Reduced compressibility and an inverse problem for a spinning gas.
A spinning ideal gas in a cylinder with a smooth surface is shown to have unusual properties. First, under compression parallel to the axis of rotation, the spinning gas exhibits reduced compressibility because energy can be stored in the rotation. Second, the spinning breaks the symmetry under which partial pressures of a mixture of gases simply add proportional to the constituent number densities. Thus, remarkably, in a mixture of spinning gases, an inverse problem can be formulated such that the gas constituents can be determined through external measurements only.


Impact of antibiotic resistance in gram-negative bacilli on empirical and definitive antibiotic therapy.
Serious infections with gram-negative pathogens continue to be associated with considerable mortality. Increasing antibiotic resistance in organisms such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae is contributing to difficulties with choosing antibiotics to prescribe for these infections. Optimization of therapy against these organisms starts with the initial empirical antibiotic choice. Surveillance data and hospital or unit antibiograms may inform this decision, although individualization of the initial regimen on the basis of prior antibiotic use and prior isolation of resistant pathogens may be more important. Combinations of antibiotics are often required empirically, and "combination antibiograms" may need to be developed for this purpose. Preliminary data suggest that extending the time over which a dose of antipseudomonal beta-lactam antibiotics is infused may improve clinical outcomes; however, this idea remains to be confirmed in randomized trials. The role of direct susceptibility testing in aiding more-rapid initiation of appropriate antibiotic therapy is also being studied. When identification and susceptibility testing is complete, the antibiotic regimen for infections due to gram-negative pathogens can be "fine tuned." On some occasions, this fine tuning necessitates the introduction of "salvage" antibiotics, such as colistin or tigecycline; on others, it necessitates de-escalation and early termination of therapy. The lack of new antibiotic options against gram-negative pathogens underscores the need for optimization of current therapies and prevention of the spread of these organisms.


Lavandula stoechas (L) a Very Potent Antioxidant Attenuates Dementia in Scopolamine Induced Memory Deficit Mice.
The objective of the current project was to explore the pharmacotherapeutic role of Lavandula stoechas (L) for the management of dementia. Dementia is considered a global challenge of current century seeking special attention of pharmacologists to explore its best remedies. Methanolic extract of aerial parts of L. stoechas was tested for phytochemical analysis along with free radical scavenging activity. Behavioral studies were performed on scopolamine induced amnesic mice by using elevated plus maze (EPM), light and dark test and hole board paradigms. Biochemical investigations were made after decapitating the mice. Their brains were isolated for biochemical estimation of acetylcholinesterase (AChE), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). Phytochemical study ensured the presence of total phenolic contents (285.91 ± 0.75 mg of GAE/g of extract), total flavonoids (134.06 ± 0.63 mg of RE/g of extract), total tannins (149.60 ± 0.93 mg of TAE/g of extract) and free radical scavenging activity (IC50 value = 76.73 μg/ml found by DPPH method). Behavioral studies indicated that animals of GVII showed higher inflexion ratio (0.40 ± 0.03) for EPM, spent most of time (227.17 ± 2.13 s) in dark area of light dark test and had many hole pockings (39.83 ± 1.88) for hole board paradigm. Moreover, biochemical studies revealed that methanolic extract of L. stoechas (800 mg/kg/p.o.) significantly (P < 0.001) reduced brain AChE and MDA levels while improved SOD, CAT, and GSH levels. Thus the findings suggest that L. stoechas stabilizes memory by enhancing cholinergic neurotransmission and by providing defense against oxidative stress in mice brain.


Investigating the Biocontrol Potential of the Natural Microbiota of the Apple Blossom.
Erwinia amylovora, the causative agent of fire blight, leads to important economic losses of apple and pear crops worldwide. This study aimed to investigate the potential of the resident microbiota of the apple blossom in combatting plant disease-causing organisms, with a focus on controlling fire blight. We obtained 538 isolates from sites around Canton Zurich, which we tested for activity against Pectobacterium carotovorum and E. amylovora. We also evaluated the isolates' activity against oomycete and fungal pathogens. Nine isolates showed activity against P. carotovorum, and eight of these against E. amylovora. Furthermore, 117 showed antifungal, and 161 anti-oomycete, activity. We assigned genera and in some cases species to 238 of the isolates by sequencing their 16S RNA-encoding gene. Five strains showed activity against all pathogens and were tested in a detached apple model for anti-E. amylovora activity. Of these five strains, two were able to antagonize E. amylovora, namely Bacillus velezensis #124 and Pantoea agglomerans #378. We sequenced the P. agglomerans #378 genome and analyzed it for secondary metabolite clusters using antiSMASH, revealing the presence of a putative bacteriocin cluster. We also showed that B. velezensis #124 exhibits strong activity against three different fungi and two oomycetes in vitro, suggesting a broader capacity for biocontrol. Our results showcase the protective potential of the natural apple blossom microbiota. We isolated two candidate biocontrol strains from apple blossoms, suggesting that they might persist at the most common entry point for the causative agent of fire blight. Furthermore, they are probably already part of the human diet, suggesting they might be safe for consumption, and thus are promising candidates for biocontrol applications.


The effect of age on the structural properties of human ribs.
Traumatic injury from motor vehicle crashes is a major cause of morbidity and mortality in the United States. The thorax is particularly at risk in motor vehicle crashes and is studied extensively by the injury biomechanics community. Unfortunately, most samples used in such research generally do not include children or the very elderly, despite the common occurrence of thorax injuries at both ends of the age spectrum. Rib fractures in particular, are one of the most common injuries, especially in the elderly, and can greatly affect morbidity, mortality, and quality of life. As the proportion of older adults in the population increases, such age-related fragility fractures will continually grow as a worldwide problem. Additionally, the risk of rib fracture significantly increases with age with confounding deleterious effects. Studies on elderly ribs are not uncommon, however very few studies exist which explore the mechanical properties and behavior of immature human bone, especially of ribs. Previous research identifying rib properties has provided useful information for numerous applications. However, no study has included a comprehensive sample of all ages (pediatric through elderly) in which ribs are tested in the same repeatable set-up. The goal of this study is to characterize differences in rib structural response across the age spectrum. One-hundred forty excised ribs from 70 individuals were experimentally tested in a custom-built pendulum fixture simulating a dynamic frontal impact. The sample includes individuals of ages ranging from six to 99 years old and includes 58 males and 12 females. Reported data include fracture location, displacement in the X and Y directions at fracture (δX, δY), force at fracture (FX), and linear structural stiffness (K). δX and K exhibit a statistically significant linear decrease with age (p<0.0001). FX reveals a trend in which a peak is reached in the young adult years (25-40). Detailed mechanical property data, as provided here, will prove useful for application in computational modeling efforts, which are vital to help prevent injury and to understand injury mechanisms from childhood through old age.


A new assay for hepatitis C virus (HCV) core antigen detection: an alternative to nucleic acid technologies in positive or indeterminate anti-HCV subjects?
Markers of viral replication are fundamental tools for understanding the mode of transmission, diagnosis and management of hepatitis C virus (HCV) infection. A new enzyme-linked immunosorbent assay for quantitative detection of free and complexed HCV core antigen (HCV Ag) has been developed. The aim of this study is to evaluate the clinical performance of the new test and compare it with the most widely used commercially available RT-PCR-based assay. To determine the cut-off value we tested 60 samples from anti-HCV negative samples and selected a qualitative cut-off value of 3 pg/ml. To evaluate the usefulness of the new assay in confirming serologically indeterminate results we collected 62 sera. To evaluate the HCV Ag and HCV-RNA relationship we tested 245 samples from patients with different clinical conditions. The results of 61 out of 62 (98.4%) anti-HCV indeterminate samples were found to agree, whereas only one serum was found to be RT-PCR positive and HCV Ag negative. We also found the results to agree in 77.6% (190/245) of the samples from infected patients, while we observed higher agreement in untreated patients, both with and without evidence of liver damage. The correlation coefficient (r) observed between HCV Ag and HCV-RNA was 0.88. The regression line meets the cut-off value at an HCV-RNA concentration of approximately 40,000 IU/ml. In conclusion, we found that the results from the total HCV Ag test agree with the RT-PCR results and therefore we believe that this test could become a useful tool for the diagnosis and management of HCV infection.


Hypertension in white South African miners.
A study was undertaken to determine the prevalence of hypertension among white South African miners, examine risk factors for hypertension, identify adverse outcomes of hypertension, and evaluate the extent and efficacy of treatment for hypertension. A total of 11686 miners was assessed. The prevalence of hypertension was comparable to that in three occupational groups in the USA and probably comparable to a group of urban males in Durban, although differences in methods did not allow precise comparison with this population. Obesity was an important risk factor. Electrocardiographic abnormalities, especially premature ventricular contractions, right and left bundle-branch block and myocardial infarction, were associated with elevated first recorded blood pressure. Of the 468 miners in the cross-sectional study who stated that they were taking antihypertensive medication, only 30% had diastolic blood pressures lower than 90 mmHg.


A multi-fidelity approach for reliability-based risk assessment of single-vehicle crashes.
Road vehicles are highly susceptible to single-vehicle crashes (SVCs) under complex road geometry and inclement weather, which can significantly threaten traffic safety and mobility of the whole traffic system. Most existing studies involve various simplifications and approximations to assess the associated SVC risks promptly, and therefore the assessment accuracy is often compromised. A novel multi-fidelity approach is developed for the reliability-based risk assessment of SVCs to balance the simulation accuracy and efficiency. Specifically, a high-fidelity transient dynamic vehicle model is introduced for a robust estimation of the vehicle dynamics under various driving environments, assisted by a low-fidelity simplified physics-based vehicle model to improve the computational efficiency. Based on the simulations of the two models, a new multi-fidelity improved cross entropy-based importance sampling (MFICE) algorithm is proposed for integrating multi-fidelity information and facilitating accurate and efficient reliability analysis. Five demonstrative cases are studied to evaluate the performance of the proposed approach, including the comparison with existing representative approaches. The results show that the proposed innovative multi-fidelity approach can provide a reliability evaluation of SVCs both accurately and efficiently, with obviously superior performance over typical state-of-the-art counterparts. Therefore, the proposed approach bears great potential on developing proactive and near real-time intelligent traffic operation and management strategies against SVCs in both normal and hazardous conditions.


Co-localization of fixative-modified glutamate and glutaminase in neurons of the spinal trigeminal nucleus of the rat: an immunohistochemical and immunoradiochemical analysis.
The spinal trigeminal nucleus (STN) is involved in processing orofacial sensory information, including tactile, thermal and nociceptive input, and relaying this information to higher brain centers, such as the thalamus. Very little information is available regarding the major excitatory neurotransmitters of this nucleus. The amino acid glutamate has been proposed as a major excitatory neurotransmitter in the central nervous system. In the present study, a novel monoclonal antibody, specific for fixative-modified glutamate, was utilized in conjunction with polyclonal antisera against glutaminase and aspartate aminotransferase (AATase) in an attempt to identify and map the locations of possible glutamatergic neurons in the STN. Co-localization experiments were performed by radiolabeling our monoclonal antibody and using this antibody in conjunction with the polyclonal antisera against glutaminase and AATase to evaluate the possible coexistence of glutamate with glutaminase or AATase in STN neurons. In all three subnuclei of the STN, immunohistochemically labeled neuronal profiles were observed with both of the polyclonal antisera and with the monoclonal antibody. Subnucleus caudalis contained the greatest number of labeled profiles per coronal section followed by subnucleus interpolaris and subnucleus oralis. The number and the distribution of immunoreactive profiles observed after the use of the glutaminase antiserum was comparable to that obtained with the monoclonal antibody. Co-localization experiments demonstrated that all glutaminase-like immunoreactive neurons also contained fixative-modified glutamate-like immunoradioactivity. These results suggest that glutamatergic neurons are present in the spinal trigeminal nucleus. The AATase antiserum labeled more neuronal profiles in each of the three subnuclei than did the glutaminase antiserum or the monoclonal antibody. In addition, co-localization experiments indicated that glutamate-like immunoreactivity was present in only two-thirds of AATase-like immunoreactive neuronal profiles. These findings suggest that glutaminase may be a more reliable marker of glutamatergic function than AATase.


Rab6 Is Required for Multiple Apical Transport Pathways but Not the Basolateral Transport Pathway in Drosophila Photoreceptors.
Polarized membrane trafficking is essential for the construction and maintenance of multiple plasma membrane domains of cells. Highly polarized Drosophila photoreceptors are an excellent model for studying polarized transport. A single cross-section of Drosophila retina contains many photoreceptors with 3 clearly differentiated plasma membrane domains: a rhabdomere, stalk, and basolateral membrane. Genome-wide high-throughput ethyl methanesulfonate screening followed by precise immunohistochemical analysis identified a mutant with a rare phenotype characterized by a loss of 2 apical transport pathways with normal basolateral transport. Rapid gene identification using whole-genome resequencing and single nucleotide polymorphism mapping identified a nonsense mutation of Rab6 responsible for the apical-specific transport deficiency. Detailed analysis of the trafficking of a major rhabdomere protein Rh1 using blue light-induced chromophore supply identified Rab6 as essential for Rh1 to exit the Golgi units. Rab6 is mostly distributed from the trans-Golgi network to a Golgi-associated Rab11-positive compartment that likely recycles endosomes or transport vesicles going to recycling endosomes. Furthermore, the Rab6 effector, Rich, is required for Rab6 recruitment in the trans-Golgi network. Moreover, a Rich null mutation phenocopies the Rab6 null mutant, indicating that Rich functions as a guanine nucleotide exchange factor for Rab6. The results collectively indicate that Rab6 and Rich are essential for the trans-Golgi network-recycling endosome transport of cargoes destined for 2 apical domains. However, basolateral cargos are sorted and exported from the trans-Golgi network in a Rab6-independent manner.


High-Dimensional Separability for One- and Few-Shot Learning.
This work is driven by a practical question: corrections of Artificial Intelligence (AI) errors. These corrections should be quick and non-iterative. To solve this problem without modification of a legacy AI system, we propose special 'external' devices, correctors. Elementary correctors consist of two parts, a classifier that separates the situations with high risk of error from the situations in which the legacy AI system works well and a new decision that should be recommended for situations with potential errors. Input signals for the correctors can be the inputs of the legacy AI system, its internal signals, and outputs. If the intrinsic dimensionality of data is high enough then the classifiers for correction of small number of errors can be very simple. According to the blessing of dimensionality effects, even simple and robust Fisher's discriminants can be used for one-shot learning of AI correctors. Stochastic separation theorems provide the mathematical basis for this one-short learning. However, as the number of correctors needed grows, the cluster structure of data becomes important and a new family of stochastic separation theorems is required. We refuse the classical hypothesis of the regularity of the data distribution and assume that the data can have a rich fine-grained structure with many clusters and corresponding peaks in the probability density. New stochastic separation theorems for data with fine-grained structure are formulated and proved. On the basis of these theorems, the multi-correctors for granular data are proposed. The advantages of the multi-corrector technology were demonstrated by examples of correcting errors and learning new classes of objects by a deep convolutional neural network on the CIFAR-10 dataset. The key problems of the non-classical high-dimensional data analysis are reviewed together with the basic preprocessing steps including the correlation transformation, supervised Principal Component Analysis (PCA), semi-supervised PCA, transfer component analysis, and new domain adaptation PCA.


The processing of Holliday junctions by BLM and WRN helicases is regulated by p53.
BLM, WRN, and p53 are involved in the homologous DNA recombination pathway. The DNA structure-specific helicases, BLM and WRN, unwind Holliday junctions (HJ), an activity that could suppress inappropriate homologous recombination during DNA replication. Here, we show that purified, recombinant p53 binds to BLM and WRN helicases and attenuates their ability to unwind synthetic HJ in vitro. The p53 248W mutant reduces abilities of both to bind HJ and inhibit helicase activities, whereas the p53 273H mutant loses these abilities. Moreover, full-length p53 and a C-terminal polypeptide (residues 373-383) inhibit the BLM and WRN helicase activities, but phosphorylation at Ser(376) or Ser(378) completely abolishes this inhibition. Following blockage of DNA replication, Ser(15) phospho-p53, BLM, and RAD51 colocalize in nuclear foci at sites likely to contain DNA replication intermediates in cells. Our results are consistent with a novel mechanism for p53-mediated regulation of DNA recombinational repair that involves p53 post-translational modifications and functional protein-protein interactions with BLM and WRN DNA helicases.


A New Multilevel CART Algorithm for Multilevel Data with Binary Outcomes.
The multilevel logistic regression model (M-logit) is the standard model for modeling multilevel data with binary outcomes. However, many assumptions and restrictions should be considered when applying this model for unbiased estimation. To overcome these limitations, we proposed a multilevel CART (M-CART) algorithm which combines the M-logit and single level CART (S-CART) within the framework of the expectation-maximization. Simulation results showed that the proposed M-CART provided substantial improvements on classification accuracy, sensitivity, and specific over the M-logit, S-CART, and single level logistic regression model when modeling multilevel data with binary outcomes. This benefit of using M-CART was consistently found across different conditions of sample size, intra-class correlation, and when relationships between predictors and outcomes were nonlinear and nonadditive.


Temporal trends and hospital variation in the management of severe hyperglycemia among patients with acute myocardial infarction in the United States.
Elevated blood glucose is associated with higher mortality in patients with acute myocardial infarction (AMI). Although clinical guidelines recommend targeted glucose control in this group, clinical trials have yielded inconclusive results. Our objective was to understand how this lack of evidence impacts the management of severe hyperglycemia in routine practice. We examined insulin use among 4,297 AMI admissions with a mean hospitalization blood glucose of ≥200 mg/dL across 55 US hospitals from 2000 to 2008. Temporal trends and interhospital variation in 2 measures of insulin use during hospitalization-any (subcutaneous, intravenous [IV], short acting, long acting) and IV insulin-were examined using hierarchical Poisson regression models. Of the 4,297 admissions, 2,618 (61%) received any insulin and 538 (13%) received IV insulin. After multivariable adjustment, a slight increase in insulin use was observed per admission year (relative risk [RR] 1.06, 95% CI 1.01-1.11). There was a modest (albeit nonsignificant) increase in IV insulin use seen before May 2004 (RR 1.18, 95% CI 0.96-1.47), with no significant change thereafter (RR 0.99, 95% CI 0.92-1.09). Marked variability in insulin use was observed across hospitals (median rate ratio 1.5 [any insulin] and 1.8 [IV insulin]), which did not change over time. Insulin use among patients with AMI and severe hyperglycemia has remained low over the past decade, with substantial and persistent interhospital variation. These observations reflect marked clinical uncertainty with regard to glucose management in AMI, underscoring the imperative for a definitive clinical trial in this field.


Impact of a Reading Priority Scoring System on the Prioritization of Examination Interpretations.
Our institution implemented a read priority scoring system to combat the known limitations of traditional methods for the prioritization of examination interpretations by radiologists. We aimed to determine the impact on report turnaround time (RTAT) and RTAT variability. On examination completion, technologists entered a read priority score (1-9) using provided definitions. We retrospectively reviewed the median RTAT and RTAT variability (i.e., interquartile range length) for radiology examinations (n = 615,541; 2011-2014). We used Spearman correlation coefficients to determine the relationships between read priority scores and the median RTAT and the RTAT variability by year. We compared median RTAT and RTAT variability between early (2011) versus late (2012-2014) adoption phases using distribution-free random permutation tests. Ranked correlations showed yearly improvement, leading to a near-perfect ranking of median RTAT (r = 0.98, p < 0.001) and a perfect ranking of RTAT variability (r = 1.00, p < 0.001) by nine levels of priority. Eight of the nine priority levels showed a reduction in median RTAT between the early and late phases, and the three most urgent levels--that is, 1, 2, and 3--improved by 23%, 5%, and 70% (all, p < 0.001), respectively. Only one priority level (4, defined as outpatient urgent [8% of studies]) showed significant worsening by 15% (p < 0.001). The three most urgent levels of priority also showed improvements in RTAT variability (61%, 17%, 71%, respectively; all, p < 0.01). Only the lowest level of priority (9) exhibited a significant worsening in RTAT variability by 9% (p < 0.01). A reading priority scoring system with defined clinical scenarios yielded desirable prioritization of examination interpretations by radiologists as evidenced by appropriate and improved stratification of RTATs and RTAT variability.


Morph-specific selection on floral traits in a polymorphic plant.
Correlations between phenotypic traits are common in many organisms, but the relative importance of nonadaptive mechanisms and selection for the evolution and maintenance of such correlations are poorly understood. In polymorphic species, morphs may evolve quantitative differences in additional characters as a result of morph-specific selection. The perennial rosette herb Primula farinosa is polymorphic for scape length. The short-scaped morph is less damaged by grazers and seed predators but is more strongly pollen limited than the long-scaped morph. We examined whether morph-specific differences in biotic interactions are associated with differences in selection on two other traits affecting floral display (number of flowers and petal size) and on one trait likely to affect pollination efficiency (corolla tube width) in three P. farinosa populations. Differences in selection between morphs were detected in one population. In this population, selection for more flowers and larger petals was stronger in the short-scaped than in the long-scaped morph, and although there was selection for narrower corolla tubes in the short-scaped morph, no statistically significant selection on corolla tube width could be detected in the long-scaped morph. In the study populations, the short-scaped morph produced more and larger flowers and wider corolla tubes. Current morph-specific selection was thus only partly consistent with trait differences between morphs. The results provide evidence of morph-specific selection on traits associated with floral display and pollination efficiency, respectively.


[Estimation of the survival rate, the relative density and the infection rate of a population of Haemagogus janthinomys Dyar (Diptera, Culicidae) from which strains of yellow fever were isolated in Brazilian Amazon].
The conditions of maintenance of YF virus in brazilian Amazonia are not yet elucidated. Generally, the presence of the virus is attested by human cases of sylvatic origin. During a survey done at the exact place where a man have probably been contaminated, it was possible for the first time in South America, to estimate the mean parity rate of a population of the potential vector Haemagogus janthinomys, from which the YF virus was actually isolated. The survival rate (Ts = 0.96), the biting rate (0.60 mosquitoes/man x hour), and the infection rate (1.71%) were also determinated for the same mosquitoes and have values compatible with the probable conditions of the human contamination. However, more data are needed, in particular in relation with other possible human contaminations and/or circulation of the YF virus in the monkey population (extension and duration of the epizootic episode), in order to know what maintenance cycle is prevalent in this region: a low level transmission, with the mosquito being a "vector-reservoir", or a "constantly moving epizootic wave".


Comparison of the Post-Caesarean Analgesic Effect of Adding Dexmedetomidine to Paracetamol and Ketorolac: A Randomized Clinical Trial.
Paracetamol and non-steroidal anti-inflammatory drugs (e.g. ketorolac) can be considered for mild to moderate post-caesarean pain. As a selective α-2 agonist adrenergic receptor, dexmedetomidine has analgesic and sedative effects without causing respiratory depression. This study aimed to evaluate the effects of adding dexmedetomidine to paracetamol or ketorolac on post-caesarean pain and the associated complications thereof. Sixty pregnant women, who were candidates for caesarean section with spinal anesthesia, were randomly assigned to either of two groups of 30 patients. For post-operative pain management, an intravenous patient-controlled analgesia (PCA) device was used for 24 hours. Dexmedetomidine (3 µg kg-1) was added to paracetamol (35 mg kg-1) in the group DP and to ketorolac (1 mg kg-1) in the group DK. Visual analog scale (VAS), Ramsay sedation scale, hemodynamic changes, rescue analgesic (meperidine) consumption, patient satisfaction, and possible complications were recorded at 6, 12, and 24, hours after surgery, and compared afterward. The pain score was significantly lower in the DK group than in the DP group (P < 0.05). The hemodynamics and sedation scale were similar in both groups. The total meperidine consumption was higher in the DP group, but it was not significantly different. Maternal satisfaction was greater in the DK group (P < 0.05). Concerning complications, the two groups did not show statistically significant differences (P = 0.4). The addition of dexmedetomidine to ketorolac, compared with its addition to paracetamol, causes further reduction in the post-operative pain score and provides more satisfaction.


TrkB induces EMT and has a key role in invasion of head and neck squamous cell carcinoma.
Head and neck squamous cell carcinoma (HNSCC) remains a significant public health problem, accounting for over 5% of all cancer-related deaths, and these deaths primarily result from metastatic disease. The molecular processes involved in HNSCC pathogenesis and progression are poorly understood, and here we present experimental evidence for a direct role of the cell surface receptor tyrosine kinase, TrkB, in HNSCC tumor progression. Using immunohistochemical analysis and transcriptional profiling of archival HNSCC tumor specimens, we found that TrkB and its secreted ligand, brain-derived neurotrophic factor (BDNF), are expresses in greater than 50% of human HNSCC tumors, but not in normal upper aerodigestive tract (UADT) epithelia. Studies with HNSCC cell lines reveal that in vitro stimulation with BDNF, the ligand for TrkB, upregulates the migration and invasion of HNSCC cells, and both transient and stable suppressions of TrkB result in significant abrogation of constitutive and ligand-mediated migration and invasion. Furthermore, enforced overexpression of TrkB results in altered expression of molecular mediators of epithelial-to-mesenchymal transition (EMT), including downregulation of E-cadherin and upregulation of Twist. Using an in vivo mouse model of HNSCC, we were able to show that downregulation of TrkB suppresses tumor growth. These results directly implicate TrkB in EMT and the invasive behavior of HNSCC, and correlate with the in vivo overexpression of TrkB in human HNSCC. Taken together, these data suggest that the TrkB receptor may be a critical component in the multi-step tumor progression of HNSCC, and may be an attractive target for much needed new therapies for this disease.


Intracerebral hematomas disappear on T2*-weighted images during normobaric oxygen therapy.
The aim of the present study was to investigate the effects of normobaric oxygen (NBO) therapy on T2*-weighted images of intracranial hemorrhages (ICHs). Two common models of ICH were performed in mice, and longitudinal T2*-weighted images of the hematomas were acquired under normoxia or NBO. The effects of NBO were also investigated on perfusion-weighted imaging, susceptibility-weighted imaging, and molecular imaging of vascular cell adhesion molecule-1 after ICH. Last, we performed neurological testing, including neuroscore, actimetry, and gait analysis (Catwalk), to study the influence of NBO on neurological outcome of mice presenting ICH. Our results demonstrated that NBO, even during a short period of time, dramatically reduces the sensitivity of T2*-weighted imaging to detect ICH. Moreover, we provide evidence that the disappearance of ICH on T2*-weighted imaging could be used to improve accuracy of perfusion-weighted imaging and to allow molecular imaging after ICH. Importantly, a 30-minute NBO preparation 24 hours after ICH onset does not influence neurological outcome. We provide an experimental demonstration that NBO significantly affects T2*-weighted imaging in ICH. Although this phenomenon could lead to inaccurate assessment of ICH volume, it could also be safely used to allow perfusion-weighted imaging and molecular imaging.


Photoprotective habits of patients with cutaneous lupus erythematosus.
Previous studies have suggested that patients with cutaneous lupus erythematosus (CLE) are deficient in sunscreen use. Use of other photoprotective methods by patients with CLE has not been assessed to our knowledge. We sought to identify demographic and clinical characteristics of patients with CLE who have the lowest overall sun-protection habits scores, and who are least likely to practice 5 individual photoprotective methods (ie, shade, sunscreen, long sleeves, hat, and sunglasses). A total of 105 patients with CLE at the University of Texas Southwestern Medical Center in Dallas completed a survey to evaluate their photoprotective practices. Additional information including demographics and clinical indicators related to CLE was collected from the patients. Patients with medium and dark skin (ie, Fitzpatrick skin types III-VI) and patients aged 31 to 50 years were the least likely CLE subgroups to practice overall photoprotection, as indicated by low sun-protection habits scores (P = .001 and P = .04, respectively). In terms of individual photoprotective methods, male patients with CLE were deficient in sunscreen use, but were more likely to wear hats than female patients with CLE. Sunscreen and sunglasses use was also significantly more infrequent in dark-skinned patients than those with Fitzpatrick skin types I to IV. Patients with CLE between the ages of 41 and 50 years were least likely to wear hats. This study was subject to reporter bias and did not cover barriers to and knowledge of photoprotection. Cultural customs and misconceptions shared by those from the general population have a significant influence on the photoprotective habits of this CLE population. These need to be addressed to improve photoprotection rates in these at-risk individuals.


Neuroprotectin D1 attenuates brain damage induced by transient middle cerebral artery occlusion in rats through TRPC6/CREB pathways.
Neuroprotectin D1 (NPD1) may serve an endogenous neuroprotective role in brain ischemic injury, yet the underlying mechanism involved is poorly understood. In the present study, we aimed to investigate whether intracerebroventricular (ICV) injection of NPD1 is neuroprotective against transient focal cerebral ischemia. We also sought to verify the neuroprotective mechanisms of NPD1. Rats subjected to 2 h ischemia followed by reperfusion were treated with NPD1 at 2 h after reperfusion. PD98059 was administered 20 min prior to surgery. Western blot analysis was performed to detect the protein levels of calpain-specific aII-spectrin breakdown products of 145 kDa (SBDP145), transient receptor potential canonical (subtype) 6 (TRPC6) and phosphorylation of cAMP/Ca2+-response element binding protein (p-CREB) at 12, 24 and 48 h after reperfusion. The immunoreactivity of p-CREB and TRPC6 was measured by quantum dot‑based immunofluorescence analysis. Infarct volume and neurological scoring were evaluated at 48 h after reperfusion. NPD1, when applied at 2 h after reperfusion, significantly reduced infarct volumes and increased neurological scores at 48 h after reperfusion, accompanied by elevated TRPC6 and p-CREB activity, and decreased SBDP145 activity. When mitogen‑activated protein kinase kinase (MEK) activity was specifically inhibited, the neuroprotective effect of NPD1 was attenuated and correlated with decreased CREB activity. Our results clearly showed that ICV injection of NPD1 at 2 h after reperfusion improves the neurological status of middle cerebral artery occlusion (MCAO) rats through the inhibition of calpain‑mediated TRPC6 proteolysis and the subsequent activation of CREB via the Ras/MEK/ERK pathway.


Predicting diffusive alveolar oxygen transfer from carbon monoxide-diffusing capacity in exercising foxhounds.
Although lung diffusing capacity for carbon monoxide (DL(CO)) is a widely used test of diffusive O2 transfer, few studies have directly related DL(CO) to O2-diffusing capacity (DL(O2)); none has used the components of Dl(CO), i.e., conductance of alveolar membrane and capillary blood, to predict DL(O2) from rest to exercise. To understand the relationship between DL(CO) and DL(O2) at matched levels of cardiac output, we analyzed cumulative data from rest to heavy exercise in 43 adult dogs, with normal lungs or reduced lung capacity following lung resection, that were studied by two techniques. 1) A rebreathing (RB) technique was used to measure Dl(CO) and pulmonary blood flow at two O2 tensions, independent of O2 exchange. DL(CO) was partitioned into CO-diffusing capacity of alveolar membrane and pulmonary capillary blood volume using the Roughton-Forster equation and converted into an equivalent DL(O2), [DL(O2)(RB)]. 2) A multiple inert-gas elimination technique (MIGET) was used to measure ventilation-perfusion distributions, O2 and CO2 exchange under hypoxia, to derive DL(O2) [DL(O2)(MIGET)] by the Lilienthal-Riley technique and Bohr integration. For direct comparisons, DL(O2)(RB) was interpolated to the cardiac output measured by the Fick principle corresponding to DL(O2)(MIGET). The DL(O2)-to-DL(CO) ratio averaged 1.61. Correlation between DL(O2)(RB) and DL(O2)(MIGET) was similar in normal and post-resection groups. Overall, DL(O2)(MIGET) = 0.975 DL(O2)(RB); mean difference between the two techniques was under 5% for both animal groups. We conclude that, despite various uncertainties inherent in these two disparate methods, the Roughton-Forster equation adequately predicts diffusive O2 transfer from rest to heavy exercise in canines with normal, as well as reduced, lung capacities.


Effect of caseinate glycation with oligochitosan and transglutaminase on the intestinal barrier function of the tryptic caseinate digest in IEC-6 cells.
Oligochitosan was used in this study to glycate commercial caseinate under the catalytic action of transglutaminase (TGase), followed by trypsin-mediated digestion. The prepared tryptic digests from both caseinate and oligochitosan-glycated caseinate were assessed and compared for their effects on the intestinal barrier function of a cell model (IEC-6 cells). Both digests had similar chemical features in the nine amino acids (except for Met) and free amino group contents, but had different glucosamine contents. Both digests at 12.5-100 μg mL-1 promoted IEC-6 cell growth by 105.6-135.1% and more importantly improved intestinal epithelial barrier integrity via increasing trans-epithelial electrical resistance, decreasing paracellular permeability from 100% to 64.1-85.4%, reducing bacterial translocation, and enhancing antibacterial activity against Escherichia coli. The obtained qPCR and western-blot assay results also demonstrated that both digests had promoting effects on the expression levels of several tight junction proteins such as ZO-1, occludin, and claudin-1. The oligochitosan-glycated caseinate digest always showed higher effects than the caseinate digest in the cells to retain the intestinal epithelial barrier function. This study thus highlights that the used TGase-type glycation endowed the oligochitosan-glycated caseinate with a potential functional food ingredient to strengthen the epithelial barrier function, which might be a helpful event to intestinal health.


Risk of colonization of central venous catheters: catheters for total parenteral nutrition vs other catheters.
Infected central venous catheters cause morbidity and mortality. To compare the risk for colonization of central venous catheters used for total parenteral nutrition with that of catheters used for other purposes. Retrospective review of prospectively acquired data on 260 patients with a stay in a surgical intensive care unit longer than 3 days. Single-lumen catheters used solely for total parenteral nutrition were inserted into the subclavian vein and cared for by a dedicated team. Catheters for other purposes were placed and cared for by other staff. Catheters were cultured if clinical findings suggested infection. Of 854 central venous catheters, 61 (7%) were used for total parenteral nutrition. During 4712 catheter days of observation, 89 catheters of all types were colonized. Risk factors for colonization included duration of catheterization (P < .001), having 3 or more lumens (hazard ratio, 1.7; 95% CI, 1.1-2.6), pulmonary artery catheterization (hazard ratio, 1.7; 95% CI, 1.1-2.7), and placement in the internal jugular vein (hazard ratio, 1.6; 95% CI, 1.1-2.5). Catheters used for total parenteral nutrition (hazard ratio, 0.14; 95% CI, 0.04-0.57) and those in the subclavian vein (hazard ratio, 0.51; 95% CI, 0.3-0.8) were at lower risk of colonization. In a multivariate Cox model, the only significant factor was a 5-fold lower risk of infection for catheters used for total parenteral nutrition (hazard ratio, 0.19; 95% CI, 0.04-0.83). Rates of colonization were lowest for catheters used solely for total parenteral nutrition, suggesting that a team approach improves patients' care.


Mechanism of photocatalytic CO2 reduction to HCO2H by a robust multifunctional iridium complex.
The tetradentate PNNP-type IrIII complex Mes-IrPCY2 ([Cl-IrIII-H]+) is reported to be an efficient catalyst for the reduction of CO2 to formate with excellent selectivity under visible light irradiation. Density functional calculations have been carried out to elucidate the mechanism and the origin of selectivity in the present work. Calculations suggest that the double-reduced complex 1-H (1[IrI-H]0) demonstrates higher activity than the single-reduced complex 2-H (2[IrIII(L˙-)-H]+), possibly owing to the higher hydride donor ability of the former compared to the latter; thus 1-H functions as the active species in the overall CO2 reduction reaction. In the HCOO- formation pathway, the hydride of 1-H performs a nucleophilic attack on CO2via an outer-sphere fashion to generate species 1-OCHO (1[IrI-OCHO]0), which then releases HCOO- to produce an IrI intermediate. A subsequent protonation and chloride coordination of the Ir center leads to the regeneration of catalyst 1[Cl-IrIII-H]+. For the CO production, a nucleophilic attack on CO2 takes place by the Ir atom of 1-Hvia an inner-sphere manner to afford complex O2C-3-H (1[O2C-IrIII-H]0), followed by a two-proton-one-electron reduction to furnish the OC-2-H complex (2[OC-IrIII(L˙-)-H]+) after liberating a H2O. Ultimately, CO is released to form 2-H. The stronger nucleophilicity as well as smaller steric hindrance of the hydride than the Ir atom of the active species 1-H (1[IrI-H]0) is found to account for the favoring of formate formation over CO formation. Meanwhile, the CO2 reduction reaction is calculated to be preferred over the hydrogen evolution reaction, and this is consistent with the experimental product distributions.


Schizotypy, Lifestyle Behaviors, and Health Indicators in a Young Adult Sample.
Problematic lifestyle behaviors and high rates of physical illness are well documented in people with schizophrenia, contributing to premature mortality. Yet, there is a notable absence of research examining general lifestyle and health issues in participants at risk for psychosis. This form of research may help identify concerns that exist during prodromal periods related to future outcomes. Accordingly, the current study examined lifestyle and health in a nonclinical sample of 530 young adults with varying levels of schizotypy. Increasing symptom severity was associated with greater somatic symptoms and poorer sleep quality across positive, negative, and disorganized domains. Elevated negative and disorganized symptoms were associated with significantly reduced health-related quality of life, while evidence for reduced engagement in health behaviors was largely limited to those with elevated negative schizotypy. No relationships emerged between symptom presentation/severity and body mass index or substance use, although zero-order correlations suggested an association between disorganized schizotypy and nicotine use. The pattern of relationships in the current study was consistent with findings from the ultra-high risk and clinical literature suggesting that lifestyle and health concerns may exist on a continuum with psychosis. Future research should seek to clarify if these patterns are associated with long-term physical or mental health outcomes.


The ovary: a target organ for 1,25-dihydroxyvitamin D3.
Using both clonal Chinese hamster ovary (CHO) cells in culture and the hen ovary, we have searched for the presence of specific 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] receptors. Receptor analyses were carried out on high salt cytosols of CHO cells and high salt extracts of hen ovarian nuclei that were originally isolated in low salt buffer. Both CHO and hen ovary contain a specific high affinity 1,25-(OH)2D3 receptor (Kd = 10(-10) - 10(-11) M), which sediments (3.3S) in high salt sucrose gradients identically to the chick intestinal receptor for 1,25-(OH)2D3. This 3.3S macromolecule from both sources absorbed to DNA-cellulose at 0.1 M KCl and eluted during a linear salt gradient at 0.2-0.22 M KCl, a property characteristic of the 1,25-(OH)2D3 receptor. Saturation analysis indicated that there are approximately 2000 copies of the receptor molecule per CHO cell. We also investigated the effect of 1,25-(OH)2D3 on ovarian cell growth in monolayer culture of CHO cells. Significant inhibition of CHO cell growth (up to 60%) was observed in the presence of physiological (100 pM) levels of 1,25-(OH)2D3 in the culture medium. This inhibition of growth was dose dependent and was accompanied by a parallel decrease in total cell protein. Concentrations of 25-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 as high as 1 nM did not affect CHO cell growth, indicating that, like receptor binding, cell proliferation is selectively influenced by 1,25-(OH)2D3 over other vitamin D metabolites. These data demonstrate that ovarian cells in mammals and birds possess the 1,25-(OH)2D3 receptor which may play a role in the effect of 1,25-(OH)2D3 on the growth of these cells in culture.


Stoichiometry of diauxic growth of a xylanase-producing Bacillus strain.
In this work, the establishment of material balances and stoichiometry of the growth of Bacillus sp. was undertaken. This strain produces high quantities of a xylanase suitable for use as bleach boost agent in chlorine-free bleaching sequences of paper pulp. As carbon dioxide plays an important role as a growth factor, bacterial growth in two fermentations, one fed with air and another fed with carbon-dioxide-enriched air, were compared. For this purpose, a method permitting the determination of the consumption of the two carbon sources, xylan and peptone, was proposed. The material balances revealed that in both cases, the bacteria first use peptone as their carbon source, and then xylan in the second part of the growth phase. The aerated culture showed diauxic growth on these two substrates, whereas carbon-dioxide-enriched air caused disappearance of the metabolic adaptation phase, and rendered biomass production more economic. The fermentation fed with air needed 30% more xylan than the fermentation fed with carbon-dioxide-enriched air for the same quantity of biomass produced.


COVID-19 and Long-Term Care Policy for Older People in Japan.
Japan's initial response to COVID-19 was similar to that of the US. However, the number of deaths in Japan has remained very low. Japan also stands out for the relatively low incidence of viral transmission in Long-Term Care Facilities (LTCFs) compared to both European countries and the United States. We argue that Japan's institutional decision to lockdown Long-Term Care facilities as early as mid-February - weeks earlier than most European countries and the US - contributed to lowering the number of deaths in LTCFs. We highlight a few lessons from the Japanese experience: (i) the presence of hierarchically organized government agencies whose sole missions are elderly care; (ii) the presence of effective communication channels between LTCFs and the regulatory authorities; and (iii) the well-established routine protocols of prevention and control in LTCFs.


A Soft Spot for Chemistry-Current Taxonomic and Evolutionary Implications of Sponge Secondary Metabolite Distribution.
Marine sponges are the most prolific marine sources for discovery of novel bioactive compounds. Sponge secondary metabolites are sought-after for their potential in pharmaceutical applications, and in the past, they were also used as taxonomic markers alongside the difficult and homoplasy-prone sponge morphology for species delineation (chemotaxonomy). The understanding of phylogenetic distribution and distinctiveness of metabolites to sponge lineages is pivotal to reveal pathways and evolution of compound production in sponges. This benefits the discovery rate and yield of bioprospecting for novel marine natural products by identifying lineages with high potential of being new sources of valuable sponge compounds. In this review, we summarize the current biochemical data on sponges and compare the metabolite distribution against a sponge phylogeny. We assess compound specificity to lineages, potential convergences, and suitability as diagnostic phylogenetic markers. Our study finds compound distribution corroborating current (molecular) phylogenetic hypotheses, which include yet unaccepted polyphyly of several demosponge orders and families. Likewise, several compounds and compound groups display a high degree of lineage specificity, which suggests homologous biosynthetic pathways among their taxa, which identifies yet unstudied species of this lineage as promising bioprospecting targets.


The diagnostic and prognostic utility of claudin expression in renal cell neoplasms.
This study evaluated the expression patterns of claudins 1, 3, 4, 7, and 8 in human renal cell carcinomas and oncocytomas and correlated expression with patient prognosis. Tissue microarrays were created from paraffin-embedded tissue samples from 141 patients with renal cell carcinomas or oncocytoma (90 clear cell, 22 papillary, 17 chromophobe renal cell carcinomas, and 12 oncocytomas). The staining pattern for claudins 3, 4, 7, and 8 was membranous and/or cytoplasmic, whereas claudin 1 was predominantly membranous in both nonneoplastic renal tissue and tumors. Negative to weak claudin 3 staining was predominantly detected in Fuhrman's grade 1 and 2 clear cell renal cell carcinomas (78%; P=0.016), suggesting that upregulation of claudin 3 potentially occurs concomitantly with increasing grade of clear cell renal cell carcinomas. In addition, Kaplan-Meier univariate analysis showed a significant inverse correlation between moderate to strong claudin 3 and 4 expression with overall survival in clear cell renal cell carcinomas (P=0.038 and P=0.031). Moderate to strong claudin 7 expression was significantly more common in chromophobe renal cell carcinomas (94%) than in oncocytomas (55%; P=0.041). Claudin 8 staining was moderate to strong in 92% of oncocytomas, which differentiated them from papillary and clear cell renal cell carcinomas (14 and 12%; both P<0.0001). Only negative to weak claudin 8 staining was detected in all chromophobe renal cell carcinomas, whereas there were no claudin 8 negative oncocytomas and 8% exhibited a weak staining pattern (P<0.0001). Due to their distinctive expression patterns, claudins 7 and 8 can be used as useful immunohistochemical markers for the separation of chromophobe renal cell carcinomas from oncocytomas, whereas claudins 3 and 4 may serve as indicators of prognosis in clear cell renal cell carcinomas.


Diagnosis of extrapulmonary tuberculosis by Gen-Probe amplified Mycobacterium tuberculosis direct test.
A total of 294 specimens collected from nonrespiratory sites of 268 patients were tested for direct detection of Mycobacterium tuberculosis complex by the Gen-Probe Amplified Mycobacterium tuberculosis Direct Test (AMTD). The specimens included ascitic, pleural, pericardial, and synovial fluids, abscess aspirates, and tissue and lymph node biopsy samples, as well as gastric aspirates and cerebrospinal fluid samples. All samples were processed by the N-acetyl-L-cysteine-sodium hydroxide decontamination procedure prior to testing. Twenty samples showed acid-fast bacilli on auramine staining, and 48 samples were positive by AMTD, 9 of which were negative for M. tuberculosis complex by culture. After reviewing the patients clinical charts to resolve discrepancies, the test result of one cerebrospinal fluid sample was considered to be false positive by AMTD. The overall sensitivity, specificity, positive predictive value, and negative predictive value were 83.9, 99.6, 97.9, and 96.3%, respectively. No significant differences were found when AMTD results obtained with specimens of nonrespiratory origin were compared with assay results obtained with samples of respiratory origin (P > 0.05). In conclusion, our results demonstrate that AMTD performs equally well with all types of specimens.


Purification and characterization of human neuropeptide Y from adrenal-medullary phaeochromocytoma tissue.
Human neuropeptide Y was isolated from acid extracts of adrenal-medullary phaeochromocytoma tissue. After (NH4)2SO4 fractionation, the neuropeptide Y-like immunoreactivity was purified from the resolubilized 80%-saturation-(NH4)2SO4 peptide-rich precipitate, by gel filtration, cation-exchange chromatography and reverse-phase high-pressure liquid chromatography. Amino acid analysis of the peptide revealed a composition almost identical with that of the pig peptide, the exception being the loss of one leucine residue and its replacement with methionine. Tryptic digestion of the peptide and subsequent amino acid analysis of the fragments further confirmed the identity of the peptide. Carboxypeptidase Y digestion of the (1-19)-peptide tryptic fragment has shown the methionine to be located at position 17 in human neuropeptide Y.


Role of molecular imaging with positron emission tomographic in aortic aneurysms.
Aortic aneurysms (AA) are often asymptomatic before the occurrence of acute, potentially fatal complications including dissection and/or rupture. Beyond aortic size, the ability to assess aortic wall characteristics and processes contributing to aneurysm development may allow improved selection of patients who may benefit from prophylactic surgical intervention. Current risk stratification for aneurysms relies upon routine noninvasive imaging of aortic size without assessing the underlying pathophysiologic processes, including features such as inflammation, which may be associated with aneurysm development and progression. The use of molecular imaging modalities with positron emission tomographic (PET) scan allows characterization of aortic wall inflammatory activity. Elevated uptake of Fuorine-2-deoxy-D-glucose (FDG), a radiotracer with elevated avidity in highly-metabolic cells, has been correlated with the development and progression of both abdominal and thoracic AA in a number of animal models and clinical studies. Other novel PET radiotracers targeting matrix metalloproteinases (MMPs), mitochondrial translocator proteins (TSPO) and endothelial cell adhesion molecules are being investigated for clinical utility in identifying progression of disease in AA. By further defining the activation of molecular pathways in assessing aortic regions at risk for dilatation, this imaging modality can be integrated into future clinical decision-making models.


[Congenital heart diseases and sports].
Congenital heart diseases are a frequent cause of cardiology consultation. New diagnostic and therapeutic techniques have allowed greater survival and quality of life of patients who wish to participate in sports. What they can do is not always easy to determine. Guidelines are helpful at the time of deciding, although finally is the doctor the one that must determine in each case the situation of the patient and the type of exercise they can do depending on the severity and type of cardiopathy.


Angiographic Coronary Spasm in a Case of Spontaneous Subarachnoid Hemorrhage Mimicking Acute Myocardial Infarction.
Neurologic stunned myocardium after subarachnoid hemorrhage (SAH) has been evidenced. Clinical presentations manifested as ST segment elevation by electrocardiography (ECG), left ventricular wall motion abnormality by echocardiography, and abnormal cardiac markers. The pathophysiology remains controversial. Coronary artery spasm has been proposed as a possible mechanism. However, most SAH patients with ECG and echocardiographic findings suggestive of myocardial infarction were lacking of angiographic evidence of vasospasm. We present a case of 66-year-old man complained chest pain with transient conscious loss on the street. He was sent to our emergency room by witness with clear consciousness and electrocardiography showing prominent ST-segment elevation. Because chest tightness was complained, emergent catheterization was arranged immediately. Coronary angiography demonstrated a narrowing lesion on mid right coronary artery without atherosclerotic change on other site. He was successfully treated with primary coronary balloon angioplasty for the narrowing lesion. Then the patient was sent to intensive care unit for further care. His following ECG demonstrated sinus rhythm with ectopic beats without ST segment elevation. Unfortunately, he became irritable and deterioration of conscious level few hour later. Computer tomography revealed subdural and subarachnoid hemorrhage. Conservative treatment was suggested by neurological surgeon consulted. The clinical presentation of the SAH patient mimicked acute myocardial infarction and coronary spasm was evidenced by angiography. We report the case and review the articles.


Hackflex: low-cost, high-throughput, Illumina Nextera Flex library construction.
We developed a low-cost method for the production of Illumina-compatible sequencing libraries that allows up to 14 times more libraries for high-throughput Illumina sequencing to be generated for the same cost. We call this new method Hackflex. The quality of library preparation was tested by constructing libraries from Escherichia coli MG1655 genomic DNA using either Hackflex, standard Nextera Flex (recently renamed as Illumina DNA Prep) or a variation of standard Nextera Flex in which the bead-linked transposase is diluted prior to use. In order to test the library quality for genomes with a higher and a lower G+C content, library construction methods were also tested on Pseudomonas aeruginosa PAO1 and Staphylococcus aureus ATCC 25923, respectively. We demonstrated that Hackflex can produce high-quality libraries and yields a highly uniform coverage, equivalent to the standard Nextera Flex kit. We show that strongly size-selected libraries produce sufficient yield and complexity to support de novo microbial genome assembly, and that assemblies of the large-insert libraries can be much more contiguous than standard libraries without strong size selection. We introduce a new set of sample barcodes that are distinct from standard Illumina barcodes, enabling Hackflex samples to be multiplexed with samples barcoded using standard Illumina kits. Using Hackflex, we were able to achieve a per-sample reagent cost for library prep of A$7.22 (Australian dollars) (US $5.60; UK £3.87, £1=A$1.87), which is 9.87 times lower than the standard Nextera Flex protocol at advertised retail price. An additional simple modification and further simplification of the protocol by omitting the wash step enables a further price reduction to reach an overall 14-fold cost saving. This method will allow researchers to construct more libraries within a given budget, thereby yielding more data and facilitating research programmes where sequencing large numbers of libraries is beneficial.


The Hepatitis C virus NS5A and core proteins exert antagonistic effects on HAMP gene expression: the hidden interplay with the MTF-1/MRE pathway.
Hepcidin, a 25-amino acid peptide encoded by the HAMP gene and produced mainly by hepatocytes and macrophages, is a mediator of innate immunity and the central iron-regulatory hormone. Circulating hepcidin controls iron efflux by inducing degradation of the cellular iron exporter ferroportin. HCV infection is associated with hepatic iron overload and elevated serum iron, which correlate with poor antiviral responses. The HCV nonstructural NS5A protein is known to function in multiple aspects of the HCV life cycle, probably exerting its activity in concert with cellular factor(s). In this study, we attempted to delineate the effect of HCV NS5A on HAMP gene expression. We observed that transient transfection of hepatoma cell lines with HCV NS5A resulted in down-regulation of HAMP promoter activity. A similar effect was evident after transduction of Huh7 cells with a recombinant baculovirus vector expressing NS5A protein. We proceeded to construct an NS5A-expressing stable cell line, which also exhibited down-regulation of HAMP gene promoter activity and significant reduction of HAMP mRNA and hepcidin protein levels. Concurrent expression of HCV core protein, a well-characterized hepcidin inducer, revealed antagonism between those two proteins for hepcidin regulation. In attempting to identify the pathways involved in NS5A-driven reduction of hepcidin levels, we ruled out any NS5A-induced alterations in the expression of the well-known hepcidin inducers SMAD4 and STAT3. Further analysis linked the abundance of intracellular zinc ions and the deregulation of the MTF-1/MRE/hepcidin axis with the observed phenomenon. This effect could be associated with distinct phases in HCV life cycle.


Smart pump alerts: all that glitters is not gold.
The implementation of smart pump technology can reduce the incidence of errors in the administration of intravenous drugs. This approach involves developing drug libraries for specific units and setting hard and soft limits for each drug. If a programming error occurs and these limits are exceeded, an alarm sounds and the infusion can be blocked. A detailed analysis of these alarms is essential in order not to bias the results in favor of a positive impact of this technology. To evaluate the results of the first analysis of the use of smart infusion pumps and to assess the significance and practical implications of the alarms sounded. The study was performed by a multidisciplinary team that consisted of a clinical pharmacist, a pediatrician from the pediatric intensive care unit (PICU), and the chief nurse of the unit. A library of 108 drugs was developed over a 7-month period and introduced into 40 syringe pumps and 12 volumetric pumps (Alaris(®) with Plus software) before being applied in 6 of the 11 beds in the PICU. After four month's use, data were analyzed using the Guardrails(®) CQI v4.1 Event Reporter program. Following the first four months of implementation, compliance with the drug library was 87%. By analyzing the alerts triggered, we were able to detect problems such as the need to increase user training, readjust limits that did not correspond to clinical practice, correct errors in the editing of the drug library and including a training profile. It is difficult to obtain accurate data on the true impact of this technology in the early stages of its implementation. This preliminary analysis allowed us to identify improvement measures to distinguish, in future evaluations, the alarms triggered by a real programming error from those caused by incorrect use.


Porcine global flash multifocal electroretinogram: possible mechanisms for the glaucomatous changes in contrast response function.
The aim of this study was to obtain a better understanding of the cellular contributions to the porcine global flash mfERG by using a pharmacologic dissection method, together with the method using variation of stimulus contrast which has been used to demonstrate mfERG changes in human glaucoma. Global flash mfERGs with different stimulus-contrast settings (99%, 65%, 49% or 29%) were recorded from 14 eyes of ten 6-week-old Yorkshire pigs in control conditions and after suppression of inner retinal responses with inhalation of isoflurance (ISO), and injections of tetrodotoxin (TTX) and N-methyl-d-aspartic acid (NMDA). ON- and OFF-pathway responses were isolated by injection of 2-amino-4-phosphonobutyric acid (APB) and cis-2,3-piperidinedicarboylic acid (PDA). The porcine global flash mfERG consisted of an early direct component (DC) and a late induced component (IC). ISO and TTX removed inner retinal contributions to the IC; NMDA application further abolished the oscillatory wavelets in the DC and removed the residual IC waveform. The inner retina contributed regular oscillation-like wavelets (W1, W2 and W3) to the DC and shaped the IC. After removing the inner retinal contributions, the porcine global flash mfERG waveform becomes comparable to that obtained with conventional mfERG stimulation. The remaining waveform (smoothed DC) was mainly contributed by the ON- and OFF-bipolar cells as revealed after APB or PDA injection. Photoreceptors contributed a small signal to the leading edge of N1. The characteristic of contrast response function of DC was demonstrated to be contributed by the inner retinal oscillation-like wavelets. We believe that the DC of the porcine global flash mfERG is mainly composed of contributions from photoreceptors, and ON- and OFF-bipolar cells, where inner retinal activity partially shaped the DC with superimposed regular wavelets. However, the IC is dominated by inner retinal activity. The contrast response functions of DC consisted of both outer retinal response and oscillation-like wavelets of the inner retinal response. Both contain different characteristics during contrast modulation of the stimulus, where the changes of W2 of the inner retinal response seem independent of contrast modulation. The DC contrast response feature depends mainly on the relative contribution of inner retinal activities; the loss of inner retinal cells may alter the DC contrast response function, making it tend toward linearity.


Metallic glasses.
Amorphous metallic alloys, relative newcomers to the world of glasses, have properties that are unusual for solid metals. The metallic glasses, which exist in a very wide variety of compositions, combine fundamental interest with practical applications. They also serve as precursors for exciting new nanocrystalline materials. Their magnetic (soft and hard) and mechanical properties are of particular interest.


Contribution of decreased serotonin release to the antidyskinetic effects of deep brain stimulation in a rodent model of tardive dyskinesia: comparison of the subthalamic and entopeduncular nuclei.
Mechanisms whereby deep brain stimulation (DBS) of the subthalamic nucleus (STN) or internal globus pallidus (GPi) reduces dyskinesias remain largely unknown. Using vacuous chewing movements (VCMs) induced by chronic haloperidol as a model of tardive dyskinesia (TD) in rats, we confirmed the antidyskinetic effects of DBS applied to the STN or entopeduncular nucleus (EPN, the rodent homolog of the GPi). We conducted a series of experiments to investigate the role of serotonin (5-HT) in these effects. We found that neurotoxic lesions of the dorsal raphe nuclei (DRN) significantly decreased HAL-induced VCMs. Acute 8-OH-DPAT administration, under conditions known to suppress raphe neuronal firing, also reduced VCMs. Immediate early gene mapping using zif268 in situ hybridization revealed that STN-DBS inhibited activity of DRN and MRN neurons. Microdialysis experiments indicated that STN-DBS decreased 5-HT release in the dorsolateral caudate-putamen, an area implicated in the etiology of HAL-induced VCMs. DBS applied to the EPN also suppressed VCMs but did not alter 5-HT release or raphe neuron activation. While these findings suggested a role for decreased 5-HT release in the mechanisms of STN DBS, further microdialysis experiments showed that when the 5-HT lowering effects of STN DBS were prevented by pretreatment with fluoxetine or fenfluramine, the ability of DBS to suppress VCMs remained unaltered. These results suggest that EPN- and STN-DBS have different effects on the 5-HT system. While decreasing 5-HT function is sufficient to suppress HAL-induced VCMs, 5-HT decrease is not necessary for the beneficial motor effects of DBS in this model.


Retinopathy of prematurity prevention, screening and treatment programmes: Progress in India.
India is home to largest number of preterm births and neonates at risk of developing retinopathy of prematurity. Being a large heterogenous country, different approaches including training of local ophthalmologists, tele-screening by ophthalmic technicians carrying wide-angle retinal cameras and use of low-cost retinal cameras by neonatal unit healthcare providers are being tested to expand the coverage of screening.


Corticotropin (ACTH)-reactive immunoglobulins in adolescents in relation to antisocial behavior and stress-induced cortisol response. The TRAILS study.
Elevated levels of corticotropin (ACTH)-reactive immunoglobulins (ACTH IgG) were found in males with conduct disorder, suggesting their involvement in the biology of antisocial behavior. We first aimed to confirm these findings in a large general population sample of adolescents. Secondly, we studied the association between ACTH IgG levels and hypothalamic-pituitary-adrenal (HPA) axis response to stress. Free and total ACTH IgG levels were measured in sera of 1230 adolescents (15-18 years). HPA axis activity was determined by measuring salivary cortisol before, during, and after a social stress test. Antisocial behavior was assessed using the Antisocial Behavior Questionnaire. ACTH peptide and IgG affinity kinetics for ACTH were assayed in a subsample of 90 adolescents selected for high or low ACTH IgG levels. In boys, higher total ACTH IgG levels were associated with higher antisocial behavior scores (β=1.05, p=0.04), especially at high levels of free ACTH IgG. In girls, antisocial behavior was associated with low free ACTH IgG levels (β=-0.20, p=0.04). Stress-induced cortisol release was associated with free ACTH IgG in boys (βareaunderthecurve=-0.67, p<0.01), and with total ACTH IgG in girls (βrecovery=0.84, p=0.05). The affinity kinetics assay showed that ACTH IgG association rates were lower in both boys and girls with high ACTH IgG levels. These data show that ACTH IgG levels are related to antisocial behavior and HPA axis response to stress in adolescents. The mechanisms behind these associations, including different ACTH binding properties of IgG in subjects with antisocial behavior, deserve further attention.


Cardiac and red blood cell glutathione peroxidase: results of a prospective randomized trial in patients on total parenteral nutrition.
Oxygen derived free radicals and peroxides result from many antitumor treatments, including radiation and anthracyclines. Doxorubicin cardiotoxicity is thought to result from free radical induced lipid peroxidation. The heart has less active detoxification enzymes than does the liver and depends on selenium dependent glutathione peroxidase (GSH-PX) for this function. We did a sequential prospective trial in patients with totally controlled parenteral diets to examine the activity of red blood cell GSH-PX in patients with and without malignant disease. Decreased GSH-PX activity was found in 54% of the patients on parenteral nutrition and was more common in the older of these patients and in those with the greatest weight loss. In the absence of selenium supplementation, the RBC GSH-PX activity declines steadily, but with supplementation this was prevented or reversed. Because selenium deficiency can manifest as a cardiomyopathy, we measured the enzyme activity in the hearts of five patients who had died. The cardiac enzyme activity correlated strongly with the RBC levels. Significantly decreased GSH-PX has been shown in animals to be associated with changes in other enzymes critical both to activation and detoxification of carcinogens as well as antitumor drugs. Abnormality of selenium status might be a previously unsuspected contributor to interpatient variation in drug effects.


A cross-sectional study of major repeaters: a distinct phenotype of suicidal behavior.
The characterization of major repeaters (individuals with ≥ 5 lifetime suicide attempts) is a neglected area of research. Our aim was to establish whether or not major repeaters are a distinctive suicidal phenotype, taking into account a wide range of potential competing risks including sociodemographic characteristics, personal and familial history, psychiatric diagnoses, and personality traits. This cross-sectional study included 372 suicide attempters admitted to a specialized unit for suicide attempters in Montpellier University Hospital, Montpellier, France, between October 12, 2000, and June 10, 2010. Logistic regression models controlling for potential confounders were used. When compared with subjects who attempted suicide < 5 times, major repeaters were more likely to be female (odds ratio [OR] = 5.54; 95% CI, 1.41-21.81), to have a lower educational level (OR = 5.1; 95% CI, 1.55-17.2), to have lifetime diagnoses of anorexia nervosa (OR = 3.45; 95% CI, 1.10-10.84) and substance dependence (OR = 5.00; 95% CI, 1.37-18.27), and to have lower levels of anger expressed outward (OR = 0.17; 95% CI, 0.06-0.47) and higher levels of trait anger (OR = 2.82; 95% CI, 1.18-6.75). Major repeaters had significantly higher suicide risk (lethality) scores (OR = 2.14; 95% CI, 1.08-4.23). Major repeaters are a distinctive suicidal phenotype characterized by a distinctive sociodemographic (ie, female gender, low education) and clinical profile (ie, trait anger, substance dependence, anorexia nervosa). If our results are replicated, specific preventive plans should be tailored to major repeaters.


Extracranial - Intracranial Bypass for Moyamoya Disease: The Influence of Racial and Socioeconomic Disparities on Non-routine Discharge - A National Inpatient Sample Analysis.
Extracranial-intracranial (EC-IC) bypass is an established therapeutic option for Moyamoya Disease (MMD). However, little is known about the effects of racial and ethnic disparities on outcomes. This study assessed trends in EC-IC bypass outcomes among MMD patients stratified by race and ethnicity. Utilizing the US National Inpatient Sample, we identified MMD patients undergoing EC-IC bypass between 2002 and 2020. Demographic and hospital-level data were collected. Multivariable analysis was conducted to identify independent factors associated with outcomes. Trend analysis was performed using piecewise joinpoint regression. Out of 14,062 patients with MMD, 1,771 underwent EC-IC bypass. Of these, 60.59% were White, 17.56% were Black, 12.36% were Asians, 8.47% were Hispanic, and 1.02% were Native Americans. Discharge to non-home was noted in 21.7% of cases, with a 6.7% death and 3.8% postoperative neurologic complications rates. EC-IC bypass was more commonly performed in Native Americans (23.38%) and Asians (17.76%). Hispanics had the longest mean length of stay (8.4 days) and lower odds of non-home discharge compared to Whites (OR: 0.64; 95% CI 0.40-1.03; p=0.04). Patients with Medicaid, private insurance, self-payers, and insurance paid by other governments had lower odds of non-home discharge than those with Medicare. This study highlights racial and socioeconomic disparities in EC-IC bypass for patients with MMD. Despite these disparities, we did not find any significant difference in the quality of care. Addressing these disparities is essential for optimizing MMD outcomes.


Preface to Special Issue of ChemSusChem on Perovskite Optoelectronics.
This Editorial introduces one of two companion Special Issues on "Halide Perovskites for Optoelectronics Applications" in ChemSusChem and Energy Technology following the ICMAT 2017 Conference in Singapore. More information on the other Special Issue can be found in the Editorial published in Energy Technology.


Analysis of Injuries and Prehospital Interventions Sustained by Females in the Iraq and Afghanistan Combat Zones.
Background: Women served in both combat and non-combat units in the recent conflicts in Iraq and Afghanistan. Moreover, the recent conflicts lacked traditional separation of civilians from combatants carrying additional risk for injury to local civilians. There is a relative paucity of data specific to this topic. We compare injury patterns and interventions performed in the prehospital, combat setting among females versus males. Methods: This is a secondary analysis of previously published data from the Department of Defense Trauma Registry. We included all subjects that had at least one prehospital intervention documented. We compared variables between females and males. Results: From January 2007 to August 2016, our inclusion criteria captured 19,485 males and 533 females. Female casualties were older (median age 29 vs. 25), less likely to have sustained injuries from explosives (48.0% vs. 56.8%), and more severely injured as measured by median composite injury scores (10 vs. 9). Most subjects were in Afghanistan for both females and males (52.9% vs. 73.9%). Among United States (US) service members, findings were similar to the overall study population, except female service members had lower median composite injury scores than males (5 vs. 9). In unadjusted analyses, females were less likely to survive to hospital discharge (OR 0.68, 95% CI 0.48-0.97). There was no difference in survival (OR 0.73, 95% CI 0.50-1.07), when controlling for confounders. In both unadjusted and adjusted analyses specific to US forces, we were unable to detect any differences in survival or for select analgesic administration. In both unadjusted and adjusted analyses specific to host nation civilians, we were unable to detect any differences in survival; however, even when controlling for confounders females were less likely to receive ketamine and IV morphine (OR 0.31, 95% CI 0.15-0.63; 0.69, 95% CI 0.49-0.98, respectively). Conclusions: Females accounted for a small proportion of total casualties within our dataset. After controlling for confounders, survival was comparable between males and females, but host nation females were less likely to receive ketamine and intravenous morphine. Future studies should seek to elucidate the reasons for these subtle differences between males and females in prehospital combat casualty care.


Evaluation of men on finasteride.
Finasteride, an orally active type II 5 alpha-reductase (5 alpha R) inhibitor, blocks conversion of testosterone (T) to dihydrotestosterone (DHT). The utility of finasteride in effectively managing benign prostatic hyperplasia has been documented. Use of the drug results in reduced prostate volume and serum levels. Patients receiving finasteride should be monitored with periodic digital-rectal examination (DRE) and serum PSA measurement. Patients with a sustained increase in serum PSA or an abnormal DRE require additional evaluation. There is no evidence that use of finasteride has an adverse effect on prostate cancer detection, if the drug's effect on serum PSA is recognized and accounted for.


Drosophila Myc restores immune homeostasis of Imd pathway via activating miR-277 to inhibit imd/Tab2.
Drosophila Myc (dMyc), as a broad-spectrum transcription factor, can regulate the expression of a large number of genes to control diverse cellular processes, such as cell cycle progression, cell growth, proliferation and apoptosis. However, it remains largely unknown about whether dMyc can be involved in Drosophila innate immune response. Here, we have identified dMyc to be a negative regulator of Drosophila Imd pathway via the loss- and gain-of-function screening. We demonstrate that dMyc inhibits Drosophila Imd immune response via directly activating miR-277 transcription, which further inhibit the expression of imd and Tab2-Ra/b. Importantly, dMyc can improve the survival of flies upon infection, suggesting inhibiting Drosophila Imd pathway by dMyc is vital to restore immune homeostasis that is essential for survival. Taken together, our study not only reports a new dMyc-miR-277-imd/Tab2 axis involved in the negative regulation of Drosophila Imd pathway, and provides a new insight into the complex regulatory mechanism of Drosophila innate immune homeostasis maintenance.


Multi-Robot Interfaces and Operator Situational Awareness: Study of the Impact of Immersion and Prediction.
Multi-robot missions are a challenge for operators in terms of workload and situational awareness. These operators have to receive data from the robots, extract information, understand the situation properly, make decisions, generate the adequate commands, and send them to the robots. The consequences of excessive workload and lack of awareness can vary from inefficiencies to accidents. This work focuses on the study of future operator interfaces of multi-robot systems, taking into account relevant issues such as multimodal interactions, immersive devices, predictive capabilities and adaptive displays. Specifically, four interfaces have been designed and developed: a conventional, a predictive conventional, a virtual reality and a predictive virtual reality interface. The four interfaces have been validated by the performance of twenty-four operators that supervised eight multi-robot missions of fire surveillance and extinguishing. The results of the workload and situational awareness tests show that virtual reality improves the situational awareness without increasing the workload of operators, whereas the effects of predictive components are not significant and depend on their implementation.


[Etiology, pathogenesis and complex prevention of insufficiency of intestinal sutures].
The concept of the intestinal sutures insufficiency are determined, groups of factors, causing this complications occurrence, are assigned. The conditions needed for primary healing of intestinal wound, criteria of intestinal suture choice are established.


Toward a post-Charter health promotion.
The past 25 years have seen enormous shifts in the environmental, political, economic and social landscapes that condition people's abilities to be healthy. Climate change is now a reality. China, India, Brazil and other 'developing' countries are emerging as new axes of political and economic power. Global capitalism has become increasingly predatory and crisis ridden, a result of unregulated and irresponsible greed of unimaginable scale. The elite response has been the increased erosion of the health and other social protection policies of redistribution that characterized the first-world run-up to the Ottawa Charter. These new realities challenge health promoters in ways unforeseen a quarter century ago. It is imperative that local determinants of health, to which health promoters give their attention, be traced to broader, even global levels of determinants. Support for groups acting at these levels should become a fundamental practice tenet. So, too, should advocacy for the social state, in which progressive taxation and hefty social investment blunt the health inequalities created by unfettered markets. As environmental and economic insecurities and inequalities increase in many of the world's countries, so does the risk of xenophobia and conflict. The roots of racism are complex; but weeding them out becomes another health promotion practice of the new millennium. There are some hopeful signs of health promoting political change, much of it emanating now from countries in the global South; but the threat of a return to health behaviourism in the face of the new global pandemic of chronic disease is real and must be confronted.


The formation of virus polyribosomes in L cells infected with vaccinia virus.
The fate of early virus messenger RNA in the cytoplasm of vaccinia-infected L cells has been studied during the first hour after infection. The RNA is made in the virus core structure from which it is rapidly released. It accumulates in the polyribsome fraction, where at least 75% is bound to ribosomes through an EDTA-sensitive link. Three distinct structures have been identified as possible intermediates in virus polyribosome formation. The first is a ribonucleoprotein complex (RNP) in which virus RNA is associated with cellular proteins. A complex having apparently similar properties, is formed when virus RNA is added to a cytoplasmic extract in vitro. The other two structures may consist of an RNP moiety associated with the small ribosomal subunit, or with a single ribosome. At least part of the RNA isolated as RNP appears to be a precursor of the virus messenger found in polyribosomes.


Individual, contextual, and social network factors affecting exposure to HIV/AIDS risk among older residents living in low-income senior housing complexes.
This study examines the influence of individual, contextual (building location and characteristics), and social network characteristics on HIV prevalence and risk behavior among people older than 50 years of age living in low-income senior housing in two cities, Hartford, Connecticut and Chicago, Illinois. The authors' study focuses on older residents of six buildings located in impoverished neighborhoods with high rates of HIV transmission through injection drug use and unprotected sexual activity, including the exchange of sex for drugs and money. The article is organized into three sections. First, the authors explore the HIV prevalence, distribution, and risk behaviors that may contribute to new infections among the buildings' older residents in general. These practices include unprotected sexual intercourse, sex with commercial sex workers, casual or multiple partners, regular use of alcohol and/or illicit drugs, and other high-risk activities that expose older residents to HIV, sexually transmitted diseases, and other negative health consequences. Next, the authors examine the relationship between building and neighborhood characteristics, the internal social organization of buildings, and the risk behaviors of individual residents by building residency. Finally, the authors use a social network analysis to identify possible entry points and transmission routes for HIV infection through drug and sexual exchanges between and among building residents and visitors. This approach also reveals variations in building structures that may facilitate the diffusion of HIV prevention efforts.


(PS)2: protein structure prediction server.
Protein structure prediction provides valuable insights into function, and comparative modeling is one of the most reliable methods to predict 3D structures directly from amino acid sequences. However, critical problems arise during the selection of the correct templates and the alignment of query sequences therewith. We have developed an automatic protein structure prediction server, (PS)2, which uses an effective consensus strategy both in template selection, which combines PSI-BLAST and IMPALA, and target-template alignment integrating PSI-BLAST, IMPALA and T-Coffee. (PS)2 was evaluated for 47 comparative modeling targets in CASP6 (Critical Assessment of Techniques for Protein Structure Prediction). For the benchmark dataset, the predictive performance of (PS)2, based on the mean GTD_TS score, was superior to 10 other automatic servers. Our method is based solely on the consensus sequence and thus is considerably faster than other methods that rely on the additional structural consensus of templates. Our results show that (PS)2, coupled with suitable consensus strategies and a new similarity score, can significantly improve structure prediction. Our approach should be useful in structure prediction and modeling. The (PS)2 is available through the website at http://ps2.life.nctu.edu.tw/.


Epidemiology of diarrhoea caused by enterotoxigenic Clostridium perfringens.
Enterotoxigenic strains of Clostridium perfringens have recently been implicated in some cases of antibiotic-associated diarrhoea. We present here the results of an epidemiological study of this disease. Five cases of diarrhoea caused by C. perfringens serotype 41 occurred during a 9-week period, and then during a 6-week period there were three cases due to serotype 27 and two due to serotype 24; in all but one case two geriatric wards were involved. In total there were 16 cases in 22 months. All cases were identified by the detection of C. perfringens enterotoxin in the faeces. The mean number of C. perfringens in these cases was 10(8.8) cfu/g of faeces. Of 37 patients who had negative test results for C. perfringens enterotoxin, 18 had positive cultures for C. perfringens, with mean faecal counts of 10(5.3) cfu/g, and nine of these patients had diarrhoea. Thirteen different serotypes were isolated from these 18 patients, including type 41 from seven patients and type 27 from one. Hand carriage of the offending serotype was demonstrated in three of four infected patients, none of four controls and two of 14 ward staff. C. perfringens of serotypes causing disease was isolated from 59% of environmental areas where there was active disease, 27% of areas where there had been disease which had since resolved and 9% of areas where there was no history of disease. The findings imply that cross infection may occur.


Exercise-induced amplitude modification of physiological action tremor of the ankle.
To determine whether exercise would affect physiological action tremor (PAT), normal male and female subjects exercised either by running or lifting weights. Surface electromyograms and acceleration recordings were analyzed using power spectral techniques to quantitate variations in amplitude and/or frequency of PAT. The results of this study show that running causes an increase in the amplitude of PAT. By having subjects run successively longer distances, a graded increase in amplitude of PAT was observed. After the subjects ran for long periods of time, PAT continued as an overt continuous oscillation. This oscillation did not greatly differ from pathological clonus. Furthermore, exercising the upper body alone by lifting weights increased the amplitude of PAT of the ankle. The results suggest that the exercise may cause alterations in the gain of the spinal reflexes which may lead to an underdamping of PAT. As the gain of the reflexes controlling PAT increases, this may lead to overt continuous oscillations, such as physiological or pathological clonus.


Effects of modifying interpretation bias on transdiagnostic repetitive negative thinking.
Repetitive negative thinking (RNT; e.g., worry and rumination) is common across emotional disorders, as is the tendency to generate negative interpretations (interpretation bias). Ameliorating negative interpretations via cognitive bias modification of interpretations (CBM-I) reduces worry/rumination, and improves mood in people diagnosed with generalized anxiety disorder (GAD) or depression. We investigated whether these findings generalize to high worry or rumination populations, irrespective of diagnosis, and whether effects are increased by enhancing emotional engagement with training with active generation of positive resolutions of ambiguity and imagery. Community volunteers with excessive worry and/or rumination, who were above clinical cut-off on anxiety and/or depression measures, were allocated to an active control condition (n = 54), interpretation training condition with prior activation of RNT (CBM_RNT; n = 54), or training condition augmented with positive outcome generation and imagery (CBM_ENH; n = 53). Interpretation bias, RNT, and mood were assessed before and following 10 Internet-based sessions completed within a 1-month period. RNT and mood questionnaires were also completed at 1-month follow-up. After training, both forms of CBM-I (vs. control) facilitated more positive interpretations and reduced negative intrusions during a worry task. At 1-month follow-up, anxiety, depression, RNT, and worry in the past week were lower in the CBM-I than control conditions, but not rumination or trait worry. Compared with standard CBM-I, the augmented form facilitated more positive interpretations, reduced negative intrusions after training, and reduced trait rumination at 1-month follow-up, but it did not augment effects on trait worry, anxiety or depression. Interpretation bias maintains transdiagnostic RNT and Internet-based CBM-I can reduce longer-term RNT. (PsycINFO Database Record (c) 2020 APA, all rights reserved).


Gal4/UAS transgenic tools and their application to zebrafish.
The ability to regulate gene expression in a cell-specific and temporally restricted manner provides a powerful means to test gene function, bypass the action of lethal genes, label subsets of cells for developmental studies, monitor subcellular structures, and target tissues for selective ablation or physiological analyses. The galactose-inducible system of yeast, mediated by the transcriptional activator Gal4 and its consensus UAS binding site, has proven to be a highly successful and versatile system for controlling transcriptional activation in Drosophila. It has also been used effectively, albeit in a more limited manner, in the mouse. While zebrafish has lagged behind other model systems in the widespread application of Gal4 transgenic approaches to modulate gene activity during development, recent technological advances are permitting rapid progress. Here we review Gal4-regulated genetic tools and discuss how they have been used in zebrafish as well as their potential drawbacks. We describe some exciting new directions, in large part afforded by the Tol2 transposition system, that are generating valuable new Gal4/UAS reagents for zebrafish research.


Reducing the harms of unsafe abortion: a systematic review of the safety, effectiveness and acceptability of harm reduction counselling for pregnant persons seeking induced abortion.
Globally, access to safe abortion is limited. We aimed to assess the safety, effectiveness and acceptability of harm reduction counselling for abortion, which we define as the provision of information about safe abortion methods to pregnant persons seeking abortion. We searched PubMed, EMBASE, ClinicalTrials.gov, Cochrane, Global Index Medicus and the grey literature up to October 2021. We included studies in which healthcare providers gave pregnant persons information on safe use of abortifacient medications without providing the actual medications. We conducted a descriptive summary of results and a risk of bias assessment using the ROBINS-I tool. Our primary outcome was the proportion of pregnant persons who used misoprostol to induce abortion rather than other methods among those who received harm reduction counselling. We included four observational studies with a total of 4002 participants. Most pregnant persons who received harm reduction counselling induced abortion using misoprostol (79%-100%). Serious complication rates were low (0%-1%). Uterine aspiration rates were not always reported but were in the range of 6%-22%. Patient satisfaction with the harm reduction intervention was high (85%-98%) where reported. We rated the risk of bias for all studies as high due to a lack of comparison groups and high lost to follow-up rates. Based on a synthesis of four studies with serious methodological limitations, most recipients of harm reduction counselling use misoprostol for abortion, have low complication rates, and are satisfied with the intervention. More research is needed to determine abortion success outcomes from the harm reduction approach. This work did not receive any funding. We registered the review in the PROSPERO database of systematic reviews (ID number: CRD42020200849).


Ca2+ entry through plasma membrane IP3 receptors.
Inositol 1,4,5-trisphosphate receptors (IP3Rs) release calcium ions, Ca2+, from intracellular stores, but their roles in mediating Ca2+ entry are unclear. IP3 stimulated opening of very few (1.9 +/- 0.2 per cell) Ca2+-permeable channels in whole-cell patch-clamp recording of DT40 chicken or mouse B cells. Activation of the B cell receptor (BCR) in perforated-patch recordings evoked the same response. IP3 failed to stimulate intracellular or plasma membrane (PM) channels in cells lacking IP3R. Expression of IP3R restored both responses. Mutations within the pore affected the conductances of IP3-activated PM and intracellular channels similarly. An impermeant pore mutant abolished BCR-evoked Ca2+ signals, and PM IP3Rs were undetectable. After introduction of an alpha-bungarotoxin binding site near the pore, PM IP3Rs were modulated by extracellular alpha-bungarotoxin. IP(3)Rs are unusual among endoplasmic reticulum proteins in being also functionally expressed at the PM, where very few IP3Rs contribute substantially to the Ca2+ entry evoked by the BCR.