Effects of a School-Based Intervention for Preventing Substance Use among Adolescents at Risk of Academic Failure: A Pilot Study of the Reasoning and Rehabilitation V2 Program.
Tobacco, alcohol and cannabis use are important health problems that contribute greatly to causes of death in worldwide. Early onset of substance use increases rapidly during adolescence and it has been associated with a wide range of adverse events. Because substance use is associated with dramatic consequences, delaying the initiation of substance use among adolescents remains a major public priority. This study examined the effectiveness of a school-based intervention program based on the application of the Reasoning and Rehabilitation V2 (R&R2) program for preventing substance use among adolescents at risk of academic failure. A sample of 142 participants (aged 13-17 years old) who were studying alternative education provision in Spain were randomly allocated to two conditions (68 experimental group, 74 control group). A pre-test survey assessing past and current substance use was conducted prior the implementation of the program, while a post-test survey was conducted about 12 months after the pre-test. The results showed a significant effect of the R&R program in the reduction of cigarette smoking, episodes of drunkenness, alcohol consumption and cannabis use. However, for daily smoking and episodes of drunkenness such benefits showed a reduction over time. These findings offer additional evidence of the effectiveness of the Reasoning and Rehabilitation V2 program in Spanish adolescent students who are exposed to substance use and suggest areas of future research.


Emerging role of microRNAs in cancer and cancer stem cells.
Cancer stem cells (CSCs), or cancer cells with stem cell properties, represent a small fraction of tumor bulk and are thought to be responsible for tumor formation and metastasis. However, the mechanisms of how CSCs are generated and regulated at the molecular level are poorly understood. Recent progress has highlighted the significance of microRNAs (miRNAs) in cancer progression and CSC function. The function and dysfunction of miRNAs in the development of cancer and CSCs have become a burgeoning area of intense research. A new finding has elucidated a mechanism of antagonistic miRNA crosstalk whereby one miRNA can inhibit another miRNA in regulating CSCs. Herein we make this short review to summarize the current understanding of the regulatory mechanisms of miRNAs in cancer and CSCs and discuss the implications of targeting CSCs for cancer therapeutics.


The suitability of alternative fatty food simulants for overall migration testing under both low- and high-temperature test conditions.
The suitability of various alternative, volatile fatty food simulants for overall migration testing was investigated under both low- and high-temperature test conditions. The overall migration into olive oil from a large number of commercially used food packaging materials applying various low- and high-temperature test conditions (e.g. 2 h at 175 degrees C, 30 min at 130 degrees C, 1 h at 100 degrees C followed by 10 days at 40 degrees C, 10 days at 20 degrees C) was determined. The results were compared with overall migration from these samples into iso-octane, 50% or 95% ethanol and isopropanol under appropriate test conditions. The samples investigated include homogeneous plastic films, laminates, coated board samples, a coated can, and articles. The results of the study indicate that iso-octane, 95% ethanol and isopropanol are suitable alternative fatty food simulants for overall migration testing under various time and temperature conditions.


A dissonant scale: stress recognition in the SAQ.
Our previous analyses using the Stress Recognition subscale of the Safety Attitudes Questionnaire (SAQ) resulted in significant effect estimates with equally opposing explanations. We suspected construct validity issues and investigated such using our own data and correlation matrices of previous published studies. The correlation matrices for each of the SAQ subscales from two previous studies by Speroff and Taylor were replicated and compared. The SAS Proc Factor procedure and the PRIORS = SMC option were used to perform Common Factor Analysis. The correlation matrices of both studies were very similar. Teamwork, Safety Climate, Job Satisfaction, Perceptions of Management and Working Conditions were well-correlated. The correlations ranged from 0.53 to 0.76. For Stress Recognition correlations ranged from -0.15 to 0.03. Common Factor Analysis confirmed the isolation of Stress Recognition. CFA returned a strong one-factor model that explained virtually all of the communal variance. Stress Recognition loaded poorly on this factor in both instances, and the CFA indicated that 96.4-100.0% of the variance associated with Stress Recognition was unique to that subscale, and not shared with the other 5 subscales. We conclude that the Stress Recognition subscale does not fit into the overall safety climate construct the SAQ intended to reflect. We recommend that this domain be omitted from overall safety climate scale score calculations, and clearly identified as an important yet distinct organizational construct. We suggest that this subscale be investigated for its true meaning, characterized as such, and findings conveyed to SAQ end users. We make no argument against Stress Recognition as an important organizational metric, rather we suggest that as a stand-alone construct its current packaging within the SAQ may be misleading for those intent on intervention development and evaluation in healthcare settings if they interpret Stress Recognition results as emblematic of safety climate.


Membranous glomerulopathy and treatment with Acthar®: a case study.
Treatment options for refractory membranous nephropathy are limited. Herein we describe the case of a 46-year-old white male with membranous nephropathy who progressed during 3 years of treatment with antihypertensive agents (specifically angiotensin-converting enzyme inhibitors and angiotensin receptor blockers), diuretics, simvastatin, prednisone, cyclosporine A, and mycophenolate mofetil. Prior to initiation of treatment with H.P. Acthar® Gel, his proteinuria level was 9,520 mg/dL (952.0 g/L) but it decreased to 2,948 mg/dL (294.8 g/L) after 10 months of Acthar therapy. After 13 months, treatment with Acthar was halted as his 24-hour urinary protein was 1,628 mg/dL (162.8 g/L); by 15 months, it was 407 mg/dL (40.7 g/L). The patient has remained free of signs and symptoms of membranous nephropathy for 1.5 years. These results support the use of Acthar as an effective and safe therapy for patients with refractory membranous nephropathy.


Differential responses to endothelial-dependent relaxation of the thoracic and abdominal aorta from male Sprague-Dawley rats.
Regional heterogeneity exists in reactivity of different vascular beds to vasoactive substances. Experiments were designed to determine if there are differences between thoracic and abdominal aorta response to acetylcholine-induced relaxation. Ten male Sprague-Dawley rats with a weighing between 200g-250g were used. The aorta was isolated and 3mm aortic rings were cut and suspended in organ baths containing physiological salt saline (PSS). Contractile and relaxation responses to noradrenaline (NA) and ACh, in the presence or absence of L-NNA and high K+ concentration were studied. Contractile response to NA was similar along the aorta. At the higher doses, ACh elicited a greater (p < 0.05) relaxation in the abdominal aorta when compared with the thoracic aorta. However, inhibition of eNOS was more effective (p<0.05) in preventing ACh-induced relaxation in the thoracic aorta when compared with the abdominal aorta. Conversely, inhibition of endothelial hyperpolarizing factor (EDHF) by high K+ concentration blocked ACh-induced relaxation to a greater extent in the abdominal aorta (p<0.05) when compared with the thoracic aorta. ACh-induced relaxation differs in the thoracic and abdominal aorta. Differences in the EDHF activity along the aorta underlie the differential response of the thoracic and abdominal aorta to ACh-induced relaxation.


Minimally invasive thoracolumbar corpectomy and reconstruction.
Minimally invasive surgical approaches have been advocated to approach ventrolateral thoracolumbar pathology. This article describes our technique for performing minimally invasive surgical thoracolumbar corpectomy and reconstruction. Twenty-five consecutive patients at a single institution were treated between 2006 and 2010 for a variety of diagnoses including tumors, infections, and trauma. Treatment variables, including operating time, estimated blood loss, number of levels treated, and complications, were collected, as were visual analog scale (VAS) scores for pain.Surgical times (mean, 188.5 minutes) and blood loss (mean, 423 mL) reflect a significant improvement over standard open corpectomy procedures. More than 60% of patients did not need blood products after the corpectomy procedure because substantial blood loss encountered during an open exposure to the spine was obviated. Similarly, operative times and anesthetic load was minimal enough for ≥80% of our patients to be extubated immediately after the corpectomy procedure. A 62% decrease in self-reported VAS scores was observed. No wound complications or radiographic evidence of implant subsidence or failure were observed at last follow-up.The advantages of the minimally invasive approach for corpectomies of the thoracolumbar spine were that an access surgeon was not needed; tissue dissection and surgical exposure were reduced, improving VAS scores postoperatively; and blood loss and operative times were minimized, preventing hemodynamic deterioration in these complex cases. Corpectomies may be performed in this fashion safely, with excellent pain relief and without many of the morbidities and difficulties associated with conventional open procedures.


Attenuation of CD4+CD25+ Regulatory T Cells in the Tumor Microenvironment by Metformin, a Type 2 Diabetes Drug.
CD4+CD25+ regulatory T cells (Treg), an essential subset for preventing autoimmune diseases, is implicated as a negative regulator in anti-tumor immunity. We found that metformin (Met) reduced tumor-infiltrating Treg (Ti-Treg), particularly the terminally-differentiated CD103+KLRG1+ population, and also decreased effector molecules such as CTLA4 and IL-10. Met inhibits the differentiation of naïve CD4+ T cells into inducible Treg (iTreg) by reducing forkhead box P3 (Foxp3) protein, caused by mTORC1 activation that was determined by the elevation of phosphorylated S6 (pS6), a downstream molecule of mTORC1. Rapamycin and compound C, an inhibitor of AMP-activated protein kinase (AMPK) restored the iTreg generation, further indicating the involvement of mTORC1 and AMPK. The metabolic profile of iTreg, increased Glut1-expression, and reduced mitochondrial membrane-potential and ROS production of Ti-Treg aided in identifying enhanced glycolysis upon Met-treatment. The negative impact of Met on Ti-Treg may help generation of the sustained antitumor immunity.


Urolithin A ameliorates experimental autoimmune encephalomyelitis by targeting aryl hydrocarbon receptor.
Urolithin A (URA) is an intestinal microbiota metabolic product from ellagitannin-containing foods with multiple biological activities. However, its role in autoimmune diseases is largely unknown. Here, for first time, we demonstrate the therapeutic effect of URA in an experimental autoimmune encephalomyelitis (EAE) animal model. Therapeutic effect was evaluated via an active and passive EAE animal model in vivo. The function of URA on bone marrow-derived dendritic cells (BM-DCs), T cells, and microglia were tested in vitro. Oral URA (25 mg/kg/d) suppressed disease progression at prevention, induction, and effector phases of preclinical EAE. Histological evaluation showed that significantly fewer inflammatory cells, decreased demyelination, lower numbers of M1-type microglia and activated DCs, as well as reduced infiltrating Th1/Th17 cells were present in the central nervous system (CNS) of the URA-treated group. URA treatment at 25 μM inhibited the activation of BM-DCs in vitro, restrained Th17 cell differentiation in T cell polarization conditions, and in a DC-CD4+ T cell co-culture system. Moreover, we confirmed URA inhibited pathogenicity of Th17 cells in adoptive EAE. Mechanism of URA action was directly targeting Aryl Hydrocarbon Receptor (AhR) and modulating the signaling pathways. Collectively, our study offers new evidence that URA, as a human microbial metabolite, is valuable to use as a prospective therapeutic candidate for autoimmune diseases.


Pituitary Adenoma on 18F-Fluciclovine PET/CT.
A 69-year-old man presented with lower urinary tract symptoms and prostate biopsy showed prostate cancer. F-Fluciclovine PET/CT revealed abnormal increased radiotracer uptake within the prostate gland, and multiple osseous structures, suspicious for tumoral involvement. Incidentally, an expansile soft tissue density mass arising from sella turcica demonstrated increased radiotracer activity. MRI showed a lobulated enhancing mass centered in the sella and eroding into the sphenoid sinus. The differential diagnosis includes pituitary macroadenoma versus prostate cancer metastasis. The tumor was resected and the pathological diagnosis was pituitary adenoma.


Single-shot three-dimensional shape measurement by low-coherent optical path difference digital holography.
A single-shot three-dimensional (3D) shape measurement by low-coherent optical path difference digital holography with small energy consumption is proposed. The use of a superluminescent diode makes it possible. Weighting of the single hologram and numerical reconstruction give the 3D shape of an object. Experimental results using a simple object (the surface of a button cell battery) are given. By comparison with experimental results using a vertical scanning method, the proposed method is confirmed. The effects of a shift interval of the hologram and a zero-order component on a measurement result are also discussed.


Donor-derived Cell-free DNA Combined With Histology Improves Prediction of Estimated Glomerular Filtration Rate Over Time in Kidney Transplant Recipients Compared With Histology Alone.
Higher Banff inflammation and chronicity scores on kidney transplant biopsies are associated with poorer graft survival, although histology alone has limitations in predicting outcomes. We investigated if integrating donor-derived cell-free DNA (dd-cfDNA, Allosure; CareDx, Inc.) with Banff biopsy scores into a predictive model for estimated glomerular filtration rate over time can improve prognostic assessment versus histology alone. We identified 180 kidney transplant patients with dd-cfDNA assessed within 1 mo of biopsy. Using linear mixed-effects models, a prediction model of Banff histology scores and dd-cfDNA on estimated glomerular filtration rate over time was derived. Nested models were compared using the likelihood-ratio test, Akaike Information Criterion, and Bayesian Information Criterion to assess if inclusion of dd-cfDNA into a model consisting of Banff biopsy scores would improve model fit. Univariate models identified significant covariate-by-time interactions for cg = 3 versus <3 (coefficient: -1.3 mL/min/1.73 m2/mo; 95% confidence interval [CI], -2.4 to -0.2; P = 0.02) and ci + ct ≥ 3 versus <3 (coefficient: -0.7 mL/min/1.73 m2/mo; 95% CI, -1.3 to -0.1; P = 0.03) and a trend toward significant covariate-by-time interaction for dd-cfDNA (coefficient: -0.5 mL/min/1.73 m2/mo; 95% CI, -1.0 to 0.1; P = 0.08). Addition of acute inflammation (i, t, and v), microvascular inflammation (g and ptc), and inflammation in area of interstitial fibrosis and tubular atrophy scores to chronicity scores (cg ≥ 3 and ci + ct ≥ 3) did not improve model fit. However, a model including dd-cfDNA with cg and ci + ct with covariate-by-time interactions had a better model fit compared with cg and ci + ct alone (likelihood-ratio test statistic = 21.1; df = 2; P < 0.001). Addition of dd-cfDNA to Banff biopsy scores provided better prognostic assessment over biopsy characteristics alone.


High speed ultraviolet digital image correlation (UV-DIC) for dynamic strains at extreme temperatures.
Digital Image Correlation (DIC) is a camera-based method of measuring full-field displacements and strains from the surface of a deforming object. It can be applied at any length scale (determined by the lenses) and any time scale (determined by the camera), and because it is non-contacting, it can also be used at temperatures much higher than can be withstood by bonded strain gauges. At extreme temperatures, materials emit light in the form of blackbody radiation, which can saturate the camera sensor. It has previously been shown that the emitted light can be effectively screened by using ultraviolet (UV) cameras, lenses, and filters; however, commercially available UV cameras are relatively slow, which limits the speed of combined UV-DIC measurements. In this study, a UV intensifier was paired with a high-speed camera, and its ability to perform UV-DIC at high temperature and high speed was investigated. The system was compared over three different experiments: (A) a quasi-static thermal expansion test at high temperature, (B) a vibration test at room temperature, and (C) the same vibration test repeated at high temperature. The system successfully performed DIC up to at least 1600 °C at frame rates of 5000 fps, which is more than 100 times faster than other examples of UV-DIC in the literature. In all cases, measurements made using the UV intensifier were much noisier than those made without the intensifier, but the intensifier enabled measurements at temperatures well above those which an unfiltered high-speed camera otherwise saturates.


CO(2) Inhibits Respiration in Leaves of Rumex crispus L.
Curly dock (Rumex crispus L.) was grown from seed in a glasshouse at an ambient CO(2) partial pressure of about 35 pascals. Apparent respiration rate (CO(2) efflux in the dark) of expanded leaves was then measured at ambient CO(2) partial pressure of 5 to 95 pascals. Calculated intercellular CO(2) partial pressure was proportional to ambient CO(2) partial pressure in these short-term experiments. The CO(2) level strongly affected apparent respiration rate: a doubling of the partial pressure of CO(2) typically inhibited respiration by 25 to 30%, whereas a decrease in CO(2) elicited a corresponding increase in respiration. These responses were readily reversible. A flexible, sensitive regulatory interaction between CO(2) (a byproduct of respiration) and some component(s) of heterotrophic metabolism is indicated.


Cell volume increase in murine MC3T3-E1 pre-osteoblasts attaching onto biocompatible tantalum observed by magnetic AC mode atomic force microscopy.
Magnetic AC mode (MACmode) atomic force microscopy (AFM) was used to study murine (mouse) MC3T3-E1 preosteoblastic cells attached to biocompatible tantalum substrates. Cell volumes of attached cells derived from AFM images were compared to volumes of detached cells in suspension measured by the Coulter sizing technique. An increase of approximately 50% in cell volume was observed when the cells attached to planar tantalum substrates and developed a flattened structure including lamellipodia. We address thoroughly the issues general to the AFM determination of absolute cell volumes, and compare our magnetic AC mode AFM measurements to hitherto reported cell volume determinations by contact mode AFM.


Whole blood histamine release rate during immunotherapy for nasal allergy.
In treating nasal allergies, desensitization is widely used on a daily basis, and its efficacy has been highly valued. With the purpose of predicting therapeutic efficacy before carrying out immunotherapy, we compared whole blood histamine release rate and various subjective symptoms before and after immunotherapy. We also compared the degrees of efficacy. Immunotherapy brought about a tendency for a reduction in the whole blood histamine release rate. This tendency appeared most marked in those patients in whom an improvement of subjective symptoms was considerable. Among subjective symptoms, the reduction in whole blood histamine release rate was strongest against nasal discharge and sneezing. In patients with a low histamine release rate prior to the initiation of immunotherapy, the improvement in subjective symptoms tended to be low.


Benefits of comprehensive inpatient education and discharge planning combined with outpatient support in elderly patients with congestive heart failure.
Multidisciplinary disease management programs for congestive heart failure have been shown to substantially reduce readmission rates, resulting in a reduction of costs. These interventions, however, have typically included changes in medical management, making it difficult to quantitate the key elements of a successful program involving education, discharge planning, and transitional care in the outpatient setting. The investigators utilized an experienced cardiac nurse educator to coordinate a targeted inpatient congestive heart failure education program coupled with comprehensive discharge planning and immediate outpatient reinforcement through a coordinated nurse-driven home health care program. The comprehensive intervention resulted in a marked reduction in 6-month readmission rates, from 44.2% to 11.4% (p=0.01). The average total cost saving for each subject in the interventional group was $1541, based on the decreased utilization of both skilled nursing services and home health care during outpatient follow-up. The costs to implement an inpatient education program were negligible, at $158 per subject. There was no difference in discharge medications or medical management protocols that would have influenced these results.


The Effect of Fluid Shear Stress on the In Vitro Release Kinetics of Sirolimus from PLGA Films.
Drug-carrying coatings of stents implanted in blood vessels are exposed to various blood flows. This study investigated the effect of fluid shear stress on the in vitro release kinetics of sirolimus from poly(lactic-co-glycolic acid) (PLGA) films. The homemade parallel plate flow chamber was used to exert quantitative shear stress on the sirolimus-carrying film. By adjusting the flow rate of the release media in the chamber, three levels of shear stress (3.6, 12.0, and 36.0 dyn/cm²) were respectively applied. For each level of shear stress employed, the release kinetics of sirolimus from the PLGA films exhibited a four-phase profile: an initial burst release phase (Phase I), a lag phase (Phase II), a second burst release phase (Phase III), and a terminal release phase (Phase IV). During Phases I and II, sirolimus was released slowly and in small amounts (<10%); however, during Phases III and IV, the drug release increased considerably. Comparisons of different shear stresses indicated that greater shear stress resulted in earlier and faster sirolimus release, with more cumulative drug release observed. PLGA film degradations (molecular weight reduction, mass loss, and surface topographical variations) were also investigated to better explain the observed drug release behavior. Consequently, fluid shear stress was found to significantly accelerate the release of sirolimus from the PLGA matrices. Therefore, this study could provide a practical method for evaluating the in vitro drug release from polymer matrices under uniform shear stress, and might help improve the design of biodegradable coatings on drug-eluting stents.


Myelolipoma of the posterior mediastinum in a patient with chronic dyserythropoietic anemia.
Myelolipoma (ML) is an uncommon benign mesenchymal neoplasia composed of mature adipose and hematopoietic tissues of uncertain etiology. Less than 3% of MLs occur in the mediastinal topography. The main differential diagnosis involves extramedullary hematopoiesis; therefore, pathological evaluation is essential for the definitive diagnosis. The authors report the case of a 50-year-old man diagnosed with congenital dyserythropoiesis and secondary hemosiderosis, who presented a posterior mediastinal tumor. The tumor was resected. It was macroscopically characterized by mature fat tissue with fibrous areas and soft consistency, which was yellowish at the cut surface. Histology revealed a well-defined nodule composed of adipocytes and hematopoietic tissue represented by erythroid, granulocytic, and megakaryocytic series, which was consistent with the diagnosis of ML located in the posterior mediastinum. There was no recurrence of the lesion during the 3-year follow-up. The aim of this report is to show the diagnosis of an unusual mediastinal lesion in the context of a chronic hematologic disease.


The Effect of a Single Bout of Exercise on Vitamin B2 Status Is Not Different between High- and Low-Fit Females.
High-fitness individuals have been suggested to be at risk of a poor vitamin B2 (riboflavin) status due to a potentially higher vitamin B2 demand, as measured by the erythrocyte glutathione reductase (EGR) activation coefficient (EGRAC). Longer-term exercise interventions have been shown to result in a lower vitamin B2 status, but studies are contradictory. Short-term exercise effects potentially contribute to discrepancies between studies but have only been tested in limited study populations. This study investigated if vitamin B2 status, measured by EGRAC, is affected by a single exercise bout in females who differ in fitness levels, and that represents long-term physical activity. At baseline and overnight after a 60-min cycling bout at 70% V·O2peak, EGR activity and EGRAC were measured in 31 young female adults, divided into a high-fit (V·O2peak ≥ 47 mL/kg/min, N = 15) and low-fit (V·O2peak ≤ 37 mL/kg/min, N = 16) group. A single exercise bout significantly increased EGR activity in high-fit and low-fit females (Ptime = 0.006). This response was not affected by fitness level (Ptime*group = 0.256). The effect of exercise on EGRAC was not significant (Ptime = 0.079) and not influenced by EGR activity. The exercise response of EGRAC was not significantly different between high-fit and low-fit females (Ptime*group = 0.141). Thus, a single exercise bout increased EGR activity, but did not affect EGRAC, indicating that vitamin B2 status was not affected. The exercise response on EGRAC and EGR did not differ between high-fit and low-fit females.


Adrenocortical tumors in children.
Etiopathogenesis and management of pediatric adrenocortical tumors (ACTs) is still obscure because of the limited number of cases. The aim of this study is to present a clear picture of the entire spectrum of pediatric ACTs by reviewing one of the largest noncollected pediatric series treated in a single medical center. Records of children treated for ACTs in our unit between 1970 and 1999, inclusive, were reviewed. Information recorded for each patient included age, sex, clinical characteristics, diagnostic methods, stage of disease, treatment, pathologic findings, and outcome. The patients were subdivided into 2 groups: group I, patients with adrenocortical carcinoma (ACC) and group II, patients with adrenocortical adenoma (ACA). These groups were analyzed with regard to parameters mentioned above. There were 30 children treated for ACTs in the study period with a mean age of 6.7 +/- 4.2 years (range, 2.5 to 13 years). Of these, 20 had ACC, and 10 had ACA. The tumors were right sided in 22 patients, left sided in 6 and bilateral in 2. Analysis of each group with regard to age and site of tumor showed no significant difference. Endocrine dysfunction was noted in 83% of the patients and virilization was the most common presentation followed by Cushing's syndrome. The most striking difference between 2 groups was the prepondarance of virilization in group II and Cushing's syndrome in group I. In the latter, 14 patients presented with palpable abdominal mass and 3 patients with distant metastases. The mean time from initial symptoms to diagnosis was 8.1 +/- 0.2 months, and this interval was similar in 2 groups, in functional and nonfunctional tumors, and in both sexes. Ultrasound scan, computerized tomography, magnetic resonance imaging, intravenous pyelography, and angiography were used for the diagnosis. All patients with ACA had localized disease, whereas 80% of the patients with ACC had regional or metastatic disease. Total excision was done in all patients with ACA, but only in 13 patients with ACCs. Of the latter, 2 patients underwent ipsilateral nephrectomy, and 1 patient had right hepatic lobectomy plus nephrectomy. Adjuvant chemotherapy consisting of mitotane (n = 12), mitotane plus cisplatin and etoposide (n = 2) was commenced. Seven patients with ACC had distant metastases postoperatively. The presence of regional disease at presentation was associated with a significantly shorter disease-free interval. All patients presenting with nonfunctional ACC (n = 4), functional ACC that have been totally resected (n = 4), and partially resected (n = 3) died of disease within the first 2.5 years after diagnosis. There was no significant difference between the functional and nonfunctional ACCs with regard to survival rate. All patients who had distant metastases postoperatively and who had partial excision died. Of the surviving 9 patients with ACC, there are 6 known long-term survivors who are still alive. ACAs are treated by total excision satisfactorily without any complication. For the time being, the most important aspect of therapy for ACCs is early diagnosis and total excision. Partial excision and advanced-stage disease are the major determinants of poor outcome. None of the clinical, laboratory, or pathologic features are reliable predictors for recurrence and discrimination of malignancy in ACTs. Because of the steadily increasing incidence of precancerous genetic syndromes of adrenal glands and poor prognosis of ACCs, childhood patients of endocrine disorders should receive a detailed and vigorous diagnostic evaluation and appropriate treatment as given to adults. Patients with ACTs should be entered into multi-institutional trials to adequately assess effective chemotherapy and radiotherapy protocols and molecular mechanisms of oncogenesis. J Pediatr Surg 36:549-554.


ROS-Sensitive Degradable PEG-PCL-PEG Micellar Thermogel.
A reactive oxygen species (ROS)-sensitive degradable polymer would be a promising material in designing a disease-responsive system or accelerating degradation of polymers with slow hydrolysis kinetics. Here, a thermogelling poly(ethylene glycol)-polycaprolactone-poly(ethylene glycol) (PEG-PCL-PEG or EG12 -CL20 -EG12 ) triblock copolymer with an oxalate group at the middle of the polymer is reported. The polymers form micelles with an average size of 100 nm in water. Thermogelation is observed in a concentration range of 8.0-37.0 wt%. In particular, the aqueous PEG-PCL-PEG triblock copolymer solutions are in a gel state at 37 °C in a concentration range of 25.0-37.0 wt%, whereas the aqueous PEG-PCL diblock copolymer solutions are in a sol state in the same concentration range at 37 °C. Thus, the gel depot could dissolve out once degradation of the triblock copolymers occurs at the oxalate group as confirmed by the in vitro experiment. In vivo gel formation is confirmed by injecting an aqueous PEG-PCL-PEG solution (36.0 wt%) into the subcutaneous layer of rats. The gel completely disappears in 21 d. A model polypeptide drug (cyclosporine A) is released over 21 d from the in situ formed gel. The micelle-based thermogel of PEG-PCL-PEG with ROS-triggering degradability is a promising injectable material for biomedical applications.


Transcriptomic and Metabolomic Approaches Deepen Our Knowledge of Plant-Endophyte Interactions.
In natural systems, plant-symbiont-pathogen interactions play important roles in mitigating abiotic and biotic stresses in plants. Symbionts have their own special recognition ways, but they may share some similar characteristics with pathogens based on studies of model microbes and plants. Multi-omics technologies could be applied to study plant-microbe interactions, especially plant-endophyte interactions. Endophytes are naturally occurring microbes that inhabit plants, but do not cause apparent symptoms in them, and arise as an advantageous source of novel metabolites, agriculturally important promoters, and stress resisters in their host plants. Although biochemical, physiological, and molecular investigations have demonstrated that endophytes confer benefits to their hosts, especially in terms of promoting plant growth, increasing metabolic capabilities, and enhancing stress resistance, plant-endophyte interactions consist of complex mechanisms between the two symbionts. Further knowledge of these mechanisms may be gained by adopting a multi-omics approach. The involved interaction, which can range from colonization to protection against adverse conditions, has been investigated by transcriptomics and metabolomics. This review aims to provide effective means and ways of applying multi-omics studies to solve the current problems in the characterization of plant-microbe interactions, involving recognition and colonization. The obtained results should be useful for identifying the key determinants in such interactions and would also provide a timely theoretical and material basis for the study of interaction mechanisms and their applications.


Enantioseparation of derivatized amino acids by capillary isoelectric focusing using cyclodextrin complexation.
Enantioseparation of dansylated as well as 6-aminoquinolyl-N-hydroxysuccinimidylcarbamate (AQC)-derivatized amino acids by means of capillary isoelectric focusing using various cyclodextrin derivatives is demonstrated. Separation is based on the enantioselective shift of the isoelectric points upon complexation with the chiral selectors. The zwitterionic, diastereomeric analyte-cyclodextrin complexes exhibited differences in the pI values up to more than 0.25 pI units. Enantioresolution was achieved for a number of derivatized amino acids and various selectors added to the carrier ampholyte solution. The hydroxypropyl-beta-cyclodextrin proved to be the best selector for this purpose. Enantioseparation as dependent on the selector concentration was evaluated in a range between 5 and 30 mM. Separation could be attained down to selector concentrations corresponding to a degree of complexation as low as 30%. The peaks appear according to the degree of complexation between the positions adopted without and with full complexation. The kinetics of complex formation and dissociation was fast enough in most instances to produce single peaks, even with complexation degrees near 0.5 and significant pI shifts. Peak widths were slightly enlarged in these instances. The method offers excellent perspectives for preparative applications.


Nickel(II)-dipeptidoamine-based tetrameric complex: structural study in solution and in solid state.
The coordination structure of M(4)L(4)H(-8) macromolecules (M = Ni(II), Cu(II), Pd(II)) containing small peptidic ligands (L = Xaa-His or Xaa-His-Yaa) has been predicted primarily on the basis of spectroscopic and potentiometric data in the literature. In this work, the neutral tetranuclear nickel(II) complex 1 formed with four double-deprotonated ligands (L = α-methyl-alanyl-histamine) was prepared, and its crystal structure was determined (C(36)H(56)N(16)Ni(4)O(4)·4.5CH(3)OH·1.5H(2)O: a = 11.2645(4) A, b = 23.5003(8) A, c = 20.9007(7) A, β = 102.321(1)°, monoclinic, P2(1)/c, Z = 4). In complex 1, the metal ions have a square planar geometry with 4N donor set consisting of the N-terminal amino nitrogen, the deprotonated amide nitrogen, the imidazole N(3) atom, and the deprotonated imidazole N(1) atom of the adjacent ligand. The latter nitrogen atom provides the connection of the four NiLH(-2) units forming a C(1) symmetrical saddle-like shape. The complexation of L with Ni(II) ion has been studied by a potentiometric method combined with UV-visible spectrophotometric titration. At pH 8.0, the predominant species is M(4)L(4)H(-8) with pK(4)(oligomerization) = 5.73. The tetranuclear structure of complex 1 was also studied in solution by (1)H and (13)C NMR spectroscopy suggesting a structure of symmetry S(4). DFT calculations on optimized structure in symmetry C(1) and S(4) have been performed to explain the observed differences in solution and in solid state. The nuclearity was also confirmed in solution by ESI-HRMS analysis.


Osmotic adjustment, symplast volume, and nonstomatally mediated water stress inhibition of photosynthesis in wheat.
At low water potential (psi(w)), dehydration reduces the symplast volume of leaf tissue. The effect of this reduction on photosynthetic capacity was investigated. The influence of osmotic adjustment on this relationship was also examined. To examine these relationships, comparative studies were undertaken on two wheat cultivars, one that osmotically adjusts in response to water deficits (;Condor'), and one that lacks this capacity (;Capelle Desprez'). During a 9-day stress cycle, when water was withheld from plants grown in a growth chamber, the relative water content of leaves declined by 30% in both cultivars. Leaf osmotic potential (psi(s)) declined to a greater degree in Condor plants. Measuring psi(s) at full turgor indicated that osmotic adjustment occurred in stressed Condor, but not in Capelle plants. Two methods were used to examine the degree of symplast (i.e. protoplast) volume reduction in tissue rapidly equilibrated to increasingly low psi(w). Both techniques gave similar results. With well-watered plants, symplast volume reduction from the maximum (found at high psi(w) for each cultivar) was the same for Condor and Capelle. After a stress cycle, volume was maintained to a greater degree at low psi(w) in Condor leaf tissue than in Capelle. Nonstomatally controlled photosynthesis was inhibited to the same degree at low psi(w) in leaf tissue prepared from well-watered Condor and Capelle plants. However, photosynthetic capacity was maintained to a greater degree at low psi(w) in tissue prepared from stressed Condor plants than in tissue from stressed Capelle plants. Net CO(2) uptake in attached leaves was monitored using an infrared gas analyzer. These studies indicated that in water stressed plants, photosynthesis was 106.5% higher in Condor than Capelle at ambient [CO(2)] and 21.8% higher at elevated external [CO(2)]. The results presented in this report were interpreted as consistent with the hypothesis that there is a causal association between protoplast (and presumably chloroplast) volume reduction at low psi(w) and low psi(w) inhibition of photosynthesis. Also, the data indicate that osmotic adjustment allows for maintenance of relatively greater volume at low psi(w), thus reducing low psi(w) inhibition of chloroplast photosynthetic potential.


[Technical aspects, indications and results of small bowel videocapsule endoscopy].
Videocapsule endoscopy is a new non-invasive endoscopic tool useful for small bowel examination. The aims of this review are to precise the technical aspects of videocapsule endoscopy, indications and results of this technique in clinical practice. Literature review. The main indication of vidéocapsule endoscopy is obscure gastrointestinal bleeding. Videocapsule endoscopy can precise the aetiology of the bleeding and guide the therapeutic approach. The second indication is Crohn's disease, in establishment of the diagnosis, evaluation of small bowel extension or in differential diagnosis of indeterminate colitis. Videocapsule endoscopy is also useful in patients with small bowel neoplasia, polyposis and some patients with celiac sprue. Videocapsule endoscopy is an important endoscopic technique which is must be quickly part of endoscopic diagnosis tools.


Identification of a Novel Cancer Stemness-Associated ceRNA Axis in Lung Adenocarcinoma via Stemness Indices Analysis.
The aim of this study was to identify a novel cancer stemness-related ceRNA regulatory axis in lung adenocarcinoma (LUAD) via weighted gene coexpression network analysis of a stemness index. The RNA sequencing expression profiles of 513 cancer samples and 60 normal samples were obtained from the TCGA database. Differentially expressed mRNAs (DEmRNAs), lncRNAs (DElncRNAs), and miRNAs (DEmiRNAs) were identified with R software. Functional enrichment analysis was conducted using DAVID 6.8. The ceRNA network was constructed via multiple bioinformatics analyses, and the correlations between possible ceRNAs and prognosis were analyzed using KaplanMeier plots. WGCNA was then applied to distinguish key genes related to the mRNA expression-based stemness index (mRNAsi) in LUAD. After combining the weighted gene coexpression and ceRNA networks, a novel ceRNA regulatory axis was identified, and its biological functions were explored in vitro and vivo. In total, 1,825 DElncRNAs, 291 DEmiRNAs, and 3,742 DEmRNAs were identified. Functional enrichment analysis revealed that the DEmRNAs might be associated with LUAD onset and progression. The ceRNA network was constructed with 14 lncRNAs, 10 miRNAs, and 52 mRNAs. KaplanMeier analysis identified 2 DEmiRNAs, 5 DElncRNAs, and 41 DEmRNAs with remarkable prognostic power. One gene (MFAP4) in the ceRNA network was found to be closely related to mRNAsi by using WGCNA. Functional investigation further confirmed that the C8orf34-as1/miR-671-5p/MFAP4 regulatory axis has important functions in LUAD cell migration and stemness. This study provides a deeper understanding of the lncRNAmiRNAmRNA ceRNA network and, more importantly, reveals a novel ceRNA regulatory axis, which may provide new insights into novel molecular therapeutic targets for inhibiting LUAD stem characteristics.


Exchange of an occluded nephroureteral stent by using a snare.
Percutaneous retrograde nephroureteral stent exchange may be complicated by catheter occlusion with calcareous debris. When a guide wire cannot be passed through the catheter, a snare may be advanced over the stent into the renal pelvis, permitting withdrawal of the occluded stent while maintaining access for placement of a new stent. This procedure was performed successfully in a 73-year-old man.


Isolation and Characterization of Carotenoid-rich Lipid Globules from Peridinium foliaceum.
Carotenoid-rich oil globules were isolated from the cytoplasm of the binucleate dinoflagellate, Peridinium foliaceum. These orange globules were collected from ruptured cells by ultracentrifugation on a sucrose density gradient, and checked for purity by electron microscopy. The osmiophilic globules were assayed for lipid (including pigment) and protein content. The lipid to protein ratio was 1.39:1, with a calculated density of the globules of 1.05 grams per cubic centimeter. The lipids were composed of hydrocarbon, wax ester (phytyl ester), triglyceride, and polar (no phospholipid) fractions. The biochemical composition indicated that the globules function as a reservoir of energy-rich components in the cell. Microspectrophotometric observations were consistent with pigment analyses which demonstrated that the globules were carotenoid-rich. In addition to beta-carotene, gamma-carotene, and canthaxanthin, the carotenogenic precursors: phytoene, phytofluence, zeta-carotene and beta-zeacarotene were isolated from the globules. Corrected fluorescence maxima of phytoene and phytofluene in hexane were recorded at 340 and 490 nanometers, respectively. Carotenes constituted 3.3% of the total oil globule lipid. The possibility of an extraplastidic carotenogenic enzyme system in P. foliaceum is discussed.


Influence of disorders of visual perception in word-to-picture matching tasks in patients with Alzheimer's disease.
Patients affected by early Alzheimer's disease were given word-to-picture matching tasks in which the foils shared lexical-semantic, phonological, or visual-perceptual features with the target. The aim of the study was to evaluate the influence of the visual perceptual deficit in lexical comprehension tasks based on pictorial material. The results demonstrated that perceptual deficits are common in Alzheimer's disease. This finding is in agreement with the hypothesis that multiple modular deficits in Alzheimer's disease contribute to impaired comprehension.


Gonadal development and plasma steroid levels during pubertal development in captive-reared striped bass, Morone saxatilis.
Puberty is the period during which full sexual development occurs and the capacity to reproduce is acquired. Despite its importance, our understanding of the endocrine regulation of puberty in lower vertebrates is still limited. The objective of the present study was to describe the changes in gonadal development and plasma steroid levels in a relatively late maturing species, the striped bass, during the first four years of life. In about 65% of the females, puberty was initiated during the third year. Although gonadosomatic index (GSI) and oocyte diameter increased during this year, this first cycle was characterized by a heterogeneous population of developing oocytes, a relatively low mean maximum oocyte diameter, and an absence of yolk granules in the oocytes. Plasma 17beta-estradiol (E(2)) levels were low in all three-year-old fish, suggesting that an insufficient stimulation of vitellogenin production by E(2) may underlie the lack of vitellogenin incorporation into developing oocytes. All monitored parameters increased during the fourth year, but were still below the values attained by older females. In about 60% of the males, puberty was initiated during the first year and all males were mature by the third year. During the first two years, several immature males initiated spermatogenesis without reaching full maturity. In mature males, mean GSI, plasma testosterone, and 11-ketotestosterone levels increased simultaneously, reaching higher values each subsequent year. Our results indicate that, similar to the situation in mammals, more than one reproductive cycle is required in striped bass before complete adulthood is reached.


The rhetoric vs. the reality in child care and protection: ideology and practice in working with fathers.
Within child care and protection, practitioners can be paralysed by a fundamental gap between the rhetoric and the reality in engaging fathers in their children's care. In an earlier paper we argued that there is a lack of an effective framework to guide practice with fathers in child care and protection work. We examined how health visitors and social workers could begin to assess how fathers could be categorized as either (or both) a risk or an asset to the child. Based on a review of the literature we now explore the limitations of current models of practice and trace the theoretical strands that influence them, drawing from the legal framework, attachment theory and models for anti-oppressive practice. We then highlight messages for practice with fathers for health care professionals involved in child protection. The working context for this paper is Scotland, although we believe that the ideas may be extrapolated to other geographical areas.


Molecular analysis of peptides from the GH loop of foot-and-mouth disease virus C-S30 using surface plasmon resonance: a role for kinetic rate constants.
A foot-and-mouth disease virus (FMDV) field variant, isolate C-S30 (also named C(1)-Barcelona), is known to contain four changes within the main antigenic site A (GH loop of capsid protein VP1, residues 136-150), at least one of which (Leu147-->Val) involves a highly conserved position, critical for antibody recognition in the reference strain C-S8c1. However, immunoenzymatic analysis of FMDV C-S30 showed it was recognised by 4C4, a monoclonal antibody that specifically targets site A. This remarkable behaviour has led us to analyse the individual and combined contributions of the four mutations to the antigenicity of C-S30, by surface plasmon resonance (SPR) and enzyme-linked immunosorbent assay (ELISA) studies of pentadecapeptides displaying all possible combinations of the four replacements. Analysis of this family of C-S30-derived analogues shows a certain level of antibody recognition by SPR. In addition, SPR data suggest that kinetic rate constants provide an indirect measure, on the one hand, of paratope accessibility (association rate constant) and, on the other hand, of peptide fitness to the same paratope (dissociation rate constant).


CA-MRSA shown to be an emerging problem.
With the significant increase in the incidents of community-acquired methicillin-resistant S. aureus (CA-MRSA), it's important for ED managers to be conversant not only in hospital-acquired MRSA, but also this less lethal version. Here are some recommendations: The appropriate treatment for an abscess, the most common manifestation of CA-MRSA, is surgery. If an antibiotic is deemed necessary, the most effective against CA-MRSA is trimethoprim/ sulfamethoxazole. You may wish to culture all abscesses to determine the precise nature of the bacterium.


Dynamic changes in accumbens dopamine correlate with learning during intracranial self-stimulation.
Dopamine in the nucleus accumbens (NAc) is an important neurotransmitter for reward-seeking behaviors such as intracranial self-stimulation (ICSS), although its precise role remains unclear. Here, dynamic fluctuations in extracellular dopamine were measured during ICSS in the rat NAc shell with fast-scan cyclic voltammetry at carbon-fiber microelectrodes. Rats were trained to press a lever to deliver electrical stimulation to the substantia nigra (SNc)/ventral tegmental area (VTA) after the random onset of a cue that predicted reward availability. Latency to respond after cue onset significantly declined across trials, indicative of learning. Dopamine release was evoked by the stimulation but also developed across trials in a time-locked fashion to the cue. Once established, the cue-evoked dopamine transients continued to grow in amplitude, although they were variable from trial to trial. The emergence of cue-evoked dopamine correlated with a decline in electrically evoked dopamine release. Extinction of ICSS resulted in a significant decline in goal-directed behavior coupled to a significant decrease in cue-evoked phasic dopamine across trials. Subsequent reinstatement of ICSS was correlated with a return to preextinction transient amplitudes in response to the cue and reestablishment of ICSS behavior. The results show the dynamic nature of chemical signaling in the NAc during ICSS and provide new insight into the role of NAc dopamine in reward-related behaviors.


Impact of starting BMI and degree of weight loss on changes in appetite-regulating hormones during diet-induced weight loss.
The aim of this study was to determine whether the hormone changes following weight loss are proportional to the degree of weight loss and to starting BMI. A very low-energy diet was used to achieve 15% weight loss. Fasting and postprandial gut hormones and leptin were measured during a meal test at baseline and at 5% (1%), 10% (2%), and 15% (2.5%) weight loss. Linear mixed-effects models were used to analyze hormone changes. From baseline to 5% weight loss, decreases were seen in fasting concentrations of leptin (-8.25 ng/mL; p < 0.001), amylin (-21.3 pg/mL; p < 0.001), and glucagon-like peptide 1 (-59.55 pg/mL; p < 0.001). There was a small further reduction in leptin between 5% and 15% weight loss (-1.88 ng/mL; p = 0.019) but not in glucagon-like peptide 1 and amylin. Fasting ghrelin showed a significant increase at 10% weight loss (41.64 pg/mL; p = 0.002), with a nonsignificant increase from 10% to 15% loss (26.03 pg/mL; p = 0.065). Postprandial changes in hormone levels were variable. There was no correlation between baseline weight and the degree of hormone changes. The majority of changes in fasting gut hormones and leptin occurred in early weight loss, with minor further changes up to 15% weight loss. Starting weight did not affect the degree of hormone change.


Electron microprobe and microradiographic studies of carious enamel lesions covered with dental calculus.
From a large number of posterior teeth with arrested natural carious lesions some 0.56 percent were found to have arrested approximal lesions with a superficial layer of calculus. The lesions were examined using quantitative microradiography for mineral content and by electron microprobe analysis for Ca, Na, Cl, Mg and P. The conditions in the plaque, which caused the formation of calculus, might also be expected to cause a remineralization of the lesions. However, the lesions examined were found to have a low mineral content in their body, and moreover, had a lower Na/Ca ratio and a higher Cl/Ca ratio than sound enamel; these are characteristics also found in carious lesions not covered with dental calculus. On the assumption that the lesions developed before any plaque calcification occurred, it is concluded that conditions which favour the calcification of plaque do not favour the remineralization of carious lesions in vivo. As only 0.5% of the carious lesions in extracted teeth were covered with calculus, it must be admitted that consecutive periods of lesion formation followed by calculus formation on the same tooth face are rare.


Retreatment With Sofosbuvir Plus Grazoprevir/Elbasvir Plus Ribavirin of Patients With Hepatitis C Virus Genotype 1 or 4 Who Previously Failed an NS5A- or NS3-Containing Regimen: The ANRS HC34 REVENGE Study.
Failure to achieve sustained virological response (SVR) with hepatitis C virus (HCV) direct-acting antiviral (DAA)-based regimens is commonly associated with emergence of resistance-associated substitutions (RASs). Retreatment of patients who failed prior DAAs remains challenging. The aim of this prospective and randomized study was to evaluate the efficacy (primary endpoint: SVR 12 weeks after end of treatment [SVR12]) and safety of sofosbuvir + grazoprevir/elbasvir + ribavirin for 16 or 24 weeks in patients who had failed to achieve SVR on previous NS5A- or NS3-based therapy and with evidence of RASs at failure. Patients were chronically infected with HCV genotype 1 or 4. Most of them had advanced fibrosis or compensated cirrhosis (liver stiffness 5.8-48.8 kPa). All patients achieved HCV RNA below the lower limit of quantification (either target detected [unquantifiable] or target not detected) during treatment. SVR12 was achieved by 25 of 26 patients. The only patient who did not reach SVR was a patient who died, but HCV RNA was negative at this time (5 weeks after stopping treatment). No patient discontinued treatment because of adverse events or virological failure. Globally, treatment was well tolerated. Our findings support the concept of retreating with sofosbuvir + grazoprevir/elbasvir + ribavirin, for 16 weeks, genotype 1 or 4 DAA-experienced patients with proven NS5A or NS3 RASs. NCT02647632.


Do Ask, Tell, and Show: Contextual Factors Affecting Sexual Orientation and Gender Identity Disclosure for Sexual and Gender Minority People.
Purpose: Sexual and gender minority (SGM) people-including members of lesbian, gay, bisexual, transgender, and queer communities-remain underrepresented in health research due to poor collection of sexual orientation and gender identity (SOGI) data. We sought to understand the contextual factors affecting how SGM research participants interact with SOGI questions to enhance participant experience and increase the accuracy and sensitivity of research findings. Methods: We recruited SGM adults for in-person semi-structured focus groups or online cognitive interviews from 2016 to 2018. During focus groups and cognitive interviews, we asked participants to respond to SOGI question sets. We employed template analysis to describe the contextual factors that affected SGM participants' responses to SOGI questions. Results: We had a total of 74 participants, including 55 participants organized into nine focus groups and 19 participants in cognitive interviews. Most self-identified as a sexual minority person (88%), and 51% identified as a gender minority person. Two main themes were: (1) the need to know the relevance (of why SOGI questions are asked) and (2) the importance of environmental and contextual cues (communicating physical safety and freedom from discrimination that influenced SOGI disclosure). Conclusions: Contextualizing the relevance of SOGI data sought could help improve the accuracy and sensitivity of data collection efforts. Environmental cues that communicate acceptance and safety for SGM individuals in research settings may support disclosure. Researchers should consider these contextual factors when designing future studies to improve research experiences for SGM individuals and increase the likelihood of future participation.


Pathophysiological Implication of Computed Tomography Images of Chronic Pulmonary Aspergillosis.
Chronic pulmonary aspergillosis (CPA) is a refractory disorder that needs long-term antifungal treatment and occasionally results in fatal respiratory failure and hemoptysis. However, the pathological features of the disorder have not been thoroughly delineated. Thirty cases were therefore analyzed clinically and histologically to elucidate the pathophysiology of CPA. The subjects comprised 14 individuals who underwent surgical removal and 16 patients who died. No subject exhibited a severely immunocompromised state. The main symptoms included cough, hemosputum, and dyspnea. Chest computed tomography (CT) findings revealed a cavity, fungus ball, and consolidation and/or ground glass opacity (GGO); 27 serial CT scans showed enlarged consolidation and/or GGO (70%), dilatation of the cavity (26%), and extension to the opposite lung (22%). Histopathological findings revealed a cavity with ulceration, bronchitis, and various degrees of organizing pneumonia (OP) that were correlated with the area of consolidation and GGO on the CT scan. The essential pathophysiology of CPA can be understood as an active state of ulceration of the cavity and/or erosive bronchitis caused by contact with the fungus ball, which may play a significant role in the development of OP. Consequently, OP is thought to reflect respiratory failure that relates to the prognosis of CPA.


Fracture complications. An overview.
No surgical procedure is free of complications. Determining the reason that a complication of a fracture repair occurred and developing a treatment plan are important if the objectives of fracture treatment are to be met. It is also necessary to deal with owners, and, sometimes, other veterinarians in meeting these objectives.


HIV Prevention: Opportunities and Challenges.
Preexposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF)-based regimens has been shown to be effective in preventing acquisition of HIV infection, with protective efficacy being dependent on adherence to treatment. Data from the PROUD (Preexposure Option for Reducing HIV in the UK) and IPERGAY (Action to Prevent Risk Exposure By and For Gay Men) studies, the later of which employed event-driven PrEP, showed a high rate of protective efficacy of PrEP with TDF and emtricitabine among men who have sex with men. Data from the ASPIRE (A Study to Prevent Infection With a Ring for Extended Use) study of a dapivirine vaginal ring showed a moderate rate of protective efficacy among women older than 21 years. Ongoing investigations are examining long-acting PrEP modalities and combination PrEP and contraception products. This article summarizes a presentation by Jeanne M. Marrazzo, MD, MPH, at the IAS-USA continuing education program, Improving the Management of HIV Disease, held in Washington, DC, in April 2016.


Low-dose treatment strategies.
Dose-comparison studies in chronic, continuously hospitalized patients show that megadoses of antipsychotic drugs are reasonably well tolerated. These findings, together with dose-comparison studies in acute patients, support the notion (and current practice) that the therapeutic index of antipsychotic drugs is wide. Recent work with outpatients indicates that fluphenazine decanoate 5 mg (versus 25 mg) every 2 weeks is effective for at least the first year. In addition, patients report feeling better when they take the lower dose. A dose-comparison study with haloperidol in newly admitted patients indicates that a 20 mg daily dose has neurotoxic effects. A similar dose-comparison study with oral fluphenazine indicates that a 5 mg daily dose is efficacious over a 3-week period. Thus, both inpatients and outpatients can be managed on doses that were formerly regarded as homeopathic. Patients taking low doses have fewer side effects (particularly less akinesia) and probably fewer dysphoric emotions than patients taking high doses, although they improve at a slower rate.


Inducible high-affinity binding site for benzo(a)pyrene in cytosol from rat liver.
By the use of the dextran-coated charcoal method the presence of a high-affinity binding site for benzo(a)pyrene in the cytosol from rat liver (R strain) has been demonstrated. This binder was saturable by ligand concentration and by time. Sucrose density gradient analysis after charcoal treatment revealed one major peak of radioactivity sedimenting at 4.4 S which was displaceable by a 100-fold molar excess of nonlabeled benzo(a)pyrene. Benzo(a)pyrene binding to liver cytosol was sensitive to protease treatment of the cytosol suggesting that the binder was a protein. Saturation and Scatchard plot analysis of benzo(a)pyrene binding indicated a high-affinity (Kd = 4.7 nmol) and a relatively low binding capacity (Bmax = 379 fmol/mg cytosolic protein), allowing, to denote this binder as a receptor for benzo(a)pyrene. Competition studies showed that this cytosolic receptor was distinct from steroid hormone receptors since benzo(a)pyrene binding was partially inhibited by aromatic carcinogens 3-methylcholanthrene and benz(a)anthracene but not by estradiol, progesterone or cortisol. R strain rats used in these experiments were sensitive to induction with 3-methylcholanthrene which produced the increase of cytochrome Pl-450 content in liver microsomes, enhanced the glutathione S-transferase activity in hepatic cytosol and produced liver hypertrophy in stimulated animals. All these effects were related to the dose of 3-methylcholanthrene used for the induction. Also, the cytosolic binding capacity for benzo(a)pyrene was increased in animals stimulated with 3-methylcholanthrene in a dose-dependent fashion. The 3-methylcholanthrene-induced binder displayed identical sedimentation velocity and kinetic parameters (Kd) to those characteristic for the benzo(a)pyrene receptor in hepatic cytosol from unstimulated animals. Conclusively, our results demonstrated that benzo(a)pyrene was bound to a receptor protein in rat liver cytosol which was inducible by the classical inducer 3-methylcholanthrene. The mechanism of induction of this receptor and its role in cell response to aromatic carcinogens still need to be elucidated.


FK 506 ameliorates the hepatic injury associated with ischemia and reperfusion in rats.
The effect of FK 506 on regeneration of the liver was studied in rats after a two-thirds partial hepatectomy after 60 min of ischemia of the unresected liver. The animals were divided into three distinct groups of 10 rats each. Group 1 (controls) received 0.5 ml saline solution intravenously 30 min after the induction of ischemia. Groups 2 and 3 were injected with FK 506 (0.3 mg/kg) intravenously 30 min after and 24 min before the induction of hepatic ischemia, respectively. The hepatic content of ATP and serum levels of ALT and lactate dehydrogenase were determined on each animal. In addition, the histological appearance and mitotic activity of the remnant liver was determined at regular 24-hr intervals after hepatic ischemia. All 10 control animals died within 72 hr. Treatment with FK 506 resulted in improved survival in groups 2 and 3 (30% and 80%, respectively). The improved survival seen in the FK 506-treated animals was reflected by a restoration of hepatic ATP content, a reduction in the serum levels of ALT and lactate dehydrogenase, an amelioration of hepatic necrosis and neutrophilic infiltration and an increase in the mitotic activity of the liver. These results suggest that FK 506 ameliorates the hepatic injury associated with ischemia/reperfusion and has a potent stimulatory effect on liver cell regeneration that may make it valuable as a hepatoprotective agent when administered to organ donors before graft harvesting.


[Entacapone for treatment of motor fluctuations in idiopathic Parkinson syndrome].
The treatment of idiopathic Parkinson's disease becomes rather difficult if levodopa-induced late complications such as motor fluctuations or dyskinesias occur. This prospective and open study shows that an add-on therapy with entacapone can significantly lower wearing-off and end-of-dose akinesia. This treatment is well tolerated and easy to perform.


Endothelin-like immunoreactivity in the nervous system of invertebrates and fish.
There have been no reports on the distribution of immunoreactive endothelin (ir-ET) in lower vertebrates and invertebrates, except for our previous studies on the nereid Neanthes diversicolor and the earthworm Eisenia foetida. In the present study, we found ET-like immunoreactivity in five species of invertebrates and two species of fish with antiserum against synthetic endothelin-1 (ET-1). Immunoreactive perikarya and nerve fibers were observed in the central nervous system of the slug Limax marginatus, the freshwater snail Indoplanorbis exustus, and the mussel Mytilus edulis in mollusks, the field cricket Gryllus bimaculatus in insects, and the tube tunicate Ciona intestinalis in protochordates. In the medaka, Oryzias latipes, ir-ET was found in the hypothalamoneurohypophysial system, the caudal neurosecretory system, the gill, and the kidney. Immunoreactive cells were also found in the mucous gland of the slug and in the adenohypophysis of the lamprey, Lampetra japonica. The wide distribution of ET-like substances in invertebrates and fish provides evidence for the case that ET found in mammals has a long evolutionary history.


The role of Ureaplasma parvum serovar-3 or serovar-14 infection in female patients with chronic micturition urethral pain and recurrent microscopic hematuria.
Ureaplasma parvum (UP) is commonly isolated in the genitor-urinary tract and may cause various clinical features, including microscopic hematuria (MH). Some UP serovars are more commonly related with specific urogenital disease, but the evidences have been conflicting. This study primarily aimed to research the possible associations between specific UP serotypes and genito-urinary pathogenicity in female patients showing MH with/without chronic micturition urethral pain (CMP). This study retrospectively reviewed 276 female patients having MH with/without CMP, who visited health screening center or female infertility clinic. All patients underwent multiplex polymerase chain reaction (PCR) tests with vaginal and urine samples to evaluate the infection rate and serotypes of UP. The antimicrobial susceptibility of UP and the predictors of CMP among UP infected patients were also analyzed. All patients were followed up at least for 6-months. Forty-nine patients (17.8%) showed urinary UP infection. Urinary UP serotyping showed the prevalence of seorvar-1, -3, -6 and -14 were 24.5%, 30.6%, 18.4% and 26.5%, respectively. 79.6% of the urinary UP positive patients accompanied vaginal UP infection. 22 patients of the cohort (8.0%) had CMP whereas serovars-3 and -14 accompanied CMP in 54.5% and 41.0% cases, respectively. No serovars-6 infection case had CMP. 26.4% of the cohort were infertile whereas 10.9% of these infertile patients were positive for urinary tract infection with UP serotype-3 or -14. Doxycycline, josamycin and pristinamycin were the most active antibiotics with the lowest rate of resistance (0.0%) for treating UP. At 1-month post-initial treatment with doxycycline, all UP serotypes were eradicated and no patient complained of urethral discomfort. However, simultaneous urinary and vaginal reinfection of serovar-3 (5 cases) and serovar-5 (1 case) were confirmed at 3-months post-initial doxycycline therapy. The logistic regression analyses revealed that serovars-3 [hazard ratio (HR) 1.354, P value 0.018] and -14 (HR 1.103, P value 0.046) were significantly associated with CMP in female patients having MH. UP serovars-3 and -14 infections could be associated with CMP in female patients having MH. Doxycycline, josamycin and pristinamycin were effective for treating UP. Serovar-3 showed higher reinfection rate than other serotypes after antibiotics treatment.


Evaluation of attitudes--dental class of 1991: a nine-year longitudinal study.
A longitudinal sample of students at a Midwest dental school was surveyed with regard to eleven attitudes about their choice of a dental career, their feelings about dental education, and their views of the dental profession. The survey was repeated seven times for the same respondents: at freshman orientation, at the end of the first, second, third, and fourth years, two and a half years, and five years following graduation. Respondents reported being optimistic about the profession, with the exception of a consistent loss of confidence in the validity of initial licensure examinations. They also felt positive about their education; although the third year placed the most stress on their positive views.


The impact of different adjuvant intravesical therapy methods on tumor biology in patients with high-risk non-muscle-invasive bladder cancer.
Expression level of the cell proliferation marker Ki-67 correlates with the degree of differentiation of tumor cells and stage in primary patients with non-muscle-invasive bladder cancer (NMIBC), but the marker is currently not used in assessing the efficacy of adjuvant intravesical therapy and risk stratification in patients with recurrent bladder tumors. A retroprospective study included 107 patients with high-risk NMIBC; the patients were divided into 2 groups. The first group included patients who received adjuvant therapy after transurethral resection of the bladder using the Bacillus Calmette-Guérin (BCG) vaccine (BCG therapy group; n = 54), the second group consisted of patients who received hyperthermic intravesical chemotherapy (HIVEC® therapy group; n = 53) using the device for local hyperthermia Combat BRS HIVEC®. Tumor recurrences were recorded in 21 (39%) patients receiving intravesical BCG therapy and in 9 (17%) patients after intravesical hyperthermic chemotherapy (p = 0.012). The expression level of Ki-67 in primary tumors did not differ; in recurrent tumors it was significantly different in both groups (32.05 ±13.80 vs 11.00 ± 6.86). The frequency of recurrence-free survival (RFS) in patients receiving chemohyperthermia was significantly higher than in patients after the BCG therapy (log-rank test result: p = 0.048). Assessment of Ki-67 expression in recurrent tumors can be a criterion for the effectiveness of intravesical bladder-preserving treatment. The use of hyperthermic chemotherapy can reduce the number of radical cystectomies in a separate group of patients with NMIBC.


Production of the Carboxylate Reductase from Nocardia otitidiscaviarum in a Soluble, Active Form for in vitro Applications.
Accessing aldehydes from carboxylate moieties is often a challenging task. In this regard, carboxylate reductases (CARs) are promising catalysts provided by nature that are able to accomplish this task in just one step, avoiding over-reduction to the alcohol product. However, the heterologous expression of CARs can be quite difficult due to the excessive formation of insoluble protein, thus hindering further characterization and application of the enzyme. Here, the heterologous production of the carboxylate reductase from Nocardia otitidiscaviarum (NoCAR) was optimized by a combination of i) optimized cultivation conditions, ii) post-translational modification with a phosphopantetheinyl transferase and iii) selection of an appropriate expression strain. Especially, the selection of Escherichia coli tuner cells as host had a strong effect on the final 110-fold increase in the specific activity of NoCAR. This highly active NoCAR was used to reduce sodium benzoate to benzaldehyde, and it was successfully assembled with an in vitro regeneration of ATP and NADPH, being capable of reducing about 30 mM sodium benzoate with high selectivity in only 2 h of reaction.


Factors Affecting Microbial Inactivation during High Pressure Processing in Juices and Beverages: A Review.
The purpose of this article is to review and discuss the factors affecting high pressure processing (HPP) in juices and beverages. The inactivation of microorganisms by HPP depends on numerous factors, including the magnitude of the pressure and the holding time, process temperature, compression and decompression rates, the microbiota, and the intrinsic properties of juices and beverages. Although extensive HPP research has been performed to characterize many of these factors, a number of issues, such as the rates of compression and decompression, still remain unresolved and need further investigation. In addition, some published results are conflicting and do not provide enough evidence to develop juice HPP "safe-harbor" parameters to achieve a minimum 5-log reduction of the pertinent microorganism and produce safe fruit juices and beverages.


Cognitive Reserve and Executive Functions in Adults with Type 2 Diabetes.
Adults with type two diabetes mellitus (DM2) show cognitive deficits within the executive function domain. The detrimental effects of DM2 over executive function (EF) performance may be mediated by factors such as cognitive reserve (CR). CR mediates cognitive performance by delaying the appearance of clinical symptoms from subjacent brain pathology or attenuating the severity of such symptoms. Our main goal was to study the effects of CR on executive functions of adults with DM2. Data from a total of 1,034 adults were included (362 women, 672 men). Subjects were categorized into four groups: subjects with DM2 and high CR (n = 235), control subjects with high CR (n = 265), subjects with DM2 and low CR (n = 298), and control subjects with low CR (n = 236). CR was quantified through 3 proxies: education, occupational complexity, and leisure activities. Executive functions were evaluated through visual scanning, verbal fluency, and backwards counting tasks. First, a series of four one-way ANOVAs was performed where group was included as a between-subject factor and executive function as a dependent variable. Second, a hierarchical multiple regression analysis was conducted to assess the weight of each CR proxy on EF performance. CR level significantly affected all executive function scores independently of the diabetes status. Hierarchical regression analyses indicated that years of education accounted for most of the variance in the model for executive function performance. In this study, we found that there is a significant effect of CR on executive function performance of DM2 subjects and education is the most important CR proxy.


Long-term stress and Helicobacter pylori infection independently induce gastric mucosal lesions in C57BL/6 mice.
Long-term psychological stresses may have a role in the pathogenesis of peptic ulcer. However, the interaction between stress and Helicobacter pylori infection in the development of peptic ulcer is not established. The aim of this study was to elucidate the roles of long-term stress and H. pylori infection in the development of gastric mucosal lesions in mice. The Sydney strain (SS1) of H. pylori was inoculated into the stomach of C57BL/J6 mice. Twelve weeks later, mice with or without H. pylori infection were exposed to long-term repeated water-immersion-restraint stress (WIRS) for 12 h per day, 3 times per week, for 8 weeks. Gastric mucosal lesions were evaluated both macroscopically (ulcer index) and microscopically (Updated Sydney System). The long-term WIRS induced mild inflammation, oedema, interstitial haemorrhage and superficial erosions in the stomach of mice both with and without H. pylori infection. The degree of mucosal inflammation or atrophy in H. pylori-infected mice was not influenced by the stress. In the mice without H. pylori infection, the ulcer index of the stressed mice was greater than that of non-stressed mice (1.66 +/- 0.39 versus 0.17 +/- 0.08, P = 0.007). In the mice with H. pylori infection, the ulcer index (mean +/- s(x)) of the stressed mice was also greater than that of non-stressed mice (2.31 +/- 0.59 versus 0.64 +/- 0.22, P = 0.027). The present study showed that long-term stress can induce gastric mucosal inflammation and erosions, and this effect may occur independently of H. pylori infection.


[Searching for a new risk factor of sudden cardiac death].
Sudden death of cardiovascular origin has been recognized as a major cause of sudden natural death. Advanced coronary atherosclerosis often co-existent, despite this, little or no coronary atherosclerosis was seen in approximately half of the sudden coronary death cases. Some components in the blood seem to induce not only the coronary atherosclerosis but also coronary spasm and/or thrombogenesis under certain conditions, which does not necessarily relate to the severity of atherosclerosis. Postmortem plasma lipids and lipoprotein levels, especially triglyceride-rich lipoprotein remnants (abbreviated as remnants) were measured as remnant-like particles-cholesterol (RLP-C) and triglyceride (RLP-TG) in two groups of Japanese subjects who died suddenly and unexpectedly due to coronary or non-coronary causes. Our study on the postmortem plasma analysis of lipids and lipoproteins indicated that RLP-C was most strongly correlated with the severity of the coronary atherosclerosis and to be the best predictor among various parameters. Furthermore, RLP-TG appeared to be highly associated with the risk of sudden coronary event or death, especially in cases without advanced coronary atherosclerosis, which might be associated with clinical events as coronary spasm or thrombosis. Biological activities of RLP from postmortem plasmas of sudden coronary death cases showed strong effects on platelet aggregation and impaired vasorelaxation in vitro. RLP determined as RLP-TG might affect on the process of spasm or on the formation of thrombus in the coronary artery at the time of sudden coronary death, independent of the severity of coronary atherosclerosis. These data might be clinically important to predict or to prevent sudden coronary death. The studies were conducted as followed: 1) Separation, purification and quantitative analysis of remnants from postmortem plasma. 2) Isolation and characterization of remnants from postmortem plasma. 2-1) Assessment of the methods of TG measurement. 2-2) Characterization of remnants by HPLC methods. 2-3) Characterization of remnants by electrophoresis. 2-4) Electron microscopical observation of remnants. 3) Lipid and lipoprotein analysis of sudden coronary death and control cases. 3-1) Lipid and lipoprotein levels of sudden coronary death and control cases. 3-2) Plasma remnant levels in the postprandial state. 3-3) Severity of coronary atherosclerosis and plasma lipid and lipoprotein levels, especially remnant levels. 3-4) Sudden coronary death cases without advanced coronary atherosclerosis and their plasma lipid, lipoprotein levels, especially remnant levels. 4) Biological activities of the remnants. 4-1) Endothelium-dependent vasodilator function in the coronary artery. 4-2) Aggregation of human blood platelets by remnants. 5) Fatty acids analysis of remnants from sudden coronary death cases. 6) Immuno-histochemical examination of various apo-lipoproteins on the coronary artery. 7) Gene analysis of plasma lipid metabolites.


Effects of a Fat-Rich Diet on the Spontaneous Release of Acetylcholine in the Neuromuscular Junction of Mice.
Western societies are facing a clear increase in the rate of obesity and overweight which are responsible for musculoskeletal pain. Some of the substances described in the environment of myofascial trigger points (MTrPs) are the same as those found in the skeletal muscle of obese people, such as cytokines. Furthermore, elevated neuromuscular neurotransmission has been associated with MTrPs. The main objective of this study is to assess whether obesity or overweight may be a facilitator of myofascial pain. The experiments were performed on male Swiss mice. One experimental group was given a typical "cafeteria" diet and another group a commercial high-fat diet for six weeks. Intramuscular adipocytes were assessed with Sudan III. The functional study was performed with electromyographic recording to determine the plaque noise and intracellular recording of miniature endplate potentials (MEPPs). The intake of a cafeteria diet showed the presence of more adipocytes in muscle tissue, but not with the fat-supplemented diet. Both experimental groups showed an increase in the plaque noise and an increase in the frequency of MEPPs that lasted several weeks after interrupting diets. In summary, the supply of a hypercaloric diet for six weeks in mice increases spontaneous neurotransmission, thus facilitating the development of MTrPs.


Involvement of orexin-2 receptors in the ventral tegmental area and nucleus accumbens in the antinociception induced by the lateral hypothalamus stimulation in rats.
Orexin, which is mainly produced by orexin-expressing neurons in the lateral hypothalamus (LH), plays an important role in pain modulation. Both kinds of orexin-1 (Ox1) and orexin-2 (Ox2) receptors have been found at high density in the ventral tegmental area (VTA) and nucleus accumbens (NAc). However, the quantity of Ox1 receptors in the VTA is more than that in the NAc. Additionally, it seems that the functional interaction between the LH, VTA and NAc implicates pain processing and modulation. In this study, we tried to examine the involvement of Ox2 receptors in the NAc and VTA using tail-flick test as an animal model of acute pain following microinjection of effective dose of carbachol (125nmol/0.5μl saline) into the LH. In this set of experiments, different doses of TCS OX2 29 as an Ox2 receptor antagonist were microinjected into the VTA (1, 7 and 20nmol/0.3μl DMSO) and the NAc (2, 10, 20 and 40nmol/0.5μl DMSO) 5min prior to carbachol administration. Administration of TCS OX2 29 into the VTA and NAc dose-dependently blocked intra-LH carbachol-induced antinociception. However, the inhibitory effect of TCS OX2 29 as an Ox2 receptor antagonist was more potent in the VTA than that in the NAc. It seems that VTA orexinergic receptors are more effective on LH stimulation-induced antinociception and the modulation of pain descending inhibitory system originated from the LH than those of the same receptors in the nucleus accumbens in rats.


[Usefulness of chosen websites concerning diseases of the spine at different stages of the therapy].
In the last years a huge increase in the accessibility to the Internet came. At the this paper we are pointing demonstration out websites, mainly English-speaking, which according to our assessment are very well designed conerning content that is published at them as well as the way of presenation of this content. Thanks to these thematic websites it is easier for the sick to find datum about one's diseases, as well as for doctors to reach patients, both with the information and with the therapeutic offer.


Different sensitivity to heatwaves across the life cycle of fish reflects phenotypic adaptation to environmental niche.
Predicting responses of marine organisms to global change requires eco-physiological assessments across the complex life cycles of species. Here, we experimentally tested the vulnerability of a demersal temperate fish (Sparus aurata) to long-lasting heatwaves, on larval, juvenile and adult life-stages. Fish were exposed to simulated coastal (18 °C), estuarine (24 °C) summer temperatures, and heatwave conditions (30 °C) and their physiological responses were assessed based on cellular stress response biomarkers (heat shock protein 70 kDa, ubiquitin, antioxidant enzymes, lipid peroxidation) and phenotypic measures (histopathology, condition and mortality). Life-stage vulnerability can be ranked as larvae > adults > juveniles, based on mortality, tissue pathology and the capacity to employ cellular stress responses, reflecting the different environmental niches of each life stage. While larvae lacked acclimation capacity, which resulted in damage to tissues and elevated mortality, juveniles coped well with elevated temperature. The rapid induction of cytoprotective proteins maintained the integrity of vital organs in juveniles, suggesting adaptive phenotypic plasticity in coastal and estuarine waters. Adults displayed lower plasticity to heatwaves as they transition to deeper habitats for maturation, showing tissue damage in brain, liver and muscle. Life cycle closure of sea breams in coastal habitats will therefore be determined by larval and adult stages.


Cancer Incidence and Mortality in Central Myanmar: Report of Nay Pyi Taw Population-Based Cancer Registry.
Cancer is a major public health problem in Myanmar, and cancer registration activities are currently underway through both hospital-based and population-based approaches. So far, there are no population-based cancer incidence and mortality estimates in the country. According to the 2014 census, the total population of Nay Pyi Taw Union Territory was 1,160,242 within the area of 70,571 km2. Nay Pyi Taw Cancer Registry team collected data of new cancer cases both actively and passively from all data sources in the region. The data were registered, updated, cross-checked, quality-assured, and analyzed in CanReg5. The results were presented as the number of cases by site, sex, and age, cumulative risk (CR), crude rate, age-specific, and age-standardized incidence rates (ASRs) per 100,000. Total 5,952 new cancer cases and 1874 cancer deaths were recorded among the population of the Nay Pyi Taw Union Territory between 2013 and 2017. The age-standardized incidence rate for all cancer sites excluding non-melanoma skin cancers in males was 125.9 and 107.3 for females. For both sexes combined, the most common cancers were lung (14%), breast (11.4%), liver (10.2%), mouth and pharynx (8.5%), and stomach cancers (7.8%). In males, the most common were lung (18.1%), liver (14.8%), mouth and pharynx (13%), stomach (8.9%) and colon, rectum, and anus (7.4%) cancers. In females, these were breast (21.2%), cervix (13.0%), lung (10.3%), stomach (6.9%) and colon, rectum, and anus (6.3%) cancers. The most common cancer deaths were caused by liver (20.8%), lung (15.7%), mouth and pharynx (9.3%), stomach (7.5%), and Colon, rectum, and anus (6.8%) cancers. The findings in this study are salient and have potential to serve as important information for the National Cancer Control Program to formulate prevention and control strategies.


Tumor perfusion using first-pass F-18 FDG PET images.
Many reports in the literature have focused on FDG PET imaging at conventional (60 minutes after injection) or delayed (several hours after injection) intervals, which exploits increased glycolysis in tumors for diagnosis. However, in rapidly growing tumors, accelerated glycolysis is, among other factors, mediated by hypoxia and poor perfusion. Interestingly, first-pass (0-2 minutes after injection) FDG PET images were shown to provide an index of perfusion. Here, we illustrate that tracer uptake by various (parts of) tumors is discrepant between first-pass and conventional PET images, probably reflecting the direct control of glucose transporter overexpression by hypoxia, resulting from poor perfusion (Warburg's hypothesis).


[Silencing hypoxia inducible factor-2α gene by small interference RNA inhibits the growth of mammosphere cells in nude mice under hypoxic microenvironment].
To explore the effects of silencing hypoxia inducible factor-2α (HIF-2α) by small interference RNA on the growth of mammosphere cells in nude mice under hypoxic microenvironment. The empty and interference vectors were transfected into MCF-7 cell. Then G418 was added to screen the positive cells to obtain stable cell line. The empty and interference vectors were inoculated subcutaneously into left and right back near hind limb of nude mice. The volume and weight of tumors were calculated respectively. The expressions of HIF-2α, CD44, OCT-4 and KLF-4 protein in xenograft tumor tissues were detected by Western blot. The expression vector of HIF-2α-siRNA was successfully established. The formation of mammosphere was lowered by silencing HIF-2α gene expression. In contract to empty vector group cell, there were obvious decreases in the volumes and weights of tumors in interference group (P < 0.05). The expression of HIF-2α protein of interference group (0.42 ± 0.01) was much lower than that of the empty vector group (0.89 ± 0.03, P < 0.05), the expression of CD44 protein of interference group (0.21 ± 0.01) was much lower than the empty vector group (0.78 ± 0.03, P < 0.05), the expression of OCT-4 protein of interference group (0.42 ± 0.01)was much lower than the empty vector group (0.68 ± 0.03, P < 0.05) and the expression of KLF-4 protein of interference group (0.34 ± 0.01) was much lower than the empty vector group (0.72 ± 0.03, P < 0.05). Silencing HIF-2α gene can effectively inhibit the growth of breast cancer stem cells in nude mice under hypoxic microenvironment. Its mechanism may be through inhibited capacity for self-renewal and proliferation of breast cancer stem cells in vivo through the down-regulated expressions of markers associated with stem cells. HIF-2α is expected to become a new target for gene therapy of breast cancer.


Periodontal status in university students.
The periodontal status of 217 5th-year students (aged 25-26 years and born in Helsinki) at the University of Helsinki was assessed. The students had been eligible for community-based dental care free of charge until the age of 18 years, after which they could obtain low-cost dental care from the Helsinki Student Health Service. Their periodontal status was determined according the community periodontal index of treatment needs; gingival retraction was recorded when 1 mm or more of the cementum was exposed. Code 0 sextant was found for 67% of the women and 57% of the men. 20% of the students examined had sextant scoring of code 3; no-one had code 4 sextants. 69% of the women and 49% of the men had gingival retraction, in average 1.5 +/- 0.5 mm. No correlation was found between the frequency of toothbrushing or the hand used for brushing and the number of retractions, nor did the number of healthy sextants correlate with the frequency of retractions. The findings emphasize the importance of better guidance regarding qualitative aspects of oral hygiene at home.


Secoisolariciresinol diglucoside prevents the oxidative stress-induced apoptosis of myocardial cells through activation of the JAK2/STAT3 signaling pathway.
Myocardial cell apoptosis mediated by oxidative stress has previously been identified as a key process in ischemic heart disease. Secoisolariciresinol diglucoside (SDG), a polyphenolic plant lignan primarily found in flaxseed, has been demonstrated to effectively protect myocardial cells from apoptosis. In the present study, the role of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) was investigated in mediating the protective effect of SDG. Findings of the present study revealed that treatment with H2O2 reduced cell viability and induced apoptosis in H9C2 rat cardiomyocytes. However, SDG was able to reduce the effect of H2O2 in a dose‑dependent manner. H2O2 reduced the expression level of phosphorylated STAT3 and inhibited the levels of B‑cell lymphoma‑extra‑large and induced myeloid leukemia cell differentiation protein, which are the STAT3 target genes. Conversely, SDG rescued phosphorylation of STAT3 and increased the levels of STAT3 target genes. Treatment with SDG alone led to a dose‑dependent increased phosphorylation of JAK2 and STAT3, without activating Src. Furthermore, the anti‑apoptotic effects of SDG were partially abolished by a JAK2/STAT3 inhibitor. In addition, molecular docking revealed that SDG may bind to the protein kinase domain of JAK2, at a binding energy of ‑8.258 kcal/mol. Molecular dynamics simulations revealed that JAK2‑SDG binding was stable. In conclusion, activation of the JAK2/STAT3 signaling pathway contributed to the anti‑apoptotic activity of SDG, which may be a potential JAK2 activator.


Differential Regulation of ERK1/2 and mTORC1 Through T1R1/T1R3 in MIN6 Cells.
The MAPKs ERK1/2 respond to nutrients and other insulin secretagogues in pancreatic β-cells and mediate nutrient-dependent insulin gene transcription. Nutrients also stimulate the mechanistic target of rapamycin complex 1 (mTORC1) to regulate protein synthesis. We showed previously that activation of both ERK1/2 and mTORC1 in the MIN6 pancreatic β-cell-derived line by extracellular amino acids (AAs) is at least in part mediated by the heterodimeric T1R1/T1R3, a G protein-coupled receptor. We show here that AAs differentially activate these two signaling pathways in MIN6 cells. Pretreatment with pertussis toxin did not prevent the activation of either ERK1/2 or mTORC1 by AAs, indicating that G(I) is not central to either pathway. Although glucagon-like peptide 1, an agonist for a G(s-)coupled receptor, activated ERK1/2 well and mTORC1 to a small extent, AAs had no effect on cytosolic cAMP accumulation. Ca(2+) entry is required for ERK1/2 activation by AAs but is dispensable for AA activation of mTORC1. Pretreatment with UBO-QIC, a selective G(q) inhibitor, reduced the activation of ERK1/2 but had little effect on the activation of mTORC1 by AAs, suggesting a differential requirement for G(q). Inhibition of G(12/13) by the overexpression of the regulator of G protein signaling domain of p115 ρ-guanine nucleotide exchange factor had no effect on mTORC1 activation by AAs, suggesting that these G proteins are also not involved. We conclude that AAs regulate ERK1/2 and mTORC1 through distinct signaling pathways.


Harnessing eugenol as a substrate for production of aromatic compounds with recombinant strains of Amycolatopsis sp. HR167.
To harness eugenol as cheap substrate for the biotechnological production of aromatic compounds, the vanillyl alcohol oxidase gene (vaoA) from Penicillium simplicissimum CBS 170.90 was cloned in an expression vector suitable for Gram-positive bacteria and expressed in the vanillin-tolerant Gram-positive strain Amycolatopsis sp. HR167. Recombinant strains harboring hybrid plasmid pRLE6SKvaom exhibited a specific vanillyl alcohol oxidase activity of 1.1U/g protein. Moreover, this strain had gained the ability to grow on eugenol as sole carbon source. The intermediates coniferyl alcohol, coniferyl aldehyde, ferulic acid, guajacol, and vanillic acid were detected as excreted compounds during growth on eugenol, whereas vanillin could only be detected in trace amounts. Resting cells of Amycolatopsis sp. HR167 (pRLE6SKvaom) produced coniferyl alcohol from eugenol with a maximum conversion rate of about 2.3 mmol/h/l of culture, and a maximum coniferyl alcohol concentration of 4.7 g/1 was obtained after 16 h biotransformation without further optimization. Beside coniferyl alcohol, traces of coniferyl aldehyde and ferulic acid were also detected.


Sexual Abuse and Assault in a Large National Sample of Children and Adolescents.
The present study sought to examine features of sexual abuse cases among a U.S. nationally representative sample of 13,052 children and adolescents, ages 0-17 years. The National Survey of Children's Exposure to Violence was collected in three different years (2008, 2011, and 2014) via telephone interviews. Information about sexual abuse and assault was obtained from youth themselves (ages 10-17) or caregivers (for children ages 0-9) using the Juvenile Victimization Questionnaire. Results indicate most offenses are at the hands of other juveniles (76.7% for males and 70.1% for females), primarily acquaintances, and occurring more frequently for adolescents aged 14-17. Whereas girls are mostly abused by males (88.4%), boys are abused by both males (45.6%) and females (54.4%). In 15% of cases, penetration is part of the abuse. Victims report being very afraid in 37.5% of episodes but not at all afraid in 19.8%. Among 10- to 17-year-olds, 66.3% of episodes are not reported to parents or any adult. Police reports occur for 19.1% of all cases. The results in the present study indicate that children and youth are exposed to sexual abuse and assault in varied ways, which require moving beyond conventional stereotypes of the problem.


[3-years outcome of follow-up of patients with chronic obstructive pulmonary disease successfully treated by percutaneous coronary intervention due to acute coronary syndrome].
Aim To evaluate results of three-year follow-up in patients after acute coronary syndrome (ACS) associated with chronic obstructive pulmonary disease (COPD) and to identify predictors for delayed serious cardiovascular adverse (SCVAE) events.Material and methods This prospective cohort study included 119 patients with verified COPD who had ACS after a successful urgent percutaneous coronary intervention and were discharged from the hospital without in-hospital complications. Incidence of and time to SCVAE (cardiovascular death, myocardial infarction, stroke, repeated unscheduled myocardial revascularization) were recorded. SCVAE predictors were identified with the Cox regression by stepwise inclusion of variables into the model.Results SCVAE occurred in 33.6 % of ACS patients with COPD. The high rate of repeated myocardial revascularization mostly contributed to the development of delayed SCVAEs (19.3 % of patients). Independent predictors of SCVAE included the total number of stenoses in major coronary artery branches; ankle-brachial index; glomerular filtration rate calculated with the CKD-EPI equation; frequent COPD exacerbations; functional residual capacity of the lungs; and 6-min walk distance.Conclusion New independent predictors of SCVAE were identified in COPD patients after ACS with percutaneous coronary intervention and stenting, including distance in the 6-min walk test, frequent COPD exacerbations, and functional residual volume of the lungs as an index of pulmonary hyperinflation.