha promoter in normal and transformed rat liver epithelial cell lines that express the endogenous gene at varying levels. This analysis revealed clear evidence of protein/DNA interaction at Sp1-like sites in the -300 and -273 region in cells actively expressing the gene but not in a normal, parental cell line that expressed very low levels of TGF alpha mRNA. Collectively, these results corroborate the functional importance of Sp1 binding elements in the -300 to -273 region, and together with previous findings, indicate that two clusters of Sp1 binding sites respectively determine levels of transcription from the -188 and -58 start sites. Our additional finding that Sp1 mRNA and protein were present at similar levels in normal and transformed cells that expressed the endogenous TGF alpha gene at markedly different levels, suggests that the activity of the TGF alpha promoter could be regulated via the accessibility of Sp1 protein.


Bactericidal antibody response of normal human serum to the lipooligosaccharide of Neisseria gonorrhoeae.
Human antibody to lipooligosaccharide (LOS) from pooled normal human serum (NHS) and human immunne serum globulin (HISG) was isolated by affinity chromatography from a Sepharose column to which Escherichia coli strain J-5 LOS had been conjugated. Fractionated antibody was tested for bactericidal activity against serum-resistant Neisseria gonorrhoeae strains JW31, WR220, or 838 or serum-sensitive strains JW31R or 1074. By enzyme-linked immunosorbent assay the eluate of antibody to LOS contained IgM, IgA, and IgG antibodies to both JW31 and JW31R LOS. The IgM fraction from NHS was bactericidal at 30 min for strains JW31R and 1074 but failed to kill strains JW31 and 838. An IgG fraction from HISG was bactericidal for strains JW31 and WR220 yet failed to kill strain JW31R. The IgA fraction from NHS did not kill either strain JW31 or JW31R. Blocking experiments indicated that IgA or IgG failed to prevent IgM-mediated killing of strain JW31R, whereas IgA blocked the IgG-mediated killing of strain JW31.


Epithelioid inflammatory myofibroblastic sarcoma: An aggressive intra-abdominal variant of inflammatory myofibroblastic tumor with nuclear membrane or perinuclear ALK.
Inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm of intermediate biological potential, which may recur and rarely metastasize. Pathologic features do not correlate well with behavior. Approximately 50% of conventional IMTs harbor ALK gene rearrangement and overexpress ALK, most showing diffuse cytoplasmic staining. Rare IMTs with a distinct nuclear membrane or perinuclear pattern of ALK staining and epithelioid or round cell morphology have been reported. These cases pursued an aggressive clinical course, suggesting that such patterns may predict malignant behavior. We describe 11 cases of IMT with epithelioid morphology and a nuclear membrane or perinuclear pattern of immunostaining for ALK. Ten patients were male and 1 was female, ranging from 7 months to 63 years in age (median, 39 y). All tumors were intra-abdominal; most arose in the mesentery or omentum, measuring 8 to 26 cm (median, 15 cm). Six tumors were multifocal at presentation. The tumors were composed predominantly of sheets of round-to-epithelioid cells with vesicular nuclei, large nucleoli, and amphophilic-to-eosinophilic cytoplasm. In all cases, a minor spindle cell component was present. Nine tumors had abundant myxoid stroma. In 7 cases neutrophils were prominent and in 3 cases lymphocytes were prominent. Plasma cells were often absent. Median mitotic rate was 4/10 HPF; 6 tumors had necrosis. By immunohistochemistry, all tumors were positive for ALK, 9 tumors showing a nuclear membrane staining pattern and 2 tumors showing a cytoplasmic pattern with perinuclear accentuation. Other positive markers were desmin (10 of 11), focal smooth muscle actin (4 of 8), and CD30 (8 of 8). All tumors were negative for MYF4, caldesmon, keratins, EMA, and S-100. Fluorescence in situ hybridization was positive for ALK gene rearrangement in 9 cases, and in 3 cases tested, a RANBP2-ALK fusion was detected by reverse transcription polymerase chain reaction. Ten patients underwent surgical resection; 1 patient was inoperable. Follow-up was available for 8 patients and ranged from 3 to 40 months (median, 13 mo). All patients experienced rapid local recurrences; 4 patients had multiple recurrences. Eight patients were treated with postoperative chemotherapy; 2 patients received additional radiotherapy. Two patients also developed metastases (both patients developed metastases to the liver; 1 patient developed metastases to the lung and lymph nodes as well). Thus far, 5 patients died of disease, 2 patients are alive with disease, and 1 patient, treated with an experimental ALK inhibitor, has no evidence of disease. In summary, the epithelioid variant of IMT with nuclear membrane or perinuclear ALK is a distinctive intra-abdominal sarcoma with a predilection for male patients. Unlike conventional IMT, abundant myxoid stroma and prominent neutrophils are common. These tumors pursue an aggressive course with rapid local recurrences and are frequently fatal. We propose the designation "epithelioid inflammatory myofibroblastic sarcoma" to convey both the malignant behavior of these tumors and their close relationship with IMT.


The catalytic mechanism of yeast thiosulfate reductase.
Thiosulfate reductase catalyzes the desulfuration of thiosulfonates while oxidizing GSH to GSSG. Kinetic studies of the enzyme-catalyzed reaction between GSH and benzenethiosulfonate have been carried out, and direct evidence for the occurrence of glutathione persulfide as an immediate product of the reaction has been obtained. The formal mechanism of this enzymic reaction has been shown to be rapid equilibrium-ordered with GSH as the leading substrate.


Dissociation between decision-making under risk and decision-making under ambiguity in premanifest and manifest Huntington's disease.
We investigated decision-making under ambiguity (DM-UA) and decision making under risk (DM-UR) in individuals with premanifest and manifest Huntington's disease (HD). Twenty individuals with premanifest HD and 23 individuals with manifest HD, on one hand, and 39 healthy individuals divided into two control groups, on the other, undertook a modified version of the Iowa Gambling Task (IGT), an adaptation of a DM-UA task, and a modified version of the Game of Dice Task (GDT), an adaptation of a DM-UR task. Participants also filled in a questionnaire of impulsivity and responded to cognitive tests specifically designed to assess executive functions. Compared to controls, individuals with premanifest HD were unimpaired in performing executive tests as well as in decision-making tasks, except for the Stroop task. In contrast, individuals with manifest HD were impaired in both the IGT and executive tasks, but not in the GDT. No sign of impulsivity was observed in individuals with premanifest or manifest HD. Our results suggest that the progression of HD impairs DM-UA without affecting DM-UR, and indicate that decision-making abilities are preserved during the premanifest stage of HD.


Smoking behaviors before and after implementation of a smoke-free legislation in Guangzhou, China.
According to the partial smoke-free legislation implemented on 1 September 2010 in Guangzhou, China, smoke-free did not cover all indoor areas. Some places have a full smoking ban (100 % smoke-free), other places have a partial smoking ban, and homes have no ban. This study aimed to compare the smoking behaviors before and after implementation of a smoke-free legislation. A repeated cross-sectional survey was conducted on smoking-related behaviors with a total of 4,900 respondents before, and 5,135 respondents after the legislation was instituted. For each wave of the survey, a three-stage stratified sampling process was used to obtain a representative sample. Pearson's Chi-square test was used to determine differences of smoking prevalence and quit ratio between the two samples. Logistic regression models were used to examine the associations of a smoke-free legislation with smoking behaviors. The overall daily smoking rate declined significantly from 20.8 % to 18.2 % (p < 0.05), especially among those aged 15-24 years. The quit ratios increased significantly (from 14.5 % to 17.9 %), but remained low among 15-44 year olds. The overall self-reported smoking behaviors in locations with a full smoking ban decreased significantly from 36.4 % to 24.3 % with the greater drops occurring in cultural venues, public transport vehicles, and government offices. Smoking in places with partial smoking bans remained high (89.6 % vs. 90.4 %), although a slight decrease was observed in some of these areas. The implementation of a smoke-free legislation did not lead to more smoking in homes (91.0 % vs 89.4 %), but smoking in homes remained high. These findings highlight the urgent need for a comprehensive smoke-free legislation covering all public places in Guangzhou, simultaneously educational interventions and campaigns promoting voluntary changes in home smoking need to occur.


Routine cryopreservation of spermatozoa is safe--evidence from the DNA methylation pattern of nine spermatozoa genes.
Assess short- and mid-term impact of cryopreservation on DNA methylation status of different genes in spermatozoa. Semen samples from 10 healthy normozoospermic men were collected at the Department of Clinical Andrology of the Centre of Reproductive Medicine and Andrology (Muenster, Germany). Each was divided into four equal aliquots: 1) untreated, 2) diluted in cryoprotectant, 3) short term (2 days) cryopreserved and 4) mid term (4 weeks) cryopreserved. Samples were "swim-up" purified prior to analysis. DNA fragmentation was measured using comet assay and Flow cytometric evaluation with Acridine Orange (FCEAO). The degree of methylation of nine genes was determined by bisulfite pyrosequencing of genomic DNA. Analysis of three maternally imprinted genes (LIT1, SNRPN, MEST), two paternally imprinted genes (MEG3, H19), two repetitive elements (ALU, LINE1), one spermatogenesis-specific gene (VASA) and one gene associated with male infertility (MTHFR) in semen samples demonstrated no alteration in methylation pattern regardless of duration of cryopreservation. The lack of any changes in the sub-fraction of the genome examined in our study, implies that sperm DNA methylation is unaffected by cryopreservation and suggests that this daily clinical routine is safe in terms of DNA methylation.


Analytical validation of a second-generation immunoassay for the quantification of N-terminal pro-B-type natriuretic peptide in canine blood.
N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been shown to have clinical utility as a biomarker in dogs with heart disease. There were several limitations associated with early diagnostic assay formats including a limited dynamic range and the need for protease inhibitors to maintain sample stability. A second-generation Cardiopet® proBNP enzyme-linked immunosorbent assay (IDEXX Laboratories Inc., Westbrook, Maine) was developed to address these limitations, and the present study reports the results of the analytical method validation for the second-generation assay. Coefficients of variation for intra-assay, interassay, and total precision based on 8 samples ranged from 3.9% to 8.9%, 2.0% to 5.0%, and 5.5% to 10.6%, respectively. Analytical sensitivity was established at 102 pmol/l. Accuracy averaged 102.0% based on the serial dilutions of 5 high-dose canine samples. Bilirubin, lipids, and hemoglobin had no effect on results. Reproducibility across 3 unique assay lots was excellent with an average coefficient of determination (r (2)) of 0.99 and slope of 1.03. Both ethylenediamine tetra-acetic acid plasma and serum gave equivalent results at time of blood draw (slope = 1.02, r (2) = 0.89; n = 51) but NT-proBNP was more stable in plasma at 25°C with median half-life measured at 244 hr and 136 hr for plasma and serum, respectively. Plasma is the preferred sample type and is considered stable up to 48 hr at room temperature whereas serum should be frozen or refrigerated when submitted for testing. Results of this study validate the second-generation canine Cardiopet proBNP assay for accurate and precise measurement of NT-proBNP in routine sample types from canine patients.


Epigenetic reprogramming around IFN1 and IFNy2 promoters in rainbow trout cells inoculated with infectious pancreatic necrosis virus (IPNV).
Infectious pancreatic necrosis virus (IPNV) has proven to effectively evade the host antiviral responses. This study clarifies whether the modulation of the antiviral immune response exerted by IPNV involves epigenetic mechanisms. An in-silico characterization of the rainbow trout IFN1 and IFNγ2 promoters was performed, identifying the islands or sequences rich in CpG dinucleotides and the putative transcription factor binding sites (TBS) for both gene promoters. RTS11 cells (rainbow trout monocyte/macrophage) were infected with IPNV, and the course of viral infection was followed up to 48 h post infection (hpi). Infected cells showed increased IFN1 and IFNγ2 transcriptional expression at 6 and 24 hpi, respectively. IPNV infection caused increases and decreases in global IFNγ2 promoter methylation at 6 and 24 hpi, respectively. The CpG dinucleotides at positions -392 and + 38 of this promoter were the most sensitive to methylation changes. The IFN1 promoter remained fully unmethylated during the course of the infection, similar to the control. The changes in the methylation pattern observed for the IFNγ2 promoter were coincident with the changes in DNA methyltransferase (DNMT) expression levels, increasing at 6 hpi and decreasing below basal level at 24 hpi. Similarly, the H4 histones associated with the IFN1 and IFNγ2 promoters were hyperacetylated at 6 hpi, subsequently decreasing their acetylation below basal levels at 24 hpi, in both promoters. Coincidentally with the above, overexpression of histone acetyltransferase (HAT) was observed at 6 hpi and of histone deacetylase (HDAC) at 24 hpi, with return to baseline of HAT. These results suggest that IPNV would epigenetically modulate the expression of IFN1 by changing acetylation levels of the histones H4 associated with its promoter. Also, the modulation of the expression of IFNy2 would be by switching methylation/demethylation levels of its promoter, in addition to changes in acetylation levels of histones H4 associated with this promoter. This study is the first to demonstrate the effect of epigenetic reprogramming after IPNV infection in salmonid cells, demonstrating that promoter methylation/demethylation level and changes in the histone code associated with promoters may play a role in the modulation of the immune response induced by the virus.


The taste of water.
Female mosquitos require a specific ion-channel protein to sense the presence of fresh water in which they can lay their eggs.


Demonstration of acid-fast bacilli in buffy coat and bone marrow smear--a diagnostic tool in pulmonary tuberculosis.
Buffy coat smears prepared from peripheral blood and bone marrow aspirate obtained from proved 60 untreated cases of pulmonary tuberculosis were stained with Ziehl-Neelsen method and thoroughly screened for presence of tubercle bacilli. Acid-fast bacilli were detected in 55% cases in buffy coat, 48.3% cases in bone marrow, 38.3% cases both in buffy coat and bone marrow and 65% cases either in buffy coat or in bone marrow or in both. Considering the fact that demonstration of acid-fast bacilli may not be possible in more than 25-50% of the suspected cases of tuberculosis, these techniques are recommended for evaluation of their utility in establishing diagnosis of tuberculosis, particularly in reference to sputum negative cases of pulmonary tuberculosis and tuberculosis of inaccessible extrapulmonary sites.


[Screening of prothrombotic state-related genes from human hepatic cDNA library].
To screen prothrombotic state-related cDNA sequences from human hepatic cDNA library. The subtracted cDNA library for differentially expressed genes in rat liver of prothrombotic state (PTS) was constructed by suppression subtractive hybridization. Positive clones were identified by differential screening. The target DNA sequences of positive cDNA clones of differentially expressed genes from rat liver of PTS were amplified by PCR. The PCR products were used as probes to screen a human hepatic cDNA library. After the first, second and third screening, the transduction of a positive lambdaTripIEx lysate into E. coli strain BM25. 8 promoted the circularization of pTripIEx. The positive circularized plasmids were identified by double enzyme digestion. The cDNA fragments of the positive plasmids were sequenced and analyzed by bioinformatics (blastn). Four PTS-related cDNA sequences were identified from human hepatic cDNA library. For 3 of them, their products of expression were respectively fibrinogen, LFIRE1, and chromosome 10 open reading frame 104 mRNA. The fourth sequence had homology with carbamoyl-phosphate synthetase 1 gene. Four PTS-related cDNA sequences have been identified from human hepatic cDNA library.


Efficient plasma metabolic fingerprinting as a novel tool for diagnosis and prognosis of gastric cancer: a large-scale, multicentre study.
Metabolic biomarkers are expected to decode the phenotype of gastric cancer (GC) and lead to high-performance blood tests towards GC diagnosis and prognosis. We attempted to develop diagnostic and prognostic models for GC based on plasma metabolic information. We conducted a large-scale, multicentre study comprising 1944 participants from 7 centres in retrospective cohort and 264 participants in prospective cohort. Discovery and verification phases of diagnostic and prognostic models were conducted in retrospective cohort through machine learning and Cox regression of plasma metabolic fingerprints (PMFs) obtained by nanoparticle-enhanced laser desorption/ionisation-mass spectrometry (NPELDI-MS). Furthermore, the developed diagnostic model was validated in prospective cohort by both NPELDI-MS and ultra-performance liquid chromatography-MS (UPLC-MS). We demonstrated the high throughput, desirable reproducibility and limited centre-specific effects of PMFs obtained through NPELDI-MS. In retrospective cohort, we achieved diagnostic performance with areas under curves (AUCs) of 0.862-0.988 in the discovery (n=1157 from 5 centres) and independent external verification dataset (n=787 from another 2 centres), through 5 different machine learning of PMFs, including neural network, ridge regression, lasso regression, support vector machine and random forest. Further, a metabolic panel consisting of 21 metabolites was constructed and identified for GC diagnosis with AUCs of 0.921-0.971 and 0.907-0.940 in the discovery and verification dataset, respectively. In the prospective study (n=264 from lead centre), both NPELDI-MS and UPLC-MS were applied to detect and validate the metabolic panel, and the diagnostic AUCs were 0.855-0.918 and 0.856-0.916, respectively. Moreover, we constructed a prognosis scoring system for GC in retrospective cohort, which can effectively predict the survival of GC patients. We developed and validated diagnostic and prognostic models for GC, which also contribute to advanced metabolic analysis towards diseases, including but not limited to GC.


Geographic differences in the associations between impaired glucose regulation and cardiovascular risk factors among young adults.
To assess geographic differences in the association between BMI, blood pressure and lipid levels with impaired glucose regulation among young adults from various geographical regions. This was a cross-sectional study including data from 6987 participants aged ≤ 30 years from India, Singapore, Australia, Greenland, Kenya and Tanzania. Impaired glucose regulation was determined by the 75-g oral glucose tolerance test. For each geographical region, BMI, blood pressure and lipids were examined and compared between participants with normal glucose tolerance and those with impaired glucose regulation. Multiple logistic regression models were used to assess the association between risk factors and impaired glucose regulation. Indian and East African people had a higher prevalence of impaired glucose regulation compared with participants from other regions, despite their lower BMI. Compared with the other regions, blood pressure was lower among Indian and Singaporean people but higher in those from Greenland. Greenlanders had the highest, while Indian and East-African people, had the lowest level of HDL cholesterol. BMI was positively associated with impaired glucose regulation in all regions, and there were no statistically significant geographic differences. In the Indian, Singaporean and Australian participants, there was a positive association between blood pressure and impaired glucose regulation. Triglycerides were positively associated with and HDL cholesterol had no association with impaired glucose regulation in all geographical regions. Higher BMI and triglyceride levels were positively associated with prevalent impaired glucose regulation in all geographical regions. There were geographic differences in the association between impaired glucose regulation and blood pressure and lipids, probably reflecting environmental and genetic factors.


Growth-modulatory effects of heparin and VEGF165 on the choriocarcinoma cell-line JEG-3 and its expression of heparanase.
Expression of heparanase (HPSE) in tumor cells is strongly associated with invasion, metastasis and angiogenesis. It also plays a key role during pregnancy, in processes of implantation as well as placentation. Vascular endothelial growth factor (VEGF) and heparin are known to alter HPSE expression, with heparin given prophylactically to women with a history of placenta-mediated complications in subsequent pregnancies. We examined the growth-modulatory effects of different concentrations of heparin and VEGF on the choriocarcinoma cell-line JEG-3 and the expression of heparanase under VEGF and heparin by proliferation assays, PCR, and western blot. Proliferation of JEG-3 cells was induced by heparin in a dose-dependent manner, whereas highly concentrated VEGF led to a decreased cell proliferation. Both agents did not influence the HPSE-expression. The presumed pregnancy-protecting effects of heparin may partially be due to an increase of trophoblast proliferation and not via regulation of HPSE expression.


In situ chemistry of osteoporosis revealed by synchrotron infrared microspectroscopy.
Reduced bone density is a well-known feature of osteoporosis, yet little is known about the changes in the chemical composition of bone or the impact of such chemical changes on fracture risks. Using ovariectomized cynomolgus monkeys (Macaca fascicularis) as a model for the menopausal onset of osteoporosis, we examined the microscopic chemical changes of bone measured by synchrotron infrared microspectroscopy as a function of time after ovariectomy. The results demonstrate that cortical bone formed 1 or 2 years after ovariectomy, as identified by fluorochrome labeling, has a higher phosphate content (PO4(3-)/matrix ratio), a lower carbonate content (CO3(2-)/matrix ratio), and more mature collagen cross-links (nonreducible cross-link/reducible cross-link ratio) than that formed in sham-operated controls. Trabecular bone after ovariectomy shows no changes in phosphate content, a lower carbonate content, and immature collagen cross-linking. Treatment with a bone turnover suppressor, (nandrolone decanoate) reverses most of the ovariectomy-induced chemical changes in the cortical bone to the levels of the ovary-intact controls, but has little effect on the trabecular bone. These results demonstrate that bone newly synthesized after ovariectomy is chemically different from healthy bone within specific bone regions, which may contribute to reduced bone quality in osteoporosis.


Hydrophobic drug delivery by self-assembling triblock copolymer-derived nanospheres.
We describe the synthesis and characterization of a family of biocompatible ABA-triblock copolymers that comprised of hydrophilic A-blocks of poly(ethylene glycol) and hydrophobic B-blocks of oligomers of suberic acid and desaminotyrosyl-tyrosine esters. The triblock copolymers spontaneously self-assemble in aqueous solution into nanospheres, with hydrodynamic diameters between 40 and 70 nm, that do not dissociate under chromatographic and ultracentrifugation conditions. These nanospheres form strong complexes with hydrophobic molecules, including the fluorescent dye 5-dodecanoylaminofluorescein (DAF) and the antitumor drug, paclitaxel, but not with hydrophilic molecules such as fluorescein and Oregon Green. The nanosphere-paclitaxel complexes retain in vitro the high antiproliferative activity of paclitaxel, demonstrating that these nanospheres may be useful for delivery of the hydrophobic drugs.


Mammalian metallothionein is functional in yeast.
Expression of two monkey metallothioneins in yeast leads to complementation of both known functions of the endogenous yeast copperthionein gene, namely copper detoxification and autoregulation of transcription. The metallothionein-like proteins of higher and lower eukaryotes are therefore functionally analogous despite their dissimilar primary sequences.


How can today's substance-using youth be helped to quit? Perspectives of college students from Bangalore, India.
Substance use among college students is increasing, yet research regarding their viewpoints on how they can be helped is sparse in India. The purpose of this study was to explore in depth the perspectives of college students as to how college youth can be helped to quit the use of psychoactive substances. Data from focus group interviews with 38 adolescent college students were analyzed qualitatively to identify their viewpoints on how today's college youth can be helped to quit substance use. Interviews were transcribed verbatim, themes and subthemes were identified. Three major themes (with subthemes) were identified: (1) Patterns of use (commonly used substances, methods of using), (2) Perceived reasons for use (to reduce negative emotions, academic pressure, peer influence, more freedom, rebellious attitudes, media influence, modeling effect, childhood trauma, distrust from family/friends, lack of knowledge regarding the adverse impact of substances, poor life skills, cultural gender-based discrimination) and (3) Interventions needed to help college youth to quit substance use (need for interventions, basic principles to follow when developing interventions, content to be included, methods to be employed for delivering the intervention). The information from this study can guide the development of a comprehensive intervention that is relevant and tailor-made to the specific needs of the college student population.


Non-crop plants used as hosts by Drosophila suzukii in Europe.
The invasive spotted wing drosophila Drosophila suzukii, a fruit fly of Asian origin, is a major pest of a wide variety of berry and stone fruits in Europe. One of the characteristics of this fly is its wide host range. A better knowledge of its host range outside cultivated areas is essential to develop sustainable integrated pest management strategies. Field surveys were carried out during two years in Italy, the Netherlands and Switzerland. Fruits of 165 potential host plant species were collected, including mostly wild and ornamental plants. Over 24,000 D. suzukii adults emerged from 84 plant species belonging to 19 families, 38 of which being non-native. Forty-two plants were reported for the first time as hosts of D. suzukii. The highest infestations were found in fruits of the genera Cornus, Prunus, Rubus, Sambucus and Vaccinium as well as in Ficus carica, Frangula alnus, Phytolacca americana and Taxus baccata. Based on these data, management methods are suggested. Ornamental and hedge plants in the vicinity of fruit crops and orchards can be selected according to their susceptibility to D. suzukii. However, the widespread availability and abundance of non-crop hosts and the lack of efficient native parasitoids suggest the need for an area-wide control approach.


Phytic Acid-Based FeCo Bimetallic Metal-Organic Gels for Electrocatalytic Oxygen Evolution Reaction.
Electrocatalysts have been developed to improve the efficiency of gas release for oxygen evolution reaction (OER), and finding a simple and efficient method for efficient electrocatalysts has inspired research enthusiasm. Herein, we report bimetallic metal-organic gels derived from phytic acid (PA) and mixed transition metal ions to explore their performance in electrocatalytic oxygen evolution reaction. PA is a natural phosphorus-rich organic compound, which can be obtained from plant seeds and grains. PA reacts with bimetallic ions (Fe3+ and Co2+ ) in a facile one-pot synthesis under mild conditions to form PA-FeCo bimetallic gels, and the corresponding aerogels are further partially reduced with NaBH4 to improve the electrocatalytic activity. Mixed valence states of Fe(II)/Fe(III) and Co(III)/Co(II) are present in the materials. Excellent OER performance in terms of overpotential (257 mV at 20 mA cm-2 ) and Tafel slope (36 mV dec-1 ) is achieved in an alkaline electrolyte. This reduction method is superior to the pyrolysis method by well maintaining the gel morphology structure. This strategy is conducive to the further improvement of the performance of metal-organic electrocatalysts, and provides guidance for the subsequent application of metal-organic gel electrocatalysts.


Anterior pancreatic duct split prior to duct-to-mucosa pancreatico-jejunal anastomosis in pancreaticoduodenectomy.
A secure pancreatic-enteric anastomosis is widely accepted as the 'Achilles heel' in reconstruction following a pancreaticoduodenectomy. Most morbidity following the procedure is related to the failure of this anastomosis, resulting in intra-abdominal collections, secondary haemorrhage, delayed gastric emptying, need for radiological interventions and re-operation for some patients. Of several techniques available, the 'duct-to-mucosa' technique is widely employed for pancreaticojejunal anastomosis. Among several refinements to facilitate this anastomosis, viz; mobilization of pancreatic stump, magnification with loupes and modifications made on the jejunal side to enable a tension free anastomosis, none seems to address the pancreatic duct in particular. The operative technique of anterior pancreatic duct split described by us enables a wider, well visualized pancreatic duct for a secure duct to mucosa pancreaticojejunal anastomosis.


Child categorization.
Categorization is a process that spans all of development, beginning in earliest infancy yet changing as children's knowledge and cognitive skills develop. In this review article, we address three core issues regarding childhood categorization. First, we discuss the extent to which early categories are rooted in perceptual similarity versus knowledge-enriched theories. We argue for a composite perspective in which categories are steeped in commonsense theories from a young age but also are informed by low-level similarity and associative learning cues. Second, we examine the role of language in early categorization. We review evidence to suggest that language is a powerful means of expressing, communicating, shaping, and supporting category knowledge. Finally, we consider categories in context. We discuss sources of variability and flexibility in children's categories, as well as the ways in which children's categories are used within larger knowledge systems (e.g., to form analogies, make inferences, or construct theories). Categorization is a process that is intrinsically tied to nearly all aspects of cognition, and its study provides insight into cognitive development, broadly construed. WIREs Cogn Sci 2011 2 95-105 DOI: 10.1002/wcs.96 For further resources related to this article, please visit the WIREs website.


[Surgical treatment of temporomandibular joint: apropos of 94 cases].
The temporomandibular joint (TMJ) is a complex entity subjected to repeated stress with several symptoms. About one-third of people have at least one of those symptoms but only few (3 to 7%) need treatment. The aim of this retrospective study was to evaluate the results of temporomandibular joint surgery in 94 patients. Several data were used for decision-making and the surgical technique was adapted to the etiology. The type of postoperative physiotherapy performed depended on the type of pathology. Most patients who underwent surgery between 1989 and 2004 were women (83%). The mean age was 30 years. We performed 179 surgical procedures and among them 151 Dautrey procedures. In 28 cases miniplates were used to avoid recurrences. In 57 cases postoperative physiotherapy was performed. The mean postoperative mouth opening increase was 4.7 mm (+ 23%). There was no infection or lost of plate. The mean of follow-up was about 14 months. With a long follow-up and an acceptable number of patients and operations, this retrospective study demonstrated the effectiveness of the Dautrey procedure in TMJ subluxations.


Application of gene-shuffling for the rapid generation of novel [FeFe]-hydrogenase libraries.
A gene-shuffling technique was identified, optimized and used to generate diverse libraries of recombinant [FeFe]-hydrogenases. Six native [FeFe]-hydrogenase genes from species of Clostridia were first cloned and separately expressed in Escherichia coli concomitantly with the assembly proteins required for [FeFe]-hydrogenase maturation. All enzymes, with the exception of C. thermocellum HydA, exhibited significant activity when expressed. Single-stranded DNA fragments from genes encoding the two most active [FeFe]-hydrogenases were used to optimize a gene-shuffling protocol and generate recombinant enzyme libraries. Random sampling demonstrates that several shuffled products are active. This represents the first successful application of gene-shuffling using hydrogenases. Moreover, we demonstrate that a single set of [FeFe]-hydrogenase maturation proteins is sufficient for the heterologous assembly of the bioinorganic active site of several native and shuffled [FeFe]-hydrogenases.


Physician Assistants and the Expanding Global Health-Care Workforce.
The physician assistant and other types of medical providers with accelerated and focused training were developed to serve the specific health-care needs of individual countries. They have an important role in providing care globally in response to physician shortages. Working in over 50 nations, these clinicians increase access to team-based health care. This perspective explores the successes and challenges of these professionals as an international community. Steps are proposed to increase global awareness and acceptance of these professionals including platforms to increase discussion, scholarly activity, and collaboration.


A description of dynamical graphs associated to elementary regulatory circuits.
The biological and dynamical importance of feedback circuits in regulatory graphs has often been emphasized. The work presented here aims at completely describing the dynamics of isolated elementary regulatory circuits. Our analytical approach is based on a discrete formal framework, built upon the logical approach of R. Thomas. Given a regulatory circuit, we show that the structure of synchronous and asynchronous dynamical graphs depends only on the length of the circuit (number of genes) and on its sign (which depends on the parity of the number of negative interactions). This work constitutes a first step towards the analytical characterisation of discrete dynamical graphs for more complex regulatory networks in terms of contributions corresponding to their embedded elementary circuits.


Consequences of metabolic syndrome on postoperative outcomes after pancreaticoduodenectomy.
To analyze immediate postoperative outcomes after pancreaticoduodenectomy regarding metabolic syndrome. In two academic centers, postoperative outcomes of patients undergoing pancreaticoduodenectomy from 2002 to 2014 were prospectively recorded. Patients presenting with metabolic syndrome [defined as at least three criteria among overweight (BMI ≥ 28 kg/m²), diabetes mellitus, arterial hypertension and dyslipidemia] were compared to patients without metabolic syndrome. Among 270 consecutive patients, 29 (11%) presented with metabolic syndrome. In univariable analysis, patients with metabolic syndrome were significantly older (69.4 years vs 62.5 years, P = 0.003) and presented more frequently with soft pancreas (72% vs 22%, P = 0.0001). In-hospital morbidity (83% vs 71%) and mortality (7% vs 6%) did not differ in the two groups so as pancreatic fistula rate (45% vs 30%, P = 0.079) and severity of pancreatic fistula (P = 0.257). In multivariable analysis, soft pancreas texture (P = 0.001), pancreatic duct diameter < 3 mm (P = 0.025) and BMI > 30 kg/m² (P = 0.041) were identified as independent risk factors of pancreatic fistula after pancreaticoduodenectomy, but not metabolic syndrome. In spite of logical reasoning and appropriate methodology, present series suggests that metabolic syndrome does not jeopardize postoperative outcomes after pancreaticoduodenectomy. Therefore, definition of metabolic syndrome seems to be inappropriate and fatty pancreas needs to be assessed with an international consensual histopathological classification.


CART cell therapy for prostate cancer: status and promise.
In recent years, the, chimeric antigen receptor T (CAR-T) cell therapy as an adoptive immunotherapy has received great attention and made great breakthroughs. CAR-T cells show great specificity, targeting, and less major histocompatibility complex restriction in tumor immunotherapy, significantly different from traditional T cells. In spite of the progress of CART-T technology in the treatment of lymphoma, leukemia, and other blood system tumor, there are still many difficulties in the treatment of solid tumors by CAR-T technology. In this review, we will make a brief summary of the present situation of CAR-T cells in the treatment of prostate cancer, and discuss the promise of the application of this technology to prostate cancer therapy.


Highly Efficient Photocatalysts: Polyoxometalate Synthons Enable Tailored CdS-MoS2 Morphologies and Enhanced H2 Evolution.
The development of photocatalysts toward highly efficient H2 evolution reactions is a feasible strategy to achieve the effective conversion of solar energy and meet the increasing demand for new energy. To this end, we prepared two different CdS-MoS2 photocatalysts with unique morphologies ranging from hexagonal prisms to tetragonal nanotubes by carefully tuning polyoxometalate synthons. These two photocatalysts, namely, CdS-MoS2-1 and CdS-MoS2-2, both exhibited remarkable photocatalytic efficiency in H2 generation, among which CdS-MoS2-2 showed superior performance. In fact, the best catalytic hydrogen desorption rate of CdS-MoS2-2 is as high as 1815.5 μmol g-1 h-1. Such performance is superior to twice that of single CdS and almost four times that of pure MoS2. This obvious enhancement can be accredited to the highly open nanotube morphology and highly dispersed heterometallic composition of CdS-MoS2-2, which represents an excellent example of the highest noble-metal-free H2 evolution photocatalysts reported so far. Taken together, these findings suggest that the development of highly dispersed heterometallic catalysts is an auspicious route to realize highly efficient conversion of solar energy and that CdS-MoS2-2 represents a major advance in this field.


Design, synthesis, and evaluation of 3C protease inhibitors as anti-enterovirus 71 agents.
Human enterovirus (EV) belongs to the picornavirus family, which consists of over 200 medically relevant viruses. A peptidomimetic inhibitor AG7088 was developed to inhibit the 3C protease of rhinovirus (a member of the family), a chymotrypsin-like protease required for viral replication, by forming a covalent bond with the active site Cys residue. In this study, we have prepared the recombinant 3C protease from EV71 (TW/2231/98), a particular strain which causes severe outbreaks in Asia, and developed inhibitors against the protease and the viral replication. For inhibitor design, the P3 group of AG7088, which is not interacting with the rhinovirus protease, was replaced with a series of cinnamoyl derivatives directly linked to P2 group through an amide bond to simplify the synthesis. While the replacement caused decreased potency, the activity can be largely improved by substituting the alpha,beta-unsaturated ester with an aldehyde at the P1' position. The best inhibitor 10b showed EC(50) of 18 nM without apparent toxicity (CC(50)>25 microM). Our study provides potent inhibitors of the EV71 3C protease as anti-EV71 agents and facilitates the combinatorial synthesis of derivatives for further improving the inhibitory activity.


Polythiophene-gold nanoparticle hybrid systems: Langmuir-Blodgett assembly of nanostructured films.
In this work, we demonstrate a simple method of synthesizing nanoscale polythiophene-gold nanoparticle (AuNP) hybrid systems assembled by the Langmuir-Blodgett (LB) method. Regio-regular poly(3-(2-methoxyethoxy)ethoxymethyl)thiophene-2,5-diyl (PMEEMT) and poly(3-dodecylthiophene) (PDDT) were employed as the polymeric constituents. The presence of PDDT improved the amphiphilicity of PMEEMT by addressing the phase separation that occurred due to convective hydrodynamic instability on the substrate. 4 layer stacks of 90% and 99% PMEEMT films exhibited uniform film structure with a significant reduction in phase separation. A detailed mechanism for minimization of the surface effect has been proposed based on the interaction of polythiophenes with the substrate. For the first time, an ex situ approach has been adopted to incorporate AuNPs into LB films without affecting the film morphology and uniformity. The incorporation of AuNPs into the polythiophene matrix, aided by the affinity of sulphur for gold, was strongly dependent on the molecular arrangement of the matrix, which in turn depended on the composition of the matrix. The hybrid polythiophene films exhibited enhanced conductivity and can be applied in sensors, photovoltaics and memory devices.


Estimation of the poroelastic parameters of cortical bone.
Cortical bone has two systems of interconnected channels. The largest of these is the vascular porosity consisting of Haversian and Volkmann's canals, with a diameter of about 50 microm, which contains a.o. blood vessels and nerves. The smaller is the system consisting of the canaliculi and lacunae: the canaliculi are at the submicron level and house the protrusions of the osteocytes. When bone is differentially loaded, fluids within the solid matrix sustain a pressure gradient that drives a flow. It is generally assumed that the flow of extracellular fluid around osteocytes plays an important role not only in the nutrition of these cells, but also in the bone's mechanosensory system. The interaction between the deformation of the bone matrix and the flow of fluid can be modelled using Biot's theory of poroelasticity. However, due to the inhomogeneity of the bone matrix and the scale of the porosities, it is not possible to experimentally determine all the parameters that are needed for numerical implementation. The purpose of this paper is to derive these parameters using composite modelling and experimental data from literature. A full set of constants is estimated for a linear isotropic description of cortical bone as a two-level porous medium. Bone, however, has a wide variety of mechanical and structural properties; with the theoretical relationships described in this note, poroelastic parameters can be derived for other bone types using their specific experimental data sets.


Macroperipatus ohausi: redescription and taxonomic notes on its status (Onychophora: Peripatidae).
Onychophora have undergone a new wave of taxonomic revisions in the last three years. After a recent revision, only two species of Macroperipatus are registered from Brazil: Macroperipatus ohausi and Macroperipatus geayi. The former was only the second species of Onychophora to be described from Brazil, and is herein redescribed, illustrated, and its taxonomic status revised. Macroperipatus ohausi had only been collected at the type locality, Petrópolis, state of Rio de Janeiro, but has not been found there since its discovery. In 2009 we collected two specimens of this species in an Atlantic rain forest fragment in Nova Iguaçu in RPPN dos Petroleiros (also state of Rio de Janeiro). The color of the new specimens was interpreted and described based on the NBS/ISCC System of Color Designation, and corresponds only weakly to that described in earlier publications on M ohausi. The identification of M. ohausi was based solely on its morphology and compared with its original description. In addition, a female syntype of M. ohausi deposited in the Zoologisches Museum (Hamburg) was examined. We reinvestigated its external morphology and concluded that the dorsal papillae have been misinterpreted in M ohausi in previous studies of its integument. The new specimens examined are conspecific with M ohausi mainly by having conical primary papillae, different sized accessory papillae, and by the number of legs. Our material resembles.the original description of M ohausi, for example, in spinous pad and nephridial tubercles, even though these features are not represented in the original description and redescription ofM. ohausi; these features are further detailed here. We concluded that the dorsal papillae morphology of M ohausi, shares diagnostic characters, for example, with representatives of the genera Peripatus and Epiperipatus. The dorsal papillae are rounded and not square as in the original description and redescription. Another argument that supports our conclusion is that the RPPN dos Petroleiros, the locality where the new samples were collected, belongs to the same mountain chain and Atlantic mosaic as the original material of M ohausi. Furthermore, a male of M. ohausi is described here for the first time. Based on our morphological data, we transfered this species to the genus Epiperipatus, proposing a new combination, E. ohausi.


Pharyngeal morphogenesis requires fras1-itga8-dependent epithelial-mesenchymal interaction.
Both Fras1 and Itga8 connect mesenchymal cells to epithelia by way of an extracellular 'Fraser protein complex' that functions in signaling and adhesion; these proteins are vital to the development of several vertebrate organs. We previously found that zebrafish fras1 mutants have craniofacial defects, specifically, shortened symplectic cartilages and cartilage fusions that spare joint elements. During a forward mutagenesis screen, we identified a new zebrafish mutation, b1161, that we show here disrupts itga8, as confirmed using CRISPR-generated itga8 alleles. fras1 and itga8 single mutants and double mutants have similar craniofacial phenotypes, a result expected if loss of either gene disrupts function of the Fraser protein complex. Unlike fras1 mutants or other Fraser-related mutants, itga8 mutants do not show blistered tail fins. Thus, the function of the Fraser complex differs in the craniofacial skeleton and the tail fin. Focusing on the face, we find that itga8 mutants consistently show defective outpocketing of a late-forming portion of the first pharyngeal pouch, and variably express skeletal defects, matching previously characterized fras1 mutant phenotypes. In itga8 and fras1 mutants, skeletal severity varies markedly between sides, indicating that both mutants have increased developmental instability. Whereas fras1 is expressed in epithelia, we show that itga8 is expressed complementarily in facial mesenchyme. Paired with the observed phenotypic similarity, this expression indicates that the genes function in epithelial-mesenchymal interactions. Similar interactions between Fras1 and Itga8 have previously been found in mouse kidney, where these genes both regulate Nephronectin (Npnt) protein abundance. We find that zebrafish facial tissues express both npnt and the Fraser gene fibrillin2b (fbn2b), but their transcript levels do not depend on fras1 or itga8 function. Using a revertible fras1 allele, we find that the critical window for fras1 function in the craniofacial skeleton is between 1.5 and 3 days post fertilization, which coincides with the onset of fras1-dependent and itga8-dependent morphogenesis. We propose a model wherein Fras1 and Itga8 interact during late pharyngeal pouch morphogenesis to sculpt pharyngeal arches through epithelial-mesenchymal interactions, thereby stabilizing the developing craniofacial skeleton.


A model of differentiation in quantum bioinformatics.
Differentiation is a universal process found in various phenomena of nature. As seen in the example of cell differentiation, the creation diversity on individual's character is caused by environmental interactions. In this paper, we try to explain its mechanism, which has been discussed mainly in Biology, by using the formalism of quantum physics. Our approach known as quantum bioinformatics shows that the temporal change of statistical state called decoherence fits to describe non-local phenomena like differentiation.