A major bristle QTL from a selected population of Drosophila uncovers the zinc-finger transcription factor poils-au-dos, a repressor of achaete-scute.
Traditional screens aiming at identifying genes regulating development have relied on mutagenesis. Here, we describe a new gene involved in bristle development, identified through the use of natural variation and selection. Drosophila melanogaster bears a pattern of 11 macrochaetes per heminotum. From a population initially sampled in Marrakech, a strain was selected for an increased number of thoracic macrochaetes. Using recombination and single nucleotide polymorphisms, the factor responsible was mapped to a single locus on the third chromosome, poils au dos, that encodes a zinc-finger-ZAD protein. The original, as well as new, presumed null, alleles of poils au dos, is associated with ectopic achaete-scute expression that results in the additional bristles. This suggests a possible role for Poils au dos as a repressor of achaete and scute. Ectopic expression appears to be independent of the activity of known cis-regulatory enhancer sequences at the achaete-scute complex that mediate activation at specific sites on the notum. The target sequences for Poils au dos activity were mapped to a 14 kb region around scute. In addition, we show that pad interacts synergistically with the repressor hairy and with Dpp signaling in posterior and anterior regions of the notum, respectively.


Changing pattern of the intraoperative blood pressure during endoscopic adrenalectomy in patients with Conn's syndrome.
Primary hyperaldosteronism caused by an aldosterone-producing adenoma of the adrenal gland is regarded as the most common type of endocrine hypertension. The aim of this study was to analyze the changing pattern of the intraoperative blood pressure during endoscopic adrenalectomy recorded in patients with Conn's syndrome compared to patients with hormone-inactive incidentaloma and its possible influence by the surgical approach. From February 1994 to March 2004, 40 patients underwent endoscopic adrenalectomy for Conn's syndrome. All patients had arterial hypertension over a median period of 84 (5-240) months and were pretreated with an aldosterone antagonist in 76.3% and with specific antihypertensive medication in 85%. Over the same period of time, endoscopic adrenalectomy was carried out in 80 patients with incidentaloma. Of these, 41 (53.2%) displayed arterial hypertension requiring drug therapy. The adrenal gland was resected using the retroperitoneal in 25 and the transperitoneal approach in 15 patients with Conn's syndrome. Conversion to an open procedure was required in two patients. Intraoperative increases in blood pressure necessitating antihypertensive therapy were observed in 17 of 40 patients (44.7%), in 11 of 40 patients (28.9%) blood pressure peaks of >200 mmHg (> 1 min) were noted. Differences between the preoperative and maximum intraoperative blood pressure were significant for the retroperitoneal approach only (systolic: p = 0.0001; diastolic: p = 0.0005), but not for the transperitoneal technique. The increase in intraoperative blood pressure in patients with Conn's syndrome was significantly higher, for both systolic (p < 0.0001) and diastolic (p = 0.0037) readings, compared to that in patients with incidentaloma undergoing endoscopic adrenalectomy during the same period of time. Our results demonstrate that relevant intraoperative increases in blood pressure occur in patients with Conn's syndrome despite prior therapy with an aldosterone antagonist, necessitating specific precautionary measures during anesthesia. Intraoperative blood pressure was significantly higher for the retroperitoneal than for the transperitoneal procedure, which leads us to advocate the latter approach for endoscopic adrenalectomy.


[Correlation between feeding index and growth development of 6-36 month-old infants in two counties of western China by applying multiple correspondence analysis].
To explore the correlation between feeding index and growth development status of infants from two counties of western China by applying the method of multiple correspondence analysis. Two sample counties were randomly selected from the ones that satisfied the research conditions in Shaanxi province and Chongqing in western China. In the study, 472 premature/low birth weight infants (PLBW) and 461 normal term infants (NT) of 6-36 months from the two counties were investigated from September 2010 to November 2010. The SPSS 19.0 software was applied to analyze the data using general statistical analysis and multiple correspondence analysis. In the two counties of western China, the proportion of infants with feeding index at the medium level was the highest, which was between 50% and 60%. In the PLBW group and the NT group, the proportion of low level of feeding index among 6-9 month-old infants was the highest, and the proportion was 33.3% for the PLBW group and 29.4% for the NT group. For both the PLBW group and the NT group, the distribution of feeding index among the different age groups showed significant difference (P<0.05).Among the infants with low level of feeding index, the growth development of the PLBW lay behind that of the NT. We could see a catching-up trend of the PLBW with medium or good level of feeding index, but their growth development index was still at a lower level than that of the NT with the same level of feeding condition. Through multiple correspondence analyses, the outcomes of PLBW corresponded and strongly correlated with low level of feeding index, low level of growth development index, mother's low education degree and low annual family income. And the outcomes of NT corresponded and strongly correlated with medium/good level of feeding index, medium level of growth development status, mother's medium/high education degree and medium/high level of annual family income. There are good correspondence correlations at different hierarchical levels of the infants' group, feeding index, growth development index and family factors in the two counties of western China. Multiple correspondence analysis could directly reveal the correlation among several variables, which is a suitable method for categorical data. The result can be illustrated directly through a two-dimensional graph and could provide the suggestion of feeding practice for different infants in western rural China.


Implementation of a comprehensive cancer control program at the worksite: year one summary report.
The worksite is an ideal forum for cancer risk assessment. We describe here the baseline characteristics of a large cohort. Participants completed surveys that assessed a variety of risk factors and behavioral mediators. Personalized feedback letters identified cancer risks. A total of 4395 surveys were received. Cancer prevalence was 6.5% (range, 4.3% to 11.2%). The most common risk factors were lack of exercise (41%; 32% to 68%), obesity (28%; 24% to 39%), and smoking (14%; 13% to 32%). Cardiovascular risk was also common (25%; 15% to 48%). Screening was fair to good for all cancers except colon cancer. The perceived risk for cancer was less than that for cardiovascular disease (P < 0.0001). Most smokers were in the pre-contemplation phase, whereas action/maintenance phases predominated for breast and colon cancer screening. Modifiable cancer risk factors can be identified in the majority of workers. Inaccurate risk perception is an important target for future interventions.


Correlative changes in total vascular capacity and resistance in carotid sinus reflex.
To attain a quantitative understanding of carotid sinus reflex control of circulation, we studied the correlation between changes in total vascular capacity (V) and total peripheral resistance (R). We used a newly devised, accurate and simple method to measure changes in V while both mean central venous and arterial pressures being kept constant. In 7 open chest dogs (7-11 Kg, mean 8.9 Kg), bilateral carotid occlusion after vagotomy reduced V by as much as 58 +/- 9 (SE) ml or approximately 8% of total blood volume while R increased by 36 +/- 5% from 0.08 +/- 0.01 mmHg-min/ml. Similar responses were obtained either in the reflex before vagotomy or with infusion of norepinephrine. Mathematical analysis with Poiseuille's law suggested that internal radius of an average resistance vessel decreased approximately 1.5 to 3 times as much as that of an average capacitance vessel. The wall to lumen ratio of the average resistance vessel estimated from the correlation was 0.3 to 0.6, being within physiological range. Therefore, the difference in vascular sensitivity may be partly owing to the wall to lumen ratio of resistance vessels. Moreover, the correlative changes in the capacitance and resistance vessels were elucidated to be significantly responsible for the characteristic hemodynamic changes in carotid sinus reflex.


Role of group VIA calcium-independent phospholipase A2 in arachidonic acid release, phospholipid fatty acid incorporation, and apoptosis in U937 cells responding to hydrogen peroxide.
Group VIA calcium-independent phospholipase A2 (iPLA2) has been shown to play a major role in regulating basal phospholipid deacylation reactions in certain cell types. More recently, roles for this enzyme have also been suggested in the destruction of membrane phospholipid during apoptosis and after oxidant injury. Proposed iPLA2 roles have rested heavily on the use of bromoenol lactone as an iPLA2-specific inhibitor, but this compound actually inhibits other enzymes and lipid pathways unrelated to PLA2, which makes it difficult to define the contribution of iPLA2 to specific functions. In previous work, we pioneered the use of antisense technology to decrease cellular iPLA2 activity as an alternative approach to study iPLA2 functions. In the present study, we followed the opposite strategy and prepared U937 cells that exhibited enhanced iPLA activity by stably expressing a plasmid containing iPLA2 cDNA. Compared with control cells, the iPLA2 -overexpressing U937 cells showed elevated responses to hydrogen peroxide with regard to both arachidonic acid mobilization and incorporation of the fatty acid into phospholipids, thus providing additional evidence for the key role that iPLA2 plays in these events. Long-term exposure of the cells to hydrogen peroxide resulted in cell death by apoptosis, and this process was accelerated in the iPLA2-overexpressing cells. Increased phospholipid hydrolysis and fatty acid release also occurred in these cells. Unexpectedly, however, abrogation of U937 cell iPLA2 activity by either methyl arachidonyl fluorophosphonate or an antisense oligonucleotide did not delay or decrease the extent of apoptosis induced by hydrogen peroxide. These results indicate that, although iPLA2-mediated phospholipid hydrolysis occurs during apoptosis, iPLA2 may actually be dispensable for the apoptotic process to occur. Thus, beyond a mere destructive role, iPLA2 may play other roles during apoptosis.


Communicating clinical nursing issues through the newspaper.
The information quality of nursing news is a critical factor in gaining public support for the acquisition of scarce resources necessary to undergird clinical nursing practice. A content analysis of 3,098 newspaper articles about nursing in 1978 was employed to examine the treatment of clinical nursing news. Among the variables studied were practice settings, educational levels, role clarity, professional activities, nurse-physician relationships, and degree of favorable image. Results revealed that the quality of news about clinical nursing varied by specialties, with maternity nursing and pediatric nursing news shown to be more progressive and community health nursing and medical-surgical nursing revealed as quite traditional. Psychiatric nursing received an inordinately low level of news coverage. Recommendations are offered to assist improvement in the amount and quality of news treatment of clinical nursing.


[Features of the surgical anatomy of the thymus gland in myasthenia patients].
The surgical anatomy of the thymus was studied intraoperatively in 220 myasthenia patients without tumors during extended thymectomy. An atypical disposition of the whole thymus (Ist variant) or its upper pole only (IInd and IIIrd variants) behind the left brachio -cephalic vein was noted in 8% of cases; mediastinal localization of the thymus (IVth variant) in 13,6% of observations; cervical localization (Vth variant) in 6,9%. Only the right lobe of the thymus ( VIth variant) or only the left lobe (VIIth variant) were found in 4,5% of observations. The technique of extended thymectomy with most frequent variants of the surgical anatomy of the thymus in patients with myasthenia is described.


Dome-like behaviour at Mt. Etna: The case of the 28 December 2014 South East Crater paroxysm.
On the 28 December 2014, a violent and short paroxysmal eruption occurred at the South East Crater (SEC) of Mount Etna that led to the formation of huge niches on the SW and NE flanks of the SEC edifice from which a volume of ~3 × 106 m3 of lava was erupted. Two basaltic lava flows discharged at a rate of ~370 m3/s, reaching a maximum distance of ~5 km. The seismicity during the event was scarce and the eruption was not preceded by any notable ground deformation, which instead was dramatic during and immediately after the event. The SO2 flux associated with the eruption was relatively low and even decreased few days before. Observations suggest that the paroxysm was not related to the ascent of volatile-rich fresh magma from a deep reservoir (dyke intrusion), but instead to a collapse of a portion of SEC, similar to what happens on exogenous andesitic domes. The sudden and fast discharge eventually triggered a depressurization in the shallow volcano plumbing system that drew up fresh magma from depth. Integration of data and observations has allowed to formulate a novel interpretation of mechanism leading volcanic activity at Mt. Etna and on basaltic volcanoes worldwide.


Gigapixel confocal imaging using a massively parallel optical probe array with single directional infinite scanning.
Here we demonstrate high-throughput gigapixel confocal imaging using a massively parallel optical probe array with single directional infinite scanning. For implementation of the single directional infinite scan with high lateral resolution, a parallelogram array micro-objective lens module, composed of two wafer-level microlens arrays, is proposed to generate a massively parallel optical probe array for integration into the confocal imaging system, including an objective-side telecentric relay lens with a low-magnification. To test the feasibility of the proposed system with single directional infinite scanning, we designed and constructed a confocal imaging system using a parallelogram array of multi-optical probes with a massively parallel array size of 200 × 140. The constructed system provides a full width-half maximum lateral resolution of 1.55 μm, as measured by the knife-edge detection method, and a field-of-view width of 28.0 mm with a sampling interval of 1 μm/pixel.


Neutrophil leukotriene generation and pulmonary dysfunction after abdominal aortic aneurysm repair.
The purpose of this study was to assess the role of polymorphonuclear neutrophil (PMN)-generated leukotriene B4 (LTB4) as an etiologic agent in the pulmonary dysfunction seen after operation in patients undergoing abdominal aortic aneurysm repair. Blood was analyzed in 10 consecutive patients undergoing elective infrarenal abdominal aortic aneurysm repair for plasma thromboxane B2, lactoferrin, C3a, and PMN-generated LTB4. There was a close linear correlation (r = 0.88; p < 0.001) between aortic clamp time and PMN LTB4 production. Conversely, aortic clamp time and the ratio of arterial oxygen pressure to fraction of inspired oxygen, a measure of pulmonary function, were inversely related (r = -0.80; p < 0.008). PMNs from patients with long aortic cross-clamp times generated three times more LTB4 than those patients with short cross-clamp times (194 +/- 29.6 vs 64.9 +/- 9.7 ng per 5 x 10(6) PMN; p < 0.05). Similarly, the pressure/inspired oxygen ratio was significantly lower on admission to the intensive care unit in patients with long cross-clamp times as compared with patients with short cross-clamp times (237 +/- 14 vs 342 +/- 5; p < 0.005). In addition, patients with long cross-clamp times remained intubated longer than patients with short times (1.6 +/- 0.2 vs 0.6 +/- 0.4 days; p < 0.05). These data suggest a causal role for LTB4 in the generation of pulmonary dysfunction in patients undergoing abdominal aortic aneurysm repair, similar to what has been shown in animal models.


Seroprevalence of tuberculosis in domesticated elk (Cervus canadensis) in Korea.
Tuberculosis is a contagious disease in animals, primarily cattle, although it also affects wild animals and humans. There are few data on the state of tuberculosis in domesticated elk (Cervus canadensis) in Korea. In order to investigate tuberculosis in elk, the effectiveness of an enzyme linked immunosorbent assay (ELISA) using MPB70 and MPB83 antigens was compared with the tuberculin skin test (TST), and seroprevalence was measured with this assay using serum samples collected from domesticated elk herds in Korea. The respective sensitivities of the MPB70 and MPB83 ELISAs were 51.9% (95% CI 42.0-61.6) and 49.1% (95% CI 39.3-58.9), and their specificities were 100.0% (95% CI 92.6-100.0) and 97.9% (95% CI 88.9-100.0), respectively, in comparison with the TST. The herd prevalence ranged from 50 to 80% and the mean herd seropositive rate was 67.7% (21 of 31). Of 819 serum samples, 163 (19.9%) were seropositive, and the within-region prevalence ranged from 18.5-58.0%. In conclusion, the ELISA using the MPB70 and MPB83 antigens showed moderate sensitivity and high specificity compared to TST in elk, and tuberculosis was assumed to be fairly prevalent in domesticated elk in Korea.


Distribution of glycated haemoglobin and its determinants in Korean youth and young adults: a nationwide population-based study.
The present study aimed to describe the distribution of and to investigate the factors associated with glycated haemoglobin (HbA1c) values in Korean youth (10-19 years old) and young adults (20-29 years old). Data from the Korea Health and Nutrition Examination Survey (2011-2015) were used. A total of 6,418 participants (male 3,140 [53.2%]) aged 10-29 years were included in the analysis. Percentiles of HbA1c were calculated and HbA1c values were compared according to age, sex, and associated factors. The mean HbA1c values (% [mmol/mol]) were 5.42 ± 0.01 (35.7 ± 0.1) for youths and 5.32 ± 0.01 (34.7 ± 0.1) for young adults (P < 0.001). Male participants showed significantly higher HbA1c level than females (P < 0.001). When age was grouped into 5-year intervals, HbA1c was the highest in those aged 10-14 years and the lowest in those aged 20-24 years. After controlling for confounding variables, the HbA1c values of youths and male participants were significantly higher than those of young adults and female participants. The present study provides nationally representative data on the distribution of HbA1c values in Korean youth and young adults. There were significant differences in the level of HbA1c according to age and sex.


Human-induced eutrophication maintains high parasite prevalence in breeding threespine stickleback populations.
Anthropogenic activities are having profound impacts on species interactions, with further consequences for populations and communities. We investigated the influence that anthropogenic eutrophication has on the prevalence of the parasitic tapeworm Schistocephalus solidus in threespine stickleback Gasterosteus aculeatus populations. We caught stickleback from four areas along the coast of Finland, and within each area from one undisturbed and one eutrophied habitat. We found the prevalence of the parasite to be lower in the eutrophied habitats at the start of the breeding season, probably because of fewer piscivorous birds that transmit the parasite. However, while the prevalence of the parasite declined across the season in the undisturbed habitat, it did less so in eutrophied habitats. We discuss different processes that could be behind the differences, such as lower predation rate on infected fish, higher food availability and less dispersal in eutrophied habitats. We found no effect of eutrophication on the proportion of infected stickleback that entered reproductive condition. Together with earlier findings, this suggests that eutrophication increases the proportion of infected stickleback that reproduce. This could promote the evolution of less parasite resistant populations, with potential consequences for the viability of the interacting parties of the host-parasite system.


[The nutritional value of raw breast milk in feeding premature babies with a birth weight of below 1500 g (author's transl)].
Raw milk expressed from the infant's own mother is the ideal initial nutrient, even for premature babies with a birth weight of below 1500 g. When these babies start to grow very rapidly from about the third week of life on, this milk is probably nutritionally inadequate. For babies with birth weights above 1500 g raw milk provided by the natural mother is the ideal nutrient at all times. This is a report of a simple and inexpensive system which enables us to collect breast milk and to test the bacterial count of each sample of milk. This milk is given to the babies without any heat treatment if the bacterial count is 10(3) per ml or less. Milk displaying bacterial counts of 10(4) to 10(5) per ml is boiled. Milk with higher bacterial counts is thrown away. Intensive counselling of the mothers as regards personal hygiene, with particular emphasis on breast hygiene and pumping technique improves the quality of the milk. In fact, 43% of the milk samples delivered to us have bacterial counts of below 10(4) per ml.


PPARα contributes to the therapeutic effect of hydrogen gas against sepsis-associated encephalopathy with the regulation to the CREB-BDNF signaling pathway and hippocampal neuron plasticity-related gene expression.
Sepsis-associated encephalopathy (SAE), a fatal complication of sepsis, contributes to cognitive impairment, high morbidity, and mortality. The molecular mechanism of hydrogen (H2) administration, as a promising strategy for the treatment of SAE, is still unclear. Peroxisome proliferator-activated receptor α (PPARα) is essential for alleviating symptoms and complications of SAE. However, little is known about the role of PPARα in SAE. This study was designed to evaluate the expression of PPARα in SAE and determine whether H2 can alleviate SAE through regulation of the cAMP response element-binding protein (CREB)-brain-derived neurotrophic factor (BDNF) signaling pathway and its downstream proteins via PPARα. After the injection of GW6471 (the PPARα inhibitor) or GW7647 (the PPARα agonist) or saline, C57BL/6 J mice were subjected to cecal ligation and puncture (CLP) or sham operation, then treated with 2% H2 by inhalation for 1 h after the operation. The 7-day survival rate was recorded, and the Y-maze test was used to assess cognitive function. Apoptotic cells were observed by TUNEL staining, and brain tissues were collected for pathological analysis by H&E staining. In addition, the levels of pro-inflammatory and anti-inflammatory cytokines (TNF-α, IL-6, IL-18, HMGB1, and IL-1β) were measured by ELISA and the expression of PPARα, CREB, BDNF and other neurotrophins, postsynaptic density protein of 95 kDa (PSD95) by Western blot. The relationship between PPARα and the CREB-BDNF signaling pathway was explored by coimmunoprecipitation (CO-IP). The results showed the expression of PPARα was decreased in SAE mice and that activation of PPARα in septic mice improved the survival rate and alleviated cognitive dysfunction. Furthermore, PPARα may have exerted anti-inflammatory and anti-apoptotic effects in septic mice. In addition, the GW6471 downregulated the expression of CREB, BDNF and other neurotrophins in SAE mice treated with H2. The expression of PSD95 was also downregulated and upregulated following the expression of PPARα. These results illustrated that H2 alleviates sepsis-induced brain injury in mice through the regulation of neurotrophins and hippocampal plasticity-related genes via PPARα by activating the CREB-BDNF signaling pathway.


Treatment of thalassemia-induced osteoporosis with intermittent pamidronate infusions: Two-year follow up.
The purpose of this study was to evaluate the bone mineral density (BMD) in 23 patients aged 7-14 years with thalassemia major and to assess the alterations in bone density in a two-year follow-up study. BMD of the lumbar spine and femoral neck was determined by dual-energy X-ray absorptiometry (DXA) at baseline, after 12 months of treatment and two years later. Pamidronate treatment (15 mg/dose, every 3 months for 1 year) was given to 23 osteoporotic (Z score below -2.5) and osteopenic (Z score -1 to -2.5) patients. After 12 months of treatment, all patients received only calcium and vitamin D supplements. After the two years of follow-up, BMD of the lumbar spine and femur was measured using DXA. Administration of pamidronate resulted in a significant increase in BMD of the femoral neck. Lumbar spine BMD after pamidronate treatment was slightly higher than at baseline, but this was statistically non-significant. After two years, femoral neck and lumbar BMD had significantly increased compared to baseline. In view of the present findings, longer follow-up studies to determine long-term treatment are fully warranted.


Factor Structure and Convergent Validity of the Short Version of the Bielefeld Partnership Expectations Questionnaire in Patients With Anxiety Disorder and Healthy Controls.
The short version of the Bielefeld Partnership Expectations Questionnaire (BPEQ-12) assesses the partner-related attachment dimensions fear of rejection, readiness for self-disclosure, and conscious need for care. The presented study investigated the factor structure in two samples and evaluated the convergent validity of scales. The sample included N = 175 patients with panic disorder and/or agoraphobia and N = 143 healthy controls. Besides, the BPEQ, the Experiences in Close Relationships Questionnaire (ECR), and the Brief Symptom Inventory (BSI) were assessed as well, and the Adult Attachment Prototype Rating (AAPR) was conducted. A confirmatory factor analysis of the three factor model (using a WLSMV estimator) revealed an acceptable model fit for the entire sample, patients and controls in terms of low RMSEA and SRMR (< 0.08) and high CFI and TLI (> 0.95). We found metric, scalar, and strict measurement invariance for the presence of anxiety disorder (ΔCFI ≤ -0.01 and ΔRMSEA ≥ 0.01). However, only for fear of rejection and readiness for self-disclosure the reliability was acceptable (Cronbach's α > 0.7), and convergent validity in terms of large correlations (r > 0.7) with the ECR scales was found in both samples. The scale conscious need for care had a questionable reliability (Cronbach's α > 0.6) and correlated only slightly with ECR-R scales. We conclude that fear of rejection and readiness for self-disclosure of the BPEQ-12 are reliable and valid scales for measuring partner-related attachment in healthy and clinical samples.


Novel protein domains and motifs in the marine planctomycete Rhodopirellula baltica.
The planctomycetes are a phylum of bacteria that have a unique cell compartmentalisation and yeast-like budding cell division and peptidoglycan-less proteinaceous cell walls. We wished to further our understanding of these unique organisms at the molecular level by searching for conserved amino acid sequence motifs and domains in the proteins encoded by Rhodopirellula baltica. Using BLAST and single-linkage clustering, we have discovered several new protein domains and sequence motifs in this planctomycete. R. baltica has multiple members of the newly discovered GEFGR protein family and the ASPIC C-terminal domain family, whilst most other organisms for which whole genome sequence is available have no more than one. Many of the domains and motifs appear to be restricted to the planctomycetes. It is possible that these protein domains and motifs may have been lost or replaced in other phyla, or they may have undergone multiple duplication events in the planctomycete lineage. One of the novel motifs probably represents a novel N-terminal export signal peptide. With their unique cell biology, it may be that the planctomycete cell compartmentalisation plan in particular needs special membrane transport mechanisms. The discovery of these new domains and motifs, many of which are associated with secretion and cell-surface functions, will help to stimulate experimental work and thus enhance further understanding of this fascinating group of organisms.


Effects of statins on the development of sepsis and organ dysfunction in hospitalized older patients in China.
This study aimed to evaluate the protective role of statins on the development of sepsis and infection-related organ dysfunction and mortality in a hospitalized older Chinese population with bacterial infections. In this retrospective cohort study, 257 older patients with bacterial infection were divided into two groups: a statin group, those who had received statin therapy for ≥1 month before admission and continued receiving statin during hospitalization; and a non-statin group, those who had never received statin or used statin for <1 month prior to admission. A multivariate logistic regression analysis was performed to identify risk and protective factors for severe sepsis. A significantly lower incidence of organ dysfunction was found in the statin group, as compared with the non-statin group (13.3% vs 31.1%, respectively; p=0.002), corresponding to adjusted rates ratio of 0.32 (95% confidence interval [CI], 0.13-0.75; p=0.009). No significant difference was found between statin and non-statin groups in 30-day sepsis-related mortality (4.4% vs 10.2%, respectively; p=0.109), incidence of intensive care unit admission (13.3% vs 16.8%, respectively; p=0.469), or length of hospital stay (20.5 vs 25.9 days, respectively; p=0.61). Statins significantly reduced the development of sepsis and infection-related organ dysfunction in hospitalized older Chinese patients but did not reduce 30-day mortality, ICU admission incidence, or length of hospital stay.


Clinical and genetic aspects of X-linked adrenoleukodystrophy.
X-linked adrenoleukodystrophy (ALD), a leukodystrophy characterized by abnormal accumulation of saturated very long chain fatty acids in brain white matter and adrenal cortex, is the most common inherited peroxisomal disorder. The biochemical defect is localized to the level of lignoceroyl-CoA synthesis, a step in the peroxisomal beta-oxidation of very long chain fatty acids. The responsible gene encodes a peroxisomal integral membrane protein of as yet unknown function which is a member of the ATP-binding cassette transporter protein superfamily. The patient gene mutations are heterogeneously distributed over the functional protein domains with a tendency to clustering in the nucleotide-binding fold. The mechanisms by which these mutations cause a loss of protein function is unknown. Diagnosis of patients and carriers, including prenatal testing, is mainly based on the clinical picture, the demonstration of increased levels of saturated very long chain fatty acids in tissues and body fluids as well as on DNA mutation analyses. There are at least six distinct clinical phenotypes ranging from the severe childhood cerebral form to asymptomatic persons. The various phenotypes commonly occur within the same kindred. Modifying genes and/or environmental factors may contribute to this phenomenon. At present, there is no proven therapy for the prevention or cure of the neurological disabilities. Several approaches are under investigation including diets, immunosuppression, bone marrow transplantation and gene therapy.


Polyamines metabolism and breast cancer: state of the art and perspectives.
Breast cancer (BC) is a common disease that generally occurs in women over the age of 50, and the risk is especially high for women over 60 years of age. One of the major BC therapeutic problems is that tumors initially responsive to chemotherapeutic approaches can progress to more aggressive forms poorly responsive to therapies. Polyamines (PAs) are small polycationic alkylamines, naturally occurring and essential for normal cell growth and development in eukaryotes. The intracellular concentration of PA is maintained within strongly controlled contents, while a dysregulation occurs in BC cells. Polyamines facilitate the interactions of transcription factors, such as estrogen receptors with their specific response element, and are involved in the proliferation of ER-negative and highly invasive BC tumor cells. Since PA metabolism has a critical role in cell death and proliferation, it represents a potential target for intervention in BC. The goal of this study was to perform a literature search reviewing the association between PA metabolism and BC, and the current evidence supporting the BC treatment targeting PA metabolism. We here describe in vitro and in vivo models, as well as the clinical trials that have been utilized to unveil the relationship between PA metabolism and BC. Polyamine pathway is still an important target for the development of BC chemotherapy via enzyme inhibitors. Furthermore, a recent promising strategy in breast anticancer therapy is to exploit the self-regulatory nature of PA metabolism using PA analogs to affect PA homeostasis. Nowadays, antineoplastic compounds targeting the PA pathway with novel mechanisms are of great interest and high social impact for BC chemotherapy.


The dangling choroid plexus: a sonographic observation of value in excluding ventriculomegaly.
To show that the position of the choroid plexus is dependent on gravity and to prove that this fact can be used as a simple means of avoiding the erroneous diagnosis of ventriculomegaly on fetal sonography, we evaluated 75 fetal sonograms retrospectively. Twenty-five fetuses had ventriculomegaly, and 50 had normal cerebral ventricles. The gestational ages ranged from 15 to 39 weeks. To show objectively that the position of the choroid plexus within the lateral ventricle was gravity dependent, we measured the choroid angle in each case. The choroid angle (the angle between the long axis of the choroid plexus and the linear midline echo on transverse axial sonograms through the body of the lateral ventricles) varied directly with ventricular size. In the group with normal-sized ventricles, the values for choroid angle followed a normal, unimodal distribution and had a mean of 14 degrees, a range of 6-22 degrees, and an SD of 4.3 degrees. In cases of ventriculomegaly, the values for choroid angle did not follow a normal distribution and ranged from 29 to 90 degrees. The choroid "dangled" from its attachment at the foramen of Monro and rested on the dependent wall of the lateral ventricle, resulting in a choroid angle that was increased over normal; the degree of the angle was dependent on the severity of the ventricular enlargement. The resting position of the choroid plexus marked the position of the lateral ventricular wall even when the reflection of ultrasound from the ventricular wall itself could not be seen. Detection of the position of the dependent choroid plexus is a simple observation that can be used to avoid the erroneous diagnosis of fetal ventriculomegaly and to help gauge the severity of true ventricular enlargement.


UK registry analysis of donor substance misuse and outcomes following pancreas transplantation.
Substance abuse is unfortunately common in organ donors. Often, these organs are declined for transplant, not only because of concerns around blood-borne virus transmission but also because of perceived poor outcomes. In kidney transplantation, previous studies have demonstrated donor smoking status significantly impacts transplant outcome, but intravenous drug use or alcohol dependence does not. This study aims to clarify these issues in pancreas transplantation. Retrospective data on all UK solid organ pancreas transplants from 1994 to 2015 were obtained from the NHSBT UK Transplant Registry. The impact of illicit drug misuse, alcohol abuse, and smoking on graft and patient survival were analyzed using Kaplan-Meier plots and a Cox regression model. A total of 1175 of the 2317 (49.5%) donors were categorized as substance misusers. Univariate survival analysis revealed no significant impact of substance misuse on 10-year graft or patient survival. Multivariate analysis confirmed substance misuse was not associated with impaired graft or patient survival. A history of donor substance misuse does not negatively impact 10-year graft or patient survival following pancreas transplantation. This is a large national registry analysis with long-term follow-up data and should therefore provide clinicians with reassurance when considering pancreas grafts from substance misuse donors.


Purification and properties of peroxidase from Nitrosomonas europaea.
Peroxidase from the obligate chemosynthetic bacterium Nitrosomonas europaea was purified 1,500-fold, and its properties were examined. The enzyme had a molecular weight of 53,000 and exhibited characteristic absorption maxima at 410, 524, and 558 mmu. The optimal pH and temperature were 7.5 and 44 C, respectively. The peroxidase reaction had an energy of activation of 5,850 cal/mole and required a primary substrate (H(2)O(2)) concentration of 7 x 10(-6)m to proceed at half maximal velocity (K(m)). Reduced cytochrome, c,p-phenylenediamine and pyrogallol acted as hydrogen donors to the purified peroxidase-H(2)O(2) complex. Conditions most suitable for the chemical oxidation of ammonium by H(2)O(2) were determined. The reaction was rapid and produced nitrite but no nitrate. Hydroxylamine was not detected as an intermediate, but it could substitute for ammonium in the system. Neither the rate nor the extent of these reactions was influenced by purified peroxidase, and no evidence was obtained to support a conclusion that the enzyme performs a vital role in the transformation of ammonium to nitrite by N. europaea.


Direct detection of Mycobacterium tuberculosis in respiratory specimens in a clinical laboratory by polymerase chain reaction.
The emergence of epidemic multiple-drug-resistant (MDR) strains of Mycobacterium tuberculosis in conjunction with an increase in the number of reported cases of tuberculosis (TB) represents a major public health problem. In light of a recent outbreak of MDR M. tuberculosis at our center, we began the development of a polymerase chain reaction (PCR) assay for the rapid diagnosis of pulmonary TB using two sets of primers, one based on the IS6110 repeated sequence of M. tuberculosis and the other based on the protein antigen b (PAB). Reaction conditions were first optimized as to the appropriate extraction protocol and the concentrations of primer pairs, nucleotides, and MgCl2. Following a preliminary evaluation of the assay with clinical specimens, extraction and amplification procedures were further modified. PAB and IS6110 primers detected between 2 and 23 and 0.023 and 0.23 CFU of M. tuberculosis, respectively, in pooled, M. tuberculosis-negative sputa by our optimized PCR assay. After routine processing for mycobacteria, 734 specimens were subsequently amplified. DNA for amplification was obtained by boiling and beating the sediments with Tween 20. For each reaction, DNA (10 microliters) was added to an amplification mixture containing 12 pmol of IS6110 primers, 20 pmol of PAB primers, 2 mM MgCl2, 200 microM nucleotides, and 2.5 U of Taq polymerase and the mixture was then amplified for 40 cycles. The sensitivity and specificity of our PCR assay were 87.2 and 97.7%, respectively. We were unable to interpret the results for seven specimens (1%). In our experience, PCR proved to be a useful rapid diagnostic test for TB in a clinical setting and a valuable epidemiological tool for determining exposure groups in the hospital setting. Our findings also underscore the need for the systematic optimization of PCR assay conditions.


In vitro effects of thermoablation on apoptosis of giant cell tumor of bone: a preliminary report.
Giant cell tumor of bone is a common benign aggressive bone tumor. Recurrent rate in the patients who have the tumor with soft tissue invasion is rather high. Use of strong chemicals such as phenol and liquid nitrogen to lessen the recurrent rate might not be used in this lesion. The experiment was carried out to discover apoptotic effects of thermoablation on giant cell tumor of bone to find out a possibility to use thermoablation in the clinic in the patients with extensive lesion. Tumor cell suspension was prepared from 4 patients who had definite diagnosis of giant cell tumor of bone. The tumor cells were subjected to thermoablation at 45, 47 and 50 degrees C for 10 to 30 minutes before were cultured at 37 degrees C for another 3 days. Osteoblasts and chondrocytes from the last 3 patients were collected,prepared and underwent thermoablation in the same fashion. Apoptosis of tumor cells, chondrocytes and osteoblasts were carried out by the use of flow cytometry. Thermoablation at 47 degrees C for 30 minutes resulted in < 50% chondrocyte and osteoblast apoptosis and 70-90% tumor cells apoptosis of 3/4 patients. Thermoablation at 47 and 50 degrees C for 20 to 30 minutes has more negative effect on giant cell tumor of bone than chondrocytes and osteoblasts. Thermoablation might be a useful tool for local tumor control in the clinic.


Postoperative ultrasonography surveillance in patients with follicular thyroid carcinoma: a multicenter study.
This study aimed to evaluate the locoregional recurrence rate of follicular thyroid carcinoma (FTC) and to assess the appropriate frequency of postoperative ultrasonography (US) surveillance for detecting tumor recurrence. The review boards of the seven participating institutions approved this study. From 2000 to 2011, 186 patients underwent at postoperative US at least once; US was performed by experienced radiologists at each institution. Based on the US and histopathological results, locoregional tumor recurrence was assessed. The T stages of the 186 patients were T1a (8.1%), T1b (21.5%), T2 (39.8%), T3 (30.6%), T4a (0%), and T4b (0%). The N stages were unknown (24.2%), N0 (71.5%), N1a (3.2%), and N1b (1.1%), and the M stages unknown (29.6%), M0 (66.1%), and M1 (4.3%). Tumors recurred in only 6 (3.2%) patients during the follow-up period over 5 years. Among them, no patients showed the initial suspicion of recurrences on routine follow-up US. The session number and interval of postoperative US differed significantly between patients with recurrence and those without recurrence. The mean interval of postoperative follow-up US at the first detection time of tumor recurrence was 37.5 ± 18.5 months (range 9-62 months). Significantly more FTCs were at an advanced N and M stage in the recurrence group than in the non-recurrence group (p < 0.05). Routine postoperative US surveillance may be unnecessary for detecting tumor recurrence after thyroid surgery in FTC patients.


The Use of Probiotics in Head and Neck Infections.
Recurrent episodes of infections in the upper respiratory tract are very common. The pathogenesis behind these recurrences is still not well understood, but much attention has been paid to the adherence of the microorganisms to epithelial structures and to the protective function of the normal bacterial flora (bacterial interference). Thus, in vitro as well as in vivo studies have shown that both aerobic and anaerobic bacteria of the normal flora in the upper respiratory tract can hinder the growth of pathogens and the establishment of a renewed infection. Studies have shown that lack of interfering bacteria facilitates recurrence of these diseases. Recolonization with interfering alpha-streptococci has been performed successfully in acute streptococcal pharyngotonsillitis, as well as in acute otitis media. The number of recurrences has significantly been lowered in these diseases after recolonization with alpha-streptococci, which is the dominating normal bacteria in the upper respiratory tract. Several mechanisms have been proposed to be responsible for this interaction, such as competition of the adhering sites at the epithelial cells, production of hydrogen peroxide, competition for nutritients, and production of specific growth inhibiting factors such as bacteriocins. Other human components like lactoferrin are also important in the defense against microorganisms, and are important parts of the unspecific and specific immune system.


Correlation between in vitro complement deposition and passive mouse protection of anti-pneumococcal surface protein A monoclonal antibodies.
The shortcomings of the licensed polysaccharide-based pneumococcal vaccine are driving efforts toward development of a protein-based vaccine that is serotype independent and effective in all age groups. An opsonophagocytic killing assay (OPKA) is used to evaluate the antibody response against polysaccharide-based pneumococcal vaccines. However, the OPKA is not reliable for noncapsular antigens. Thus, there is a need to develop an in vitro surrogate for protection for protein vaccine candidates like pneumococcal surface antigen A (PspA). PspA is a serologically variable cell surface virulence factor. Based on its sequence, PspA has been classified into families 1 (clade 1 and 2), 2 (clades 3, 4 and 5), and 3 (clade 6). Here, we report the characterization of 18 IgG anti-PspA monoclonal antibodies (anti-PspA(hkR36A) MAbs) generated from mice immunized with heat-killed strain R36A (clade 2). An enzyme-linked immunosorbent assay (ELISA)-based analysis of the reactivity of the MAbs with recombinant PspAs from the 6 clades indicated that they were family 1 specific. This was confirmed by flow cytometry using a hyperimmune serum generated against PspA from R36A. Eight MAbs that bind at least one clade 1- and clade 2-expressing strain were evaluated for complement deposition, bactericidal activity, and passive protection. The anti-PspA(hkR36A) MAb-dependent deposition of complement on pneumococci showed a positive correlation with passive protection against strain WU2 (r = 0.8783, P = 0.0041). All of our protective MAbs showed bactericidal activity; however, not all MAbs that exhibited bactericidal activity conferred protection in vivo. The protective MAbs described here can be used to identify conserved protection eliciting B cell epitopes for engineering a superior PspA-based vaccine.


Evaluation of biochemical parameters and local and systemic levels of osteoactive and B-cell stimulatory factors in gestational diabetes in the presence or absence of gingivitis.
Gestational diabetes mellitus (GDM) is defined as varying glucose intolerance, with first onset or recognition in pregnancy. This study evaluates clinical and biochemical parameters in a possible association between GDM and gingivitis. A total of 167 pregnant females was included in the study. There were 101 females with GDM and 66 females without GDM. Subgroups were created according to the presence or absence of gingival inflammation. Plaque index, bleeding on probing, and probing depth were recorded at four sites per tooth. Serum, saliva, and gingival crevicular fluid (GCF) levels of interleukin (IL)-6, IL-8, soluble receptor activator of nuclear factor-kappa B ligand (sRANKL), osteoprotegerin (OPG), B-cell activating factor (BAFF), and a proliferation-inducing ligand (APRIL) were determined by enzyme-linked immunosorbent assay. Data were analyzed by Kruskal-Wallis and Mann-Whitney U tests and Spearman correlation analysis. Age and anthropometric indices were higher in the GDM than non-GDM group (P <0.0001). Clinical periodontal recordings, serum BAFF, IL-8, and saliva sRANKL levels were higher in the GDM group (P <0.05). Saliva IL-6 level was higher in the GDM with gingivitis group than non-GDM with gingivitis group (P = 0.044). Serum and GCF BAFF (P <0.0001), serum, saliva, and GCF APRIL (P <0.0001; P <0.0001; P = 0.032, respectively), GCF OPG (P = 0.036), and serum and saliva sRANKL (P <0.0001) were higher in the GDM with gingivitis group than GDM without gingivitis group. The inflammatory response seems to be more pronounced in females with GDM. The observed increase in both local and systemic levels of inflammatory cytokines may suggest an interaction between gingivitis and GDM.


The use of rapid prototyping in the preoperative planning of distraction osteogenesis of the cranio-maxillofacial skeleton.
In cranio-maxillofacial surgery, the principle of distraction osteogenesis (DO) can be used for the reconstruction of the deformed skull, midface complex, mandible and alveolar ridge. Optimal results can only be obtained with accurate planning of the osteotomies and accurate positioning of the distraction device. In addition, the surgical planning must be transferred very precisely to the patient in the operating theater. The clinical accuracy and utility of stereolithographic models in cranio-maxillofacial distraction osteogenesis of the midface, mandible and alveolar ridge will be demonstrated. Thirteen patients were treated by DO in the cranio-maxillofacial skeleton. Five patients suffered from midface retrusion and were treated by a LeFort III advancement. One patient suffered from an aseptic necrosis of the condylar process of the mandible and had a reconstruction of the condylar process by DO. Seven patients underwent an osteotomy of the alveolar ridge of the mandible with subsequent placement of distraction screws and implants because of advanced atrophy of the mandible. Following preoperative acquisition and conversion of the CT-scan data, a model was fabricated by stereolithography (SLA). Simulation of the osteotomies and placement of distraction devices was performed on these models, then surgical guides were used to transfer the surgical planning to the patient in the operating theater. Pre- and postoperative facial photographs and X-rays were compared to evaluate the accuracy of the transfer procedure. In all cases, matching of pre- and postoperative facial photographs and X-rays showed reconstruction of the bony structures to be as accurate as planned on the SLA models. Transfer of the surgical plan by means of custom-made surgical guides was optimal in all cases. Preoperative planning of distraction osteogenesis of the cranio-maxillofacial skeleton and transfer to the operating theater by custom-made surgical guides remains the standard procedure for the planning of complex distraction cases. However, improvements in surgical simulation software and accurate virtual-reality surgery will probably make the use of these models redundant in the future.


A photocleavable and mass spectrometry identifiable cross-linker for protein interaction studies.
In this paper, we present the results of proof-of-concept experiments using a novel photocleavable and mass spectrometry identifiable cross-linker pcPIR (photocleavable protein interaction reporter). pcPIR can be dissociated under UV irradiation either off- or online before the introduction to the mass spectrometers. Photo dissociation of cross-linkers is different from either the gas phase or the chemical cleavage of cross-linkers. Different types of cross-links can be identified using the pcPIR mass relationships, where the mass of cross-linked precursor equals the sum of the masses of the released products and reporter. Since pcPIR is cleaved prior to the entrance to the mass spectrometer, the released peptides are available to be sequenced with routine collision-induced dissociation (CID) MS/MS experiments and database search algorithms. In this report, the pcPIR strategy of identifying the cross-linked peptides with on- and off-line photocleavage coupled with novel targeted data dependent LC-MS/MS is demonstrated with the use of standard peptides, bovine serum albumin (BSA), and human hemoglobin tetramer protein complex.


Identification of protein disulfide isomerase 1 as a key isomerase for disulfide bond formation in apolipoprotein B100.
Apolipoprotein (apo) B is an obligatory component of very low density lipoprotein (VLDL), and its cotranslational and posttranslational modifications are important in VLDL synthesis, secretion, and hepatic lipid homeostasis. ApoB100 contains 25 cysteine residues and eight disulfide bonds. Although these disulfide bonds were suggested to be important in maintaining apoB100 function, neither the specific oxidoreductase involved nor the direct role of these disulfide bonds in apoB100-lipidation is known. Here we used RNA knockdown to evaluate both MTP-dependent and -independent roles of PDI1 in apoB100 synthesis and lipidation in McA-RH7777 cells. Pdi1 knockdown did not elicit any discernible detrimental effect under normal, unstressed conditions. However, it decreased apoB100 synthesis with attenuated MTP activity, delayed apoB100 oxidative folding, and reduced apoB100 lipidation, leading to defective VLDL secretion. The oxidative folding-impaired apoB100 was secreted mainly associated with LDL instead of VLDL particles from PDI1-deficient cells, a phenotype that was fully rescued by overexpression of wild-type but not a catalytically inactive PDI1 that fully restored MTP activity. Further, we demonstrate that PDI1 directly interacts with apoB100 via its redox-active CXXC motifs and assists in the oxidative folding of apoB100. Taken together, these findings reveal an unsuspected, yet key role for PDI1 in oxidative folding of apoB100 and VLDL assembly.


On the need for a new psychotherapy research paradigm: comment on Westen, Novotny, and Thompson-Brenner (2004).
Basic, process, and outcome research have the potential to inform clinical practice. However, as D. Westen, C. M. Novotny, and H. Thompson-Brenner observed in their timely analysis, the current dominant paradigm for psychotherapy outcome research--the randomized clinical trial--is not fulfilling this potential. The field's reliance on the medical model and manual-based interventions has contributed to the gap between research and clinical practice. Greater collaboration between practitioners and researchers, a focus on therapeutic principles rather than treatment packages, and systemic changes in how scholarly efforts are reinforced are needed to shift the current research paradigm.


A role for the substance P/NK-1 receptor complex in cell proliferation and apoptosis in oral lichen planus.
To determine whether substance P (SP) and NK-1 receptor (NK-1R) are expressed in oral lichen planus (OLP) and are related to cell proliferation and apoptosis in this disease. Tissue samples from 50 OLP patients and 26 healthy controls were studied. Immunohistochemistry was performed with anti-SP, anti-NK-1R, anti-ki-67 and anti-caspase-3 monoclonal antibodies and the clinical and pathological data of the OLP patients were evaluated. With the exception of NK-1R expression in epithelial cell membrane and cytoplasm, all markers were more frequently present in OLP patients than in controls (P < 0.05). Higher cytoplasmatic expression of NK-1R was associated with higher epithelial expression of caspase-3 (P < 0.05). Higher epithelial expression of NK-1R and SP was associated with higher suprabasal and basal epithelial expression of ki-67 (P < 0.05 and P < 0.005, respectively). Actions of the SP/NK-1R complex may contribute to the immune disorder underlying OLP and trigger stimuli to induce cell proliferation. These results indicate that this complex might play a role in the malignant transformation of OLP.


New model for magnetism in ultrathin fcc Fe on Cu(001).
Using soft-x-ray resonant magnetic scattering in combination with first-principles calculations for noncollinear magnetic configurations we present a new model of the magnetism in ultrathin fcc Fe films on Cu(001). We find the presence of blocks with robust magnetic structure, while the relative directions of the moments of different blocks are sensitive to the detailed atomic structure and temperature. The magnetic noncollinearity is directly demonstrated, which has not been possible so far.


Importance of anterior commissure in recurrence of early glottic cancer after laser endoscopic resection.
To analyze the impact of anterior commissure involvement on rates of local control, recurrence, and laryngeal preservation in patients with early glottic cancer (T1a-T2 lesions, staged according to the TNM staging system) treated with laser microsurgical resection. Retrospective review. A tertiary university referral center. Forty-eight patients with early glottic (T1-T2a) cancer. Laser endoscopic resection of glottic cancer. Evaluation of local control and larynx preservation rates. Among 48 patients presenting with early glottic cancer, the anterior commissure was involved in 24 cases. The local control rate was 79% (19 cases), and the larynx preservation rate was 96% (23 cases). In the 24 cases without anterior commissure involvement, the local control rate was 96% (23 cases) and the corresponding larynx preservation rate was 100% (24 cases). The rate of local recurrence with anterior commissure involvement was 21% (5 cases) and was 4% (1 case) when this site was not compromised by the tumor. This difference was not statistically significant (P = .08). When the anterior commissure was compromised by a lesion, more surgical margins taken from the patient after the completion of surgery (additional margins) were compromised by squamous cell carcinoma (SCC) on permanent section (33% [8 cases]) compared with 0% from patients with anterior commissure involvement (P = .003), despite the fact that these margins were negative for disease on frozen section. Cases with additional margins compromised by SCC on permanent section (P = .004) and T1 lesions (P = .009) had a higher rate of recurrence. This study shows the tendency toward greater additional margins compromised by SCC and a higher rate of tumor recurrence in lesions with anterior commissure involvement after laser microsurgery for early glottic carcinoma. Higher recurrence rates were observed in cases with compromised additional margins and in T1 cases.


Recent insights into antidepressant therapy: Distinct pathways and potential common mechanisms in the treatment of depressive syndromes.
There is an urgent, unmet clinical need for faster and more efficient antidepressant drugs with higher response rates. In animal models of depression it was shown in the last few years that inhibition of three signaling molecules (BDNF, p11 and Homer1a) prevents efficacy of antidepressant therapy. These data not only show the crucial role of these factors for the treatment of depression, but may also point towards a better understanding of the molecular changes responsible for successful antidepressant therapy. Reviewing the literature concerning BNDF, p11 and Homer1a we here describe a molecular network in which these molecules interact with each other finally leading to facilitation of AMPA receptor signaling and plasticity, corroborating the current idea of AMPA receptors being a promising drug target in depression.


Restitution analysis of alternans using dynamic pacing and its comparison with S1S2 restitution in heptanol-treated, hypokalaemic Langendorff-perfused mouse hearts.
Action potential duration (APD) and conduction velocity restitution explain the dependence of these parameters on the previous diastolic interval (DI). It is considered to be an adaptive mechanism for preserving diastole at fast heart rates. Hypokalaemia is known to induce ventricular arrhythmias that could be prevented by heptanol, the gap junction uncoupler, mediated through increases in ventricular refractory period (VERP) without alterations in APDs. The present study investigated alternans and restitution properties during normokalaemia, hypokalaemia alone or hypokalaemia with heptanol (0.1 mM) in Langendorff-perfused mouse hearts using a dynamic pacing protocol. APD90 alternans were elicited in the epicardium and endocardium during normokalaemia. Hypokalaemia increased the amplitudes of epicardial APD90 alternans when basic cycle lengths (BCLs) were ≤65 msec, which was associated with increases in maximum APD90 restitution gradients, critical DIs and APD90 heterogeneity. Heptanol (0.1 mM) did not exacerbate or reduce the APD90 alternans or alter these restitution parameters further. By contrast, endocardial APD90 alternans did not show increases in amplitudes during hypokalaemia at short BCLs studied, and restitution parameters were also unchanged. This was true whether in the presence or absence of 0.1 mM heptanol. The study demonstrates that anti-arrhythmic effects of heptanol exerted during hypokalaemia occurred despite exacerbation of APD90 alternans. This would suggest that even in the presence of arrhythmogenic APD90 alternans, arrhythmias could still be prevented by influencing VERP alone. Restitution data obtained here by dynamic pacing were compared to previous data from S1S2 pacing.


Induced trefoil factor family 1 expression by trans-differentiating Clara cells in a murine asthma model.
Asthma is a chronic inflammatory disease of the airways that is accompanied by goblet cell metaplasia and mucus hypersecretion. Trefoil factor family (TFF) peptides represent major secretory products of the respiratory tract and are synthesized together with mucins. In the murine lung, TFF2 is mainly expressed, whereas TFF1 transcripts represent only a minor species. TFF peptides are well known for their motogenic and anti-apoptotic effects, and they modulate the inflammatory response of bronchial epithelial cells. Here, an established mouse model of asthma was investigated (i.e., exposure to Aspergillus fumigatus [AF] antigens). RT-PCR analysis of lung tissue showed elevated levels particularly of TFF1 transcripts in AF-sensitized/challenged animals. In contrast, transcripts encoding Clara cell secretory protein (CCSP/CC10) were strongly diminished in these animals. For comparison, the expression of the goblet cell secretory granule marker mCLCA3/Gob-5, the mucins Muc1-Muc6 and Muc19, and the secretoglobins ScgB3A1 and ScgB3A2, as well as the mammalian ependymin-related gene MERP2, were monitored. Immunohistochemistry localized TFF1 mainly in cells with a mixed phenotype (e.g., TFF1-positive cells stain with the lectin wheat germ agglutinin (WGA), which recognizes mucins characteristic of goblet cells). In addition, these cells express CCSP/CC10, a Clara cell marker. When compared with mucins or CCSP/CC10, TFF1 was stored in a different population of secretory granules localized at the more basolateral portion of these cells. Thus, the results presented indicate for the first time that allergen exposure leads to the trans-differentiation of Clara cells toward a TFF1-expressing mucous phenotype.


An Analysis of Otolaryngology in Avicenna's Canon of Medicine: Utilizing the Original Arabic Text.
Avicenna authored The Canon of Medicine, a principal medical textbook for over 600 years. Our primary goal is to systematically review and translate relevant portions of The Canon in its original Arabic and correlate to Sardo's 2014 translation, focusing on otolaryngology, to present an accurate representation of Avicenna's impact and highlight notable discrepancies. Secondarily, we aim to review the literature for citations discussing Avicenna's contributions to otolaryngology and identify misinterpretations. Notably, Avicenna may have described the shape of the cochlea 500 years before its believed discovery in humans by Eustachius (1552) and Falloppius (1561). There are also obscurities in Avicenna's descriptions of the etiology of epistaxis and airway management. It is essential to remain critical of historical texts and safeguard the accurate propagation of information to preserve the integrity of historical context and timelines of scientific advancement.


Absence of major histocompatibility complex class II mediated immunity in pipefish, Syngnathus typhle: evidence from deep transcriptome sequencing.
The major histocompatibility complex (MHC)-mediated adaptive immune system is the hallmark of gnathostome immune defence. Recent work suggests that cod-like fishes (Gadidae) lack important components of the MHC class II mediated immunity. Here, we report a putative independent loss of functionality of this pathway in another species, the pipefish Syngnathus typhle, that belongs to a distantly related fish family (Syngnathidae). In a deep transcriptome sequencing approach comprising several independent normalized and non-normalized expressed sequence tag (EST) libraries with approximately 7.5 × 10(8) reads, sequenced with two next generation platforms (454 and Illumina), we were unable to identify MHC class IIα/β genes as well as genes encoding associated receptors. Along with the recent findings in cod, our results suggest that immune systems of the Euteleosts may be more variable than previously assumed.


Surface-Energetic Heterogeneity of Nanoporous Solids for CO2 and CO Adsorption: The Key to an Adsorption Capacity and Selectivity at Low Pressures.
This study has been focused on surface energetic heterogeneity of zeolite (H-mordenite, "HM"), activated carbon ("RB2") and metal-organic framework family ("Z1200") materials and their isotherm features in adsorption of CO2 and CO at 25 degrees C and low pressures ≤ 850 Torr. The nanoporous solids showed not only distinctive shape of adsorption isotherms for CO2 with relatively high polarizability and quadrupole moment but also different capacities in the CO2 adsorption. These differences between the adsorbents could be well correlated with their surface nonuniformity. The most heterogeneous surfaces were found with the HM that gave the highest CO2 uptake at all pressures allowed, while the Z1200 consisted of completely homogeneous surfaces and even CO2 adsorption linearly increased with pressure. An intermediate character was indicated on the surface of RB2 and thus this sorbent possessed isotherm features between the HM and Z1200 in CO2 adsorption. Such different surface energetics was fairly consistent with changes in CO2/CO selectivity on the nanoporous adsorbents up to equilibrated pressures near 850 Torr.


[Gas exchange and physical work capacity of natives of different geographical regions].
A study was carried out to investigate exercise tolerance, gas exchange and external respiration of Latin-American students who lived in Moscow for a year. As controls Soviet students residing in and around Moscow were used. The above parameters were measured at a different time of the day in response to a hypercapnic exposure. Exercise tolerance was determined using the test PWC170. External respiration and gas exchange were investigated at rest and during 5 min exercises with a load of 1 and 2 Wt/kg body weight. CO2 sensitivity was determined by means of the rebreathing method. In the evening the Latin-American students showed a trend towards an increase of the cardiorespiratory activity and exercise tolerance. The Soviet students did not display changes in exercise tolerance. The Latin-American students showed an increase in the morning and a decrease in the evening of external respiration reactions. The Soviet students exhibited opposite variations. Direct alveolar measurements demonstrated an increase of pCO2 in the alveolar air in the Latin-American students in the evening and a decrease of the parameter in the Soviet students. It is suggested that cyclic changes in external respiration in response to hypercapnia are associated with exercise tolerance.


Results from the International Consensus Conference on Myo-inositol and d-chiro-inositol in Obstetrics and Gynecology: the link between metabolic syndrome and PCOS.
In recent years, interest has been focused to the study of the two major inositol stereoisomers: myo-inositol (MI) and d-chiro-inositol (DCI), because of their involvement, as second messengers of insulin, in several insulin-dependent processes, such as metabolic syndrome and polycystic ovary syndrome. Although these molecules have different functions, very often their roles have been confused, while the meaning of several observations still needs to be interpreted under a more rigorous physiological framework. With the aim of clarifying this issue, the 2013 International Consensus Conference on MI and DCI in Obstetrics and Gynecology identified opinion leaders in all fields related to this area of research. They examined seminal experimental papers and randomized clinical trials reporting the role and the use of inositol(s) in clinical practice. The main topics were the relation between inositol(s) and metabolic syndrome, polycystic ovary syndrome (with a focus on both metabolic and reproductive aspects), congenital anomalies, gestational diabetes. Clinical trials demonstrated that inositol(s) supplementation could fruitfully affect different pathophysiological aspects of disorders pertaining Obstetrics and Gynecology. The treatment of PCOS women as well as the prevention of GDM seem those clinical conditions which take more advantages from MI supplementation, when used at a dose of 2g twice/day. The clinical experience with MI is largely superior to the one with DCI. However, the existence of tissue-specific ratios, namely in the ovary, has prompted researchers to recently develop a treatment based on both molecules in the proportion of 40 (MI) to 1 (DCI).


Prebiotic dimer and trimer peptide formation in gas-phase atmospheric nanoclusters of water.
Insight into the origin of prebiotic molecules is key to our understanding of how living systems evolved into the complex network of biological processes on Earth. By modelling diglycine and triglycine peptide formation in the prebiotic atmosphere, we provide a plausible pathway for peptide growth. By examining different transition states (TSs), we conclude that the formation of diglycine and triglycine in atmospheric nanoclusters of water in the prebiotic atmosphere kinetically favors peptide growth by an N-to-C synthesis of glycines through a trans conformation. Addition of water stabilizes the TS structures and lowers the Gibbs free activation energies. At temperatures that model the prebiotic atmosphere, the free energies of activation with a six water nanocluster as part of the TS are predicted to be 16 kcal mol-1 relative to the prereactive complex. Examination of the trans vs. cis six water transition states reveals that a homodromic water network that maximizes the acceptor/donor nature of the six waters is responsible for enhanced kinetic favorability of the trans N-to-C pathway. Compared to the non-hydrated trans TS, the trans six-water TS accelerates the reaction of diglycine and glycine to form triglycine by 13 orders of magnitude at 217 K. Nature uses the trans N-to-C pathway to synthesize proteins in the ribosome, and we note the similarities in hydrogen bond stabilization between the transition state for peptide synthesis in the ribosome and the transition states formed in nanoclusters of water in the same pathway. These results support the hypothesis that small oligomers formed in the prebiotic atmosphere and rained onto earth's surface.


Response of fluctuating asymmetry to arsenic toxicity: support for the developmental selection hypothesis.
The effect of exposure to sodium arsenite during development was tested on adult fluctuating asymmetry (FA) in sternopleural bristle number, bristle number, body size and survivorship in Drosophila melanogaster. Three genetic strains of flies were used, CT-106, PVM and Oregon-R, and arsenite concentrations ranged from relatively mild, sub-lethal doses, to concentrations with pronounced negative effects on survivorship. At arsenite concentrations of 1.0 and 0.125 mM, mortality was on average 38% greater than in controls, and surviving flies emerged significantly smaller and had fewer bristles than controls. Neither the effect of arsenite or the genotype x environment interaction on asymmetry were significant. However, given the high mortality, any increase in FA could have been masked by the outcome of developmental selection against developmentally unstable phenotypes. We tested for this effect by contrasting FA values between (1) flies reared at the highest concentrations used previously, (2) flies reared at sub-lethal dosage, and (3) controls. Positional fluctuating asymmetry (PFA), which is expected to be a sensitive indicator of underlying developmental stability, was significantly reduced among flies reared at the highest concentration, and at which flies suffered significant mortality. Moreover, the slope of the regression relating mean PFA to emergence per bottle was significantly positive. These data support the hypothesis that developmental selection occurred in this experiment, and that the expected positive relationship between asymmetry and stress may be altered when the stressor eliminates individuals from the population. In contrast, FA of flies reared at sub-lethal dosage did not differ from that in controls, a result that fails to support the hypothesis that arsenite disrupts developmental stability. Our results call for caution in FA-based biomonitoring, especially of potentially lethal forms of stress, because in the presence of developmental selection, and under the common assumption that FA should increase under stress, erroneous conclusions may be drawn about the health and well being of a population. It is suggested that FA-based biomonitoring efforts integrate the use of FA with other bioindicators, and experimentally validate any expected FA-stress relationship before attempting to infer the presence of environmental stress.


Interfacial Oxygen Octahedral Coupling-Driven Robust Ferroelectricity in Epitaxial Na0.5Bi0.5TiO3 Thin Films.
The oxygen octahedral rotation (OOR) forms fundamental atomic distortions and symmetries in perovskite oxides and definitely determines their properties and functionalities. Therefore, epitaxial strain and interfacial structural coupling engineering have been developed to modulate the OOR patterns and explore novel properties, but it is difficult to distinguish the 2 mechanisms. Here, different symmetries are induced in Na0.5Bi0.5TiO3 (NBT) epitaxial films by interfacial oxygen octahedral coupling rather than epitaxial strain. The NBT film grown on the Nb:SrTiO3 substrate exhibits a paraelectric tetragonal phase, while with La0.5Sr0.5MnO3 as a buffer layer, a monoclinic phase and robust ferroelectricity are obtained, with a remanent polarization of 42 μC cm-2 and a breakdown strength of 7.89 MV cm-1, which are the highest record among NBT-based films. Moreover, the interfacial oxygen octahedral coupling effect is demonstrated to propagate to the entire thickness of the film, suggesting an intriguing long-range effect. This work provides a deep insight into understanding the structure modulation in perovskite heterostructures and an important avenue for achieving unique functionalities.


Preconditioned Stochastic Gradient Descent.
Stochastic gradient descent (SGD) still is the workhorse for many practical problems. However, it converges slow, and can be difficult to tune. It is possible to precondition SGD to accelerate its convergence remarkably. But many attempts in this direction either aim at solving specialized problems, or result in significantly more complicated methods than SGD. This paper proposes a new method to adaptively estimate a preconditioner, such that the amplitudes of perturbations of preconditioned stochastic gradient match that of the perturbations of parameters to be optimized in a way comparable to Newton method for deterministic optimization. Unlike the preconditioners based on secant equation fitting as done in deterministic quasi-Newton methods, which assume positive definite Hessian and approximate its inverse, the new preconditioner works equally well for both convex and nonconvex optimizations with exact or noisy gradients. When stochastic gradient is used, it can naturally damp the gradient noise to stabilize SGD. Efficient preconditioner estimation methods are developed, and with reasonable simplifications, they are applicable to large-scale problems. Experimental results demonstrate that equipped with the new preconditioner, without any tuning effort, preconditioned SGD can efficiently solve many challenging problems like the training of a deep neural network or a recurrent neural network requiring extremely long-term memories.


Three-month follow-up of arterial blood gas determinations in candidates for long-term oxygen therapy. A multicentric study.
One hundred seventeen patients with severe chronic obstructive pulmonary disease whose PaO2 in a stable clinical state ranged from 41 to 59 mmHg, were included in a multicentric controlled study on the effects of long-term O2 therapy (LTO), and the results of the 3-month probationary period are given here. Arterial blood gases were checked every month in order to assess the stability of hypoxemia. Time 0 represented the beginning and T3 the end of the probationary period. Patients whose PaO2 at T3 was still between 41 and 59 mmHg could be accepted for the long-term study (Group A), whereas patients whose PaO2 had increased over 59 mmHg were excluded (Group B). Only 77 patients could be followed up regularly from T0 to T3 (40 patients were lost to follow-up, missed some visits, or suffered from acute exacerbations of the disease) and 23 of them had a PaO2 at T3 that exceeded 59 mmHg (Group B), allowing the inclusion of 54 patients (Group A) in the long-term study. Patients in Groups A and B did not differ with regard to pulmonary volumes, PaCO2 at T0 or a past history of right heart failure. Arterial O2 tension at T0 was slightly and significantly (p less than 0.02) lower in Group A (51.3 +/- 5.5 mmHg) than in Group B (54.5 +/- 3.8 mmHg), but there was an important overlapping of individual results from one group to another.(ABSTRACT TRUNCATED AT 250 WORDS)


Incidence of osteonecrosis of the jaw by the use of osteoclast inhibitors in patients with bone metastases: a retrospective cohort study.
The use of osteoclast inhibitors in metastatic bone disease, increase bone mineral density and reduce the risk of fracture, patients with osteonecrosis have been reported after the chronic use of these inhibitors. In our country, the use of osteoclast inhibitors is in the context of osteoporosis and bone metastases, so it is important to describe the incidence of this complication in Mexican population. To describe the incidence of osteonecrosis of the jaws at the Centro Médico Nacional 20 de Noviembre, during the period from January 1st, 2010 to June 1st, 2016. This is a retrospective cohort study developed at the Centro Medico Nacional 20 Noviembre, ISSSTE, Mexico. We included all patients who received bisphosphonates or denosumab in the context of metastatic bone disease due to solid tumors and who had osteonecrosis of the jaw. A 802 patients who used bisphosphonates or denosumab in metastatic bone disease (699 bisphosphonates and 103 denosumab). Of these, 28 (3.5%) patients presented osteonecrosis. The median use of zoledronic acid for the presence of osteonecrosis was 25 months (15-49 months) and for Denosumab it was 16 months (11-35 months), without finding significant differences between the use of drugs p = 0.511 and the risk of osteonecrosis. Drug-induced osteonecrosis has a low incidence in Mexican population, denosumab does not show a greater number of cases of osteonecrosis compared to bisphosphonates; no association was found between functional status, number of metastatic bone sites, nor use of antigenic or tyrosine kinase inhibitors as factor associated with osteonecrosis of the jaws.


Sex effects on net protein and energy requirements for growth of Saanen goats.
Requirements for growth in the different sexes remain poorly quantified in goats. The objective of this study was to develop equations for estimating net protein (NPG) and net energy (NEG) for growth in Saanen goats of different sexes from 5 to 45 kg of body weight (BW). A data set from 7 comparative slaughter studies (238 individual records) of Saanen goats was used. Allometric equations were developed to determine body protein and energy contents in the empty BW (EBW) as dependent variables and EBW as the allometric predictor. Parameter estimates were obtained using a linearized (log-transformation) expression of the allometric equations using the MIXED procedure in SAS software (SAS Institute Inc., Cary, NC). The model included the random effect of the study and the fixed effects of sex (intact male, castrated male, and female; n = 94, 73, and 71, respectively), EBW, and their interactions. Net requirements for growth were estimated as the first partial derivative of the allometric equations with respect to EBW. Additionally, net requirements for growth were evaluated based on the degree of maturity. Monte Carlo techniques were used to estimate the uncertainty of the calculated net requirement values. Sex affected allometric relationships for protein and energy in Saanen goats. The allometric equation for protein content in the EBW of intact and castrated males was log10 protein (g) = 2.221 (±0.0224) + 1.015 (±0.0165) × log10 EBW (kg). For females, the relationship was log10 protein (g) = 2.277 (±0.0288) + 0.958 (±0.0218) × log10 EBW (kg). Therefore, NPG for males was greater than for females. The allometric equation for the energy content in the EBW of intact males was log10 energy (kcal) = 2.988 (±0.0323) + 1.240 (±0.0238) × log10 EBW (kg); of castrated males, log10 energy (kcal) = 2.873 (±0.0377) + 1.359 (±0.0283) × log10 EBW (kg); and of females, log10 energy (kcal) = 2.820 (±0.0377) + 1.442 (±0.0281) × log10 EBW (kg). The NEG of castrated males was greater than that of intact males and lower than that of females. Using degree of maturity for estimating NPG and NEG, we could remove the differences between sexes. These results indicate that NPG and NEG differ among sexes in growing Saanen goats, and this difference should be accounted for by feeding systems. Including the degree of maturity as predictor cancels out those differences across sexes in protein and energy requirements.


Sum1, a highly conserved WD-repeat protein, suppresses S-M checkpoint mutants and inhibits the osmotic stress cell cycle response in fission yeast.
The S-M checkpoint ensures that entry into mitosis is dependent on completion of DNA replication. In the fission yeast Schizosaccharomyces pombe, the SM checkpoint mutant cdc2-3w is thought to be defective in receiving the checkpoint signal. To isolate genes that function in the checkpoint pathway, we screened an S. pombe cDNA library for genes that, when overexpressed, could suppress the checkpoint defect of cdc2-3w. Using this approach, we have identified a novel gene, sum1+ (suppressor of uncontrolled mitosis). sum1+ encodes a highly conserved WD-transducin repeat protein with striking sequence similarity to the human transforming growth factor (TGF)-beta-receptor interacting protein TRIP-1 and to the translation initiation factor 3 subunit eIF3-p39, encoded by the TIF34 gene in Saccharomyces cerevisiae. S. pombe sum1+ is an essential gene, required for normal cell growth and division. In addition to restoring checkpoint control, overexpression of sum1+ inhibits the normal cell cycle response to osmotic stress. Furthermore, we demonstrate that inactivation of the stress-activated MAP kinase pathway, required for cell cycle stress response, restores the S-M checkpoint in cdc2-3w cells. These results suggest that Suml interacts with the stress-activated MAP kinase pathway and raise the possibility that environmental conditions may influence the checkpoint response in fission yeast.


[Occupational allergic IgE-mediated disease from Boletus edulis: case report].
Fungal components can cause allergic symptoms either through inhalation, ingestion or contact. Allergic disease from occupational exposure to Boletus edulis (BE) has only seldom been reported. Report on a female worker who developed respiratory and skin symptoms from occupational exposure to BE in selecting and packing dried mushrooms. She never had symptoms after eating mushrooms. An environmental study was performed by personal air samplings and settled dust collection. The RAST-inhibition procedure was used to detect BE allergen potency in collected dust. The subject underwent clinical evaluation, spirometry, skin prick-tests, RAST methacoline and specific inhalation challenge with BE extract. A follow-up study was made 2, 4 and 8 months after the first evaluation and after cessation of exposure. BE allergens were found in the settled dust. Clinical examination showed eczema on the face and hands. The worker had hyper-eosinophilia, bronchial hyper-responsiveness to methacoline, no allergy to common inhalants and foods, positive prick-test and RAST for BE. The specific inhalation challenge induced broncho-constriction. At follow-up we observed a progressive clinical and functional improvement. Our data show that BE can induce cutaneous and respiratory symptoms from occupational exposure to dried mushroom dusts. The pathogenesis is an IgE-allergy. Our patient had no symptoms from ingestion, which supports the hypothesis that respiratory allergy is due to mushroom antigens that differ from those involved in food-related allergic reactions.


Search for the standard model higgs Boson in the ZH-->nunubb channel in 5.2 fb{-1} of pp collisions at sqrt[s]=1.96 TeV.
A search is performed for the standard model Higgs boson in 5.2 fb{-1} of pp collisions at sqrt[s]=1.96 TeV, collected with the D0 detector at the Fermilab Tevatron Collider. The final state considered is a pair of b jets and large missing transverse energy, as expected from pp-->ZH-->nunubb production. The search is also sensitive to the WH-->lnubb channel when the charged lepton is not identified. For a Higgs boson mass of 115 GeV, a limit is set at the 95% C.L. on the cross section multiplied by branching fraction for [pp-->(Z/W)H](H-->bb) that is a factor of 3.7 larger than the standard model value, consistent with the factor of 4.6 expected.


Genetic profiles and prediction of the success of young athletes' transition from middle- to long-distance runs: an exploratory study.
The aim of the study was to assess whether an aerobic-favoring genetic profile can predict the success of a shift from middle- to long-distance running. Thirteen elite middle-distance runners were divided into successful and nonsuccessful groups in their shift toward long-distance runs. All the runners began their training program at the age of 14-15, and after 6-7 years, changed focus and adjusted their training program to fit longer running distances. The participants' personal records in the longer events were set at the age of 25-27, about 3-5 years after the training readjustment took place. The endurance genetic score based on 9 polymorphisms was computed as the endurance genetic distance score (EGDS9). The power genetic distance score (PGDS5) was computed based on 5 power-related genetic polymorphisms. The mean EGDS9 was significantly higher among the successful group than the nonsuccessful group (37.1 and 23.3, respectively, p < .005, effect size 0.75), while the mean PGDS5 was not statistically different between the 2 groups (p = .13). Our findings suggest the possible use of genetic profiles as an added tool for determining appropriate competitive transition and specialization in young athletes involved in early phases of talent development.


A chromatin immunoprecipitation screen reveals protein kinase Cbeta as a direct RUNX1 target gene.
RUNX1 (also known as AML1) is a DNA-binding transcription factor that functions as a tumor suppressor and developmental determinant in hematopoietic cells. Target promoters have been identified primarily through the use of differential expression strategies and candidate gene approaches but not biochemical screens. Using a chromatin immunoprecipitation screen, we identified protein kinase Cbeta as a direct RUNX1 target gene and demonstrate that endogenous RUNX1 binds the chromatinized protein kinase Cbeta promoter of U937 cells. A phylogenetically conserved RUNX1-binding site within the PKCbeta promoter binds RUNX1 in electrophoretic mobility shift analyses and confers RUNX1 responsiveness on a heterologous promoter. Changes in RUNX1 activity affect endogenous protein kinase Cbeta expression, and a dominant-negative form of RUNX1 protects U937 cells from apoptotic stimuli previously shown to be dependent on protein kinase Cbeta. This protection can be reversed by the ectopic expression of protein kinase Cbeta. Together these findings demonstrate that protein kinase Cbeta is a direct, downstream target of RUNX1 and links RUNX1 to a myeloid apoptotic pathway.


Economic insecurity exposure and cognitive function in late life.
This study took the State-owned Enterprises (SOE) reform from 1996 to 2002 in China as a natural experiment to explore the consequences of economic insecurity exposure during early-adulthood and mid-adulthood on cognitive function in later life. Data were obtained from the China Health and Retirement Longitudinal Survey (CHARLS), 2014 and 2015. CHARLS is a nationally representative survey covering 28 provinces in China. A total of 4536 urban dwellers born earlier than 1971 (aged 25 years old and above at the start of the SOE reform in 1996) were included in our analyses. Using province-year-level economic loss from the layoffs, we examined the impact of economic insecurity exposure on the cognitive function score by using a difference-in-differences model with 1996-2002 as the cut-off. Individuals exposed to economic insecurity have significantly decreased cognitive function, in which a 1% point increase in expected economic loss would decrease the cognitive function score by 0.09 (95% CI: -0.17 to -0.01). Given that the average intensity of expected economic loss was 11.59% and the mean score of cognitive function was 21.26, exposure to the SOE reforms led to an average decrease in the cognitive function score by at least 4.91%. Providing cognitive health surveillance and psychological counselling may be important for preventing cognitive decline among those experiencing economic insecurity.


Esoteric Connective Tissue Therapy for chronic low back pain to reduce pain, and improve functionality and general well-being compared with physiotherapy: study protocol for a randomised controlled trial.
Low back pain causes more global disability than any other condition. Once the acute pain becomes chronic, about two-thirds of sufferers will not fully recover after 1-2 years. There is a paucity of effective treatments for non-specific, chronic low back pain. It has been noted that low back pain is associated with changes in the connective tissue in the affected area, and a very low-impact treatment, Esoteric Connective Tissue Therapy (ECTT), has been developed to restore flexibility in connective tissue. ECTT uses patterns of very small, circular movements, to the legs, arms, spine, sacrum and head, which anecdotally are effective in pain relief. In an unpublished single-arm phase I/II trial with chronic pain patients, ECTT showed a 56% reduction in pain after five treatments and 45% and 54% improvements at 6 months and 7-9 years of follow-up respectively. The aim of this randomised controlled trial is to compare ECTT with physiotherapy for reducing pain and improving physical function and physical and mental well-being in patients with chronic low back pain. The trial will be held at two hospitals in Vietnam. One hundred participants with chronic low back pain greater than or equal to 40/100 on the visual analogue scale will be recruited and randomised to either ECTT or physiotherapy. Four weekly treatments will be provided by two experienced ECTT practitioners (Treatment Group, 40 minutes each) and hospital-employed physiotherapy nurses (Control Group, 50 minutes). The primary outcomes will be changes in pain, physical function per the Quebec Pain Functionality Questionnaire and physical and mental well-being recorded by the Short Form Health Survey (SF-36), with mixed modelling used as the primary statistical tool because the data are longitudinal. Initial follow-up will be at either 4 or 8 months, with a second follow-up after 12 months. The trial design has important strengths, because it is to be conducted in hospitals under medical supervision, because ECTT is to be compared with a standard therapy and because the assessor and analyst are to be blinded. The findings from this trial will provide evidence of the efficacy of ECTT for chronic low back pain compared with standard physiotherapy treatment. Australian New Zealand Clinical Trials Registry, ACTRN12616001196437 . Registered on 30 August 2016.


Capsular distension in high-energy femoral shaft fractures is associated with occult femoral neck fracture: a preliminary retrospective comparative study.
To determine the association between hip capsular distension, the computed tomography (CT) capsular sign, and lipohemarthrosis as they relate to occult femoral neck fracture (FNF) in the setting of ipsilateral femoral shaft fracture (FSF). Retrospective comparative study. Level 1 trauma center. Two hundred and forty-two patients with high-energy FSF and no evidence of FNF on preoperative radiographs and pelvis CT. All patients were stabilized with non-reconstruction style nails. Pelvis CT scans were examined for hip capsular distension irrespective of the other side, differing side-to-side measurements of capsular distension (i.e., the CT capsular sign), and lipohemarthrosis. FNF was observed for on postoperative radiographs. Relative risk (RR), number needed to treat (NNT), sensitivity (SN), and specificity (SP) were determined. Fifty-eight patients (24.0%) had capsular distension. Forty-two patients (17.4%) had differing capsular measurements (i.e., the CT capsular sign), and 16 (6.6%) had symmetrical distension from bilateral hip effusions. Eight patients (3.3%) had lipohemarthrosis. Four FNFs (1.7%) were identified. Three patients had capsular distension, 2 had CT capsular signs, and 1 had lipohemarthrosis. The last patient had no CT abnormalities. Only capsular distension (RR = 10, CI = 1.001-90, P = 0.049; SN = 75%, SP = 77%; NNT = 22) and lipohemarthrosis (RR = 23, CI = 1.6-335, P = 0.022; SN = 50%, SP = 96%; NNT = 8) were associated with occult FNF. Capsular distension is associated with FNF irrespective of the contralateral hip. Preemptive stabilization using a reconstruction nail could be considered in the setting of capsular distension or lipohemarthrosis to prevent displacement of an occult FNF. Diagnostic Level III.


[Treatment of myeloma and and expected prognostic progress].
Some progress in the treatment of multiple myeloma (MM) has been recently obtained due to a better knowledge of prognosis factors and of indications of conventional chemotherapies. More over, two new therapeutic approaches appear very promising, including the use of alpha-interferon and the introduction of high dose chemotherapy protocols used alone or in combination with total body irradiation and hematopoietic transplantation. All available therapeutic strategies and their place in the management of patients with MM are successively discussed.


One-Step Synthesis and Functionalization of High-Salinity-Tolerant Magnetite Nanoparticles with Sulfonated Phenolic Resin.
Superparamagnetic nanoparticles are being actively developed for various applications in oil fields. A key requirement for such nanoparticles is the long-term stability of their dispersion under harsh subsurface conditions such as high salinity and high temperature. In this study, through functionalization of the surface of the magnetite nanoparticles with a sulfonated phenolic resin, stable dispersions of the nanoparticles in 5 wt % NaCl solution at neutral to basic pH were achieved. Sulfonated phenolic resin is aromatic in nature and can endure high temperatures; moreover, the strongly anionic sulfonate groups facilitate sufficient electrostatic repulsion between the particles even in a highly saline environment. Sulfonated phenolic resin was synthesized by heating a mixture of 4-hydroxybenzenesulfonic acid and formaldehyde at 1:1 molar ratio. Then, by synthesizing magnetite nanoparticles by a co-precipitation process in a solution of sulfonated phenolic resin, one-pot synthesis/surface functionalization was accomplished, which not only simplifies the manufacturing process but also can potentially lower the cost of production owing to the use of readily available phenolic resins. The reliability of the technique was confirmed by the detailed characterization of the nanoparticle through size distribution analysis, thermogravimetric analysis, ζ-potential measurements, transmission electron microscopy imaging, and energy-dispersive X-ray spectroscopy mapping. Further, Langevin curve was generated for evaluating the superparamagnetism of the nanoparticles.


Defining the optimal duration for normothermic regional perfusion in the kidney donor: A porcine preclinical study.
Kidneys from donation after circulatory death (DCD) are highly sensitive to ischemia-reperfusion injury and thus require careful reconditioning, such as normothermic regional perfusion (NRP). However, the optimal NRP protocol remains to be characterized. NRP was modeled in a DCD porcine model (30 minutes of cardiac arrest) for 2, 4, or 6 hours compared to a control group (No-NRP); kidneys were machine-preserved and allotransplanted. NRP appeared to permit recovery from warm ischemia, possibly due to an increased expression of HIF1α-dependent survival pathway. At 2 hours, blood levels of ischemic injury biomarkers increased: creatinine, lactate/pyruvate ratio, LDH, AST, NGAL, KIM-1, CD40 ligand, and soluble-tissue-factor. All these markers then decreased with time; however, AST, NGAL, and KIM-1 increased again at 6 hours. Hemoglobin and platelets decreased at 6 hours, after which the procedure became difficult to maintain. Regarding inflammation, active tissue-factor, cleaved PAR-2 and MCP-1 increased by 4-6 hours, but not TNF-α and iNOS. Compared to No-NRP, NRP kidneys showed lower resistance during hypothermic machine perfusion (HMP), likely associated with pe-NRP eNOS activation. Kidneys transplanted after 4 and 6 hours of NRP showed better function and outcome, compared to No-NRP. In conclusion, our results confirm the mechanistic benefits of NRP and highlight 4 hours as its optimal duration, after which injury markers appear.