Single lead atrial synchronised pacing in patients with cardiogenic shock after acute myocardial infarction.
A pacing system requiring only a single lead was used to establish atrial synchronised pacing in eight patients with complete atrioventricular block and cardiogenic shock following acute myocardial infarction. Spontaneous atrial activity was sensed through electrodes positioned on the pacing lead and used to trigger ventricular demand pacing. A normal atrioventricular relation could be established in each of these critically ill patients without the complexity of inserting and finding a stable position for an additional atrial sensing lead. Atrial synchronised pacing at the spontaneous sinus rate had distinct haemodynamic advantages compared with conventional ventricular pacing at 100 beats/min. Mean cardiac output for the group was 3.3 1/min with atrial synchronised pacing compared with 2.6 1/min with conventional pacing, a significant difference of 27%. Peak systolic pressure averaged respectively 91 and 73 mm Hg in the two pacing modes. With conventional ventricular pacing a pronounced phasic alteration in blood pressure was observed, dependent on the altering relation of the paced beats to spontaneous atrial activity. Atrial synchronised pacing abolished this effect and resulted in a stable blood pressure at or above the peak pressure achieved with conventional pacing. Atrial synchronised pacing with a single lead system can be established rapidly. This mode of pacing has appreciable and significant haemodynamic superiority over conventional ventricular pacing in patients with cardiogenic shock and atrioventricular block following acute myocardial infarction.


Ruthenium(III) chloride complex with a tridentate bis(arylimino)pyridine ligand: synthesis, spectra, X-ray structure, 9-ethylguanine binding pattern, and in vitro cytotoxicity.
The synthetic, spectroscopic, structural, and biological studies of a bis(arylimino)pyridine Ru(III) chloride compound containing the ligand, 2,6-bis(2,4,6-trimethylphenyliminomethyl)pyridine are reported. The bis(arylimino)pyridine ligand, with three donor nitrogen atoms, was synthesized by condensation of 2,6-pyridinedicarboxaldehyde with 2,4,6-trimethylaniline. The Ru(III) complex, with formula [RuCl 3(L1)](H 2O) (RuL1), where L1 = 2,6-bis(2,4,6-trimethylphenyliminomethyl)pyridine, was structurally determined on the basis of analytical and spectroscopic (IR, UV-vis, ESI-MS) studies. A straightforward strategy to fully characterize the paramagnetic compound using advanced (1)H NMR is reported. This new complex is a prototype for a series of new anticancer Ru(III) and Ru(II) compounds with improved cytostatic properties; likely to be modified in a desirable manner due to the relatively facile ligand modification of the bis(imino)pyridines and their molecular architecture. The present Ru(III) complex is the first example of this family of Ru(III)/Ru(II) anticancer compounds with the aimed physicochemical characteristics. Although the ligand itself is moderately active in selected cell lines (EVSA-T and MCF-7), the activity of the [Ru(L1)Cl 3] complex has increased significantly for a broad range of cancer cell lines tested in vitro (IC 50 values = 11 approximately 17 microM). Reaction of the RuL1 species with the DNA model base 9-ethylguanine (9EtGua) was found to produce in a redox reaction the species trans-[Ru(II)(L1)(9EtGua) 2(H 2O)](ClO 4) 2 (abbreviated as RuL1-9EtGua), which was studied in solution and also in the solid state, by X-ray crystallography. The structure comprises the as yet unknown trans-bis(purine)Ru(II) unit.


Expression of RRM1 and its association with resistancy to gemcitabine-based chemotherapy in advanced nasopharyngeal carcinoma.
Gemcitabine has high activity against nasopharyngeal carcinoma (NPC). The level of ribonucleotide reductase subunit M1 (RRM1) expression is closely related to the efficacy of gemcitabine on non-small cell lung cancer and pancreatic cancer. However, the expression of RRM1 and its association with sensitivity to gemcitabine-based chemotherapy in advanced NPC is not known. In this study, we retrospectively collected 48 formalin-fixed, paraffin-embedded NPC tissues to evaluate the expression of RRM1 using immunohistochemistry. All patients were diagnosed and treated with gemcitabine-based chemotherapy at Sun Yat-sen University Cancer Center. RRM1 expression was positive in 17(35%) patients. RRM1 expression was not associated with sex, age, performance status, WHO histological type, number of distant metastases, previous treatment, or cycles of gemcitabine-based chemotherapy(P> 0.05). The progression-free survival of the RRM1-positive group was shorter than that of the RRM1-negative group (5 months vs. 7 months, P = 0.036), and the response rate of the RRM1-positive group was somewhat lower than that of the RRM1-negative group (51.6% vs. 35.3%, P = 0.278). There was no significant difference in median survival between the RRM1-positive and RRM1-negative groups (22 months vs. 19 months, P = 0.540). Our results show that RRM1-negative expression is related with longer progression-free survival in advanced NPC patients treated with gemcitabine-based regimens.


Caspase 3 role and immunohistochemical expression in assessment of apoptosis as a feature of H1N1 vaccine-caused Drug-Induced Liver Injury (DILI).
Drug-Induced Liver Injury (DILI) changes, occur post exposure to natural or chemical compounds including apoptosis. To assess the H1N1 vaccine-caused DILI by histochemical and immunohistochemical methods. This 2014's experimental study was conducted on 70 albino rats. They were given ArepanrixTM H1N1 vaccine and were divided into 7 groups; 10 mice each, as control (non-vaccinated), vac2 and vac4 injected with 1st and 2nd doses of vaccine (suspension only) and euthanized after 3 weeks each, vac5 euthanized 6 weeks after 2nd dose, mix2 and mix4 injected with 1st and 2nd doses of vaccine (mixture of suspension and adjuvant) and euthanized after 3 weeks each, mix5 and euthanized 6 weeks after 2nd dose. Histopathological evaluation and histochemical assessment of metabolic protein, glycogen and collagen changes using PAS, bromophenol blue, Mallory's trichrome and immunohistochemistry for caspase 3 on liver tissue paraffin sections were done. Image analysis system Leica QIIN 500 was used. Data were analyzed by SPSS software, using descriptive statistics and ANOVA. Histopathological changes ranging from subtle up to necrosis were noticed, mainly in mix groups. Metabolic protein and glycogen changes were the maximum in mix5 group (p<0.01). Collagen deposition in sinusoids was higher in mix groups, and maximally in vac5 and mix5. Apoptotic hepatocytes expressing diffuse strong nuclear and cytoplasmic caspase 3 were the highest in mix5. H1N1 vaccine can cause DILI by either direct toxic or idiosyncratic metabolic type reactions rather than immunologic hypersensitivity type. It ranges from subtle changes up to necrosis. Caspase 3 is pivotal in liver damage etiology, apoptosis induction and processing. Follow up for at least 2 months after the 2nd dose of H1N1 vaccine is recommended to rule out H1N1-induced DILI.


How do leaf wetting events affect gas exchange and leaf lifespan of plants from seasonally dry tropical vegetation?
Foliar uptake of dew is likely an important mechanism of water acquisition for plants from tropical dry environments. However, there is still limited experimental evidence describing the anatomical pathways involved in this process and the effects of this water subsidy on the maintenance of gas exchange and leaf lifespan of species from seasonally dry tropical vegetation such as the Brazilian caatinga. We performed scanning electron, bright-field and confocal microscopic analyses and used apoplastic tracers to examine the foliar water uptake (FWU) routes in four woody species with different foliar phenology and widely distributed in the caatinga. Leaves of plants subjected to water stress were exposed to dew simulation to evaluate the effects of the FWU on leaf water potentials, gas exchange and leaf lifespan. All species absorbed water through their leaf cuticles and/or peltate trichomes but FWU capacity differed among species. Leaf wetting by dew increased leaf lifespan duration up to 36 days compared to plants in the drought treatment. A positive effect on leaf gas exchange and new leaf production was only observed in the anisohydric and evergreen species. We showed that leaf wetting by dew is relevant for the physiology and leaf lifespan of plants from seasonally dry tropical vegetation, especially for evergreen species.


[Domestic violence in Chile].
According to recent surveys, there is a high prevalence of domestic violence (DV) in Chile. A systematic review was conducted in PubMed, Scielo, and Lilacs with the MesH terms "Chile", "Mental Health", "Health", "Domestic Violence", to explore the impact of DV on health in Chile. Eleven studies fulfilled the inclusion criteria. Two studies were prospective, exploring the influence of DV on maternal-infant health. Nine studies explored the influence of DV on mental health in adults. DV was associated with deranged mental health indicators specially anxiety and depressive symptoms and suicidal ideation. Similar results were observed among mothers who were victims of violence and their children. It is concluded that DV is a complex phenomenon with serious effects on health. However the number of studies on the subject is low and new follow up studies are required. Predictive models for DV and effective preventive measures are urgently needed.


Effects from hydrogen bonding and rigidity on selectivity in tartaric acid-based chiral selectors for enantioselective liquid chromatography.
Tartaric acid-based selectors 1 ((R,R)-O,O'-Bis(dimethylbenzoyl)-N,N'-diallyl-N,N'-dimethyl tartaramide) and 2 ((R,R)-N-allyl-O,O'-bis(dimethylbenzoyl) tartarimide) were synthesized, immobilized on silica, and evaluated as chiral stationary phases in enantioselective chromatography. Comparison with the commercially available column Kromasil-CHI-1, based on selector 3 ((R,R)-O,O'-Bis(dimethylbenzoyl)-N,N'-diallyl tartaramide) resulted in the conclusion that amide NH functions are essential to chiral recognition on this sorbent. Furthermore, NH functions contribute significantly to retention of analytes except for alcohols. It was also found that flexibility of the benzoyl moieties is essential to selectivity.


Nucleotide polymorphisms upstream of the X-chromosome opsin gene array tune L:M cone ratio.
In support of the long-held idea that cone ratio is genetically determined by variation linked to the X-chromosome opsin gene locus, the present study identified nucleotide differences in DNA segments containing regulatory regions of the L and M opsin genes that are associated with significant differences in the relative number of L versus M cones. Specific haplotypes (combinations of genetic differences) were identified that correlated with high versus low L:M cone ratio. These findings are consistent with the biological principle that DNA sequence variations affect binding affinities for protein components of complexes that influence the relative probability that an L versus M opsin gene will be silenced during development, and in turn, produce variation in the proportion of L to M cones.


Ketamine enhances autophagy and endoplasmic reticulum stress in rats and SV-HUC-1 cells via activating IRE1-TRAF2-ASK1-JNK pathway.
Background Ketamine-related cystitis (KC) has been researched in many clinical studies, but its exact mechanism is ambiguous and needs further research. Methods We established a KC rat model and analyzed physiological, biochemical, and urodynamic parameters of ketamine (KET)-related bladder injury. Bladder histologic feature, reactive oxygen species (ROS), autophagy-, apoptosis-, and endoplasmic reticulum stress (ERS)-related markers were examined by hematoxylin and eosin staining, Masson staining, ROS kit, quantitative real-time polymerase chain reaction, and western blot. In vitro, effects of 0.01, 0.1, and 1 mM KET on cell vitality, apoptosis, ROS level, autophagy-, apoptosis-, and ERS-related markers were examined again. Effects of KET-1 and salubrinal on complex formation, autophagy-, apoptosis-, and ERS-related markers were examined by Co-Immunoprecipitation and western blot. After transfection with shIRE1, complex formation, cell biological behaviors, ROS level, autophagy-, apoptosis-, and ERS-related markers were examined again. Results KET induced bladder hyperactivity and injury. KET facilitated urinary frequency, ROS production, and induced bladder histologic injury by activating autophagy-, apoptosis-, and ERS-related markers in rats. In vitro, KET (0.01, 0.1, and 1 mM) restrained cell vitality and elevated apoptosis and ROS level via activating autophagy-, apoptosis-, and ERS-related markers. Moreover, salubrinal reversed the promotion of KET-1 on complex formation, autophagy-, apoptosis-, and ERS-related marker expressions. After transfection with shIRE1, shIRE1 weakened complex formation induced by KET-1, and the effects of KET-1 on cells were offset by shIRE1. Conclusion KET enhanced autophagy and ERS in vivo and in vitro via restraining IRE1-TRAF2-ASK1-JNK pathway.


End-stage kidney at the onset of nephrotic syndrome in a 4-year-old girl.
A previously healthy Japanese girl aged 4 years suddenly developed idiopathic nephrotic syndrome (INS) associated with acute renal failure (ARF). Despite prompt initiation of hemodialysis and prednisolone treatment, her ARF did not recover. A percutaneous renal biopsy performed within a month from the onset of INS revealed lesions of end-stage kidney, which is unusual for the acute stage of INS. Although the etiology of her ARF remains speculative, an acute exacerbation of an underlying chronic disease, such as non-nephrotic focal segmental glomerulosclerosis might be the cause.


IgM Immunoglobulin Influences Recovery after Cervical Spinal Cord Injury by Modulating the IgG Autoantibody Response.
Spinal cord injury (SCI) results in the development of detrimental autoantibodies against the lesioned spinal cord. IgM immunoglobulin maintains homeostasis against IgG-autoantibody responses, but its effect on SCI recovery remains unknown. In the present study we investigated the role of IgM immunoglobulin in influencing recovery after SCI. To this end, we induced cervical SCI at the C6/C7 level in mice that lacked secreted IgM immunoglobulin [IgM-knock-out (KO)] and their wild-type (WT) littermate controls. Overall, the absence of secretory IgM resulted in worse outcomes as compared with WT mice with SCI. At two weeks after injury, IgM-KO mice had significantly more IgG antibodies, which fixed the complement system, in the injured spinal cord parenchyma. In addition to these findings, IgM-KO mice had more parenchymal T-lymphocytes as well as CD11b+ microglia/macrophages, which co-localized with myelin. At 10 weeks after injury, IgM-KO mice showed significant impairment in neurobehavioral recovery, such as deteriorated coordination, reduced hindlimb swing speed and print area. These neurobehavioral detriments were coupled with increased lesional tissue and myelin loss. Taken together, this study provides the first evidence for the importance of IgM immunoglobulin in modulating recovery after SCI and suggests that modulating IgM could be a novel therapeutic approach to enhance recovery after SCI.


The women's health movement.
This article provides a brief overview of the history, current status, and future directions of the Women's Health Movement. The links between feminism and women's health issues are drawn and reasons for their simultaneous occurrence are suggested. It is shown that health issues are seen by the Movement has suspended in the larger social context from which they arise.


Ethical dilemmas and moral distress in oncology nursing practice.
Although ethical values and principles guide oncology nursing practice, nurses often are challenged to fulfill every professional core duty and responsibility in their everyday practice. Nurses commonly encounter clinical situations that have ethical conflicts, and they often have difficulty recognizing and articulating them. Unresolved conflicts can cause feelings of frustration and powerlessness, which can lead to compromises in patient care, job dissatisfaction, disagreements among those in the healthcare team, and burnout. This article reviews the ethical principles and values individual nurses bring to their practice as well as those basic to the profession of nursing. This article also discusses ethical conflicts in oncology practice and describes how nurses, especially students and novice nurses, may react to such situations with moral uncertainty or distress. In addition, a process for analyzing and resolving ethical problems in clinical situations is outlined. Increasing awareness and dialogue about ethical issues is an important first step in the process. Additional resources in the clinical setting may encourage nurses to actively participate in ethical decision making and take deliberate action as moral agents.


intansv: an R package for integrative analysis of structural variations.
Identification of structural variations between individuals is very important for the understanding of phenotype variations and diseases. Despite the existence of dozens of programs for prediction of structural variations, none of them is the golden standard in this field and the results of multiple programs were usually integrated to get more reliable predictions. Annotation and visualization of structural variations are important for the understanding of their functions. However, no program provides these functions currently as far as we are concerned. We report an R package, intansv, which can integrate the predictions of multiple programs as well as annotate and visualize structural variations. The source code and the help manual of intansv is freely available at https://github.com/venyao/intansv and http://www.bioconductor.org/packages/devel/bioc/html/intansv.html.


[Multiplex ligation-dependent probe amplification for detecting submicroscopic chromosomal abnormalities in Chinese children with global developmental delay or intellectual disability].
To evaluate the feasibility of screening large cohorts of patients with developmental delay or intellectual disability (DD/ID) with multiplex ligation-dependent probe amplification (MLPA). The peripheral blood samples were collected and DNA extracted from 276 patients with DD/ID from June 2012 to December 2013. MLPA was employed, including two distinct kits SALSA P036 and P070 for sub-telomere screening and SALSA P245 for 22 common microdeletion and microduplication syndromes. MLPA analysis revealed 58 (21%) cases of chromosome aberrations. Among 32 cases of subtelomeric rearrangements on one chromosome, there were deletion (n = 25) and duplication (n = 7); subtelomeric deletions on p and q arms of one chromosome (n = 2); subtelomeric rearrangements on 2 chromosomes, one deletion and other duplication (n = 9); subtelomeric rearrangements on 3 chromosomes, 2 duplications and other deletion (n = 1). There were 1 case of subtelomeric rearrangements on chromosome X. A total of 11 syndromes were detected among 22 common microdeletion and microduplication syndromes and 6 located at subtelomeric regions. MLPA is an effective cytogenetic diagnostic tool for detecting chromosomal abnormalities, such as DD/ID.


Serotonin Regulation of the Prefrontal Cortex: Cognitive Relevance and the Impact of Developmental Perturbation.
The prefrontal cortex is essential for both executive function and emotional regulation. The interrelationships among these behavioral domains are increasingly recognized, as well as their sensitivity to serotonin (5-hydroxytryptamine, 5-HT). Prefrontal cortex receives serotonergic inputs from the dorsal and median raphe nuclei and is modulated by multiple subtypes of 5-HT receptor across its layers and cell types. Extremes of serotonergic modulation alter mood regulation in vulnerable individuals, yet the impact of serotonin under more typical physiological parameters remains unclear. In this regard, new tools are permitting a closer examination of the behavioral impact of the serotonin system. Optogenetic and chemogenetic manipulations of dorsal raphe 5-HT neurons reveal that serotonin has a greater impact on executive function than previously appreciated. Domains that appear sensitive to fluctuations in 5-HT neuronal excitability include patience and cognitive flexibility. This work is broadly consistent with ex vivo research investigating how 5-HT regulates prefrontal cortex and its output projections. A growing literature suggests 5-HT modulation of these prefrontal circuits is unexpectedly flexible to alteration during development by genetic, behavioral, environmental or pharmacological manipulations, with lasting repercussions for cognition and emotional regulation. Here, we review the cellular and circuit mechanisms of prefrontal serotonergic modulation, investigate recent research into the cognitive consequences of the serotonergic system, and probe the lasting consequences of developmental perturbations. Understanding both the complexity of the prefrontal serotonin system and its sensitivity during development are essential to learn more about the vulnerabilities of this system in mood and anxiety disorders and the underappreciated cognitive consequences of these disorders and their treatment.


Risk and Protective Factors Associated With Intimate Partner Violence Against Chinese Women: A Systematic Review.
Intimate partner violence (IPV) is a global health challenge leading to various detrimental health outcomes. Chinese women are a vulnerable population often overlooked in IPV research. Guided by the social-ecological model, this systematic review aims to synthesize literature on the risk and protective factors for IPV among Chinese women. A comprehensive search was conducted in nine major English and Chinese databases for articles with data collected since 2006 on adult Chinese women, leading to 29 papers in the final analysis. Risk and protective factors associated with IPV identified in this review include factors at the individual level such as demographics (e.g., a younger age, unplanned pregnancy, abortion, having children, and migration), socioeconomic status (e.g., income and partners' education level), attitudinal factors (e.g., attitudes justifying IPV and traditional beliefs about gender roles), behavioral factors (e.g., alcohol use of women, partners' alcohol use and frequency, and partners' high frequency of gambling), adverse childhood experiences (e.g., witnessed violence in childhood), and other personal characteristics (e.g., chronic illness and good health status). Factors at the relationship level include conflicts, power in intimate relationships, and social capital (e.g., the size of social networks, network participation of women and their partners, and social control). Community-level factors related to geographic locations were also explored while no factors were identified at the societal level. None of the included studies examined the intersections of factors within the same level or across different levels. Recommendations for future research, practice, and policy are also discussed.


Ultrasonographic evaluation of the endometrium and correlation with endometrial sampling in postmenopausal patients treated with tamoxifen.
Seventy-two asymptomatic, postmenopausal women treated with tamoxifen for breast cancer were studied prospectively with vaginal ultrasonography, followed by endometrial sampling. Seventy-one patients demonstrated an endometrial echo of more than 5 mm, and one displayed an endometrial echo of less than 5 mm. No patient with an endometrial echo of less than 5 mm displayed any endometrial pathology. Different endometrial pathologic conditions were found when the endometrial echo was over 5 mm. When classifying those patients whose ultrasonic endometrial widths were wider than 5 mm, on the basis of different endometrial histologic findings, no obvious correlation was found between the various pathologic endometrial findings and endometrial thickness. Thus, a "thicker" endometrial sonographic image did not necessarily correlate with pathologic endometrial findings. When ultrasonic endometrial thickness of 5 mm was considered the upper limit of normal, the sensitivity of ultrasonography in correlating to positive histologic findings was 91% and the specificity was 96%. These findings suggest that there is good correlation between endometrial width measured by ultrasonographic assessment and histologic findings.


Apoptosis is induced by docosahexaenoic acid in breast cancer cells via death receptor and mitochondria-mediated pathways.
In the present study, the antitumor effect of n‑3 fatty acid was evaluated, and the effect of docosahexaenoic acid (DHA) on the induction of apoptosis and its underlying mechanism were examined. Flow cytometry and western blot analysis were performed to analyze apoptosis and the expression of protein factors in human breast cancer cells. The data revealed that DHA inhibited the viability of MCF‑7 breast cancer cells in vitro, and promoted cell death by the induction of apoptosis. DHA decreased the expression of B‑cell lymphoma 2 (Bcl‑2), whereas the expression of Bcl‑2‑associated X protein was increased. DHA was also shown to promote the release of Smac/Diablo and cytochrome c from the mitochondria. DHA increased the levels of cleaved caspase‑8, ‑9 and ‑3. Additionally, the protein expression of tumor necrosis factor‑related apoptosis‑inducing ligand, death receptor 4 and Fas were increased following DHA treatment. In conclusion, DHA caused apoptosis of the human breast cancer cells in vitro through the death receptor and mitochondria‑mediated pathways. The results of this study encourage further investigation of the effect of fish oil on the prevention and treatment of human breast cancer.


Nasal airflow and brain activity: is there a link?
Over the past few decades, evidence has emerged suggesting that nasal airflow asymmetry and brain asymmetry are linked. The nose exhibits asymmetrical airflow, with the dominant airflow alternating from one nasal passage to the other over a period of hours. Some authors have suggested a correlation between cerebral hemisphere dominance and nostril dominance. Others have proposed an association between rhythmic fluctuations in nasal airflow and corresponding fluctuations in cerebral hemisphere activity. Based on ancient yoga breathing techniques, newer evidence suggests that altering nasal airflow can influence brain activity, with reports of improved cognitive function caused by unilateral forced nostril breathing. It seems that a nasal airflow stimulus may have an activating effect on the brain, as it has also been shown to trigger seizure activity in epileptic patients. This article explores these theories in detail, reviews the evidence, and presents new models linking nasal airflow and brain activity.


Spontaneous resolution of congenital Brown's Syndrome - a case report.
The natural history of congenital Brown Syndrome is poorly understood and documented. In our experience, few adult cases are encountered in clinical practice. A case of bilateral congenital Brown syndrome is described, showing spontaneous resolution of clinical signs. Evidence of almost complete resolution over the years is also shown on serial Lees charts. To our knowledge, an objective record of such progressive improvement has not been previously reported. Knowledge of the natural history of Congenital Browns syndrome is useful in understanding the mechanism and also in the decision to delay surgery until full orbital growth has occurred.


Population modification of Anopheline species to control malaria transmission.
Vector control strategies based on population modification of Anopheline mosquitoes may have a significant role in the malaria eradication agenda. They could consolidate elimination gains by providing barriers to the reintroduction of parasites and competent vectors, and allow resources to be allocated to new control sites while maintaining treated areas free of malaria. Synthetic biological approaches are being used to generate transgenic mosquitoes for population modification. Proofs-of-principle exist for mosquito transgenesis, the construction of anti-parasite effector genes and gene-drive systems for rapidly introgressing beneficial genes into wild populations. Key challenges now are to develop field-ready strains of mosquitoes that incorporate features that maximize safety and efficacy, and specify pathways from discovery to development. We propose three pathways and a framework for target product profiles that maximize safety and efficacy while meeting the demands of the complexity of malaria transmission, and the regulatory and social diversity of potential end-users and stakeholders.


Catalytic domain of the p120 Ras GAP binds to RAb5 and stimulates its GTPase activity.
Ras is a master GTPase switch controlling multiple signal transduction cascades in the regulation of cell proliferation and differentiation. Rab5 is a local GTPase switch that is localized on early endosomes and controls early endosome fusion. This study demonstrates that the catalytic domain of p120 GTPase-activating protein (GAP), a well known Ras GAP, is able to interact physically with Rab5 and stimulate its GTPase activity. This GAP activity toward Rab5, however, cannot be extended to other Rab GTPases such as Rab3, Rab4, and Rab6, indicating that it is not a generic GAP for the Rab family of GTPases that regulate intracellular membrane fusion during endocytosis and exocytosis. The findings indicate a level of structural similarity between Ras and Rab5 unexpected from their primary sequences. They also suggest a possible signal transduction regulation of the Rab5-dependent endosome fusion via the Ras GAP.


Prexasertib, a cell cycle checkpoint kinase 1 and 2 inhibitor, in BRCA wild-type recurrent high-grade serous ovarian cancer: a first-in-class proof-of-concept phase 2 study.
High-grade serous ovarian carcinoma is characterised by TP53 mutations, DNA repair defects, and genomic instability. We hypothesised that prexasertib (LY2606368), a cell cycle checkpoint kinase 1 and 2 inhibitor, would be active in BRCA wild-type disease. In an open-label, single-centre, two-stage, proof-of-concept phase 2 study, we enrolled women aged 18 years or older with measurable, recurrent high-grade serous or high-grade endometrioid ovarian carcinoma. All patients had a negative family history of hereditary breast and ovarian cancer or known BRCA wild-type status, measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, Eastern Cooperative Oncology Group performance status score 0-2, and adequate haematological, renal, hepatic, and bone-marrow function. Patients received intravenous prexasertib 105 mg/m2 administered over 1 h every 14 days in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint of investigator-assessed tumour response, based on RECIST version 1.1, was assessed per protocol (assessable patients who had undergone CT imaging at baseline and attended at least one protocol-specified follow-up) and by intention to treat. The final analysis of this cohort of patients with BRCA wild-type high-grade serous ovarian carcinoma is reported here. This ongoing trial is registered with ClinicalTrials.gov, number NCT02203513, and continues to enrol patients for the BRCA-mutated ovarian cancer cohort. Between Jan 20, 2015, and Nov 2, 2016, we enrolled 28 women with a median age of 64 years (IQR 58·0-69·5) who had previously received a median of 5·0 (IQR 2·5-5·0) systemic therapies. Most patients (22 [79%]) had platinum-resistant or platinum-refractory disease. All women received at least one dose of prexasertib, but four (14%) of 28 patients were not assessable for RECIST response. Eight (33%, 95% CI 16-55) of 24 patients assessable per protocol had partial responses. In the intention-to-treat population, eight (29%, 95% CI 13-49) of 28 had a partial responses. The most common (in >10% patients) grade 3 or 4 treatment-emergent adverse events were neutropenia in 26 (93%) of 28 patients, reduced white blood cell count in 23 (82%), thrombocytopenia in seven (25%), and anaemia in three (11%). Grade 4 neutropenia was reported in 22 (79%) patients after the first dose of prexasertib and was transient (median duration 6 days [IQR 4-8]) and recovered without growth-factor support in all cases. The treatment-related serious adverse event of grade 3 febrile neutropenia was reported in two (7%) patients. One patient died during the study due to tumour progression. Prexasertib showed clinical activity and was tolerable in patients with BRCA wild-type high-grade serous ovarian carcinoma. This drug warrants further development in this setting, especially for patients with platinum-resistant or platinum-refractory disease. Intramural Research Program of the National Institutes of Health and National Cancer Institute.


Demand and availability of Intensive Care beds. A study based on the data collected at the SUEM 118 Central of Padua from October 1996 to December 2001.
This study aims to evaluate the management of intensive care beds according to the demands received by the SUEM 118 of Padua. It has been carried out by examining the reports drawn up by SUEM physicians from October 1996 to December 2001. The study rated the number of patients for whom an admission to the Intensive Care Unit (ICU) was required, according to the specific clinical situation at the moment of the request. A secondary objective was to evaluate if the critically ill patients had been admitted and treated in the most appropriate medical facility. The research is based on 7 087 reports concerning a population of adult and pediatric patients for whom an ICU bed was required in the period previously mentioned. For each report, it analyses the following data (keeping them anonymous): date of demand, main pathology and severity of clinical condition, sex and age, provenence and destination. Even though the number of annual demands for an ICU bed made to SUEM Central 118 has remained unchanged (approximately 1 350 per year), the number of beds made available in the operating rooms of the Hospital of Padua markedly increased. What has been experienced so far, and the data collected in this study has revealed, was that the requests for an intensive treatment for the overall population (hospitalized and non hospitalized) increased disproportionally in relation to the availability of ICU beds. In fact, the total number of hospitalizations in the different ICUs rose steadily year by year (from 3 495 in 1996 to 4 640 in 2001). The Hospital of Padua is a landmark center for patients who need specialized treatment. It is therefore important to increase the assistance and safety standards of its ICUs. In recent years there has been a great need for specialized ICUs either for more aggressive procedures (neurosurgical, cardiosurgical, respiratory, cardiologic, etc.) or for the increased use of adequate and invasive treatment for advanced diseases. The available resources of ICU beds should be more rationally distributed between the peripheral and the Regional Hospitals, since the activation of an ICU bed in the operating theatre is a valid, transient option.


A new multicomponent NPQ mechanism in the diatom Cyclotella meneghiniana.
In the present study we report that in the diatom Cyclotella meneghiniana the diatoxanthin-dependent non-photochemical quenching of chlorophyll fluorescence (NPQ) is heterogeneous and consists of three different components. (i) A transient NPQ component that generates immediately upon illumination, depends on the transthylakoid proton gradient as well as on the light intensity, and is modulated by the initial diatoxanthin content of the cells. It is located in the antenna complexes of C. meneghiniana and is comparable with the transient NPQ observed in vascular plants. (ii) A steady-state NPQ component is observed during later stages of the high-light illumination and depends on the diatoxanthin content formed by the light-activated diadinoxanthin cycle. (iii) A fast relaxing NPQ component is seen upon a transition of high-light-illuminated cells to complete darkness. This component relaxes within a time frame of tens of seconds and its extent is correlated with the amount of diatoxanthin formed during the phase of actinic illumination. It cannot be observed in dithiothreitol-treated cells where the de-epoxidation of diadinoxanthin to diatoxanthin is suppressed. The fast relaxing component can be interpreted as a relaxation of part of the steady-state NPQ. The different diatoxanthin-dependent components are characterized by different quenching efficiencies of diatoxanthin. Diatoxanthin involved in the transient NPQ exhibits a 2-fold higher quenching efficiency compared with diatoxanthin participating in the steady-state NPQ. It is proposed that the different quenching efficiencies of diatoxanthin are caused by the existence of different diatoxanthin pools within the antenna system of C. meneghiniana.


Long-range-corrected Rung 3.5 density functional approximations.
Rung 3.5 functionals are a new class of approximations for density functional theory. They provide a flexible intermediate between exact (Hartree-Fock, HF) exchange and semilocal approximations for exchange. Existing Rung 3.5 functionals inherit semilocal functionals' limitations in atomic cores and density tails. Here we address those limitations using range-separated admixture of HF exchange. We present three new functionals. LRC-ωΠLDA combines long-range HF exchange with short-range Rung 3.5 ΠLDA exchange. SLC-ΠLDA combines short- and long-range HF exchange with middle-range ΠLDA exchange. LRC-ωΠLDA-AC incorporates a combination of HF, semilocal, and Rung 3.5 exchange in the short range, based on an adiabatic connection. We test these in a new Rung 3.5 implementation including up to analytic fourth derivatives. LRC-ωΠLDA and SLC-ΠLDA improve atomization energies and reaction barriers by a factor of 8 compared to the full-range ΠLDA. LRC-ωΠLDA-AC brings further improvement approaching the accuracy of standard long-range corrected schemes LC-ωPBE and SLC-PBE. The new functionals yield highest occupied orbital energies closer to experimental ionization potentials and describe correctly the weak charge-transfer complex of ethylene and dichlorine and the hole-spin distribution created by an Al defect in quartz. This study provides a framework for more flexible range-separated Rung 3.5 approximations.


Magnetic resonance imaging of oropharyngeal cancer.
Magnetic resonance imaging (MRI) is a powerful tool for cross-sectional analysis of head and neck anatomy and pathology. This is especially true with regard to oropharyngeal neoplasms, where soft tissue spread, nodal disease, perineural extension, and osseous involvement may significantly alter therapy and prognosis. In this article, we will provide a background on oropharyngeal cancers and MRI techniques and strategies, describing potential advantages of MRI with regard to particular anatomic subsites of the oropharynx. Future imaging trends in perfusion and diffusion MRI of such cancers are also discussed.


Effective optical smoothing scheme to suppress laser plasma instabilities by time-dependent polarization rotation via pulse chirping.
In this paper, we propose a novel effective optical smoothing scheme to suppress laser plasma instabilities (LPIs) by time-dependent polarization rotation (TPR) on a picosecond timescale. The polarization rotation with time-dependent frequency is generated by the superposition of chirped light pulses with dynamic frequency shift and counter-rotating circular polarization. Compared to light without polarization rotation or pulse chirping, such superposed light with TPR has a broader spectrum and lower temporal coherence. Using the one-dimensional fluid laser-plasma-instability code (FLAME) and PIC simulation, TPR is demonstrated working well in suppressing parametric backscattering, which provides an effective approach to suppress LPIs. In the meantime, a significant improvement of irradiation uniformity of the chirped pulses is achieved by the introduction of proper spatial phase modulation and grating dispersion.


[Clinical, electromyography and pathologic-anatomic studies in myopathy--a contribution to rational diagnostic strategy].
A total of 189 patients underwent clinical, electromyographical and patho-anatomical examination (by muscle biopsy). 102 of the patients suffered from myopathy, 45 patients from neurogenic muscle diseases. 31 patients were suffering from chronic renal insufficiency and 11 patients from chronic alcoholism. The statistic elaboration of the findings was done by the multivariate analysis of variance (MANOVA) and discriminant analysis, in order to determine the diagnostic value of single parameters of investigation and to demonstrate diagnostically effective parameter combinations for diagnosing myopathies. Employing the discriminant function for the differentiation of myopathies and neurogenic muscle diseases yielded in patients with chronic renal insufficiency predominantly (30 cases) references to a neurogenic lesion of the proximal muscles and in the patients with chronic alcoholism relatively often (6 cases) references to a myogenic lesion of the proximal muscles.


Treatment of serious complications following endovascular aortic repair for type B thoracic aortic dissection.
Objective This study aimed to describe treatment of serious complications after primary thoracic endovascular aortic repair (TEVAR) in type B aortic dissection. Methods From June 2008 to March 2016, serious complications occurred in 58 patients without Marfan syndrome who received TEVAR for type B aortic dissection. Results Complications included endoleak, distal true lumen collapse, retrograde dissection, stroke, stent-graft (SG) migration and mistaken deployment, lower limb ischaemia, and SG fracture. Treatment included endovascular repair, surgical procedures, or conservative medication. Forty-six patients recovered from complications. Twelve patients were not cured. The median follow-up time was 29.5 months (2-61 months). The overall 30-day mortality rate was 1.7% (1/58) and the total mortality rate following secondary complications was 8.6% (5/58). The causes of death were stroke and aortic rupture. Conclusion Some treatments need to be performed after TEVAR because of severe complications. A reduction in these complications can be achieved by optimal evaluation of patients, selection of SGs, and specialized endovascular manipulation.


Persistent organochlorine pesticides in serum and risk of Parkinson disease.
Pesticides have been implicated as likely environmental risk factors for Parkinson disease (PD), but assessment of past exposure to pesticides can be difficult. No prior studies of pesticide exposure and PD used biomarkers of exposure collected before the onset of PD. Our investigation examined the association between prospective serum biomarkers of organochlorine pesticides and PD. We conducted a nested case-control study within the Finnish Mobile Clinic Health Examination Survey, with serum samples collected during 1968-1972, and analyzed in 2005-2007 for organochlorine pesticides. Incident PD cases were identified through the Social Insurance Institution's nationwide registry and were confirmed by review of medical records (n = 101). Controls (n = 349) were matched for age, sex, municipality, and vital status. Adjusted odds ratios (ORs) of PD were estimated using logistic regression. Little association emerged with a summary score of the 5 organochlorine pesticides found at high levels, and only increasing dieldrin concentrations trended toward a higher risk of PD (OR per interquartile range [IQR] 1.28, 95% confidence interval [CI] 0.97-1.69, p = 0.08). Because of possible strong confounding by cigarette smoking among smokers, we ran additional analyses restricted to never smokers (n = 68 cases, 183 controls). In these analyses, increasing dieldrin concentrations were associated with increased odds of PD (OR per IQR 1.95, 95% CI 1.26-3.02, p = 0.003). None of the other organochlorine pesticides were associated with PD in these analyses. These results provide some support for an increased risk of Parkinson disease with exposure to dieldrin, but chance or exposure correlation with other less persistent pesticides could contribute to our findings.


[Polyclonal activated circulating B-lymphocytes in patients with rheumatoid arthritis].
Peripheral B lymphocytes were studied to investigate the role of polyclonal B-cell activation in the pathogenesis of rheumatoid arthritis (RA). Proliferative responses to anti-mu antibodies coupled to sepharose used as a B-cell-specific mitogen were reduced as compared to healthy controls. When cell surface antigens were studied by flow cytometry employing monoclonal antibodies, B cells from patients with RA showed enhanced expression of Interleukin-2 (IL-2) receptor. In-vivo-activated, in-vitro spontaneously proliferating Epstein-Barr virus transformed B cells positive for immunoglobulin M, G, and A were obtained from patients with RA. In summary, our findings suggest the presence of polyclonal activated B cells in the peripheral blood of patients with RA, and a close relationship of polyclonal activated B cells and the activity of the disease process.


20-Deoxyingenol alleviates intervertebral disc degeneration by activating TFEB in nucleus pulposus cells.
Intervertebral disc degeneration (IVDD) is a prevalent degenerative disease with significant adverse implications for patients' quality of life and socioeconomic status. Although the precise etiology of IVDD remains elusive, the senescence of nucleus pulposus cells is recognized as the primary pathogenic factor of IVDD; however, drugs that may targetedly inhibit senescence are still lacking. In the current study, we evaluated the small-molecule active drug 20-Deoxyingenol(20-DOI) for its effects on combating senescence and delaying the progression of IVDD. In vitro experiments revealed that the administration of 20-DOI displayed inhibitory effects on senescence and the senescence-related cGAS-STING pathway of nucleus pulposus cells. Additionally, it exhibited the ability to enhance lysosome activity and promote autophagy flux within nucleus pulposus cells. Subsequent investigations elucidated that the inhibitory impact of 20-DOI on nucleus pulposus cell senescence was mediated through the autophagy-lysosome pathway. This effect was diminished in the presence of transcription factor EB (TFEB) small hairpin RNA (shRNA), thereby confirming the regulatory role of 20-DOI on the autophagy-lysosome pathway and senescence through TFEB. In vivo experiments demonstrated that 20-DOI effectively impeded the progression ofIVDD in rats. These findings collectively illustrate that 20-DOI may facilitate the autophagy-lysosomal pathway by activating TFEB, thereby suppressing the senescence in nucleus pulposus cells, thus suggesting 20-DOI as a promising therapeutic approach for IVDD.


Formation and structure of stable aggregates in binary diffusion-limited cluster-cluster aggregation processes.
Binary diffusion-limited cluster-cluster aggregation processes are studied as a function of the relative concentration of the two species. Both, short and long time behaviors are investigated by means of three-dimensional off-lattice Brownian Dynamics simulations. At short aggregation times, the validity of the Hogg-Healy-Fuerstenau approximation is shown. At long times, a single large cluster containing all initial particles is found to be formed when the relative concentration of the minority particles lies above a critical value. Below that value, stable aggregates remain in the system. These stable aggregates are composed by a few minority particles that are highly covered by majority ones. Our off-lattice simulations reveal a value of approximately 0.15 for the critical relative concentration. A qualitative explanation scheme for the formation and growth of the stable aggregates is developed. The simulations also explain the phenomenon of monomer discrimination that was observed recently in single cluster light scattering experiments.


Inactivation of SMAD4 tumor suppressor gene during gastric carcinoma progression.
Mothers against decapentaplegic homologue 4 (SMAD4) is a tumor suppressor gene associated with gastrointestinal carcinogenesis. The aim of the present study is to more precisely characterize its role in the development and progression of human gastric carcinoma. The expression of SMAD4 was investigated in 283 gastric adenocarcinomas and related lesions, as well as in 9 gastric carcinoma cell lines. We also analyzed the methylation status of SMAD4 gene by using methylation-specific PCR, examined loss of heterozygosity (LOH) of this gene locus by using a vicinal marker, and detected exon mutation of SMAD4 through exon-by-exon amplification. Moreover, we assessed whether MG132, a proteasome inhibitor, affected the SMAD4 protein level. We found loss of SMAD4 protein expression in the cytoplasm (36 of 114, 32%) and in the nucleus (46 of 114, 40%) of gastric cancer cells. The loss of nuclear SMAD4 expression in primary tumors correlated significantly with poor survival, and was an independent prognostic marker in multivariate analysis. We also found a substantial decrease in SMAD4 expression at both the RNA and protein level in several human gastric carcinoma cell lines. In addition, we found that LOH (20 of 70, 29%) and promoter hypermethylation (4 of 73, 5%) were associated with the loss of SMAD4 expression. SMAD4 protein levels were also affected in certain gastric carcinoma cell lines following incubation with MG132. Taken together, our results indicate that the loss of SMAD4, especially loss of nuclear SMAD4 expression, is involved in gastric cancer progression. The loss of SMAD4 in gastric carcinomas was due to several mechanisms, including LOH, hypermethylation, and proteasome degradation.


Posttranslational regulation of p53 tumor suppressor protein function.
Alteration of the p53 gene by deletion and mutation is the most common denominator yet identified among human cancers (Hollstein et al., 1991; Caron de Fromental and Soussi, 1992). The involvement of the p53 gene in such a broad scope of human cancers warrants further investigation into its mechanism of action in regulating cell growth. The wild-type p53 protein restricts cell growth in the G1 phase of the cell cycle by regulating the transcription of genes and possibly, by influencing DNA replication. Elucidating the cell growth restriction of p53 will require identification and characterization of the genes whose expression is regulated by p53 and the proteins that interact with p53 to regulate its DNA-binding and transactivation functions. A model for the regulation of p53 biochemical function is proposed that extends further and builds on the conformational hypothesis for regulation of p53 function hypothesized by Milner (1991) and Ullrich et al. (1992a). The conformational hypothesis of regulation of p53 function states that the conformation of p53 determines whether it expresses growth-suppressing or growth-promoting biological activity. Mutations observed in human cancer lock p53 in a growth-promoting conformation. We expand the conformational hypothesis in a regulatory model that includes binding proteins, kinases/phosphatases, redox modifier proteins, and homo/hetero-oligomerization, which modulate the tertiary structure of the protein. Different conformational modes of p53 interact differently with initiation complexes at gene promoters and at origins of DNA replication. Each form of p53, depending on its interaction with proteins and gene transcription-initiation complexes, will mediate distinct biological effects on cells ranging from growth suppression to growth promotion. Furthermore, depending on its conformational state, p53 can repress or activate other transcription factors thus indirectly affecting gene regulation. We propose that each cell and tissue type expresses unique quantities and types of p53-binding proteins and modifying enzymes that regulate the interaction of p53 with promoters of genes necessary for control of growth of a specific cell or tissue. It is anticipated that defects in the expression of p53 regulatory proteins are involved in a portion of those tumors expressing normal p53. Defects in the p53 biochemical pathway may thus be even more prevalent in human cancers than is now realized.


New indications for botulinum toxin type A in treating facial wrinkles of the mouth and neck.
Botulinum toxin type A (BTX-A) is commonly used to smooth hyperkinetic lines in the periocular and forehead areas of the upper face, but has been used less frequently for indications in the lower face and neck. This study was designed to determine whether botulinum toxin treatment of the mouth and neck areas is as clinically successful as treatment of the upper face. This was a retrospective study of patients who were treated with botulinum toxin type A (BOTOX, Allergan, Inc) to soften hyperkinetic facial wrinkles. Of 100 patients randomly selected from a single clinical practice, 91 met the inclusion criteria and were divided into two groups for analysis: the 56 patients in Group 1 did not receive treatment in the mouth and neck areas, while the 35 patients in Group 2 were treated at least once in the mouth and neck areas. Patients were surveyed for periods ranging from seven to 49 months. Most patients in each group had a single BTX-A procedure during this period. Both groups of patients had comparable improvement of wrinkles both at the evaluation immediately after the neuromuscular blockade and during followup. In comparison with patients whose treatment was confined to the upper face, patients who received global treatment with BTX-A, including BTX-A injections in the mouth and neck areas, were injected in more sites per procedure and had more procedures in combination with other therapies. Patient satisfaction with botulinum toxin treatment and outcomes was high in both groups. BTX-A is an important tool within the therapeutic spectrum for the treatment of hyperkinetic facial wrinkles, including those in the areas of the mouth and neck.


Evaluation of mannitol salt agar, CHROMagar Staph aureus and CHROMagar MRSA for detection of meticillin-resistant Staphylococcus aureus from nasal swab specimens.
Mannitol salt agar (MSA), CHROMagar Staph aureus (CSA) and CHROMagar MRSA (CSA-MRSA) were evaluated with nasal surveillance specimens for their ability to detect Staphylococcus aureus and meticillin-resistant S. aureus (MRSA). CSA was found to be more sensitive than MSA in detecting S. aureus (98 versus 84.3 %; P=0.03). CSA and CSA-MRSA were equivalent in the ability to detect MRSA at 24 h (89.7 versus 87.2 %) and at 48 h (94.9 versus 94.9 %). When combined with Staphaurex slide confirmation testing, both CSA and CSA-MRSA were highly specific (100 %) media for detecting MRSA from nasal swab specimens.


Intestinal mucus trapping in the rapid expulsion of Trichinella spiralis by rats: induction and expression analyzed by quantitative worm recovery.
Rats were immunized with a Trichinella spiralis infection restricted by chemotherapy to the intestine (the T/M regime) or with a complete infection that resulted in the deposition of muscle larvae. After an oral challenge infection, rapid expulsion could be demonstrated in both groups within 20 min and with 100% recovery of the infectious dose from the stomachs and intestines of infected animals. Immune and nonimmune groups were distinguished by the large numbers of worms in the intestinal lumens of immune rats and large numbers of worms in the intestinal walls in nonimmune rats. Infectious larvae persisted in the stomach lumens for longer in the immune rats. There was no quantitative difference in worm distribution in the intestine during rapid expulsion in rats immunized with the T/M regime or those given a complete infection. However, in the complete infection group 69% of the luminal worms were trapped in mucus; this did not occur during rapid expulsion in rats immunized with the T/M regime. Mucus trapping was observed only when muscle larvae had matured to the infectious stage in muscle (28 days after the primary infection). Complete infection rats challenged at 14 or 21 days did not display significant mucus trapping of larvae in the intestinal lumen. We conclude that (i) mucus trapping is not essential for rapid expulsion and (ii) mucus trapping is produced by systemic exposure to target antigens of the infectious larvae.


Rationale for the posterior-stabilized rotating-platform knee.
The nonposterior-stabilized mobile-bearing knee and the posterior-stabilized fixed-bearing design have been successfully used for the past three decades. Lessons learned from their use have culminated in the design of a posteior-stabilized mobile-bearing knee that incorporates beneficial features of both. The posterior-stabilized mobile-bearing knee is aimed at addressing polyethylene wear issues related to the fixed-bearing design, and improve upon stability and range of motion typical of nonposterior-stabilized mobile-bearing knee designs.


Rapid estimation of thermodynamic parameters and vapor pressures of volatile materials at nanoscale.
Non-isothermal measurements of thermodynamic parameters and vapor pressures of low-volatile materials are favored when time is a crucial factor to be considered, such as in the case of detection of hazardous materials. In this article, we demonstrate that optical absorbance spectroscopy can be used non-isothermally to estimate the thermodynamic properties and vapor pressures of volatile materials with good accuracy. This is the first method to determine such parameters in nanoscale in just minutes. Trinitrotoluene (TNT) is chosen because of its low melting temperature, which makes it impossible to determine its thermodynamic parameter by other rising-temperature techniques, such as thermogravimetric analysis (TGA). The well-characterized vapor pressure of benzoic acid is used to calibrate the spectrometer in order to determine the vapor pressure of low-volatile TNT. The estimated thermodynamic properties of both benzoic acid and TNT are in excellent agreement with the literature. The estimated vapor pressure of TNT is one order of magnitude larger than that determined isothermally using the same method. However, the values are still within the range reported in the literature. The data indicate the high potential for use of rising-temperature absorbance spectroscopy in determining vapor pressures of materials at nanometer scale in minutes instead of hours or days.


Discovery of a novel smectic-C{*} liquid-crystal phase with six-layer periodicity.
We report the discovery of a new smectic-C{*} liquid-crystal phase with six-layer periodicity by resonant x-ray diffraction. Upon cooling, the new phase appears between the SmC{alpha}{*} phase having a helical structure and the SmC{d4}{*} phase with four-layer periodicity. This SmC{d6}{*} phase was identified in two mixtures which have an unusual reversed SmC{d4}{*}-SmC{*} phase sequence. The SmC{d6}{*} phase shows a distorted clock structure. Three theoretical models have predicted the existence of a six-layer phase. However, our experimental findings are not consistent with the theories.


Practical approach for measuring heat capacity of pharmaceutical crystals/glasses by modulated-temperature differential scanning calorimetry.
A practical protocol to obtain accurate heat capacity values of pharmaceutical compounds using modulated-temperature differential scanning calorimetry was established. Three pharmaceutical compounds, acetaminophen, indomethacin, and tri-O-methyl-β-cyclodextrin were used as model compounds. Powder samples did not produce reproducible results, presumably due to inclusion of gas in gap of powders that influenced the measured heat capacity and thermal homogeneity in the sample. Thus, the amorphous characteristics were evaluated using quench-cooled samples. Crystalline samples were obtained by partially melting the sample to allow recrystallization using the residual crystal as a template. Optimum sample mass was about 10 mg. Use of too small sample size resulted in poor reproducibility due to localization of the sample in the pan, while too large size resulted in low heat capacity values probably because of heterogeneity of the sample temperature. The optimum modulation period was in the range of 60 s and 90 s, to which the ramp rates of 2°C/min and 1°C/min, respectively, were applied. The ramp amplitude was less significant in the evaluation. This information should help in comprehending basic characteristics of pharmaceutical compounds.


Sensory irritation and pulmonary irritation by airborne allyl acetate, allyl alcohol, and allyl ether compared to acrolein.
The propene derivatives, allyl acetate, allyl alcohol, allyl ether, and acrolein were investigated for their property as sensory irritant in Ssc:CF-1 mice. The concentration of the chemicals necessary to depress the respiratory rate by 50% ( RD50 ) due to sensory irritation of the upper respiratory tract were 2.9, 3.9, 5.0 and 2.9 p.p.m., respectively. The potency of these propene derivatives varied very little for their concentration in air, in p.p.m., to depress the respiratory rate by 50%. However, when the potency is expressed in terms of thermodynamic activity acrolein was found to be 10 times more potent than the other propene derivates. This may be explained either by a higher reactivity of the carbon-carbon double bond or the involvement of the aldehyde group in a secondary chemical binding. No secondary chemical binding can be invoked for allyl acetate, allyl alcohol or allyl ether. In general, the chemical structure CH2 = CH-CH-O may be suspected to allow a molecule to act as a strong sensory irritant. The TLV's were predicted from the relation: TLV approximately equal to 0.03 X RD50 and were found to be 0.1, 0.1, 0.15, and 0.1 for allyl acetate, allyl alcohol, allyl ether, and acrolein, respectively. No pulmonary irritation was found at the concentration causing a 50% decrease in respiratory rate.


How Early-Life Gut Microbiota Alteration Sets Trajectories for Health and Inflammatory Bowel Disease?
Inflammatory bowel disease (IBD) is a recurrent chronic inflammatory condition of the intestine without any efficient therapeutic regimens. Gut microbiota, which plays an instrumental role in the development and maturation of the immune system, has been implicated in the pathogenesis of IBD. Emerging evidence has established that early-life events particularly maternal influences and antibiotic treatment are strongly correlated with the health or susceptibility to disease of an individual in later life. Thus, it is proposed that there is a critical period in infancy, during which the environmental exposures bestow a long-term pathophysiological imprint. This notion sheds new light on the development of novel approaches for the treatment, i.e., early interventions, more precisely, the prevention of many uncurable chronic inflammatory diseases like IBD. In this review, we have integrated current evidence to describe the feasibility of the "able-to-be-regulated microbiota," summarized the underlying mechanisms of the "microbiota-driven immune system education," explored the optimal intervention time window, and discussed the potential of designing early-probiotic treatment as a new prevention strategy for IBD.


Easy removal of nasal magnets.
This article uses a case report and discussion to demonstrate the removal of magnets which have become lodged in the nasal cavity as a result of using magnet-backed earrings to decorate the alae. If bi-alar decoration is used, removal of nasal magnets can present more of a challenge than other nasal foreign bodies. This is because of their attraction to each other through the septum and because of the edema that can form around the magnets. This case discusses that removal of magnets lodged in the nares can be easily achieved with minimal trauma, by the use of a household pocket magnet.


Genetic susceptibility to lung cancer with special emphasis on CYP1A1 and GSTM1: a study on host factors in relation to age at onset, gender and histological cancer types.
Genetically based differences in metabolism, related to MspI restriction site and Ile-Val polymorphisms of the cytochrome P450 (CYP) 1A1 gene and the null genotype of glutathione transferase class mu (GSTM1), have been reported to be associated with lung cancer susceptibility. The present study was set up to establish the frequencies of the polymorphic genotypes of CYP1A1 and GSTM1 in Sweden, to evaluate a possible increased incidence of the genotypes associated with higher lung cancer risks among Swedish lung cancer patients and to try to make a combined risk estimate for carriers of multiple risk alleles. In a healthy control group, all under 66 years of age, 53% (174/329) of the subjects were of the GSTM1(-) genotype, while in a hospital control group 49% (39/79) carried the GSTM1(-) genotype. In the investigated lung cancer patients this genotype was found in 56% (165/296) and among those patients diagnosed before 66 years of age the deficient genotype was found in 60% (78/131). The highest proportion of the GSTM1(-) genotype was found in patients diagnosed with adenocarcinoma (63%, 29/46) and small cell carcinoma (72%, 21/29) before 66 years of age and among female squamous cell carcinoma patients (79%, 15/19). The allelic variants in CYP1A1 were equally distributed in lung cancer patients and controls. The m1/m2 and m2/m2 genotypes of the MspI site and the Ile/Val genotype were, however, slightly over-represented in squamous cell carcinoma patients. Among patients with squamous cell carcinoma diagnosed before 66 years of age the m1/m2 genotype was found in 28% (10/36), whereas the same genotype was observed in 16% (52/329) of healthy control subjects. A combined risk of squamous cell carcinoma was indicated for patients, diagnosed before 66 years of age, carrying both GSTM1(-) and m2 alleles (OR = 3.0, 95% CI = 1.2-7.2).


Degradation of ethyl paraben by heat-activated persulfate oxidation: statistical evaluation of operating factors and transformation pathways.
A factorial design methodology was implemented to evaluate the importance of ethyl paraben (EP) concentration (500-1500 μg/L), sodium persulfate concentration (400-500 mg/L), temperature (40-60 °C), reaction time (2-30 min), water matrix (pure water or secondary treated wastewater), and initial solution pH (3-9) on EP removal by heat-activated persulfate oxidation. All individual effects, except the solution pH, were statistically significant and so were the second-order interactions of ethyl paraben concentration with temperature or the reaction time. The influence of the water matrix was crucial, and the efficiency of the process was lower in secondary treated wastewater due to the presence of natural organic matter and inorganic salts that compete with ethyl paraben for the reactive oxygen species. Liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS) was employed to identify major transformation by-products (TBPs); 13 compounds were detected as TBPs of EP. Degradation occurred through (i) hydroxylation, (ii) dealkylation, and (iii) oligomerization reactions leading to TBPs with ether and biphenyl structures. Oligomerization reactions were found to be the dominant pathway during the first steps of the reaction. The toxicity of 500 μg/L EP in secondary treated wastewater was tested against marine bacteria Vibrio fischeri; toxicity increased during the first minutes due to the production of several TBPs, but it consistently decreased thereafter.


The role of Plasmodium V-ATPase in vacuolar physiology and antimalarial drug uptake.
To ensure their survival in the human bloodstream, malaria parasites degrade up to 80% of the host erythrocyte hemoglobin in an acidified digestive vacuole. Here, we combine conditional reverse genetics and quantitative imaging approaches to demonstrate that the human malaria pathogen Plasmodium falciparum employs a heteromultimeric V-ATPase complex to acidify the digestive vacuole matrix, which is essential for intravacuolar hemoglobin release, heme detoxification, and parasite survival. We reveal an additional function of the membrane-embedded V-ATPase subunits in regulating morphogenesis of the digestive vacuole independent of proton translocation. We further show that intravacuolar accumulation of antimalarial chemotherapeutics is surprisingly resilient to severe deacidification of the vacuole and that modulation of V-ATPase activity does not affect parasite sensitivity toward these drugs.


Data-driven technique for disruption prediction in GOLEM tokamak using stacked ensembles with active learning.
In a tokamak, disruption is defined as losing control over a confined plasma resulting in sudden extinction of the plasma current. Machine learning offers potent solutions to classify plasma discharges into disruptive and non-disruptive classes. Evolving experimental programs reduce the performance of machine learning models, and also, the need for labeling the huge volume of data incurs more labor cost and time. This paper proposes a data-driven based machine learning technique that employs an active learning approach for labeling and classification of plasma discharges. The designed model uses 117 normally terminated shots and 70 disruptive shots with 14 labeled diagnostic signals. The stacking classifier is built over three base learners: logistic regression, reduced error pruning tree, and categorial boost algorithm, and the logistic regression technique is used at the meta-learner. An active learning approach is proposed for labeling the unlabeled dataset using a modified uncertainty sampling technique with minimal queries. The proposed model queries the unlabeled data to an oracle based on a selection strategy with uncertainty sampling using entropy metrics. The new labeled data and the class probabilities of the base classifiers are channeled to the final predictor for classifying the plasma discharge. The proposed model achieves an accuracy of 98.75% in classifying the disruptive vs non-disruptive discharges, with a minimally trained dataset, and also, it is free from aging of predictors.


Escalated M-VAC chemotherapy and recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) in patients with advanced urothelial tract tumors.
The M-VAC regimen (methotrexate, vinblastine, adriamycin, and cisplatin) has significant antitumor activity in patients with advanced urothelial tract cancer. Growth factors may provide the possibility of treating patients with higher doses of chemotherapy, for longer periods, with less morbidity, and improved results. A trial of an escalated dosage of M-VAC with recombinant GM-CSF (rhGM-CSF) was initiated. 23 patients were treated with an escalated dose of M-VAC every 2 weeks plus rhGM-CSF 250 micrograms/m2 s.c. days 4-10. Dose level I (n = 13) was 1.65 times the dose of standard M-VAC. Adriamycin and cisplatin were given at 2.5 times the dose of standard M-VAC. Dose level II (n = 10) was a relative dose intensity of 1.95. Adriamycin and cisplatin were both given at 2.9 times the dose. The response rate was 70% (95% CI 60%-80%). Seven patients (30%) had CR, and 9 (39%) had a PR. Five (22%) patients had stable disease and 2 (9%) had progression. Of the CR patients, 3 had the CR confirmed pathologically (CRp). Response occurred in 11 patients treated at dose level I and 5 at dose level II. Toxicity was primarily hematologic. Dose level II was too toxic due to thrombocytopenia. Non-hematologic toxicity was minimal. The value of this schedule (dose level I) compared to standard M-VAC will be further evaluated in a randomized trial to be initiated by the Genitourinary Group of the EORTC.


Psychogenic palatal tremor.
We describe a case of psychogenic palatal tremor. The diagnosis was supported by clinical criteria and neurophysiological testing, including frequency analysis and jerk-locked back-averaging. We discuss the differential diagnosis of palatal tremor as well as the role of neurophysiological testing in the diagnosis of psychogenic movement disorders.


Video-assisted Thoracoscopic Resection of a Giant Bulla in Vanishing Lung Syndrome: case report and a short literature review.
A 36-year-old Caucasian man was admitted to our hospital with acute onset of left-sided chest pain. Computed Tomography confirmed the presence of a giant bulla on the apex of the lower lobe of the left lung. A video-assisted thoracic surgery (VATS) with bullectomy was performed using two linear endostaplers. Additionally pleurectomy was performed. No serious complications occurred in the postoperative course, as the patient showed good lung re-expansion and no prolonged air leakage.VATS bullectomy is a suitable and eminent technique to approach giant bullous emphysema and definitely fulfils a role in its treatment.


Final report on the amended safety assessment of sodium polynaphthalenesulfonate and sodium naphthalenesulfonate.
Sodium Polynaphthalenesulfonate (SPNS) and Sodium Naphthalenesulfonate (SNS) are sodium salts of naphthalene sulfonic acid. SPNS was used as an emulsion stabilizer, surfactant--hydrotrope, and/or surfactant--suspending agent at concentrations between 0.1% and 0.4%, in a wide range of products, including one lipstick. SNS is described as a surfactant--hydrotrope; no current uses were reported, but information was provided indicating that use concentrations would be typically below 2%. SNS is manufactured by reacting naphthalene with sulfuric acid to produce a sulfonic acid, which is then reacted with sodium hydroxide to produce the final product. The polymer form uses the sulfonic acid intermediate in a reaction with formaldehyde and water under conditions of heat and pressure to form the polymer sulfonic acid form, to which sodium hydroxide is added to make the final SPNS. The residue level of formaldehyde was 0.09%. Only around 1% of SNS in a 1-mg/ml solution applied to porcine skin penetrated the skin after 24 h, a similar amount was found noncovalently bound to the skin, and the concentration of material applied to the surface of the skin was largely unchanged. Both chemicals were not toxic in acute oral or dermal studies. In a subchronic oral toxicity study in rats, the effects noted were increases in urinary sugar in females and urine protein concentrations in males. Although undiluted SPNS was not a significant eye irritant in rabbits, undiluted SNS was a moderate eye irritant in rabbits. At 2%, SNS was a minimal eye irritant in rabbits. Undiluted SNS was at most a mild irritant in Guinea pigs, and was nonirritating at 20% and 2%. In a delayed contact hypersensitivity test in Guinea pigs, 30% SNS used in the induction phase and in the challenge phase produced no reactions. In a Guinea pig maximization test, 1% SNS used with Freund's complete adjuvant (FCA) injected in the initial sensitization, 50% SNS applied topically in the second sensitization, and up to 30% SNS applied topically in the challenge phase did not produce any irritation or sensitization. Both ingredients were negative in Ames mutagenesis assays. In clinical studies, SNS was neither an irritant (tested up to 2%), cumulative irritant (tested up to 1%), nor a sensitizer (tested up to 1%). The Panel considered the low penetration in concert with the low concentrations of use of these ingredients and the absence of significant overall toxicity and the limited negative genotoxicity findings sufficient to support a conclusion that SNS and SPNS are safe as used in cosmetic formulations intended to be applied to the skin. Use of SPNS in a lipstick formulation, was not considered to be different from application to the skin in that the barrier properties of the skin do not apply when these ingredients may contact mucous membranes or may be ingested. Accordingly, the Panel concluded that the available data are insufficient to support the safety of SNS and SPNS in cosmetic formulations that may contact mucous membranes or be ingested. The additional data needed to make a safety assessment for these uses include dermal reproductive and developmental toxicity data and one genotoxicity assay in a mammalian system, and if that study is positive, then a 2-year dermal carcinogenicity study using National Toxicology Program (NTP) methods may be needed.


MRI ventilation abnormalities predict quality-of-life and lung function changes in mild-to-moderate COPD: longitudinal TINCan study.
: COPD biomarkers are urgently required for clinical trials of new therapies. We evaluated the longitudinal change and relationship of MRI and CT biomarkers of COPD with St. George's Respiratory Questionnaire (SGRO) and FEV1 worsening over 30 months. Among imaging biomarkers, only the longitudinal change in MRI ventilation defect percent (VDP) was greater in ever-smoker (n=34/p<0.05) and COPD (n=48/p<0.0001) subgroups compared with never-smokers (n=42). Only the longitudinal change in VDP was correlated with change in SGRQ (r=0.26/p=0.03), and only baseline VDP predicted longitudinal change in SGRQ>minimum clinically important difference (p=0.047) in mild-to-moderate COPD. These data strongly support the use of MRI intermediate endpoints in COPD studies. NCT02723474; Status: Recruiting.


Safety and efficacy of stenting nonthrombotic iliac vein lesions in octogenarians and nonagenarians in an office setting.
Objectives Treatment options for venous insufficiency are rapidly evolving in the office setting and include venography, intravascular ultrasound, and venous stenting. Non-thrombotic iliac vein lesions assessment and treatment in an office setting is currently an area of interest. The purpose of this study is to demonstrate the safety and efficacy of evaluating non-thrombotic iliac vein lesion with this office-based procedure in octogenarians and nonagenarians. Methods From January 2012 through December 2013, 300 non-thrombotic iliac vein lesion limbs in 192 patients with venous insufficiency ≥80 years old were evaluated for non-thrombotic iliac vein lesion. Patients were evaluated and treated with venography, intravascular ultrasound, and stent placement for significant lesions demonstrated by greater than 50% diameter or cross-sectional area reduction. Group 1: 168 of these patients were octogenarians; female/male ratio was 1.75:1, bilateral in 89/168 patients (53%), left sided in 131/259 limbs (51%), right sided in 128 limbs (49%), average age 83.5 ± 2.6 years (range 80-89) compared to Group 2: 24 nonagenarians; female/male was 3:1, bilateral in 17/24 patients (70%), left sided in 20/41 limbs (49%), right sided in 21/41 limbs (51%), average age 92.9 ± 2.2 years (range 90-99). Stent related outcomes were evaluated with communication to the patient within 24 h to assess post-procedure pain followed by serial iliocaval ultrasonography. Results Out of the 300 limbs evaluated, in Group 1, 86% of limbs had stents placed compared to 90% in Group 2 and 11% of both groups had two stents placed. Overall improvement in pain, edema, and ulcers was reported in 147 (59%) of octogenarians and 24 (65%) of nonagenarians. There were no surgical site infections, pseudo-aneurysms, arteriovenous fistulas, or femoral artery injuries. No patients required transfusion within three days post-operatively and there were no 30-day mortalities in both sets of patients. Conclusions Our results demonstrate that there is no statistical difference in the outcome of performing venography, intravascular ultrasound, and stent placement in an office-based setting in octogenarians and nonagenarians. Both groups maintained a similar safety profile with low morbidity and mortality. In conclusion, we believe that the treatment of non-thrombotic iliac vein lesion in an office-based setting is safe and efficacious in both groups.


Liver failure from delayed hepatitis B reactivation in anti-HBc-positive patient following rituximab for B-cell lymphoma.
A 93-year-old man was admitted with 1 week of frank jaundice and abdominal pain. His medical history included diffuse large B-cell lymphoma treated with rituximab and cyclophosphamide, hydroxydaunomycin, oncovin and prednisolone (R-CHOP) chemotherapy 10 months prior. His investigations revealed marked hyperbilirubinemia with a total bilirubin of 355 μmol/L, along with a 17-fold elevation in alanine transaminase and impaired hepatic synthetic function. He tested hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (HBsAb) negative, hepatitis B core antibody (HBcAb) positive and had elevated hepatitis B virus DNA level at 13 691 IU/L. This was in the setting of radiological evidence of suspected cirrhosis. He was later found to have tested positive for HBcAb and negative for HBsAg and HBsAb prior to chemotherapy, but had not received antiviral prophylaxis. He was diagnosed with fulminant hepatitis secondary to delayed hepatitis B reactivation in the setting of rituximab. Hepatitis B reactivation and the role of screening and antiviral prophylaxis in isolated HBcAb-positive patients is reviewed.


In vitro synergistic interaction of alligator and human estrogen receptors with combinations of environmental chemicals.
The effect of mixtures of environmental chemicals with hormonal activity has not been well studied. To investigate this phenomenon, the estrogen receptor (ER) from the American alligator (aER) or human (hER) was incubated with [3H]17beta-estradiol in the presence of selected environmental chemicals individually or in combination. The environmental chemicals included the insecticide chlordane, which has no estrogenic activity, and the pesticides dieldrin and toxaphene, which have very weak estrogenic activity. Chlordane, dieldrin, and toxaphene individually demonstrated no appreciable displacement of [3H]17beta-estradiol from aER and hER at the concentration tested. A combination of these chemicals inhibited the binding of [3H]17beta-estradiol by 20 to 40%. Alachlor, a chemical recently discovered to have weak estrogenic activity, also displaced [3H]17beta-estradiol more effectively in combination with dieldrin than alone. These results indicate that combinations of some environmental chemicals inhibit [3H]17beta-estradiol binding in a synergistic manner. This suggests that the ER may contain more than one site for binding environmental chemicals. The possibility that the ER binds multiple environmental chemicals adds another level of complexity to the interaction between the environment and the endocrine system.


[Untersuchung des Tränenfilms und histologische Untersuchung der Augenlider von Möpsen].
To determine if qualitative tear film and histological changes of the eyelid margins in pugs compared to other brachycephalic dogs could be potential contributing factors to the high prevalence of corneal diseases in this breed. Ophthalmic examin ation (including tear film break-up time [TFBUT] and meibometry) was undertaken on three groups (pugs with and without ophthalmologic abnormalities as well as on other brachycephalic breeds with history of ophthalmologic abnormalities). Histology of eyelid tissue obtained during medial canthoplasty was performed, using hematoxylin-eosin and oil-red-O-staining. Seventy-eight pugs and 11 brachycephalic dogs were included. Mean ages were 3.54 and 5.5 years respectively. STT 1 values below 15 mm/min were found in 12 of 150 eyes of pugs and in three of 18 eyes of other brachycephalic dogs. Tear film break-up time values below 20 seconds were determined in 118 of 126 eyes of pugs, and in eight of 18 eyes of other brachycephalic dogs. Meibometry values over 100 MU were only identified in 20 of 147 eyes of pugs and 12 of 20 eyes in other brachycephalic dogs. Eyelid tissue of 21 pugs and 11 brachycephalic dogs was obtained. All pugs had a higher number of inflammatory cells in eyelid tissue than other brachycephalic breeds. Young pugs are often presented with STT 1 values within the reference range and low TFBUT and meibometry values. As other brachycephalic breeds are often presented with STT 1 values within reference ranges as well as low TFBUT values, the only marked difference between pugs and other brachycephalic breeds are low meibometry values and the higher number of inflammatory cells in the medial canthal lid margins.


Delayed-onset haematoma formation after cochlear implantation.
This paper presents our experience on delayed-onset haematoma formation after cochlear implantation, a topic which has not been well discussed in the literature. Retrospective case review study. Five children who had undergone cochlear implant surgery at 1.5 to 4 years of age (median, 2.5 years) were studied. The haematoma episodes occurred 2-12 years (median, 6 years) after cochlear implantation. Two patients had recurrent episodes. Two of the seven haematoma episodes were managed by needle aspiration alone, four by incision and drainage alone, and one by both needle aspiration and incision and drainage. Other than one patient with coagulopathy, there were no obvious predisposing factors, including trauma. The majority of delayed-onset haematomas occurred without obvious predisposing factors. Needle aspiration can differentiate a haematoma from an abscess or cerebrospinal fluid leakage, and it provides an effective immediate therapeutic solution. However, aseptic techniques are emphasised to minimise the chances of an uncomplicated haematoma converting into a septic one.


Propylene glycol-free melphalan as conditioning regimen for autologous transplantation in myeloma.
High-dose melphalan has been the drug of choice for preparative regimens for autologous stem cell transplantation in multiple myeloma. Propylene-free melphalan (Evomela™) is a newer formulation of melphalan, which incorporates Captisol® to produce a stable product upon reconstitution. In addition to avoiding propylene glycol with its' potential side effects, this approach improves the overall stability of reconstituted melphalan and can ensure intended dose delivery. In this paper, we review the published literature regarding this formulation. We focus on its' chemistry, pharmacokinetics and clinically available data for its use in myeloma autologous stem cell transplantation setting.


Improving child protection in the emergency department: a systematic review of professional interventions for health care providers.
This systematic review evaluated the effectiveness of professional and organizational interventions aimed at improving medical processes, such as documentation or clinical assessments by health care providers, in the care of pediatric emergency department (ED) patients where abuse was suspected. A search of electronic databases, references, key journals, and conference proceedings was conducted and primary authors were contacted. Studies whose purpose was to evaluate a strategy aimed at improving ED clinical care of suspected abuse were included. Study methodologic quality was assessed by two independent reviewers. One reviewer extracted the data, and a second checked for completeness and accuracy. Six studies met the inclusion criteria: one randomized controlled trial (RCT), one quasi-RCT, and four observational studies. Study quality ranged from modest (observational studies) to good (trials). Variation in study interventions and outcomes limited between-study comparisons. The quasi-RCT supported self-instructional education kits as a means to improve physician knowledge for both physical abuse (mean +/- standard deviation [SD] pretest score = 13.12 +/- 2.36; mean +/- SD posttest score = 18.16 +/- 1.64) and sexual abuse (mean +/- SD pretest score = 10.81 +/- 3.20; mean +/- SD posttest score = 18.45 +/- 1.79). Modest-quality observational studies evaluated reminder systems for physician documentation with similar results across studies. Compared to standard practice, chart checklists paired with an educational program increased physician consideration of nonaccidental burns in burn cases (59% increase), documentation of time of injury (36% increase), and documentation of consistency (53% increase) and compatibility (55% increase) of reported histories. Decisional flow charts for suspected physical abuse also increased documentation of nonaccidental physical injury (69.5% increase; p < 0.0001) and had a similar significant effect as checklists on increasing documentation of history consistency and compatibility (69.5 and 70.0% increases, respectively; p < 0.0001) when compared to standard practice. No improvements were noted in these studies for documentation of consultations or current status with child protective services. The introduction of a specialized team and crisis center to standardize practice had little effect on physician documentation, but did increase documentation of child protective services involvement (22.7% increase; p < 0.005) and discharge status (23.7% increase; p < 0.02). Referral to social services increased in one study following the introduction of a chart checklist (8.6% increase; p = 0.018). A recently conducted multisite RCT did not support observational findings, reporting no significant effect of educational sessions and/or a chart checklist on ED practices. The small number of studies identified in this review highlights the need for future quality studies that address care of a vulnerable clinical population. While moderate-quality observational studies suggest that education and reminder systems increase clinical knowledge and documentation, these findings are not supported by a multisite randomized trial. The limited theoretical base for conceptualizing change in health care providers and the influence of the ED environment on clinical practice are limitations to this current evidence base.


Excessive closure of the right eye: a new sign of infarction in the territory of the ipsilateral right middle cerebral artery.
In right middle cerebral territory infarction a new sign, excessive closure of the right eye ipsilateral to the lesion and mild closure of the left eye on command, was noted. The excessive ipsilateral eye closure was not observed on spontaneous eye closure.


Assessment of antidiabetic potential of Cynodon dactylon extract in streptozotocin diabetic rats.
This study was undertaken to investigate the hypoglycemic and antidiabetic effect of single and repeated oral administration of the aqueous extract of Cynodon dactylon (Family: Poaceae) in normal and streptozotocin induced diabetic rats, respectively. The effect of repeated oral administration of aqueous extract on serum lipid profile in diabetic rats was also examined. A range of doses, viz. 250, 500 and 1000mg/kg bw of aqueous extract of Cynodon dactylon were evaluated and the dose of 500mg/kg was identified as the most effective dose. It lowers blood glucose level around 31% after 4h of administration in normal rats. The same dose of 500mg/kg produced a fall of 23% in blood glucose level within 1h during glucose tolerance test (GTT) of mild diabetic rats. This dose has almost similar effect as that of standard drug tolbutamide (250mg/kg bw). Severely diabetic rats were also treated daily with 500mg/kg bw for 14 days and a significant reduction of 59% was observed in fasting blood glucose level. A reduction in the urine sugar level and increase in body weight of severe diabetic rats were additional corroborating factors for its antidiabetic potential. Total cholesterol (TC), low density lipoprotein (LDL) and triglyceride (TG) levels were decreased by 35, 77 and 29%, respectively, in severely diabetic rats whereas, cardioprotective, high density lipoprotein (HDL) was increased by 18%. These results clearly indicate that aqueous extract of Cynodon dactylon has high antidiabetic potential along with significant hypoglycemic and hypolipidemic effects.


Diagnostic accuracy of early computed tomographic angiography for visualizing medium sized inferior and posterior projecting carotid system aneurysms.
Conventional angiography, generally referred to as intra-arterial digital subtraction angiography, still remains the gold standard reference method for the diagnosis of intracranial aneurysms, helical computed tomography angiography (CTA) is a new non-invasive volumetric imaging method. This study was conducted to screen patients presenting with subarachnoidhemorrhage by CTA before conventional digital subtraction angiography (DSA) and subsequently comparing the results for various aneurysm projections. In a prospective study, 99 consecutive patients with an initial diagnosis of subarachnoid hemorrhage were screened for aneurysms with CTA followed by conventional DSA. There were 17 cases with negative angiograms in whom repeat angiograms, three months later were negative for 15 cases, while two cases were found to bear aneurysm on the repeat examination. Eighty two patients had at least one proven aneurysm on initial DSA and two on the repeat angiogram. Out of 84 patients, five underwent endovascular treatment and 79 patients who underwent surgical clipping were considered for projection evaluation. Sensitivity of CTA was 98.78% (95% confidence interval [CI], 93.4-99.7%), while the specificity was 100% (95% CI, 81.57-100%) and the kappa coefficient of agreement between CTA and DSA was 96.5%. The most significant discrepancies with DSA findings were for visualizing the projection of inferior and posterior projecting proximal anterior circulation aneurysms. Helical CTA was in good concordance with DSA for screening of cerebral aneurysms; however, for exact visualization of the aneurysm neck and its projection, especially if it is inferior or posterior, DSA remains the gold standard.


The impact of threat of shock-induced anxiety on alerting, orienting, and executive function in women: an ERP study.
The present study used a combination of the Threat-of-Shock paradigm and the Attention Network Test (ANT) to investigate how induced anxiety affects alerting, orienting, and executive control and whether individual differences in threat sensitivity moderate these effects. Forty-two female subjects completed the ANT task in alternation under shock-threat and no-shock ("safe") conditions while event-related potentials (ERPs) were recorded. The results showed that anxiety induced by the threat of shock had a significant impact on alerting and executive control functions at the neural level. Specifically, alerting-related N1 and stimulus-preceding negativity (SPN) differences between double cue and no cue conditions were greater in the threat versus safe state, suggesting that the induced anxiety promoted the early perception of cues and preparation for the target. Moreover, executive control-related P3 and sustained potential (SP) differences between incongruent and congruent trials were greater in the threat versus safe state, indicating that the induced anxiety might improve the attentional allocation efficiency and stimulate subjects to recruit more cognitive resources to resolve conflicts. However, orienting-related ERPs were not affected by the threat of shock, but the threat of shock promoted the processing efficiency of spatial-cue at the behavioral level. Analysis of individual differences revealed that trait anxiety moderated the attentional allocation efficiency when performing executive control related tasks in the threat versus safe state. Our findings demonstrate the adaptive significance of the threat of shock-induced anxiety in that being in an anxious state can enhance individuals' alerting, orienting, and executive functions.


A Retrospective Multicenter Study of 1898 Liquefied Petroleum Gas-Related Burn Patients in Eastern China From 2011 to 2015.
Liquefied petroleum gas (LPG) is a widely used environment-friendly fuel. Previous studies have shown an increasing number of LPG-related burns. Our study was designed to evaluate the epidemiologic pattern of these injuries and provide recommendations for burn prevention. This retrospective study included all patients with LPG-related burns from eight burn centers in Zhejiang Province, China between 2011 and 2015. Database variables included patient demographics, accident characteristics, and injury characteristics. The association between different categorical variables was identified using the chi-square test. And the association between two or more means of quantitative variables was analyzed by the one-way analysis of variance or t-test. A total of 1898 patients were included, 47.31% were males and 52.69% were females. The predominant age group was 31 to 70 years (74.50%), and the majority were poorly educated and the incidence peaked from June to September. The most common place of occurrence was home (74.08%) and gas leak (96.52%) was the most common cause. The four limbs (43.33%) were the most frequently affected areas; the mean burn area was 25.19 ± 20.97% of the total body surface area and most patients (46.89%) suffered from moderate burns. The mean length of hospital stay was 17.66 ± 16.55 days and the majority of patients (89.36%) recovered with a 0.84% mortality rate. Our findings reflected that the increase in incidence rate was alarming, and the causes resulting in LPG-related burns have not gained much attention yet. Therefore, this calls for simple but strict measures aiming at each hazardous step during the use of LPG to prevent these burn injuries.