Early Endothelial Activation in a Mouse Model of Graft vs Host Disease Following Chemotherapy.
Allogenic hematopoietic stem cell transplant (allo-HSCT) can lead to sinusoidal obstruction syndrome (SOS) and graft-versus-host disease (GvHD) in some individuals. GvHD is characterised by an immune triggered response that arises due to donor T cells recognizing the recipient tissue as "foreign". SOS results in impaired liver function due to microvascular thrombosis and consequent obstruction of liver sinusoids. Endothelial damage occurs following chemotherapy and allo-HSCT and is strongly associated with GvHD onset as well as hepatic SOS. Animal models of GvHD are rarely clinically relevant, and endothelial dysfunction remains uncharacterised. Here we established and characterised a clinically relevant model of GvHD wherein Balb/C mice were subjected to myeloablative chemotherapy followed by transplantation of bone marrow (BM) cells± splenic T-cells from C57Bl6 mice, resulting in a mismatch of major histocompatibility complexes (MHC). Onset of disease indicated by weight loss and apoptosis in the liver and intestine was discovered at day 6 post-transplant in mice receiving BM+T-cells, with established GvHD detectable by histology of the liver within 3 weeks. Together with significant increases in pro-inflammatory cytokine gene expression in the liver and intestine, histopathological signs of GvHD and a significant increase in CD4+ and CD8+ effector and memory T-cells were seen. Endothelial activation including upregulation of vascular cell adhesion molecule (VCAM)- 1 and downregulation of endothelial nitric oxide synthase (eNOS) as well as thrombosis in the liver indicated concomitant hepatic SOS. Our findings confirm that endothelial activation is an early sign of acute GvHD and SOS in a clinically relevant mouse model of GvHD based on myeloablative chemotherapy. Preventing endothelial activation may be a viable therapeutic strategy to prevent GvHD.


Randomized phase II open-label study of mFOLFOX6 in combination with linifanib or bevacizumab for metastatic colorectal cancer.
Although CRC is the third most commonly diagnosed cancer in the United States, second-line CRC treatment is limited. In this trial we examined the efficacy and safety of linifanib, an oral, potent, selective tyrosine kinase inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptor families, with mFOLFOX6, compared with bevacizumab and mFOLFOX6, in previously treated metastatic CRC. One hundred forty-eight patients with advanced CRC previously treated with fluoropyrimidine or irinotecan received bevacizumab (10 mg/kg, intravenous), low-dose linifanib (7.5 mg), or high-dose linifanib (12.5 mg), with mFOLFOX6. The primary end point was progression-free survival (PFS). Secondary objectives included overall survival (OS), objective response rate (ORR), and safety. No statistically significant differences in PFS occurred between bevacizumab and linifanib doses (low, hazard ratio [HR], 1.453 [95% confidence interval [CI], 0.830-2.539]; high, HR, 1.257 [95% CI, 0.672-2.351]). Median OS values were similar for bevacizumab and high-dose linifanib (bevacizumab, 16.5 months [95% CI, 13.0-not available]; high-dose linifanib, 16.4 months [95% CI, 11.9-21.7]; low-dose linifanib, 12.0 months [95% CI, 10.1-13.0]). ORRs were similar (bevacizumab, 34.7% [95% CI, 21.7-49.6]; low-dose linifanib, 24.0% [95% CI, 13.1-38.2]; high-dose linifanib, 22.4% [95% CI, 11.8-36.6]). Median cycles of 5-fluorouracil were reduced in the linifanib arms, versus the bevacizumab arm. Grade 3/4 adverse event occurrences were more frequent with linifanib. Palmar-plantar erythrodysesthesia, hypothyroidism, and thrombocytopenia were more common with high-dose linifanib than bevacizumab. Combining linifanib with mFOLFOX6 as a second-line treatment for metastatic CRC did not improve PFS, radiographic findings, or duration of response versus bevacizumab and mFOLFOX6.


Complications in Endoscopic Ear Surgery.
The aim of this study was to examine the premise that endoscopic ear surgery (EES) is associated with a low rate of complications (intraoperative and postoperative). Retrospective review at two institutions. Tertiary referral center. The study included 825 patients who underwent exclusive EES between 2008 and 2016 at the Otorhinolaryngology-Head and Neck Surgery Department of Modena University Hospital, and between 2014 and 2016 at the Otorhinolaryngology-Head and Neck Surgery Department of Verona University Hospital. Exclusive endoscopic ear surgery between 2008 and 2016 (tympanoplasties, second look or revision tympanoplasties, myringoplasties, stapedoplasties, canalplasties, ossiculoplasties, and exploratory tympanotomies). All surgical procedures were performed by two experienced surgeons. For each procedure, intraoperative, and early and delayed postoperative complications were evaluated. The most common ear pathologies for which patients were sent for EES were cholesteatoma (33.6%), chronic otitis media (36.3%) and otosclerosis (26.8%). There was no case of major intraoperative complications such as injury to the dura or vascular structures. We observed minor intraoperative complications in 4.1% of the cases. Only 1.3% of patients experienced early postoperative complications. Delayed complications affected less than 1% of the cohort. Data from this study confirm the safety of the endoscopic technique, with very low complication rates, indicating that EES is a reliable therapeutic option, in particular, for tympanoplasties, myringoplasties, and stapedoplasties, as well as second look procedures. We have reported our experience with EES morbidity so that it can be compared with data from other centers using the same surgical technique.


Integrative etiopathogenetic models of psychotic disorders: methods, evidence and concepts.
Integrative models of the etiopathogesnesis of psychotic disorders are needed since a wealth of information from such diverse fields as neurobiology, psychology, and the social sciences is currently changing the concepts of mental disorders. Several approaches to integrate these streams of information into coherent concepts of psychosis are feasible and will need to be assessed in future experimental studies. Common to these concepts are the notion of psychotic disorders as brain disorders and a polythetic approach in that it is increasingly realized that a multitude of interindividually partially different pathogenetic factors interact in individual persons in a complex fashion resulting in the clinical symptoms of psychosis.


Targeting of the pedunculopontine nucleus by an MRI-guided approach: a cadaver study.
Laboratory evidence suggests that the pedunculopontine nucleus (PPN) plays a central role in the initiation and maintenance of gait. Translational research has led to reports on deep brain stimulation (DBS) of the rostral brainstem in parkinsonian patients. However, initial clinical results appear to be rather variable. Possible factors include patient selection and the wide variability in anatomical location of implanted electrodes. Clinical studies on PPN DBS efficacy would, therefore, benefit from an accurate and reproducible method of stereotactic localization of the nucleus. The present study evaluates the anatomical accuracy of a specific protocol for MRI-guided stereotactic targeting of the PPN in a human cadaver. Imaging at 1.5 and 9.4 T confirmed electrode location in the intended region as defined anatomically by the surrounding fiber tracts. The spatial relations of each electrode track to the nucleus were explored by subsequent histological examination. This confirmed that the neuropil surrounding each electrode track contained scattered large neurons morphologically consistent with those of the subnucleus dissipatus and compactus of the PPN. The results support the accuracy of the described specific MR imaging protocol.


Namodenoson Inhibits the Growth of Pancreatic Carcinoma via Deregulation of the Wnt/β-catenin, NF-κB, and RAS Signaling Pathways.
Namodenoson, an A3 adenosine receptor (A3AR) agonist, is currently being used in a phase III trial in advanced liver cancer. We examined the anti-growth effect of namodenoson on pancreatic carcinoma cells and investigated the molecular mechanism involved. BxPC-3 pancreatic carcinoma cells were cultured with namodenoson (5-20 nM for 24 h at 37 °C), and the Presto Blue assay was used to monitor cell growth. Western blot analyses were performed on BxPC-3 cells (20 nM namodenoson for 24 h at 37 °C) to evaluate the expression levels of cell growth regulatory proteins. In vivo studies involved the subcutaneous inoculation of BxPC-3 cells into nude mice, randomizing the mice into namodenoson (10 μg/kg twice daily for 35 days) vs. control, and monitoring tumor size twice weekly. Treatment with namodenoson was associated with the significant dose-dependent inhibition of BxPC-3 cell growth, which was mitigated by the A3AR antagonist MRS1523. Western blot analyses showed that namodenoson treatment modulated the expression of NF-κB, as well as proteins in the Wnt/β-catenin and the RAS signaling pathways, leading to the upregulation of apoptotic proteins (Bad, Bax). In vivo studies also showed the significant inhibition of pancreatic carcinoma tumor growth with namodenoson. In conclusion, our findings support the continued development of namodenoson as a treatment for pancreatic cancer.


[Guillain-Barré syndrome and its frontiers]
Knowledge concerning Guillain-Barré syndrome (GBS) has been largely extended these past ten years. The first description by Guillain, Barre and Strohl in 1916 established the main clinical and biological characteristics of the syndrome: acute motor weakness affecting at least one limb associated with areflexia. The syndrome was at first restricted to the concept of an acute inflammatory demyelinating polyneuropathy after the first large electrophysiological and histological studies (Asbury et al., 1969). This restricted definition of the GBS was changed by the report of Feasby in 1986 of an axonal variant of the syndrome. This proposal remained controversial until large studies reported that GBS in Northern China occurs in epidemics, predominantly involving young adults and children and characterized electrophysiologically by pure motor axonal features (AMAN). Additional studies showed that another GBS variant may result from an attack against both motor and sensory axons (AMSAN). Previously in 1956 CM Fisher described a clinical triad of ataxia, areflexia and ophthalmoplegia associated with albumino-cytologic dissociation and excellent recovery which was considered immediately part of the GBS. The physiopathology of the syndrome was recently determined (anti-GQ1b antibodies). A number of clinical variant of more limited scope have also been described. Plasma exchanges and intravenous immunoglobulin (IVIg) are the gold standard therapies for the demyelinating form and probably for the other variants despite the absence of controlled trials.


Decarboxylative Iodination and Suzuki-Miyaura Coupling Reactions to Access Chiral 3,3'-Diaryl-1,1'-bi-2-naphthols.
An efficient synthesis of the enantiomerically pure 3,3'-bis-arylated BINOLs is accomplished through decarboxylative iodination of the dimethyl ether derivative of BINOL-3,3'-dicarboxylic acid followed by Suzuki-Miyaura coupling using a one-pot protocol. The decarboxylative iodination is effected with the dimethyl ether derivative of BINOL-3,3'-dicarboxylic acid using iodine as a terminal oxidant and the cheaply available K3PO4 as a base under neat conditions. This protocol facilitated the introduction of the aryl group at the 3,3'-position on the binaphthyl system using aryl boronic acid through a palladium-catalyzed Suzuki-Miyaura coupling reaction.


An evaluation of the suitability, readability, quality, and usefulness of online resources for family caregivers of patients with cancer.
Evaluate the suitability, readability, quality, and usefulness of publicly available online resources for cancer caregivers. Resources identified through a Google search and environmental scan were evaluated using the Suitability Assessment of Materials (SAM), an online readability text analysis tool, the DISCERN (quality), and caregivers' unmet needs checklist (usefulness). Descriptive analyses and cluster analysis to identify the group of resources with the highest SAM and DISCERN scores were performed. 55 resources were evaluated. The suitability of 48/55 (87%) resources were categorized as adequate (SAM scores 40-69), with no resources ranking in the superior category (SAM scores > 70%). The readability of 51/55 (93%) resources exceeded 9th grade reading level. The mean quality score as a percentage was 49% (SD 11.5). On average resources addressed 9.9/33 unmet needs (SD = 5.8). A high-quality cluster was identified and included 15 (27%) websites. Online resources for cancer caregivers are not optimal in terms of their suitability, readability, quality, and usefulness. The highest ranked resources include, Cancer Council Australia's booklet, Caring for Someone with Cancer, and the American Cancer Society's webpages, Caregivers and Families. Study findings will allow healthcare professionals to better address cancer caregivers' needs by recommending the most optimal resources.


The complex interaction between atrial fibrillation and heart failure in elderly patients.
Heart failure (HF) and atrial fibrillation (AF) often coexist. Subjects with permanent AF show the highest prevalence of HF. Patients with incident AF have HF in a great number of cases and, reciprocally, in patients with incident HF, an AF can be frequently found. The simultaneous presence of the two conditions is associated with mortality rates higher than those observed in individuals with only one or none of them. Interestingly, HF and AF could synergistically promote in elderly patients the development of disability and dementia. Inflammatory mechanisms coupled with changes of renin-angiotensin system, hormonal pathways and neuro-mediators could simultaneously promote left atrium remodeling and sustain both HF and AF. Beta-blockers and digoxin seem to have small therapeutic effect and limited influence on prognosis in these very complex patients. Sinus rhythm restoration could slow down the progression of disability in symptomatic subjects. Recent evidence seem to suggest that upstream therapy coupled with rehabilitation, and that AV node ablation associated with cardiac resynchronization therapy could benefit subjects with HF and AF. In conclusion, elderly patients simultaneously presenting problems of cardiac function and arrhythmia are an important challenge for geriatric medicine, and request important efforts to improve their functional profile and prognosis.


[Effect of instenon on the uterine contractile activity].
The effect of instenon upon the uterine contractile activity was studied in pregnant rats. The drug administration at a dose resulted in significant suppression of the myometrium contractility. The effect was not decreased when instenon was injected against the background of oxytocin. On the other hand, the concurrent injection of oxytocin upon a single or long-term administration of instenon produced a pronounced stimulating action on the myometrium contractility.


Awareness of Breast Cancer among Female Care Givers in Tertiary Cancer Hospital, China
Objective: Breast cancer is a worldwide public health issue and most common cancer diagnosed among women including China, where advanced stages at diagnosis appears to be increasing and an ever-rising incidence twice as fast as global rates. The study was conducted to describe the awareness of breast cancer and associated factors among care giver women in tertiary Cancer Hospital, China. Methods: Institutional based cross-sectional study was conducted among 261 women selected by systematic random sampling. Information provided by the participants was converted into awareness scores for analysis using SPSS version 23. Awareness scores were dichotomized in to 'good awareness and 'poor awareness' taking median score=11 as the cut-off point. Data analysis was performed using the binary logistic regression. A p-value of <0.05 was considered statistically significant. Result: The study showed that 46.7% of the respondents had good awareness. Breast lump was the most commonly known symptom of cancer by 61.7% of the respondents. Slightly more than half of the study participants acknowledged having a past history of breast cancer, drinking alcohol and having close relative with breast cancer as potential risk factors for breast cancer (63.6%, 58.6%, and 55.6% respectively). Nevertheless, a vast majority of the study participants were unable to appreciate modifiable risk factors of the disease. More than half of the participants had never/rarely checked their breasts and all of the participants wrongly answered breast cancer knowledge age related risk. Awareness level was significantly associated with entertainment preference (OR=3.57; 95%CI=1.71, 7.44) and residence setting areas (OR=2.4; 95%CI=1.04, 5.69). Conclusion: The study indicated suboptimal awareness while entertainment preference and residence setting were significantly associated with awareness level. Public awareness campaigns should be made by dissemination of information about breast cancer through health education and printed Medias with great emphases on women living in rural areas.


Variations in Cause-of-Death Determination for Sudden Unexpected Infant Deaths.
To quantify and describe variation in cause-of-death certification of sudden unexpected infant deaths (SUIDs) among US medical examiners and coroners. From January to November 2014, we conducted a nationally representative survey of US medical examiners and coroners who certify infant deaths. Two-stage unequal probability sampling with replacement was used. Medical examiners and coroners were asked to classify SUIDs based on hypothetical scenarios and to describe the evidence considered and investigative procedures used for cause-of-death determination. Frequencies and weighted percentages were calculated. Of the 801 surveys mailed, 60% were returned, and 377 were deemed eligible and complete. Medical examiners and coroners classification of infant deaths varied by scenario. For 3 scenarios portraying potential airway obstruction and negative autopsy findings, 61% to 69% classified the death as suffocation/asphyxia. In the last scenario, which portrayed a healthy infant in a safe sleep environment with negative autopsy findings, medical examiners and coroners classified the death as sudden infant death syndrome (38%) and SUID (30%). Reliance on investigative procedures to determine cause varied, but 94% indicated using death scene investigations, 88% full autopsy, 85% toxicology analyses, and 82% medical history review. US medical examiners and coroners apply variable practices to classify and investigate SUID, and thus, they certify the same deaths differently. This variability influences surveillance and research, impacts true understanding of infant mortality causes, and inhibits our ability to accurately monitor and ultimately prevent future deaths. Findings may inform future strategies for promoting standardized practices for SUID classification.


Pantethine rescues phosphopantothenoylcysteine synthetase and phosphopantothenoylcysteine decarboxylase deficiency in Escherichia coli but not in Pseudomonas aeruginosa.
Coenzyme A (CoA) plays a central and essential role in all living organisms. The pathway leading to CoA biosynthesis has been considered an attractive target for developing new antimicrobial agents with novel mechanisms of action. By using an arabinose-regulated expression system, the essentiality of coaBC, a single gene encoding a bifunctional protein catalyzing two consecutive steps in the CoA pathway converting 4'-phosphopantothenate to 4'-phosphopantetheine, was confirmed in Escherichia coli. Utilizing this regulated coaBC strain, it was further demonstrated that E. coli can effectively metabolize pantethine to bypass the requirement for coaBC. Interestingly, pantethine cannot be used by Pseudomonas aeruginosa to obviate coaBC. Through reciprocal complementation studies in combination with biochemical characterization, it was demonstrated that the differential characteristics of pantethine utilization in these two microorganisms are due to the different substrate specificities associated with endogenous pantothenate kinase, the first enzyme in the CoA biosynthetic pathway encoded by coaA in E. coli and coaX in P. aeruginosa.


IpsiHand Bravo: an improved EEG-based brain-computer interface for hand motor control rehabilitation.
Stroke and other nervous system injuries can damage or destroy hand motor control and greatly upset daily activities. Brain computer interfaces (BCIs) represent an emerging technology that can bypass damaged nerves to restore basic motor function and provide more effective rehabilitation. A wireless BCI system was implemented to realize these goals using electroencephalographic brain signals, machine learning techniques, and a custom designed orthosis. The IpsiHand Bravo BCI system is designed to reach a large demographic by using non-traditional brain signals and improving on past BCI system pitfalls.


Large artery stiffening with weight gain in humans: role of visceral fat accumulation.
We tested the hypothesis that weight gain would increase arterial stiffness in healthy nonobese adults. To address this, we overfed 14 nonobese men (age: 23+/-1 years) approximately 1000 kcal/d for 6 to 8 weeks until a 5-kg weight gain was achieved. Carotid diameters (high-resolution ultrasound) and pressures (applanation tonometry), body composition (dual energy x-ray absorptiometry), and abdominal fat distribution (computed tomography) were measured at baseline and following 4 weeks of weight stability at each individual's elevated body weight. Overfeeding increased body weight 5.1+/-0.1 kg and body fat 3.4+/-0.4 kg (both P<0.001) in 45+/-7 days. Total abdominal fat increased 46+/-7 cm(2) with weight gain due to increases in both subcutaneous (30+/-6 cm(2)) and visceral fat (15+/-4 cm(2); all P<0.01). As hypothesized, weight gain increased arterial stiffness 13+/-6% and decreased arterial compliance 21+/-4% (both P<0.05). Furthermore, those individuals above the median increase in abdominal visceral fat demonstrated a significantly greater increase in arterial stiffness (0.97+/-0.29 versus 0.06+/-0.36 U; P<0.05) compared with those below the median. Consistent with these observations, the only correlates of the changes in arterial stiffness with weight gain were the increases in total abdominal fat (r=0.794), abdominal visceral fat (r=0.651), and waist circumference (r=0.470; all P<0.05). Taken together, these findings suggest that modest weight gain is associated with increases arterial stiffness in nonobese men. The degree of large artery stiffening with weight gain seems to be determined, in part, by the amount of abdominal visceral fat gain. Importantly, this relation is independent of the amount of total body fat gained.


Vitamin B6 deficiency is prevalent in primary and secondary myelofibrosis patients.
Vitamin B6 (VB6) deficiency contributes to oncogenesis and tumor progression in certain cancers, and is prevalent in cancer patients in general. VB6 is also an essential element of heme synthesis, and deficiency can lead to anemia. Primary myelofibrosis (PMF) and secondary myelofibrosis (sMF) are myeloproliferative neoplasms often presenting with anemia along with other cytopenias. We performed a prospective study to determine whether PMF and sMF patients suffer from VB6 deficiency, and whether VB6-deficient patients show improvement of anemias with VB6 supplementation. Twelve PMF patients and 11 sMF patients were analyzed. A total of 16 of 23 patients (69.6%) were found to have VB6 deficiency, but VB6 supplementation with pyridoxal phosphate hydrate did not elevate hemoglobin levels in deficient patients. None of the patients presented with vitamin B12, iron, or copper deficiencies. Four patients showed serum folate levels below the lower limit of normal and eight patients showed serum zinc levels below the lower limit of normal; however, these deficiencies were marginal and unlikely to contribute to anemia. Compared to VB6-sufficient patients, VB6-deficient patients showed significantly lower serum folate levels and higher serum copper levels. Studies elucidating the relationship of VB6 deficiency and etiology of PMF/sMF are warranted.


Effect of Foot Reflexology on Pain, Fatigue, and Quality of Sleep after Kidney Transplantation Surgery: A Parallel Randomized Controlled Trial.
The study was a parallel randomized controlled trial. Patients admitted to the transplantation ward participated in the study. Fifty-three eligible patients were allocated into the foot reflexology group (n = 26) and the control group (n = 27) by using the stratified randomization method. Finally, 25 participants in each group finished the study. The intervention group received foot reflexology for 30 minutes once a day for three consecutive days, and no reflexology was applied in the control group. The intervention started on the second day after surgery. Pain, fatigue, and quality of sleep were measured on the first, second (before intervention), third, fourth, and eleventh days after surgery. Data were collected using visual analogue scale for measuring pain and fatigue and Verran and Snyder-Halpern sleep scale for measuring quality of sleep. In each group, 25 patients finished the study. The mean pain score in the foot reflexology and control groups decreased from 9.44 ± 0.96 and 9.36 ± 0.91 on the day of surgery to 1.32 ± 0.94 and 4.32 ± 1.68 on the eleventh day after surgery, respectively. The mean fatigue score in the reflexology and control groups decreased from 8.76 ± 1.27 and 8.6 ± 1.26 on the day of surgery to 1.24 ± 1.2 and 3.92 ± 1.63 on the eleventh day after surgery, respectively. The mean sleep score in the foot reflexology and control groups increased from 33.38 ± 11.22 and 39.59 ± 12.8 on the day of surgery to 69.43 ± 12.8 and 56.27 ± 8.03 on the eleventh day after surgery, respectively. While pain, fatigue, and sleep quality scores improved in both groups, those in the intervention group showed significantly greater improvement compared with the control group (P < 0.001). No significant difference was found between the two groups in the use of acetaminophen on the first, second, third, fourth, and eleventh days after surgery (P > 0.05). Foot reflexology may reduce pain and fatigue and improve sleep quality of patients after kidney transplantation.


Is there a role for dacomitinib, a second-generation irreversible inhibitor of the epidermal-growth factor receptor tyrosine kinase, in advanced non-small cell lung cancer?
Non-small cell lung cancer (NSCLC) is a highly lethal disease. During the past 20 years, the epidermal growth factor receptor (EGFR) has been a relevant target for anticancer drug-design, and a large family of EGFR tyrosine kinase inhibitors (TKI) were designed, which improved therapeutic outcomes compared to conventional chemotherapy in NSCLC patients with specific EGFR mutations. However, resistance to these inhibitors occurs; therefore, the debate on which inhibitor should be used first is still open. Dacomitinib was approved in 2018 for the first-line treatment of NSCLC with EGFR activating mutations. This manuscript reviews the properties of dacomitinib, including the current information from clinical trials and its potential application as stand-alone therapy, or in combination. Dacomitinib is a second-generation EGFR-TKI that has demonstrated significant improvement in overall survival in a phase III randomized study compared with gefitinib, a first-generation TKI. However, the rapid development and approval of a new generation of TKIs (osimertinib), with better clinical profiles, raises the question of which role can dacomitinib play in NSCLC. Further studies are required to evaluate the efficacy of this drug on brain metastases, as a second-line treatment after third-generation TKIs, or in combination with other types of treatments.


Common Variants in Osteopontin and CD44 Genes as Predictors of Treatment Outcome in Radiotherapy and Chemoradiotherapy for Non-Small Cell Lung Cancer.
Osteopontin (OPN)-CD44 signaling plays an important role in promoting tumor progression and metastasis. In cancer, OPN and CD44 overexpression is a marker of aggressive disease and poor prognosis, and correlates with therapy resistance. In this study, we aimed to evaluate the association of single nucleotide polymorphisms (SNPs) in the OPN and CD44 genes with clinical outcomes in 307 non-small cell lung cancer (NSCLC) patients treated with radiotherapy or chemoradiotherapy. The potential impact of the variants on plasma OPN levels was also investigated. Multivariate analysis showed that OPN rs11730582 CC carriers had a significantly increased risk of death (p = 0.029), while the CD44 rs187116 A allele correlated with a reduced risk of locoregional recurrence (p = 0.016) in the curative treatment subset. The rs11730582/rs187116 combination was associated with an elevated risk of metastasis in these patients (p = 0.016). Furthermore, the OPN rs1126772 G variant alone (p = 0.018) and in combination with rs11730582 CC (p = 7 × 10-5) was associated with poor overall survival (OS) in the squamous cell carcinoma subgroup. The rs11730582 CC, rs187116 GG, and rs1126772 G, as well as their respective combinations, were independent risk factors for unfavorable treatment outcomes. The impact of rs11730582-rs1126772 haplotypes on OS was also observed. These data suggest that OPN and CD44 germline variants may predict treatment effects in NSCLC.


Loss of B cells and their precursors is the most constant feature of GATA-2 deficiency in childhood myelodysplastic syndrome.
GATA-2 deficiency was recently described as common cause of overlapping syndromes of immunodeficiency, lymphedema, familiar myelodysplastic syndrome or acute myeloid leukemia. The aim of our study was to analyze bone marrow and peripheral blood samples of children with myelodysplastic syndrome or aplastic anemia to define prevalence of the GATA2 mutation and to assess whether mutations in GATA-2 transcription factor exhibit specific immunophenotypic features. The prevalence of a GATA2 mutation in a consecutively diagnosed cohort of children was 14% in advanced forms of myelodysplastic syndrome (refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and myelodysplasia-related acute myeloid leukemia), 17% in refractory cytopenia of childhood, and 0% in aplastic anemia. In GATA-2-deficient cases, we found the most profound B-cell lymphopenia, including its progenitors in blood and bone marrow, which correlated with significantly diminished intronRSS-Kde recombination excision circles in comparison to other myelodysplastic syndrome/aplastic anemia cases. The other typical features of GATA-2 deficiency (monocytopenia and natural killer cell lymphopenia) were less discriminative. In conclusion, we suggest screening for GATA2 mutations in pediatric myelodysplastic syndrome, preferentially in patients with impaired B-cell homeostasis in bone marrow and peripheral blood (low number of progenitors, intronRSS-Kde recombination excision circles and naïve cells).


Widening Access; Developing an eLearning Resource for Health and Social Care Professionals Caring for Children and Young People with Cancer.
Cancer is a key priority worldwide, and caring for children and young people with cancer requires a range of specific knowledge, skills and experience in order to deliver the complex care regimes both within the hospital or community environment. The aim of this paper is to disseminate work undertaken to design and develop pedagogical practice and innovation through an eLearning resource for health care professionals caring for children and young people with cancer across the globe. The work undertaken evaluated an existing cancer course (which has been withdrawn) that was developed and delivered through the Paediatric Oncology Nurses Forum, Royal College Nursing (Nurse Educators) and Warwick University. The evaluation consisted of 26 open and closed questions relating to the previous resource and was circulated to all health and social care professionals involved directly within specialist oncology services through the Children's Cancer and Leukaemia Group. Questionnaires were sent out to a convenience sample of 773 health care professionals and the response rate was 14%. The findings identified that the course was predominantly accessed by nurses, but other health care professionals also found it useful. Participants highlighted several areas where they believed content could be developed or was lacking. This included areas such as palliative and end of life care, nutrition, sepsis and teenagers and young people. This feedback was then used to develop a site dedicated to the care of children and young people with cancer.


Novel mutation in ENG gene causing Hereditary Hemorrhagic Telangiectasia in a Peruvian family.
Hereditary Hemorrhagic Telangiectasia (HHT) is a rare disorder of vascular development. Common manifestations include epistaxis, telangiectasias and arteriovenous malformations (AVMs) in multiple organs. Most patients have deletions or missense mutations in the ENG or ACVRL1 gene respectively, significantly affecting endothelium homeostasis. We analyzed the ENG gene in five members of a Peruvian family affected by HHT. One novel mutation was found in exon four of the ENG gene c.408delA, at aminoacid residue 136. This mutation changes the subsequent reading frame producing an early stop at residue 162, preserving only one fourth of the normal protein of 658 aa. This mutation was found in the four affected members of family.


MolAxis: a server for identification of channels in macromolecules.
MolAxis is a freely available, easy-to-use web server for identification of channels that connect buried cavities to the outside of macromolecules and for transmembrane (TM) channels in proteins. Biological channels are essential for physiological processes such as electrolyte and metabolite transport across membranes and enzyme catalysis, and can play a role in substrate specificity. Motivated by the importance of channel identification in macromolecules, we developed the MolAxis server. MolAxis implements state-of-the-art, accurate computational-geometry techniques that reduce the dimensions of the channel finding problem, rendering the algorithm extremely efficient. Given a protein or nucleic acid structure in the PDB format, the server outputs all possible channels that connect buried cavities to the outside of the protein or points to the main channel in TM proteins. For each channel, the gating residues and the narrowest radius termed 'bottleneck' are also given along with a full list of the lining residues and the channel surface in a 3D graphical representation. The users can manipulate advanced parameters and direct the channel search according to their needs. MolAxis is available as a web server or as a stand-alone program at http://bioinfo3d.cs.tau.ac.il/MolAxis.


Testing paleolimnological predictions with molecular data: the origins of Holarctic Eubosmina.
Zooplankton of the family Bosminidae have a unique paleolimnological record in many Holarctic lakes that provides a near continuous record of morphological change for thousands of years. If this morphological change could be interpreted reliably, then a rarely achieved direct observation of macroevolution would be feasible. We tested paleolimnological predictions derived from morphological variation found in the genus Eubosmina using mtDNA and nuclear DNA sequence variation from geographically distant Holarctic sites. The mtDNA and nDNA trees were congruent but genetic divergence was inversely associated with morphological divergence. The three most genetically divergent groups belonged to Eubosmina longispina, whose phylogeography and genetic divergence was consistent with glacial vicariance. The genetic evidence also supported the hypothesis that at least two Nearctic species were recent European introductions. Finally, the genetic evidence was consistent with paleolimnology in the finding of several proposed species undergoing rapid morphological evolution and being post-glacially derived from European E. longispina. The results suggested that lacustrine bosminids are susceptible to geographic speciation processes, and that morphological interpretation of diversity in paleolimnology can be markedly improved by genetic studies.


A common immunoregulatory locus controls susceptibility to actively induced experimental allergic encephalomyelitis and experimental allergic orchitis in BALB/c mice.
Previous studies have shown that differential susceptibility to actively induced experimental allergic encephalomyelitis (EAE) and experimental allergic orchitis (EAO) exists among various BALB/c substrains. Of eight substrains studied for EAE and 13 for EAO, BALB/cJ mice are phenotypically the most resistant to disease induction. Resistance to both diseases is controlled by single recessive mutations unlinked to any of the known alleles distinguishing BALB/cJ mice. In this study, segregation analysis employing a second generation backcross population shows that resistance to both EAE and EAO is due to a mutation in a common immunoregulatory gene. The role of immunoregulatory cells in controlling EAE resistance was examined using adoptive transfer protocols. BALB/cJ mice immunized with spinal cord homogenate plus adjuvants generate immunoregulatory spleen cells (SpC) that, when transferred to naive BALB/cByJ recipients, reduce the incidence and severity of EAE. Treatment of such cells with either cytotoxic monoclonal anti-Thy1.2 or anti-CD4 plus C' before transfer abrogates the ability of BALB/cJ SpC to inhibit disease. In contrast, neither SpC from adjuvant-immunized BALB/cJ nor spinal cord homogenate- plus adjuvant-primed BALB/cByJ donors influences the incidence or severity of disease observed in recipients. In addition, the role of environment in influencing susceptibility to EAE and EAO in BALB/c mice is documented. Taken together, these results support the existence of a common disease susceptibility locus in the pathways leading to two autoantigenically distinct CD4+ T cell-mediated, organ-specific, autoimmune diseases.


Opinion Mining From Social Media Short Texts: Does Collective Intelligence Beat Deep Learning?
The era of big data has, among others, three characteristics: the huge amounts of data created every day and in every form by everyday people, artificial intelligence tools to mine information from those data and effective algorithms that allow this data mining in real or close to real time. On the other hand, opinion mining in social media is nowadays an important parameter of social media marketing. Digital media giants such as Google and Facebook developed and employed their own tools for that purpose. These tools are based on publicly available software libraries and tools such as Word2Vec (or Doc2Vec) and fasttext, which emphasize topic modeling and extract low-level features using deep learning approaches. So far, researchers have focused their efforts on opinion mining and especially on sentiment analysis of tweets. This trend reflects the availability of the Twitter API that simplifies automatic data (tweet) collection and testing of the proposed algorithms in real situations. However, if we are really interested in realistic opinion mining we should consider mining opinions from social media platforms such as Facebook and Instagram, which are far more popular among everyday people. The basic purpose of this paper is to compare various kinds of low-level features, including those extracted through deep learning, as in fasttext and Doc2Vec, and keywords suggested by the crowd, called crowd lexicon herein, through a crowdsourcing platform. The application target is sentiment analysis of tweets and Facebook comments on commercial products. We also compare several machine learning methods for the creation of sentiment analysis models and conclude that, even in the era of big data, allowing people to annotate (a small portion of) data would allow effective artificial intelligence tools to be developed using the learning by example paradigm.


Acute effects of furosemide on left ventricular contractility in dogs.
The acute effects of the intravenous administration of large doses of furosemide on the left ventricle were studied in a controlled open-chest dog preparation. The data revealed that there was no direct effect of furosemide on the ventricular myocardium. This suggests that any acute cardiovascular effects seen clinically after the use of furosemide would most likely be due to changes in the effective circulating blood volume, direct effects upon certain vascular beds, electrolyte alterations, and possible secondary reflex cardiovascular effects rather than to any direct cardiac effects.


[Extent of damage to different intraocular lenses by neodymium:YAG laser treatment--an experimental study].
Neodymium:YAG laser capsulotomy frequently damages the intraocular lens (IOL). This damage, mainly caused by acoustic shock wave and thermal conduction, results in opacities in the IOL, which may cause glare or image degradation. Because of the introduction of new IOL materials in cataract surgery, investigation of YAG laser resistance of these IOL materials seems to be necessary. A total of 17 standard IOLs of different types and classes of materials were tested as follows: Class I: Acrylate a) PMMA, compression molding, b) PMMA, compression molding, heparin-surface modified, c) acrylate/methacrylate copolymer; Class II: Silicone: a) Polydimethylsiloxane, b) Polydimethyldiphenylsiloxane; Class III: Hydrogel: a) poly-hydroxyethylmethacrylate (poly-HEMA), b) polyacrylate-hydrogel; Class IV: Thermoset polymer: methylmethacrylate, hydroxyethylmethacrylate, ethylene glycol dimethacrylate. Each IOL was placed in a rectangular transparent acrylic test chamber filled with balanced salt solution and subjected to irradiation from a Q-switched Nd:YAG laser. The laser beam was focused on the posterior surface and inside of the IOLs. The optic of the IOL was divided into four target zones and each zone was subjected to 40 bursts inside the lens and 40 bursts on the posterior surface of the lens. Laser power settings were: 1.1 mJ, 1.1 mJ with 0.4 mm defocus, 2.1 mJ and 4 mJ and one burst was applied (wave length 1064 nm, fundamental mode, duration 7 +/- 2 nanoseconds, spot size 15 microns in air). Following exposure, each lens was examined by light microscopy for the interior damage and by scanning electron microscopy for the posterior surface damage. For quantitative analysis, the extent of each superficial damage was evaluated by an image analysis system using at least original magnification x 1400. Each IOL material demonstrated specific morphologic damage patterns. Intralenticular damage: Class I: cracks with radiating fractures with smaller extent in group Ic; Class II: blistered snowball-like inclusions; Class III: localized small holes, exception: IIIb: with very short radiating fractures; Class IV: stellar pits with short radiating fractures. For silicone superficial posterior damage sites a splash crater pattern with irregular melted edges was observed, while acrylate damage sites demonstrated a melted or stellate crater pattern with slightly raised edges. The silicone, poly-HEMA and the acrylic IOLs containing HEMA presented highest YAG laser resistance with the smallest amount of posterior damage in comparison to PMMA-IOLs. There was no marked increase in damage size in these IOL materials with higher energy exposure in this set-up. For each material consistent and characteristic specific morphologic damage patterns were observed. Foldable optic materials were more resistant against Nd:YAG-laser photodisruption than rigid optic materials. Individual laser strategies for each IOL-material and design should be deducted.


The Saccharomyces cerevisiae alcohol acetyl transferase gene ATF1 is a target of the cAMP/PKA and FGM nutrient-signalling pathways.
The ATF1-encoded Saccharomyces cerevisiae yeast alcohol acetyl transferase I is responsible for the formation of several different volatile acetate esters during fermentations. A number of these volatile esters, e.g. ethyl acetate and isoamyl acetate, are amongst the most important aroma compounds in fermented beverages such as beer and wine. Manipulation of the expression levels of ATF1 in brewing yeast strains has a significant effect on the ester profile of beer. Northern blot analysis of ATF1 and its closely related homologue, Lg-ATF1, showed that these genes were rapidly induced by the addition of glucose to anaerobically grown carbon-starved cells. This induction was abolished in a protein kinase A (PKA)-attenuated strain, while a PKA-overactive strain showed stronger ATF1 expression, indicating that the Ras/cAMP/PKA signalling pathway is involved in this glucose induction. Furthermore, nitrogen was needed in the growth medium in order to maintain ATF1 expression. Long-term activation of ATF1 could also be obtained by the addition of the non-metabolisable amino acid homologue beta-L-alanine, showing that the effect of the nitrogen source did not depend on its metabolism. In addition to nutrient regulation, ATF1 and Lg-ATF1 expression levels were also affected by heat and ethanol stress. These findings help in the understanding of the effect of medium composition on volatile ester synthesis in industrial fermentations. In addition, the complex regulation provides new insights into the physiological role of Atf1p in yeast.


Disfiguring burn scars and adolescent self-esteem.
Although children with burn scars are reported to have positive self-concepts, social and sexual maturation can be expected to stimulate anxiety, depression and diminished self-esteem in adolescents with disfiguring scars. This study examines complex self-regard of adolescents with burn scars. The following were hypothesized: (1) adolescents with disfiguring burn scars would view themselves as less competent than unburned normative samples; (2) subjects' perceived competence would be incongruent with the importance ascribed to the domains of physical appearance and athletic competence and (3) depression/anxiety would correlate negatively with perceived competence. Subjects were 14 adolescents: 6 male and 8 female, 13-20 years old, at least 2 years post-burn injury (TBSA = 39% +/- 23%). All had scars in at least 2 of the following areas: head/face, neck, chest, hands, genitals. Each subject was administered the Harter Self Perception Profile, a standardized measure of self-competence and value in 8 domains plus a general competence measure. The subjects were also assessed for anxiety/depression by the Child Behavioral Checklist. Overall, adolescents in this sample exhibited a similar or higher degree of self-worth as compared to their peers. However, the athletic competence and physical appearance sub-domains of self-worth for the burn survivors were significantly lower as compared to the normative group. Half of the participants rated the importance of physical appearance to be higher than their level of personal competence in this area, making for distressing emotions. Mood was similar to the normative group and mood correlated significantly with self-worth.


Drivers of cyanobacterial diversity and community composition in mangrove soils in south-east Brazil.
Cyanobacteria act as primary producers of carbon and nitrogen in nutrient-poor ecosystems such as mangroves. This important group of microorganisms plays a critical role in sustaining the productivity of mangrove ecosystems, but the structure and function of cyanobacteria assemblages can be perturbed by anthropogenic influences. The aim of this work was to assess the community structure and ecological drivers that influence the cyanobacterial community harboured in two Brazilian mangrove soils, and examine the long-term effects of oil contamination on these keystone species. Community fingerprinting results showed that, although cyanobacterial communities are distinct between the two mangroves, the structure and diversity of the assemblages exhibit similar responses to environmental gradients. In each ecosystem, cyanobacteria occupying near-shore areas were similar in composition, indicating importance of marine influences for structuring the community. Analysis of 16S rRNA sequences revealed the presence of diverse cyanobacterial communities in mangrove sediments, with clear differences among mangrove habitats along a transect from shore to forest. While near-shore sites in both mangroves were mainly occupied by Prochlorococcus and Synechococcus genera, sequences retrieved from other mangrove niches were mainly affiliated with uncultured cyanobacterial 16S rRNA. The most intriguing finding was the large number of potentially novel cyanobacteria 16S rRNA sequences obtained from a previously oil-contaminated site. The abundance of cyanobacterial 16S rRNA sequences observed in sites with a history of oil contamination was significantly lower than in the unimpacted areas. This study emphasized the role of environmental drivers in determining the structure of cyanobacterial communities in mangrove soils, and suggests that anthropogenic impacts may also act as ecological filters that select cyanobacterial taxa. These results are an important contribution to our understanding of the composition and relative abundance of previously poorly described cyanobacterial assemblages in mangrove ecosystems.


Factors associated with injuries among first-division Rwandan female soccer players.
Female soccer has grown tremendously in the last decade. Studies have suggested that female soccer players are more susceptible to injuries than their male counterparts, and their vulnerability is due mainly to intrinsic factors such as their anatomical and physiological structure. To establish factors associated with soccer injuries among first-division Rwandan female soccer players. In a descriptive cross-sectional study, self-administered questionnaires were used to investigate factors associated with injuries among soccer players. Almost half of the 300 participants (45%) indicated having been injured in the three seasons prior to the study. More than half (52.6%) were recurrent injuries. The ankle was the most common body part injured. Intrinsic factors associated with injuries were age, excessive ankle range of motion, pre-menstrual symptoms, and previous injury (p-value < 0.05). Extrinsic factors associated with injuries were use of oral contraceptive pills, (OCP), competition level, use of protective equipment, and player's position. The large number of recurring injuries was notable, emphasizing the importance of prevention strategies and access to adequately trained medical personnel as research has shown a significant reduction in the prevalence of recurring injuries after the introduction of effective prevention programmes.


Microbial contamination in dental unit waterlines.
The quality of water in a dental unit is of considerable importance because patients and dental staff are regularly exposed to water and aerosol generated from the dental unit. The aim of this study was to evaluate the occurrence of microbial contamination in dental unit waterlines. Water samples were collected aseptically from the waterlines (reservoir, triple-syringe, high-speed) of 15 dental units. After serial dilution to 1:10(6) in APHA, the samples were seeded by the pour-plate technique and cultured in plate count agar (Difco) for 48 h at 32 degrees C. Analysis was based on the number of colony forming units (CFU). The Wilcoxon non-parametric test indicated that the levels of water contamination were highest in the triple-syringe (13 of 15) and in the high-speed (11 of 15); both levels were higher than those of the water reservoir. There was no significant statistical difference between the level of contamination in the triple-syringe and the high-speed as determined by the Mann-Whitney test [p(H0) = 40.98%; Z = - 0.2281]. Because biofilm forms on solid surfaces constantly bathed by liquid where microorganisms are present, these results indicate that the water in the dental unit may be contaminated by biofilm that forms in these tubules.


[Health/nursing teaching in a new proposal of academic restructuration].
This study has as objective the presentation of a proposal of curricular restructure, evaluating its influence in the health instruction, focusing the nursing school. It presents, initially, the real panorama of superior education in Brazil. After that, it shows one curricular restructure proposal. Finally, it approaches the nursing/health teaching configuration in this proposal. This study points to the need of construction of a regenerated university, in its interface with the health graduation. It supports the development of educative practices adherent to the life context and to the plurality and singularity of the real social processes.


ORFans in Mitochondrial Genomes of Marine Polychaete Polydora.
Most characterized metazoan mitochondrial genomes are compact and encode a small set of proteins that are essential for oxidative phosphorylation, as well as rRNA and tRNA for their expression. However, in rare cases, invertebrate taxa have additional open reading frames (ORFs) in their mtDNA sequences. Here, we sequenced and analyzed the mitochondrial genome of a polychaete worm, Polydora cf. ciliata, part of whose life cycle takes place in low-oxygen conditions. In the mitogenome, we found three "ORFan" regions (544, 1,060, and 427 bp) that have no resemblance to any standard metazoan mtDNA gene but lack stop codons in one of the reading frames. Similar regions are found in the mitochondrial genomes of three other Polydora species and Bocardiella hamata. All five species share the same gene order in their mitogenomes, which differ from that of other known Spionidae mitogenomes. By analyzing the ORFan sequences, we found that they are under purifying selection pressure and contain conservative regions. The codon adaptation indices (CAIs) of the ORFan genes were in the same range of values as the CAI of conventional protein-coding genes in corresponding mitochondrial genomes. The analysis of the P. cf. ciliata mitochondrial transcriptome showed that ORFan-544, ORFan-427, and a portion of the ORFan-1060 are transcribed. Together, this suggests that ORFan-544 and ORFan-427 encode functional proteins. It is likely that the ORFans originated when the Polydora/Bocardiella species complex separated from the rest of the Spionidae, and this event coincided with massive gene rearrangements in their mitochondrial genomes and tRNA-Met duplication.


The prevalence, risk factors and clinical implications of dehydration in older patients: a cross-sectional study.
Adequate hydration is essential for the maintenance of physiological functions. Older adults may not be able to maintain adequate hydration, which is often not recognized. Our aim was to investigate the prevalence, risk factors and clinical implications of dehydration in older adults. This cross-sectional study included 964 older adults in one geriatric outpatient clinic in Turkey. Dehydration was defined as a calculated [1,86 × (Na+K)+1,15×glucose+urea +14] plasma osmolarity of ≥ 295 mOsm/L. Clinical characteristics and measures of comprehensive geriatric assessments of patients with dehydration and normohydration were compared. Predictors of dehydration were assessed using logistic regression analysis. Mean age was 79.9 ± 7.7 years, (71.7% female). The prevalence of dehydration was 31%. Female patients, diabetes mellitus (DM), chronic renal failure (CKD), a higher risk of falling (based on Timed Up and Go test), probable sarcopenia, dependence based on basic and instrumental daily living activities (BADL and IADL) were more common in the dehydrated group (p < 0.05). After adjusting for age and gender, dependency on BADL and IADL, the risk of falling were still higher in the dehydrated group (p < 0.05). There were significant relationships between dehydration and risk of falling (OR 1.38, 95% CI 1.00-1.90; p < 0.05), after adjustment for age, gender, DM, CKD. Dehydration is common among older adults and is associated with a dependency, probable sarcopenia, and an increased risk of falling. Screening for dehydration and taking preventive measures may be beneficial in avoiding the negative consequences associated with dehydration.


A randomized trial of inhaled levodopa (CVT-301) for motor fluctuations in Parkinson's disease.
Although levodopa is the most effective oral PD therapy, many patients experience motor fluctuations, including sudden loss of dose effect and delayed benefit. CVT-301 is a levodopa inhalation powder with the potential for rapid onset of action. The objective of this study was to evaluate CVT-301 self-administered by PD patients to relieve OFF episodes. PD patients with ≥2 hours per day of OFF time despite oral levodopa ≥4 times per day were randomized to CVT-301 or placebo for 4 weeks, to be used up to 3 times per day for OFF episodes. After 2 weeks, the study-drug dose was escalated from 35 to 50 mg. The primary end point was mean change in UPDRS Part III score from a predose OFF state to the average of postdose scores obtained at 10, 20, 30, and 60 minutes, as assessed in-clinic at the end of week 4. Home diaries were recorded. Eighty-six patients used the study drug at an average frequency of 2.1 times per day for CVT-301 and for placebo. At 4 weeks, least-squares mean change in UPDRS Part III score favored CVT-301 by 7.0 points (P < 0.001). A treatment effect was evident at 10 minutes. At 4 weeks, least-squares mean OFF-time change from baseline favored CVT-301 by 0.9 hours per day (P = 0.045). The most frequently reported adverse events in the CVT-301 group were dizziness, cough, and nausea, each in 7% (3 of 43 patients). CVT-301 self-administered during OFF episodes provided rapid improvement of motor function, and daily OFF time was significantly reduced at the higher dose. CVT-301 was generally safe and well-tolerated. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.


Low-intensity fires mitigate the risk of high-intensity wildfires in California's forests.
The increasing frequency of severe wildfires demands a shift in landscape management to mitigate their consequences. The role of managed, low-intensity fire as a driver of beneficial fuel treatment in fire-adapted ecosystems has drawn interest in both scientific and policy venues. Using a synthetic control approach to analyze 20 years of satellite-based fire activity data across 124,186 square kilometers of forests in California, we provide evidence that low-intensity fires substantially reduce the risk of future high-intensity fires. In conifer forests, the risk of high-intensity fire is reduced by 64.0% [95% confidence interval (CI): 41.2 to 77.9%] in areas recently burned at low intensity relative to comparable unburned areas, and protective effects last for at least 6 years (lower bound of one-sided 95% CI: 6 years). These findings support a policy transition from fire suppression to restoration, through increased use of prescribed fire, cultural burning, and managed wildfire, of a presuppression and precolonial fire regime in California.


Moderate Effect of Flavonoids on Vascular and Renal Function in Spontaneously Hypertensive Rats.
Many studies have shown that flavonoids are effective as antihypertensive drugs in arterial hypertension. In the present work, we have analyzed the effects of some flavonoid extracts in the spontaneous hypertensive rat model (SHR). An important feature of this study is that we have used a low dose, far from those that are usually applied in human therapy or experimental animals, a dose that responded to the criterion of a potential future commercial use in human subjects. Treatments were carried out for 6 and 12 weeks in two groups of SHR rats, which received apigenin, lemon extract, grapefruit + bitter orange (GBO) extracts, and cocoa extract. Captopril was used as a positive control in the SHR group treated for 6 weeks (SHR6) and Diosmin was used as the industry reference in the SHR group treated for 12 weeks (SHR12). Captopril and GBO extracts lowered the high arterial pressure of the SHR6 animals, but none of the extracts were effective in the SHR12 group. Apigenin, lemon extract (LE), GBO, and captopril also improved aortic vascular relaxation and increased plasma and urinary excretion of nitrites, but only in the SHR6 group. Kidney and urinary thiobarbituric acid reactive substances (TBARS) were also significantly reduced by GBO in the SHR6 rats. Apigenin also improved vascular relaxation in the SHR12 group and all the flavonoids studied reduced urinary thiobarbituric acid reactive substances (TBARS) excretion and proteinuria. Vascular abnormalities, such as lumen/wall ratio in heart arteries and thoracic aorta, were moderately improved by these treatments in the SHR6 group. In conclusion, the flavonoid-rich extracts included in this study, especially apigenin, LE and GBO improved vascular vasodilatory function of young adult SHRs but only the GBO-treated rats benefited from a reduction in blood pressure. These extracts may be used as functional food ingredients with a moderate therapeutic benefit, especially in the early phases of arterial hypertension.


In situ generated AgBr-enhanced ZnO nanorod-based photoelectrochemical aptasensing via layer-by-layer assembly.
A robust aptasensor for Ag(+) was proposed for the first time using an enhanced ZnO nanorod-based photoelectrochemistry by in situ generated AgBr via layer-by-layer assembly. This work opens up new avenues for application of one-dimensional ZnO nanorod arrays in photoelectrochemical sensing. Additionally, the strategy of employing in situ generated narrow-bandgap semiconductors paves a new way for photoelectrochemical sensing.


The natural progression of VGAMs and the need for urgent medical attention: a systematic review and meta-analysis.
Vein of Galen aneurysmal malformations (VGAMs) are congenital disorders that may require emergency treatment and some may cause sudden death before medical attention is provided. Some patients also have a spontaneous thrombosis. To understand the natural progression of VGAMs through a systematic literature review. We examined PubMed to identify studies published between July 1973 and March 2015. We determined the proportion of patients with VGAM who died before receiving medical attention, who received emergency treatment, or had a spontaneous thrombosis. We pooled estimates of proportions with corresponding 95% CIs calculated using the raw (ie, untransformed) proportions. The 31 studies obtained described the outcome of 754 patients with VGAM. The probability of sudden death risk was 4% (95% CI 1% to 7%; I2=51.6%); of an emergency operation was 46% (95% CI 34% to 58%; I2=93.2%); and of spontaneous thromboses 1% (95% CI 0% to 2%; I2=0%) of cases. Differences between age and clinical outcomes of patients with spontaneous thromboses were significant according to the rank test (Mann-Whitney U test, Z=-2.398, p=0.016), both having a linear correlation (χ2 test, p=0.022). Over time, the rate of preoperative sudden death in patients with VGAM gradually declined and the rate of emergency operations gradually increased. The outcome of patients with early spontaneous thromboses was good. Our study provides a definitive description of the natural progression of VGAMs and the need for urgent medical attention.


Balneotherapy in elderly patients: effect on pain from degenerative knee and spine conditions and on quality of life.
Balneotherapy is an established treatment modality for musculoskeletal disease, but few studies have examined the efficacy of spa therapy in elderly patients with degenerative spine and joint diseases. To assess the effects of balneotherapy on chronic musculoskeletal pain, functional capacity, and quality of life in elderly patients with osteoarthritis of the knee or with chronic low back pain. The 81 patients in the study group underwent a 1 day course of 30 minute daily baths in mineral water. Changes were evaluated in the following parameters: pain intensity, functional capacity, quality of life, use of non-steroidal anti-inflammatory or analgesic drugs, subjective disease severity perceived by the patients, investigator-rated disease severity, and severity of pain perceived by the patients. We analyzed the results of 76 subjects as 5 did not complete the study. Compared to baseline, all monitored parameters were significantly improved by balneotherapy in both investigated groups. Moreover, the favorable effect was prolonged for 3 months after treatment. This study showed that balneotherapy is an effective treatment modality in elderly patients with osteoarthritis of the knee or with chronic low back pain, and its benefits last for at least 3 months after treatment.


Contained power morcellation within an insufflated isolation bag.
To describe a technique for contained power morcellation within an insufflated isolation bag at the time of uterine specimen removal during minimally invasive gynecologic procedures. Over the study period of January 2013 to April 2014, 73 patients underwent morcellation of the uterus or myomas within an insufflated isolation bag at the time of minimally invasive hysterectomy or myomectomy. This technique involves placing the specimen into a large plastic bag within the abdomen, exteriorizing the opening of the bag, insufflating the bag within the peritoneal cavity, and then using a power morcellator within the bag to remove the specimen in a contained fashion. Procedures were performed at four institutions and included multiport laparoscopy, single-site laparoscopy, multiport robot-assisted laparoscopy, or single-site robot-assisted laparoscopy. Demographic and perioperative characteristics were collected for the cases. Surgical specimen morcellation within an insufflated isolation bag was successfully used in all cases. The median operative time was 114 minutes (range 32-380 minutes), median estimated blood loss was 50 mL (range 10-500 mL), and the median specimen weight was 257 g (range 53-1,481 g). There were no complications related to the contained morcellation technique nor was there visual evidence of tissue dissemination outside of the isolation bag. Morcellation within an insufflated isolation bag is a feasible technique. Methods for morcellating uterine tissue in a contained manner may provide an option to minimize the risks of open power morcellation while preserving the benefits of minimally invasive surgery. II.


Simultaneous and extensive removal of the East Asian lithospheric root.
Much evidence points to a dramatic thinning of East Asian lithosphere during the Mesozoic, but with little precision on when, or over what time scale. Using geochemical constraints, we examine an extensive compilation of dated volcanic samples from Russia, Mongolia and North China to determine when the lithosphere thinned and how long that process took. Geochemical results suggest that magmatism before 107 Ma derived from metasomatised subcontinental lithospheric mantle (SCLM), whereas after 107 Ma, melt predominantly derived from an asthenospheric source. The switch to an asthenospheric magma source at ~107 Ma occurred in both Mongolia and North China (>1600 km apart), whereas in eastern Russia the switch occurred a little later (~85 Ma). Such a dramatic change to an asthenospheric contribution appears to have taken, from beginning to end, just ~30 Myrs, suggesting this is the duration for lithospheric mantle weakening and removal. Subsequent volcanism, through the Cenozoic in Mongolia and North China does not appear to include any contribution from the removed SCLM, despite melts predominantly deriving from the asthenosphere.


Pediatric Inflammatory Bowel Disease.
Inflammatory bowel diseases (IBDs) are chronic, immune-mediated disorders that include Crohn's disease and ulcerative colitis. A pediatric onset of disease occurs in about 10% of all cases. Clinical presentation of IBD with rectal bleeding or perianal disease warrants direct referral for endoscopic evaluation. In the absence of red-flag symptoms, a combination of patient history and blood and fecal biomarkers can help to distinguish suspected IBD from other causes of abdominal pain or diarrhea. The therapeutic management of pediatric IBD has evolved by taking into account predictors of poor outcome, which justifies the upfront use of anti-tumor necrosis factor therapy for patients at high risk for complicated disease. In treating patients with IBD, biochemical or endoscopic remission, rather than clinical remission, is the therapeutic goal because intestinal inflammation often persists despite resolution of abdominal symptoms. Pediatric IBD comes with unique additional challenges, such as growth impairment, pubertal delay, the psychology of adolescence, and development of body image. Even after remission has been achieved, many patients with IBD continue to experience nonspecific symptoms like abdominal pain and fatigue. Transfer to adult care is a well-recognized risk for disease relapse, which highlights patient vulnerability and the need for a transition program that is continued by the adult-oriented IBD team. The general pediatrician is an invaluable link in integrating these challenges in the clinical care of patients with IBD and optimizing their outcomes. This state-of-the-art review aims to provide general pediatricians with an update on pediatric IBD to facilitate interactions with pediatric gastrointestinal specialists.


Health professionals' recognition of co-occurring alcohol and depressive disorders in youth: a survey of Australian general practitioners, psychiatrists, psychologists and mental health nurses using case vignettes.
To examine whether health professionals who commonly deal with mental disorder are able to identify co-occurring alcohol misuse in young people presenting with depression. Between September 2006 and January 2007, a survey examining beliefs regarding appropriate interventions for mental disorder in youth was sent to 1,710 psychiatrists, 2,000 general practitioners (GPs), 1,628 mental health nurses, and 2,000 psychologists in Australia. Participants within each professional group were randomly given one of four vignettes describing a young person with a DSM-IV mental disorder. Herein is reported data from the depression and depression with alcohol misuse vignettes. A total of 305 psychiatrists, 258 GPs, 292 mental health nurses and 375 psychologists completed one of the depression vignettes. A diagnosis of mood disorder was identified by at least 83.8% of professionals, with no significant differences noted between professional groups. Rates of reported co-occurring substance use disorders were substantially lower, particularly among older professionals and psychologists. GPs, psychologists and mental health professionals do not readily identify co-occurring alcohol misuse in young people with depression. Given the substantially negative impact of co-occurring disorders, it is imperative that health-care professionals are appropriately trained to detect such disorders promptly, to ensure young people have access to effective, early intervention.


Boys gymnastics injuries: A 9-year retrospective review.
Young male gymnasts are a frequently injured, yet infrequently studied population. Literature on gymnastics injuries has focused primarily on female gymnasts at elite and collegiate levels. Gymnastics equipment, rules, and training methods have continued to evolve over the past few decades so the previous data likely does not reflect current injury patterns. Our study aimed to provide a description of injury patterns for contemporary club-level, pre-collegiate male gymnasts. This was a retrospective chart review of 163 gymnastics injuries from 84 male subjects ages 4-19 years. Subjects were seen between 2010 and 2019 in pediatric sports medicine clinics. Gymnast demographics, injury locations, injury types, and gymnastics apparatus were collected as available. Our cohort had a mean age of 12.5 ± 3.0 years, gymnastics participation for 8.1 ± 2.9 years, and gymnastics level of 7.4 ± 1.7. Overuse injuries (59.5%) were more common than acute injuries (40.5%). The most common injury locations were lower extremity (42.3%), followed by upper extremity (32.5%), spine/trunk (19.6%), and head/neck (5.5%). The leading injury types were strains (16.6%) and apophysitis (12.9%). The most common apparatus for injury was floor (25%) followed by vault (20%). Binomial logistic regressions revealed that higher gymnastics level (OR = 5.19, p = .031) and younger age (OR = 4.05, p = .012) were predictors of lower extremity injuries. Our data show that injuries among club-level, young male gymnasts were most frequently located in the lower extremities. This contrasts older studies of primarily elite male gymnasts where injuries were more common in upper extremities. Overuse injuries were most prevalent in our cohort, and the most frequent injury types were strains and apophysitis.


Counter-rotating spin-polarised ring currents in odd-electron carbocycles.
We propose a molecular-orbital model to explain how majority and minority spins in odd-π-electron carbocycles sustain counter-rotating magnetic-field-induced ring currents. The model is based on the ipsocentric approach to magnetic response, in which ring currents are dominated by frontier-orbital contributions obeying angular-momentum selection rules. Coupled unrestricted Hartree-Fock ab initio calculations of the ring-current responses for singly charged benzene and planarised cyclo-octatetraene ions confirm the predictions of the qualitative model, and are consistent with correlated MP2 spin-polarised current calculations.


Evaluation of inhibitory action of novel non β-lactam inhibitor against Klebsiella pneumoniae carbapenemase (KPC-2).
The use of three classical β-lactamase inhibitors (Clavulanic acid, tazobactam and sulbactam) in combination with β-lactam antibiotics is presently the mainstay of antibiotic therapy against Gram-negative bacterial infections. However these inhibitors are unable to inhibit carbapenemase KPC-2 effectively. They being β-lactam derivatives behave as substrates for this enzyme instead of inactivating it. We have initiated our study to check the in vitro inhibition activity of the two novel screened inhibitors (ZINC01807204 and ZINC02318494) in combination with carbapenems against KPC-2 expressing bacterial strain and their effect on purified enzyme KPC-2. The MIC values of meropenem and ertapenem showed maximum reduction (8 folds) in combination with screened compounds (ZINC01807204 and ZINC02318494). CLSM images also depicted their strong antibacterial activity in comparison to conventional β-lactamase inhibitors. Moreover no toxic effect has been shown on HeLa cell line. Though the IC50 value of ZINC01807204 was high (200 µM), it exhibited fairly good affinity for KPC-2 (Ki = 43.82 µM). With promising results this study identifies ZINC01807204 as a lead molecule for further optimization and development of more potent non β-lactam inhibitors against KPC-2.


The mediating effect of burnout on the relationship between structural empowerment and organizational citizenship behaviours.
We used Kanter's (1977) structural empowerment theory to examine the influence of structural empowerment and emotional exhaustion on healthcare professionals' use of organizational citizenship behaviours directed at the organization (OCBO) and peers (OCBI). Organizational citizenship behaviours (OCB) are discretionary behaviours that are not rewarded directly by the organization but have been linked to positive outcomes, such as increased job satisfaction and lower turnover intentions. Promoting OCB can help employees and organizations flourish despite current challenges in the healthcare system. Structural empowerment may influence the frequency and type of OCB by reducing burnout. We conducted multiple mediated regression analyses to test two hypothesized models about relationships between empowerment, emotional exhaustion and two types of OCB (OCBI and OCBO) in a sample of 897 healthcare professionals in five Canadian hospitals. Emotional exhaustion was found to be a significant mediator of the relationship between empowerment and OCBO. The predicted mediation of the empowerment/OCBI relationship by emotional exhaustion was not supported. Exhaustion was an important mediator of empowering working conditions and OCBO, but was not significantly related to OCBI. Empowerment was significantly related to both OCBO and OCBI. Promoting empowerment among healthcare workers may decrease burnout and promote OCB. Specific managerial strategies are discussed in the present study.


Deficient LAR expression decreases basal forebrain cholinergic neuronal size and hippocampal cholinergic innervation.
A role in neural development for protein tyrosine phosphatase (PTPase) receptors has been suggested by the finding of aberrant neurite outgrowth in Drosophila mutants lacking functional leukocyte common antigen-related (LAR) PTPase receptors; however, PTPase functions in the mammalian nervous system remain to be established. In transgenic mice containing a gene trap in the LAR gene, only trace expression of full-length LAR transcripts was found. In these mice, the size of basal forebrain cholinergic neurons was significantly reduced and cholinergic innervation of the dentate gyrus was markedly decreased. These findings constitute the first demonstration of an aberrant neuronal phenotype in a mammalian PTPase mutant and support the hypothesis that LAR-type PTPase receptors function to establish and/or maintain neuronal networks.


[Biosynthesis and secretion of collagen in normal and SV-40 virus-transformed human embryonal fibroblasts].
The biosynthesis and secretion of collagen proteins was studied in cultures of normal human embryo fibroblasts at different passages and growth stages as well as in cultures of human embryo fibroblasts transformed by oncogenic virus SV-40. It was found that normal fibroblasts maintain at a constant level the collagen synthesis throughout 20 passages, which is typical of proliferating and resting cells. Virus-transformed cells produce 3-4 times less collagen proteins on a per cell count. Normal and transformed fibroblasts do not differ in terms of total protein synthesis. Secretion of collagen and non-collagen proteins in transformed cell cultures appeared to be much lower than in normal cell cultures. Study of synthesized proteins by polyacrylamide gel electrophoresis showed that both types of cells secrete collagen proteins predominantly as polymers containing interchain S-S bonds of 3-helix molecules. Study of the protein-synthesizing activity of two polysomal fractions, i.e. membrane bound and free polysomes, isolated from the cells of both types in a cell-free system showed that membrane-bound polysomes from transformed fibroblasts synthesize collagen much less actively in comparison with normal cells. However, in transformed cells free polysomes, in contrast with normal cells, are active participants of a cell-free collagen protein synthesis.


Decreased cerebrospinal fluid concentrations of substance P in treatment-resistant depression and lack of alteration after acute adjunct vagus nerve stimulation therapy.
Recent preclinical and clinical research has demonstrated that the neuropeptide substance P (SP) plays a role in the central nervous system (CNS) response to stress, and perhaps in the etiology of major depression and/or anxiety disorders. The nature of this role, however, is poorly understood. A limited body of evidence suggests that in medication-free depressed patients, cerebrospinal fluid (CSF) concentrations of SP may be elevated relative to healthy controls. Two studies have shown that antidepressant treatment does not significantly change CSF concentrations of SP. Using standard lumbar puncture techniques, baseline CSF samples were obtained from 19 medication-free healthy controls and 19 medicated patients with treatment-resistant depression (TRD). Mean CSF SP concentration was significantly lower in TRD patients on psychotropic medications than in the group of healthy subjects. After 10-12 weeks of treatment with adjunct vagus nerve stimulation (VNS), CSF SP concentrations were not significantly changed. Low CSF SP may reflect a biological marker of the subtype of severe and chronic depression that is resistant to standard therapies.


Gustatory effects of miraculin, monellin and thaumatin in the Saguinus midas tamarin monkey studied with electrophysiological and behavioural techniques.
A comparative electrophysiological and behavioural study has been made in 17 closely related monkeys of the new world species, Saguinus midas tamarin. The electrical activity in the chorda tympani proper nerve of two of the monkeys was recorded during the application to the tongues of 0.02% monellin and thaumatin, 0.5% miraculin and stimuli representing the four taste qualities. It was observed that monellin and thaumatin gave no or little response and that miraculin enhanced the response to the sour stimulus, but not that to any other taste quality. Behavioural studies were then made with a two-bottle preference test in 15 monkeys. It was found that the animals did not discriminate or discriminated poorly between water and thaumatin or monellin. After miraculin they changed their strong rejection of 0.02 M citric acid, in a choice between water and acid, into a strong preference for the acid. These results show a close relation between the electrophysiological and the behavioural data.


Is food insecurity related to overweight and obesity in children and adolescents? A summary of studies, 1995-2009.
In the USA, several nutrition-related issues confront the normal growth, maturation and development of children and adolescents including obesity and food insecurity. The purpose of this paper is to provide a review of the concept of food insecurity and a summary of studies that have examined the association between food insecurity and overweight/obesity in children and adolescents. Besides the initial case report, we review 21 studies (16 cross-sectional and five prospective studies) that have been published on this topic as of December 2009. As there is limited literature in this area, we review studies that sample children and adolescents in the USA. The results are mixed with positive, negative and null associations. The reasons for the mixed results are difficult to disentangle. Among earlier studies, small samples hampered definitive conclusions. More recent studies with larger samples have overcome these limitations and tend to find no associations between these constructs. Nonetheless, all of the studies to date have shown that food insecurity and overweight co-exist - that is, even though there may not be statistically significant differences in overweight between food-insecure and food-secure children, the prevalence of overweight remains relatively high in food-insecure children.


Distribution and dynamics of nematocyte populations in Hydra attenuata.
The distribution and dynamics of the 4 nematocyte populations of Hydra attenuata were investigated. Ninety-seven per cent of all nematocytes, including all 4 types, are mounted in the battery cells of the tentacles. The remaining 3%, including 2 types (stenoteles and holotrichous isorhizas) are mounted in the ectoderm of the body column. Eight-two per cent of all nematocytes are desmonemes; 11%, atrichous isorhizas; 5%, stenoteles; and 2%, holotrichous isorhizas. The density of each nematocyte population increases along the length of the tentacle towards the tip. The percentages of the total nematocytes per quarter of tentacle for each of the 4 quarters starting at the base is 15, 18, 25 and 42% respectively. The turnover time of the nematocyte populations in the tentacles was measured with 2 methods. First, the transit time for a carbon-marked battery cell from the base to the tip of the tentacle was measured. Secondly, the time required to replace the unlabelled nematocytes in the tentacles with [3H]proline-labelled nematocytes was measured. In both cases the time was 7--9 days. Based on these data (distribution and turnover time) a model was constructed for the dynamics of the nematocyte populations in the tentacles. The numbers of nematocytes produced dialy in the body column as predicted by the model are in reasonable agreement with the measured values.


The role of the headgear timer in extraoral co-operation.
The aim of this research was to study headgear co-operation using an objective measuring instrument, the Compliance Science System (CSS). Forty-six patients were included in the investigation, 32 girls and 14 boys (10-15 years of age; mean 13 years). The patients, who were not informed that they were being monitored, were instructed to wear the headgear, with an electronic module timer attached to the neckstrap, for 16 hours per day. At the end of 2 months (T1), the time for which the headgear was worn was measured. At this stage the patients were divided into two groups: group 1 (unco-operative patients) who wore the headgear for less than 16 hours per day, and group 2 (co-operative patients) who wore the headgear for at least 16 hours per day. Only the unco-operative patients were informed that they had been monitored, and a subsequent 4 month treatment period was initiated for both groups. The time was also measured at the end of the second (T2) and third (T3) 2 month treatment periods. The unco-operative patients increased their use of the headgear to approximately 4.5 to 6 hours per day (P < 0.05). All of the co-operative patients also used their headgear as recommended during the 4 month period.


How hornbills handle heat: sex-specific thermoregulation in the southern yellow-billed hornbill.
At a global scale, thermal physiology is correlated with climatic variables such as temperature and aridity. There is also evidence that thermoregulatory traits vary with fine-scale microclimate, but this has received less attention in endotherms. Here, we test the hypothesis that avian thermoregulation varies with microclimate and behavioural constraints in a non-passerine bird. Male and female southern yellow-billed hornbills (Tockus leucomelas) experience markedly different microclimates while breeding, with the female sealing herself into a tree cavity and moulting all her flight feathers during the breeding attempt, becoming entirely reliant on the male for provisioning. We examined interactions between resting metabolic rate (RMR), evaporative water loss (EWL) and core body temperature (Tb) at air temperatures (Ta) between 30°C and 52°C in male and female hornbills, and quantified evaporative cooling efficiencies and heat tolerance limits. At thermoneutral Ta, neither RMR, EWL nor Tb differed between sexes. At Ta >40°C, however, RMR and EWL of females were significantly lower than those of males, by ∼13% and ∼17%, respectively, despite similar relationships between Tb and Ta, maximum ratio of evaporative heat loss to metabolic heat production and heat tolerance limits (∼50°C). These sex-specific differences in hornbill thermoregulation support the hypothesis that avian thermal physiology can vary within species in response to fine-scale microclimatic factors. In addition, Q10 for RMR varied substantially, with Q10 ≤2 in some individuals, supporting recent arguments that active metabolic suppression may be an underappreciated aspect of endotherm thermoregulation in the heat.


Primary hyperaldosteronism is associated with increased mortality and morbidity in patients with hypertension and diabetes.
Primary hyperaldosteronism (PA) is a common cause of hypertension. It is more prevalent in patients with diabetes. We assessed the cardiovascular impact of PA in patients with established hypertension and diabetes. Data from the National Inpatient Sample (2008-2016) was used to identify adults with PA with hypertension and diabetes comorbidities and then compared to non-PA patients. The primary outcome was in-hospital death. Secondary outcomes included ischemic stroke, hemorrhagic stroke, acute renal failure, atrial fibrillation, and acute heart failure. A total of 48,434,503 patients with hypertension and diabetes were included in the analysis, of whom 12,850 (0.03%) were diagnosed with primary hyperaldosteronism (PA). Compared to patients with hypertension and diabetes but no PA, those with PA were more likely to be younger [63(13) vs. 67 (14), male (57.1% vs. 48.3%), and African-Americans (32% vs. 18.5%) (p<0.001 for all). PA was associated with a higher risk of mortality (adjusted OR 1.076 [1.076-1.077]), ischemic stroke [adjusted OR 1.049 (1.049-1.05)], hemorrhagic stroke [adjusted OR 1.05 (1.05-1.051)], acute renal failure [adjusted OR 1.058 (1.058-1.058)], acute heart failure [OR 1.104 (1.104-1.104)], and atrial fibrillation [adjusted OR 1.034 (1.033-1.034)]. As expected, older age and underlying cardiovascular disease were the strongest predictors of mortality. However, the female gender conferred protection [OR 0.889 (0.886-0.892]. Primary hyperaldosteronism in patients with hypertension and diabetes is associated with increased mortality and morbidity.


[Treatment of a tetraplegic patient with chronic constipation with the Tibetan remedy Padma Lax--a case report].
In spinal cord injuries disturbed defecation, constipation and their concomitant disorders are frequent clinical symptoms. They may severely impair the quality of life of the affected patients. The presented case study and two more case reports, summarized in table form, outline therapeutic difficulties and therapy options in the treatment of constipation in paraplegic patients. A 69-year-old male patient with tetraplegia below C4 suffered from disturbed defecation, constipation with recurrent co-prostasis and pronounced meteorism which impeded breathing. Padma Lax was applied for several months, and constipation and the concomitant meteorism were noticeably reduced. The herbal preparation based on a formula from Tibetan Medicine may offer new therapeutic options in the care and treatment of patients with severe constipation. This report could also give first indications for controlled clinical studies in tetraplegic patients.


Peroral placement of a self-expandable covered metallic stent using an overtube for malignant gastroduodenal obstructions.
To evaluate the technical feasibility and safety of overtube-guided covered metallic stent placement as palliative treatment for patients with inoperable malignant gastric outlet obstructions. To relieve the symptoms of severe nausea and recurrent vomiting in five patients with inoperable gastric cancer, we used an overtube (Long overtube; Sumitomo Bakelite, Tokyo, Japan) to place large-diameter, self-expandable, covered esophageal Ultraflex stents (inner diameter 22-28 mm, length 10 or 12 cm; Boston Scientific, Watertown, MA, USA). Success was defined both technically and clinically. The stent placement was technically successful in all patients and resulted in improvement of symptoms in all five patients, four of whom were thereafter able to ingest solid food. The remaining patient, a 94-year-old man, was unable to ingest food because of dysmasesis. During the mean follow-up of 17 weeks, there was no stent reocclusion and no life-threatening complications developed. The placement of a large diameter, self-expandable, covered esophageal stent using an overtube appears to be effective for the palliative treatment of malignant gastric outlet obstruction.


Response bias in "remembering" emotional stimuli: a new perspective on age differences.
Older adults sometimes show a recall advantage for emotionally positive, rather than neutral or negative, stimuli (S. T. Charles, M. Mather, & L. L. Carstensen, 2003). In contrast, younger adults respond "old" and "remember" more often to negative materials in recognition tests. For younger adults, both effects are due to response bias changes rather than to enhanced memory accuracy (S. Dougal & C. M. Rotello, 2007). We presented older and younger adults with emotional and neutral stimuli in a remember-know paradigm. Signal-detection and model-based analyses showed that memory accuracy did not differ for the neutral, negative, and positive stimuli, and that "remember" responses did not reflect the use of recollection. However, both age groups showed large and significant response bias effects of emotion: Younger adults tended to say "old" and "remember" more often in response to negative words than to positive and neutral words, whereas older adults responded "old" and "remember" more often to both positive and negative words than to neutral stimuli.


[Geoinformational model of the carbon reserve of the Russian tundra zone].
We present a summary of our own gas measurement data on biogenic fluxes of CO2 in various ecosystems of the Russian tundra zone, using seasonal and geographical extrapolations based on mathematical simulation modeling. The model follows construction principles of geoinformational systems and consists of (1) a computer map of tundra landscape boundaries; (2) a meterological database; (3) a model of changes of the phytomass; and (4) the actual model of carbon fluxes. The model, which uses a 10-day step, allows estimates of regional and landscape-associated macroscopic carbon fluxes and predicts the response of the tundras to climatic changes. The data obtained are in good agreement with independently obtained estimates of the major characteristics of tundra carbon balance.


Sibutramine is effective for weight loss and diabetic control in obesity with type 2 diabetes: a randomised, double-blind, placebo-controlled study.
To assess the efficacy and tolerability of sibutramine 15 mg once daily as a weight reduction agent in overweight and obese patients (body mass index (b.m.i.) > 26 kg/m2) with type 2 diabetes when given with a customised, reduced-calorie diet, and to evaluate the influence of weight loss on diabetic control. Randomised, placebo-controlled, double-blind, parallel-group, 12-week study conducted at two hospital-based obesity/diabetes clinics. Patients were men and women aged 30-65 years, with b.m.i. > 26 kg/m2 and < or = 35 kg/m2 and treated or untreated type 2 diabetes diagnosed > or = 6 months previously. Each patient was given sibutramine 15 mg or placebo once daily and advised to follow a customised diet of 500 kcal/day less than the individual's energy needs. The principal measure of efficacy was change in body weight (b.w.). Additional efficacy measurements were changes in b.m.i., body composition as measured by dual-energy X-ray absorptiometry, and change in waist and hip measurements. Changes in diabetic control were assessed by blood glucose levels fasting and after a standard test meal, fasting insulin level, and glycosylated haemoglobin level. Adverse events (AEs) were monitored at each visit, and routine laboratory safety tests were done at 4-week intervals. Ninety-one patients were randomised into the study, 44 to placebo and 47 to sibutramine 15 mg once daily. Eighty-three patients (91%) completed the study, 40 (91%) on placebo and 43 (91%) on sibutramine. Mean weight reduction from baseline was statistically significantly greater with sibutramine than with placebo at every measurement and at the end of the study (2.4 vs. 0.1 kg at week 12; p < 0.001; intent-to-treat). The proportion of patients who lost > 5% of their baseline b.w. was 19% in the sibutramine group and 0% in the placebo group (p < 0.001; 95% confidence interval: 9, 30). Patients receiving sibutramine lost significantly more fat mass compared with those receiving placebo, as a percentage (1.0% vs. 0.1%; p < 0.05) and in absolute terms (1.8 vs. 0.2 kg, p < 0.001). Loss of lean mass was not significantly different between the groups. Mean peak blood glucose concentration after a standard test meal decreased by 1.1 mmol/l in the sibutramine treatment group but increased by 0.5 mmol/l in the placebo group (p = 0.04; difference in means, 1.6, 95% confidence interval: -3.3, -0.1). Mean fasting blood glucose decreased by 0.3 mmol/l with sibutramine and increased by 1.4 mmol/l with placebo. Mean glycosylated haemoglobin levels decreased by 0.3% units with sibutramine treatment, and were unchanged with placebo. However, more sibutramine-treated patients (33%) than placebo-treated patients (5%) achieved decreases in glycosylated haemoglobin of 1% unit or more (p < 0.05). Sibutramine 15 mg was safe and well tolerated, and AEs were mostly mild or moderate in severity. No significant differences were found between treatment groups in blood pressure. No clinically significant conduction or rhythm abnormalities were observed on ECG. Sibutramine 15 mg once daily with a customised, reduced-calorie diet significantly reduced weight compared with placebo in overweight and obese patients (b.m.i. > 26 kg/m2) with type 2 diabetes. Sibutramine was well tolerated, and significant improvement in diabetic control was seen in conjunction with weight reduction on sibutramine treatment.


Modulation of humoral response to a 12-amino-acid site on the poliovirus virion.
Most monoclonal antibodies to poliovirus 3 but not poliovirus 1 require a single 12-amino-acid sequence in virion protein VP1 for neutralization (site 1). None of the available monoclonal antibodies requiring this site bound virions after tryptic cleavage of site 1. This result allowed the amount of site 1-specific antibodies to be determined in an antiserum by comparing its reactivity with virus and trypsin-cleaved virus. Antisera to poliovirus 3 Sabin strain (PS3) but not poliovirus 1 Sabin showed site 1 immunodominance, consistent with the frequency of isolation of site 1-specific monoclonal antibodies to these viruses. Cleavage of site 1 prior to immunization dramatically reduced the immunogenicity of this site in PS3. However, the antiserum against trypsin-cleaved PS3 still had a high neutralization titer, demonstrating that sites other than site 1 can elicit a neutralizing response to PS3. Other antisera to PS3 showed significant variability in the response to site 1, indicating that other factors, such as the genetic background of inbred mouse strains, the species immunized, and the immunization protocol, also affect immunodominance. In particular, a serum from a human infant recently immunized with oral trivalent vaccine had little response to site 1.