Bisoprolol versus celiprolol on dynamic hyperinflation, cardiopulmonary exercise and domiciliary safety in COPD: a single-centre, randomised, crossover study.
Chronic obstructive pulmonary disease (COPD) is frequently associated with cardiovascular disease. The utility of beta-blockers for treating patients with COPD may be beneficial, but their safety remains uncertain, including worsening of dynamic hyperinflation (DH) during exercise. We hypothesised that among cardioselective beta-blockers celiprolol, due to its partial beta-2 agonist activity, may be safer than bisoprolol on exercise DH. We measured isotime inspiratory capacity (IC) during cycle endurance testing in eleven moderate-severe COPD subjects, alongside other non-invasive cardiopulmonary exercise, bioreactance cardiac output, pulmonary function, biomarkers and daily domiciliary measures. Participants received titrated doses of either bisoprolol (maximim 5 mg) or celiprolol (maximum 400 mg) in randomised crossover fashion, each over 4 weeks. Clinically relevant DH occurred between resting and exercise isotime IC but showed no significant difference with either beta-blocker compared with post-run-in pooled baseline or between treatments. There were no other significant differences observed for remaining exercise ventilatory; non-invasive cardiac output; resting pulmonary function; beta-2 receptor and cardiac biomarkers; domiciliary pulmonary function, oxygen saturation and symptom outcomes, either between treatments or compared with baseline. No significant adverse effects occurred. Significant DH in moderate-severe COPD subjects was no different between bisoprolol or celiprolol or versus baseline. A broad spectrum of other non-invasive cardiopulmonary and domiciliary safety outcomes was equally reassuring. Bronchoprotection with a concomitant long-acting muscarinic antagonist might be an important safety measure in this context. NCT02380053.


An Unusually Massive Hemorrhagic Superficial Infrapatellar Bursa Excised in a One-stage Procedure: Case Report.
Superficial infrapatellar bursitis may be traumatic, inflammatory, or infectious. It rarely attains massive dimensions. Open excision can be performed as a one-stage or a two-stage procedure, and endoscopy can be an alternative. We report a chronic, unusually massive, hemorrhagic infrapatellar bursa which we resected totally in a single stage procedure with no significant complications. A 65-year-old male farmer presented with a chronic massive swelling in front of the right knee which first appeared 4 years earlier and had no effect on his general condition. The mass was excised in a one-stage procedure and it was found to be a hemorrhagic bursitis. The wound healed uneventfully and, on follow-up 7 weeks later, the patient was able to perform full flexion and extension of the knee. Two-stage procedures for excision are effective, but one-stage procedures are equally effective in chronic cases, provided the dissection is performed meticulously and atraumatically.


Identifying the Underlying Educational Needs That Contribute to the Professional Practice Gap.
This article addresses how nursing professional development practitioners and nurse planners can meet the educational design process criterion 2 in the American Nurses Credentialing Center Primary Accreditation process that also corresponds with the Association for Nursing Professional Development's Scope and Standards of Practice. J Contin Educ Nurs. 2018;49(2):52-54.


Diagnostic performance of the urinary deoxypyridinoline in spinal tuberculosis.
This study investigated the diagnostic significance of urinary deoxypyridinoline measurement as a screening tool for spinal tuberculosis in patients with pulmonary tuberculosis.Urinary deoxypyridinoline levels were measured by automated chemiluminescence immunoassay and automated chemistry methods in patients with spinal (n=33) and pulmonary tuberculosis (n=33) and in healthy controls (n=30). Urinary deoxypyridinoline was divided by urinary creatine to exclude the factors of body mass index and urine dilution. The results underwent validity analysis. The measurements of urinary deoxypyridinoline in the spinal tuberculosis, pulmonary tuberculosis, and control groups were 14.9 ± 9.8, 6.4 ± 2.6, and 6.3 ± 2.0 μmol/molCr, respectively. Compared with the other 2 groups, the urinary deoxypyridinoline level in the spinal tuberculosis group was significantly increased (P=.001 and P=.000, respectively). However, urinary deoxypyridinoline levels were not significantly different between the pulmonary tuberculosis and control groups (P=.751). The receiver operating characteristic curve in the spinal tuberculosis group was 0.83. For deoxypyridinoline, the sensitivity (88%) and specificity (95%) were seen at the cutoff level of 8.0 μmol/molCr. The false positive and false negative were 12% and 5%, respectively. Diagnostic validity of the method was 93%.Bone metabolism alteration occurs during the progression of spinal tuberculosis, which can be reflected by the sensitivity and specificity of urinary deoxypyridinoline. The detection of urinary deoxypyridinoline is a benefit of screening patients with pulmonary tuberculosis for spinal tuberculosis.


Do Migration Characteristics Influence the Utilization of Basic Public Health Services in Internal Elderly Migrants in China?
Background: The literature shows that migration characteristics are a potential pathway through which migration can influence basic healthcare service utilization. The goal of the study was to explore the effect of migration characteristics on the utilization of basic public health services for internal elderly migrants in China and to identify the pathways that might promote their utilization of basic public health services. Methods: We studied 1,544 internal elderly migrants. The utilization of basic public health services was determined through participation in free health checkups organized by community health service institutions in the past year. Migration characteristics were represented by years of residence and reasons for migration. Other variables included demographic characteristics and social factors, e.g., the number of local friends and exercise time per day were measured to represent social contacts. Multivariate binary logistic regression was employed to explore the association of the variables with the likelihood of using community health services. Results: A total of 55.6% of respondents were men, and the mean age was 66.34 years (SD 5.94). A low level of education was observed. A total of 59.9% of migrants had been residents for over 10 years, and the main reason for migrating was related to family. Of these migrants, 12.9% had no local friends. Furthermore, 5.2% did not exercise every day. Social contacts were complete mediators of the impact of migration characteristics on the utilization of primary healthcare. Conclusion: Our study highlighted the mediating role of social factors in the relationship between migration characteristics and the utilization of basic public health services among Chinese internal elderly migrants. The findings supported the need to increase the opportunities for social contacts between local elderly individuals and internal elderly migrants.


Bagasse minority pathway expression: Real time study of GH2 β-mannosidases from bacteroidetes.
After being isolated from a sugarcane pile, the bacterium Chitinophaga sp. CB10 demonstrated to be a rich source of carbohydrases, with 350 predicted CAZyme domains. CB10 was able to grow on carbohydrates of different structural complexities: glucose, carboxymethylcellulose, corn starch, galactomannan, Aloe vera gum and sugarcane bagasse. The sugarcane bagasse is a rich source of complex polymers, and the diversity of metabolites released by its enzymatic hydrolysis has an important role for green chemistry, including minority pathways such as the degradation of mannan conjugates. In this sense, CB10 demonstrated considerable levels of gene expression for mannanases, and was stable for a period of 96-144 hours in the presence of sugarcane bagasse as sole carbon source. The bacterium showed respectively 4.8x and 5.6x expression levels for two genes predicted for GH2 β-mannosidase: one located within a gene cluster identified as "polysaccharide utilization loci" (PUL), and another a classic β-mannosidase. These enzymes shared less than 45% of identity with enzymes characterized from the genus Chitinophaga belonging to the phylum Bacteroidetes. The degree of novelty-as demonstrated by the low identity with previously characterized enzymes; the remarkable capability to grow in different substrates; mannanase activity, evidenced by the release of residual oligosaccharides in the cultivation with galactomannan (HPLC-RID, 12.3 mMol); associated to the ability of mannanases expression in a low concentration of inductor conditions (sugarcane bagasse, 0.2%) indicate the high potential for the application of CB10 as a source of enzymes in the production of oligosaccharides from biomass. This capacity might prove to be very valuable for the biorefinery process of pre-biotic precursors and other functional oligosaccharides focused on the food and pharmaceutical industries.


Introduction to the second edition of 'Diagnostic Cytopathology of Serous Fluids' as CytoJournal Monograph (CMAS) in Open Access.
Serous fluids are excessive accumulation of fluids in a serous cavity as effusion. However, traditionally this area also covers cytopathologic evaluation of washings of these cavities including pelvic/peritoneal washing. This is the introductory review article in series on this topic with the application of simplified algorithmic approaches. The series would be compiled finally as a book after minor modifications of individual review articles to accommodate the book layout on the topic as second edition of 'Diagnostic Cytopathology of Serous Fluids' book. The approach is primarily directed towards detection of neoplastic cells based on morphology alone or with the help of various ancillary tests, including commonly applied immunocytochemistry to be interpreted as second foreign population with application of SCIP (subtractive coordinate immunoreactivity pattern) approach in effusion fluid tapings. As the role of molecular pathology tests is increasing, this component as ancillary testing will also be covered as applicable. Because a picture and sketches are worth a thousand words, illustrations and figures are included generously even at the risk of moderate repetition. The clinically important serous cavities include peritoneal cavity, pericardial cavity, and two pleural cavities. The primary topic of this series is specimens from these cavities as effusion fluids and washings including cytopathologic evaluation of peritoneal/pelvic washing. It is expected that some readers may not read the entire series or the final book from beginning to end, but refer to the individual review articles and chapters sporadically during their clinical practice. Considering this practical limitation, some brief repetition may be observed throughout the book. Some of the important themes will be highlighted as italicized and bolded text for quick reference. Dedicated articles/chapters are assigned for technical and other reference material as appendices. Tables, algorithms, sketches, and combination of pictures are included generously for quick reference. Most of the illustrations are attempted to be labeled appropriately with arrows and other indicators to avoid equivocation, especially for beginners in the field. This introductory review article describes general details under the following three broad headings: Histology and general cytology of serous cavity lining Effusion (general considerations) Ancillary techniques in brief.


Limits of HLA mismatching in unrelated hematopoietic cell transplantation.
HLA matching between the donor and recipient improves the success of unrelated hematopoietic cell transplantation (HCT). Matched donors are available for only a minority of patients. Further information is needed to evaluate the limits of HLA mismatching. We examined the association of mortality with HLA-A, -B, -C, -DRB1, and -DQB1 mismatching in 948 patients who received a T-replete unrelated HCT for treatment of a marrow disorder. A single HLA allele or antigen mismatch was associated with increased mortality among patients with chronic myeloid leukemia (CML) within 2 years after diagnosis compared to patients with no HLA mismatch, but not among those with more advanced malignancy. In particular, a single HLA-C mismatch conferred increased risk of mortality compared to matches. There was a suggestion for increased mortality with multiple mismatches involving HLA-DQB1 compared to multiple mismatches not involving HLA-DQB1. Donors with a single HLA allele or antigen mismatch may be used for HCT when a fully matched donor is not available for patients with diseases that do not permit time for a lengthy search. Whenever possible, HLA-C mismatches should be avoided for patients with early stage CML, and HLA-DQB1 mismatches should be avoided for patients with multiple mismatches.


Development of a shoulder-mounted robot for MRI-guided needle placement: phantom study.
This paper presents new quantitative data on a signal-to-noise ratio (SNR) study, distortion study, and targeting accuracy phantom study for our patient-mounted robot (called Arthrobot). Arthrobot was developed as an MRI-guided needle placement device for diagnostic and interventional procedures such as arthrography. We present the robot design and inverse kinematics. Quantitative assessment results for SNR and distortion study are also reported. A respiratory motion study was conducted to evaluate the shoulder mounting method. A phantom study was conducted to investigate end-to-end targeting accuracy. Combined error considering targeting accuracy, respiratory motion, and structure deformation is also reported. The SNR study showed that the SNR changes only 2% when the unpowered robot was placed on top of a standard water phantom. The distortion study showed that the maximum distortion from the ground truth was 2.57%. The average error associated with respiratory motion was 1.32 mm with standard deviation of 1.38 mm. Results of gel phantom targeting studies indicate average needle placement error of 1.64 mm, with a standard deviation of 0.90 mm. Noise and distortion of the MR images were not significant, and image quality in the presence of the robot was satisfactory for MRI-guided targeting. Combined average total error, adding mounting stability errors and structure deformation errors to targeting error, is estimated to be 3.4 mm with a standard deviation of 1.65 mm. In clinical practice, needle placement accuracy under 5 mm is considered sufficient for successful joint injection during shoulder arthrography. Therefore, for the intended clinical procedure, these results indicate that Arthrobot has sufficient positioning accuracy.


Pulse pressure, arterial stiffness, and drug treatment of hypertension.
Epidemiological studies in the past decade have stressed the importance of pulse pressure as an independent risk factor for cardiovascular morbidity and mortality. We briefly review the epidemiological evidence and discuss in more detail the pathophysiological basis for this observation and the therapeutic consequences. We focus on the vascular determinants of increased pulse pressure. Both longitudinal and cross-sectional components of the vascular system contribute to the shape of the arterial pressure wave and, thereby, to pulse pressure. The primary longitudinal component is the architecture of the arterial tree, which determines the major reflection sites for the pressure wave. The cross-sectional architecture of the vascular system consists of a geometric (diameter) and a structural (composition vessel wall) component. Both diameter and composition of the vessel wall vary greatly when going from central to more peripheral arteries. We review the implications for the functional properties of various arterial segments. Finally, we discuss the therapeutic consequences of targeting pulse pressure rather than mean blood pressure with various drug classes. Among the antihypertensive agents, nitrates, NO donors, and drugs that interfere with the renin-angiotensin-aldosterone system may offer useful tools to lower pulse pressure, in addition to mean blood pressure. Future developments may include non-antihypertensive agents that target collagen or other components of the arterial wall matrix. However, large-scale clinical trials will have to confirm the therapeutic value of these agents in the treatment of increased pulse pressure and arterial stiffness.


[Investigation, securing of evidence and judgment in violations of animal welfare regulations].
For successful implementation of proceedings against violation of animal welfare regulations, sound investigation, securing of evidence, and assessment of the facts is essential. Recommendations are given to carry through as well as hints for drafting the reports required.


Risk of acute respiratory disease among pregnant women during influenza A epidemics.
The medical literature contains little information on the occurrence of excess morbidity among pregnant women during recent influenza epidemics. Rates of medical visits for acute respiratory disease (ARD) among pregnant and nonpregnant members of a large prepaid practice population were examined. Use of medical services for ARD was ascertained for approximately 1,000 pregnant women and 3,000 nonpregnant women during each of four epidemic periods (1975, 1976, 1978, 1979) and a nonepidemic period (1977). Comparing the combined epidemic periods with the nonepidemic period, there were significant excesses of 23.7 (standard error (SE) = 8.1) ARD contacts per 1,000 attributable to epidemic influenza for pregnant women and 10.2 (SE = 3.4) for nonpregnant women. ARD hospitalization rates among pregnant women were low (2 per 1,000), and there were no maternal deaths. The significant ARD excess among pregnant women was concentrated in the 1978 period with reappearance of the A/Russia H1N1 subtype in the community and was confined to those under age 25 who would not have ben previously exposed to this subtype (94.4 (SE = 28.5]. These findings indicate that recent influenza epidemics caused only modest excess ARD morbidity among pregnant women, and significant excess occurred only in association with antigenic shift. These findings support current national policy recommendations with respect to influenza vaccination of pregnant women.


THE RELATIONSHIP BETWEEN CORE ENDURANCE AND BACK DYSFUNCTION IN COLLEGIATE MALE ATHLETES WITH AND WITHOUT NONSPECIFIC LOW BACK PAIN.
Physical activity and sports can be associated with low back pain. However, little is known about the relationship between core stability and nonspecific low back pain (LBP) among athletes. The purpose of this study was to investigate the relationship between core endurance and back dysfunction in collegiate male athletes with and without nonspecific LBP. Fifty-five male collegiate athletes from a variety of sports were recruited for this study. Their mean age was 21.50 ± (2.54) years, mean weight was 70.96 ± (5.33) kg., and mean height was 174.38 ± (4.37) cm. Thirty athletes with non-specific LBP and twenty five healthy athletes were assessed using McGill's anterior, posterior, and left and right plank core endurance tests (seconds) and for dysfunction using the Micheli functional scale (MFS). Pearson's product moment correlations examined the relationships between core endurance and MFS. There were significant differences regarding the measured core endurance tests between the healthy athletes group and the nonspecific LBP group (p < 0.05). Additionally, good negative (r = -0.794) and moderate negative (r = -0.541) correlations were found between MFS and trunk extensor and flexor endurance tests, respectively in the group with nonspecific LBP. The results of this study imply that poor core endurance is likely associated with nonspecific LBP in collegiate athletes. Injury risk reduction and back management programs for the athletic population should include strategies that emphasize endurance of the core muscles especially the trunk extensors and flexors. 2b.


Polymorphisms in the thymidylate synthase and dihydropyrimidine dehydrogenase genes predict response and toxicity to capecitabine-raltitrexed in colorectal cancer.
Pharmacogenetics is an increasingly useful field where the genetic studies are becoming an important tool for predicting drug toxicity and/or efficacy. Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) gene polymorphisms could be highly informative tools in the clinical handling of colorectal cancer patients, who are following fluoropyrimidine based chemotherapy. Fifty-eight patients, with non-resectable metastatic colorectal cancer, were treated with capecitabine and raltitrexed, every three weeks. Patients were divided in a good-response group (complete and partial response) and a poor-response group (stable and progression). A genotype panel TS-DPD was evaluated. Results show that TS genotype analysis clearly differentiates patients with a worst response to a 5-fluorouracil based chemotherapy. DPD genotype was shown to be highly informative for prediction of toxicity of the treatment. These polymorphisms could represent an accurate, rapid and effective determination panel, indicative of resistance and toxicity for patients undergoing fluoropyrimidine based treatment.


Clinical Features and Prognosis According to Immunophenotypic Subtypes Including the Early T-Cell Precursor Subtype of T-Lymphoblastic Lymphoma in the Japanese Pediatric Leukemia/Lymphoma Study Group ALB-NHL03 Study.
We reviewed the immunophenotypic subtypes of pediatric T-cell lymphoblastic lymphoma in the Japanese Pediatric Leukemia/Lymphoma Study Group ALB-NHL03 study. Of the 104 patients, 40 patients each had sufficient data to evaluate the immunophenotypes and early T-cell precursor (ETP) subtype. Pro-T, pre-T, intermediate T, and mature T cells were observed in 1, 9, 21, and 9 cases, respectively. The 3-year event-free survival (EFS) rates of those with pro-T/pre-T, intermediate T, and mature T cells were 80.0±12.6%, 71.4±9.9%, and 88.9±10.5%, respectively (P=0.546). There were 8 and 32 cases of ETP and non-ETP subtypes, with 3-year EFS rates of 75.0±15.3% and 71.9±8.0%, respectively (P=0.828), indicating that the immunophenotypic subtype was not predictive of EFS in this study.


An immunohistochemical and ultrastructural study of cultured intracranial hemangiopericytoma.
Surgically excised intracranial hemangiopericytomas from three patients were cultured in vitro and they were examined by immunohistochemistry and electron microscopy to trace the origin of intracranial hemangiopericytomas compared to meningiomas. In all of the three hemangiopericytoma cell cultures, the matrix stained positively for vimentin and desmin. Two stained positive for actin and laminin. Cultured meningioma cells were positive in vimentin staining but negative in others. Hemangiopericytomas continued to have prominent intracytoplasmic intermediate filaments, microfilaments forming dense bodies and pinocytotic vesicles. Reconstruction of only a few cell junctions of zonula adherens type after subcultivation were observed in hemangiopericytoma, while there were neither whorl formations nor cell junctions found, such as desmosomes and junctional complexes, which are common in cultured meningioma cells. These results suggest that intracranial hemangiopericytoma has something in common with muscle cell, endothelial cell and fibroblast which form the vascular and perivascular tissues, and it is distinguishable from meningioma.


Effects of ship-induced waves on aquatic ecosystems.
Most larger water bodies worldwide are used for navigation, and the intensity of commercial and recreational navigation is expected to further increase. Navigation profoundly affects aquatic ecosystems. To facilitate navigation, rivers are trained and developed, and the direct effects of navigation include chemical and biological impacts (e.g., inputs of toxic substances and dispersal of non-native species, respectively). Furthermore, propagating ships create hydrodynamic alterations, often simply summarized as waves. Although ship-induced waves are recognized as influential stressors, knowledge on their effects is poorly synthesized. We present here a review on the effects of ship-induced waves on the structure, function and services of aquatic ecosystems based on more than 200 peer reviewed publications and technical reports. Ship-induced waves act at multiple organizational levels and different spatial and temporal scales. All the abiotic and biotic components of aquatic ecosystems are affected, from the sediment and nutrient budget to the planktonic, benthic and fish communities. We highlight how the effects of ship-induced waves cascade through ecosystems and how different effects interact and feed back into the ecosystem finally leading to altered ecosystem services and human health effects. Based on this synthesis of wave effects, we discuss strategies for mitigation. This may help to develop scientifically based and target-oriented management plans for navigational waters that optimize abiotic and biotic integrity and their ecosystem services and uses.


A comparison of rat models that best mimic immune-driven preeclampsia in humans.
Preeclampsia (PE), a hypertensive pregnancy disorder, can originate from varied etiology. Placenta malperfusion has long been considered the primary cause of PE. However, we and others have showed that this disorder can also result from heightened inflammation at the maternal-fetal interface. To advance our understanding of this understudied PE subtype, it is important to establish validated rodent models to study the pathophysiology and test therapies. We evaluated three previously described approaches to induce inflammation-mediated PE-like features in pregnant rats: 1) Tumor necrosis factor-α (TNF-α) infusion via osmotic pump from gestational day (GD) 14-19 at 50ng/day/animal; 2) Polyinosinic:polycytidylic acid (Poly I:C) intraperitoneal (IP) injections from GD 10-18 (alternate days) at 10mg/kg/day/animal; and, 3) Lipopolysaccharide (LPS) IP injections from GD 13-18 at 20ug-70ug/kg/day per animal. Maternal blood pressure was measured by tail-cuff. Upon sacrifice, fetal and placenta weights were recorded. Placenta histomorphology was assessed using H&E sections. Placenta inflammation was determined by quantifying TNF-α levels and inflammatory gene expression. Placenta metabolic and mitochondrial health were determined by measuring mitochondrial respiration rates and placenta NAD+/NADH content. Of the three rodent models tested, we found that Poly I:C and LPS decreased both fetal weight and survival; and correlated with a reduction in region specific placenta growth. As the least effective model characterized, TNF-α treatment resulted in a subtle decrease in fetal/placenta weight and placenta mitochondrial respiration. Only the LPS model was able to induce maternal hypertension and exhibited pronounced placenta metabolic and mitochondrial dysfunction, common features of PE. Thus, the rat LPS model was most effective for recapitulating features observed in cases of human inflammatory PE. Future mechanistic and/or therapeutic intervention studies focuses on this distinct PE patient population may benefit from the employment of this rodent model of PE.


[A case of mesoblastic nephroma in adulthood].
We report a rare adult case of mesoblastic nephroma. A right renal mass was detected in a 51-year-old woman by ultrasonography. The radiographic examination revealed that the mass was the hypovasucular tumor, but there was a possibility of a malignant tumor. We therefore operated on her for right radical nephrectomy. The tumor was 40 X 52 mm in size and had several cysts. Based on the histological analysis, we diagnosed it as congenital mesoblastic nephroma consisting of spindle cells.


Helicobacter pylori prevalence in endoscopy and medical staff.
The epidemiology and mode of transmission of Helicobacter pylori is currently unclear; it is postulated that the human stomach is the natural reservoir and that spread occurs by faecal-oral or oral-oral transmission. The aim of this study was to assess the prevalence of H. pylori in gastroenterologists and gastroenterology nurses compared with internists, general nurses and the normal population. An enzyme-linked immunosorbent assay technique (sensitivity 96%, specificity 88%) was used to detect circulating H. pylori immunoglobulin G antibodies in 39 gastroenterologists, 107 gastroenterology nurses, 25 internists and 42 general nurses. These subjects were compared to an age- and sex-matched Caucasian population obtained by random sampling of an urban population area. The overall prevalence of H. pylori in gastroenterologists was 69% compared to 40% of internists (P < 0.01), 17% of gastroenterology nurses (P < 0.001), 19% of general nurses (P < 0.01) and 32% of controls (P < 0.01). There was no significant difference in H. pylori prevalence between the gastroenterology nurses and controls, general nurses and controls. The prevalence in gastroenterologists increased with years of practice to levels greater than age-matched controls. The prevalence in gastroenterology nurses increased with age and years of working and was similar to age-matched control subjects. These findings of an increased prevalence of H. pylori infection in gastroenterologists performing endoscopy support human-to-human transmission possibly from patients to medical staff.


Germ cells enter meiosis in a rostro-caudal wave during development of the mouse ovary.
Germ cells in the mouse embryo remain undifferentiated until about 13.5 days post-coitum (dpc), when male germ cells enter mitotic arrest and female germ cells enter meiosis. The molecular signals and transcriptional control mechanisms governing the differential fate of germ cells in males and females remain largely unknown. In order to gain insights into the behavior of germ cells around this period and into likely mechanisms controlling entry into meiosis, we have studied by wholemount in situ hybridization the expression pattern of two germ cell-specific markers, Oct4 and Sycp3, during mouse fetal gonad development. We observed a dynamic wave of expression of both genes in developing ovaries, with Oct4 expression being extinguished in a rostro-caudal wave and Sycp3 being upregulated in a corresponding wave, during the period 13.5-15.5 dpc. These results indicate that entry into meiosis proceeds in a rostro-caudal progression, in turn suggesting that somatically derived signals may contribute to the control of germ cell entry into meiosis in developing ovaries.


Function and Biosynthesis of Cell Wall α-1,3-Glucan in Fungi.
Although α-1,3-glucan is a major cell wall polysaccharide in filamentous fungi, its biological functions remain unclear, except that it acts as a virulence factor in animal and plant pathogenic fungi: it conceals cell wall β-glucan on the fungal cell surface to circumvent recognition by hosts. However, cell wall α-1,3-glucan is also present in many of non-pathogenic fungi. Recently, the universal function of α-1,3-glucan as an aggregation factor has been demonstrated. Applications of fungi with modified cell wall α-1,3-glucan in the fermentation industry and of in vitro enzymatically-synthesized α-1,3-glucan in bio-plastics have been developed. This review focuses on the recent progress in our understanding of the biological functions and biosynthetic mechanism of cell wall α-1,3-glucan in fungi. We briefly consider the history of studies on α-1,3-glucan, overview its biological functions and biosynthesis, and finally consider the industrial applications of fungi deficient in α-1,3-glucan.


Hemorrhagic Shock as Complication of Intramural Intestinal Bleeding.
Introduction. Mural intestinal hematoma (MIH) is an uncommon complication of anticoagulant therapy. Hemorrhagic shock has been rarely reported as a revealing modality. Results. We report two cases of shock induced by mural intestinal hematoma in patients under oral anticoagulant for aortic prosthetic valve and atrial fibrillation. Patients were admitted to the ICU for gastrointestinal tract bleeding associated with hemodynamic instability. After resuscitation, an abdominal CT scan has confirmed the diagnosis showing an extensive hematoma. Medical treatment was sufficient and there was no need for surgery. Conclusion. Gastrointestinal bleeding associated with shock in patients treated by oral anticoagulant should alert physicians to research a probable MIH. Urgent diagnosis and appropriate medical treatment can avoid surgical interventions.


The Influence of Tattoos on Health Care Experiences.
Background Tattoos are an artistic, visible reflection of an individual's personality and life. According to Goffman and subcultural identity theory, the population with tattoos wants to be different from mainstream society. Method A qualitative descriptive phenomenological research process was used. Results Twelve participants described deep personal identity connections to their large, visible tattoos. They experienced positive reactions (n = 2, 16%), no reaction/acknowledgment (n = 7, 58%), or negative reactions (n = 3, 25%) from health care providers. Conclusion Comments made by health care providers tend to be remembered regardless of the context and can contribute to health and care disparities. Participants who received negative reactions to their tattoos switched providers. Those who received no reactions could have felt insignificant. Ongoing culturally sensitive education is important. Tattoos can start meaningful conversations that allow health care providers to gain valuable insight. [J Contin Educ Nurs. 2022;53(4):178-184.].


Fluorescence imaging of peripheral nerve function and structure.
Peripheral nerve injuries are common and can cause catastrophic consequences. Although peripheral nerves have notable regenerative capacity, full functional recovery is often challenging due to a number of factors, including age, the type of injury, and delayed healing, resulting in chronic disorders that cause lifelong miseries and significant financial burdens. Fluorescence imaging, among the various techniques, may be the key to overcome these restrictions and improve the prognosis because of its feasibility and dynamic real-time imaging. Intraoperative dynamic fluorescence imaging allows the visualization of the morphological structure of the nerve so that surgeons can reduce the incidence of medically induced injury. Axoplasmic transport-based neuroimaging allows the visualization of the internal transport function of the nerve, facilitating early, objective, and accurate assessment of the degree of regenerative repair, allowing early intervention in patients with poor recovery, thereby improving prognosis. This review briefly discusses peripheral nerve fluorescent dyes that have been reported or could potentially be employed, with a focus on their role in visualizing the nerve's function and anatomy.


Advanced oxidation protein products induce catabolic effect through oxidant-dependent activation of NF-κ B pathway in human chondrocyte.
Advanced oxidation protein products (AOPPs) have been shown to participate in the progression of rheumatoid arthritis (RA). However, the effect of AOPPs accumulation on catabolic effect in human chondrocyte and the underlying mechanism(s) remain unclear. The present study demonstrated that AOPPs inhibited cell viability and glycosaminoglycan (GAG) production in human chondrocyte. Exposure of chondrocyte to AOPPs significantly increased the production of catabolic factors, such as cyclooxygenase-2 (COX-2), matrix metalloproteinase 3 (MMPs)-3 and MMP-13. AOPPs stimulation induced ROS generation and NF-κ B p65 phosphorylation, which could be inhibited by soluble receptor for advanced glycan end products (sRAGE), NADPH oxidase inhibitor (apocynin), ROS scavenger (N-acetyl-cysteine, NAC). Furthermore, NF-κ B inhibitor Bay11-7082 significantly reversed the AOPPs-induced expression of catabolic factors and phosphorylation of NF-κ B p65. Targeting AOPPs-triggered catabolic effect might be as a promising option for patients with RA.


Neural activity during emotion recognition after combined cognitive plus social cognitive training in schizophrenia.
Cognitive remediation training has been shown to improve both cognitive and social cognitive deficits in people with schizophrenia, but the mechanisms that support this behavioral improvement are largely unknown. One hypothesis is that intensive behavioral training in cognition and/or social cognition restores the underlying neural mechanisms that support targeted skills. However, there is little research on the neural effects of cognitive remediation training. This study investigated whether a 50 h (10-week) remediation intervention which included both cognitive and social cognitive training would influence neural function in regions that support social cognition. Twenty-two stable, outpatient schizophrenia participants were randomized to a treatment condition consisting of auditory-based cognitive training (AT) [Brain Fitness Program/auditory module ~60 min/day] plus social cognition training (SCT) which was focused on emotion recognition [~5-15 min per day] or a placebo condition of non-specific computer games (CG) for an equal amount of time. Pre and post intervention assessments included an fMRI task of positive and negative facial emotion recognition, and standard behavioral assessments of cognition, emotion processing, and functional outcome. There were no significant intervention-related improvements in general cognition or functional outcome. fMRI results showed the predicted group-by-time interaction. Specifically, in comparison to CG, AT+SCT participants had a greater pre-to-post intervention increase in postcentral gyrus activity during emotion recognition of both positive and negative emotions. Furthermore, among all participants, the increase in postcentral gyrus activity predicted behavioral improvement on a standardized test of emotion processing (MSCEIT: Perceiving Emotions). Results indicate that combined cognition and social cognition training impacts neural mechanisms that support social cognition skills.


[Ultrasonographic assessment of carotid atherosclerosis for the differentiation of ischemic cardiomyopathy and dilated cardiomyopathy].
We assessed the clinical value of carotid intima-media thickness (IMT) for the differentiation of ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM). We studied 38 patients who showed left ventricular dilation and low ejection fraction (< 40%) by cardiac catheterization. There were 15 patients with ICM which was defined as stenosis of > 75% at one major branch or more. Twenty-three patients were found to have DCM as diagnosed by histological examination using biopsy specimens. Carotid IMT visualized by B-mode imaging was measured at 16 sites in the extracranial carotid arteries, and the maximum IMT, mean IMT, and plaque score were calculated. These parameters together with cardiovascular risk factors including age, sex, hypertension, diabetes mellitus, hypercholesterolemia, cigarette smoking, and obesity were compared between the ICM and the DCM groups. The maximum IMT, mean IMT, and plaque score in the ICM group were 2.80 +/- 1.63 mm, 1.21 +/- 0.36 mm, 13.05 +/- 8.12, respectively, which were significantly higher than the corresponding parameters in the DCM group (1.19 +/- 0.51 mm, 0.73 +/- 0.15 mm, 1.52 +/- 2.51; p < 0.001, respectively). Furthermore, plaque score of greater than 5 was found to be an excellent diagnostic parameter for ICM with 91% sensitivity and 100% specificity. The cardiovascular risk factors did not differ between the two groups. Our observations demonstrate that assessment of carotid IMT is a clinically useful tool to differentiate ICM and DCM in patients with left ventricular dysfunction. In particular, coronary angiography should be recommended in patients with a plaque score of greater than 5.


Drug-related acute renal failure in hospitalised patients.
The information available on the incidence and the characteristics of patients with acute renal failure (ARF) related to drugs is scarce. To estimate the incidence of drug-related ARF in hospitalised patients and to compare their characteristics with those of patients with ARF due to other causes. We selected a prospective cohort of patients with ARF during hospital admission (July 2010-July 2011). Information on patients' demographics, medical antecedents, ARF risk factors, ARF severity according to the RIFLE classification and hospital drug administration was collected. We analysed the relationship of drugs with the ARF episodes using Spanish Pharmacovigilance System methods and algorithm. A total of 194 cases had an episode of hospital-acquired ARF. The median age of patients was 72 years [IQR 20]; 60% were men. The ARF incidence during hospitalization was 9.6 per 1,000 admissions. According to the RIFLE classification, a risk of kidney damage or kidney injury was present in 77.8% of cases. In 105 (54.1%) cases, ARF was drug-related; the drugs most frequently involved were diuretics, agents acting on the renin-angiotensin system, immunosuppressants, β-blocking agents, calcium channel blockers, contrast media and non-steroid anti-inflammatory drugs. Patients with drug-related ARF had more multi-morbidity, fewer ARF risk factors and lower mortality. Half of ARF episodes during hospitalisation were drug related. Patients with drug-related ARF had higher cardiovascular morbidity than those with ARF related to other causes, but they had a lower frequency of ARF risk factors and mortality.


PrecursorFinder: a customized biosynthetic precursor explorer.
Synthetic biology has a great potential to produce high value pharmaceuticals, commodities or bulk chemicals. However, many biosynthetic target molecules have no defined or predicted biosynthetic pathways. Biosynthetic precursors are crucial to create biosynthetic pathways. Thus computer-assisted tools for precursor identification are urgently needed to develop novel metabolic pathways. To this end, we present PrecursorFinder, a computational tool that explores biosynthetic precursors for the query target molecules using chemical structure, similarity as well as MCS (maximum common substructure). This platform comprises more than 60 000 compounds biosynthesized for being promising precursors, which are extracted from >500 000 scientific literatures and manually curated by more than 100 people over the past 8 years. The PrecursorFinder could speed up the process of biosynthesis research and make synthetic biology or metabolic engineering more efficient. PrecursorFinder is available at: http://www.rxnfinder.org/precursorfinder/. Supplementary data are available at Bioinformatics online.


K-clique percolation in free association networks and the possible mechanism behind the [Formula: see text] law.
It is important to reveal the mechanisms of propagation in different cognitive networks. In this study, we discuss the k-clique percolation phenomenon as related to the free association networks including the English Small World of Words project (SWOW-EN). We compared different semantic networks and networks of free associations for various languages. Surprisingly, k-clique percolation for all [Formula: see text] 6-7 is possible on free association networks of different languages. Our analysis suggests new universality patterns for a community organization of free association networks. We conjecture that our result can provide a qualitative explanation of Miller's [Formula: see text] rule for the capacity limit of working memory. A new model of network evolution extending the preferential attachment is suggested, providing the observed value of [Formula: see text].


Carrier Dynamics of Efficient Triplet Harvesting in AgBiS2 /Pentacene Singlet Fission Solar Cells.
Singlet fission is a process by which an organic semiconductor is able to generate two triplet excitons from a single photon. If charges from the triplets can be successfully harvested without heavy losses in energy, then this process can enable a single-junction solar cell to surpass the Shockley-Queisser limit. While singlet fission processes are commonly observed in several materials, harvesting the resulting triplets is difficult and has been demonstrated with only a few transport materials. Here, transient absorption spectroscopy is used to investigate singlet fission and carrier transfer processes at the AgBiS2 /pentacene (AgBiS2 /Pc) heterojunction. The successful transfer of triplets from pentacene to AgBiS2 and the transfer of holes from AgBiS2 to pentacene is observed. Further singlet fission in pentacene by modifying the crystallinity of the pentacene layer and have fabricated the first singlet fission AgBiS2 /Pc solar cell is enhanced. Singlet fission devices exhibit higher external quantum efficiency compared with the control devices, and thus demonstrating the significant contribution of charges from the singlet fission process.


Corneal Confocal Microscopy in the Diagnosis of Small Fiber Neuropathy: Faster, Easier, and More Efficient Than Skin Biopsy?
Chronic pain may affect 30-50% of the world's population and an important cause is small fiber neuropathy (SFN). Recent research suggests that autoimmune diseases may be one of the most common causes of small nerve fiber damage. There is low awareness of SFN among patients and clinicians and it is difficult to diagnose as routine electrophysiological methods only detect large fiber abnormalities, and specialized small fiber tests, like skin biopsy and quantitative sensory testing, are not routinely available. Corneal confocal microscopy (CCM) is a rapid, non-invasive, reproducible method for quantifying small nerve fiber degeneration and regeneration, and could be an important tool for diagnosing SFN. This review considers the advantages and disadvantages of CCM and highlights the evolution of this technique from a research tool to a diagnostic test for small fiber damage, which can be a valuable contribution to the study and management of autoimmune disease.


Hostility in drug dependent individuals: its relation to specific drugs, and oral or intravenous use.
Although a number of studies have suggested that hostility and drug dependence may be related, there are few systematic studies of this issue. Using the Hostility and Direction of Hostility Questionnaire, the present study compares several drug-dependent groups of patients. Results showed that the intravenous in-patient group was more hostile on several variables than their out-patient counterparts, and also more hostile than an oral in-patient group. Barbiturate abusers were found to have high levels of hostility; amphetamine abusers were the least hostile group, and narcotic dependent patients were intermediate between the two. Correlations between scales of the HDHQ were all positive, and most were both high and statistically significant, suggesting that hostility represents a relatively generalized trait in drug-dependent subjects. The results are discussed both in terms of patient selection factors--the differential pressures on different types of patients, and in terms of direct drug effects. It is suggested that the hostility of drug-dependent patients may represent an important problem of personal functioning and may require special attention in treatment programmes.


Correlation of abnormal second trimester maternal serum alpha-fetoprotein (MSAFP) levels and adverse pregnancy outcome.
This study investigated the relationship between abnormal second trimester MSAFP levels and adverse pregnancy outcome. The findings revealed an association between low birth weight, prematurity and antepartum haemorrhage with abnormal unexplained high levels of second trimester MSAFP levels. However, macrosomia and increased gestational age at delivery were reported in relation to unexplained low levels of MSAFP in the second trimester. The positive predictive values for this test were poor (9-12%), that would question the use of this test to formulate a treatment plan. As the negative predictive values were high (96%), this test might be used to reassure women about their pregnancy.


Cholecystokinin facilitates neuronal excitability in the entorhinal cortex via activation of TRPC-like channels.
Cholecystokinin (CCK) is one of the most abundant neuropeptides in the brain, where it interacts with two G protein-coupled receptors (CCK-1 and CCK-2). Activation of both CCK receptors increases the activity of PLC, resulting in increases in intracellular calcium ion (Ca(2+)) release and activation of PKC. Whereas high density of CCK receptors has been detected in the superficial layers of the entorhinal cortex (EC), the functions of CCK in this brain region have not been determined. Here, we studied the effects of CCK on neuronal excitability of layer III pyramidal neurons in the EC. Our results showed that CCK remarkably increased the firing frequency of action potentials (APs). The effects of CCK on neuronal excitability were mediated via activation of CCK-2 receptors and required the functions of G proteins and PLC. However, CCK-mediated facilitation of neuronal excitability was independent of inositol trisphosphate receptors and PKC. CCK facilitated neuronal excitability by activating a cationic channel to generate membrane depolarization. The effects of CCK were suppressed by the generic, nonselective cationic channel blockers, 2-aminoethyldiphenyl borate and flufenamic acid, but potentiated by gadolinium ion and lanthanum ion at 100 μM. Depletion of extracellular Ca(2+) also counteracted CCK-induced increases in AC firing frequency. Moreover, CCK-induced enhancement of neuronal excitability was inhibited significantly by intracellular application of the antibody to transient receptor potential channel 5 (TRPC5), suggesting the involvement of TRPC5 channels. Our results provide a cellular and molecular mechanism to help explain the functions of CCK in vivo.


Homogenization-resistant spermatids in testicular tissue stored under suboptimal conditions-Effect of time and temperature.
Reproductive assessments on wild animals are often hampered due to practical problems during sample collection. For example, the time between death and tissue collection as well as sample storage conditions will affect the quality of the tissue. The aim of this study was to examine the effect of less optimal, field-like conditions, that is different temperatures and variable storage time, on the quantification of homogenization-resistant spermatids in testicular tissue, using the bull as a model. One bull testis was kept in +5°C for 216 hr, from which (n = 68) samples were taken at different time points for storage in -20°C or +21°C. Some samples were frozen, thawed and then refrozen. The tissue was homogenized, and the number of spermatids was quantified manually with a counter chamber. Compared to the samples taken at 0 hr, the number of spermatids was unchanged until 120 hr storage in +5°C and in frozen samples from the same time-point. After 72-hr storage in room temperature, there was a marked drop in the number of spermatids. Refreezing of samples resulted in a markedly lower number of spermatids. Frozen samples did not have significantly decreased numbers of spermatids compared to refrigerated samples. In conclusion, different storage conditions do not seem to affect the spermatids resistance to homogenization until day 3, but if kept in cool conditions it is possible to use samples up until 5 days of storage. The method is a good choice for suboptimal sampling conditions.


Total gastrectomy for gastric cancer: 12-year data and review of the effect of performing lymphadenectomy.
A total of 1,272 patients with gastric cancer were admitted to our institute for surgery during 12 years (1975-1986). Of these, 1,059 (83.4%) underwent gastrectomy. Among these, 252 (23.8%) were total gastrectomy (TG), involving 160 (63.5%) cases of cancer mainly located in the upper third of the stomach, 81 (32.1%) in the middle third and 11 (4.4%) in the lower third. Radical TG was performed in 65.9% and palliative TG in 34.1%. Roux-en-Y reconstruction was selected in 80%, jejunal interposition in 17.6% and double tract in 2.4%. The survival rate was improved by introducing extended lymph node dissection, especially in the cases of stage III & IV cancer in which a combined pancreatico-splenectomy could lead to cure when associated with lymphadenectomy. In cases of a positive serosal exposure, the 5-year survival rate was increased by extended lymphadenectomy from 21% to 46% (p < 0.02). Anastomotic leakage occurred in 4.2%. The postoperative mortality rate was 1.6%, occurring in only 4 patients.


Assessment of cardiovascular disease risk factors and diabetes mellitus in Australian prisons: is the prisoner population unhealthier than the rest of the Australian population?
This paper compares the prevalence estimates of diabetes and cardiovascular disease (CVD) risk factors in the Indigenous and non-Indigenous New South Wales (NSW) prisoner population in 1996 and 2001, and also compares the 2001 prevalence estimates with Australian population data. In 1996 and 2001, 789 and 916 prisoners, respectively, in NSW underwent a face-to-face interview covering behavioural risks and physical and mental health. Weight, height and blood pressure were recorded and blood was taken for measurement of cholesterol and random blood sugar. The prevalence of hypertension, hypercholesterolaemia and smoking were lower in the 2001 prison survey as compared with the 1996 survey but the prevalence of smoking was extremely high in both the prison surveys (88% in 1996 and 79% in 2001). There were no differences in the age and sex-adjusted prevalence estimates for any condition except that the prison sample had a higher standardised morbidity ratio for angina than the AusDiab population. This study highlights the high prevalence of CVD risk factors, particularly in younger prisoners, when compared with the Australian non-prison population. Programs should be put in place to routinely screen for chronic disease conditions and to educate Australian prisoners regarding CVD and diabetes risk factors and their long-term management.


China experts' consensus on preventive and interceptive orthodontic treatments of malocclusions of children.
Malocclusion is one of the three most common oral diseases reported by World Health Organization(WHO). In China, its incidence rate is rising. Malocclusion seriously affects the dental and maxillofacial function, facial appearance and growth development of nearly 260 million children in China, and what is more, it affects their physical and mental health development. Malocclusion occurrence is related to genetic and environmental factors. Early treatment of malocclusion can create a good dental and maxillofacial development environment, correct abnormal growth and control the adverse effects of abnormal genetic factors. It can effectively reduce the prevalence of children's malocclusion and enhance their physical and mental health. This is an urgent need from the economic perspective of our society, so it has great practical and social significance. Experts from the project group "standard diagnose and treatment protocols for early orthodontic intervention of malocclusions of children" which initiated by China National Health Institute of Hospital Administration wrote the "China Experts' Consensus on Preventive and Interceptive Orthodontic Treatments of Malocclusions of Children", which aims to guide and popularize the clinical practice, improve the clinical theory and practice level, and accelerate the disciplinary development of early treatment of children's malocclusion in China. The consensus elaborates the harmfulness of malocclusion and the necessity of early treatment, and brings up the principles and fundamental contents. Based on the law of dental and maxillofacial development, this paper puts forward the guiding suggestions of preventive and interceptive treatments in different stages of dental development ranging from fetus to early permanent dentition. It is a systematic project to promote and standardize the early treatment of malocclusion. Through scientific and comprehensive stratified clinical practice and professional training, the clinical system of early treatment of malocclusion in China will eventually be perfected, so as to comprehensively care for children's dental and maxillofacial health, and improve their oral and physical health in China.


Stereoselective kinetics of warfarin binding to human serum albumin: effect of an allosteric interaction.
Kinetic and equilibrium binding studies were performed on the interaction of warfarin enantiomers with human serum albumin (HSA) in the absence and presence of lorazepam acetate (LoAc) enantiomers. Binding kinetics were followed by recording changes in the fluorescence of warfarin upon binding to HSA using the stopped-flow technique. The binding of (R)-warfarin displayed an exponentially increasing fluorescence, satisfying the two-step mechanism reported previously for the racemate, i.e., a diffusion controlled pre-equilibrium is followed by a slower rearrangement of the complex. In the case of (S)-warfarin, the signal was biphasic: a fast fluorescence enhancement was followed by a slow decline. The different kinetic features indicate that the equilibrium conformations of the [(S)-warfarin-HSA] and [(R)-warfarin-HSA] complexes are achieved via different mechanisms. The phenomenon was seen in buffers of different pH and compositions. Equilibrium binding measurements indicated significantly lower molar intrinsic fluorescence for the (S)-warfarin complex, suggesting differences in the microenvironments of the bound enantiomers. In the presence of (S)-LoAc, the allosterically enhanced binding of (S)-warfarin manifested itself in accelerated relaxation kinetics. In accordance with the low molar intrinsic fluorescence determined for the stable ternary complex, the amplitude of the decline in fluorescence became larger.


Pharmacy Residency School-wide Match Rates and Modifiable Predictors in ACPE-accredited Colleges and Schools of Pharmacy.
Objective. To analyze the modifiable predictors of institution-wide residency match rates. Methods. This was a retrospective analysis of colleges and schools of pharmacy data and school-wide PGY-1 pharmacy residency match rates for 2013 through 2015. Independent variables included NAPLEX passing rates, history of ACPE probation, NIH funding, academic health center affiliation, dual-degree availability, program length, admit-to-applicant ratio, class size, tuition, student-driven research, clinically focused academic tracks, residency affiliation, U.S. News & World Report rankings, and minority enrollment. Results. In a repeated measures model, predictors of match results were NAPLEX pass rate, class size, academic health center affiliation, admit-to-applicant ratio, U.S. News & World Report rankings, and minority enrollment. Conclusion. Indicators of student achievement, college/school reputation, affiliations, and class demographics were significant predictors of institution-wide residency match rates. Further research is needed to understand how changes in these factors may influence overall match rates.


Suppression of molecular inflammatory pathways by Toll-like receptor 7, 8, and 9 antagonists in a model of IL-23-induced skin inflammation.
Psoriasis is a complex inflammatory disease resulting from the activation of T helper (Th) 1 and Th17 cells. Recent evidence suggests that abnormal activation of Toll-like receptors (TLRs) 7, 8 and 9 contributes to the initiation and maintenance of psoriasis. We have evaluated the effects of TLR antagonists on the gene expression profile in an IL-23-induced skin inflammation model in mice. Psoriasis-like skin lesions were induced in C57BL/6 mice by intradermal injection of IL-23 in the dorsum. Two TLR antagonists were compared: IMO-3100, an antagonist of TLRs 7 and 9, and IMO-8400, an antagonist of TLRs 7, 8 and 9, both of which previously have been shown to reduce epidermal hyperplasia in this model. Skin gene expression profiles of IL-23-induced inflammation were compared with or without TLR antagonist treatment. IL-23 injection resulted in alteration of 5100 gene probes (fold change ≥ 2, FDR < 0.05) including IL-17 pathways that are up-regulated in psoriasis vulgaris. Targeting TLRs 7, 8 and 9 with IMO-8400 resulted in modulation of more than 2300 mRNAs while targeting TLRs 7 and 9 with IMO-3100 resulted in modulation of more than 1900 mRNAs. Both agents strongly decreased IL-17A expression (>12-fold reduction), normalized IL-17 induced genes such as beta-defensin and CXCL1, and normalized aberrant expression of keratin 16 (indicating epidermal hyperplasia). These results suggest that IL-23-driven inflammation in mouse skin may be dependent on signaling mediated by TLRs 7, 8, and 9 and that these receptors represent novel therapeutic targets in psoriasis vulgaris and other diseases with similar pathophysiology.


A method for the study of the dynamics of atherosclerotic involvement of human coronary arteries.
A method able to reveal the progression of atherosclerosis from children to mature adults is proposed, based on the successive light microscopic examination of similar selected topographic sites of the coronary arterial tree placed in sequence according to age, sex and branching anatomical pattern. The dynamic reconstruction of thousands of static views revealed a linear and parallel increase in the number of all types of early atherosclerotic lesions: fibromuscular plaques, intimal necrotic areas, incorporated microthrombi and fatty streaks. Some endogenous and exogeneous risk factors for coronary heart disease accelerated this age-related rate of progression and also gave rise to particular cycles of evolution toward lesions of possible clinical significance.


Hazara Nairovirus Requires COPI Components in both Arf1-Dependent and Arf1-Independent Stages of Its Replication Cycle.
Hazara nairovirus (HAZV) is an enveloped trisegmented negative-strand RNA virus classified within the Nairoviridae family of the Bunyavirales order and a member of the same subtype as Crimean-Congo hemorrhagic fever virus, responsible for fatal human disease. Nairoviral subversion of cellular trafficking pathways to permit viral entry, gene expression, assembly, and egress is poorly understood. Here, we generated a recombinant HAZV expressing enhanced green fluorescent protein and used live-cell fluorescent imaging to screen an siRNA library targeting genes involved in cellular trafficking networks, the first such screen for a nairovirus. The screen revealed prominent roles for subunits of the coat protein 1 (COPI)-vesicle coatomer, which regulates retrograde trafficking of cargo between the Golgi apparatus and the endoplasmic reticulum, as well as intra-Golgi transport. We show the requirement of COPI-coatomer subunits impacted at least two stages of the HAZV replication cycle: an early stage prior to and including gene expression and also a later stage during assembly and egress of infectious virus, with COPI-knockdown reducing titers by approximately 1,000-fold. Treatment of HAZV-infected cells with brefeldin A (BFA), an inhibitor of Arf1 activation required for COPI coatomer formation, revealed that this late COPI-dependent stage was Arf1 dependent, consistent with the established role of Arf1 in COPI vesicle formation. In contrast, the early COPI-dependent stage was Arf1 independent, with neither BFA treatment nor siRNA-mediated ARF1 knockdown affecting HAZV gene expression. HAZV exploitation of COPI components in a noncanonical Arf1-independent process suggests that COPI coatomer components may perform roles unrelated to vesicle formation, adding further complexity to our understanding of cargo-mediated transport.IMPORTANCE Nairoviruses are tick-borne enveloped RNA viruses that include several pathogens responsible for fatal disease in humans and animals. Here, we analyzed host genes involved in trafficking networks to examine their involvement in nairovirus replication. We revealed important roles for genes that express multiple components of the COPI complex, which regulates transport of Golgi apparatus-resident cargos. COPI components influenced at least two stages of the nairovirus replication cycle: an early stage prior to and including gene expression and also a later stage during assembly of infectious virus, with COPI knockdown reducing titers by approximately 1,000-fold. Importantly, while the late stage was Arf1 dependent, as expected for canonical COPI vesicle formation, the early stage was found to be Arf1 independent, suggestive of a previously unreported function of COPI unrelated to vesicle formation. Collectively, these data improve our understanding of nairovirus host-pathogen interactions and suggest a new Arf1-independent role for components of the COPI coatomer complex.


Current status of deceased donor split liver transplantation in Japan.
The aim of this study was to analyze the outcomes of deceased donor split liver transplantation (LT) in Japan. Among 257 deceased donor LTs, 36 recipients underwent split LT until the end of 2014. The clinical data of donors and recipients were collected from the national organ transplant network and 11 liver transplant institutions, and the outcomes of split LT were evaluated. Most of the whole livers were divided using the ex-situ splitting technique. Twelve livers were divided to left lateral segment/extended right lobe grafts and six livers to left lobe/right lobe grafts. The common underlying liver diseases consisted of graft failure in 11 patients, followed by acute liver failure in nine. Seventeen cases (48.6%) suffered from surgical complications, including biliary complications in six, all of which occurred in the cases receiving right-sided lobe grafts; intra-abdominal hemorrhage in five; and vascular complications in four. The overall graft 1-year and 3-year survival rates were 91.0% and 87.1%, respectively. An initial experience of deceased donor split LT in Japan shows acceptable outcomes despite the high incidence of surgical complications. Further advances in the development of the splitting technique are necessary to expand the application of split LT.


A comparison of emergency medical services times for stroke and myocardial infarction.
Since stroke symptoms are often vague, and acute therapies for stroke are more recently available, it has been hypothesized that stroke patients may not be treated with the same urgency as myocardial infarction (MI) patients by emergency medical services (EMS). To examine this hypothesis, EMS transport times were examined for both stroke and MI patients who used a paramedic-level, county-based EMS system for transportation to a single hospital during 1999. Patients were first identified by their hospital discharge diagnosis as stroke (ICD-9 430-436, n = 50) or MI (ICD-9 410, n = 55). Trip sheets with corresponding transport times were retrospectively obtained from the 911 center. A separate analysis was performed on patients identified by dispatchers with a chief complaint of stroke (n = 85) or MI (n = 372). Comparing stroke and MI patients identified by ICD-9 codes, mean EMS transport times in minutes did not meaningfully differ with respect to dispatch to scene arrival time (8.3 vs 8.9, p = 0.61), scene time (19.5 vs 21.4, p = 0.23), and transport time (13.7 vs 16.2, p = 0.10). Mean total call times in minutes from dispatch to hospital arrival were similar between stroke and MI patients (41.5 vs 46.4, p = 0.22). Results were similar when comparing patients identified by dispatchers with a chief complaint indicative of stroke or MI. In this single county, EMS response times were not different between stroke and MI patients. Replication in other EMS settings is needed to confirm these findings.


The effects of four insect growth-regulating (IGR) insecticides on honeybee (Apis mellifera L.) colony development, queen rearing and drone sperm production.
This study assessed the effects of exposure to IGRs on the long-term development of the honeybee colony, viability of queens and sperm production in drones and integrated the data into a honeybee population model. Colonies treated with diflubenzuron resulted in a short-term reduction in the numbers of adult bees and brood. Colonies treated with fenoxycarb declined during the season earlier and started the season slower. The number of queens that successfully mated and laid eggs was affected in the fenoxycarb treatment group but there were no significant differences in the drone sperm counts between the colonies. An existing honeybee population model was modified to include exposure to IGRs. In the model, fenoxycarb reduced the winter size of the colony, with the greatest effects following a June or an August application. Assuming a 'larvae per nurse bee' ratio of 1.5 for brood rearing capability, the reduction in winter size of a colony following a fenoxycarb application was at its worst about 8%. However, even if only those bees reared within 2 weeks of the IGR being applied are subject to premature ageing, this might significantly reduce the size of over-wintering colonies, and increase the chance of the bee population dwindling and dying in late winter or early spring.


Perspectives on parenteral micronutrient shortages.
Micronutrients are essential components of parenteral nutrition (PN). Problems related to deficiency and toxicity occur during routine practice, which could be related to the content of commercial sources, inadequate prescribed doses, and the high frequency of at-risk patients receiving PN. Shortages of commercial products result in increased risk of deficiency. Even though there are recommendations to conserve supplies for those at highest risk, practices that provide no micronutrients or doses less than desired are not safe. This article reviews the evidence describing patients at risk for micronutrient deficiency, the rationale for micronutrient product reformulation, and characteristics of deficiency observed during shortages of micronutrient products.


Incidence of advanced neoplasia during surveillance in high- and intermediate-risk groups of the European colorectal cancer screening guidelines.
Background and study aims: The European guidelines for quality assurance in colorectal cancer (CRC) screening have established high-risk (≥ 5 adenomas or an adenoma ≥ 20 mm) and intermediate-risk (3 - 4 adenomas or at least one adenoma 10 - 19 mm in size, or villous histology, or high grade dysplasia) groups with different endoscopic surveillance intervals. The aim of this study was to evaluate the difference in the incidence of advanced neoplasia (advanced adenoma or CRC) between the two risk groups. Patients and methods: This retrospective group study included patients meeting high- or intermediate-risk criteria for adenomas detected in CRC screening programs and the COLONPREV study before European guidelines were adopted in Spain (June 2011) with a 3-year surveillance recommendation according to Spanish guidelines. The primary outcome measure was the incidence of advanced neoplasia in patients undergoing surveillance. The secondary outcome measure was the CRC incidence. We used an adjusted proportional hazards regression model to control confounding variables. Results: The study included 5401 patients (3379 intermediate risk, 2022 high risk). Endoscopic surveillance was performed in 65.5 % of the patients (2.8 ± 1 years). The incidence of advanced neoplasia in the high- and intermediate-risk groups was 16.0 % (59.0 cases/1000 patient-years) and 12.3 % (41.2 cases/1000 patient-years), respectively. The CRC incidence was 0.5 % (1.4 cases/1000 patient-years) and 0.4 % (1 case/1000 patient-years), respectively. The advanced neoplasia and CRC attributable risk to the high risk group was of 3.7 % and 0.1 %, respectively. In the proportional hazards analysis, the risk of advanced neoplasia was greater in the high-risk group (hazard ratio [HR] 1.5, 95 % confidence interval [CI] 1.2 - 1.8), with no significant differences in the CRC incidence (HR 1.6, 95 %CI 0.6 - 3.8). Conclusions: Patients meeting high-risk criteria have a higher incidence of advanced neoplasia during endoscopic surveillance. No differences were found in the CRC incidence at a 3-year surveillance recommendation.


Expression of endotoxic activities by synthetic monosaccharide lipid A analogs with alkyl-branched acyl substituents.
Synthetic monosaccharide lipid A analogs with alkyl-branched acyl substituents instead of the usual ester-branched acyl substituents were investigated for their biological activities. The activities were compared with those of a representative synthetic monosaccharide lipid A analog with an ester branch (GLA-60) and synthetic complete lipid A (506) to estimate the role of the attaching mode of the branched side chains for expression of endotoxic activities. Among the analogs with alkyl branches, GLA-146 and GLA-147, which have C12 and C14 alkyl side chains, respectively, showed strong endotoxic activities. These analogs exhibited comparable or stronger activities than those of GLA-60 in murine macrophage activation activities to induce mediators such as tumor necrosis factors, interleukin 6, and nitric oxide and in mitogenic activity towards murine spleen cells; however, these activities were weaker than the respective activities of 506. With respect to lethal toxicity to galactosamine-sensitized mice, the analogs showed stronger activity than that of GLA-60 and activity closer to that of 506. With respect to adjuvant activity, no significant activity was observed in the analogs, while the activities of GLA-60 and 506 were strong. When lipopolysaccharide-resistant C3H/HeJ mice were used, the activities described above were not observed either for the analogs under investigation nor for GLA-60 and 506. These findings indicate that the ester type of branch in lipid A and its analogs does not play an indispensable role in the expression of various endotoxic activities. However, it may play some role in the expression of adjuvant activity and in lowering the level of toxicity.


Intermolecular ionic interactions serve as a possible switch for stem release in the staphylococcal bi-component toxin for β-barrel pore assembly.
The β-strand stem release system of staphylococcal β-barrel pore-forming toxin γ-hemolysin was investigated. Mutations at K15 and R16 in the cap domain of Hlg2 decreased hemolytic activity more markedly than their effect on erythrocyte binding. In addition, D122N mutation of LukF prestem lost the activity with Hlg2 R16A, indicating that electrostatic interactions between residues in the Hlg2 cap and prestem of adjacent LukF in the ring-shaped complex might serve as a switch for stem release.


Construction, comparison and evolution of networks in life sciences and other disciplines.
Network approaches have become pervasive in many research fields. They allow for a more comprehensive understanding of complex relationships between entities as well as their group-level properties and dynamics. Many networks change over time, be it within seconds or millions of years, depending on the nature of the network. Our focus will be on comparative network analyses in life sciences, where deciphering temporal network changes is a core interest of molecular, ecological, neuropsychological and evolutionary biologists. Further, we will take a journey through different disciplines, such as social sciences, finance and computational gastronomy, to present commonalities and differences in how networks change and can be analysed. Finally, we envision how borrowing ideas from these disciplines could enrich the future of life science research.


The Prospective Effects of Coping Strategies on Mental Health and Resilience at Five Months after HSCT.
Hematopoietic stem cell transplantation (HSCT) is a stressful event that engenders psychological distress. This study examines the prospective effects of coping strategies during hospitalization on resilience and on various mental-health dimensions at five months after transplantation. One hundred and seventy patients (Mage = 52.24, SD = 13.25) completed a questionnaire assessing adjustment strategies during hospitalization, and 91 filled out a questionnaire five months after HSCT (Mage = 51.61, SD = 12.93). Multiple regression analyses showed that a fighting spirit strategy positively predicted resilience (p < 0.05), whereas anxious preoccupations predicted anxiety (p < 0.05), poorer mental QoL (p < 0.01), and were associated with an increased risk of developing PTSD (OR = 3.27, p < 0.01; 95% CI: 1.36, 7.84) at five months after transplantation. Hopelessness, avoidance, and denial coping strategies were not predictive of any of the mental health outcomes. Finally, the number of transplantations was negatively related to a fighting spirit (p < 0.01) and positively related to hopelessness-helplessness (p < 0.001): Conclusions: These results highlight the importance of developing psychological interventions focused on coping to alleviate the negative psychological consequences of HSCT.


Assembling Microgels via Dynamic Cross-Linking Reaction Improves Printability, Microporosity, Tissue-Adhesion, and Self-Healing of Microgel Bioink for Extrusion Bioprinting.
Extrusion bioprinting has been widely used to fabricate complicated and heterogeneous constructs for tissue engineering and regenerative medicine. Despite the remarkable progress acquired so far, the exploration of qualified bioinks is still challenging, mainly due to the conflicting requirements on the printability/shape-fidelity and cell viability. Herein, a new strategy is proposed to formulate a dynamic cross-linked microgel assembly (DC-MA) bioink, which can achieve both high printability/shape-fidelity and high cell viability by strengthening intermicrogel interactions through dynamic covalent bonds while still maintaining the relatively low mechanical modulus of microgels. As a proof-of-concept, microgels are prepared by cross-linking hyaluronic acid modified with methacrylate and phenylboric acid groups (HAMA-PBA) and methacrylated gelatin (GelMA) via droplet-based microfluidics, followed by assembling into DC-MA bioink with a dynamic cross-linker (dopamine-modified hyaluronic acid, HA-DA). As a result, 2D and 3D constructs with high shape-fidelity can be printed without post-treatment, and the encapsulated L929 cells exhibit high cell viability after extrusion. Moreover, the addition of the dynamic cross-linker (HA-DA) also improves the microporosity, tissue-adhesion, and self-healing of the DC-MA bioink, which is very beneficial for tissue engineering and regenerative medicine applications including wound healing. We believe the present work sheds a new light on designing new bioinks for extrusion bioprinting.


Choices, choices: the application of multi-criteria decision analysis to a food safety decision-making problem.
In the food safety arena, the decision-making process can be especially difficult. Decision makers are often faced with social and fiscal pressures when attempting to identify an appropriate balance among several choices. Concurrently, policy and decision makers in microbial food safety are under increasing pressure to demonstrate that their policies and decisions are made using transparent and accountable processes. In this article, we present a multi-criteria decision analysis approach that can be used to address the problem of trying to select a food safety intervention while balancing various criteria. Criteria that are important when selecting an intervention were determined, as a result of an expert consultation, to include effectiveness, cost, weight of evidence, and practicality associated with the interventions. The multi-criteria decision analysis approach we present is able to consider these criteria and arrive at a ranking of interventions. It can also provide a clear justification for the ranking as well as demonstrate to stakeholders, through a scenario analysis approach, how to potentially converge toward common ground. While this article focuses on the problem of selecting food safety interventions, the range of applications in the food safety arena is truly diverse and can be a significant tool in assisting decisions that need to be coherent, transparent, and justifiable. Most importantly, it is a significant contributor when there is a need to strike a fine balance between various potentially competing alternatives and/or stakeholder groups.


Modulation of retinal differentiation by oncogenes: effect of the v-src gene on expression of choline acetyltransferase and glutamine synthetase.
Expression of the protooncogene c-src in chick neural retina is developmentally regulated and associated with neural differentiation. In the present study, chick neural retina (NR) cell cultures from 7 day embryos were exposed to the exogenous src oncogene, the c-src counterpart, to establish the effect of expression of v-src on specific retinal cellular differentiation. NR cells from 7 day chick embryos were placed in monolayer or rotation culture and infected with Rous sarcoma virus (RSV) containing a single transforming gene. Other cultures were infected with a transforming defective mutant of RSV which still possesses mitogenic activity for NR cells. While control cultures showed typical neuronal and Muller cell morphologies at the light and electron microscopic level, NR cells infected with RSV exhibited dramatic morphological alterations in monolayer culture and cell aggregates. However, the mutant src gene induced mitosis without accompanying transforming properties. When aggregate cultures were treated with hydrocortisone to induce glutamine synthetase (GS) expression in Muller cells, control cultures showed the typical immunofluorescence pattern of GS staining, while RSV infected cultures showed no GS fluorescence. Cultures infected with mutant RSV showed some staining for GS. In contrast, choline acetyltransferase activity was shown to increase in both monolayer and aggregate cultures of retinal cells following v-src expression. These data indicate that the presence of excess v-src in differentiating cultures of NR inhibits the expression of some neural specific enzymes and enhances the presence of other specific proteins. Moreover, continually growing cultures of oncogene-altered retinal cells may be useful as models to study gene expression in development of the nervous system.


[Nutritional status of elderly Brazilians: a multilevel approach].
The objectives of this study were to diagnose the nutritional status of the elderly Brazilian population and to identify associated factors. The study used data from the Brazilian Household Budget Survey (2008/2009) for 20,114 elderly, whose nutritional status was assessed by body mass index (BMI). Associated factors were tested with the Pearson chi-square test and multilevel linear models. The hierarchical analysis showed a significant effect of state of Brazil on BMI variance (p-value = 0.001). The individual level showed a negative association (p-value < 0.001) with Asian-descendant race, male gender, living alone, and older age and a positive association with per capita income. Underweight was more prevalent among elderly in rural areas (26.3%) and in the Northeast (23.7%) and Central regions (20.9%), and obesity was more prevalent in the South (45.1%) and Southeast (38.3%) and in cities (39%). The study suggests the importance of further in-depth research on nutritional status of elderly based on contextual variables.


The effect of caffeine intake and passive smoking on umbilical cord blood unit's quality parameters.
Today cord blood (CB) is a valuable source of hematopoietic stem cells to treat many hematological disorders. One of the limitations of CB utilization is the reduced number of nucleated cells including stem cells. Therefore, CB banks around the world have developed strategies in an attempt to improve donor selection and the quality of the CB inventory. This study aimed to determine the impact of passive smoking and caffeine consumption on CB quality. CBs were obtained from mothers who gave birth at King Abdulaziz Medical City. All mothers gave their informed consent. Personal interviews about the mother's demographics, smoking status and exposure, and caffeine consumption executed, followed by a chart review to analyze maternal and neonatal factors. Laboratory testing was performed on all collected CB units. Using descriptive statistics, maternal and newborn factors were analyzed. T-test or Mann-Whitney U Test, as appropriate, for continuous variables analysis to study the effect of second hand smoking and coffee consumption for the primary outcome. Our study demonstrated a reduction in CB MNC, including lymphocytes, in caffeine consumers among pregnant donors, as well as a reduction in cell potency activities, including total CFU and BFU-E. The effect of passive cigarette smoking on the same cohort was insignificant. Outcome of this study will help in optimizing the quality and quantity of stem cell harvesting from CB to get the maximum benefit and such knowledge will raise the awareness among pregnant women.


Mass fingerprinting of toxic fractions from the venom of the Indian red scorpion, Mesobuthus tamulus: biotope-specific variation in the expression of venom peptides.
The red scorpion, Mesobuthus tamulus, is found in two distinct biotopes within the Indian state of Maharastra-a tropical, sea-level biotope and a semi-arid biotope, up to 600 m. Scorpions from these two geographical areas show marked differences in toxicity. Using mass spectrometry, we have shown biotope-specific variation in the expression of peptides from scorpions collected from these two distinct areas. Matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOFMS) and reversed-phase liquid chromatography/electrospray ionisation mass spectrometry (LC/ESI-MS) were assessed as techniques for obtaining mass fingerprint data. On line LC/ESI-MS was judged to be the method of choice and unique biotope-specific mass fingerprints, with key diagnostic markers, were obtained.


Effects of dietary oat, barley, and guar gums on serum and liver lipid concentrations in diet-induced hypertriglyceridemic rats.
Effects of dietary oat, barley, and guar gums on serum and liver triglyceride or cholesterol concentrations were examined in diet-induced hypertriglyceridemic rats. Male Sprague-Dawley rats were fed a hypertriglyceridemic diet that contained 20% coconut oil, 17.5% fructose, 17.5% sucrose, and 5% cellulose at 4 weeks of age for 14 days. In the gum-supplemented diets, 2% cellulose was replaced by oat gum, barley gum, or guar gum. Hypertriglyceridemia was observed in the control group, whereas serum cholesterol concentration was not increased. All of the gums lowered serum and liver cholesterol concentrations except barley gum which had no significant effect on liver cholesterol. Both oat and barley gums suppressed the elevation of serum and liver triglyceride concentrations but guar gum had no effect.


Creating A Nationwide Nonpartisan Initiative for Family Caregivers in Political Party Platforms.
Policymakers have been slow to support family caregivers, and political agendas mostly fail to address the cost burdens, impact on employment and productivity, and other challenges in taking on long-term care tasks. This project set out to raise policymakers' awareness of family caregivers through proposals to Republican and Democratic party platforms during the 2016 political season. The Family Caregiver Platform Project (FCPP) reviewed the state party platform submission process for Democratic and Republican parties in all 50 states and the District of Columbia. We built a website to make each process understandable by caregiver advocates. We designed model submissions to help volunteers tailor a proposal and recruited caregiver advocates participating in their state process. Finally, we mobilized a ground operation in many states and followed the progress of submissions in each state, as well as the formation of the national platforms. In 39 states, at least one party, Republican or Democrat, hosted a state party platform process. As of September 2016 FCPP volunteers submitted proposals to 29 state parties in 22 states. Family caregiver language was added to eight state party platforms, one state party resolution, two bipartisan legislative resolutions, and one national party platform. The FCPP generated a non-partisan grassroots effort to educate and motivate policymakers to address caregiving issues and solutions. Democratic party leaders provided more opportunities to connect with political leaders, with seven Democratic parties and one Republican party, addressing family caregiver issues in their party platforms.


The effect of commercial steam pasteurization on the levels of Enterobacteriaceae and Escherichia coli on naturally contaminated beef carcasses.
The aim of the study was to assess the reduction achieved by steam pasteurization of beef carcasses of Escherichia coli, Enterobacteriaceae and total aerobic mesophilic plate counts (APCs). In total, 30 carcass halves were exposed to steam pasteurization (90 degrees C, 10 s exposure time) and the 30 corresponding carcass halves remained as untreated controls. The neck, midline and rump were sampled on each carcass half. Significant reductions in E. coli incidence (P < 0.05) and counts, 0.5 log10 CFU 1000 cm(-2) (P < 0.05), were observed on rump sites only. Significant reductions (>0.8 log10 CFU 1000 cm(-2)) of Enterobacteriaceae were observed at all carcass sites sampled (P < 0.05). Enterobacteriaceae reductions (>2 log10 CFU 1000 cm(-2)) were highly significant at the more contaminated sites (P < 0.001). Reductions in total APCs were inconsistent. Steam pasteurization significantly reduced the level of E. coli and Enterobacteriaceae at more contaminated sites, but did not result in complete decontamination. Therefore, steam pasteurization should be classed as an aid to hygienic beef processing, but not as a critical control point.


Globalization of human infectious disease.
Globalization has facilitated the spread of numerous infectious agents to all corners of the planet. Analysis of the Global Infectious Disease and Epidemiology Network (GIDEON) database quantitatively illustrates that the globalization of human infectious agents depends significantly on the range of hosts used. Infectious agents specific to humans are broadly and uniformly distributed, whereas zoonotic infectious agents are far more localized in their geographical distribution. Moreover, these patterns vary depending on transmission mode and infectious agent taxonomy. This dichotomy is unlikely to persist if certain aspects of globalization (for example, exotic species introductions) continue unabated. This raises a serious concern for public health and leaves nations with the task of determining the infectious agents that have the greatest potential to establish within their borders. At the advent of a century characterized by an apparent increase in emerging infectious diseases, these results have critical implications for public-health policy and future research pathways of infectious disease ecology.


Increased skin tumorigenesis in mice lacking pi class glutathione S-transferases.
The activity of chemical carcinogens is a complex balance between metabolic activation by cytochrome P450 monooxygenases and detoxification by enzymes such as glutathione S-transferase (GST). Regulation of these proteins may have profound effects on carcinogenic activity, although it has proved impossible to ascribe the observed effects to the activity of a single protein. GstP appears to play a very important role in carcinogenesis, although the precise nature of its involvement is unclear. We have deleted the murine GstP gene cluster and established the effects on skin tumorigenesis induced by the polycyclic aromatic hydrocarbon 7, 12-dimethylbenz anthracene and the tumor promoting agent 12-O-tetradecanoylphorbol-13-acetate. After 20 weeks, a highly significant increase in the number of papillomas was found in the GstP1/P2 null mice [GstP1/P2(-/-) mice, 179 papillomas, mean 9.94 per animal vs. GstP1/P2(+/+) mice, 55 papillomas, mean 2.89 per animal, (P < 0.001)]. This difference in tumor incidence provides direct evidence that a single gene involved in drug metabolism can have a profound effect on tumorigenicity, and demonstrates that GstP may be an important determinant in cancer susceptibility, particularly in diseases where exposure to polycyclic aromatic hydrocarbons is involved, for instance in cigarette smoke-induced lung cancer.


[Effect of Reading a Book on a Tablet Computer on Cerebral Blood Flow in the Prefrontal Cortex].
By measuring cerebral blood flow in the prefrontal cortex, we aimed to determine how reading a book on a tablet computer affects sleep. Seven students (7 men age range, 21-32 years) participated in this study. In a controlled illuminance environment, the subjects read a novel in printed form or on a tablet computer from any distance. As the subjects were reading, the cerebral blood flow in their prefrontal cortex was measured by near-infrared spectroscopy. The study protocol was as follows. 1) Subjects mentally counted a sequence of numbers for 30 s as a pretest to standardized thinking and then 2) read the novel for 10 min, using the printed book or tablet computer. In step 2), the use of the book or tablet computer was in a random sequence. Subjects rested between the two tasks. Significantly increased brain activity (increase in regional cerebral blood flow) was observed following reading a novel on a tablet computer compared with that after reading a printed book. Furthermore, the region around Broca's area was more active when reading on a tablet computer than when reading a printed book. Considering the results of this study and previous studies on physiological characteristics during nonrapid eye movement sleep, we concluded that reading a book on a tablet computer before the onset of sleep leads to the potential inhibition of sound sleep through mechanisms other than the suppression of melatonin secretion.


Mucoepidermoid carcinoma of the liver.
An autopsy case of mucoepidermoid carcinoma of the liver associated with congenital cysts in a 78-year-old man was reported. The liver weighed 1,900 g, and there was a massive tumor of 11 X 10 X 6.5 cm in the left lobe with multiple sero-mucinous cysts. Histologically, the tumor cells consisted of four types of cells: mucus-secreting cells, squamous cells, intermediate cells, and oxyphilic cells. The variety of tumor cells quite resembled that of mucoepidermoid carcinoma of the salivary gland. The sero-mucinous cysts were lined with a single layer of cuboidal or columnar cells and were not communicated with the biliary ducts. Part of the cysts with benign lining cells was in continuity with tumor cells of the intermediate type. Discussion was made on the histogenesis of hepatic mucoepidermoid carcinoma in particular emphasis on the association of the congenital cysts.


Temporal and spectral basis of the features perceived in repeated noise.
When a half-second segment of a noise is played repeatedly, it initially creates a "whooshing" perception. With longer listening, however, individual features like "clanks" and "rasping" emerge. It is easy to tap the period of the perceived structure. This offers a possibility to investigate the mechanisms underlying the perception of these distinct features. The present study addresses the subject of the temporal and spectral extent of the physical correlates of these percepts. Five subjects participated in this study, and their tapping is in notable, although not perfect correlation. The physical correlate of the features can be confined in time to intervals as small as 100 ms. This segment of the stimulus is processed largely independently from the rest of the noise sample. Spectral processing is, in general, local. Some features, however, are spread over more than one octave. In 3 cases out of 25, across-channel processing is apparent.


Changes in Pulmonary Functions of Adolescents with Pectus Excavatum Throughout the Nuss Procedure.
We aimed to determine the longitudinal changes in pulmonary functions of adolescents with Pectus Excavatum who underwent the Nuss procedure, the minimally invasive repair of pectus excavatum (MIRPE). Lung function measurements were performed before bar implantation (T0), at least six weeks to ten months after implantation (T1a), at least eleven months to sixty-one months after bar implantation (T1b) and at least two weeks after bar explantation (T2). Data of 114 patients (83.3% male) whose median age at implantation was 15.6 years and at explantation 18.7 years were analyzed. Shortly after implantation at T1a a significant decline of vital capacity (VC; n = 82), forced vital capacity (FVC; n = 78) and forced expiratory volume in 1 second (FEV1; n = 80) compared to T0 was seen. At T1b a significant decline for the residual volume (RV; n = 83), the residual volume/total lung capacity ratio (RV/TLC; n = 81), the total specific airway resistance (sRaw; n = 80) and the total airway resistance (Raw; n = 84) also compared to T0 was measured. In the comparison of T1b to T2 a significant increase of VC, FVC (n = 67), FEV1 (n = 69), TLC (n = 67) and a significant decrease of Raw (n = 66), sRaw, RV (n = 65) and the RV/TLC (n = 64) ratio could be observed. In the direct analysis between T0 and T2, after the explantation of the bar a significant increase in VC (n = 54), FVC (n = 52), and TLC (n = 55) and a significant decrease of RV (n = 51) and the RV/TLC index (n = 50), and in airway resistance parameters like Raw (n = 52) and sRaw (n = 51) could be detected. Lung function values along with markers of airway resistance improve in patients after the complete procedure of MIRPE. Level II.