Molecular parameters of type IV alpha-internexin and type IV-type III alpha-internexin-vimentin copolymer intermediate filaments.
During neuronal development, a dynamic replacement mechanism occurs in which the type VI nestin and type III vimentin intermediate filament proteins are replaced by a series of type IV proteins beginning with alpha-internexin. We have explored molecular details of how the type III to type IV replacement process may occur. First, we have demonstrated by cross-linking experiments that bacterially expressed forms of alpha-internexin and vimentin form heterodimer molecules in vitro that assemble into copolymer intermediate filaments. We show using a urea disassembly assay that alpha-internexin molecules are likely to be more stable than those of vimentin. Second, by analyses of the induced cross-links, we have determined the axial lengths of alpha-internexin homodimer and alpha-internexin-vimentin heterodimer molecules and their modes of alignments in filaments. We report that these dimensions are the same as those reported earlier for vimentin homopolymer molecules and, by implication, are also the same for the other neuronal type IV proteins. These data suggest that during neuronal development, alpha-internexin molecules are readily assimilated onto the pre-existing vimentin cytoskeletal intermediate filament network because the axial lengths and axial alignments of their molecules are the same. Furthermore, the dynamic replacement process may be driven by a positive equilibrium due to the increased stability of the alpha-internexin network.


Acute hyperglycemia regulates transcription and posttranscriptional stability of PKCbetaII mRNA in vascular smooth muscle cells.
Acute hyperglycemia may contribute to the progression of atherosclerosis by regulating protein kinase C (PKC) isozymes and by accelerating vascular smooth muscle cell (VSMC) proliferation. We investigated acute glucose regulation of PKCbeta gene expression in A10 cells, a rat aortic smooth muscle cell line. Western blot analysis showed that PKCbetaII protein levels decreased with high glucose (25 mM) compared to normal glucose (5.5 mM), whereas PKCbetaI levels were unaltered. PKCbeta mRNA levels were depleted by 60-75% in hyperglycemic conditions. To elucidate whether high glucose regulated PKCbeta expression via the common promoter for PKCbetaI and PKCbetaII, deletion constructs of the PKCbeta promoter ligated to CAT as reporter gene were transfected into A10 cells. Construct D (-411 to +179CAT) showed quenching in high glucose (25 mM) and suggested the involvement of a carbohydrate response element in the 5' promoter region of the PKCbeta gene. In actinomycin D-treated A10 cells, a 60% decrease in PKCbeta mRNA with high glucose treatment indicated that posttranscriptional destabilization by glucose was also occurring. We have demonstrated that glucose-induced posttranscriptional destabilization of PKCbetaII message is mediated via a nuclease activity present in the cytosol. The specificity of glucose to posttranscriptionally destabilize PKCbetaII mRNA, but not the PKCbetaI mRNA, was confirmed in both A10 cells and primary cultures from human aorta.


[The influence of current social, medical, and political trends on the future of otorhinolaryngology].
All medical specialties are changing permanently, including otorhinolaryngology. Analyzing trends in social changes, medical progress, and political decisions will allow the effects of these on ENT medicine to be at least partially anticipated. Demographic changes and medical progress lead to an increasing demand for medical treatments. In addition, increasing numbers of female physicians are observed, as are many changes in the lifestyles of young physicians. Medical treatment will develop toward more individualized therapies in the future. ENT surgery will become a more ambulatory medical specialty. Driven by political decisions, digital medicine will become more important. Particular services once provided by physicians will be delegated to non-physician professionals. The lack of physicians and the progress in medicine require better networking between in- and outpatient services in the future. The potential of such collaborations is currently not completely realized. However, these developments will also increase the cost of health care. These trends will develop otorhinolaryngology into a conservative and surgical ambulatory care driven medical specialty. Embedded in decentralized networks and cooperations, and supported by IT technologies and specialized non-physician professionals, ENT physicians will work in hospitals as well as in practices on a permanent basis. Nevertheless, the question of funding these changes has yet to be clarified.


Divergent maternal behavioral patterns in two genetic animal models of depression.
Maternal behavior was examined in Flinders Sensitive-Line (FSL) and Wistar-Kyoto (WKY) rats, two different genetic animal models of depression. Behavioral patterns were assessed by undisturbed observations in the nest [Post-Partum Days (PPD) 4 and 9] and post-disturbance observations ("retrieval tests") on PPD 10. Litters were randomly allocated to a mild chronic-stress condition (limiting available bedding between PPD 2 and 9) or a standard rearing condition. The findings indicated that FSL dams did not differ from control dams in the undisturbed observations. However, in the post-disturbance observations FSL dams exhibited less pup-directed behaviors, a shorter latency to first pup carrying/retrieval and more self-directed behaviors than controls (the latter effect only in dams' interaction with whole litter). In contrast, WKY dams performed more pup-directed activities (e.g., nursing and licking) and less self-directed activities in both the undisturbed and post-disturbance observations (in both dams' interaction with single-pup and with the whole-litter) compared to controls. Accordingly, WKY dams exhibited a shorter latency for first pup-licking bout (in both post-disturbance observations). The early life mild chronic-stress used in the study ('limited-bedding') had a minor effect on the dams' behavior. Overall, the study investigated for the first time the maternal behavior of WKY dams and suggests that these dams show an almost opposite behavioral pattern to that of FSL dams. The results are discussed with regard to earlier findings in the FSL strain and behavioral patterns documented in depressed human mothers.


Percutaneous management of occluded biliary duct endoprostheses.
To present interventional methods for percutaneous treatment of patients with occluded bile duct endoprostheses. Thirteen patients with endoscopically inserted occluded or damaged bile duct endoprostheses and recurrent jaundice were treated percutaneously. Endoscopic treatment was not available in 2 cases and unsuccessful in 11 other patients. Eleven interventions were performed under systemic sedation and local anaesthesia and 2 under general anaesthesia. The endoprostheses were dislodged to the bowel using different interventional devices. Adequate bile duct drainage was subsequently achieved by insertion of self-expanding metallic stents. All procedures were accomplished successfully and without immediate serious complications. Two metallic stents and 18 plastic endoprostheses were dislodged to the bowel using percutaneous interventional techniques. One plastic endoprosthesis became bent in the duodenum and had to be removed endoscopically due to abdominal pain. None of the other endoprostheses left in the bowel caused any symptoms. Two patients died during the first week after the procedure due to progressive liver failure. Occluded bile duct endoprostheses can be safely dislodged to the bowel and replaced by metallic stents using percutaneous interventional techniques.


Symptomatic Subclavian Steal During Pregnancy in a Woman Status Post Coarctation Repair in Infancy.
A 24-year-old woman with a history of coarctation repair by subclavian flap aortoplasty presented at 15 weeks' gestation with transient episodes of vision loss. She was diagnosed with subclavian steal syndrome and underwent left carotid artery to subclavian artery bypass at 17 weeks' gestation. She has had no recurrence of symptoms at ten months of postoperative follow-up. Despite the anatomic substrate for subclavian steal in patients with this type of surgical repair, neurologic symptoms are uncommon. It is possible that the pregnancy-induced fall in systemic vascular resistance triggered symptoms in this previously asymptomatic patient.


Menkes' syndrome: an updated review.
Menkes' syndrome is an X-linked recessive multisystem disease which is usually fatal prior to 5 years of age. Though originally felt to be a disorder of copper deficiency, it now appears to be a copper storage disease, with the observed defects resulting from inappropriate systemic copper distribution. Disorders in the metabolism of metallothionein, a metalloprotein involved in cellular copper transport, may be the primary defect in this syndrome. This review summarizes the relevant clinical and pathologic findings seen in this condition to date. It also describes some of the abnormalities in the metabolism of copper and metallothionein in these infants.


Mesenchymal tumours of the mediastinum--part I.
The mediastinum is an anatomically defined space in which organs and major blood vessels reside with surrounding soft tissue elements. The thymus is an important organ in the mediastinum, and many of the masses encountered in the mediastinum are related to this organ. Most neoplasms diagnosed in the mediastinum are epithelial tumours (thymomas and thymic carcinomas), lymphomas or germ cell tumours. In contrast, soft tissue tumours of the mediastinum are rare. In 1963, Pachter and Lattes systematically reviewed soft tissue pathology of the mediastinum, covering the hitherto described [2, 226, 227] In this review, based on the 2013 WHO classification of soft tissue tumours and the 2015 WHO classification of tumours of the lung, pleura, thymus and heart, we provide an updated overview of mesenchymal tumours that may be encountered in the mediastinum.


Practices and attitudes of Japanese oncologists and palliative care physicians concerning terminal sedation: a nationwide survey.
To clarify the frequency of practice of sedation therapy for terminally ill cancer patients and to identify physicians' attitudes toward sedation. Questionnaires were mailed to 1,436 Japanese oncologists and palliative care physicians with a request to report their practice of and attitudes toward palliative sedation therapy. A total of 697 physicians returned questionnaires (response rate, 49.6%). Use of mild, intermittent-deep, or continuous-deep sedation for physical and psychologic distress was reported by 89% and 64%, 70% and 46%, and 66% and 38%, respectively. In vignettes in which physicians were asked whether they would use sedation for a patient with refractory dyspnea or with existential distress, 14% and 15%, respectively, chose continuous-deep sedation as a strong possibility. Those physicians less confident with psychologic care and with higher levels of professional burnout were more likely to choose continuous-deep sedation. In vignettes in which they were asked whether they use sedation for a patient with depression or delirium, 39% and 31%, respectively, considered psychiatric treatment to be a strong possibility, and 42% and 50% regarded continuous-deep sedation as a potential treatment option. Physicians less involved in caring for the terminally ill and less specialized in palliative medicine were significantly less likely to choose psychiatric treatment. Sedation is frequently used for severe physical and psychologic distress of cancer patients. Physicians' clinical experiences with the terminally ill and their levels of professional burnout influence the decisions. Training and education for physicians in regard to end-of-life care and valid clinical guidelines for palliative sedation therapy are necessary.


Mutational analysis of the N-terminal domain of UreR, the positive transcriptional regulator of urease gene expression.
The Escherichia coli plasmid-encoded urease, a virulence factor in human and animal infections of the urinary and gastroduodenal tracts, is induced when the substrate urea is present in the growth medium. Urea-dependent urease expression is mediated at the transcriptional level by the AraC-like activator UreR. Previous work has shown that a peptide representing the N-terminal 194 amino-acid residues of UreR binds urea at a single site, full-length UreR forms an oligomer, and the oligomerization motif is thought to reside in the N-terminal portion of the molecule. The C-terminal domain of UreR contains two helix-turn-helix motifs presumed to be necessary for DNA binding. In this study, we exploited mutational analyses at the N-terminal domain of UreR to determine if this domain dimerizes similar to other AraC family members. UreR mutants were analyzed for the ability to activate transcription of lacZ from an ureDp-lacZ transcriptional fusion. A construct encoding the N-terminal 194 amino acids of UreR, eluted as an oligomer by gel filtration and had a dominant negative phenotype over the wild-type ureR allele. We hypothesize that this dominant negative phenotype results from the formation of inactive heterodimers between wild-type and truncated UreR. Dominant negative analysis and cross-linking assays demonstrated that E. coli UreR is active as a dimer and dimerization occurs within the first 180 residues.


Cryptosporidiosis.
In the United States, the four groups at high risk of cryptosporidiosis are animal handlers, foreign travelers, children in day care centers and immunocompromised patients, including those with acquired immunodeficiency syndrome. In immunocompetent patients, the sporadic diarrheal illness is self-limited. Diagnosis is made by the identification of Cryptosporidium oocysts in stool specimens, but these parasites are easily overlooked and may be confused with yeast. At present, there is no specific therapy for this infection.


Controls for phytolith accumulation in Moso bamboo leaves across China.
Phytoliths are amorphous silica formed gradually in plant tissue, which have great potential to mitigate climate change due to their resistance to decomposition and their ability to occlude organic carbon. The accumulation of phytoliths is regulated by multiple factors. However, the factors controlling its accumulation remain unclear. Here, we investigated phytolith content in Moso bamboo leaves of different ages collected from 110 sampling sites of their main distribution regions across China. The controls for phytolith accumulation were studied by correlation and random forest analyses. Our results showed that phytolith content is leaf age-dependent (16-month-old leaf >4-month-old leaf >3-month-old leaf). Phytolith accumulation rate in Moso bamboo leaves is significantly correlated with mean monthly temperature (MMT) and mean monthly precipitation (MMP). About 67.1 % of the variance of the phytolith accumulation rate could be explained by multiple environmental factors, mainly MMT and MMP. Therefore, we conclude that the weather is the major driver that regulates the phytolith accumulation rate. Our study provides a unique dataset for estimating phytolith production rate and the potential carbon sequestration of phytolith through climatic factors.


[RCT on discharge planning for high utilisers of mental health care: conduct and quality of the intervention].
To evaluate feasibility of a structured discharge planning intervention for high utilisers of mental health care developed in a multicentre RCT. Data of N = 241 participants (discharge and 3-month follow-up) allocated to the intervention group are analysed with regard to the intervention's quality of implementation, acceptance, and changes in needs. The intervention was well accepted among patients and staff. However, a subgroup of participants showed manual violations. Total and unmet needs could be reduced between baseline and follow-up. Amount and change of needs substantially varied by centre and there was a trend towards variation by dose. The intervention was feasible. Further analyses are needed to explore differential efficacy.


Nonalcoholic fatty liver disease as a risk factor for Clostridium difficile-associated diarrhea.
Clostridium difficile is the most common cause of infectious nosocomial diarrhea among adults in developed countries. Nonalcoholic fatty liver disease (NAFLD) is considered the most common chronic liver disease and it is associated with bacterial infections. Our goal was to assess whether NAFLD considered a risk factor for C. difficile-associated diarrhea (CDAD). We conducted a retrospective study of patients admitted with CDAD at Baruch Padeh Medical Center, Poria, Israel during a period of four years. Data on demographic characteristics, clinical signs, underlying conditions, presence of fatty liver based on computed tomography/ultrasonography imaging and several risk factors for CDI were collected. The control group included patients with diarrhea who were negative for CDT and had been hospitalized during the same period. The controls were matched for age (±5 years) and gender. Totally, 115/164 patients with CDAD met the inclusion criteria. The control group was consisted of 115 hospitalized patients with non-CDAD. The mean age of all the participants (230) was 69.57 ± 18 years. NAFLD was found in 76/115 (66%) patients with CDAD vs. 35/115 (30.4%) in the control group, P < 0.001. Moreover, we found significant associations between CDAD group and metabolic syndrome, prior use of antibiotic in the last 3 months, NAFLD and high serum levels of C-reactive protein. Multivariate analysis showed that NAFLD, odds ratio 1.51, 95% confidence interval 1.2-1.95, P = 0.05 was significantly associated with CDAD. This retrospective study showed that NAFLD is a risk factor for CDAD. Moreover, metabolic syndrome and high serum levels of C-reactive protein were significantly associated with the risk of CDAD.


Adult-onset Still's disease with multiple lymphadenopathy: a case report and literature review.
Adult-onset Still's disease (AOSD) often presents with systemic multiple lymphadenopathy. In addition to the common paracortical and mixed patterns in AOSD lymph node histopathological features, other morphological patterns include diffuse, necrotic, and follicular patterns. However, to date, there have been few reports on the histopathological description of AOSD lymph nodes. An 18-year-old woman presented 2 months earlier with pain in her large joints with painless rash formation; bilateral posterior cervical lymph node, left supraclavicular lymph node, and left posterior axillary lymph node enlargement, and no tenderness. Left cervical lymph node resection was performed for pathological examination. The lymph node structure was basically preserved, and subcapsular and medullary sinus structures were observed. Many histiocytes in the sinus were observed, the cortical area was reduced, a few lymphoid follicles of different sizes were observed, and some atrophy and hyperplasia were noted. The lymphoid tissue in the paracortical region of the lymph node was diffusely proliferative and enlarged, mainly comprising histiocytes with abundant cytoplasm, immunoblasts and numerous lymphocytes with slightly irregular, small- to medium-sized nuclei. Nuclear karyorrhexis was easily observed, showing a few nuclear debris and the "starry sky" phenomenon, accompanied by abundantly branching high endothelial small vessels with few scattered plasma cells and eosinophil infiltration. Lymphoid follicle immunophenotype with reactive proliferative changes was observed. Approximately 40% of the cells in the paracortical region were positive for Ki-67, and the histiocytes expressed CD68, CD163, and some expressed S-100, with the absence of myeloperoxidase. The immunoblasts expressed CD30 and CD20, not ALK or CD15. Background small- to medium-sized T cells expressed CD2, CD3, CD5, CD7, CD4, and CD8; the number of CD8-positive T cells was slightly predominant, and a small number of T cells expressed granzyme B and T-cell intracellular antigen 1. The patient received a comprehensive medical treatment after the operation, and her condition was stable without progression at the 11-month follow-up evaluation. The pathological features of AOSD lymphadenopathy raises the awareness of AOSD among pathologists and clinicians and aids in the diagnosis and differential diagnosis of AOSD lymphadenopathy from other reactive lymphadenopathies (lupus lymphadenitis, etc.) and lymphomas.


You can help your clients change.
Nurses are in an excellent position to assist clients to change behaviors that will improve their health. The client is the expert on what to change and which method will work best. Matching your approach to the client's stage of change will motivate the client to move along the continuum of change.


Contactless impedance measurement by magnetic induction--a possible method for investigation of brain impedance.
Using a primary coil that induces eddy currents in a volume conductor, and a pair of secondary coils configured to form a differential transformer, it is possible to measure the conductivity of a volume conductor by the magnetic fields of the induced eddy currents. This method is especially favourable for measuring impedance of the brain, as the low conductance of the surrounding skull interferes only very slightly with the measuring process. In a simulation experiment a life-size skull model was filled with NaCl solutions of different concentrations in each half, so as to model the impedances of a normal and an oedematous hemisphere. The impedance differences could be clearly detected by a coil system of 25 mm diameter.


Impact of number of co-existing rotors and inter-electrode distance on accuracy of rotor localization.
Conflicting evidence exists on the efficacy of focal impulse and rotor modulation on atrial fibrillation ablation. A potential explanation is inaccurate rotor localization from multiple rotors coexistence and a relatively large (9-11mm) inter-electrode distance (IED) of the multi-electrode basket catheter. We studied a numerical model of cardiac action potential to reproduce one through seven rotors in a two-dimensional lattice. We estimated rotor location using phase singularity, Shannon entropy and dominant frequency. We then spatially downsampled the time series to create IEDs of 2-30mm. The error of rotor localization was measured with reference to the dynamics of phase singularity at the original spatial resolution (IED=1mm). IED has a significant impact on the error using all the methods. When only one rotor is present, the error increases exponentially as a function of IED. At the clinical IED of 10mm, the error is 3.8mm (phase singularity), 3.7mm (dominant frequency), and 11.8mm (Shannon entropy). When there are more than one rotors, the error of rotor localization increases 10-fold. The error based on the phase singularity method at the clinical IED of 10mm ranges from 30.0mm (two rotors) to 96.1mm (five rotors). The magnitude of error of rotor localization using a clinically available basket catheter, in the presence of multiple rotors might be high enough to impact the accuracy of targeting during AF ablation. Improvement of catheter design and development of high-density mapping catheters may improve clinical outcomes of FIRM-guided AF ablation.


Brief report: childhood disintegrative disorder as a likely manifestation of vitamin B12 deficiency.
Childhood disintegrative disorder is a rare disorder, characterized by regression of acquired skills after a period of normal development. The case of childhood disintegrative disorder presented here was found to have vitamin B12 deficiency and hyperhomocysteinemia on extensive evaluation to find a probable cause for regression. This case illustrates the need for a thorough evaluation of all cases of childhood disintegrative disorder so that treatable causes of regression, like vitamin B12 deficiency, are not missed.


The effects of age, sex, and genotype on self-report drunkenness following a challenge dose of alcohol.
Age is a potential source of variation that contributes to differences between, but not within, twin pairs. In most genetic analyses of twin data, linear and other functions of age are usually removed prior to model fitting. This correction is typically applied only within twin groups of the same sex and zygosity, and no heterogeneity test of age regressions is performed. Here we include age as a variable in the model-fitting procedure and allow for tests of heterogeneity of age regressions across sex and zygosity groups. The LISREL formulation of the approach is illustrated with data collected from Australian twins on subjective impressions of drunkenness following alcohol consumption. The results indicate significant negative covariation of impressions of drunkenness with age. The data support a simple model of additive genetic and unique environmental variation. No evidence was found for sex differences in genetic or environmental components of variation.


Nurse Telephone Counseling Services as a "Gatekeeper" in an Internet-Based Digital Doctor Reception: A Mixed Questionnaire Survey.
Objective: A large number of different types of digital innovations for health and medical care have been developed in Sweden under the concept of eHealth. Employees' interest is of great importance in determining the success of different new digital interventions and technologies. Purpose: In this study, we aimed to elucidate the nurses' experiences as a first "gatekeeper" in an Internet-based Digital Doctor Reception (DDR) concept. Methods: Our 16 informants were recruited among nurses who participated in a DDR pilot project that was completed in April 2019. A mixed questionnaire survey was used to elucidate the nurses' experiences of collaboration & challenges, technical functionality, and DDR as an activity. The results were descriptively summarized with index values (IVs, 0-1.0), supplemented with a 10-point Likert-type scale that estimated satisfaction and views regarding personal experiences. Results: Collaboration and challenges were experienced as fairly good (IV, 0.58), and technical functionality was experienced as good (IV, 0.80). The experience of DDR as an activity was described positively with an IV of 0.75. The overall experience of the concept (IV, 0.68), corresponds well to the median satisfaction value of 6.5 (interquartile range, 6-9). Content analysis identified 2 main categories: "Facilitators in using DDR experienced by nurses" and "Barriers in using DDR experienced by nurses." Nurses generally felt positive about participating in the development of an eHealth service. However, they suggested that DDR triaging should take place at the health care center level. The nurses also observed that certain patient groups were excluded from the DDR concept, and sometimes experienced this new way of triaging as less challenging. Conclusion: The informants in our study generally described satisfaction and an overall good experience with the DDR concept. However, some informants felt that the concept was sometimes more stressful and less challenging compared with normal working methods.


Optogenetic activation of striatal D1R and D2R cells differentially engages downstream connected areas beyond the basal ganglia.
The basal ganglia (BG) are a group of subcortical nuclei responsible for motor and executive function. Central to BG function are striatal cells expressing D1 (D1R) and D2 (D2R) dopamine receptors. D1R and D2R cells are considered functional antagonists that facilitate voluntary movements and inhibit competing motor patterns, respectively. However, whether they maintain a uniform function across the striatum and what influence they exert outside the BG is unclear. Here, we address these questions by combining optogenetic activation of D1R and D2R cells in the mouse ventrolateral caudoputamen with fMRI. Striatal D1R/D2R stimulation evokes distinct activity within the BG-thalamocortical network and differentially engages cerebellar and prefrontal regions. Computational modeling of effective connectivity confirms that changes in D1R/D2R output drive functional relationships between these regions. Our results suggest a complex functional organization of striatal D1R/D2R cells and hint toward an interconnected fronto-BG-cerebellar network modulated by striatal D1R and D2R cells.


Online Courses Provide Robust Learning Gains and Improve Learner Confidence in the Foundational Biomedical Sciences.
The early stages of medical school involve education in a number of foundational biomedical sciences including genetics, immunology, and physiology. However, students entering medical school may have widely varying levels of background in these areas due to differences in the availability and quality of prior education on these topics. Even students who have recently taken formal courses in these subjects may not feel confident in their level of preparation, leading to anxiety for early-stage medical students. These differences can make it difficult for instructors to create meaningful learning experiences that are appropriate for all students. Additionally, actual or perceived differences in preparation may lead fewer students from diverse backgrounds to apply to medical school. Therefore, creating an efficient and scalable way to increase students' knowledge and confidence in these topics addresses an important need for many medical schools. We recorded pre- and post-course quiz scores for 9790 individuals who completed HMX online courses, developed in accordance with evidence-based learning practices and covering the fundamentals of biochemistry, genetics, immunology, pharmacology, and physiology. Each question was accompanied by a Likert scale question to assess the learner's confidence in their answer. Learners' median post-course quiz performance and self-assessed confidence significantly increased relative to pre-course quiz performance for each course. Improvements were consistent across US-based medical schools, non-US medical schools, and course runs open to the public. This indicates that online courses created using evidence-based learning practices can lead to significant increases in knowledge and confidence for many learners, helping prepare them for further medical education. The online version contains supplementary material available at 10.1007/s40670-022-01660-4.


Growth and sex ratio of nestlings in two species of crows: how important is hatching asynchrony?
In experimental studies of avian hatching paterns offspring sex has been neglected. This may be a problem if nestling growth and mortality is sex biased, and if this bias is influenced by hatching spread. In a field study of two crow species, the magpie Pica pica and the hooded crow Corvus corone cornix, we manipulated hatching spread. Both species have asynchronous hatching, and adult males are larger than females by 12-14%. The sex ratios obtained from the different experimental groups on day 24 post-hatch (total sample n = 403) did not deviate significantly from unity, nor did the sex ratios obtained among young newly hatched in an incubator (total sample n = 305). Male and female offspring were of similar size at hatching but males were larger on day 24 post-hatch. Males seemed to be more costly to rear than females, judging by the 20% difference in the mean amounts of food found in the gizzards of the young on day 24 post-hatch. Dimorphism in body size did not seem to be influenced by degree of hatching spread. Asynchronous hatching did not seem to be needed to produce high quality offspring of the larger sex (i.e. males), nor did asynchronous hatching help to ensure equal parental investment in male and female progeny. One reason for the latter negative results may be that the size dimorphism of the two crow species studied were relatively small.


[Congenital mesoblastic nephroma: diagnosis and treatment of one case].
The congenital mesoblastic nephroma (CMN) described by Bolande et al. in 1967 is a renal tumor often discovered in neonatal period and early childhood. It's usually considered as a benign tumor with good prognostic for which nephrectomy is the reference treatment. But some cases of local recidives and metastatic sites had been described in the literature. For these reasons histologic analysis and quality of follow up are very important. In this observation we describe a neonatal kind of CMN and we discuss this pathology.


[Interpretation of the metabolic study in renal lithiasis and its treatment].
Urolithiasis is a common disease, and is an important health problem that is associated with a great economic burden. The nature of stone disease varies according by dietary and lifestyle factors, including, among others, climate variations. The majority of patients will suffer a new lithiasic episode at some point in their life, unless preventive measures, such as changing lifestyles and dietary habits, are put in place to avoid it. The risk factors involved in lithogenesis should be evaluated in order to reduce recurrences. In the majority of these patients, metabolic changes are observed in the urine that predispose lithogenesis. The kind of evaluation depends on stone composition and on the clinical presentation. A diagnosis of systemic and renal diseases of lithogenic nature can be diagnosed with these studies, and they also enable the adoption of precise prophylactic measures that achieve control of recurrence in a great number of patients.


The role of the antigen processing machinery in the regulation and trafficking of intracellular -Toll-like receptor molecules.
Intracellular Toll-like receptors (TLRs) are key components of the innate immune system. Their expression in antigen-presenting cells (APCs), and in particular dendritic cells (DCs), makes them critical in the induction of the adaptive immune response. In DCs, they interact with the chaperone UNC93B1 that mediates their trafficking from the endoplasmic reticulum (ER) to endosomes where they are cleaved by proteases and activated. All these different steps are also shared by major histocompatibility complex class-II (MHCII) molecules. Here, we will discuss the tight relationship intracellular TLRs have with the antigen processing machinery in APCs for their trafficking and activation.


The Australian Orthopaedic Association National Joint Replacement Registry.
In the financial year ending June 2002, 26 689 hip replacements and 26089 knee replacements (total, 52778) were performed in Australia. Hip and knee replacement procedures have increased between 5%-10% each year for the past 10 years, with a combined increase in hip and knee replacement of 13.4% in the past year. The revision rate for hip replacement surgery in Australia is unknown but is estimated to be 20%-24%; the revision rate for hip replacement surgery in Sweden is 7%. Although data collection for the Registry is voluntary, it has 100% compliance from hospitals undertaking joint-replacement surgery.


Psychometric properties of the stress control mindset measure in university students from Australia and the UK.
Beliefs about the consequences of stress, stress mindsets, are associated with health and performance outcomes under stress. This article reports the development and examination of the psychometric properties of a measure of stress mindset: The Stress Control Mindset Measure (SCMM). The measure is consistent with theory on mindsets about self-attributes and conceptualizes stress mindset as the extent to which individuals endorse beliefs that stress can be enhancing. The study adopted a correlational cross-sectional survey design in two student samples. Undergraduate students from an Australian university (Sample 1, N = 218) and a UK university (Sample 2, N = 214) completed the SCMM and measures of health and well-being outcomes. Confirmatory factor analyses supported a four-factor structure and strict measurement invariance across samples (ΔCFI < 0.01). Reliability, convergent validity, discriminant validity, and concurrent validity of the overall SCMM were supported in both samples. Incremental validity was supported for most outcomes, accounting for significantly more variance (between 2.2% and 5.9%) in health and well-being outcomes than an existing measure. Current data provide preliminary support for the SCMM as a reliable and valid measure with good psychometric properties and theoretically consistent relations with health outcomes under stress. Findings provide initial evidence supporting the potential utility of the SCMM in future research examining relations between stress mindsets and health and performance outcomes.


Scalp topography of mechanically and electrically evoked somatosensory potentials in man.
Scalp topography of somatosensory evoked potentials following mechanical (SEPs(M)) and electrical (SEPs(E)) stimulation of the left middle finger was investigated with linked ear reference in 21 normal young adults. A small plastic ball (touch) or needle (pain) was used for the mechanical stimulation. With mechanical stimulation, at least 3 positive and 3 negative potentials (P19(M), N24(M), P29(M), N36(M), P49(M) and N61(M] were found in the post-rolandic area contralateral to the stimulation. The wave form in SEPs(M) was similar to those in SEPs(E), but the peak latency of each component in SEPs(M) was 1-4 msec longer than that in SEPs(E). Earlier components such as P19(M), N24(M) and P29(M) were not as clearly recognized as corresponding components in SEPs(E). However, the wave form recorded on the hemisphere ipsilateral to the stimulation or in the frontal area contralateral to the stimulation showed a greater difference from subject to subject. P19(M), N24(M) and P29(M) correlated positively both with arm length and height of the subject. There was no significant difference of the wave form between the linked ear reference and the bipolar (C4-Fz) derivation. Wave form of SEPs(M) by needle stimulation did not significantly differ from that by plastic ball stimulation.


Cerebral dysfunction in alcoholism and presenile dementia. A comparison of two groups of patients with similar reduction of the cerebral blood flow.
Fifteen chronic alcoholics and 15 presenile patients were matched in pairs with regard to their mean hemisphere cerebral blood parameters-an index of brain metabolism. The distribution of the regional cerebral blood flow was similar in the two groups. The alcoholics performed significantly better in all psychometric tests than the presenile patients and more alcoholics than presenile patients were still employed and working. Nine presenile patients and one alcoholic showed symptoms indicating brain stem dysfunction. The measurements of the cerebral blood blow were made at rest while the psychometric testings and the evaluation of the social performance gave information about the brain at work. It is suggested that cerebral dysfunction in alcoholics to some extent can be partly overcome by brain activation procedures. In contrast, the defects of higher mental functions in presenile dementia cannot be compensated for.


Methods for estimating HIV prevalence: A comparison of extrapolation from surveys on infection rate and risk behaviour with back-calculation for the Netherlands.
To compare HIV prevalence estimates (total number infected) by using extrapolation from surveys on infection rate and risk behaviour (EIR) in specific segments of the population and back-calculation (BC) on reported AIDS cases. To discuss potential sources of bias and error, and to identify areas for improvement of the methodology. Systematic comparison and epidemiological assessment of data input, underlying assumptions, and output. Low, possibly unbiased and high estimates of HIV prevalence as of January 1996 for homo/bisexual men, injecting drug users. heterosexual men and women with multiple partners, and blood transfusion recipients and haemophiliacs were derived from surveys and continuous data collections on HIV infection rate and risk behaviour in the Netherlands between 1992 and 1996. These were compared with estimates (point and 95 % CI) by empirical Bayesian BC on AIDS cases 1982-1995. The estimate of HIV prevalence by EIR was 13,806 with low and high estimates of 9619 and 17,700, respectively. The HIV prevalence estimate by BC was 8812 (95% CI: 7759-9867). The available data from EIR are too limited for accurate estimates of HIV prevalence. EIR estimates could be improved considerably with more precise data on prevalence of risk behaviours and HIV prevalence rate for homosexual men. More confidence can be put in the BC estimates, but these could be underestimates because of the age effect on incubation time, pre-AIDS treatment and relapse of risk behaviour. BC estimates could be improved by a better representation of the incubation time distribution (including the effect of age there-upon), better data on the effectiveness and uptake of pre-AIDS antiretroviral treatment and prophylaxis of opportunistic infections, and on the level of underreporting.


Application of a cellular test battery in the decision point approach to carcinogen identification.
The assessment of the potential carcinogenicity of a chemical requires a systematic approach taking into account various types of data. Important information on the DNA reactivity and other genetic effects of chemicals can be obtained from a battery of cellular tests. A battery is described which includes DNA repair in hepatocytes, mutagenesis in Salmonella typhimurium, mutagenesis, chromosome alterations, and transformation in mammalian cells. The interpretation of findings in this battery for the identification of potential carcinogenicity of chemicals is discussed.


Titanium alloys with varying surface micro-area potential differences have antibacterial abilities and a favorable cellular response.
Surface micro-area potential difference (MAPD) can achieve bacteriostatic performance independent of metal ion dissolution. To study the influence of MAPD on antibacterial properties and the cellular response, Ti-Ag alloys with different surface potentials were designed and prepared by changing the preparation and heat treatment processes. Ti-Ag alloys (T4, T6, and S) were prepared by vacuum arc smelting, water quenching, and sintering. Cp-Ti was set as a control group in this work. The microstructures and surface potential distributions of the Ti-Ag alloys were analyzed by SEM and energy dispersive spectrometry. Plate counting and live/dead staining methods were used to evaluate the antibacterial properties of the alloys, and the mitochondrial function, ATP levels, and apoptosis were assessed in MC3T3-E1 cells to analyze the cellular response. Due to the formation of the Ti-Ag intermetallic phase in the Ti-Ag alloys, Ti-Ag (T4) without the Ti-Ag phase had the lowest MAPD, Ti-Ag (T6) with a fine Ti2Ag phase had a moderate MAPD, and Ti-Ag (S) with a Ti-Ag intermetallic phase had the highest MAPD. The primary results demonstrated that the Ti-Ag samples with different MAPDs exhibited different bacteriostatic effects, ROS expression levels, and apoptosis-related protein expression levels in cells. The alloy with a high MAPD exhibited a strong antibacterial effect. A moderate MAPD stimulated cellular antioxidant regulation (GSH/GSSG) and downregulated the expression of intracellular ROS. MAPD could also promote the transformation of the inactive mitochondria to biologically active mitochondria by increasing the ΔΨm and reducing apoptosis. The results here indicated that moderate MAPD not only had bacteriostatic effects but also promoted mitochondrial function and inhibited cell apoptosis, which provides a new strategy to improve the surface bioactivity of titanium alloys and a new idea for titanium alloy design. There are some limitations of the mechanism of MAPD. However, researchers will become increasingly aware of the advantages and disadvantages of MAPD and MAPD might provide an affordable solution of peri-implantitis.


Giant axonopathy characterized by intermediate location of axonal enlargements and acceleration of neurofilament transport.
It has previously been shown that 2,5-hexanedione (2,5-HD) and its 3,4-dimethyl derivative (3,4-DMHD) induce neurofilamentous accumulations at prenodal sites in distal and proximal, respectively, regions of peripheral axons. For 2,5-HD, neurofilament (NF) transport is accelerated and this is thought to be directly related to the appearance of the axonal enlargements. For 3,4-DMHD, however, the rate of NF transport cannot be assessed owing to the very proximal position of NF accumulation. In the present study, it is shown that administration to rats of 3-methyl-2,5-hexanedione, the structural 'average' of 2,5-HD and 3,4-DMHD, induces NF accumulations at midway axonal positions of the sciatic and optic systems, and results in acceleration of NF in the sections of optic axons proximal to the enlargements. These results suggest that a common mechanism underlies all gamma-diketone neuropathies, and that the proximodistal pattern of axonal enlargements represents pharmacokinetic variables rather than differences in mode of action. The neurotoxicity of gamma-diketones probably arises from pyrrolation of lysine epsilon-amino groups in crucial regions of NF or related proteins responsible for maintaining the proper supramolecular organization of the cytoskeleton. Acceleration of NF transport appears to be a common characteristic of chemically induced axonopathies, regardless of location, and this is contrary to the theory that gamma-diketone-induced NF accumulation results primarily from a progressive cross-linking of NF occurring subsequent to pyrrole formation.


Sertoli cell transplants: their use in the treatment of neurodegenerative disease.
The efficacy of treating neurodegenerative diseases with the transplantation of fetal tissue has been demonstrated in animal models of Parkinson's disease, Huntington's disease and stroke. In the clinical setting, neural transplantation as a treatment for patients with Parkinson's disease has shown promising results. However, for this treatment method to be effective neuronal survival needs to be improved through either trophic support or localized immunoprotection. Co-transplanting Sertoli cells, which express many nutritive, regulatory, trophic and immunosuppressive factors, with fetal neural cells could provide both of these requirements. Such a strategy could enhance the recovery benefits associated with transplantation and decrease the need for, and the risks associated with, long-term systemic immunosuppression.


What Happened to the Wages of Mexican Immigrants? Trends and Interpretations.
Over the past several decades the wages earned by Mexican immigrants stagnated relative to those earned by native Mexican Americans and non-Hispanic whites. In this article we draw on data from the decennial census and American Community Survey to understand why and how this stagnation occurred. We test two competing explanations: a decline in the quality of successive cohorts of Mexican immigrants and a shift in the political economy that increased the number of people lacking full labor rights in the United States while increasing discrimination and exclusion against such people. We present evidence in favor of the latter explanation by showing that observed quality increased rather than decreased and that what happened instead was a systematic decline in the returns to various measures of human capital and a wholesale drop in wages for all immigrants after 2000.


Enhanced tolerance to drought stress in transgenic rice plants overexpressing a small heat-shock protein, sHSP17.7.
Exposure of rice (Oryza sativa L.) seedlings to a high temperature (42 degrees C) for 24 h resulted in a significant increase in tolerance to drought stress. To try to determine the mechanisms of acquisition of tolerance to drought stress by heat shock, the rice small heat-shock protein gene, sHSP17.7, the product of which was shown to act as molecular chaperones in vitro and in vivo in our previous study, was overexpressed in the rice cultivar "Hoshinoyume". Western and Northern blot analyses showed higher expression levels of sHSP17.7 protein in three transgenic lines than in one transgenic line. Drought tolerance was assessed in these transgenic lines and wild-type plants by withholding water for 6 days for evaluation of the ability of plants to continue growth after water-stress treatments. Although no significant difference was found in water potential of seedlings between transgenic lines and wild-type plants at the end of drought treatments, only transgenic seedlings with higher expression levels of sHSP17.7 protein could regrow after rewatering. Similar results were observed in survival rates after treatments with 30% polyethylene glycol (PEG) 3640 for 3 days. These results suggest that overproduction of sHSP17.7 could increase drought tolerance in transgenic rice seedlings.


Long-Term Outcome of Gastric Mild-Moderate Dysplasia: A Real-World Clinical Experience.
The natural course of gastric mild-moderate dysplasia in a country with high incidence of gastric cancer (GC) is relatively unknown. We aimed to determine the long-term cumulative incidence of and risk factors for advanced neoplasia in patients with gastric dysplasia. This was a single-center observational study including all consecutive patients diagnosed with gastric mild-moderate dysplasia between 2000 and 2017. Follow-up data were collected until December 2019. We determined the cumulative incidence of advanced neoplasia and identified risk factors with Cox regression. A total of 3489 consecutive participants were followed for a median of 4.19 years from initial mild-moderate dysplasia diagnosis. The median surveillance interval between index endoscopy and next follow-up endoscopy was 1.08 years, and more than half of patients had at least 3 surveillance gastroscopies. During the study period, the majority of participants did not show disease progression, either with dysplasia not detected (51.4%) or with persistent dysplasia (46.1%). There were 88 (2.9%) patients (5.13 per 1000 patient-years) who progressed to advanced neoplasia within a median of 4.3 years. The annual incidence of advanced neoplasia and GC were 0.43% and 0.26%, respectively, within 5 years of mild-moderate dysplasia diagnosis. Increasing age, male sex, moderate dysplasia, dysplasia detected in fundus or cardia at index endoscopy, and persistent Helicobacter pylori infection during follow-up were independent risk factors for developing advanced neoplasia. Even in a country with high incidence of GC, the majority of patients with gastric mild-moderate dysplasia did not experience disease progression in the long term. Intensified surveillance during the first 5 years after mild-moderate dysplasia detection is suggested.


Special considerations in the management of adult patients with acute leukaemias and myeloid neoplasms in the COVID-19 era: recommendations from a panel of international experts.
The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 is a global public health crisis. Multiple observations indicate poorer post-infection outcomes for patients with cancer than for the general population. Herein, we highlight the challenges in caring for patients with acute leukaemias and myeloid neoplasms amid the COVID-19 pandemic. We summarise key changes related to service allocation, clinical and supportive care, clinical trial participation, and ethical considerations regarding the use of lifesaving measures for these patients. We recognise that these recommendations might be more applicable to high-income countries and might not be generalisable because of regional differences in health-care infrastructure, individual circumstances, and a complex and highly fluid health-care environment. Despite these limitations, we aim to provide a general framework for the care of patients with acute leukaemias and myeloid neoplasms during the COVID-19 pandemic on the basis of recommendations from international experts.


Mitochondrial toxicity of diclofenac and its metabolites via inhibition of oxidative phosphorylation (ATP synthesis) in rat liver mitochondria: Possible role in drug induced liver injury (DILI).
Diclofenac is a widely prescribed NSAID, which by itself and its reactive metabolites (Phase-I and Phase-II) may be involved in serious idiosyncratic hepatotoxicity. Mitochondrial injury is one of the mechanisms of drug induced liver injury (DILI). In the present work, an investigation of the inhibitory effects of diclofenac (Dic) and its phase I [4-hydroxy diclofenac (4'-OH-Dic) and 5-hydroxy diclofenac (5-OH-dic)] and Phase-II [diclofenac acyl glucuronide (DicGluA) and diclofenac glutathione thioester (DicSG)] metabolites, on ATP synthesis in rat liver mitochondria was carried out. A mechanism based inhibition of ATP synthesis is exerted by diclofenac and its metabolites. Phase-I metabolite (4'-OH-Dic) and Phase-II metabolites (DicGluA and DicSG) showed potent inhibition (2-5 fold) of ATP synthesis, where as 5-OH-Dic, one of the Phase-I metabolite, was a less potent inhibitor as compared to Dic. The calculated kinetic constants of mechanism based inhibition of ATP synthesis by Dic showed maximal rate of inactivation (Kinact) of 2.64 ± 0.15 min(-1) and half maximal rate of inactivation (KI) of 7.69 ± 2.48 μM with Kinact/KI ratio of 0.343 min(-1) μM(-1). Co-incubation of mitochondria with Dic and reduced GSH exhibited a protective effect on Dic mediated inhibition of ATP synthesis. Our data from this study strongly indicate that Dic as well as its metabolites could be involved in the hepato-toxic action through inhibition of ATP synthesis.


Prostaglandin E1 inhibits acute cell dehydration thirst.
Intraperitoneally injected PGE1 (100 micrograms/Kg) inhibits specifically the drinking induced by both IP and IV 2 M NaCl (6 ml/Kg) and compound 48/80 (100 micrograms/Kg, IP). Probenecid (150 mg/Kg, IP) which is not a dipsogen, has no effect on the PGE1 induced inhibition of acute cell dehydration thirst. It is concluded the PGE1 acts upon the peripheral mast cells, inhibiting their secretion and thus affecting the water intake associated with the activation of these cells either by hypertonicity or specific stimulants of amine release. These results raise the possibility that endogenous prostaglandins might be involved in the modulation of some of the signals which convey to the brain information on the tonicity of the body fluids.


Grape seed and skin extracts inhibit platelet function and release of reactive oxygen intermediates.
Red wine and purple grape juice contain polymeric flavonoids with antioxidant properties believed to be protective against cardiovascular events but the alcohol and sugar content of these beverages has curtailed their medicinal use. Acute cardiac events are also associated with enhanced inflammation and thrombosis. In this study, the extracts from grape skins or seeds were examined for their anti-inflammatory properties and effect on platelet release of reactive oxygen intermediates. Incubation of platelets with seed or skin extract led to a decrease in platelet aggregation from 68.8+/-19.8% to 45+/-3.6% for seeds and to 27+/-7.2% for skin, respectively (P<0.05). Platelet incubation with grape skin or seed extracts led to a marked decrease in superoxide release from 73+/-6.2 to 2+/-3.4 for grape seeds and to 0.33+/-0.57 for grape skin (chemilum. units; P<0.05) as well as a significant increase in radical-scavenging activity, decrease in reactive oxygen species release by confocal microscopy, and enhanced platelet NO was measured using an NO-sensitive microelectrode. These effects were dose dependent for both grape extracts. Coincubation with seeds and skins led to additive inhibition of platelet aggregation, enhanced NO release, and prevented superoxide production. Incubation with seed or skin extracts led to an immediate attenuation of release of the inflammatory mediator, soluble CD40 ligand. Thus, the extracts from purple grape skins and seeds inhibit platelet function and platelet-dependent inflammatory responses at pharmacologically relevant concentrations. These findings suggest potentially beneficial platelet-dependent antithrombotic and anti-inflammatory properties of purple grape-derived flavonoids.


Advancing cartilage tissue engineering: the application of stem cell technology.
The treatment of cartilage pathology and trauma face the challenges of poor regenerative potential and inferior repair. Nevertheless, recent advances in tissue engineering indicate that adult stem cells could provide a source of chondrocytes for tissue engineering that the isolation of mature chondrocytes has failed to achieve. Various adjuncts to their propagation and differentiation have been explored, such as biomaterials, bioreactors and growth hormones. To date, all tissue engineered cartilage has been significantly mechanically inferior to its natural counterparts and further problems in vivo relate to poor integration and deterioration of tissue quality over time. However, adult stem cells--with their high rate of proliferation and ease of isolation--are expected to greatly further the development and usefulness of tissue engineered cartilage.


Numerical simulation data of building integrated solar thermal collectors under diverse conditions.
This dataset presents the thermal performance of building-integrated flat solar collectors with a uniform and multiple riser structure. The input data of the numerical model were obtained with the use of the PVGIS tool. Solar radiation and ambient temperature values at slopes 0°, 45°, and 90° were extracted and used as boundary conditions. Numerical calculations were carried using Finite Element (FE) analysis. Three-dimensional transient models were developed to calculate the investigated configurations' thermal performance based on the environmental temperature, the solar radiation, and the inclination angle. The numerical model was validated with the use of an experimental data set showing a good agreement between the two models with RMSE of 5%. Data of hourly heat flux through the building masonry with the building-integrated solar collector and the average fluid temperature of each system is presented.


Cannabinoid Receptor Type 2 Agonist Attenuates Acute Neurogenic Pulmonary Edema by Preventing Neutrophil Migration after Subarachnoid Hemorrhage in Rats.
We evaluated whether JWH133, a selective cannabinoid type 2 receptor (CB2R) agonist, prevented neurogenic pulmonary edema (NPE) after subarachnoid hemorrhage (SAH) by attenuating inflammation. Adult male rats were assigned to six groups: sham-operated, SAH with vehicle, SAH with JWH133 (0.3, 1.0, or 3.0 mg/kg) treatment 1 h after surgery, and SAH with JWH133 (1.0 mg/kg) at 1 h with a selective CB2R antagonist, SR144528 (3.0 mg/kg). The perforation model of SAH was performed and pulmonary wet-to-dry weight ratio was evaluated 24 and 72 h after surgery. Western blot analyses and immunohistochemistry were evaluated 24 h after surgery. JWH133 (1.0 mg/kg) significantly and most strongly improved lung edema 24 h after SAH. SR144528 administration significantly reversed the effects of JWH133 (1.0 mg/kg). SAH-induced increasing levels of myeloperoxidase (MPO) and decreasing levels of a tight junction (TJ) protein, junctional adhesion molecule (JAM)-A, were ameliorated by JWH133 (1.0 mg/kg) administration 24 h after SAH. Immunohistochemical assessment also confirmed substantial leukocyte infiltration in the outside of vessels in SAH, which were attenuated by JWH133 (1.0 mg/kg) injection. CB2R agonist ameliorated lung permeability by inhibiting leukocyte trafficking and protecting tight junction proteins in the lung of NPE after SAH.


Fatigue behavior of Ti-6Al-4V alloy in saline solution with the surface modified at a micro- and nanoscale by chemical treatment.
This work evaluated the influence of the surface modification using acid etching combined with alkaline treatment on the fatigue strength of Ti-6Al-4V ELI alloy. The topography developed by chemical surface treatments (CST) was examined by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Increased roughness and effective surface area were investigated and compared with the Ti-6Al-4V samples without modification. Surface composition was analyzed by energy dispersive X-ray spectroscopy (EDS). Axial fatigue resistance of polished and modified surfaces was determined by stepwise load increase tests and staircase test method. Light microscopy and SEM were employed to examine the fracture surface of the tested specimens. According to the results, a similar fatigue behavior was found and a negligible difference in the fatigue crack nucleation was observed for the Ti-6Al-4V with CST in comparison to the samples without treatment.


MiRNA-mRNA integrative analysis reveals epigenetically regulated and prognostic miR-103a with a role in migration and invasion of carboplatin-resistant ovarian cancer cells that acquired mesenchymal-like phenotype.
DNA methylation, histone modifications, and miRNAs affect ovarian cancer (OC) progression and therapy response. Identification of epigenetically downregulated miRNAs in drug-resistant OC cell lines with a possible role in drug resistance and/or drug-induced mesenchymal-like phenotype. MiRNA profiling was performed on parental and carboplatin-resistant OC cells, MES-OV and MES-OV CBP. RT-qPCR validation, epigenetic modulation and other CBP-resistant OC cell lines were used to select miRNAs of interest. The integration of miRNA-predicted target genes and differentially expressed genes (DEGs), pathway and functional analysis were used for forecasting their biological role. Data mining was performed to determine their possible prognostic and predictive values. MiRNA profiling revealed 48 downregulated miRNAs in OC cells whose drug sensitivity and metastatic potential were impacted by epigenetic modulators. Of the fourteen selected, nine were validated as changed, and seven of these restored their expression upon treatment with epigenetic inhibitors. Only three had similar expression patterns in other OC cell lines. MiRNA-mRNA integrative analysis resulted in 56 target DEGs. Pathway analysis revealed that these genes are involved in cell adhesion, migration, and invasion. The functional analysis confirmed the role of miR-103a-3p, miR-17-5p and miR-107 in cell invasion, while data mining showed their prognostic and predictive values. Only miR-103a-3p was epigenetically regulated at the constitutive level. High throughput miRNA and cDNA profiling coupled with pathway analysis and data mining delivered evidence for miRNAs which can be epigenetically regulated in drug-resistant, mesenchymal-like OC cells as possible markers to combat therapy-induced short overall survival and tumor metastatic potential.


The demographic, social, and conceptual contexts of aging and vision loss.
Age-related changes to the eye and functional implications of vision loss are well-known. However, these changes occur in the context of broad demographic and social changes. The structural demographic changes in the United States, the social context of vision and aging, and the conceptual model of disablement are reviewed. The International Classification of Impairments, Disabilities, and Handicaps (ICIDH) was published by the World Health Organization (WHO) in 1980, and may serve as a model for our better understanding of how the structural demographic changes, the social context of vision and aging, and the conceptual model of disablement are affecting public policy in eye and vision care. At present, there is no comprehensive national policy that addresses the eye and visual rehabilitation of older persons who have lost vision. Defining a conceptual context may help us develop public policy to meet the demands of the aforementioned social and demographic changes.


Human prefrontal cortex: evolution, development, and pathology.
The prefrontal cortex is critical to many cognitive abilities that are considered particularly human, and forms a large part of a neural system crucial for normal socio-emotional and executive functioning in humans and other primates. In this chapter, we survey the literature regarding prefrontal development and pathology in humans as well as comparative studies of the region in humans and closely related primate species. The prefrontal cortex matures later in development than more caudal regions, and some of its neuronal subpopulations exhibit more complex dendritic arborizations. Comparative work suggests that the human prefrontal cortex differs from that of closely related primate species less in relative size than it does in organization. Specific reorganizational events in neural circuitry may have taken place either as a consequence of adjusting to increases in size or as adaptive responses to specific selection pressures. Living in complex environments has been recognized as a considerable factor in the evolution of primate cognition. Normal frontal lobe development and function are also compromised in several neurological and psychiatric disorders. A phylogenetically recent reorganization of frontal cortical circuitry may have been critical to the emergence of human-specific executive and social-emotional functions, and developmental pathology in these same systems underlies many psychiatric and neurological disorders, including autism and schizophrenia.


Teichomycins, new antibiotics from Actinoplanes teichomyceticus Nov. Sp. I. Description of the producer strain, fermentation studies and biological properties.
A soil isolate of Actinoplanes that produces the chemically unrelated new antibiotics teichomycins A1 and A2 has been proposed as a new species named Actinoplanes teichomyceticus nov. sp. (ATCC 31121). Studies of medium and fermentation conditions indicated that the highest antibiotic titers, ca 900 u/ml, are obtained in a medium containing 1% (w/v) glucose, 1% cotton seed meal, 1% malt extract, and 0.4% yeast extract. Both teichomycin A1 and teichomycin A2 are highly active against gram-positive bacteria. Teichomycin A1 shows some activity against gram-negative bacteria. Both antibiotics cured mice experimentally infected with sensitive bacteria and showed low acute toxicity. Of the two antibiotics teichomycin A2 is the more active.


Three-dimensional phase-contrast magnetic resonance angiography: a useful clinical adjunct to gadolinium-enhanced three-dimensional renal magnetic resonance angiography?
To assess the value of three-dimensional (3D) phase-contrast (PC) magnetic resonance angiography (MRA) after gadolinium (Gd)-enhanced 3D MRA for renal artery imaging. Twenty-one patients with suspected renal artery hypertension were reviewed. All studies included Gd-enhanced 3D MRA and 3D PC MRA. Blinded interpretation of the images was performed for each technique independently and in combination. Conventional X-ray angiography was used for diagnostic correlation when available. Renal artery stenosis was present in 7 (16.3%) of 43 renal arteries, confirmed by X-ray angiography. MRA images demonstrated 100% sensitivity and 74% specificity for Gd-enhanced 3D MRA and 100% sensitivity and 94% specificity for 3D PC MRA. All vessels were diagnosed correctly when both image sets were viewed. 3D PC MRA can improve the specificity of renal MRA by decreasing the number of false-positive Gd-enhanced 3D MRA interpretations.


Acute oral selenium intoxication with ten times the lethal dose resulting in deep gastric ulcer.
A 48-year-old woman presented after taking 2000 mg of selenium dioxide, corresponding to 10 times the experimental lethal dose in animals. She presented with mildly altered consciousness and hematemesis. Endoscopy revealed mucosal damage throughout the oral cavity, esophagus, and stomach. There was no evidence of perforation. After intubation and gastric lavage, hemodialysis was performed. The patient was discharged uneventfully on the 16(th) day. This case highlights a very rare acute selenium intoxication. Serum and urinary selenium levels and serum glutathione peroxidase activities during the patient's course were followed, as well as the mucosal corrosive damage caused by the selenium.


Development of a Device to Obtain Platelet-Rich Plasma (PRP).
Objective To present an innovative device that applies the double centrifugation method to obtain platelet-rich plasma (PRP), assessing whether there was an effective increase in the concentration of platelets. Method Ten volunteers underwent blood collection. The samples were separated in 20 ml syringes, sealed and subjected to the double centrifugation protocol at 1,100 revolutions per minute (rpm) for 15 minutes, resulting in the separation of red blood cells, plasma with platelets, and leukocytes. Then, 10 ml syringes were added to remove 9 ml, respecting the "buffy coat" parameter, collecting 8 ml above and 1 ml below for the second centrifugation and transferring again to the 20 ml syringe. The plasma was again centrifuged at 1,550 rpm for 10 minutes; as a result, it was divided into two parts: at the top, consisting of low platelet plasma (LPP), and at the bottom, by the platelet button. Part of the LPP was discarded, leaving only 3 ml with the platelet button. The cells were then counted. Results This innovative device was able to increase the concentration of platelets by almost three times compared with the baseline. In addition, the preparation time for the PRP was adequate, lasting only 35 to 40 minutes. Conclusions Platelet-rich plasma was successfully obtained by the double centrifuge protocol, allowing its clinical use. In addition, obtaining through the presented device promotes greater applicability in the preparation of PRP in specific centers, furthermore, being a quick and economical way to obtain PRP.


Carbon-13 depletion in an estuarine bivalve: Detection of marine and terrestrial food sources.
Stable carbon isotope analysis was used to define the food sources of bivalve Chione (Austrovenus) stutchburyi in the Avon-Heathcote Estuary, Christchurch, New Zealand. δ13C values of C. stutchburyi tissue were significantly different (from -16.7‰ to -23.5‰ relative to the PDB standard) at five locations separated by less than 4 km but subject to different hydrological regimes. This is related to differences in the isotopic composition of the suspended particulate matter of the inflowing water. C. stutchburyi is shown to utilise carbon of terrestrial and marine origin depending upon its position within the estuary and local hydrology.


Preparation of 3-epi-ecdysone and 3-epi-20-hydroxyecdysone.
3-Dehydro-ecdysone and 3-dehydro-20-hydroxyecdysone were prepared and characterized. Reduction of these compounds with NaBH4 gave 3-epi-ecdysone and 3-epi-20-hydroxyecdysone, which were characterized fully by mass and p.m.r. spectrometry as well as by derivative formation.


Self-Report Measures of Hand Pain Intensity: Current Evidence and Recommendations.
Successful management of problems related to the hands and upper extremities begins with a comprehensive assessment of the pain experience and related factors. Pain intensity is the domain most commonly assessed, and pain relief is often the primary goal of treatment. Because pain is a private and subjective experience, self-report is considered the gold standard of pain measurement. This article describes and discusses the strengths and weaknesses of the most commonly used self-report scales used to measure hand pain intensity, and gives recommendations to help clinicians select from among the various options for measuring the intensity of hand pain.


Spatial Distribution of Epidemiological Cases of Dengue Fever in Suriname, 2001-2012.
To characterize the frequency, incidence and severity of dengue fever in Suriname and to detect historic clusters of disease by integrating epidemiological data into a spatial visualization platform. The frequency, incidence and severity of all reported dengue fever (DF) and dengue haemorrhagic fever (DHF) cases in Suriname from 2001 to 2012 were calculated and stratified by demographic factors. Using a geographic information systems (GIS) platform, we visualized the distribution of DF cases and used Moran's I to detect autocorrelation. Furthermore, a retrospective spatial Poisson probability model was used to identify local clusters of DF within Suriname. Local clusters were divided into neighborhoods and individual DF cases were mapped to the street level. In Suriname, cases of DF emerge in cyclical patterns (three to five years) with seasonal peaks following the short and the long rainy season. Chi-square analysis indicated a statistically significant (p < 0.05) difference between age group, ethnicity and district and the onset of DHF. The spatial analysis detected spatial autocorrelation and four statistically significant (p < 0.05) clusters were identified in the two most populated districts of Paramaribo and Wanica. In Suriname, identification of demographic and environmental risk factors that contribute to the development of DHF is essential to determine how preventive action can be more effectively allocated. The integration of epidemiological data into a GIS platform allowed for the identification of historic epidemiological clusters of dengue which will be used to guide environmental health studies in Suriname.


Basal testosterone concentrations after the application of a slow-release GnRH agonist implant are associated with a loss of response to buserelin, a short-term GnRH agonist, in the tom cat.
Slow-release GnRH agonist implants are considered an effective, reversible alternative to surgical castration in male tom cats. Individual differences exist regarding the onset of efficacy and might be delayed in some animals. Single measurements of testosterone (T) might result in basal concentrations also in intact male cats. Consequently, GnRH stimulation tests are performed to measure T increase in intact animals and to differentiate castrated from intact male cats. In this study, five tom cats were treated with a 4.7-mg deslorelin implant and GnRH stimulation tests using buserelin were performed before treatment and at 4-week intervals afterward until Week 20. After the last test in Week 20 all animals were castrated. Four of five animals had basal T after 4 weeks and-in contrast to pretreatment-application of buserelin did not result in any further T increase. In one animal, T was low after implant insertion, but not basal; however, a GnRH stimulation test induced a slight increase of T in Week 8 and 16 only and no response in Weeks 4, 12, and 20. Testicular volume was significantly decreased and penile spines disappeared in all cats. Testicular histology showed mixed atrophy, but also fully elongated spermatids in three of five male cats making infertility questionable. Because of the loss of the stimulatory effect of short-term GnRH application (buserelin), it can be assumed that long-term GnRH agonists also act by some mechanisms of downregulation of pituitary GnRH receptors in the tom cat.


Correction: Psychometric evaluation of the Chinese version of the fear of intimacy with helping professionals scale.
[This corrects the article DOI: 10.1371/journal.pone.0196774.].


Twin reversed arterial perfusion sequence in conjoined, acardiac, acephalic twins associated with a normal triplet. A case report.
Twin reversed arterial perfusion (TRAP) sequence and development of an acardiac monster is a rare event. Even more rare are conjoined acardiac, acephalic twins complicating a triplet pregnancy with TRAP sequence. The mortality for the acardius is 100%, and morbidity for the normal, pump fetus is 50%. The morbidity of the pump twin or triplet is attributed mostly to in utero congestive heart failure. A 24-year-old woman, gravida 1, para 0, at 35 weeks' intrauterine pregnancy, gave birth via low transverse cesarean section to a normal female and a pair of conjoined, acardiac, acephalic, pelvipagus twins. The diagnosis of acardius in multiple gestation pregnancy, with no fetal heart tone on ultrasound, must be ruled out in every case so that proper counseling, management and avoidance of complications in these patients can be achieved.


Prediction of extravasation in pelvic fracture using coagulation biomarkers.
To evaluate the usefulness of coagulation biomarkers, which are easy and quick to analyze in emergency settings, for prediction of arterial extravasation due to pelvic fracture. The medical records of pelvic fracture patients transferred to the emergency department of Gunma University Hospital between December 2009 and May 2015 were reviewed. Patients were divided into two groups, those with (Extra(+)) and without (Extra(-)) arterial extravasation on enhanced CT or angiography. Levels of fibrin degradation products (FDP), D-dimer, fibrinogen, the ratio of FDP to fibrinogen, the ratio of D-dimer to fibrinogen, systolic blood pressure, heart rate, the Glasgow Coma Scale, pH, base excess, hemoglobin and lactate levels, the pattern of pelvic injury, and injury severity score were measured at hospital admission, and compared between the two groups. Parameters with a significant difference between the two groups were used to construct receiver operating characteristic (ROC) curves. The study included 29 patients with pelvic fracture. FDP, D-dimer, the ratio of FDP to fibrinogen and the ratio of D-dimer to fibrinogen were the most useful parameters for predicting arterial extravasation due to pelvic fracture. FDP, D-dimer, the ratio of FDP to fibrinogen, the ratio of D-dimer to fibrinogen, and hemoglobin and lactate levels were significantly higher in the Extra(+) group than in the Extra(-) group (FDP, 354.8μg/mL [median] versus 96.6μg/mL; D-dimer, 122.3μg/mL versus 42.1μg/mL; the ratio of FDP to fibrinogen, 3.39 versus 0.42; the ratio of D-dimer to fibrinogen, 1.14 versus 0.18; hemoglobin, 10.5g/dL versus 13.5g/dL; lactate, 3.5mmol/L versus 1.7mmol/L). The area under the ROC curves for FDP, D-dimer, the ratio of FDP to fibrinogen, the ratio of D-dimer to fibrinogen, hemoglobin and lactate levels were 0.900, 0.882, 0.918, 0.900, 0.815 and 0.765, respectively. Coagulation biomarkers, and hemoglobin and lactate levels could be useful to predict the existence of arterial extravasation due to pelvic fracture. The ratio of FDP to fibrinogen and the ratio of D-dimer to fibrinogen were the most accurate markers. Coagulation biomarkers may enable more rapid and specific treatment for pelvic fracture.


[Ethical-legal aspects of the civil responsibility of physicians in professional practice].
The ethical-juridical concepts related to the civil responsibility of medical activity in liberal practice are brought up to date. To this end, the arguments which guide the shaping up of the contractual relationship between the physician and the client are analysed, as also are the foundations on which the notion of guilt--an essential component of civil responsibility, whether relating to technical acts of to those within the field of medical humanism--are grounded. The answers presented for the solution of this question by European juridical systems are given.


GriddingMachine, a database and software for Earth system modeling at global and regional scales.
Land and Earth system modeling is moving towards more explicit biophysical representations, requiring increasing variety of datasets for initialization and benchmarking. However, researchers often have difficulties in identifying and integrating non-standardized datasets from various sources. We aim towards a standardized database and one-stop distribution method of global datasets. Here, we present the GriddingMachine as (1) a database of global-scale datasets commonly used to parameterize or benchmark the models, from plant traits to vegetation indices and geophysical information and (2) a cross-platform open source software to download and request a subset of datasets with only a few lines of code. The GriddingMachine datasets can be accessed either manually through traditional HTTP, or automatically using modern programming languages including Julia, Matlab, Octave, Python, and R. The GriddingMachine collections can be used for any land and Earth modeling framework and ecological research at the regional and global scales, and the number of datasets will continue to grow to meet the increasing needs of research communities.


Morphological changes in trichostrongylid eggs after treatment with fenbendazole.
The influence of daily doses of 0.05-0.1 mg fenbendazole/kg body weight on egg development was tested in twenty-seven lambs artificially infected with Haemonchus contortus plus Trichostrongylus colubriformis or Ostertagia circumcincta, as well as in two additional sheep naturally infected with Nematodirus spp. Atypical eggs were detected before a reduction in the number of eggs. Atypical eggs had blastomeres of different sizes and shapes; knot-like, crater-like or bubble-like. In isolated cases eggs with atypical first larvae were recognizable. Morphologically changes eggs occurred in the reproductive organs of female O. circumcincta worms. None, or only a very small number of third stage larvae, could be cultured from the faeces of treated sheep.


High specific activity tritium-labeled N-(2-methoxybenzyl)-2,5-dimethoxy-4-iodophenethylamine (INBMeO): a high-affinity 5-HT2A receptor-selective agonist radioligand.
The title compound ([3H]INBMeO) was prepared by an O,O-dimethylation reaction of a t-BOC protected diphenolic precursor using no carrier added tritiated iodomethane in DMF with K(2)CO(3). Removal of the t-BOC protecting group and purification by HPLC afforded an overall yield of 43%, with a radiochemical purity of 99% and specific activity of 164Ci/mmol. The new radioligand was suitable for labeling human 5-HT(2A) receptors in two heterologous cell lines and had about 20-fold higher affinity than [(3)H]ketanserin.


Progress in predicting inter-residue contacts of proteins with neural networks and correlated mutations.
This article presents recent progress in predicting inter-residue contacts of proteins with a neural network-based method. Improvement over the results obtained at the previous CASP3 competition is attained by using as input to the network a complex code, which includes evolutionary information, sequence conservation, correlated mutations, and predicted secondary structures. The predictor was trained and cross-validated on a data set comprising the contact maps of 173 non-homologous proteins as computed from their well-resolved three-dimensional structures. The method could assign protein contacts with an average accuracy of 0.21 and with an improvement over a random predictor of a factor greater than 6, which is higher than that previously obtained with methods only based either on neural networks or on correlated mutations. Although far from being ideal, these scores are the highest reported so far for predicting protein contact maps. On 29 targets automatically predicted by the server (CORNET) the average accuracy is 0.14. The predictor is poorly performing on all alpha proteins, not represented in the training set. On all beta and mixed proteins (22 targets) the average accuracy is 0.16. This set comprises proteins of different complexity and different chain length, suggesting that the predictor is capable of generalization over a broad number of features.


Cell polarity in plants: when two do the same, it is not the same....
In unicellular and multicellular organisms, cell polarity is essential for a wide range of biological processes. An important feature of cell polarity is the asymmetric distribution of proteins in or at the plasma membrane. In plants such polar localized proteins play various specific roles ranging from organizing cell morphogenesis, asymmetric cell division, pathogen defense, nutrient transport and establishment of hormone gradients for developmental patterning. Moreover, flexible respecification of cell polarities enables plants to adjust their physiology and development to environmental changes. Having evolved multicellularity independently and lacking major cell polarity mechanisms of animal cells, plants came up with alternative solutions to generate and respecify cell polarity as well as to regulate polar domains at the plasma membrane.


[Risk factors of schistosomiasis transmission in marshland and lake regions in midstream of Yangtze River].
To study the risk factors of schistosomiasis related to household economic condition and individual behavior in marshland and lake regions, so as to provide evidences for schistosomiasis control. Six villages were sampled with the stratified cluster sampling method, 2 339 villagers from 1 247 households were surveyed by a questionnaire and meanwhile their sera were assayed for schistosomiasis by IHA. The Logistic regression was used to analyze the relationship between the results of serological examinations and risk factors. The Logistic regression model fitted well (R2 = 0.598 4) and it indicated that there existed a regressive relationship between the antibody positive rate and the endemic situation of village, family economic status, age, education level and infection history of schistosomiasis. Suitable measures should be made in according to the local economic situation, endemic type and population to control the transmission of schistosomiasis effectively.


Ubiquinone binding protein used for determination of coenzyme Q.
The conventional method of assaying for the ubiquinone (CoQ) content of biological samples is to partition CoQ into an organic phase and separate it from contaminants by high-performance liquid chromatography (HPLC). HPLC is an accurate method of quantifying CoQ content but is not ideal for routine clinical analyses. This paper describes the development of a rapid method for assaying the CoQ content of biological samples based on the binding of CoQ to a CoQ binding peptide. The 14-amino acid binding peptide was chemically synthesized, and conditions for immobilizing the peptide on microfuge tubes were established. CoQ could be selectively bound to the immobilized peptide, eluted, and determined spectrophotometrically. Limits of detection for the method were 0.25 to 5 nmol CoQ. To test biological samples, CoQ was isolated from cultures of Saccharomyces cerevisiae grown in oleic acid medium. The recovery of CoQ samples using the binding assay ranged from 99 to 102% of the values obtained with HPLC. The assay described here provides an inexpensive, rapid method for determining the CoQ content of large numbers of biological samples in a variety of laboratory settings.


A new approach to the classification of human leukaemias: measurement of the relative abundance of a specific RNA sequence by means of molecular hybridisation.
A recombinant plasmid library representing polyadenylated RNAs in the leucocytes of a Ph1-positive chronic granulocytic leukaemia (CGL) has been constructed. One recombinant (designated pCG14) isolated from this library contains a DNA sequence complementary to a small polyadenylated RNA that is abundant in RNA from CGL leucocytes. The relative concentrations of pCG14 RNA in the RNAs from a variety of normal and leukaemic leucocytes and human haemopoietic cell lines have been measured with a molecular hybridisation assay. This has shown that pCG14 RNA is 10 to 50 times more abundant in RNA from CGL leucocytes than in the RNAs from these other cells. The data indicate that the occurrence of pCG14 RNA in high abundance is sufficiently characteristic of a CGL leucocyte population to distinguish it from other populations of leucocytes. They suggest that the measurement of the concentrations of specific RNA species in leucocyte RNA by means of molecular hybridisation with cloned complementary DNAs may provide additional markers for the objective classification of human leukaemias which could be particularly useful since the method exploits a criterion different from any currently in use.


Molecular systematics of the Amphisphaeriaceae based on cladistic analyses of partial LSU rDNA gene sequences.
The Amphisphaeriaceae is an important family of ascomycetes within the Xylariales. There has been, however, disagreement regarding the taxonomic placement of many genera within this family and whether it should be confined to ascomycetes producing Pestalotiopsis-like anamorphs. In this study, phylogenetic relationships among members of the Amphisphaeriaceae are investigated using partial sequences of the 28S rDNA. Molecular data provided further evidence to support the association of several coelomycetous genera with the ascomycetous Amphisphaeriaceae. Phylogenetic analyses also show that all ascomycetous genera possessing Pestalotiopsis-like anamorphs are monophyletic and confirm the anamorphic-teleomorphic connections of some. There is, however, insufficient evidence to support the restriction of Amphisphaeriaceae to genera, which produce Pestalotiopsis-like anamorphs, because the phylogenetic placement of Amphisphaeria umbrina is not fully resolved and its affinities with other members received low bootstrap support. The results also indicate that Iodosphaeria and Arecophila should be excluded from the Amphisphaeriaceae. The placement of Lanceispora in the Amphisphaeriaceae is doubtful. A broad concept of the family Amphisphaeriaceae is advocated until further data are available.


Characteristics and outcomes of patients diagnosed with norovirus gastroenteritis after allogeneic hematopoietic stem cell transplantation based on immunochromatography.
Norovirus gastroenteritis (NV-GE) is a highly transmittable disease that can lead to fatal outcomes in vulnerable populations including patients after hematopoietic stem cell transplantation (HSCT). Prompt detection of NV is therefore important for HSCT recipients. Immunochromatography (IC) can be used to easily and rapidly diagnose NV-GE by detecting NV antigens. In this study, we examined 642 stool specimens in patients who developed diarrhea after allogeneic HSCT between January 2007 and June 2011. NV was detected in 10 of 350 (2.9 %) HSCT recipients. The median onset of symptoms was 36 days (range 3-93) after HSCT. The median duration of symptoms was 42 days (3-135). A second or subsequent allogeneic HSCT was associated with a higher incidence of NV-GE (P = 0.034). Of four patients who underwent colonoscopy, two showed intestinal graft-versus-host disease (GVHD) histopathology, whereas the other two showed no evidence of GVHD, and thus no need for intensified immunosuppression. None of the patients died of NV-GE. In conclusion, IC may be useful in the differential diagnosis of diarrhea after allogeneic HSCT, and could enable the appropriate adjustment of immunosuppressive drugs and prompt preventive measures.


Racial and Ethnic Inequities in Health: Examining the Contributions of the American Journal of Epidemiology to Advancing the Science.
The perverseness of racial and ethnic inequities in the United States continues to implore the investigation of their causes. While there have been improvements in the health of the US population, these improvements have not been equally distributed. To commemorate the 100th anniversary of the American Journal of Epidemiology, in this commentary, we aim to highlight the Journal's contributions to: 1) the definition and use of race and ethnicity in research, and 2) understanding racial and ethnic inequities, both empirically and methodologically, over the past decade. We commend the Journal for its contributions and for spearheading many of the challenges related to measuring and interpreting racial and ethnic data for the past 20 years. We identify 3 additional areas in which the Journal could make further impact to address racial and ethnic inequities: 1) devote a section in every issue of the Journal to scientific papers that make substantive epidemiologic or methodological contributions to racial and ethnic inequities in health; 2) update the Journal's guidelines for authors to include justifying the use of race and ethnicity; and 3) diversify the field of epidemiology by bringing a new cadre of scholars from minoritized racial and ethnic groups who represent the most affected communities into the research process.


Mice lacking global Stap1 expression do not manifest hypercholesterolemia.
Autosomal dominant familial hypercholesterolemia (ADH; MIM#143890) is one of the most common monogenic disorders characterized by elevated circulatory LDL cholesterol. Initial studies in humans with ADH identified a potential relationship with variants of the gene encoding signal transducing adaptor family member protein 1 (STAP1; MIM#604298). However, subsequent studies have been contradictory. In this study, mice lacking global Stap1 expression (Stap1-/-) were characterized under standard chow and a 42% kcal western diet (WD). Mice were studied for changes in different metabolic parameters before and after a 16-week WD regime. Growth curves, body fats, circulatory lipids, parameters of glucose homeostasis, and liver architecture were studied for comparisons. Surprisingly, Stap1-/- mice fed the 16-week WD demonstrated no marked differences in any of the metabolic parameters compared to Stap1+/+ mice. Furthermore, hepatic architecture and cholesterol content in FPLC-isolated lipoprotein fractions also remained comparable to wild-type mice. These results strongly suggest that STAP1 does not alter lipid levels, that a western diet did not exacerbate a lipid disorder in Stap1 deficient mice and support the contention that it is not causative for hyperlipidemia in ADH patients. These results support other published studies also questioning the role of this locus in human hypercholesterolemia.


Biomechanical properties of oesophagus wall under loading.
In this investigation, firstly, the biomechanical properties of different parts of oesophagus were determined. Oesophagus stress and strain are the greatest in the cervical part for all age groups. The human oesophagus deforms unevenly, depending on the direction of load in relation to the organ's axis, it exhibits anisotropical behaviour. With the age the values of mechanical parameters of the oesophagus wall reduce, in particular beginning from 45 years of age, but the modulus of elasticity increases. Biomechanical properties of the oesophagus depend on the architecture of its structure. By loading the organ in the circumferential direction, microfibrilae rupture and deformation of the muscular fibres occurs. With increase of load, collagenous fibres straighten and microruptures in collagenous fibrilae occur. With stretching of oesophagus longitudinally, collagenous fibres partially preserve their wavy and helical configuration. Therefore, higher resistance of the oesophageal wall occurs in the longitudinal direction.


Arsenic-induced neurotoxicity: a mechanistic appraisal.
Arsenic is a metalloid found in groundwater as a byproduct of soil/rock erosion and industrial and agricultural processes. This xenobiotic elicits its toxicity through different mechanisms, and it has been identified as a toxicant that affects virtually every organ or tissue in the body. In the central nervous system, exposure to arsenic can induce cognitive dysfunction. Furthermore, iAs has been linked to several neurological disorders, including neurodevelopmental alterations, and is considered a risk factor for neurodegenerative disorders. However, the exact mechanisms involved are still unclear. In this review, we aim to appraise the neurotoxic effects of arsenic and the molecular mechanisms involved. First, we discuss the epidemiological studies reporting on the effects of arsenic in intellectual and cognitive function during development as well as studies showing the correlation between arsenic exposure and altered cognition and mental health in adults. The neurotoxic effects of arsenic and the potential mechanisms associated with neurodegeneration are also reviewed including data from experimental models supporting epidemiological evidence of arsenic as a neurotoxicant. Next, we focused on recent literature regarding arsenic metabolism and the molecular mechanisms that begin to explain how arsenic damages the central nervous system including, oxidative stress, energy failure and mitochondrial dysfunction, epigenetics, alterations in neurotransmitter homeostasis and synaptic transmission, cell death pathways, and inflammation. Outlining the specific mechanisms by which arsenic alters the cell function is key to understand the neurotoxic effects that convey cognitive dysfunction, neurodevelopmental alterations, and neurodegenerative disorders.


Incident arthritis in relation to excess weight.
This article reports incidence rates of arthritis, based on data for people aged 40 or older who were followed over six years. The association between excess weight and arthritis, controlled for possible confounders, is also studied. Data are from the household components of cycle 1.1 of Statistics Canada's Canadian Community Health Survey (2000/01) and from the first four cycles of the National Population Health Survey (1994/95 to 2000/01). The prevalence of arthritis in 2000/01 was estimated using cross-sectional data; 1994/95-to-2000/01 incidence density is based on longitudinal data. Logistic regression was used to study the association between excess weight and arthritis (respondent-reported, doctor-diagnosed), while controlling for age, household income, smoking, number of physician consultations, strenuous daily activity, and other factors. In 2000/01, 19% of men and 31% of women aged 40 or older reported having been diagnosed with arthritis. Incidence rates of arthritis were 31 and 48 cases per 1,000 person-years for men and women, respectively. For both sexes, the odds ratio for obesity (based on self-reported height and weight) in association with subsequent arthritis was significantly elevated, at 1.6.