Population-based estimated reference creatinine values: a novel method of a robust electronic acute kidney injury alert system.
Acute kidney injury (AKI) is common in hospitalized patients. Despite the progress that has been made in the last decade, early identification of AKI cases remains a challenge. In recent years, electronic AKI alert (e-AKI alert) systems have been tested and are usually based on changes in serum creatinine (Cr) values. However, these methods do not include one of the common scenarios, i.e. when there is no available preadmission Cr value available for a patient to compare and hence an e-AKI alert cannot be issued. Therefore, it is essential to have an alternative algorithm to produce e-AKI alerts in such scenarios. We have developed e-AKI alert algorithms which compare serum Cr values at presentation with previous results, within KDIGO AKI guideline-specified classifications. However, where a comparator is not available, we have produced a 'population-based reference Cr value' age and sex matched from 137,000 serum Cr values extracted from blood tests in general practice from our Telepath system. Cr results were split by gender, and then within each group the Cr were stratified according to year of age. The median Cr for each individual year of age was identified and plotted versus age to give separate graphs for males and females that gave excellent fits (R(2)) to cubic regressions. Population-based estimated reference Cr measurements from community blood test results is a more robust method of baseline Cr value estimation in generating potential e-AKI alerts to help early recognition and treatment of AKI cases leading to improved outcome.


Wnt/β-catenin pathway transactivates microRNA-150 that promotes EMT of colorectal cancer cells by suppressing CREB signaling.
A hallmark of aberrant activation of the Wnt/β-catenin signaling pathway has been observed in most colorectal cancers (CRC), but little is known about the role of non-coding RNAs regulated by this pathway. Here, we found that miR-150 was the most significantly upregulated microRNA responsive to elevated of Wnt/β-catenin signaling activity in both HCT116 and HEK293T cells. Mechanistically, the β-catenin/LEF1 complex binds to the conserved TCF/LEF1-binding element in the miR-150 promoter and thereby transactivates its expression. Enforced expression of miR-150 in HCT116 cell line transformed cells into a spindle shape with higher migration and invasion activity. miR-150 markedly suppressed the CREB signaling pathway by targeting its core transcription factors CREB1 and EP300. Knockdown of CREB1 or EP300 and knockout of CREB1 by CRISPR/Cas9 phenocopied the epithelial-mesenchymal transition (EMT) observed in HCT116 cells in response to miR-150 overexpression. In summary, our data indicate that miR-150 is a novel Wnt effector that may significantly enhance EMT of CRC cells by targeting the CREB signaling pathway.


The non-Huntington disease choreas: Five new things.
Chorea can be due to a wide variety of causes. In this review, I provide updates on several recently identified genetic and autoimmune causes of chorea, and review evidence supporting the use of deep brain stimulation in chorea. New genes that may cause chorea include ADCY5 (encoding for adenylate cyclase 5) C9ORF72 (in addition to amyotrophic lateral sclerosis and frontotemporal dementia), and those responsible for the neurodegeneration with brain iron accumulation disorders. Novel autoantibodies are increasingly being identified as associated with a variety of neurologic syndromes, including chorea, in both paraneoplastic and non-paraneoplastic settings. Deep brain stimulation can be a useful intervention in patients with chorea who do not respond to oral medications, whether due to neurodegenerative or nondegenerative causes. New causes of chorea continue to be identified. Correct diagnosis is essential for prognostication and treatment.


Progress in the management of primary and recurrent ovarian carcinomatosis with peritonectomy procedure and HIPEC in a high volume centre.
The treatment of advanced primary or recurrent ephitelial ovarian cancer still remains an open and a critical question. The addition of HIPEC to cytoreductive surgery has shown improving overall survival rates. The aim of our study is to describe the progress in its management in our Unit and what we have learned after more than 350 HIPEC procedures. From 1997 to 2016 we conducted a retrospective analysis from a prospective database. We described and analyzed 4 cut-points, 1997-2004, 2009, 2012 and 2016. From 1997 to September 2016, 358 patients have been operated in our Unit by CRS with peritonectomy procedures plus HIPEC for stage IIIc and IV ovarian cancer. The HIPEC procedures rate was 4,7 HIPEC per years in the first years up to 35 HIPEC/year in last era. Mean age was 56,7 years (28-78). Median PCI was 15,8. (range 3-36). R0-cytoreduction was 95%. Severe morbidity and mortality were observed in 15 % and 2%, respectively. The 3 y OS was 77% in primary and 79% in recurrent ovarian cancer. The stage IV was not a risk factor for survival. R1 cytoreduction and positive lymph nodes were risk factors in multivariate analysis. The addition of HIPEC to CRS improves overall survival rates for primary and recurrent ovarian cancer. This therapeutic strategy was incorporated twenty years ago for a few teams in the world and today there is an emerging and strong evidence that could consider it as an standard treatment for the ovarian carcinomatosis.


The Bacillus subtilis cell division proteins FtsL and DivIC are intrinsically unstable and do not interact with one another in the absence of other septasomal components.
The bacterial septum appears to comprise a macromolecular assembly of essential cell division proteins (the 'septasome') that are responsible for physically dividing the cell during cytokinesis. FtsL and DivIC are essential components of this division machinery in Bacillus subtilis. We used yeast two-hybrid analysis as well as a variety of biochemical and biophysical methods to examine the proposed interaction between Bacillus subtilis FtsL and DivIC. We show that FtsL and DivIC are thermodynamically unstable proteins that are likely to be unfolded and therefore targeted for degradation unless stabilized by interactions with other components of the septasome. However, we show that this stabilization does not result from a direct interaction between FtsL and DivIC. We propose that the observed interdependence of DivIC and FtsL stability is a result of indirect interactions that are mediated by other septasomal proteins.


Low blood concentration of hydroxychloroquine is a marker for and predictor of disease exacerbations in patients with systemic lupus erythematosus.
To study the possible relationship between whole-blood hydroxychloroquine (HCQ) concentrations and clinical efficacy of HCQ in patients with systemic lupus erythematosus (SLE). Whole-blood HCQ concentrations were measured, under blinded conditions, in 143 unselected patients with SLE who had been receiving HCQ 400 mg daily for at least 6 months. The relationship of these concentrations to current disease activity and to subsequent exacerbations during 6 months of followup was investigated. At baseline, 23 patients had active disease (mean +/- SD SLE Disease Activity Index 12.4 +/- 7.5). The mean whole-blood HCQ concentration in this group was significantly lower than that in the 120 patients with inactive disease (694 +/- 448 ng/ml versus 1,079 +/- 526 ng/ml; P = 0.001). Among the 120 patients who had inactive disease at baseline, the mean HCQ concentration at baseline in the 14 (12%) who had disease exacerbations during followup was significantly lower than that in the patients whose disease remained inactive. Multivariate logistic regression showed that the HCQ concentration was the only predictor of exacerbation (odds ratio 0.4 [95% confidence interval 0.18-0.85], P = 0.01). Receiver operating characteristic curve analysis showed that a whole-blood HCQ concentration cutoff of 1,000 ng/ml had a negative predictive value of 96% for exacerbation during followup. Low whole-blood HCQ concentrations are associated with SLE disease activity and are a strong predictor of disease exacerbation. Regular drug assaying and individual tailoring of treatment might help to improve the efficacy of HCQ treatment in patients with SLE.


High Post-treatment α-Fetoprotein Levels and Aspartate Aminotransferase-to-Platelet Ratio Index Predict Hepatocellular Carcinoma in Hepatitis C Virus Decompensated Cirrhotic Patients with Sustained Virological Response After Antiviral Therapy.
Although eradication of hepatitis C virus (HCV) decreases the risk of hepatocellular carcinoma (HCC) development, a considerable level of risk remains in cirrhotic patients with advanced liver disease. Yet, data for the effect of serum markers on HCC development in this population after viral eradication are still lacking. Seventy-eight consecutive patients with HCV infection and decompensated cirrhosis were administered interferon-based regimens at our hospital between August 2008 and December 2013. Thirty-four achieved sustained virological response and were enrolled in the study. Occurrence of HCC was evaluated every 3-6 months post-treatment. The mean age of the 34 patients was 55.7 ± 8.3 years (range: 39-70) old. Compared with baseline, at 24 weeks post-treatment the serum levels were significantly decreased for α-fetoprotein (AFP) (12.20 ± 4.12 versus 8.37 ± 2.75 ng/mL, P < 0.001), aspartate aminotransferase (AST) (58.44 ± 15.12 versus 36.59 ± 11.22 IU/L, P < 0.001), and AST-to-platelet ratio index (APRI) (2.21 ± 0.74 versus 1.35 ± 0.61, P < 0.001) but significantly increased for platelet count (69.65 ± 17.46 versus 73.65 ± 18.0 × 103/μL, P = 0.022). Median follow-up time was 41.4 ± 16.8 (range: 9-71) months, and 5 patients (14.7%) developed HCC. Post-treatment APRI ≥1.5 and AFP ≥10 ng/mL were associated with HCC development (both P < 0.01). Post-treatment AFP and APRI maybe are useful markers to further classify HCC risk in HCV-decompensated cirrhotic patients after viral eradication.


Redox and Calcium Alterations of a Müller Cell Line Exposed to Diabetic Retinopathy-Like Environment.
Diabetic retinopathy (DR) is a common complication of diabetes mellitus and is the major cause of vision loss in the working-age population. Although DR is traditionally considered a microvascular disease, an increasing body of evidence suggests that neurodegeneration is an early event that occurs even before the manifestation of vasculopathy. Accordingly, attention should be devoted to the complex neurodegenerative process occurring in the diabetic retina, also considering possible functional alterations in non-neuronal cells, such as glial cells. In this work, we investigate functional changes in Müller cells, the most abundant glial population present within the retina, under experimental conditions that mimic those observed in DR patients. More specifically, we investigated on the Müller cell line rMC-1 the effect of high glucose, alone or associated with activation processes and oxidative stress. By fluorescence microscopy and cellular assays approaches, we studied the alteration of functional properties, such as reactive oxygen species production, antioxidant response, calcium homeostasis, and mitochondrial membrane potential. Our results demonstrate that hyperglycaemic-like condition per se is well-tolerated by rMC-1 cells but makes them more susceptible to a pro-inflammatory environment, exacerbating the effects of this stressful condition. More specifically, rMC-1 cells exposed to high glucose decrease their ability to counteract oxidative stress, with consequent toxic effects. In conclusion, our study offers new insights into Müller cell pathophysiology in DR and proposes a novel in vitro model which may prove useful to further investigate potential antioxidant and anti-inflammatory molecules for the prevention and/or treatment of DR.


Predictors of pain in general ageing populations: results from a multi-country analysis based on ATHLOS harmonized database.
Pain is a common symptom, often associated with neurological and musculoskeletal conditions, and experienced especially by females and by older people, and with increasing trends in general populations. Different risk factors for pain have been identified, but generally from studies with limited samples and a limited number of candidate predictors. The aim of this study is to evaluate the predictors of pain from a large set of variables and respondents. We used part of the harmonized dataset of ATHLOS project, selecting studies and waves with a longitudinal course, and in which pain was absent at baseline and with no missing at follow-up. Predictors were selected based on missing distribution and univariable association with pain, and were selected from the following domains: Socio-demographic and economic characteristics, Lifestyle and health behaviours, Health status and functional limitations, Diseases, Physical measures, Cognition, personality and other psychological measures, and Social environment. Hierarchical logistic regression models were then applied to identify significant predictors. A total of 13,545 subjects were included of whom 5348 (39.5%) developed pain between baseline and the average 5.2 years' follow-up. Baseline risk factors for pain were female gender (OR 1.34), engaging in vigorous exercise (OR 2.51), being obese (OR 1.36) and suffering from the loss of a close person (OR 1.88) whereas follow-up risk factors were low energy levels/fatigue (1.93), difficulties with walking (1.69), self-rated health referred as poor (OR 2.20) or average to moderate (OR 1.57) and presence of sleep problems (1.80). Our results showed that 39.5% of respondents developed pain over a five-year follow-up period, that there are proximal and distal risk factors for pain, and that part of them are directly modifiable. Actions aimed at improving sleep, reducing weight among obese people and treating fatigue would positively impact on pain onset, and avoiding vigorous exercise should be advised to people aged 60 or over, in particular if female or obese.


Relationships among Bone Quality, Implant Osseointegration, and Wnt Signaling.
A variety of clinical classification schemes have been proposed as a means to identify sites in the oral cavity where implant osseointegration is likely to be successful. Most schemes are based on structural characteristics of the bone, for example, the relative proportion of densely compact, homogenous (type I) bone versus more trabeculated, cancellous (type III) bone. None of these schemes, however, consider potential biological characteristics of the bone. Here, we employed multiscale analyses to identify and characterize type I and type III bones in murine jaws. We then combined these analytical tools with in vivo models of osteotomy healing and implant osseointegration to determine if one type of bone healed faster and supported osseointegration better than another. Collectively, these studies revealed a strong positive correlation between bone remodeling rates, mitotic activity, and osteotomy site healing in type III bone and high endogenous Wnt signaling. This positive correlation was strengthened by observations showing that the osteoid matrix that is responsible for implant osseointegration originates from Wnt-responsive cells and their progeny. The potential application of this knowledge to clinical practice is discussed, along with a theory unifying the role that biology and mechanics play in implant osseointegration.


[Impact of a capitation payment system on healthcare coordination].
To evaluate the impact of the catalan pilot project of capitation payment on healthcare coordination from a qualitative perspective. An exploratory, descriptive, qualitative study was carried out by means of document analysis and individual interviews. A criterion sample of documents and of informants was selected: purchasers (9) and providers (26) managers, and health professionals (16). A content analysis was conducted, with mixed generation of categories and data segmentation by informants' groups, themes, and areas. The study area consisted of the 5 pilot zones. According to the informants, the pilot test facilitated a shared vision of the area and improved communication among providers. Nevertheless, changes introduced as a consequence of the project to improve healthcare coordination were scarce. A virtual alliance among providers with shared objectives and structural changes was found in just one area. Healthcare coordination mechanisms were exchanged, with variable use. Perceived barriers to change were uncertainty, providers' fears of losing their identity, lack of interest, and the management limits of some providers. The designed and implemented capitation payment system failed to generate enough incentives to stimulate changes in healthcare coordination. The weaknesses identified by this evaluation should be resolved before extending the pilot project to the rest of Catalonia.


Late-onset systemic lupus erythematosus in Latin Americans: a distinct subgroup?
To examine the characteristics of patients who developed late onset systemic lupus erythematosus (SLE) in the GLADEL (Grupo Latino Americano de Estudio del Lupus) cohort of patients with SLE. Patients with SLE of less than two years of disease duration, seen at 34 centers of nine Latin American countries, were included. Late-onset was defined as >50 years of age at time of first SLE-related symptom. Clinical and laboratory manifestations, activity index (SLEDAI), and damage index (SLICC/ACR- DI) were ascertained at time of entry and during the course (cumulative incidence). Features were compared between the two patient groups (<50 and ≥50) using descriptive statistics and hypothesis tests. Logistic regression was performed to examine the association of late-onset lupus, adjusting for other variables. Of the 1480 patients included, 102 patients (6.9 %) had late-onset SLE, 87% of which were female. Patients with late-onset SLE had a shorter follow-up (3.6 vs. 4.4 years, p < 0.002) and a longer time to diagnosis (10.1 vs. 5.8 months, p < 0.001) compared to the younger onset group. Malar rash, photosensitivity, and renal involvement were less prevalent while interstitial lung disease, pleural effusions, and sicca symptoms were more frequent in the older age group (p > 0.05). In multivariable analysis, late onset was independently associated with higher odds of ocular (OR = 3.66, 95% CI = 2.15-6.23), pulmonary (OR = 2.04, 95% CI = 1.01-4.11), and cardiovascular (OR = 1.76, 95% CI = 1.04-2.98) involvement and lower odds of cutaneous involvement (OR = 0.41, 95% CI = 0.21-0.80), number of cumulative SLE criteria (OR = 0.79, 95% CI = 0.64-0.97), use of cyclophosphamide (OR = 0.47, 95% CI = 0.24-0.95), and anti-RNP antibodies (OR = 0.43, 95% CI = 0.20-0.91). A Cox regression model revealed a higher risk of dying in older onset than the younger-onset SLE (OR = 2.61, 95% CI = 1.2-5.6). Late-onset SLE in Latin Americans had a distinct disease expression compared to the younger-onset group. The disease seems to be mild with lower cumulative SLE criteria, reduced renal/mucocutaneous involvements, and less use of cyclophosphamide. Nevertheless, these patients have a higher risk of death and of ocular, pulmonary, and cardiovascular involvements.


Electrostatic Adsorption Behavior of Zwitterionic Copolymers on Negatively Charged Surfaces.
To investigate the effect of the surface properties and the coating layer properties on surface modification via electrostatic adsorption, the electrostatic adsorption behavior of zwitterionic copolymers on negatively charged surfaces was studied. A series of positively charged zwitterionic copolymers and a series of negatively charged surfaces, including porous substrates and dense films, were fabricated. The electrostatic adsorption behavior of the zwitterionic copolymers on the negatively charged porous substrates was confirmed using the contact angles and fluorescently labeled protein adsorption experiments. The adsorption behavior of the zwitterionic copolymers on the negatively charged dense films was confirmed using quartz crystal microbalance determination and a fluorescently labeled protein adsorption experiment. The results indicated that a lower charge density on the zwitterionic copolymer brings about a higher adsorption mass on the charged surface, whereas an extremely low charge density on the coating layer results in a lower adsorption mass on the charged surface, due to weak interaction. A high density of the film surface charge is beneficial for surface adsorption, whereas an extremely high density of the film surface charge leads to low surface adsorption due to steric hindrance of the negatively charged sites. This work provides an insight into the best strategy for surface modification via electrostatic adsorption.


Spatial and temporal variability of Alexandrium cyst fluxes in the Gulf of Maine: Relationship to seasonal particle export and resuspension.
Quantification of Alexandrium cyst fluxes through the Gulf of Maine water column is central to understanding the linkage between the source and fate of annual Alexandrium blooms in the offshore waters. These blooms often lead to paralytic shellfish poisoning (PSP) and extensive closures of shellfish beds. We report here on time-series sediment trap deployments completed at four offshore locations in the gulf between 2005 and 2010 as components of two ECOHAB-GOM field programs. Data presented documents the substantial spatial and temporal fluctuations in Alexandrium fundyense cyst fluxes in the gulf. Cyst delivery out of the euphotic zone peaked primarily between July and August following annual spring-summer Alexandrium blooms and was greatest in the western gulf. At all sites, cyst flux maxima to the subsurface waters were rarely coincident with seasonal peaks in the total mass export of particulate material indicating that cyst delivery was primarily via individually sinking cysts. Where persistent benthic nepheloid layers (BNLs) exist, significant sediment resuspension input of cysts to the near-bottom water column was evidenced by deep cyst fluxes that were up to several orders of magnitude greater than that measured above the BNL. The largest cyst fluxes in the BNL were observed in the eastern gulf, suggesting greater resuspension energy and BNL cyst inventories in this region. Temporal similarities between peak cyst export out of the upper ocean and peak cyst fluxes in the BNL were observed and document the contribution of seasonal, newly formed cysts to the BNL. The data however also suggest that many Alexandrium cells comprising the massive, short-lived blooms do not transition into cysts. Time-series flow measurements and a simple 1D model demonstrate that the BNL cyst fluxes reflect the combined effects of tidal energy-maintained resuspension, deposition, and input of cysts from the overlying water column.


The neural basis of maternal responsiveness to infants: an fMRI study.
Using fMRI, we examined the neural correlates of maternal responsiveness. Ten healthy mothers viewed alternating blocks of video: (i) 40 s of their own infant; (ii) 20 s of a neutral video; (iii) 40 s of an unknown infant and (iv) 20 s of neutral video, repeated 4 times. Predominant BOLD signal change to the contrasts of infants minus neutral stimulus occurred in bilateral visual processing regions (BA 19,21,37,38); to own infant minus unknown infant in right anterior temporal pole (BA 38), left amygdala and visual cortex (BA 19), and to the unknown infant minus own infant contrast in bilateral orbitofrontal cortex (BA 10,47) and medial prefrontal cortex (BA 8) [corrected] These findings suggest that amygdala and temporal pole may be key sites in mediating a mother's response to her infant and reaffirms their importance in face emotion processing and social behaviour.


The T-box gene family: emerging roles in development, stem cells and cancer.
The T-box family of transcription factors exhibits widespread involvement throughout development in all metazoans. T-box proteins are characterized by a DNA-binding motif known as the T-domain that binds DNA in a sequence-specific manner. In humans, mutations in many of the genes within the T-box family result in developmental syndromes, and there is increasing evidence to support a role for these factors in certain cancers. In addition, although early studies focused on the role of T-box factors in early embryogenesis, recent studies in mice have uncovered additional roles in unsuspected places, for example in adult stem cell populations. Here, I provide an overview of the key features of T-box transcription factors and highlight their roles and mechanisms of action during various stages of development and in stem/progenitor cell populations.


Injury surveillance in the ED: design, implementation, and analysis.
Comprehensive, population-based surveillance for nonfatal injuries requires uniform methods for data collection from multiple hospitals. To show issues related to design and implementation of multihospital, emergency department (ED), injury surveillance, a city-wide system in the United States is discussed. From October 1, 1995 to September 30, 1996 all injury-related ED visits among District of Columbia residents <3 years of age were ascertained at the 10 hospitals where city children routinely sought care. Information was abstracted from 2,938 injury-related, ED visits (132.7 visits/1,000 person-years). Based on this experience, suggestions to facilitate design of multihospital, injury surveillance in other locations are offered. Importantly, injury-related visits were reliably ascertained from ED logs, and for most variables, a systematic sample of injury-related visits was representative of the total injured population. However, there is a need for more complete documentation of circumstances surrounding injuries and for standardization of data elements on ED logs and treatment records.


Cardiac amyloidosis secondary to multiple myeloma.
Amyloidosis is a multisystemic disease caused by extracellular deposition of pathologic beta fibrillar proteins in multiple organs. Deposited fibrils can be either innunoglobulin light chanis or amyloid-A protein. The incidence of anyloidosis derived from anyloid-A protein, usually associated to an underlying disease, has been dimisishing over the decades in the United States producing clinical evidence of cardiac involvement in less than 5% of all cases. The extent of cardiac involvement is the determining prognostic factor. Early diagnosis and therapy aimed at the underlying disease may halt progression of cardiac dysfuction and improve prognosis. We report a case of a 63-year-old man who was diagnosed with cardiac amyloidosis secondary to multiple myeloma.


Congenital Analbuminemia in a Korean Male Diagnosed with Single Nucleotide Polymorphism in the ALB Gene: The First Case Reported in Korea.
Congenital analbuminemia (CAA) is an autosomal recessive disease characterized by extremely low serum levels of albumin. CAA is caused by various homozygous or heterozygous mutations of the ALB gene. Patients often exhibit no clinical symptoms, aside from rare accompanying conditions, such as fatigue, ankle edema, and hypotension. This case report describes the case of a 28-year-old asymptomatic Korean male referred to our center with hypocalcemia, vitamin D deficiency, and hypoalbuminemia who was diagnosed with CAA. To determine the cause of hypoalbuminemia in the patient, laboratory tests, radiological examination, and DNA sequencing were performed. The patient was confirmed to not exhibit any other clinical conditions that can induce hypoalbuminemia and was diagnosed with CAA using DNA sequencing. The present case of CAA is the first to be reported in Korea.


A personal reflection: family survival in the pediatric intensive care unit.
Being the parent of a child hospitalized in a pediatric intensive care unit can be frightening and very stressful. This personal reflection is written by a father whose son was a patient in such a unit and conveys his feelings and thoughts about the experience. This is the first of a 2-part article. The second article will discuss "The Family Survival Guide to the Intensive Care Unit" in detail.


Pneumothorax and Pneumomediastinum Complicating Organophosphate Poisoning: A Case Series of Complications Less Understood.
Organophosphate compounds are used as insecticides in agricultural and domestic settings throughout the world. Acute organophosphorus (OP) poisoning is a major public health issue. Early diagnosis of OP poisoning and prompt atropinization can save lives. Respiratory failure may occur in patients with OP poisoning for many reasons, including aspiration of gastric contents, excessive secretions, pneumonia, and sepsis complicating acute respiratory distress syndrome. Till date, however, spontaneous pneumothorax and pneumomediastinum have not been reported in cases of OP poisoning. This report presents two similar cases of OP poisoning in which spontaneous pneumothorax and pneumomediastinum developed following OP ingestion.


Pattern of malignant solid tumors and lymphomas in children in the east delta of Egypt: A five-year study.
Worldwide, the incidence and mortality rates of childhood cancers differ. The study of incidence patterns and survival rates in childhood malignancies is important in aiding in the planning of treatment centers and in obtaining further information with regard to the etiology. Few studies have investigated the survival in cases of childhood solid tumors in Egypt. The aim of the current study was to evaluate the patterns, frequency and outcome of solid tumors and lymphomas in children admitted to and followed up at the Pediatric Oncology Department of Zagazig University Hospital (Zagazig, Egypt) over a duration of 5 years (January 2004 to December 2008). A retrospective study was conducted, which included 155 children with solid tumors and lymphomas. The medical records were reviewed and the relevant data collected, in particular, those concerning demographic, clinical, histopathological, laboratory and imaging data as well as the treatment plans and outcomes. The mean age of patients was 5.6±3.04 years at diagnosis. The patients comprised 94 males and 61 females. Non-Hodgkin lymphoma (NHL) was the most common tumor type, followed by neuroblastoma (31.0 and 29.0%, respectively). When patients were stratified in terms of age (<5, ≥5 but <10, and ≥10 years), the <5-years-of-age group exhibited the greatest number of patients. Fever, pallor and pain were the most frequent initial clinical presentations among the patients and stage II was the most common stage (39.1%) followed by stage IV, III and I (35.0, 20.3 and 5.6% respectively). The overall 5-year survival rate in the study group was 66.7%. The survival rate was significantly higher in patients with Wilm's tumor and Hodgkin lymphoma, followed by NHL (92.0, 88.0 and 72.0%, respectively; P<0.001), while the mortality rate was significantly higher in patients with neuroblastoma (P<0.001). In conclusion, NHL and neuroblastoma were the most common tumors; the survival rates were higher in patients with Wilm's tumor and Hodgkin lymphoma and lower in patients with neuroblastoma. A larger multicenter study is required to further investigate the conclusions drawn from this study.


Pulmonary surfactants and their role in pathophysiology of lung disorders.
Surfactant is an agent that decreases the surface tension between two media. The surface tension between gaseous-aqueous interphase in the lungs is decreased by the presence of a thin layer of fluid known as pulmonary surfactant. The pulmonary surfactant is produced by the alveolar type-II (AT-II) cells of the lungs. It is essential for efficient exchange of gases and for maintaining the structural integrity of alveoli. Surfactant is a secretory product, composed of lipids and proteins. Phosphatidylcholine and phosphatidylglycerol are the major lipid constituents and SP-A, SP-B, SP-C, SP-D are four types of surfactant associated proteins. The lipid and protein components are synthesized separately and are packaged into the lamellar bodies in the AT-II cells. Lamellar bodies are the main organelle for the synthesis and metabolism of surfactants. The synthesis, secretion and recycling of the surfactant lipids and proteins is regulated by complex genetic and metabolic mechanisms. The lipid-protein interaction is very important for the structural organization of surfactant monolayer and its functioning. Alterations in surfactant homeostasis or biophysical properties can result in surfactant insufficiency which may be responsible for diseases like respiratory distress syndrome, lung proteinosis, interstitial lung diseases and chronic lung diseases. The biochemical, physiological, developmental and clinical aspects of pulmonary surfactant are presented in this article to understand the pathophysiological mechanisms of these diseases.


[Utility of McGRATH MAC for a Patient with a Large Epiglottic Cyst].
A 76-year-old man with an epiglottic cyst was scheduled for transoral rigid endoscopic epiglottic cystectomy under general anesthesia. The epiglottic cyst was found accidentally when he had an operation of radical cystectomy 2 weeks before. When he had the radical cystectomy, the ventilation through a mask was easy. He had no subjective respiratory symptoms. We chose rapid induction with propofol, remifentanl, and rocuronium. When we inserted the McGRATH MAC laryngoscope, we could only see a big epiglottic cyst not vocal cord but the pressure on the neck enabled the laryngologist to see the vocal cord. We could identify the space through which we could insert tracheal tube without touching the cyst. After the operation, his trachea was extubed.


Increased seizure threshold related to tamoxifen.
Both animal and human evidence suggest that estrogen has a modulatory role in seizure threshold, although there have been no reports to date suggesting the relevance of this to ECT practice. We describe the case of a woman who had been receiving maintenance ECT for several years with a stable seizure threshold. She developed breast cancer and ultimately agreed to begin estrogen deprivation therapy with tamoxifen; this treatment regimen resulted in an increased seizure threshold, necessitating an increase in stimulus power settings. ECT practitioners should be aware that estrogen deprivation therapy may have the potential to alter seizure threshold.


Babesia gibsoni cytochrome b mutations in canine blood samples submitted to a US veterinary diagnostic laboratory.
Babesiosis caused by Babesia gibsoni is recognized throughout the world and can be difficult to treat. Resistance to atovaquone is associated with mutations in the B. gibsoni mitochondrial genome, specifically the M128 position of cytochrome b (cytb). The prevalence of cytb mutations in North America has not been reported. The objective of our study was to describe the prevalence of cytb M128 mutations in B. gibsoni in canine blood samples submitted to a US veterinary diagnostic laboratory. A secondary objective was to determine whether or not some dogs had wild-type cytb in our initial samples then had M128 mutations detected in follow-up samples. One-Hundred seventy-four dogs that tested positive for the presence of B. gibsoni between 2012 and 2017. Case series of consecutive samples submitted to a veterinary diagnostic laboratory. Partial B. gibsoni cytb genes were amplified by polymerase chain reaction and screened for the presence of mutations at the M128 position. The overall prevalence of M128 mutants was 3.5% (6/173 dogs) in the initial samples. The incidence of new cytb mutants in dogs that tested positive for B. gibsoni, which then had follow-up testing, was 12.1% (5/41). Conclusions and Clinic Importance: Our study reaffirms that B. gibsoni infection is widespread and most commonly detected in American Staffordshire Terrier/American Pit Bull Terrier dogs (128/174, 74% of the infected dogs in our study). The prevalence of cytb mutations does not warrant pretreatment genotyping.


Experimental study of crossover from capillary to viscous fingering for supercritical CO2-water displacement in a homogeneous pore network.
Carbon sequestration in saline aquifers involves displacing brine from the pore space by supercritical CO(2) (scCO(2)). The displacement process is considered unstable due to the unfavorable viscosity ratio between the invading scCO(2) and the resident brine. The mechanisms that affect scCO(2)-water displacement under reservoir conditions (41 °C, 9 MPa) were investigated in a homogeneous micromodel. A large range of injection rates, expressed as the dimensionless capillary number (Ca), was studied in two sets of experiments: discontinuous-rate injection, where the micromodel was saturated with water before each injection rate was imposed, and continuous-rate injection, where the rate was increased after quasi-steady conditions were reached for a certain rate. For the discontinuous-rate experiments, capillary fingering and viscous fingering are the dominant mechanisms for low (logCa ≤ -6.61) and high injection rates (logCa ≥ -5.21), respectively. Crossover from capillary to viscous fingering was observed for logCa = -5.91 to -5.21, resulting in a large decrease in scCO(2) saturation. The discontinuous-rate experimental results confirmed the decrease in nonwetting fluid saturation during crossover from capillary to viscous fingering predicted by numerical simulations by Lenormand et al. (J. Fluid Mech.1988, 189, 165-187). Capillary fingering was the dominant mechanism for all injection rates in the continuous-rate experiment, resulting in monotonic increase in scCO(2) saturation.


TGF-β (Transforming Growth Factor-β) Signaling Protects the Thoracic and Abdominal Aorta From Angiotensin II-Induced Pathology by Distinct Mechanisms.
The role of TGF-β (transforming growth factor-β) signaling in abdominal aortic aneurysm (AAA) formation is controversial. Others reported that systemic blockade of TGF-β by neutralizing antibodies accelerated AAA development in angiotensin II-infused mice. This result is consistent with other studies suggesting that TGF-β signaling prevents AAA. Development of a therapy for AAA that exploits the protective actions of TGF-β would be facilitated by identification of the mechanisms through which TGF-β prevents AAA. We hypothesized that TGF-β signaling prevents AAA by its actions on aortic medial smooth muscle cells. We compared the prevalence, severity, and histopathology of angiotensin II-induced AAA among control mice (no TGF-β blockade), mice with antibody-mediated systemic neutralization of TGF-β, and mice with genetically based smooth muscle-specific loss of TGF-β signaling. Surprisingly, we found that systemic-but not smooth muscle-specific-TGF-β blockade significantly increased the prevalence of AAA and tended to increase AAA severity, adventitial thickening, and aortic wall macrophage accumulation. In contrast, abdominal aortas of mice with smooth muscle-specific loss of TGF-β signaling differed from controls only in having a thinner media. We examined thoracic aortas of the same mice. Here we found that smooth muscle-specific loss of Tgfbr2-but not systemic TGF-β neutralization-significantly accelerated development of aortic pathology, including increased prevalence of intramural hematomas, medial thinning, and adventitial thickening. Our results suggest that TGF-β signaling prevents both abdominal and thoracic aneurysmal disease but does so by distinct mechanisms. Smooth muscle extrinsic signaling protects the abdominal aorta and smooth muscle intrinsic signaling protects the thoracic aorta.


New properties of Drosophila fab-7 insulator.
In the Abd-B 3' cis-regulatory region, which is subdivided into a series of iab domains, boundary elements have previously been detected, including the Fab-7 element providing for the autonomous functioning of the iab-6 and iab-7 cis-regulatory domains. Here, it has been shown that a single copy of the 860-bp Fab-7 insulator effectively blocks the yellow and white enhancers. The eye and testis enhancers can stimulate the white promoter across the pair of Fab-7, which is indicative of a functional interaction between the insulators. Unexpectedly, Fab-7 has proved to lose the enhancer-blocking activity when placed near the white promoter. It seems likely that Fab-7 strengthens the relatively weak white promoter, which leads to the efficient enhancer-promoter interaction and insulator bypass.


Targets of c-Jun NH(2)-terminal kinase 2-mediated tumor growth regulation revealed by serial analysis of gene expression.
Although the c-Jun NH(2)-terminal kinase (JNK) pathway has been implicated in mediating cell growth and transformation, its downstream effectors remain to be identified. Using JNK2 antisense oligonucleotides (JNK2AS), we uncovered previously a role for JNK2 in regulating cell cycle progression and survival of human PC3 prostate carcinoma cells. Here, to identify genes involved in implementing JNK2-mediated effects, we have analyzed global gene expression changes in JNK2-deprived PC3 cells using Serial Analysis of Gene Expression. More than 40,000 tags each were generated from control and PC3-JNK2AS libraries, corresponding to 15,999 and 20,698 unique transcripts, respectively. Transcripts corresponding to transcription factors, stress-induced genes, and apoptosis-related genes were up-regulated in the PC3-JNK2AS library, revealing a significant stress response after the inhibition of JNK2 expression. Genes involved in DNA repair, mRNA turnover, and drug resistance were found to be down-regulated by inhibition of JNK2 expression, further highlighting the importance of JNK2 signaling in regulating cell homeostasis and tumor cell growth.


The DPSIR Model for Environmental Risk Assessment of Municipal Solid Waste in Dar es Salaam City, Tanzania.
Environmental risk has become an area of major concern and research, drawing special attention. This study on the environmental risk assessment (ERA) of Dar es Salaam Municipal Solid Waste comes at a time when the Government of Tanzania is becoming increasingly concerned about dealing with high levels of pollution from municipal solid waste (MSW). The paper employed the Driving force-Pressure-State-Impact-Response (DPSIR) model to establish an environmental risk indicator system and the analytical hierarchy process (AHP) to calculate and analyze risk values, based on the actual situation of MSW in the city of Dar es Salaam. It lists several measures that have been taken in response to the current significantly high levels of pollution, which have assisted in maintaining the environmental risk index (ERI) at a medium level (0.4⁻0.6) during the period from 2006⁻2017. However, these measures have not been adequate enough to manage the external pressure. The ERI has been increasing gradually, calling for timely formulation of demand-specific waste management policies to reduce the possibility of reaching the critical point in near future. With the use of the DPSIR model for ERA, this study has become highly valuable, providing empirical justification to reduce environmental risk from MSW, which is one of the main sources of environmental pollution in the urban areas of developing countries.


Feasibility of structured light plethysmography for the evaluation of lung function in preschool children with asthma.
Structured light plethysmography (SLP) is a new noninvasive technology to capture the movement of the thoracic and abdominal wall, and to assess some parameters indicative for lung function. The purpose of the study was to evaluate the feasibility of SLP in children with asthma. A total of 52 patients were enrolled: 25 with asthma exacerbation (group 1), 13 with well-controlled asthma (group 2), and 14 healthy controls (group 3). Every patient underwent SLP evaluation and a lung function test. SLP evaluations showed that the ratio of inspiratory flow at 50% of tidal volume (Vt) to expiratory flow at 50% of Vt, in which Vt is taken to be the exhaled chest wall movement, and flow is taken to be the time derivative of the chest wall movement (IE50) value increased in group 1 compared with groups 2 and 3, with statistical significance (p = 0.018); the data were consistent with the spirometry parameter. A correlation between the IE50 and forced expiratory volume in the first second of expiration was highlighted (r = -0.35, p = 0.019). SLP assessed airway obstruction, and its use in clinical practice could be applied in preschool children in future studies.


Relative survival and excess mortality following primary percutaneous coronary intervention for ST-elevation myocardial infarction.
High survival rates are commonly reported following primary percutaneous coronary intervention for ST-elevation myocardial infarction, with most contemporary studies reporting overall survival. The aim of this study was to describe survival following primary percutaneous coronary intervention for ST-elevation myocardial infarction corrected for non-cardiovascular deaths by reporting relative survival and investigate clinically significant factors associated with poor long-term outcomes. Using the prospective UK Percutaneous Coronary Intervention registry, primary percutaneous coronary intervention cases ( n=88,188; 2005-2013) were matched to mortality data for the UK populace. Crude five-year relative survival was 87.1% for the patients undergoing primary percutaneous coronary intervention and 94.7% for patients <55 years. Increasing age was associated with excess mortality up to four years following primary percutaneous coronary intervention (56-65 years: excess mortality rate ratio 1.61, 95% confidence interval 1.46-1.79; 66-75 years: 2.49, 2.26-2.75; >75 years: 4.69, 4.27-5.16). After four years, there was no excess mortality for ages 56-65 years (excess mortality rate ratio 1.27, 0.95-1.70), but persisting excess mortality for older groups (66-75 years: excess mortality rate ratio 1.72, 1.30-2.27; >75 years: 1.66, 1.15-2.41). Excess mortality was associated with cardiogenic shock (excess mortality rate ratio 6.10, 5.72-6.50), renal failure (2.52, 2.27-2.81), left main stem stenosis (1.67, 1.54-1.81), diabetes (1.58, 1.47-1.69), previous myocardial infarction (1.52, 1.40-1.65) and female sex (1.33, 1.26-1.41); whereas stent deployment (0.46, 0.42-0.50) especially drug eluting stents (0.27, 0.45-0.55), radial access (0.70, 0.63-0.71) and previous percutaneous coronary intervention (0.67, 0.60-0.75) were protective. Following primary percutaneous coronary intervention for ST-elevation myocardial infarction, long-term cardiovascular survival is excellent. Failure to account for non-cardiovascular death may result in an underestimation of the efficacy of primary percutaneous coronary intervention.


Development of methods based on low-temperature partitioning (LTP) for monitoring cresols and chlorophenols in sewage sludge, soil, and water in column leaching.
Cresols and chlorophenols are chemical contaminants that are potentially toxic to humans and can be found in sewage sludge. These chemical contaminants can migrate into the sludge-soil-water system when sludge is used as a conditioner for agricultural soils. Thus, the objective of this study was to develop methodologies based on extraction with low-temperature partitioning (LTP) to determine cresols and chlorophenols in sewage sludge, soil, and water. The analysis was performed by gas chromatography coupled with mass spectrometry (GC-MS). The validated methods were applied to monitor cresols and chlorophenols in a column-leaching study of a sludge-soil-water system. Satisfactory results were achieved for selectivity, limit of quantification (LOQ), linearity, accuracy, and precision. In the column leaching study, only 2,4,6-trichlorophenol was quantified in sludge samples after 20 days of the experiment. None of the studied compounds were quantified in soil and leached water samples, due to the degradation promoted by the microorganisms present in the sewage sludge. Finally, validated methods were suitable for monitoring cresols and chlorophenols in the sludge-soil-water system.


Adjuvant chemoradiotherapy (gemcitabine-based) in pancreatic adenocarcinoma: the Pisa University experience.
The role of adjuvant chemoradiotherapy in patients with pancreatic adenocarcinoma (PA) is controversial. In this study we aimed to assess the feasibility, disease-free survival (DFS) and overall survival (OS) of adjuvant chemoradiotherapy (gemcitabine based) in patients with resected PA and their correlation with prognostic factors. 122 resected patients (stage ≥IIa) treated between February 1999 and December 2013 were analyzed. Two cycles of gemcitabine (1,000 mg/m2 on days 1, 8 and 15 every 28 days) were administered before concomitant radiotherapy (45 Gy/25 fractions) and chemotherapy (gemcitabine 300 mg/m2 weekly). Median follow-up was 22.7 months (range 4-109). Gastrointestinal toxicity (G3), neutropenia (G3-G4) and cardiac toxicity (G2-G3) were observed in 2.4%, 10.6% and 1.6% of patients, respectively. OS at 12, 24 and 60 months was 79%, 55% and 31%, respectively (median 25 months). Two-year OS in patients with postoperative Karnofsky performance status (KPS) ≤70 and ≥80 was 37.1% and 62.3%, respectively (p<0.0001). OS was better in the group of patients with a postoperative CA 19-9 level ≤100 U/mL (p = 0.014). Median DFS was 17 months. The combination of concomitant gemcitabine and radiotherapy in patients with radically resected PA was well tolerated and associated with a low incidence of local recurrences. Five-year OS was significantly influenced by postoperative KPS and CA 19-9 values.


An unusual cause of school refusal.
A 6-year-old school boy was brought to the child developmental specialist with complaints of school absenteeism and school refusal behaviour of 7 months duration. Before the onset of school refusal, he had two episodes of unresponsiveness with abnormal posturing preceded by vertigo, which were diagnosed and managed as epileptic seizures. Following these episodes, he started avoiding school due of episodic palpitations, 'nervousness' and sweating. However, the episodes of unresponsiveness did not recur. His symptoms were attributed to stress/anxiety by both the examining physicians as well as the parents because repeated clinical evaluation including 12-lead ECG done three times and echocardiography were normal. Fortunately the sixth time, the diagnosis was clinched on an ECG when he presented to the paediatrician with tachycardia and hypotension.


Hypothalamic-pituitary-adrenal axis in lethal canine Staphylococcus aureus pneumonia.
The clinical significance and even existence of critical illness-related corticosteroid insufficiency is controversial. Here, hypothalamic-pituitary-adrenal (HPA) function was characterized in severe canine Staphylococcus aureus pneumonia. Animals received antibiotics and titrated life-supportive measures. Treatment with dexamethasone, a glucocorticoid, but not desoxycorticosterone, a mineralocorticoid, improves outcome in this model. Total and free cortisol, adrenocorticotropic hormone (ACTH). and aldosterone levels, as well as responses to exogenous ACTH were measured serially. At 10 h after the onset of infection, the acute HPA axis stress response, as measured by cortisol levels, exceeded that seen with high-dose ACTH stimulation but was not predictive of outcome. In contrast to cortisol, aldosterone was largely autonomous from HPA axis control, elevated longer, and more closely associated with survival in early septic shock. Importantly, dexamethasone suppressed cortisol and ACTH levels and restored ACTH responsiveness in survivors. Differing strikingly, nonsurvivors, sepsis-induced hypercortisolemia, and high ACTH levels as well as ACTH hyporesponsiveness were not influenced by dexamethasone. During septic shock, only serial measurements and provocative testing over a well-defined timeline were able to demonstrate a strong relationship between HPA axis function and prognosis. HPA axis unresponsiveness and high aldosterone levels identify a septic shock subpopulation with poor outcomes that may have the greatest potential to benefit from new therapies.


Heteromorphic NiCo2S4/Ni3S2/Ni Foam as a Self-Standing Electrode for Hydrogen Evolution Reaction in Alkaline Solution.
Considerable works have been devoted on developing high-efficiency nonplatinum electrocatalysts for hydrogen evolution reaction (HER). Herein, 3D heteromorphic NiCo2S4/Ni3S2 nanosheets network has been constructed on Ni foam (denoted as NiCo2S4/Ni3S2/NF) serving as a self-standing electrocatalyst through directly thermal sulfurization of a single-source NiCo-layered double hydroxide precursor. The resultant NiCo2S4/Ni3S2/NF electrode exhibits outstanding electrocatalytic HER performance with an extremely low onset overpotential of 15 mV and long-term durability in alkaline solution. Such enhanced HER performance can be credited to (1) the massive exposed active sites provided by mixed transition metal chalcogenides (NiCo2S4 and Ni3S2), (2) the strong interfacial interaction at NiCo2S4/Ni3S2 heterojunction interfaces with the strengthened H binding, and (3) the porous highly conductive Ni foam substrate with accelerated electron transfer. This work opens up a new direction to fabricate effective and non-noble-metal electrodes for water splitting and hydrogen generation.


Response surface optimized ultrasonic-assisted extraction of flavonoids from Sparganii rhizoma and evaluation of their in vitro antioxidant activities.
An efficient ultrasound-assisted extraction technique was employed to extract total flavonoids from Sparganii rhizoma. The optimum extraction conditions for the highest yield of total flavonoids were ethanol concentration 53.62%, ultrasonication time 29.41 min and ultrasound power 300 W, which were determined using response surface methodology. The extraction yields of the optimal ultrasound-assisted extraction were higher than using conventional extraction. The crude extract was then purified on a polyamide resin, whereby the flavonoids content in the purified extract increased to 94.62%. The antioxidant activities of the purified flavonoids including DPPH radical scavenging activity, ABTS+ radical scavenging activity, reducing power, hydroxyl radical scavenging activity and superoxide anion scavenging activity, were evaluated in vitro, which suggested that the flavonoids showed significant antioxidant activities. Rutin, kaempferol and formononetin were identified in the extract by comparing relative retention times and UV-Vis spectra with those of reference standards.


Cholinergic enzymes and inflammatory markers in rats infected by Sporothrix schenckii.
The aim of this study was to evaluate the cholinesterase activity in serum, whole blood, and lymphocytes, as well as to verify its relation to immune response in rats experimentally infected by Sporothrix schenckii. For this study, 63 Wistar rats (Rattus norvegicus), male, adult were divided into three groups: the negative control group (GC: n = 21), the group infected subcutaneously (GSC: n = 21), and the group infected intraperitoneally (GIP: n = 21). The groups were divided into subgroups and the following variables were evaluated at 15, 30, and 40 days post-infection (PI): acetylcholinesterase (AChE) activity in lymphocytes and whole blood, butyrylcholinesterase (BChE) activity in serum, cytokines levels (IL-1, IL-6, TNFα, and INF-γ), immunoglobulins levels (IgA, IgG, IgM, and IgE), and protein profile by electrophoresis. Both infected groups showed increased levels of inflammatory parameters (P < 0.05) in tissue and inflammatory infiltrates. The activities of AChE in lymphocytes and BChE in serum increased (P < 0.05) significantly in animals from the GSC group on day 40 PI compared to the GC group. Regarding the GIP, there was a marked increase in the AChE activity in lymphocytes on days 30 and 40 PI, and in whole blood on days 15, 30, and 40 PI compared to GC. Furthermore, IL-10, an anti-inflammatory cytokine, was also present in high levels during chronic systemic S. schenckii infections in animals. Therefore, it is concluded that cholinesterase has an important modulatory role in the immune response during granulomatous infection by S. schenckii.


Team training at an outreach dental unit.
A cohort of eighty nine undergraduate dental students worked for one year on two clinics completing a total of 3901 days work. Most of this time (63%) was spent at a site with shared nursing support, but despite this another site with dedicated nursing support produced approximately the same output. Students and nurses preferred working as a team rather than sharing; 98% of the students completed a questionnaire on the role of dental nurses and the majority identified chairside assistance as being the most important contribution to the increased throughput of patients.


Tumor cell proliferation and survival in patients with prostate cancer followed expectantly.
Prostate cancers have different biological potentials, and aggressive tumors are difficult to identify when still localized. Tumor cell proliferation determined by MIB-1 expression has been suggested as an important predictor for outcome in several human cancers including the prostate. We test the possible prognostic value of tumor cellular proliferation in prostate cancer patients treated with no intent to cure. Formalin fixed, paraffin embedded tumor tissue obtained at the time of diagnosis from 221 patients originating from a well known complete Danish prostate cancer population was immunohistochemically investigated. The tumor cell proliferation rate was determined using the MIB-1 antibody. Tumors were clinically localized in 57% of the patients. Tumor cell proliferation rate expressed by the MIB-1 score significantly correlated with tumor stage (p <0.001) and malignancy grade (p <0.001). The MIB-1 score, divided into low and high by the median value, showed significant association with disease specific survival in the entire study population (p <0.0001), as well as in the 125 patients suffering from clinically localized disease (p=0.018). Multivariate analyses showed that MIB-1 was a significant (p=0.0003) prognostic factor in the entire population, including advanced disease stages. However, in the theoretically curable clinically localized subpopulation MIB-1 was not significant (p=0.08) contrary to histopathological grade (p=0.02), erythrocyte sedimentation rate (p=0.02) and T classification (p=0.035). Prostate tumor cell proliferation, expressed by MIB-1 immunoreactivity, demonstrated significant association with disease specific survival. However, MIB-1 is a close alternative to histopathological grade in describing the natural history of clinically localized prostate cancer. The additional prognostic value and the practical consequence of tumor cell proliferation remain to be clarified.


Curriculum Leadership of Rural Teachers: Status Quo, Influencing Factors and Improvement Mechanism-Based on a Large-Scale Survey of Rural Teachers in China.
Revealing the general status quo of teacher curriculum leadership has great theoretical, policy, and practical significance. However, large-scale empirical investigations in this area are rare, and there is even less attention to the current situation of rural teacher curriculum leadership. Based on the survey of 2,966 rural teachers in 20 provinces of China, this paper presented the status quo of rural teacher curriculum leadership and examined influencing factors through multiple linear regression analysis. It was found that curriculum leadership of rural teachers was at a low level with backward leadership views, lack of practical ability, and low sense of identity. Regression analysis demonstrated that individual field factors had a significant impact on teachers' curriculum leadership. Specifically, the higher the teachers' leadership willingness, trust in others, and self-efficacy, the higher the curriculum leadership. The school field was also an important influential aspect. In particular, the formation of a common vision and teacher community by the school and the appropriate empowerment of the principal had a significant positive impact on the curriculum leadership of rural teachers. Based on these key findings, several improvement suggestions are put forward at the end, which can be used as references for other countries to develop improvement plans on rural teacher curriculum leadership.


Antigen-specific suppressor T cell interactions. I. Induction of an MHC-restricted suppressor factor specific for L-glutamic acid50-L-tyrosine50.
The synthetic polymers L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) and L-glutamic acid50-L-tyrosine50 (GT) stimulate specific suppressor T cells in certain strains of mice. Extracts from these T cells contain factors (TsF) that inhibit GAT- or GT-specific antibody responses by normal spleen cells or proliferative responses by primed T cells. We constructed T cell hybridomas that constitutively produce GAT-TsF or GT-TsF, which functionally and serologically are identical to factors extracted from suppressor T cells. In this report we demonstrate that monoclonal GT-TsF can induce specific unresponsiveness in vivo or in vitro and that this unresponsiveness is due to development of second-order antigen-specific suppressor T cells. T cell hybridomas were constructed by fusion of BW5147 with GT-TsF1 induced second-order suppressor T cells and clones that produced suppressor factor (GT-TsF2) were isolated and characterized. GT-TsF2 differs from the GT-TsF1 used to induce it in that GT-TsF1 acts across allogeneic barriers whereas GT-TsF2 does not. This restriction is controlled by genes in the H-2 gene complex and maps to the I-J subregion. GT-TsF2 is antigen-specific in suppressive activity and also in its antigen-binding site(s). Thus, GT-TsF2 closely resembles the carrier-specific, I-J+, genetically restricted factor described by Tada and his colleagues. Because GT-TsF2 was induced by GT-TsF1, we suggest cells producing GT-TsF1 are an early cell in the pathway of suppression, and that this cell is required for the activation of antigen-specific, MHC-restricted TsF.


Analysis of HumFABP2 as a polymorphic human genetic marker in the Turkish population.
To examine the allele frequencies of HumFABP2 locus in 155 individuals from different regions of Turkey. The study was carried out in Cumhuriyet University Hospital, Sivas, Turkey, between March and June 2006. The allele and genotype frequencies for HumFABP2 were determined by polymerase chain reaction (PCR) using the manufacturer's recommended protocol, and using the commercially available Macherey-Nagel DNA isolation kit. The PCR amplification was carried out in a Perkin-Elmer GeneAmp PCR System 9600 thermal cycler following the manufacturer's recommendations. The allele frequencies in the Turkish population was computed, and the heterozygote rate was calculated. In this population study of 155 samples, we found 75 (48.39%) heterozygote and 80 (51.61%) homozygote. The results showed heterozygotic cases as 150/250 bp, and homozygotic cases as 150 bp. Allele frequency data of HumFABP2 as a PCR-based genetic marker could be used in identity testing to estimate the frequency of a multiple PCR based profile in the Turkish population.


Long term impact of the endocrine disruptor tributyltin on male fertility following a single acute exposure.
Declining rate of human fertility is a growing concern, where lifestyle and environmental factors play an important role. We recently demonstrated that tributyltin (TBT), an omnipresent endocrine disruptor, affects testicular cells in vitro. In this study, male Wistar rats were gavaged a single dose of 10, 20, and 30 mg/kg TBT-chloride (TBTC) (to mimic accidental exposure in vivo) and sacrificed on day 3 and day 7, respectively. TBT bioavailability was evaluated by estimating total tin content, and essential metal levels were analyzed along with redox molecules (ROS and GSH/GSSG) to understand the effect on physiological conditions. Blood-testicular barrier (BTB) disruption, levels of associated proteins and activity of proteolytic enzymes were evaluated to understand the effect on BTB. Histological analysis of tissue architecture and effect on protein expression of steroidogenic, stress and apoptotic markers were also evaluated. Widespread TBTC pollution can be an eventual threat to male fertility worldwide.


Lipopolysaccharide induced Interleukin-6 production is mediated through activation of ERK 1/2, p38 MAPK, MEK, and NFκB in chicken thrombocytes.
Thrombocytes express Toll-like receptor 4 and apparently use both mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NFKB) pathways for nuclear signaling. However, it is not well known if the same enzyme systems found in mammalian cells are fully functional in chickens. Therefore, kinase inhibitors were used with thrombocytes to block kinases in lipopolysaccharide (LPS) stimulated cells to determine if interleukin (IL)-6 expression and production would be diminished. Results demonstrated that extracellular-signal-regulated kinase (ERK)1/2 and p38 MAPK pathways influence gene expression of IL-6 through treatment with either ERK or p38 MAPK inhibitor. In addition, thrombocyte lysates from cells treated with ERK, p38, mitogen-activated protein kinase kinase (MEK)1/2 and inhibitor of nuclear factor kappa-B kinase (IKK) inhibitor showed different levels of the phosphorylated form of ERK1/2, p38 and NFκB. Furthermore, IL-6 gene expression and production were significantly upregulated in LPS stimulated thrombocytes relative to all inhibitor-treated cells.


Administration of pigment epithelium-derived factor delivered by adeno-associated virus inhibits blood-retinal barrier breakdown in diabetic rats.
To evaluate the effect of the recombinant adeno-associated virus (rAAV) vector that expresses human pigment epithelium-derived factor (hPEDF) on reducing blood-retinal barrier (BRB) breakdown in the experimental diabetic rat model. Diabetes was induced by an intraperitoneal (i.p.) injection of streptozotocin (STZ) into 10-week-old male Wister rats. rAAV2-cytomegalovirus (CMV)-hPEDF was delivered into the right eyes by intravitreal injection on the first day after diabetes induction. The contralateral eyes received intravitreal injection of rAAV2-CMV-green fluorescent protein as the paired control. Gene delivery and expression of vascular endothelial growth factor (VEGF), occludin, and intercellular adhesion molecule-1 (ICAM-1) were determined with reverse transciptase PCR or western blotting. BRB breakdown changes were quantified by measuring albumin leakage from retinal blood vessels after an intravenous (i.v.) injection of Evans blue albumin. Retinal transfection with the hPEDF gene construct led to sustained hPEDF gene expression for 6 months, significantly suppressing VEGF mRNA expression in the retina after 1, 3, and 6 months of diabetes induced by STZ compared with paired controls. Moreover, hPEDF dramatically reduced the levels of retinal ICAM-1 but increased the expression of occludin. Furthermore, BRB breakdown was much lower in hPEDF-injected diabetic animals in comparison with controls after 6 months. A single intravitreal injection of rAAV2-CMV-hPEDF can relieve BRB breakdown in STZ-induced diabetic rats for 6 months. The effect is associated with downregulation of retinal VEGF mRNA and ICAM-1 expression and a reduction in the loss of retinal occludin induced by diabetes. The approach of gene transfer may reduce diabetic macular edema, providing long-term protection for diabetic patients at risk of macular edema.


A Meta-Analysis of eHealth Interventions on Ischaemic Heart Disease Health Outcomes.
Electronic Health (eHealth) interventions as a secondary prevention tool to empower patients' health in decision-making and behaviour. With the growing body of evidence supporting the use of eHealth interventions, the intention is to conduct a meta-analysis on various health outcomes of eHealth interventions among ischaemic heart disease (IHD) patients. Based on PRISMA guidelines, eligible studies were searched through databases of Web of Science, Scopus, PubMed, EBSCOHost, and SAGE (PROSPERO registration CRD42021290091). Inclusion criteria were English language and randomised controlled trials published between 2011 to 2021 exploring health outcomes that empower IHD patients with eHealth interventions. RevMan 5.4 was utilised for meta-analysis, sensitivity analysis, and risk of bias (RoB) assessment while GRADE software for generating findings of physical health outcomes. Non-physical health outcomes were analysed using SWiM (synthesis without meta-analysis) method. This review included 10 studies, whereby, six studies with 895 participants' data were pooled for physical health outcomes. Overall, the RoB varied significantly across domains, with the majority was low risks, a substantial proportion of high risks and a sizeable proportion of unclear. With GRADE evidence of moderate to high quality, eHealth interventions improved low density lipoprotien (LDL) levels in IHD patients when compared to usual care after 12 months of interventions (SMD -0.26, 95% CI [-0.45, -0.06], I2 = 0%, p = 0.01). Significance appraisal in each domain of the non-physical health outcomes found significant findings for medication adherence, physical activity and dietary behaviour, while half of the non-significant findings were found for other behavioural outcomes, psychological and quality of life. Electronic Health interventions are found effective at lowering LDL cholesterol in long-term but benefits remain inconclusive for other physical and non-physical health outcomes for IHD patients. Integrating sustainable patient empowerment strategies with the advancement of eHealth interventions by utilising appropriate frameworks is recommended for future research.


A one-year study of trivalent influenza vaccines in primed and unprimed volunteers: immunogenicity, clinical reactions and protection.
Three hundred volunteers were divided into two age groups, 14-30 years and 31-60 years. Each participant was immunized intramuscularly with a subunit, whole virus or absorbed whole virus vaccine, containing A/Bangkok/1/79 (H3N2), A/Brazil/11/78 (H1N1) and B/Singapore/222/79 influenza virus. Serum haemagglutination-inhibition (HI) antibody response, protection, and reactogenicity were studied after one and two doses of the vaccines. Primary immunization induced much higher percentages of HI antibody titres greater than or equal to 100 against all three vaccine viruses and much higher geometric mean titres (GMT) in volunteers with pre-immunization titres greater than or equal to 18 as compared to those with pre-immunization titres less than 18. Secondary immunization did not result in an increase of GMTs or antibody titres greater than or equal to 100 in volunteers with pre-immunization titres less than 18. On the whole, the response to the subunit vaccine was similar to that to the other two vaccines. To influenza B/Singapore/222/79 virus the response was lowest after administration of the whole virus vaccine in the age group 31-60 years. Over 50% of the HI titres greater than or equal to 100 found after immunization in the different vaccine and age groups were still present after one year. Serologically established infections during the winter months following immunization amounted to 15% in the subunit vaccine group, 6% in the whole virus vaccine group, and 10% in the adsorbed whole virus vaccine group. Local and systemic reactions to all three vaccines were mild in nature. Local reactions after primary immunization were much less frequent following administration of the subunit vaccine as compared to the other two vaccines, especially in the younger age group. In comparison to primary immunization, after booster immunization the incidence of local reactions was higher for the subunit vaccine and lower for the adsorbed whole virus vaccine. In the age group 14-30 years the incidence of local reactions after primary as well as booster immunization was much greater in females than in males, especially when the adsorbed whole virus vaccine was used.


The perceptual reality of tone chroma in early infancy.
It has often been advanced that pitch is a two-dimensional perceptual attribute, its two dimensions being: (1) tone height, a perceptual quality monotonically related to frequency; and (2) tone chroma, a quality shared by tones forming an octave interval. However, given that many musically uneducated adults do not seem to perceive tone chroma, this model is controversial. We investigated the sensitivity of three-month-old infants to tone chroma by means of a behavioral habituation-dishabituation procedure. Infants were presented with two successive melodic sequences of pure tones, the second sequence being a distorted version of the first one. The distortion consisted in shifting the frequency of some of the original tones, through a seventh or a ninth for some infants, through an octave for others. In the former case, infants displayed significant novelty reactions. In the latter case, significant novelty reactions were observed when the two sequences differed in melodic contour, but not when they had the same contour. These results suggest that young infants are sensitive to both tone height and tone chroma, and thus that tone chroma perception does not necessitate some form of musical experience.


Molecular and functional interactions among monocytes/macrophages and smooth muscle cells and their relevance for atherosclerosis.
Macrophages, smooth muscle cells (SMCs), and their interactions have key roles in the pathogenesis of atherosclerotic vascular diseases. In atheroma development, the phenotype of macrophages and SMCs change, which may influence the disease progression. Accumulating data on the phenotypes exhibited by these cells within atherosclerotic lesions raise many questions regarding the mechanisms and factors that might control the transition of cell phenotype. SMCs often reside in vascular lesions in close proximity to macrophage clusters and are most likely influenced by factors released from these proinflammatory phagocytes. Moreover, macrophages may be influenced by direct contact with SMCs or soluble factors released by these cells. Macrophages may promote activation and induce proatherogenic functions of SMCs, and SMCs may modulate macrophage phenotype. Addressing the mechanisms involved in SMC-macrophage crosstalk that lead to phenotypic modulation of both cell types may provide new insight into atherogenesis and new targets for therapies of various vascular diseases.


Electronic, mechanical and gas sensing properties of two-dimensional γ-SnSe.
Two-dimensional (2D) materials are excellent candidates for advanced flexible electronics and gas sensors. Herein, we systematically investigate the layer-dependent electronic structures, mechanical properties and gas sensing characteristics of the newly synthesized γ-SnSe based on first-principles calculations. Bulk γ-SnSe is a typical van der Waals layered material with an indirect narrow band gap, while monolayer and multilayer γ-SnSe can be obtained through mechanical exfoliation due to its low cleavage energy. The band gap of γ-SnSe gradually increases with decreasing layers, reaching a value of 2.25 eV for the monolayer due to weakened interlayer coupling. Mechanical analysis reveals strong anisotropy in multilayer γ-SnSe, whereas the monolayer exhibits a negative Poisson's ratio (-0.023/-0.025). Additionally, based on the analysis of electronic structures, adsorption energies and charge transfer of the host materials after adsorption of various gases, it is found that the γ-SnSe monolayer demonstrates enhanced sensitivity and selectivity towards NO, NO2, and SO2 compared to CO, CO2, H2S and NH3. These findings highlight the potential of γ-SnSe as an excellent gas-sensitive material for the detection of nitrogen oxides and sulfur dioxide.


Characterizing Sirtuin 3 Deacetylase Affinity for Aldehyde Dehydrogenase 2.
Mitochondrial aldehyde dehydrogenase (ALDH2) plays a central role in the detoxification of reactive aldehydes generated through endogenous and exogenous sources. The biochemical regulation of enzyme activity through post-translational modification provides an intricate response system regulating mitochondrial detoxification pathways. ALDH2 is a known target of lysine acetylation, which arises as a consequence of mitochondrial bioenergetic flux and sirtuin deacetylase activity. The mitochondrial deacetylase Sirtuin 3 (SIRT3) has been reported to alter ALDH2 lysine acetylation status, yet the mechanism and consequence of this interaction remain unknown. The in vitro results presented here provide a novel biochemical approach using stable-isotope dilution mass spectrometry to elucidate which lysine residues are targeted by SIRT3 for deacetylation. Furthermore, HPLC-MS/MS and computational modeling elucidate a potential role for acetyl-Lys369 on ALDH2 in perturbing normal β-nicotinamide adenine dinucleotide (NAD+) cofactor binding.


Assessment of Outcome of Oral Supplementation of Vitamin D3 as an Adjunct to Scaling and Root Planing in Chronic Periodontitis Patients with Type II Diabetes Mellitus - A Randomized Controlled Clinical Trial.
Both diabetes and periodontitis affect millions of people worldwide and Vitamin D insufficiency may create a conducive environment for the progression of diabetes and periodontal disease. The aim of the study was to assess the outcome of oral supplementation of Vitamin D3 in patients with Type 2Diabetes Mellitus with generalized chronic periodontitis, as an adjuvant toscaling and root planing. A total of 92 patients, including 46 each in non-diabetic and diabetec group. Clinical parameters including Plaque Index (PI), Gingival Bleeding Index (GBI), Probing Pocket Depth (PPD), Clinical Attachment Level (CAL), levels of Vitamin D in serum, and Fasting Blood sugar were assessed at the baseline. SRP was finished for each participant in the trial. Following SRP, the first 25people in each group got 60,000 IU of oral vitamin D3 granules once a week for eight weeks, while the remaining 21 subjects from each group did not. At the conclusion of the 8th week following interventions, all the indicators were reviewed. Following SRP and Vitamin D supplementation there was a measurably critical reduction in every one of the periodontal clinical indicators in both groups. In both groups, there was a statistically significant rise in serum vitamin D levels. In addition to SRP, vitamin D supplementation shows promise as a host immunomodulatory drug in the management of periodontitis, particularly in patients with diabetes mellitus.


Effects of tanshinones mediated by forkhead box O3a transcription factor on the proliferation and apoptosis of lung cancer cells.
According to global cancer statistics in 2012, lung cancer (LC) was the most frequently diagnosed cancer and the leading cause of cancer-associated mortality among males worldwide. Owing to the limited therapeutic approaches available, novel methods for treating LC are required. Tanshinones (Ts) have previously been proved to be effective in treating cardiovascular disease, inflammatory disease and cancer, and have been reported to regulate cell proliferation and apoptosis of LC. The underlying molecular mechanism of action of Ts remains unclear. Furthermore, forkhead box O3a (FoxO3a) has been reported to be a critical gene in cell apoptosis. Therefore, the A549 lung cancer cell line was transfected with FoxO3a small interfering RNA (siRNA) or scrambled siRNA, and the cells which exhibited the most successful transfection efficacy were selected for further investigation into the underlying molecular mechanism of the influence of Ts on FoxO3a in LC cells. Various concentrations of Ts were assigned to experimental groups I-IV (5, 10, 20 and 30 µmol/l Ts, respectively). An MTT assay revealed that Ts inhibited cell proliferation in a dose- and time-dependent manner compared with the control group (CON; without Ts administration) with a maximal dose of 20 µmol/l at 72 h treatment (P<0.05). Similarly, compared with CON, flow cytometry results revealed that Ts induce LC cell apoptosis in a dose-dependent manner (P<0.05). Consistently, the expression levels of FoxO3a mRNA and protein were restored following treatment with Ts in a dose-dependent manner, alongside caspase-3 activation. On the basis of these results, we hypothesize that Ts regulate LC cell proliferation and apoptosis by triggering an apoptotic cascade through the FoxO3a/caspase-3 signaling pathway.


Bacteria-Directed Construction of ZnO/CdS Hollow Rods and Their Enhanced Photocatalytic Activity.
Zinc oxide (ZnO) hollow rods were fabricated by precipitation method with Bacillus subtilis as template. CdS nanoparticles were then decorated on the surface of the ZnO rods through hydrothermal method. The as-prepared samples were characterized using X-ray diffraction, scanning electron microscopy, high-resolution transmission electron microscope and ultraviolet-visible spectroscopy techniques. The ZnO/CdS composite hollow rods copied the morphology of Bacillus subtiis. A possible formation mechanism of the rods was proposed. The photocatalytic activity of the samples was further evaluated through the photodegradation of Rhodamine B under a simulated solar-light irradiation. Results indicated that the photocatalytic activity of the rods improved greatly.


Acoustic Streaming Generated by Sharp Edges: The Coupled Influences of Liquid Viscosity and Acoustic Frequency.
Acoustic streaming can be generated around sharp structures, even when the acoustic wavelength is much larger than the vessel size. This sharp-edge streaming can be relatively intense, owing to the strongly focused inertial effect experienced by the acoustic flow near the tip. We conducted experiments with particle image velocimetry to quantify this streaming flow through the influence of liquid viscosity ν , from 1 mm 2 /s to 30 mm 2 /s, and acoustic frequency f from 500 Hz to 3500 Hz. Both quantities supposedly influence the thickness of the viscous boundary layer δ = ν π f 1 / 2 . For all situations, the streaming flow appears as a main central jet from the tip, generating two lateral vortices beside the tip and outside the boundary layer. As a characteristic streaming velocity, the maximal velocity is located at a distance of δ from the tip, and it increases as the square of the acoustic velocity. We then provide empirical scaling laws to quantify the influence of ν and f on the streaming velocity. Globally, the streaming velocity is dramatically weakened by a higher viscosity, whereas the flow pattern and the disturbance distance remain similar regardless of viscosity. Besides viscosity, the frequency also strongly influences the maximal streaming velocity.


Differential effects of B and T lymphocyte attenuator and programmed death-1 on acceptance of partially versus fully MHC-mismatched cardiac allografts.
Although fully MHC-mismatched murine cardiac allografts are rapidly rejected, allografts mismatched at only MHC class I or class II alleles survive long term; the immunologic basis for the long-term survival of MHC class I- or II-mismatched allografts is unknown. We examined the roles of two recently described inhibitory receptors, B and T lymphocyte attenuator (BTLA) and programmed death-1 (PD-1), in the survival of partially or fully MHC-mismatched allografts using gene-deficient recipients as well as through use of blocking mAbs in wild-type hosts. Partially MHC-mismatched allografts showed strong induction of BTLA, but not PD-1 mRNA and survived long term in wild-type recipients, whereas targeting of BTLA or its ligand, herpesvirus entry mediator, but not PD-1, prompted their rapid rejection. By contrast, fully MHC-mismatched cardiac allografts were acutely rejected in wild-type recipients despite the induction of both BTLA and PD-1. Targeting of PD-1 in several fully MHC-mismatched models accelerated rejection, whereas targeting of BTLA unexpectedly enhanced PD-1 induction by alloreactive CD4 and CD8 T cells and prolonged allograft survival. In vitro studies using allogeneic dendritic cells and T cells showed that at low levels of T cell activation, BTLA expression was primarily induced, but that with increasing degrees of T cell activation, the expression of PD-1 was strongly up-regulated. These data suggest that BTLA and PD-1 exert distinct inhibitory actions in vivo, with the BTLA/herpesvirus entry mediator pathway appearing to dominate in regulating responses against a restricted degree of allogeneic mismatch.


Echocardiographic parameters and indices in 23 healthy Maltese dogs.
Echocardiography is a primary tool used by veterinarians to evaluate heart diseases. In recent years, various studies have targeted standard echocardiographic values for different breeds. Reference data are currently lacking in Maltese dogs and it is important to fill this gap as this breed is predisposed to myxomatous mitral valve disease, which is a volume overload disease. To establish the normal echocardiographic parameters for Maltese dogs. In total, 23 healthy Maltese dogs were involved in this study. Blood pressure measurements, thoracic radiography, and complete transthoracic echocardiography were performed. The effects of body weight, age and sex were evaluated, and the correlations between weight and linear and volumetric dimensions were calculated by regression analysis. The mean vertebral heart size was 9.1 ± 0.4. Aside from the ejection fraction, fractional shortening, and the left atrial to aorta root ratio, all the other echocardiographic parameters were significantly correlated with weight. This study describes normal echocardiographic parameters that may be useful in the echocardiographic evaluation of Maltese dogs.


Proteomic profile of osteoclast membrane proteins: identification of Na+/H+ exchanger domain containing 2 and its role in osteoclast fusion.
Osteoclast formation and bone resorption are multiple processes that involve the participation of specialized membrane structures and their associated proteins. In this study, we used an MS to analyze the profile of proteins associated with osteoclast membranes and focused on the function of channel proteins in osteoclast differentiation and function. We filtered out with a SEQUEST score greater than 10 and a peptide hit number of more than 2, resulting in the identification of 499 proteins that were commonly found in both macrophages and osteoclasts, 96 proteins selectively found in osteoclasts, and 179 proteins selectively found in macrophages. The proteins that were selectively found in osteoclasts were classified based on their localizations: plasma membrane (17%), ER/Golgi and lysosome/endosome (15%), mitochondrion (18%), nucleus (13%), cytosol (19%), and unknown (18%). Proteins associated with osteoclast function such as v-ATPase, IGF2R, TRAP, and cathepsin K were found in osteoclasts as previously shown. We found several ion channel proteins such as Ank and Nhedc2 and signaling molecules such as Dock5 and RAB-10 in osteoclasts. Inhibition of the Na(+)/H(+) exchanger family by amiloride suppressed RANKL-induced osteoclast fusion and bone resorption. In addition, shRNA for Nhedc2 inhibited osteoclast differentiation. Our results provide a proteomic profile of osteoclast membrane proteins and identify Nhedc2, which is probably associated with proton transport in osteoclasts, as a regulator of osteoclast function.


Lesions caused by cardiovascular flukes (Digenea: Spirorchidae) in stranded green turtles (Chelonia mydas).
Evidence of infection with spirorchid flukes (Digenea: Spirorchidae) was sought at necropsy of 96 stranded green turtles, Chelonia mydas, that were examined during the course of a survey of marine turtle mortality in southeastern Queensland, Australia. Three species of spirorchid (Hapalotrema mehrai, H. postorchis, and Neospirorchis schistosomatoides) were identified. Severe disease due to spirorchid fluke infection (spirorchidiasis) was implicated as the principal cause of mortality in 10 turtles (10%), and appeared to be one of multiple severe problems in an additional 29 turtles (30%). Although flukes were observed in only 45% of stranded C. mydas in this study, presumed spirorchid fluke infection was diagnosed in an additional 53% of turtles, based principally on characteristic necropsy lesions and to a lesser extent on the histopathological detection of spirorchid eggs. Characteristic necropsy lesions included miliary spirorchid egg granulomas, which were observed most readily on serosal surfaces, particularly of the small intestine. Cardiovascular lesions included mural endocarditis, arteritis, and thrombosis, frequently accompanied by aneurysm formation. Resolution of thrombi was observed to occur via a combination of granuloma formation about indigestible components (spirorchid fluke egg shells) and exteriorization through the vessel wall, which resulted in granulomatous nodules on the adventitial surface. Septic aortic thrombosis complicated by disseminated bacterial infection, observed in five turtles, was recorded for the first time. Egg granulomas were ubiquitous in turtle tissues throughout this study. Although they generally appeared to be mild or incidental lesions, they were occasionally associated with severe multifocal granulomatous pneumonia or meningitis.


Orbital Decompression for Thyroid Eye Disease.
Although most cases of thyroid eye disease (TED) can be managed medically, some refractory or severe cases are treated surgically with orbital decompression. Due to a lack of randomized controlled trials comparing surgical techniques for orbital decompression, none have been deemed superior. Thus, each case of TED is managed based on patient characteristics and surgeon experience. Surgical considerations include the extent of bony wall removal, the surgical approach, the choice of incision, and the use of fat decompression. Outcomes vary based on surgical indications and techniques; hence, vision can improve or worsen after the surgery.


Same-sex cohabitors and health: the role of race-ethnicity, gender, and socioeconomic status.
A legacy of research finds that marriage is associated with good health. Yet same-sex cohabitors cannot marry in most states in the United States and therefore may not receive the health benefits associated with marriage. We use pooled data from the 1997 to 2009 National Health Interview Surveys to compare the self-rated health of same-sex cohabiting men (n = 1,659) and same-sex cohabiting women (n = 1,634) with that of their different-sex married, different-sex cohabiting, and unpartnered divorced, widowed, and never-married counterparts. Results from logistic regression models show that same-sex cohabitors report poorer health than their different-sex married counterparts at the same levels of socioeconomic status. Additionally, same-sex cohabitors report better health than their different-sex cohabiting and single counterparts, but these differences are fully explained by socioeconomic status. Without their socioeconomic advantages, same-sex cohabitors would report similar health to nonmarried groups. Analyses further reveal important racial-ethnic and gender variations.


Cardiovascular risk in newly diagnosed type 2 diabetes patients in India.
Type 2 diabetes mellitus (T2DM) worldwide continues to increase, in particular in India. Early T2DM diagnosis followed by appropriate management will result in more cardiovascular event free life years. However, knowledge of the cardiovascular profile of newly diagnosed T2DM patients is still limited. The aim of this study was to understand the extent of cardiovascular disease (CVD) risk of newly diagnosed T2DM patients in India. A cross sectional observational study was conducted to evaluate clinical laboratory and socio-demographic parameters of 5,080 newly diagnosed T2DM patients (48.3 ± 12.8 years of age; 36.7% female). In addition, we determined their cardiovascular risk according to the guidelines of the Lipid Association of India (LAI) and the criteria of the QRISK3 score. Of the newly T2DM diagnosed patients in India 2,007(39.5%) were classified as "High risk" and 3,073 (60.5%) were classified as "Very high risk" based on LAI criteria. On average, patients had 1.7 ± 0.9 major atherosclerotic cardiovascular disease (ASCVD) risk factors. Low HDL-C value was the most frequent major risk (2,823; 55.6%) followed by high age (2,502; 49.3%), hypertension (2,141; 42.1%), smoking/tobacco use (1,078; 21.2%) and chronic kidney disease stage 3b or higher (568; 11.2%). In addition, 4,192 (82.5%) patients appeared to have at least one cholesterol abnormality and, if the latest LAI recommendations are applied, 96.5% (4,902) presented with lipid values above recommended targets. Based on the QRISK3 calculation Indian diabetes patients had an average CVD risk of 15.3 ± 12.3%, (12.2 ± 10.1 vs. 17.1 ± 13.5 [p<0.001] for females and males, respectively). Newly diagnosed Indian T2DM patients are at high ASCVD risk. Our data therefore support the notion that further extension of nationwide ASCVD risk identification programs and prevention strategies to reduce the occurrence of cardiovascular diseases are warranted.


Septin4_i1 regulates apoptosis in hepatic stellate cells through peroxisome proliferator-activated receptor-γ/Akt/B-cell lymphoma 2 pathway.
Apoptosis of activated hepatic stellate cells (HSCs) has been verified as a potential mechanism to aid in hepatic fibrosis remission. Earlier research suggests that Septin4_i1 may sensitize hepatocellular carcinoma cells to serum starvation-induced apoptosis. Here, we aimed to investigate the effect of Septin4_i1 on HSC apoptosis and explore the associated signaling pathways. We found that Septin4_i1 can induce apoptosis in LX-2 cells and that this is accompanied by an up-regulation in cleaved-caspase-3 and peroxisome proliferator-activated receptor-γ (PPAR-γ) expression and a down-regulation in α-SMA expression. Over-expression of Septin4_i1 reduced phosphorylated Akt and B-cell lymphoma 2 (Bcl-2) expression but had no effect on the expression of p53 and death receptor (DR)-5. The decreased expression of Bcl-2 and the increased expression of cleaved-caspase-3 induced by Sept4_i1 could be reversed by GW501516, a PPAR-β/δ agonist that has been reported by others to enhance Akt signaling. In addition, GW9662, an antagonist of PPAR-γ, could also inhibit apoptosis in LX-2 cells induced by Sept4_i1. In conclusion, our data suggest that Sept4_i1 induces HSC apoptosis by inhibiting Akt and Bcl-2 expression and up-regulating PPAR-γ expression.


Aequus communis sententia: defining levels of interoperability.
Interoperability is a common understanding of the meaning of data between a sending and receiving computer system [1]. The level of interoperability required varies with application needs. The specification of data in enough detail to create a common shared meaning between organizations is a complex task as systems work within organizational and human factors contexts as well as having specific technical requirements. Aequus communis sententia translates from Latin to the "level of common meaning." In this manuscript, we define an Ontology of Interoperability. The scale asks reviewers of a specification to define it's level in terms of Syntactic, Semantic and Pragmatic Interoperability. We tested the scale by having five medical Informaticians rate a set of ANSI standard specifications and we report the inter-rater variability of the interoperability rating scheme. We learned that some elements of the scale presented more difficulty for our reviewers and based on our findings we present a final version of the interoperability scale in our discussion. Our interoperability rating ontology has high inter-rater reliability and is a relatively simple mechanism for comparing the levels of interoperability afforded by different specifications or the same specification over multiple versions.


Accuracy of computer-assisted implant placement with insertion templates.
The purpose of this study was to assess the accuracy of computer-assisted implant insertion based on computed tomography and template-guided implant placement. A total of 246 implants were placed with the aid of 3D-based transfer templates in 181 consecutive partially edentulous patients. Five groups were formed on the basis of different implant systems, surgical protocols and guide sleeves. After virtual implant planning with the CoDiagnostiX Software, surgical guides were fabricated in a dental laboratory. After implant insertion, the actual implant position was registered intraoperatively and transferred to a model cast. Deviations between the preoperative plan and postoperative implant position were measured in a follow-up computed tomography of the patient's model casts and image fusion with the preoperative computed tomography. The median deviation between preoperative plan and postoperative implant position was 1.0 mm at the implant shoulder and 1.4 mm at the implant apex. The median angular deviation was 3.6º. There were significantly smaller angular deviations (P=0.000) and significantly lower deviations at the apex (P=0.008) in implants placed for a single-tooth restoration than in those placed at a free-end dental arch. The location of the implant, whether in the upper or lower jaw, did not significantly affect deviations. Increasing implant length had a significant negative influence on deviations from the planned implant position. There was only one significant difference between two out of the five implant systems used. The data of this clinical study demonstrate the accuracy and predictable implant placement when using laboratory-fabricated surgical guides based on computed tomography.