[Reconsidering children's dreams. A critical review of methods and results in developmental dream research from Freud to contemporary works].
Examining children's dream development is a significant challenge for researchers. Results from studies on children's dreaming may enlighten us on the nature and role of dreaming as well as broaden our knowledge of consciousness and cognitive development. This review summarizes the main questions and historical progress in developmental dream research, with the aim of shedding light on the advantages, disadvantages and effects of different settings and methods on research outcomes. A typical example would be the dreams of 3 to 5 year-olds: they are simple and static, with a relative absence of emotions and active self participation according to laboratory studies; studies using different methodology however found them to be vivid, rich in emotions, with the self as an active participant. Questions about the validity of different methods arise, and are considered within this review. Given that methodological differences can result in highly divergent outcomes, it is strongly recommended for future research to select methodology and treat results more carefully.


'Goose bumps' as presenting feature of intraventricular glioblastoma multiforme.
'Goose-bumps' seizures are rare manifestations of epilepsy. They are rarely reported by patients and can be easily dismissed by clinicians. Clinically, it carries some diagnostic localising value especially with unilateral onset. In this report, we present a case of intraventricular glioblastoma multiforme with ipsilateral goose bumps and review the literature.


Anatomy of the cranial nerves in the basal cisterns. A radiologic post-mortem investigation.
A post-mortem radiologic investigation of the basal cisterns has been made with special regard to the cranial nerves. The cisterns were removed in one piece together with the adjacent brain structures and the skull base. The anatomy of the cranial nerves as seen at cisternography and the frequency of their identification have been analysed. The application in clinical cisternography of the information obtained is discussed.


Urinary symptoms following external beam radiotherapy of the prostate: Dose-symptom correlates with multiple-event and event-count models.
This study aimed to compare urinary dose-symptom correlates after external beam radiotherapy of the prostate using commonly utilised peak-symptom models to multiple-event and event-count models which account for repeated events. Urinary symptoms (dysuria, haematuria, incontinence and frequency) from 754 participants from TROG 03.04-RADAR trial were analysed. Relative (R1-R75 Gy) and absolute (A60-A75Gy) bladder dose-surface area receiving more than a threshold dose and equivalent uniform dose using exponent a (range: a ∈[1 … 100]) were derived. The dose-symptom correlates were analysed using; peak-symptom (logistic), multiple-event (generalised estimating equation) and event-count (negative binomial regression) models. Stronger dose-symptom correlates were found for incontinence and frequency using multiple-event and/or event-count models. For dysuria and haematuria, similar or better relationships were found using peak-symptom models. Dysuria, haematuria and high grade (⩾ 2) incontinence were associated to high dose (R61-R71 Gy). Frequency and low grade (⩾ 1) incontinence were associated to low and intermediate dose-surface parameters (R13-R41Gy). Frequency showed a parallel behaviour (a=1) while dysuria, haematuria and incontinence showed a more serial behaviour (a=4 to a ⩾ 100). Relative dose-surface showed stronger dose-symptom associations. For certain endpoints, the multiple-event and event-count models provide stronger correlates over peak-symptom models. Accounting for multiple events may be advantageous for a more complete understanding of urinary dose-symptom relationships.


Amikacin initial dosage in patients with hypoalbuminaemia: an interactive tool based on a population pharmacokinetic approach.
To characterize amikacin population pharmacokinetics in patients with hypoalbuminaemia and to develop a model-based interactive application for amikacin initial dosage. A population pharmacokinetic model was developed using a non-linear mixed-effects modelling approach (NONMEM) with amikacin concentration-time data collected from clinical practice (75% hypoalbuminaemic patients). Goodness-of-fit plots, minimum objective function value, prediction-corrected visual predictive check, bootstrapping, precision and bias of parameter estimates were used for model evaluation. An interactive model-based simulation tool was developed in R (Shiny and R Markdown). Cmax/MIC ratio, time above MIC and AUC/MIC were used for optimizing amikacin initial dose recommendation. Probabilities of reaching targets were calculated for the dosage proposed. A one-compartment model with first-order linear elimination best described the 873 amikacin plasma concentrations available from 294 subjects (model development and external validation groups). Estimated amikacin population pharmacokinetic parameters were CL (L/h) = 0.525 + 4.78 × (CKD-EPI/98) × (0.77 × vancomycin) and V (L) = 26.3 × (albumin/2.9)-0.51 × [1 + 0.006 × (weight - 70)], where CKD-EPI is calculated with the Chronic Kidney Disease Epidemiology Collaboration equation. AMKdose is a useful interactive model-based application for a priori optimization of amikacin dosage, using individual patient and microbiological information together with predefined pharmacokinetic/pharmacodynamic (PKPD) targets. Serum albumin, total bodyweight, estimated glomerular filtration rate (using the CKD-EPI equation) and co-medication with vancomycin showed a significant impact on amikacin pharmacokinetics. A powerful interactive initial dose-finding tool has been developed and is freely available online. AMKdose could be useful for guiding initial amikacin dose selection before any individual pharmacokinetic information is available.


[T1 and T2 mapping: new perspectives in cardiac magnetic resonance imaging].
Cardiac magnetic resonance (MR) imaging is currently considered the gold standard for characterizing changes in myocardial structure, in particular to assess myocardial edema and focal fibrosis. In spite of this potential capability, the traditional MR sequences usually employed for these purposes have significant limitations and provide only qualitative information. Recent developments in cardiac MR imaging techniques currently provide clinically-feasible mapping of T1 and T2 relaxation times, thus providing a quantitative assessment of the parameters of interest. Myocardial edema can be evaluated using T2 mapping techniques. These have shown a superior performance compared to the traditional T2-weighted and STIR sequences, both in acute inflammatory cardiomyopathies and in acute ischemic injury. T1 mapping techniques, performed both with and without contrast medium, enable to quantify diffuse myocardial fibrosis and to assess myocardial edema and infiltration. This article will review current methodologies for cardiac T1 and T2 parametric mapping and their potential and limitations in the assessment of myocardial damage.


Diffusion abnormalities in temporal lobes of children with temporal lobe epilepsy: a preliminary diffusional kurtosis imaging study and comparison with diffusion tensor imaging.
In this preliminary study, we aimed to investigate the abnormalities of water diffusion in children with temporal lobe epilepsy (TLE). Eight children with unilateral TLE (according to electroencephalography, EEG) and eight age- and sex-matched controls were recruited. Diffusion tensor imaging (DTI)/diffusional kurtosis imaging (DKI) acquisitions were performed. Radial diffusivity (λ(⊥)), axial diffusivity (λ(∥)), mean diffusivity (MD) and fractional anisotropy (FA) maps were calculated for both DTI and DKI, and radial kurtosis (K(⊥)), axial kurtosis (K(∥)) and mean kurtosis (MK) maps were calculated for DKI only. Mann-Whitney test showed that, for white matter in the temporal lobe, DKI-derived λ(∥) , MD and K(∥) were significantly different in bilateral temporal lobes and EEG-abnormal and EEG-normal sides of the temporal lobe between patients and controls, whereas DTI showed no abnormalities. For gray matter, DKI detected significantly higher MD and MK in the same three comparisons, whereas DTI detected abnormalities only in the comparison between bilateral temporal lobes and between EEG-normal sides in cases and left-right matched sides in controls. No significant difference was observed between EEG-abnormal and EEG-normal sides in cases. These preliminary results indicate that DKI is more sensitive than DTI for the detection of diffusion abnormalities in the temporal lobes of children with TLE, even when EEG signals are normal. These findings pave the way for the application of DKI for in-depth studies on TLE in children.


[Squamous cell carcinoma on a leg ulcer in the West Indies].
The epidemiology of carcinoma developing on a leg ulcer is poorly, although high incidence rates are reported in Africa. Retrospective study of cases reported in Guadeloupe, a tropical country with a large population from African descent and with high quality health care level. Sixteen cases, mean age 71, were diagnosed over a 10-Year period in the only referral hospital. The annual incidence was an estimated 0.4/100,000. Preceding ulcers had a long course (mean of 27 Years) and had various causes. Social distress was the rule (14/16 patients). One third of the clearly differentiated (15/16) squamous cell-type tumors exhibited metastatic extension on presentation. At Year 3, the mortality rate was of 40 p. cent. The best survival rate (6 remissions/8 cases) was associated with primary limb amputation. Malignant ulcers appeared more frequent in Guadeloupe than in the influent countries of the North, but with an instance 4-fold lower than in Africa. Like many other tropical diseases, socio-behavioral factors may play a major role.


[Diagnosis and treatment of divided nevus of the penis in children: A case report and literature review].
To explore the diagnosis and treatment of divided nevus of the penis (DNP) in children. We retrospectively analyzed the clinical data on a case of DNP treated by surgical resection and transplantation of free skin graft of the inner preputial plate, and searched PubMed, CNKI and Wanfang database prior to March 2021 for relevant literature, followed by analysis of the clinical characteristics, diagnosis and treatment of DNP. The free skin graft on the left side of the glans survived well. Postoperative pathology showed the DNP to be a complex pigmented nevus. The patient was followed up for 3 months, during which no obvious color difference was observed in the appearance of the glans, and nor evident abnormality in the function and sensation of the penis. A total of 12 studies meeting the inclusion criteria were retrieved from the databases, reporting the clinical features, diagnosis and treatment of 36 cases of DNP. Most of the lesions were found between 6 and 15 years old. Preoperative diagnostic methods included skin biopsy, puncture biopsy, and electronic dermatoscopy, surgical treatments involved transplantation of free skin graft of the inner preputial plate, transplantation of free skin graft of oral mucosa, direct resection and suturing, dressing change after resection, and laser therapy. The postoperative pathological types of DNP included intradermal nevus, mixed nevus, melanocytic nevus, blue nevus, epithelioid melanocytoma, and malignant melanoma. All the patients were successfully treated with excellent prognosis. Divided nevus of the penis in children is a rare type of pigmented nevus. Dermoscopy can effectively improve the accuracy of clinical diagnosis of the disease. Surgical treatment of DNP before puberty is recommended, and transplantation of free skin graft of the inner prepuce is one of the effective methods for its treatment, with the advantages of minor trauma, less blood loss during and after operation, and good cosmetic effect.


p38 MAPK Inhibition Improves Synaptic Plasticity and Memory in Angiotensin II-dependent Hypertensive Mice.
The pathogenesis of hypertension-related cognitive impairment has not been sufficiently clarified, new molecular targets are needed. p38 MAPK pathway plays an important role in hypertensive target organ damage. Activated p38 MAPK was seen in AD brain tissue. In this study, we found that long-term potentiation (LTP) of hippocampal CA1 was decreased, the density of the dendritic spines on the CA1 pyramidal cells was reduced, the p-p38 protein expression in hippocampus was elevated, and cognitive function was impaired in angiotensin II-dependent hypertensive C57BL/6 mice. In vivo, using a p38 heterozygous knockdown mice (p38(KI/+)) model, we showed that knockdown of p38 MAPK in hippocampus leads to the improvement of cognitive function and hippocampal synaptic plasticity in angiotensin II-dependent p38(KI/+) hypertensive mice. In vitro, LTP was improved in hippocampal slices from C57BL/6 hypertensive mice by treatment with p38MAPK inhibitor SKF86002. Our data demonstrated that p38 MAPK may be a potential therapeutic target for hypertension-related cognitive dysfunction.


The Influence of (Poly)phenol Intake in Saliva Proteome: Short- and Medium-Term Effects of Apple.
The relationship between salivary proteome and dietary habits was studied in previous works, where a relationship between salivary proteins like cystatins and polyphenol/tannin levels in diet was observed. However, it remains to be elucidated if this association results from an effect of polyphenol-rich food ingestion on saliva composition. The aim of this work was to test the effects of apple intake on the saliva proteome, both in the short and medium term (after 4 days of continuous intake). By incubating saliva samples with apple phenolic-rich extract, protein bands containing α-amylase, S-type cystatins, and proline-rich proteins (PRPs) appeared in the fraction that precipitated, showing the potential of these (poly)phenols to precipitate salivary proteins. Among these, it was salivary cystatins that presented changes in their levels both in the saliva samples collected immediately after apple intake and in the ones collected after 4 days of intake of an extra amount of apple. These results support the thought that intake is reflected in the salivary proteome. The effect of a polyphenol-rich food, like the apple, on salivary cystatin levels is in line with results observed in animal models and, due to the involvement of these proteins in oral food perception, it would be interesting to explore in future studies the effect of these changes on sensory perception and acceptance of polyphenol-rich food.


Construction and application of a bovine immune-endocrine cDNA microarray.
A variety of commercial DNA arrays specific for humans and rodents are widely available; however, microarrays containing well-characterized genes to study pathway-specific gene expression are not as accessible for domestic animals, such as cattle, sheep and pigs. Therefore, a small-scale application-targeted bovine immune-endocrine cDNA array was developed to evaluate genetic pathways involved in the immune-endocrine axis of cattle during periods of altered homeostasis provoked by physiological or environmental stressors, such as infection, vaccination or disease. For this purpose, 167 cDNA sequences corresponding to immune, endocrine and inflammatory response genes were collected and categorized. Positive controls included 5 housekeeping genes (glyceraldehydes-3-phosphate dehydrogenase, hypoxanthine phosphoribosyltransferase, ribosomal protein L19, beta-actin, beta2-microglobulin) and bovine genomic DNA. Negative controls were a bacterial gene (Rhodococcus equi 17-kDa virulence-associated protein) and a partial sequence of the plasmid pACYC177. In addition, RNA extracted from un-stimulated, as well as superantigen (Staphylococcus aureus enterotoxin-A, S. aureus Cowan Pansorbin Cells) and mitogen-stimulated (LPS, ConA) bovine blood leukocytes was mixed, reverse transcribed and PCR amplified using gene-specific primers. The endocrine-associated genes were amplified from cDNA derived from un-stimulated bovine hypothalamus, pituitary, adrenal and thyroid gland tissues. The array was constructed in 4 repeating grids of 180 duplicated spots by coupling the PCR amplified 213-630 bp gene fragments onto poly-l-lysine coated glass slides. The bovine immune-endocrine arrays were standardized and preliminary gene expression profiles generated using Cy3 and Cy5 labelled cDNA from un-stimulated and ConA (5 microg/ml) stimulated PBMC of 4 healthy Holstein cows (2-4 replicate arrays/cow) in a time course study. Mononuclear cell-derived cytokine and chemokine (IL-2, IL-1alpha, TNFalpha, IFN-gamma, TGFbeta-1, MCP-1, MCP-2 and MIP-3alpha) mRNA exhibited a repeatable and consistently low expression in un-stimulated cells and at least a two-fold increased expression following 6 and 24 h ConA stimulation as compared to 0 h un-stimulated controls. In contrast, expression of antigen presenting molecules, MHC-DR, MHC-DQ and MHC-DY, were consistently at least two-fold lower following 6 and 24 h ConA stimulation. The only endocrine gene with differential expression following ConA stimulation was prolactin. Additionally, due to the high level of genetic homology between ovine, swine and bovine genes, RNA similarly acquired from sheep and pigs was evaluated and similar gene expression patterns were noted. These data demonstrate that this application-targeted array containing a set of well characterized genes can be used to determine the relative gene expression corresponding to immune-endocrine responses of cattle and related species, sheep and pigs.


Screening and Prevention of Barrett's Esophagus.
Barrett's esophagus (BO) is a risk factor for esophageal adenocarcinoma. However, screening for BO is difficult since it is not yet clear who should be screened and which screening method is cost-effective. Screening methods could be upper endoscopy at the time of the first screening colonoscopy, transnasal endoscopy, esophageal capsule endoscopy, or cytosponge. In order to prevent the development of BO or its neoplastic progression, there are modifiable risk factors like obesity or smoking that can be influenced. In addition, several drugs like proton pump inhibitors, aspirin, nonsteroidal anti-inflammatory drugs and statins have shown promising effects in mostly observational studies. However, data from prospective randomized trials are scarce in order to draw final conclusions.


Rapid progression to gummatous syphilitic hepatitis and neurosyphilis in a patient with newly-diagnosed HIV.
We review the literature on hepatic involvement in patients with HIV and syphilis co-infection and describe a case of rapid progression to neurosyphilis and presumed gummatous syphilitic hepatitis in a patient newly diagnosed with HIV. To our knowledge, this is the first case of syphilitic hepatitis with gummas described in the HIV population.


A modelling analysis of financial incentives for hepatitis C testing and treatment uptake delivered through a community-based testing campaign.
Financial incentives may reduce opportunity costs associated with people who become lost to follow-up in hepatitis C treatment programs. We estimated the impact that different financial incentive amounts would need to have on retention in care to maintain the same unit cost per (1) RNA-positive person completing testing (defined as awareness of RNA status) and (2) RNA diagnosed person initiating treatment. Costing data were obtained from a 2019 community-based testing campaign focused on engaging people who inject drugs. For different financial incentive amounts, we modelled the corresponding improvements in retention in care that would be needed to maintain the same overall (1) unit cost per testing completion and (2) unit cost per treatment initiation. In the testing campaign, the unit cost per RNA-positive person completing testing was A$3215 and the unit cost per RNA diagnosed person initiating treatment was A$1055. Modelling found that an incentive of A$500 per RNA-positive person completing testing would result in more people completing testing for the same unit cost if the percentage of attendees receiving their test results increased from 63% to 74%. An incentive of A$200 per RNA diagnosed person initiating treatment would result in more people initiating treatment for the same unit cost if the percentage initiating treatment increased from 67% to 83%. Monetary incentives for completing testing and initiating treatment may be an effective way to increase retention in care without increasing the overall unit cost of completing testing/initiating treatment.


Figure-ground organization and object recognition processes: an interactive account.
Traditional bottom-up models of visual processing assume that figure-ground organization precedes object recognition. This assumption seems logically necessary: How can object recognition occur before a region is labeled as figure? However, some behavioral studies find that familiar regions are more likely to be labeled figure than less familiar regions, a problematic finding for bottom-up models. An interactive account is proposed in which figure-ground processes receive top-down input from object representations in a hierarchical system. A graded, interactive computational model is presented that accounts for behavioral results in which familiarity effects are found. The interactive model offers an alternative conception of visual processing to bottom-up models.


[Effect of 21-gene recurrence score on chemotherapy decisions for patients with estrogen receptor-positive, epidermal growth factor receptor 2-negative and lymph node-negative early stage-breast cancer].
Objective: To investigate the effect of 21-gene recurrence score on adjuvant chemotherapy decisions for patients with estrogen receptor (ER)-positive, epidermal growth factor receptor 2 (HER-2)-negative and lymph node (LN)-negative early stage-breast cancer. Methods: One hundred and forty-eight patients with ER+ , HER-2- and LN- early stage breast cancer were recruited in the Ruijin hospital, Shanghai Jiao Tong University School of Medicine. The 21-gene recurrence score (RS)assay was performed and systemic therapeutic decisions were made before and after knowing the RS results under multidisciplinary discussion. The effects of RS assay and the other influential factors on adjuvant chemotherapy decision were further analyzed. Results: After knowing the RS results, treatment decisions were changed in 26 out of 148 patients(17.6%). Among them, 9 out of 26 patients were not recommended for chemotherapy; 16 of 26 had treatment recommendation changed to chemotherapy, and chemotherapy regimen was changed in the last one patient. Multivariate analysis showed that RS, age and histological grade were independent factors of decision-making for adjuvant chemotherapy. Conclusion: Our results suggest that 21-gene recurrence score significantly influences decision making for adjuvant chemotherapy in patients with ER+ , HER-2- and LN- early stage breast cancer.


Association of fluconazole pharmacodynamics with mortality in patients with candidemia.
Recent studies of nonneutropenic patients with candidemia or candidiasis suggest that fluconazole pharmacodynamic parameters correlate with clinical outcomes; however, additional data of correlation to mortality in patients with candidemia would be valuable. We assessed the impact of MICs for Candida, fluconazole pharmacodynamics, and patient characteristics on all-cause mortality with use of a prospective cohort of 96 hospitalized patients with candidemia. Among 84 patients for whom Candida isolates were available for testing, the most frequent Candida species isolated were Candida albicans (44%), followed by Candida parapsilosis (20.2%), and Candida glabrata (20.2%). Fluconazole resistance (MIC of >or=64 microg/ml) was present in 7 (8.3%) to 10 (11.9%) of 84 isolates, depending on the MIC endpoint determination method (50% or 80% inhibition read at 24 or 48 h). Overall mortality occurred in 27 (28.1%) of 96 patients, and nonsurvivors were more likely to have fluconazole-resistant isolates (25% versus 6.7%; P = 0.02). Multivariable analysis demonstrated an association between fluconazole resistance and mortality, but it did not reach statistical significance (odds ratio, 5.3; 95% confidence interval, 0.8 to 33.4; P = 0.08). By pharmacodynamic analysis, a fluconazole area under the concentration-time curve/MIC of <11.5 or MIC of >or=64 was associated with increased patient mortality (P <or= 0.09). These data support previous findings of an antifungal exposure-response relationship to mortality in patients with candidemia. In addition, similar MICs were obtained using a 24- or 48-h MIC endpoint determination, thus providing the opportunity to assess earlier the impact of isolate susceptibility on therapy.


Decentralization and primary health care: some negative implications in developing countries.
Decentralization is a highly popular concept, being a key element of Primary Health Care policies. There are, however, certain negative implications of decentralization that must be taken into account. These are analyzed in this article with particular reference to developing countries. The authors criticize the tendency for decentralization to be associated with state limitations, and discuss the dilemma of relating decentralization, which is the enhancement of the different, to equity, which is the promotion of equivalence. Those situations in which decentralization can strengthen political domination are described. The authors conclude by setting out a checklist of warning questions and issues to be taken into account to ensure that decentralization genuinely facilitates the Primary Health Care orientation of health policy.


Impact of airway challenges on cardiovascular risk in asthma - a randomized controlled trial.
People experiencing asthma exacerbations are at increased risk of cardiovascular events. To better understand the relationship between asthma exacerbations and cardiovascular risk, this randomized case-control, cross-over controlled trial assessed the immediate systemic inflammatory and vascular responses to acutely induced pulmonary inflammation and bronchoconstriction in people with asthma and controls. Twenty-six people with asthma and 25 controls underwent three airway challenges (placebo, mannitol, and methacholine) in random order. Markers of cardiovascular risk, including serum C-reactive protein, interleukin-6, and tumor necrosis factor, endothelial function (flow-mediated dilation), microvascular function (blood-flow following reactive hyperemia), and arterial stiffness (pulse wave velocity) were evaluated at baseline and within one hour following each challenge. The systemic responses in a) asthma/control and b) positive airway challenges were analyzed. (ClinicalTrials.gov reg# NCT02630511). Both the mannitol and methacholine challenges resulted in clinically significant reductions in forced expiratory volume in 1 second (FEV1) in asthma (-7.6% and -17.9%, respectively). Following positive challenges, reduction in FEV1 was -27.6% for methacholine and -14.2% for mannitol. No meaningful differences in predictors of cardiovascular risk were observed between airway challenges regardless of bronchoconstrictor response. Neither acutely induced bronchoconstriction nor pulmonary inflammation and bronchoconstriction resulted in meaningful changes in systemic inflammatory or vascular function. These findings question whether the increased cardiovascular risk associated with asthma exacerbations is secondary to acute bronchoconstriction or inflammation, and suggest that other factors need to be further evaluated such as the cardiovascular impacts of short-acting inhaled beta-agonists.


Pulmonary embolism and thrombotic thrombocytopenic purpura in acute promyelocytic leukemia treated with all-trans retinoic acid.
We describe a patient with acute promyelocytic leukemia (APL) who developed pulmonary embolism (PE) and thrombotic thrombocytopenic purpura (TTP) during remission induction all-trans retinoic acid (ATRA) therapy. A 44-year-old man was diagnosed with APL and was treated with ATRA. On day 14, he developed PE, and on day 24, he developed TTP. Both PE and TTP occurred in association with leukocytosis due to ATRA administration. The PE responded to dexamethasone and TTP responded to plasma infusion. The PE and TTP remitted, and he achieved complete remission of APL. To our knowledge, there have been no reports of TTP occurring as a complication of ATRA therapy.


[Increased cardiovascular risk after gestational diabetes].
The Dutch diabetes guideline advises GPs to screen for diabetes every year in the first five years after the birth of the youngest child, by simply measuring fasting glucose. Based on the increased risk for cardiovascular disease in women with a history of gestational diabetes, it seems appropriate to not only screen for diabetes, but to combine that with monitoring all the other features of the insulin resistance syndrome. Even without a disturbance in glucose tolerance, that could stimulate helpful lifestyle interventions at an earlier stage.


A nationwide surveillance study of rheumatic diseases among Japanese children.
To estimate the number of children with rheumatic diseases, a questionnaire was distributed to the pediatrics department of 1,290 hospitals in Japan in June 1994. From this survey, 1,606 cases with juvenile rheumatoid arthritis (JRA), 906 cases with systemic lupus erythematosus (SLE), 320 cases with dermatomyositis/polymyositis (DM/PM), 28 cases with scleroderma (PSS), 70 cases with Sjögren's syndrome (Sjs), 93 cases with mixed connective tissue disease (MCTD), 25 cases with aortitis syndrome, 20 cases with polyarteritis (PN) and 51 cases with Behçet disease were reported. The crude annual incidence rates per 100,000 among the childhood population were estimated as JRA, 0.83; SLE, 0.47; DM/PM, 0.16; PSS, 0.01; Sjs, 0.04; MCTD, 0.05; aortitis syndrome, 0.01; PN, 0.01; and Behçet disease, 0.03. The present study reveals that there are more children with rheumatic diseases than are estimated from the reported cases in the literature and the number of children who are receiving Assistance Medical Costs Insurance covered by the Japanese government.


Myiasis infestation in advanced oral squamous cell carcinoma.
Oral myiasis is a rare manifestation in humans and is vulnerable to attack in conditions leading to persistent mouth opening along with poor oral hygiene, suppurating lesions and cancerous wound, mainly in tropical countries. Myiasis is diagnosed clinically based on the presence of maggots and traditional management is the mechanical removal of the larvae. This is a case report of myiasis in a 44-year-old man diagnosed with invasive oral squamous cell carcinoma. The treatment consisted of manual removal of the larvae and cleaning with aqueous chlorhexidin 0.12%. The patient's management was antisepsis, larval removal and general care, performed weekly. The patient died 2 months later. The management of patients by healthcare service and hygiene orientations is recommended to prevent oral myiasis infestation, mainly in patients living in fly breeding habitats and who do not comply with basic oral hygiene measures, which may be make individuals more prone to develop myiasis.


Thrombolysis for intraventricular hemorrhage.
Intraventricular hemorrhage is a frequent complication of intracerebral hemorrhage and is independently associated with significant morbidity and mortality. Intraventricular fibrinolytic therapy is used with increasing frequency to accelerate clot clearance. We review the recent evidence and discuss the therapeutic benefits as well as the current concerns and limitations of fibrinolytic use in this setting.


Synovial metaplasia, a specialized form of repair.
Synovial metaplasia is a change seen most frequently in the tissues surrounding silicone breast prostheses and in healing tissue adjacent to joint prostheses. It has also been described in skin and soft tissues, most frequently in healing or healed traumatic or surgical wounds. We report a case of synovial metaplasia occurring in a hitherto unreported location, namely, adjacent to a silicone low-pressure voice prosthesis. A review of cases of synovial metaplasia reported in the literature revealed that in most cases, spaces that form adjacent to foreign material (most commonly silicone breast prostheses) and the smooth gliding surfaces of the foreign material that resist penetration by fibroblast processes are frequent associated findings that precede the occurrence of synovial metaplasia. Thus, synovial metaplasia might represent a specialized form of healing in cases that have this combination of physical features.


Esophageal Cancer and associated Factors among Uzbek-Turkmen and Other Ethnic Groups in the Northern Part of Afghanistan
Background: A high incidence rate of esophageal cancer has been observed in the Northern part of Afghanistan, particularly among those of Uzbek-Turkmen ethnicity. However, there is a paucity of published data from which to compare the prevalence of environmental risk factors for esophageal cancer between Uzbek-Turkmen and other ethnic groups. Thus, we investigated the prevalence of environmental risk factors associated with esophageal cancer in the Northern part of Afghanistan, focusing on ethnicity differences. Methods: This retrospective study covered 168 patients diagnosed with esophageal cancer based on endoscopic findings when attending an outpatient clinic from October 2013 to April 2016. Demographic data and burden of relevant environmental risk factors were compared between Uzbek-Turkmen and other ethnic groups. Results: In the total of 168 patients (108 Uzbek-Turkmen and 60 other ethnicities), males had significantly higher rates of opium use, chewing nass (a mixture of tobacco, ash and lime), and smoking than female patients. The mean age of the Uzbek-Turkmen group was 62.9 years, while that of the other ethnic group cases was 59.1. The prevalence of opium use, chewing nass and hot tea consumption was significantly higher in the Uzbek-Turkmen group. Conclusions: This study showed that there were significant differences in prevalence of opium, nass, and hot tea consumption between Uzbek-Turkmen and the other ethnic group patients with esophageal cancer in the northern part of Afghanistan.


The role of USP34 in the fixation of titanium implants in murine models.
Ubiquitin-specific protease 34 (USP34), a member of the ubiquitin-specific protease family, regulates osteogenic differentiation of bone marrow mesenchymal stem cells via bone morphogenetic protein signaling. This study aimed to investigate the role of USP34 in fixation of titanium implants in mouse models. Eight-week-old Usp34-knockout (Prx1-Cre;Usp34f/f ) mice and their Usp34 wild-type (Usp34f/f ) control littermates were used. Experimental titanium implants were inserted into the distal ends of femurs and the edentulous area of maxillae. Two and four weeks after surgery, samples of femur and maxilla were obtained, and micro-computed tomography scanning, histomorphometric analyses, and push-in tests were performed on the samples. Compared with controls, Prx1-Cre;Usp34f/f mice showed reduced bone volume for both femurs and maxillae; a decreased femoral bone-implant contact ratio (BIC) at 2 wk [mean (standard error of the mean): 62.17% (2.15%) vs. 44.06% (3.45%)] and 4 wk [72.46% (1.61%) vs. 64.53% (1.93%)]; decreases in femoral bone volume fraction (BV/TV) and push-in resistance; and lower BIC and BV/TV of the maxillae. Taken together, our data demonstrate that specific deletion of Usp34 in mesenchymal stem cells impairs fixation of titanium implants in mice.


Summation theorems for flux and concentration control coefficients of dynamic systems.
Metabolic control analysis (MCA) was developed to quantify how system variables are affected by parameter variations in a system. In addition, MCA can express the global properties of a system in terms of the individual catalytic steps, using connectivity and summation theorems to link the control coefficients to the elasticity coefficients. MCA was originally developed for steady-state analysis and not all summation theorems have been derived for dynamic systems. A method to determine time-dependent flux and concentration control coefficients for dynamic systems by expressing the time domain as a function of percentage progression through any arbitrary fixed interval of time is reported. Time-dependent flux and concentration control coefficients of dynamic systems, provided that they are evaluated in this novel way, obey the same summation theorems as steady-state flux and concentration control coefficients, respectively.


The influence of lymphatic drainage in experimental Trypanosoma cruzi infection.
The rapid disappearance of infective forms of Trypanosoma cruzi from the site of inoculation as well as the initial phase of infection produced by the parasite are not yet fully understood. To investigate this problem we used the hamster as an animal model considering the existence of the cheek pouch--a peculiar region devoid of lymphatic vessels. T. cruzi trypomastigotes were inoculated into the cheek pouch or into the footpad of animals previously infected or not with the same parasite. The results were followed from 3 up to 21 days postinoculation, by histological examination. In the cheek pouch of normal animals a large number of parasites could be seen up to 15 days post-inoculation and the inflammatory infiltrate had a focal distribution. Conversely, in the footpad the infiltrate was diffuse and no parasites could be detected. These observations indicate that the lymphatic system is the main route of T. cruzi dissemination from the site or inoculation. When hamsters were first inoculated in the footpad and 7 days later in the pouch, the inflammatory infiltrate at this point was less aggressive and no parasites could be detected.


Enhanced biological motion perception in deaf native signers.
We conducted two studies to test how deaf signed language users perceive biological motions. We created 18 Biological Motion point-light displays (PLDs) depicting everyday human actions, and 18 Scrambled control PLDs. First, we conducted an online behavioral rating survey, in which deaf and hearing raters identified the biological motion PLDs and rated how easy it was for them to identify the actions. Then, we conducted an EEG study in which Deaf Signers and Hearing Non-Signers watched both the Biological Motion PLDs and the Scrambled PLDs, and we computed the time-frequency responses within the theta, alpha, and beta EEG rhythms. From the behavioral rating task, we show that the deaf raters reported significantly less effort required for identifying the Biological motion PLDs, across all stimuli. The EEG results showed that the Deaf Signers showed theta, mu, and beta differentiation between Scrambled and Biological PLDs earlier and more consistently than Hearing Non-Signers. We conclude that native ASL users exhibit experience-dependent neuroplasticity in the domain of biological human motion perception.


Clear cell ameloblastoma in a young child--an enigma in diagnosis.
Clear cell ameloblastoma is an odontogenic tumour with aggressive behaviour usually noticed in 6th decade of life. It is histologically characterized by an ameloblastomatous component intermixed with an extensive clear cell component. Here is a case report of an unusual occurrence in a 5-year-old child. The rarity of this tumour and young age of the patient are some of the rare features, which need documentation. The importance of its diagnosis and various differential diagnoses are discussed.


Acute pseudogout in the absence of synovial fluid Leukocytes.
A case of acute pseudogout that occurred in the absence of synovial fluid leukocytes is described. This finding implies that there may be an alternative inflammatory mechanism for acute pseudogout that does not depend on polymorphonuclear leukocytes.


Clinical spectrum of children receiving palliative care in Malaysian Hospitals.
Awareness for paediatric palliative care has resulted in the impetus for paediatrician-led palliative care services across Malaysia. However, there is paucity of local data on patients receiving hospital-based paediatric palliative care. We aim to review the clinical spectrum of patients referred to these services. An observational study of children aged between 0-18 years receiving palliative care at 13 hospitals between 1st January and 31st December 2014 was carried out. There were 315 patients analysed, 90 (28.6%) and 46 (14.6%) were neonates and adolescents respectively. The main ICD-10 diagnostic categories for all patients were identified to be 'Congenital malformations, deformations and chromosomal abnormalities' 117 (37.1%), 'Diseases of nervous system' 76 (24.1%) and 'Neoplasms' 60 (19.0%). At referral 156 (50%) patients had holistic needs assessments. Patients with 'Diseases of nervous system' were assessed to have significantly more physical needs than the other two diagnostic categories. Majority of patients who knew of their diagnosis and prognosis were those with malignancy. Over a fifth of referrals were at their terminal admission. Of 144 who died, 111 (77.1%) had advanced care plans. There was bereavement follow-up in 98 (68.1%) patients. Patients referred for palliative care have varied diagnoses and needs. To ensure all paediatricians are competent to deliver quality care to all children, further education and training initiatives is imperative.


Stable carbon, oxygen, and nitrogen, isotope analysis of plants from a South Asian tropical forest: Implications for primatology.
Stable isotope analysis of primate tissues in tropical forest contexts is an increasingly popular means of obtaining information about niche distinctions among sympatric species, including preferences in feeding height, forest canopy density, plant parts, and trophism. However, issues of equifinality mean that feeding height, canopy density, as well as the plant parts and plant species consumed, may produce similar or confounding effects. With a few exceptions, researchers have so far relied largely on general principles and/or limited plant data from the study area as references for deducing the predominant drivers of primate isotope variation. Here, we explore variation in the stable carbon (δ13 C), nitrogen (δ15 N), and oxygen (δ18 O) isotope ratios of 288 plant samples identified as important to the three primate species from the Polonnaruwa Nature Sanctuary, Sri Lanka, relative to plant part, season, and canopy height. Our results show that plant part and height have the greatest effect on the δ13 C and δ18 O measurements of plants of immediate relevance to the primates, Macaca sinica, Semnopithecus priam thersites, and Trachypithecus vetulus, living in this monsoonal tropical forest. We find no influence of plant part, height or season on the δ15 N of measured plants. While the plant part effect is particularly pronounced in δ13 C between fruits and leaves, differential feeding height, and plant taxonomy influence plant δ13 C and δ18 O differences in addition to plant organ. Given that species composition in different regions and forest types will differ, the results urge caution in extrapolating general isotopic trends without substantial local baselines studies.


Copper-Catalyzed Tandem Cyclization/Direct C(sp2)-H Annulation of Azide-Ynamides via α-Imino Copper Carbenes: Access to Azepino[2,3-b:4,5-b']diindoles.
A novel copper-catalyzed tandem cyclization/direct C(sp2)-H annulation of phenyl azide-ynamides via α-imino copper carbenes has been developed, which provides a concise and flexible approach for the construction of a range of valuable azepino[2,3-b:4,5-b']diindoles in mostly good to excellent yields with high chemoselectivities. This tandem reaction also exhibits a broad substrate scope, excellent functional group tolerance, simple operation, and mild reaction conditions.


Insulin-like growth factor I in the dog: a study in different dog breeds and in dogs with growth hormone elevation.
A radioimmunoassay (RIA) devised for the measurement of human insulin-like growth factor I (IGF I) was employed for the measurement of canine IGF I. Canine IGF I was extracted from plasma specimens by gel chromatography. Columns were eluted with 1 M acetic acid and the fractions representing the 55 to 85% bed volume were pooled, lyophilized and reconstituted with assay buffer. Serial dilutions of canine IGF I from both normal and acromegalic dogs when added to the RIA system gave a similar displacement pattern of human [125I]IGF I as the one obtained by the addition of unlabelled human IGF I. The dose-response curve obtained by canine IGF I paralleled the one obtained by human IGF I. Logit-log transformation and least squares fitting resulted in straight line fitting of the standard curve between 0.039 and 5 ng IGF I added per tube. The within-assay coefficient of variation (CV) was 16.7% and the between-assay CV was 21.8%. Plasma IGF I concentrations in normal dogs appeared to be a function of body size. The concentrations were 36 +/- 27 ng/ml in Cocker Spaniels, 87 +/- 33 ng/ml in Beagles, 117 +/- 34 ng/ml in Keeshonds, and 280 +/- 23 ng/ml in German Shepherds (mean +/- SEM). The mean IGF I level in a group of dogs with growth hormone (GH) elevation was 700 +/- 90 ng/ml. Though this group of dogs comprised both small and large dogs, the mean IGF I level significantly differed from the one found in German Shepherds, the largest breed studied (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


Advancements in bait technology to control Glossina swynnertoni Austen, the species of limited distribution in Kenya and Tanzania border: A review.
Glossina swynnertoni is a savannah tsetse that is largely confined to the Serengeti-Mara [a very small part of East Africa covering northern Tanzania (Arusha and Manyara regions and parts of Shinyanga and Mara regions) extending Maasai Mara ecosystem in southwestern Kenya]. Nevertheless, it is of great concern to human and animal health and is one of the top target tsetse species for eradication. To achieve this eradication objective, it is important to know about its behaviour so that the appropriate tools/measures especially the right traps can be applied against it. In this paper G. swynnertoni is reviewed in terms of its behaviour, and development of traps for its survey and control. Glossina swynnertoni control is of paramount importance in Tanzania tourism industry and country's income. Since, G. swynnertoni is also distributed in national parks, control is vital as it might reduce tourists excursion/movement, by transmitting the African trypanosomiasis among travelers. Different literature search engines such as Google Scholar and PubMed were deployed for literature search. It was found that the behaviour of G. swynnertoni is relatively similar but unique from other tsetse flies. Its feeding cycle is 2½-3 days as opposed to 3-4 days observed in other tsetse species. The flight activity pattern varied between sex, with male having their peak at 1100-1200 hrs and females 1400-1600 hrs. The activity in both sexes decline rapidly towards the dusk (1700-1800 hrs). It was further that host odours, relatively smaller and vertically oriented devices, as well as host movement are the main attractive factors to this tsetse species, which can be exploited to design efficient artificial devices for control of G. swynnertoni . Therefore, due to its restricted distribution and threat it poses on tourism industry, deliberate efforts need to be made against G. swynnertoni as a next candidate to be eradicated using artificial bait technology.


Atypical toxoplasmic retinochoroiditis.
We report a case of re-activation of Toxoplasma gondii as a cause of atypical retinal necrosis in an immunocompetent individual. The rapid development of necrotising confluent retinochoroiditis and vitreous inflammation necessitated urgent aqueous humor PCR analysis, which was positive for T gondii. The patient was treated with two intravitreal injections of clindamycin, along with oral sulphadiazine, pyrimethamine, folinic acid and prednisolone. He developed central retinal arterial occlusion, as a complication of toxoplasmic retinochoroiditis, and immediate anterior chamber paracentesis was performed with visual recovery. The injection of intravitreal clindamycin with concomitant oral therapy was associated with control of toxoplasmic retinochoroiditis and resolution of vitreous inflammation.


Internalized HIV-related stigma in women of color obtaining care at an HIV specialty center in Los Angeles County, California.
The current study examined the role of internalized HIV-related stigma in antiretroviral therapy adherence, viral load, and retention in care among women of color living with HIV in Los Angeles County, California. African American and Hispanic/Latino women 18 years of age and older completed a one-time brief survey between September 2017 and February 2018. Descriptive statistics, and univariable and multivariable logistic regressions were used to analyze the data. Seventy-six participants enrolled in the study and 74 completed the entire survey. Seventy-six percent of respondents were Hispanic/Latino, 24% were African American, 71% were unemployed, and 54% had less than a high school education. Thirty-five percent were defined as having "high" stigma with a score in the upper quartile of the scale. Being unemployed, having a high school education or less, and not meeting the Health Resources and Services Administration's annual retention in care measure were associated with "high" stigma. When controlling for education and employment status, those reporting "high" stigma vs. "low" stigma were 18.8 times more likely to not meet the criteria for annual retention in care (OR = 18.8, 95% CI = 1.9-189.2, p = 0.013). Stigma-reduction interventions targeting healthcare settings may be necessary to improve patient retention and engagement in care.


Novel roles of protease inhibitors in infection and inflammation.
The local balance between proteinase inhibitors and proteinases determines local proteolytic activity. Various studies have demonstrated the importance of serine proteinase inhibitors in regulating the activity of serine proteinases that are released by leucocytes during inflammation. Recently it has been shown that these inhibitors may also display functions that are distinct from those associated with the inhibition of leucocyte-derived proteinases. In this review the results of selected studies focusing on three inhibitors of neutrophil elastase, i.e. alpha(1)-proteinase inhibitor, secretory leucocyte proteinase inhibitor and elafin, are presented, with the aim of illustrating their possible involvement in the regulation of inflammation, host defence against infection, tissue repair and extracellular matrix synthesis.


Generative modeling for label-free glomerular modeling and classification.
Generative modeling using GANs has gained traction in machine learning literature, as training does not require labeled datasets. This is perfect for applications in biological datasets, where large labeled datasets are often difficult and expensive to acquire. However, generative models offer no easy way to encode real images into feature-sets, something that is desirable for network explainability and may yield potentially informative image features. For this reason, we test a VAE-GAN architecture for label-free modeling of glomerular structural features. We show that this network can generate realistic looking synthetic images, and be used to interpolate between images. To prove the biological relevance of the network encodings, we classify small-labeled sets of encoded glomeruli by biopsy Tervaert class and for the presence of sclerosis, obtaining a Cohen's kappa values of 0.87 and 0.78 respectfully.


Nucleoli of peripheral blood lymphocytes in patients with chronic lymphocytic leukemia.
Morphological and cytochemical changes of the nuclei were investigated by the method of Smetana in peripheral blood lymphocytes of patients with chronic lymphocytic leukemia nontreated and treated with Leukeran. The material was divided into groups according to Rai. In the lymphocytes of the patients with nucleolar coefficient and the proportion of dense nucleoli and micronucleoli were increased, while at the same time, the proportion of ring-shaped nucleoli, the main form of nucleoli in the lymphocytes of healthy subjects, was decreased. The changes in the values of different nucleolar parameters indicated the successive stages of the diseases and served as an auxiliary distinctive feature of leukemic lymphocytes.


Nonabstinent drinking goals in the treatment of alcoholism. A clinical typology.
Traditional views in the field of alcoholism have been that alcoholics must achieve and maintain abstinence from alcohol in order to be rehabilitated. In turn, abstinence has been used as the sole or primary criterion of successful treatment. However, abstinence is not necessarily correlated with improvement in other areas of overall adjustment, such as emotional, interpersonal, vocational, and physical health. The recent advent of nonabstinent alcoholism treatment programs, in addition to other clinical data, suggests the need for more specific definitions of nonabstinence, attenuated drinking, controlled drinking, and normal thinking.


Mouse glandular kallikrein genes. Structure and partial sequence analysis of the kallikrein gene locus.
Mouse glandular kallikreins are encoded by a family of closely linked genes which are located on chromosome 7 at a site corresponding to the genetically defined Tam-1, Prt-4, and Prt-5 loci. We have characterized 24 kallikrein genes by genomic cloning and restriction mapping of 310 kilobase pairs of BALB/c mouse DNA. Most of these genes are highly homologous, have the same exon/intron organization, and are linked in clusters of up to 11 genes. Partial sequence analysis of the kallikrein genes has facilitated identification of those members of the family for which protein sequence data exist and assignment of those which are pseudogenes or encode proteins of unknown function. We find that a maximum of 14 mouse kallikrein genes have the potential to encode functional proteins.


Metadynamics simulations reveal a Na+ independent exiting path of galactose for the inward-facing conformation of vSGLT.
Sodium-Galactose Transporter (SGLT) is a secondary active symporter which accumulates sugars into cells by using the electrochemical gradient of Na+ across the membrane. Previous computational studies provided insights into the release process of the two ligands (galactose and sodium ion) into the cytoplasm from the inward-facing conformation of Vibrio parahaemolyticus sodium/galactose transporter (vSGLT). Several aspects of the transport mechanism of this symporter remain to be clarified: (i) a detailed kinetic and thermodynamic characterization of the exit path of the two ligands is still lacking; (ii) contradictory conclusions have been drawn concerning the gating role of Y263; (iii) the role of Na+ in modulating the release path of galactose is not clear. In this work, we use bias-exchange metadynamics simulations to characterize the free energy profile of the galactose and Na+ release processes toward the intracellular side. Surprisingly, we find that the exit of Na+ and galactose is non-concerted as the cooperativity between the two ligands is associated to a transition that is not rate limiting. The dissociation barriers are of the order of 11-12 kcal/mol for both the ion and the substrate, in line with kinetic information concerning this type of transporters. On the basis of these results we propose a branched six-state alternating access mechanism, which may be shared also by other members of the LeuT-fold transporters.


[Os odontoideum. Etiology, clinical aspects, therapy].
The etiology of os odontoideum is still controversial. In most patients, it is found by accident because of neurological symptoms and/or painful range of motion of the cervical spine. Upon recognition of the os odontoideum, it is unknown whether or not immediate surgery is beneficial. This is in contrast to an "unstable" os odontoideum, which could result in atlantoaxial instability or compression of the myelon. In this study, we present the results of our treatment of four patients with an unstable os odontoideum. In all four cases, a C1-2 fusion was performed (3 x Magerl/Seemann, 1 GallieBrooks). Postoperatively, we found a complete regression of neurological symptoms in three patients and one was significantly improved. The range of motion of the cervical spine was free of pain in all patients. As a result, we strongly support immediate surgical treatment of an unstable os odontoideum in order to prevent severe and life-threatening neurological complications.


Biomonitoring heavy metals in estuaries: a field comparison of two brown algae species inhabiting upper estuarine reaches.
Biomonitoring dissolved heavy metals within estuaries, particularly at their upper reaches, frequently has to rely on several biomonitors; rarely a single species thrives all along the salinity gradient. To properly do so, it must be established whether those biomonitors actually accumulate heavy metals alike. In this study, two brown seaweeds from the upper section of three NW Spain estuaries--the widely-known Fucus vesiculosus and the estuarine Fucus ceranoides--were compared as metal biomonitors. Both species were collected at five locations where they either coexist or live close to each other and their heavy metal content (Cu, Cr, Mn, Zn, Fe, Al) was measured. Analyses were appropriately replicated for each species x location combination to allow a statistically reliable detection of differences in bioaccumulation, with particular emphasis on the magnitude of interspecific differences. The lack of significant differences for Cu, Mn, and Zn contents in F. ceranoides and F. vesiculosus supports the feasibility of their joint use to monitor these metals along the estuaries. Conversely, F. ceranoides concentrated significantly higher levels of Cr, Fe, and Al than F. vesiculosus and hence combining data for both fucoids to monitor these elements seems impractical. The correlation of species differences together with a similar Al:Fe ratio in both weed tissue and sediment suggest that Cr, Fe, and Al tissue-burdens might be considerably biased by sediment retained on the surface of the weed. Parallel analyses of Al and/or Fe in seaweeds and sediments could serve to keep track of this interference and may help to combine data from both fucoids for monitoring elements like Cr.


Variability of gray and white matter during normal development: a voxel-based MRI analysis.
This study was aimed at investigating regional and local variability of brain tissue during normal human brain development. We investigated high-resolution MR-imaging data using SPM99 (Wellcome Department, University College London, UK). A pixel-wise variation coefficient of gray and white matter was calculated to visualize local variability. Data from 200 normal children (5-18 years) were analyzed. We found a profound interaction between variability of brain structures and normal development in both gray and white matter. Variability in gray and white matter shows regionally specific, age-related variations, possibly offering a new tool for the assessment of subtle brain abnormalities. Our results emphasize the necessity to take this variability into account when planning pediatric neuroimaging studies.


Future directions for serotonin and antidepressants.
Despite the widespread use of antidepressant medications that block serotonin (5-hydroxytryptamine; 5-HT) and/or norepinephrine (NE) transporters, such as SSRIs (selective serotonin reuptake inhibitors) or SNRIs (serotonin and norepinephrine reuptake inhibitors), the underlying neurobiological basis of action of these agents is poorly understood. Increases in serotonergic function are hypothesized to have beneficial effects on depressive symptoms. However, which of the 14 different neuronal receptors sensitive to 5-HT accounts for the therapeutic effects of SSRIs and SNRIs remains undetermined. The development of drugs that activate or block specific 5-HT receptors may help to circumvent the two main limitations of current antidepressants: low efficacy and delayed onset of therapeutic action. What follows is a short summary of the author's views on this matter.


The role of integrin beta in schizophrenia: a preliminary exploration.
Integrins are transmembrane heterodimeric (αβ) receptors that transduce mechanical signals between the extracellular milieu and the cell in a bidirectional manner. Extensive research has shown that the integrin beta (β) family is widely expressed in the brain and that they control various aspects of brain development and function. Schizophrenia is a relatively common neurological disorder of unknown etiology and has been found to be closely related to neurodevelopment and neurochemicals in neuropathological studies of schizophrenia. Here, we review literature from recent years that shows that schizophrenia involves multiple signaling pathways related to neuronal migration, axon guidance, cell adhesion, and actin cytoskeleton dynamics, and that dysregulation of these processes affects the normal function of neurons and synapses. In fact, alterations in integrin β structure, expression and signaling for neural circuits, cortex, and synapses are likely to be associated with schizophrenia. We explored several aspects of the possible association between integrin β and schizophrenia in an attempt to demonstrate the role of integrin β in schizophrenia, which may help to provide new insights into the study of the pathogenesis and treatment of schizophrenia.


Gene Expression Profiling in BRAF-Mutated Melanoma Reveals Patient Subgroups with Poor Outcomes to Vemurafenib That May Be Overcome by Cobimetinib Plus Vemurafenib.
Purpose: The association of tumor gene expression profiles with progression-free survival (PFS) outcomes in patients with BRAFV600-mutated melanoma treated with vemurafenib or cobimetinib combined with vemurafenib was evaluated.Experimental Design: Gene expression of archival tumor samples from patients in four trials (BRIM-2, BRIM-3, BRIM-7, and coBRIM) was evaluated. Genes significantly associated with PFS (P < 0.05) were identified by univariate Cox proportional hazards modeling, then subjected to unsupervised hierarchical clustering, principal component analysis, and recursive partitioning to develop optimized gene signatures.Results: Forty-six genes were identified as significantly associated with PFS in both BRIM-2 (n = 63) and the vemurafenib arm of BRIM-3 (n = 160). Two distinct signatures were identified: cell cycle and immune. Among vemurafenib-treated patients, the cell-cycle signature was associated with shortened PFS compared with the immune signature in the BRIM-2/BRIM-3 training set [hazard ratio (HR) 1.8; 95% confidence interval (CI), 1.3-2.6, P = 0.0001] and in the coBRIM validation set (n = 101; HR, 1.6; 95% CI, 1.0-2.5; P = 0.08). The adverse impact of the cell-cycle signature on PFS was not observed in patients treated with cobimetinib combined with vemurafenib (n = 99; HR, 1.1; 95% CI, 0.7-1.8; P = 0.66).Conclusions: In vemurafenib-treated patients, the cell-cycle gene signature was associated with shorter PFS. However, in cobimetinib combined with vemurafenib-treated patients, both cell cycle and immune signature subgroups had comparable PFS. Cobimetinib combined with vemurafenib may abrogate the adverse impact of the cell-cycle signature. Clin Cancer Res; 23(17); 5238-45. ©2017 AACR.


Transient left bundle branch block after posture change to the prone position during general anesthesia: A case report.
The prone position is commonly used in spinal surgery. There have been many studies on hemodynamic changes in the prone position during general anesthesia. We report a rare case of transient left bundle branch block (LBBB) in a prone position. Electrocardiogram (ECG) of a 64-year-old man scheduled for spinal surgery showed normal sinus rhythm change to LBBB after posture change to the prone position. Twelve lead ECG revealed LBBB. His coronary angio-computed tomography results showed right coronary artery with 30% to 40% stenosis and left circumflex artery with 40% to 50% stenosis. The patient was diagnosed with stable angina and second-degree atrioventricular block of Mobitz type II. Nitroglycerin was administered intravenously during surgery. Adequate oxygen was supplied to the patient. After surgery, the patient was prescribed clopidogrel, statins, angiotensin II receptor blocker, and a permanent pacemaker was inserted. Surgery was completed without complications. After surgery, the transient LBBB changed to a normal sinus rhythm. The patient did not complain of chest pain or dyspnea. The prone position causes significant hemodynamic changes. A high risk of cardiovascular disease may cause ischemic heart disease and ECG changes. Therefore, careful management is necessary.


miRNAs and target genes in the blood as biomarkers for the early diagnosis of Parkinson's disease.
Parkinson's disease (PD) is the second most common neurodegenerative disease, and it is a multifactorial disease with no definite diagnostic index. The aim of this study is to construct a molecular network to find molecules that play important roles in the progression of PD with the goal of using them diagnostically and for early intervention. We downloaded two gene expression profiles (GSE54536 and GSE100054) from the Expression Omnibus (GEO) database to analyze possible markers. The Genes were analyzed with GEO2R. There were 1790 and 967 differentially expressed genes (DEGs) in GSE54536 and GSE100054 respectively. A total of 125 genes co-exist in the DEGs of the two data sets. KEGG pathway analysis showed that 125 DEGs were enriched in Aldosterone synthesis and secretion, Gap junctions, Platelet activation, Rap1 signaling pathway, and Estrogen signaling pathway. There were 20 hub genes among 125 DEGs analyzed by PPI that involved in Platelet activation, Inflammatory response, Innate immune response, B cell receptor signaling, Stimulatory C-type lectin receptor signaling, Lipopolysaccharide response, Leukocyte migration, and Regulation of cell proliferation. Additionally, 42 differences in miRNAs were found in GSE100054. We constructed a miRNA-mRNA regulatory network depicting interactions between the predicted genes and the 125 DEGs. 34 miRNA-mRNA pairs were obtained. We found GNAQ and TMTC2 were the most important mRNAs in the network analyzed by Cytoscape APP centiscape, and their degrees in centiscape2.2 were all 10. has-miR-142 was the most important miRNA (the highest degree is 4 in centiscape2.2), which forms miRNA-mRNA pairs with GNAQ, TMTC2, BEND2, and KYNU. This study provides data of potential biomarkers and therapeutic targets for PD diagnosis and treatment. Among them, hsa-miR-142 is a critical miRNA in the PD network, and may be involved in PD progression by regulating GNAQ, TMTC2, BEND2, and KYNU.


Nurses' perceptions of reflective practice.
Reflective practice has become an accepted part of nursing development. The authors of this article asked clinicians and managers in their trust how they thought reflective practice may be enhanced. The study has enabled the trust to develop reflective practice in a number of ways which may benefit clinicians, managers and patients.


Effects of early deafness on development of brain stem auditory neurons.
Early destruction of the otocyst (embryonic precursor of the inner ear) in chick embryos results in complex changes in developing central auditory pathways. In the cochlear nucleus angularis (NA) and nucleus magnocellularis (NM), 30% to 40% of the neurons die after otocyst removal, the survivors are shrunken, and some neurons in the NA migrate to an abnormal position in the brain stem. The characteristic forms of cochlear nucleus neurons develop normally in the absence of cochlear nerve input, however. In the nucleus laminaris (NL), development of normal dendritic size is dependent on a normal inner ear, but most of the highly specialized dendritic organization of this nucleus, which is important for low-frequency sound localization, can develop normally in the absence of cochlear influences. Otocyst removal induces formation of a permanent functional aberrant axonal projection to the ipsilateral NM from the contralateral NM. Although these aberrant axons form functional glutamatergic synapses, these show immature functional properties, suggesting that cochlear nerve inputs are necessary for normal maturation of glutamate receptors on auditory neurons. Treatment of chick embryo for a brief period in ovo with 6-cyano-7-nitroquinoxaline-2,3-dione, a quinoxalinedione antagonist of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate-kainate subtype of glutamate receptor, completely and permanently prevents the neuronal loss in the NM produced by otocyst removal. The work reviewed has 1) identified aspects of development in central auditory neurons that are perturbed by profound early sensorineural loss, 2) identified aspects of development that appear independent of cochlear influences, and 3) suggested a potential chemotherapeutic approach to prevention of central neuronal death after early damage to the cochlea.


THE EFFECT OF COEXISTENCE ON COMPETITIVE OUTCOME IN TRIBOLIUM CASTANEUM AND TRIBOLIUM CONFUSUM.
We describe an experiment exploring the effects of coexistence and population differentiation on the competitive outcome of two species of Tribolium flour beetles, T. castaneum and T. confusum. The only manipulation was whether the populations used in the competitive phase of the study were raised initially in mixed-species communities, single-species populations, or in the standard culture conditions used to maintain stocks in the laboratory. Any treatment effects observed were due to natural selection acting within populations and genetic drift. In the competitive phase, we examined 10 mixed-species communities and 10 pairs of single-species populations. We replicated each community 15 times to provide an assessment of the distribution of competitive outcome. Statistical analysis demonstrates the lineages within the treatments became highly differentiated for all measures of competitive outcome: the outcome of competition (which species won), time to extinction of one of the competing species, and census history. The fraction of the variance that is among lineages has been referred to as the group or community heritability. All of these measures of competitive outcome had high community level heritabilities indicating that competitive ability would evolve rapidly as a result of group or community level selection. In contrast, competitive outcome was not affected by whether the two species had coexisted prior to the competitive phase. This indicates that the outcome of competition was not systematically changed by processes acting within the two species communities.


Optimal heat emissivity control of n population system based on individual size-distribution.
This paper generalizes a class of controllability problems based on the scale structure population system model. Based on the comparison principle of linear systems, the solution of the nonlinear system model is obtained by referring to the fixed point theorem. The non-negative, boundedness, existence, and uniqueness of the solution of the system model are established. The optimality condition is described in detail by means of a normal cone and conjugate system under the condition of proving the continuous dependence of the state environment on the solution to control variables.


Molecular cloning and characterization of a novel Y-box gene from planarian Dugesia japonica.
Y-box binding protein (YB protein) is an ancient conserved multifunctional DNA/RNA-binding protein. A novel YB protein DjY2 gene from planarian Dugesia japonica was cloned by RACE method and characterized. This cDNA contains 689 bp with a putative open reading frame of 197 amino acids. It has a predicted molecular mass of 22.14 kDa and an isoelectric point of 9.67. Whole-mount in situ hybridization and relative quantitative real-time PCR were used to study the spatial and temporal expression pattern of DjY2 in the process of planarian regeneration. Results showed that DjY2 was expressed in many parts of the body in intact planarian, but the expression level was low in head and pharynx. The transcripts of DjY2 was significantly increased both at the head parts and the tail parts after amputation, especially at the site of cutting. The spatial expression gradually recovered to the state of intact planarian with the time of regeneration. Our results indicated that DjY2 might participate in the process of regeneration in planarian.


[Diagnostic problem of ordinary chronic urticaria].
On the basis of literature data new classification of chronic urticaria was presented, depending on pathogenetic factors and clinical picture. The most frequent causes of the disease, such as food, drugs, infectious and hormonal factors were discussed in detail. The relationship between ordinary chronic urticaria and other systemic diseases was underlined.


Knowledge, Awareness, and Attitudes about Research Ethics among Dental Faculty in the Middle East: A Pilot Study.
Objective. To assess the knowledge, awareness, and attitudes of dental faculty regarding research ethics and research ethics committees (RECs). Design. Through convenience sampling, we distributed a survey to academics at dental faculties at two universities in the Middle East. We used descriptive, chi-square, and logistic regression statistics to analyze the data. Results. Our response rate was 62.5%. A large majority (>90%) held positive attitudes towards RECs; however, almost half (44.0%) thought that RECs would delay research. Less than half (36.8%) had received prior training in research ethics, and the average score they achieved on the questions on research ethics was only 40.2%. Most (>90%), however, were favorable towards research ethics education. Finally, some faculty held attitudes regarding certain research ethics practices that were not optimal. Conclusions. We conclude that among the dental faculties participating in our study, there is broad-based acceptance of RECs and training in research ethics, while there are knowledge gaps in research ethics. We recommend further studies to determine the generalizability of our findings to other institutions.


Telemedicine approach for psoriasis management, time for application? A systematic review of published studies.
Psoriasis is a common chronic inflammatory skin condition. It has a chronic course with multiple evolving relapses and patients require long-term treatment and follow-up. Teledermatology was introduced for diagnosis, treatment and follow-up of chronic diseases. Thus, we performed a systematic review for collecting the evidence regarding the efficacy of telemedicine in psoriasis management. Out of 287 records, we included seven studies (four of which were randomized controlled trials). We found that telemedicine alone or combined with usual care had the same or higher efficacy of psoriasis management compared to usual care or control group. We recommend further studies for assessing the pros and cons of this intervention which can replace conventional strategies especially in pandemic times.


Disinfection of Multidrug Resistant Escherichia coli by Solar-Photocatalysis using Fe-doped ZnO Nanoparticles.
Spread of antibiotic resistant bacteria through water, is a threat to global public health. Here, we report Fe-doped ZnO nanoparticles (Fe/ZnO NPs) based solar-photocatalytic disinfection (PCD) of multidrug resistant Escherichia coli (MDR E. coli). Fe/ZnO NPs were synthesized by chemical precipitation technique, and when used as photocatalyst for disinfection, proved to be more effective (time for complete disinfection = 90 min) than ZnO (150 min) and TiO2 (180 min). Lipid peroxidation and potassium (K+) ion leakage studies indicated compromisation of bacterial cell membrane and electron microscopy and live-dead staining confirmed the detrimental effects on membrane integrity. Investigations indicated that H2O2 was the key species involved in solar-PCD of MDR E. coli by Fe/ZnO NPs. X-ray diffraction and atomic absorption spectroscopy studies showed that the Fe/ZnO NPs system remained stable during the photocatalytic process. The Fe/ZnO NPs based solar-PCD process proved successful in the disinfection of MDR E. coli in real water samples collected from river, pond and municipal tap. The Fe/ZnO NPs catalyst made from low cost materials and with high efficacy under solar light may have potential for real world applications, to help reduce the spread of resistant bacteria.


Efficacy of diclofenac in lateral epicondylitis of the elbow also treated with immobilization. The University of Montreal Orthopaedic Research Group.
To evaluate the efficacy of an oral nonsteroidal anti-inflammatory drug in the treatment of lateral epicondylitis. Multicenter double-blind randomized controlled trial in which the following hypothesis was tested: whether diclofenac sodium provided a 20% or greater improvement over rest and cast immobilization in the response rate to treatment of lateral epicondylitis beyond and over rest in an experimental group compared with a control group after 4 weeks of treatment. Recruitment from urban general practices and referrals to 4 university hospitals. During a 1-year period, 206 subjects aged 18 to 60 years with lateral epicondylitis were recruited from the clientele treated by family physicians. Thirty subjects refused to participate and 47 presented with exclusion criteria, leaving 129 subjects who entered the study. One subject withdrew after 21 days. The experimental group was treated with a daily dose of diclofenac sodium (150 mg) for 28 days, while the control group received a placebo during the same period. In addition, both groups were immobilized in a cast for 14 days and were told not to perform repetitive movements of the involved limb for 21 days. Measuring instruments consisted of grip strength measurements with a squeeze dynamometer, a visual analog pain scale, a visual analog function scale, and an 8-item pain-free function index. A statistically and clinically significant reduction of pain was associated with treatment with diclofenac, but no clinically significant difference in grip strength or functional improvement could be detected between the 2 groups. Secondary effects (diarrhea and abdominal pain) were significantly more frequent in the diclofenac-treated group. Taking into account the limited improvement noted over rest and cast immobilization and the number of associated adverse events, it is difficult to recommend the use of diclofenac in the treatment of lateral epicondylitis at the dosage used in this study.


In-solution conformational analysis of the XCYCH3 moiety for small esters and ethers with all combinations of X, Y = O, S.
Favorable steric and electrostatic fit of a ligand to a receptor is of central interest in theoretical drug design. This paper considers the effects of non-protic solvents, in comparison with the gas phase, on the preferred conformation of the XCYCH3 moiety of simple aliphatic esters and heterocyclic methyl ethers with all combinations of the X and Y atoms as oxygen and sulfur. An IEF-PCM/B97D/aug-cc-pv(t+d)z continuum dielectric solvent study in chloroform and acetonitrile explores the through-space polarization effect of the environment on the conformational preference, not affected by possible solute-solvent hydrogen bond formation. The inherently favored structure for the present molecules is important, since the hypothetical oxygen and sulfur lone-pairs point approximately in opposite directions in the cis conformation of esters, whereas the trans and gauche conformations for the methyl group in ethers define nearly parallel or perpendicular directionality for the lone pairs of the ring heteroatoms and the O or S atoms connecting to the ring. These different preferences for the studied two families of compounds allow for designing formation of hydrogen bonds with a protein in fairly different regions of the latter still within the ligand-binding cavity. For a fine-tuning of these hydrogen bonds, a replacement of an oxygen atom of the ligand by a sulfur atom could be a straightforward possibility.


Can Community Health Center funding enhance health services for Native American tribes and organizations?
This paper reports on the applicability of the Public Health Service Act (42 USC, 254b) Section 330 Community Health Center program to Arizona Native American tribes and organizations. Data review and analysis consisted of a review of two federal government documents concerning the funding of Community Health Center applications and a review of questionnaire responses received from the Arizona Native American health care community. Findings indicate a general lack of knowledge among the Arizona Native American health care community about the program as well as a need for capacity building among Arizona Native American tribes and organizations. As currently designed, the program has built-in barriers that prevent Native American tribes and organizations from applying for funding. Changes must be made to the existing program and local-level seminars must be offered to make this program and funding more readily available to Arizona Native American tribes and organizations.


Osteoblastoma: a study of 12 cases.
This study comprises of 12 cases of osteoblastoma. There were 8 males and 4 females, with a mean age of 17.8 years. The vertebral column, including the sacrum was the most frequent site (10 of 12 cases). Radiologically the lesions were lytic, well circumscribed and expansile. The histology consisted of intercommunicating osteoid seams lined by plump osteoblasts with numerous intervening ectatic stromal vessels. Despite these characteristic features, the distinction of osteoblastoma from osteoblastic osteosarcoma can at times be very problematic. The lack of lace-like osteoid or sheets of osteoblasts, and inconspicuous mitotic activity are useful distinguishing features. The purpose of this communication is to highlight the microscopic features for the correct recognition of osteoblastoma and its distinction from other osteoid forming bone lesions.


Neurotoxic lesions of the rat perirhinal cortex fail to disrupt the acquisition or performance of tests of allocentric spatial memory.
Rats with neurotoxic lesions of the perirhinal cortex (n = 9) were compared with sham controls (n = 14) on a working memory task in the radial arm maze. Rats were trained under varying levels of proactive interference and with different retention intervals. Finally, performance was assessed when the maze was switched to a novel room. None of these manipulations differentially impaired rats with perirhinal lesions. Rats were next trained on delayed matching-to-place in the water maze. Even with retention delays of 30 min, there was no evidence of a deficit. Although interactions between the perirhinal cortex and hippocampus may be important for integrating object-place information, the perirhinal cortex is often not necessary for tasks that selectively tax allocentric spatial memory.


The use of massive bone allografts for intercalary reconstruction and arthrodeses after tumor resection. A multicentric European study.
A multicentric study was conducted by the European Musculoskeletal Oncology Society on 113 cases of resection for tumors of the major long bones and reconstruction with massive allografts, as intercalary diaphyseal or for arthrodesis. The follow-up was at least 12 months. There was a 14% incidence of infection, with a higher frequency (18.5%) in intercalary grafts as compared to arthrodeses (7%). Fracture of the graft occurred in 15.5% of the cases with a prevalence in the humerus (28.5%) as compared to the tibia (21.4%) and femur (14.7%). Fracture constantly occurred after osteosynthesis with screws, in 16% of the cases after osteosynthesis with a plate, and in 12.5% of the cases after osteosynthesis with an intramedullary nail. It was observed in 32% of the grafts preserved at -30 degrees, in 17% of those irradiated, and in 7% and 7.6% of those preserved at -180 degrees and -80 degrees, respectively. Delayed union and non-union was observed in 57% of the cases: 63% in intercalary grafts, 48% in arthrodeses. Final results after treatment of complications were excellent and good in 63% of the entire series. The results should, however, be evaluated after 3 years, as during this period of time important transformation phenomena of the graft occur. Complications are observed in 75% of the cases, but they may be reduced if planning is correct and surgery is accurate. Each complication may be dealt with and resolved without high risks for preservation of the limb.


Functional biochar in enhanced anaerobic digestion: Synthesis, performances, and mechanisms.
Anaerobic digestion technology is crucial in bioenergy recovery and organic waste management. At the same time, it often encounters challenges such as low organic digestibility and inhibition of toxic substances, resulting in low biomethane yields. Biochar has recently been used in anaerobic digestion to alleviate toxicity inhibition, improve the stability of anaerobic digestion processes, and increase methane yields. However, the practical application of biochar is limited, for the properties of pristine biochar significantly affect its application in anaerobic digestion. Although much research focuses on understanding original biochar's fundamental properties and functionalization, there are few reviews on the applications of functional biochar and the effects of critical properties of pristine biochar on anaerobic digestion. This review systematically reviewed functionalization strategies, key performances, and applications of functional biochar in anaerobic digestion. The properties determining the role of biochar were reviewed, the synthesis methods of functional biochar were summarized and compared, the mechanism of functional biochar was discussed, and the factors affecting the function of functional biochar were reviewed. This review provided a comprehensive understanding of functional biochar in anaerobic digestion processes, which would be helpful for the development and applications of engineered biochar.


Neutron bang time detector based on a light pipe.
A neutron bang time detector consisting of a scintillator, light pipe, photomultiplier tube (PMT), and high-bandwidth oscilloscope has been implemented on the 60-beam, 30 kJ OMEGA Laser Facility at the University of Rochester's Laboratory for Laser Energetics. Light from the scintillator, located 23 cm from the target, is transmitted from the target bay through a 9.6-m-long, 2 in. diameter polished stainless steel pipe to the PMT. The PMT signal is recorded by two channels of a 6 GHz, 10 GSs Tektronix 6604 oscilloscope. The OMEGA optical fiducial pulse train is recorded on the third oscilloscope channel using a fast photodiode to provide the timing reference to the laser. This bang time detector is absolutely temporally calibrated and has been demonstrated to measure the bang time for neutron yields above 1x10(9) with an accuracy of better than 25 ps.


Caring and uncaring encounters within nursing and health care from the cancer patient's perspective.
The aim of this phenomenological study was to explore caring and uncaring encounters with nurses and other health professionals from the perspective of the person who has been diagnosed and treated for cancer. Through thematic analysis of in-depth dialogues with five women and four men in the remission or recovery phase of cancer, three major categories regarding caring and uncaring encounters were identified. The essential structure of a caring encounter was found to be threefold: 1. the nurse/health professional perceived as caring: an indispensable companion on the cancer trajectory; 2. the resulting mutual trust and caring connection; and 3. the perceived effect of the caring encounter: a sense of solidarity, empowerment, well-being, and healing. The essential structure of an uncaring encounter is also threefold: 1. the nurse/health professional perceived as uncaring: an unfortunate hindrance to the perception of well-being and healing; 2. the resulting sense of mistrust and disconnection; and 3. the perceived effect of the uncaring encounter: a sense of uneasiness, discouragement, and a sense of being broken down. The findings emphasize the primacy of competence in professional caring, as well as that of genuine concern, openness and a willingness to connect with others. The often devastating effects of uncaring encounters on the recipient of nursing and health care raises the question whether uncaring as an ethical and a professional problem should perhaps be dealt with as malpractice in nursing and health care.


Effect of Jianweiyuyang granule on gastric ulcer recurrence and expression of VEGF mRNA in the healing process of gastric ulcer in rats.
To investigate the effect of Jianweiyuyang (JWYY) granule on gastric ulcer recurrence and its mechanism in the treatment of gastric ulcer in rats. Gastric ulcer in rats was induced according to Okeba's method with minor modification and the recurrence model was induced by IL-1beta. The expression of vascular endothelial growth factor mRNA (VEGF mRNA) was examined by reverse transcription polymerase chain reaction in gastric ulcer and microvessel density (MVD) adjacent to the ulcer margin was examined by immunohistochemistry. MVD was higher in the JWYY treatment group (14.0+/-2.62) compared with the normal, model and ranitidine treatment groups (2.2+/-0.84, 8.8+/-0.97, 10.4+/-0.97) in rats (P<0.01). The expression level of VEGF mRNA in gastric tissues during the healing process of JWYY treatment group rats significantly increased compared with other groups (normal group: 0.190+/-0.019, model group: 0.642+/-0.034, ranitidine group: 0.790+/-0.037, P<0.01). JWYY granules can stimulate angiogenesis and enhance the expression of VEGF mRNA in gastric ulcer rats. This might be the mechanism for JWYY accelerating the ulcer healing, and preventing the recurrence of gastric ulcer.


c-myc is required for osteoclast differentiation.
The role of the receptor activator of nuclear factor kappaB (NF-kappaB) ligand (RANKL)-a tumor necrosis factor (TNF)-related cytokine-in osteoclast formation has been established clearly. However, the downstream signaling pathways activated by this cytokine remain largely unknown. To identify genes that play a role in osteoclastogenesis, we used RAW 264.7 mouse monocytes as a model system for the differentiation of multinucleated osteoclasts from mononucleated precursors. RAW 264.7 cells were induced with RANKL to form multinucleated giant osteoclast-like cells (OCLs) that expressed a number of osteoclast-specific markers and were able to form resorption pits on both calcium phosphate films and bone slices. This system was used to identify genes that are regulated by RANKL and may play a role in osteoclast differentiation. The proto-oncogene c-myc was strongly up-regulated in RANKL-induced OCLs but was absent in undifferentiated cells. Expression of Myc partners Max and Mad, on the other hand, was constant during OCL differentiation. We expressed a dominant negative Myc in RAW 264.7 cells and were able to block RANKL-induced OCL formation. Northern Blot analysis revealed a delay and a significant reduction in the level of messenger RNA (mRNA) for tartrate-resistant acid phosphatase (TRAP) and cathepsin K. We conclude that c-myc is a downstream target of RANKL and its expression is required for RANKL-induced osteoclastogenesis.


Proximal tubular cells promote fibrogenesis by TGF-beta1-mediated induction of peritubular myofibroblasts.
In proteinuric nephropathies with increasingly severe defects of the glomerular filtering barrier, interstitial fibrogenesis is a major effector of scarring. An early event in this process is the peritubular accumulation of myofibroblasts that express alpha-smooth muscle actin (alpha-SMA) and contribute to abnormal matrix production. Common trigger factors are poorly understood. Enhanced protein trafficking may play a role by up-regulating inflammatory and fibrogenic genes in proximal tubular cells. The remnant kidney model in rats was used to (1) analyze interactions between activated proximal tubular cells, peritubular cells expressing the myofibroblast marker, and inflammatory cells at time intervals (days 7, 14, and 30) after surgery, and (2) evaluate the effects of angiotensin-converting enzyme inhibitor (ACEi) on protein trafficking, fibrogenic signaling, and alpha-SMA expression. Abnormal uptake of ultrafiltered proteins by proximal tubular cells (IgG staining) occurred at an early stage (day 7) and was subsequently associated with macrophage and alpha-SMA+ cell accumulation into the peritubular interstitium. alpha-SMA+ cells clustered with macrophages into the interstitium. These changes were associated with appearance of transforming growth factor-beta1 (TGF-beta1) mRNA in proximal tubular cells and in the infiltrating cells with time. At day 30, focal alpha-SMA staining also was found in the tubular cells and in peritubular endothelial cells on semithin ultracryosections. ACEi prevented both proteinuria and abnormal protein accumulation in tubular cells, as well as the inflammatory and fibrogenic reaction with peritubular alpha-SMA expression. Profibrogenic signaling from both proximal tubular cells on challenge with filtered protein and inflammatory cells is implicated as a key candidate trigger of progressive tubulointerstitial injury.


The growing use of echocardiography--a double-edged sword?
I believe that the growing volume of echocardiographic services is indeed a double-edge sword. On the one hand, it provides eloquent testimony to the versatility and perceived value of echocardiography to patient care. On the other hand, it underlines the significant resources consumed by providing these services. In these times of "do more with less," doing more can have some negative consequences. I believe that we must each act in a responsible manner, doing our part to be sure that the services we provide are truly needed. We must ask ourselves, and discuss with our referring physicians, "How will the results of this study alter patient care?" On occasion, we may find that a requested study really does not need to be performed. At the very least, this dialogue should allow us to refine the focus of the study and provide the most useful information to the treating physician. We must collect good outcomes data documenting those circumstances in which echocardiography improves outcomes and those clinical settings in which echocardiography is not helpful. We must continue to improve our skills to provide the best services to our patients. And we must also continue to adapt to changes in the health care environment. At the same time, I do not think that we can or should sacrifice quality in an effort to control costs. Clearly, incorrect or misleading information cannot be either cost-effective or good for patient care. We must therefore continue to uphold high professional standards and to work with regulatory agencies ensure that the resources allocated to echocardiographic services are adequate to do them well. ASE's mission statement, which emphasizes that we are "...dedicated to excellence in the development and application of cardiovascular ultrasound to patient care," demands no less.


Ovarian cancer screening.
Ovarian cancer is the fourth commonest cause of cancer deaths in women. Multimodal screening with serum CA125 and transvaginal ultrasonography have been shown to improve survival. However, the results so far do not justify routine screening until the impact of screening on mortality has been assessed in larger randomized trials.


[Vestibular cochlear disturbances in multiple sclerosis].
To specify the character of vestibular cochlear disturbances in multiple sclerosis (MS) and mechanisms of their formation, the objective quantitative evaluation of experimental caloric nystagmus using the computer electronystagmographic method and a comparison of hearing impairment with asymmetry of vestibular reactions were conducted in 48 patients with MS. The peculiarities of vestibular disturbance found in the study suggest a predominance of central vestibular syndrome with both subtentorial and supratentorial traits. The influence of the heat stimulus of vestibular analyzer (hot water caloric test) in multiple sclerosis revealed during computer electronystagmography may have diagnostic value.


Dicer and microRNAs protect adult dopamine neurons.
MicroRNAs (miRs) are important post-transcriptional regulators of gene expression implicated in neuronal development, differentiation, aging and neurodegenerative diseases, including Parkinson's disease (PD). Several miRs have been linked to PD-associated genes, apoptosis and stress response pathways, suggesting that deregulation of miRs may contribute to the development of the neurodegenerative phenotype. Here, we investigate the cell-autonomous role of miR processing RNAse Dicer in the functional maintenance of adult dopamine (DA) neurons. We demonstrate a reduction of Dicer in the ventral midbrain and altered miR expression profiles in laser-microdissected DA neurons of aged mice. Using a mouse line expressing tamoxifen-inducible CreERT2 recombinase under control of the DA transporter promoter, we show that a tissue-specific conditional ablation of Dicer in DA neurons of adult mice led to decreased levels of striatal DA and its metabolites without a reduction in neuronal body numbers in hemizygous mice (DicerHET) and to progressive loss of DA neurons with severe locomotor deficits in nullizygous mice (DicerCKO). Moreover, we show that pharmacological stimulation of miR biosynthesis promoted survival of cultured DA neurons and reduced their vulnerability to thapsigargin-induced endoplasmic reticulum stress. Our data demonstrate that Dicer is crucial for maintenance of adult DA neurons, whereas a stimulation of miR production can promote neuronal survival, which may have direct implications for PD treatment.