Current dietary exposure to polychlorodibenzo-p-dioxins, polychlorodibenzofurans, and dioxin-like polychlorobiphenyls in Italy.
This study deals with an assessment of dietary exposure to polychlorodibenzo-p-dioxins (PCDDs), polychlorodibenzofurans (PCDFs), and dioxin-like polychlorobiphenyls (DL-PCBs) for the Italian general population, obtained by combining data from a national food consumption survey with contamination concentrations of European foodstuffs available on the market. The distribution of PCDD, PCDF, and DL-PCB dietary intake(s) in the Italian population was investigated to assess to what extent the variability in dietary habits may cause higher exposures to the previously mentioned contaminants. Results indicate that the main contributions to total PCDD, PCDF, and DL-PCB intake are due to fish and fish products (44%) and to milk and dairy products (27%). The mean PCDD, PCDF, and DL-PCB intake (total toxic equivalents) via food was estimated 5.34, 3.37, and 2.28 pg World Health Organization (WHO)-TE/kg of body weight (kg-bw) per day for the three age groups 0-6 (breastfeeding excluded), 7-12, and 13-94 years old, respectively. The highest exposures due to variation in dietary habits are in general within a factor of 2-3. From the mean exposure estimated for the general population (adults), it can be inferred that a consistent part of it would exceed the tolerable daily intake of 2 pg WHO-TE/kg-bw adopted by the Scientific Committee on Food of the European Commission in 2001.


Investigating the Effect of Supportive Interventions on Initiation of Breastfeeding, Exclusive Breastfeeding, and Continuation of Breastfeeding in Adolescent Mothers: A Systematic Review and Meta-Analysis.
Introduction: The initiation of breastfeeding, exclusive breastfeeding, and its duration for 2 years in adolescent mothers is less than adult mothers. The purpose of this study is to determine the effect of supportive interventions on the initiation of breastfeeding, exclusive breastfeeding, and continuation of breastfeeding in adolescent mothers. Methods: Web of Science, PubMed, Scopus, Cochrane Library, EMBASE, ProQuest, SID, Iranmedex, and Google Scholar were searched to find English and Persian clinical trial studies without time limit. The Cochrane checklist was used to check the bias of the articles. Data analysis was done using STATA version 11. I-squared index was used to check the heterogeneity, and funnel plot and Begg test were used to examine the publication bias. The combined odds ratio (OR) and random effects model were used to combine the studies and perform meta-analysis. Results: Of 492 articles, 11 articles were entered to the systematic review. Of 11 articles, three articles were entered to the meta-analysis. The supportive interventions included educational and counseling interventions, home visit, and peer support. The results of the present random effects meta-analysis model showed that the combined OR was 3.38 with 95% confidence interval (1.66-6.88, p = 0.001), thus that, breastfeeding initiation in the intervention group was higher than the control group. Conclusion: Supportive interventions such as educational and counseling interventions, home visits, and peer support are suitable strategies to promote breastfeeding in adolescent mothers. Therefore, it is suggested to integrate these strategies in prenatal and postpartum care of adolescent mothers.


Borrelia lusitaniae Infection Mimicking Headache, Neurologic Deficits, and Cerebrospinal Fluid Lymphocytosis.
Headache with neurologic deficits and cerebrospinal fluid lymphocytosis (HaNDL) is a rare headache syndrome included in the Classification of Headache of the International Headache Society as a "headache attributed to non-infectious inflammatory intracranial disease." We report one 15-year-old patient with clinical history and cerebrospinal fluid findings compatible with the diagnosis of HaNDL in whom Borrelia lusitaniae was identified in cerebrospinal fluid by polymerase chain reaction.


Exploring the structure-permeation relationship of topical tricyclic antidepressants used for skin analgesia.
The purpose of this study was to evaluate the skin permeation of tricyclic antidepressants (TCAs) with propamine moiety to select candidates for the development of topical analgesics to treat cutaneous pain. We sought to establish the structure-permeation relationship (SPR) of topical TCAs. The lipophilicity, melting point, and aqueous solubility were determined to develop the physicochemical characterization. The TCA permeation into pig and nude mouse skins was estimated using Franz diffusion cell. TCAs and lidocaine were comparatively examined for cutaneous analgesia by pinprick assay. Cutaneous tolerance to TCAs was assessed using nude mouse skin. The skin deposition increased following the increase of lipophilicity after excluding the effect of solubility, with clomipramine exhibiting the highest skin retention. A contrary result was observed for TCA penetration into the receptor. Of the permeants tested, clomipramine demonstrated the best skin-targeting ability. Nortriptyline and clomipramine demonstrated selective uptake into the hair follicles, exhibiting a 2.5-fold higher follicular accumulation than desipramine. Replacement of nitrogen with carbon in the seven-member ring increased skin absorption. The tertiary amine TCAs demonstrated higher absorption than the secondary amine TCAs. The position of the double bond also affected skin transport. Topical clomipramine had a longer duration of analgesic action than lidocaine (240min versus 60min). Exploring the SPR revealed that clomipramine could be an analgesic candidate drug for future development.


miRNA-205 is a candidate tumor suppressor that targets ZEB2 in renal cell carcinoma.
This study aims to characterize the function of downregulated MicroRNA miR-205 in renal cell carcinoma (RCC), and show how the downstream zinc finger E-box-binding homeobox 2 (ZEB2) is negatively regulated by miR-205. The expression of miR-205 was detected in RCC and adjacent non-tumor tissues using real-time polymerase chain reaction (PCR). The expression of miR-205 and ZEB2 was detected in RCC cell lines using real-time PCR. The luciferase reporter assay was used to assess ZEB2 as a target of miR-205. Protein levels of ZEB2, E-cadherin, and vimentin were measured by western blot after overexpression of miR-205 in ACHN cells. In vivo functions of miR-205 in ACHN cells were measured by MTT assays, migration and invasion assays, and flow cytometry. MiR-205 was significantly downregulated in RCC samples and cell lines compared with matched non-tumor tissues and HK-2 cells, respectively. No significant difference was found in miR-205 expression between well differentiated and poorly to moderately differentiated groups or between phase I and phase II-III. ZEB2 was upregulated in RCC cell lines compared with expression in HK-2 cells. Upregulation of miR-205 expression caused the downregulation of ZEB2 and vimentin, and the upregulation of E-cadherin in ACHN cells. miR-205 also inhibited proliferation, migration, and invasion, and induced apoptosis of ACHN cells. miR-205 is a candidate tumor suppressor that targets ZEB2 in RCC.


Telemedicine for urban uninsured: a pilot framework for specialty care planning for sustainability.
A national approach to medical care for the uninsured is for the provision of primary and preventive care through Community Health Centers. Access to specialty care for both Medicaid and uninsured patients is in decline even though specialty care has been shown to be cost-effective and improve outcomes. The consequences could result in further deterioration of the health of the uninsured and underinsured populations and increasing costs born by the insured and safety net providers. Telemedicine can provide specialty services efficiently if planned with a business model to sustain the program. This paper outlines a pilot framework to plan and cost-justify telemedicine specialty care for the uninsured and marginally insured. This potential framework is supported by data from an urban community with the highest concentration of uninsured in the country: Houston, Texas. Further study and evaluation will be needed once the framework and tools are implemented to empirically prove the sustainability of telemedicine specialty care for the urban uninsured.


Analysis and recognition of characteristics of digitized tongue pictures and tongue coating texture based on fractal theory in traditional Chinese medicine.
Simple fractal dimensions have been proposed for use in the analysis of the characteristics of digitized tongue pictures and tongue coating texture, which could further the establishment of objectified classification criteria under the conditions of expanding sample size. However, detailed descriptions on simple fractal dimensions have been limited. Therefore, BP (back propagation) neural network model classifiers could be designed by further calculation of the multiple fractal spectrum characteristics of digitized tongue pictures in order to classify and recognize the thin/thick or greasy characteristics of tongue coating. The fractal dimensions of sample data of 587 digitized tongue pictures were collected in a standard environment. A statistical analysis was conducted on the calculation results of the sample data, and the sensitivity of the fractal dimensions to the thin/thick and greasy characteristics of digitized tongue pictures was observed. As the overlap region resulted from a range of values of a single parameter, another 8 characteristic parameters of the multiple fractal spectra of the digitized tongue pictures were further proposed as the elements in the input layer of the three-layers BP neural network. Automatic recognition classifiers were designed and trained for the characteristics of digitized tongue pictures and tongue coating textures. The simple fractal dimension was sensitive to the thin/thick and greasy characteristics of digitized tongue pictures and could better judge the characteristics of the thickness of the tongue coating. A classifier with characteristic parameters of multiple fractal spectra as the input vectors identified by the BP neural network models could effectively increase the accuracy rate judged by the characteristics of the tongue coating texture.


Biochemical and immunochemical analysis of avian beta 1 and mammalian beta 2-adrenergic receptors.
We have studied the molecular properties of avian beta 1-adrenergic receptor and human beta 2-adrenergic receptor. The turkey erythrocytes beta 1-receptor has been solubilized in active form by digitonin and has been purified to homogeneity by affinity chromatography followed by electroelution from polyacrylamide gel. The photoactivable ligand, iodocyanopindololdiazirine, labels specifically a major 45 kDa and minor 55 kDa polypeptide in turkey erythrocytes, whereas in A431, it labels two polypeptides of molecular weights 65 kDa and 55 kDa. Both types of receptors are N- and possibly O-glycosylated but the turkey beta 1 receptor has only complex carbohydrates whereas the human beta 2 receptor has in addition oligo mannosidic polysaccharidic moiety. Polyclonal and monoclonal antibodies were raised against the beta 1- and beta 2-adrenergic receptors. Polyclonal antibodies were found to mimic beta-adrenergic agonists by stimulating adenylate cyclase upon binding to the receptors. The monoclonal antibodies precipitated both intact and affinity labeled receptors which they also revealed on immunoblots.


Diagnostics for energetic particle studies on the HL-2A tokamak.
About 13 kinds of diagnostics for energetic particle physics studied on the HuanLiuqi-2A (commonly referred to as HL-2A) tokamak are described in this paper. Their measurement ranges, resolutions, and arrangement are presented. Three under-construction diagnostics including imaging fast ion D-alpha, scintillator matrix (for hard X-ray detection), and bundle fission chamber are described in detail.


Efficient statistical inference for stochastic reaction processes.
We address the problem of estimating unknown model parameters and state variables in stochastic reaction processes when only sparse and noisy measurements are available. Using an asymptotic system size expansion for the backward equation, we derive an efficient approximation for this problem. We demonstrate the validity of our approach on model systems and generalize our method to the case when some state variables are not observed.


Comparison of palonosetron with ondansetron in prevention of postoperative nausea and vomiting in patients receiving intravenous patient-controlled analgesia after gynecological laparoscopic surgery.
Postoperative nausea and vomiting (PONV) are common complications after anesthesia and surgery. This study was designed to compare the effects of palonosetron and ondansetron in preventing PONV in high-risk patients receiving intravenous opioid-based patient-controlled analgesia (IV-PCA) after gynecological laparoscopic surgery. One hundred non-smoking female patients scheduled for gynecological laparoscopic surgery were randomly assigned into the palonosetron group (n = 50) or the ondansetron group (n = 50). Palonosetron 0.075 mg was injected as a bolus in the palonosetron group. Ondansetron 8 mg was injected as a bolus and 16 mg was added to the IV-PCA in the ondansetron group. The incidences of nausea, vomiting and side effects was recorded at 2 h, 24 h, 48 h and 72 h, postoperatively. There were no significant differences between the groups in the incidence of PONV during 72 h after operation. However, the incidence of vomiting was lower in the palonosetron group than in the ondansetron group (18% vs. 4%, P = 0.025). No differences were observed in use of antiemetics and the side effects between the groups. The effects of palonosetron and ondansetron in preventing PONV were similar in high-risk patients undergoing gynecological laparoscopic surgery and receiving opioid-based IV-PCA.


Crystallization and preliminary X-ray diffraction analysis of the SOD-TAT fusion protein.
The superoxide dismutase (SOD) family of proteins are necessary to protect oxygen-utilizing cells from the toxicity of reactive oxygen species. The delivery of SOD into tissues is severely limited by its size and biochemical properties. A cell-membrane-permeable SOD, SOD-TAT, has been demonstrated to have the ability to be directly transduced into mammalian cells. In this study, the SOD-TAT fusion protein was expressed, purified and crystallized. Crystals of the SOD-TAT fusion protein diffracted to 3.20 Å resolution and belonged to space group C121.


Ultrasonographic findings in the epididymis of pediatric patients with testicular torsion.
Although grayscale ultrasound and color Doppler ultrasound characteristics of the torsed testis are well established in the literature, less is known about its anatomic partner: the epididymis. The purpose of this study was to describe the ultrasound characteristics of the epididymis in pediatric patients with testicular torsion, and to describe their potential role as prognostic criteria for testicular salvage outcomes. During a retrospective review of 217 pediatric patients with acute testicular torsion during 2009-2016, morphological features of the epididymis from scrotal ultrasounds (size, parenchymal characteristics, and vascular flow of both epididymis heads), as well as patient demographics, time duration, surgical outcomes, histopathology results, and follow-up periods were analyzed. Mean epididymis size and twisting degree were significantly higher in the torsed testes than in the contralateral epididymis (P < 0.001) (Summary table). Cystic structures in the epididymis were identified: a higher number of cysts was associated with testicular non-viability (P = 0.025) and higher twisting degree (P = 0.017). Histopathologic examination showed that these spaces were infiltrated connective tissue most likely formed by venous congestion and vessel rupture. Scrotal ultrasound can provide information on testicular morphology and viability, as well as morphological changes in the epididymis over time in pediatric patients with testicular torsion. These findings may provide potential prognostic information regarding testicular viability, as a higher number of cystic spaces in the epididymis was associated with a higher rate of testicular non-viability and a higher twisting degree. In addition, the epididymis size (volume) can change during the time course of the ischemic state. This was the first study to describe and analyze epididymis ultrasound findings in pediatric patients with testicular torsion and to correlate them with testicular salvage outcomes. Further prospective studies are needed to determine the role of epididymis ultrasound findings as a potential pre-operative prognostic tool.


Markedness and the grammar in lexical diffusion of fricatives.
This paper examines the contributions of markedness and a child's grammar to the process of lexical diffusion in phonological acquisition. Archival data from 19 preschoolers with functional phonological delays were submitted to descriptive analyses of productive sound change in fricatives. Children's presenting fricative inventory, the fricatives newly learned, and their position of occurrence were varied, with word frequency and neighbourhood density measured. Results indicated that lexical diffusion of fricatives occurred differentially by word position. Positional, featural and structural markedness further converged such that change in unmarked structure of any type was implemented in low frequency words. A child's presenting fricative inventory was not directly affiliated with systematic patterns of diffusion. These results have clinical applications for the evaluation of productive sound change and theoretical implications for deterministic models of lexical diffusion and processing models of word recognition.


Nifedipine interaction with tacrolimus in liver transplant recipients.
To examine the possible drug interaction between nifedipine and tacrolimus in liver transplant recipients. A retrospective study was done comparing two groups of liver transplant recipients. The starting time for comparison was the same after transplant. One group (n = 22) consisted of hypertensive patients who were treated with nifedipine; the other group (n = 28) did not receive nifedipine. The two groups were compared over 1 year. The effect of nifedipine on tacrolimus was measured in terms of tacrolimus whole blood trough concentrations, daily tacrolimus dosages, and cumulative tacrolimus dosages at 1, 3, 6, and 12 months. All patient charts were reviewed with regard to concurrent medication that could affect the metabolism of tacrolimus and eventually affect tacrolimus concentrations and dosages. All required information was retrieved from medical records. There was a statistically significant difference between daily dosage requirements of tacrolimus at 90 (p = 0.03), 180 (p = 0.004), and 365 (p = 0.0004) days between the nifedipine and no-nifedipine groups. The tacrolimus daily dosage in the nifedipine group was decreased by 26%, 29%, and 38% at 3, 6, and 12 months, respectively, compared with the dosage of the no-nifedipine group. Statistically significant differences in cumulative dosages of tacrolimus were observed at 180 (p = 0.02) and 365 (p = 0.003) days between the nifedipine and no-nifedipine groups, with cumulative dosage reduction of 25% and 31% by 6 and 12 months, respectively, in the nifedipine group compared with the no-nifedipine group. Nifedipine decreased the daily and cumulative dosage requirement of tacrolimus. The interaction observed between nifedipine and tacrolimus is the first reported in humans and is clinically important. As a result of this drug interaction, it is recommended that blood concentrations of tacrolimus be monitored during coadministration of these drugs and that the tacrolimus dosage be adjusted accordingly.


Biomarker-based approach to determine etiology and severity of pulmonary hypertension: Focus on microRNA.
Pulmonary arterial hypertension (PAH) is characterized by remodeling of the pulmonary arteries, and defined by elevated pulmonary arterial pressure, measured during right heart catheterization. There are three main challenges to the diagnostic and therapeutic process of patients with PAH. First, it is difficult to differentiate particular PAH etiology. Second, invasive diagnostic is required to precisely determine the severity of PAH, and thus to qualify patients for an appropriate treatment. Third, the results of treatment of PAH are unpredictable and remain unsatisfactory. MicroRNAs (miRNAs) are small non-coding RNAs that regulate post transcriptional gene-expression. Their role as a prognostic, and diagnostic biomarkers in many different diseases have been studied in recent years. MiRNAs are promising novel biomarkers in PAH due to their activity in various molecular pathways and processes underlying PAH. Lack of biomarkers to differentiate between particular PAH etiology and evaluate the severity of PAH, as well as paucity of therapeutic targets in PAH open a new field for the possibility to use miRNAs in these applications. In our article, we discuss the potential of miRNAs use as diagnostic tools, prognostic biomarkers and therapeutic targets in PAH.


Gastroesophageal reflux disease-related symptom assessment in subjects with malignant dysphagia receiving esophageal stents.
Concerns remain over the ability to stent across of the lower esophageal sphincter (LES) for esophageal adenocarcinoma and the effects of gastroesophageal (GE) reflux. Thus, the aim of this study was to demonstrate minimal quality-of-life (QOL) side effects in patients undergoing esophageal stenting across the LES. An Institutional Review Board-approved prospective clinical trial evaluated the results of the Gastrointestinal Symptom questionnaire that includes a validated GE reflux disease (GERD) assessment (GERD-HRQL) and a dysphagia assessment. Consecutive patients were enrolled in this clinical trial, with 81 per cent male, 19 per cent female, median age of 62 years, with adenocarcinoma of the GE junction as their diagnosis. The median dysphagia score was 3 (only liquids can be tolerated) prestent and was improved to a median score of 0 (ability to eat all foods) poststent (P = 0.01). The median GERD score was 0 (none) prestent and did not change with a median score of 0 (none) poststent (P = 0.2). All GERD-related questions were unchanged prestent and poststent in all categories, specifically: frequency of GERD, time of day of reflux, pain behind breastbone, and pain medications. There was also no difference in regurgitation frequency (median prestent 1 vs poststent 0, P = 0.08), texture (prestent 2 [semisolid] vs poststent 1 [liquid]). There was only a statistical change in the ability to belch (prestent 0 [no ability] to poststent 1 [ability]), P = 0.02) and the ability to vomit. Esophageal stenting across the GE junction for dysphagia relief in esophageal malignancies does not adversely effect a patient's QOL in regard to reflux-related symptoms.


Biofabrication of Acer palmatum-Mediated Multifunctional CuO Nanoparticles for Dye Removal, Antibacterial-Antifungal Activity, and Molecular Docking.
Copper oxide nanoparticles (CuONPs) are used in many fields from electronics to medicine due to their multifunctionality, and therefore, their production with environmentally friendly methods is a current issue. In this study, biofabricated CuONPs were obtained by using the leaf extract of Acer palmatum plant originating from the Far East to enlighten the characteristics of the novel nanoparticles differentiating from those existing in the literature. Multifunctional nature of the CuONPs was evaluated by the antibacterial, antifungal, and decolorative applications and also by performing molecular docking analysis. The fabricated CuONPs were characterized using ultraviolet-visible spectroscopy (UV-vis), Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and dynamic light scattering (DLS). The absorbance seen at 270 nm in the SPR band obtained by UV-vis spectroscopy proved the presence of CuONPs, while the 602, 560, and 540 cm-1 vibrations obtained in the FT-IR spectroscopy indicated the same result. SEM images proved that the nanoparticles were in spherical form with sizes ranging from 140 to 225 nm. The result of DLS analysis showed that the average particle size was 229 nm in diameter, and CuONPs had monodisperse systems (polydispersity index, 0.184). The dye removal potency of CuONPs was also investigated by using remazol brilliant blue R (RBBR) and napthol blue black (NBB). Decolorizations (74 and 86%) of RBBR and NBB were obtained in 90 min at 50 °C, respectively. The strong antibacterial properties of the synthesized CuONPs were observed on both Gram (-) and Gram (+) bacterial strains by disk diffusion and optical analyses, and their antifungal activity was close to that of Amphotericin B, which was applied as a positive control. Molecular docking analysis was performed with Escherichia coli dihydrofolate reductase and Staphylococcus aureus DNA Gyrase B to analyze the antibacterial mechanisms of CuONP and observed that they exhibit good interactions with their targets with binding energies of -12.562 and -8.797 kcal/mol, respectively. Our findings suggested that CuONPs are crucial in the mechanisms of folate metabolism and DNA replication associated with bacterial proliferation. This work will provide significant guidance for the biofabrication of CuONPs and their medical and industrial applications.


Effects of statins on nitric oxide/cGMP signaling in human umbilical vein endothelial cells.
Human umbilical vein endothelial cells (HUVECs) were established as in vitro models for the modulation of endothelial function and cell viability by statins. Emphasis was placed on the biphasic effects of the drugs on nitric oxide (NO) bioavailability and cytotoxicity, as well as drug interference with the interaction of endothelial NO synthase (eNOS) with caveolin-1 (Cav-1). Incubation of HUVECs with fluvastatin, lovastatin or cerivastatin for 24 h caused an approximately 3-fold upregulation of eNOS expression that was associated with increased eNOS activity and accumulation of cGMP. Cerivastatin exhibited the highest potency with an EC50 of 13.8 +/- 2 nM after 24 h, while having no effect after only 30 min. The effects of statins on eNOS expression were similar in control and Cav-1 knockdown cells, but the increase in eNOS activity was less pronounced in Cav-1-deficient cells. Statin-triggered cytotoxicity occurred at approximately 10-fold higher drug concentrations (maximal toxicity at 1-10 microM), was sensitive to mevalonate, and was significantly enhanced in the presence of NG-nitro-L-arginine. The overexpression of eNOS induced by clinically relevant concentrations of statins may contribute to the beneficial vascular effects of the drugs in patients. Stimulation of NO synthesis and cytotoxicity appear to share a common initial mechanism but involve distinct downstream signaling cascades that exhibit differential sensitivity to HMG-CoA reductase inhibition.


Origin of the Diplaziumhachijoense complex (Athyriaceae).
We analyzed the phylogeny of the Diplaziumhachijoense complex using plastid trnL-F and low-copy nuclear marker AK1 DNA sequences. Based on allele constitution, triploid apogamous species of the D.hachijoense complex appeared to have originated from the hybridization of triploid apogamous species and diploid sexual species by recurrent hybridization events. These results suggested that triploid apogamous ferns can achieve hybridization with diploid sexual species by producing diploid spores with irregular meiosis in sporogenesis. Furthermore, the present study predicted the involvement of several unknown species associated with hybridization. More sampling of Callipteris species from China and adjacent areas is required to determine the relationships among unknown species and the D.hachijoense complex.


[Immunosuppressive / immunomodulating therapies in myasthenia gravis-at present and in the near future].
Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular transmission that is primarily caused autoantibodies specific to the neuromuscular junction and is characterized by fatigability and weakness of the striated muscles. Immunosuppression is the mainstay of treatment for MG, and patients with MG are currently treated with immunomodulating or immunosuppressive agents. This review summarizes the current situation and perspective of medical therapy for MG, focusing on mechanisms of action and clinical application of corticosteroids and different classes of immunomodulating or immunosuppressive drugs used for MG. Immunosuppressive treatment is indicated for patients with disabling weakness, not sufficiently managed with cholinesterase inhibitors. Prednisolone (PSL) is used in the great majority of patients. Tacrolimus and cyclosporine are the first-line immunosuppressants, whereas azathioprine is a conventional but less frequently used medication in Japan. The incidence of late- and elderly-onset MG is reported to be increasing. The risk of complications in corticosteroid treatment appears to depend on drug dosage, treatment duration, and patients' characteristics, and the serious side effects should be increased in late- and elderly- onset MG. Although nonspecific, current immunosuppressive treatment is highly effective in most MG patients, the need for prolonged administration and unwanted effects are still relevant limitations to its use.


Apatinib treatment combined with chemotherapy for advanced epithelial ovarian cancer: a case report.
Apatinib is a novel oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which has been proved by clinical trials to be effective and safe for patients with chemotherapy-refractory gastric cancer. To date, there is no study or case report on apatinib treatment for patients with ovarian cancer. Here, we present the case of a 50-year-old Chinese woman with advanced ovarian cancer, who received apatinib at a daily dose of 500 mg for 28 days per cycle after failure of fourth-line chemotherapy. Favorable oncologic outcome was achieved in this case after treatment with apatinib. The patient's progression-free survival is now 11.3 months, and she is taking apatinib and capecitabine as maintenance treatment. The common side effect of apatinib was fatigue; however, the toxicity of apatinib was controllable and tolerable. Thus, apatinib may be an option for chemotherapy-refractory advanced epithelial ovarian cancer, but this still warrants further investigation.


Comparative pathogenicity of Vibrio spp., Photobacterium damselae ssp. damselae and five isolates of Aeromonas salmonicida ssp. achromogenes in juvenile Atlantic halibut (Hippoglossus hippoglossus).
Juvenile Atlantic halibut (~100 mg, Hippoglossus hippoglossus) were exposed to Vibrio proteolyticus, a Vibrio spp. isolate, Photobacterium damselae ssp. damselae and five different isolates of Aeromonas salmonicida ssp. achromogenes via an hour-long bath immersion to ascertain their variation in pathogenicity to this fish species. Results were analysed using Kaplan-Meier survival analysis. Analysis of the data from challenges using A. salmonicida ssp. achromogenes revealed three survival values of zero and a spread of values from 0 to 28.43. Challenges using a Vibrio spp isolate, V. proteolyticus and P. damselae resulted in Kaplan-Meier survival estimates of 31.21, 50.41 and 57.21, respectively. As all bacterial species tested could induce juvenile halibut mortalities, they must all be considered as potential pathogens. However, the degree of pathogenicity of A. salmonicida is isolate dependent.


Methyl 5(6)-4-2-pyridyl piperazino carbamoyl benzimidazole-2-carbamate--a new broad spectrum anthelmintic.
Methyl 5(6)-4-2-pyridyl piperazino carbamoyl benzimidazole-2-carbamate (CDRI Comp. 81-470) was tested against various nematode and cestode infections in different experimental and domestic animals. The compound showed 100% effectivity against adult of Ancylostoma ceylanicum (hookworm) in hamsters (6.25 mg/kg p.o. X 1), Nippostrongylus brasiliensis (trichostrongylid) in rats (100 mg/kg p.o. X 3), Hymenolepis nana (cestode) in rats (25 mg/kg p.o. X 1) and Syphacia obvelata (oxyurid) in mice (12.5 mg/kg p.o. X 3). It was also found highly effective against artificial and natural helminth parasites of higher animals. The compound removed all, A. caninum and A. ceylanicum (hookworms) and Toxocara sp. (ascarid) from dogs at a dose of 10 mg/kg p.o. X 3; A. tubaeformis (hookworm) and Toxocara sp. at 25 mg/kg p.o. X 3 and 2.5 mg/kg p.o. X 3 respectively from cats and Ascaridia galli (ascarid) at 10 mg/kg p.o. X 3 from fowl. The compound in doses of 1500 mg/kg by oral route and 1000 mg/kg by i.p. route did not cause any mortality or produce adverse effect in mice. The expanded anthelmintic action and large therapeutic index indicate compound's great anthelmintic potentiality.


Thymol Elicits HCT-116 Colorectal Carcinoma Cell Death Through Induction of Oxidative Stress.
Colon cancer is one of the most deadly and common carcinomas occurring worldwide and there have been many attempts to treat this cancer. The present work was designed in order to evaluate thymol as a potent drug against colon cancer. Cytotoxicity of thymol at different concentrations was evaluated against a human colon carcinoma cell line (HCT-116 cells). Fluorescent staining was carried out to evaluate the level of ROS as well as mitochondrial and DNA fragmentation and immunoblot analysis were performed to confirm apoptosis and mitoptosis. Results of the study demonstrated that thymol efficiently created an oxidative stress environment inside HCT-116 cells, a colorectal carcinoma cell line, through induction of ROS production along with intense damage to DNA and mitochondria, as observed through Hoechst and rhodamine 123 staining, respectively. Moreover, expression of PARP-1, p-JNK, cytochrome-C and caspase-3 proteins was up-regulated, suggesting HCT-116 cells underwent mitoptotic cell death. Therefore, thymol could be used as a potent drug against colon cancer due to its lower toxicity and prevalence in natural medicinal plants.


Total Glucosides of Paeony Promote Intestinal Motility in Slow Transit Constipation Rats through Amelioration of Interstitial Cells of Cajal.
Using an atropine-diphenoxylate-induced slow transit constipation (STC) model, this study explored the effects of the total glucosides of paeony (TGP) in the treatment of STC and the possible mechanisms. A prospective experimental animal study. The constipation model was set up in rats with an oral gavage of atropine-diphenoxylate and then treated with the TGP. The volume and moisture content of the faeces were observed and the intestinal kinetic power was evaluated. Meanwhile, the colorimetric method and enzyme linked immunosorbent assay (ELISA) were employed to determine the changes of nitric oxide (NO), nitric oxide synthase (NOS), vasoative intestinal peptide (VIP) and the P substance (SP) in the serum, respectively. The protein expressions of c-kit and stem cell factor (SCF) were assessed by immunohistochemical analysis and western blot, respectively, and the mRNA level of c-kit was measured by a reverse transcription polymerase chain reaction (RT-PCR). The TGP attenuated STC responses in terms of an increase in the fecal volume and moisture content, an enhancement of intestinal transit rate and the reduction of NO, NOS and VIP in the serum. In addition, the c-kit, a labeling of interstitial cells of Cajal (ICC) increased at both protein and mRNA levels. SCF, which serves as a ligand of c-kit also increased at protein level. The analysis of our data indicated that the TGP could obviously attenuate STC through improving the function of ICC and blocking the inhibitory neurotransmitters such as NO, NOS and VIP.


Variability in Phelan-McDermid syndrome: The impact of the PNPLA3 p.I148M polymorphism.
The PNPLA3 gene maps in the 22q13 region and can have modifying effects on the phenotype of patients with Phelan-McDermid syndrome (PMS). The PNPLA3 p.I148M variant was detected in two PMS patients presenting with refractory seizures, gastrointestinal issues, and liver dysfunction. The p.I148M variant leads to macrovescicular steaosis and predisposes to liver disorders from steatohepatitis to fibrosis. Accumulation of lipid macrovescicles in the hepatocytes affects several pathways, including the metabolismof anti-epileptics, possibly leading to the lack of response to anti-epileptic treatments reported in the two cases. Screening for the p.I148M variant can identify PMS patients at higher risk for liver dyfunction and help designing personalized therapeutic protocols.


Novel protein inhibitor of calmodulin-dependent cyclic nucleotide phosphodiesterase from glioblastoma multiforme.
Previous investigations from our laboratory have demonstrated a significant reduction in the catalytic function of the 60 kDa and 63 kDa isozymes of calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE) when comparing human cerebral tissue that was free of tumor and glioblastoma multiforme (GBM) and gliosarcoma [Lal S., Raju R. V. S., Macaulay R. B. J., and Sharma R. K. (1996) Can. J. Neurol. Sci., 23, 245-250]. The results suggested the possibility of an endogenously produced inhibitor of CaMPDE expressed in these tumors. Further investigation has initially characterized the presence of a heat-labile, protein inhibitor of both the 60 kDa and 63 kDa isozymes of CaMPDE. Sephacryl S-200 gel filtration column chromatography indicated that the inhibitor has an apparent molecular weight of 22 kDa and experimental evidence demonstrates that this inhibitor protein may act independently of calmodulin, and is therefore a novel CaMPDE inhibitor. Previous work on non-CNS tumors has shown high levels of CaMPDE activity and absence of an inhibitor. This suggests that a different mechanism may exist for the proliferation of these subsets of tumors.


Histochemical studies of end-plate formation in free autologous muscle transplants in cats.
End-plate formation in free autologous transplants of previously denervated whole muscles in adult cats were studied with a histochemical technique for cholinesterase. Grafts from 5 to 40 weeks old have been examined. The original end-plates degenerated and could not be seen in transplants older than 9 weeks. New, immature end-plates formed at many sites in the transplants. They were seen as early as 5 weeks after transplantation. They progressively increased in number during the first 12 weeks. In the oldest transplants the end-plates were relatively mature and appeared in clusters or were scattered.


Dairy cow hoof impact and slide measurements for common Ontario dairy farm floorings.
In the context of understanding lameness and injury from slipping, our objective was to characterize hoof impact and slide of 5 cows walking on 6 flooring surfaces commonly used in Ontario dairy farms: diamond-grooved concrete (DC), sanded epoxy-covered concrete (EC), grooved rubber mat (GR), high-profile rubber mat (HR), low-profile rubber mat (LR), and turf grass (TG; Kentucky bluegrass/fescue mix). Surface hardness was measured on each surface using a Clegg Impact Soil Tester. Five trained lactating Holstein cows were each walked over all 6 surfaces sequentially in a randomized order. Walking speeds were determined from 60-fps videos. A 3-axis accelerometer attached to the lateral claw of each hindfoot captured continuous horizontal (aH), vertical (aV), lateral (aTLat), and medial (aTMed) accelerations at 2,500 Hz during each trial, from which peak values were identified. Data from 45°-rosette strain gauges glued to the dorsal surface of both medial and lateral hooves allowed for the calculation of principal strains (ε1 and ε2). From continuous data, several data points were extracted from 3 to 6 stances/trial: peak values of aH, aV, and aT for the impact phase of the stance; midstance values of ε1 and ε2 as proxies for force on the foot; magnitudes of normal (i.e., consistent and repeatable) sliding on the surface during the support phase; and 3 timing events to capture the cadence of the motion. All aH and aV signals were inspected onscreen to identify irregularities between the end of impact and beginning of breakover that indicated hoof slipping, which was observed on all surfaces. The effects on all measured variables of surface, cow, speed, and hoof (and all significant higher-order factors) were assessed by ANOVA in SAS 9.4 (SAS Institute Inc.), after verifying data normality. Values of aHmax, indicating grip on the surface from highest to lowest, ranked the surfaces in this order: LR, DC, HR, GR, EC, and TG. Ranking on aVmax, indicating most to least cushioning of the hoof on impact, ranked the surfaces in this order: DC, HR, GR, EC, LR, and TG. Differences in ranking among these and other significant impact variables indicate that future studies of lameness on different surfaces need to include all significant variables identified here. We detected no surface and strain interactions in either the ε1 or ε2 strain, indicating that the surfaces do not affect the overall loads on the foot at midstance. Additionally, lateral and medial hooves may have different roles in a stance. The results highlight the capacity to evaluate flooring types with this technology, and the study provides a tool for future work to examine the role of flooring types in the causation of lameness.


The Effect of a Health Education Intervention on Jordanian Participants' Colorectal Cancer Knowledge, Health Perceptions, and Screening Practices.
Globally, colorectal cancer (CRC) is the second and third most commonly diagnosed cancer in women and men, respectively. The aim of this study is to test the effectiveness of a health education intervention on the current level of Jordanians' CRC knowledge, health perceptions, and screening practices. A convenience sampling method was used to recruit a sample of 197 average-risk Jordanian adults aged 50 to 75 years. The sample was collected from outpatient departments of Jordan University and Al-Basheer Hospitals in Amman. This study used quasi-experimental design, and a rolling enrollment method was implemented to randomly assign the participants into intervention and control groups. Baseline results indicated that Jordanian average-risk participants were not well informed about CRC and screening recommendations. One-fourth perceived themselves to be susceptible to CRC. About one-third comprehended the seriousness of CRC, most recognized the benefits of CRC screening, and fewer than half believed there were barriers preventing them from participating in CRC screening. Four weeks after intervention implementation, there was a significantly higher level of knowledge, as well as increased susceptibility and severity perceptions, screening via fecal occult blood test, and intentions to undergo screening via colonoscopy or sigmoidoscopy. The findings support the implementation of a health education intervention as an effective way to enhance levels of knowledge and promote positive health perceptions regarding CRC and screening recommendations. This study may provide Jordanian and other nurses with a theory-based educational intervention to improve the quality of nursing care and reduce costs.


[Producing intravenous medications in a pharmacy].
The authors explain the different intravenous mixtures and the types of preloaded syringes elaborated in a centralized unit, analysing their profitability and evaluating their repercussion on the daily work nurses have to perform. This study was carried out in the Hospital de Poniente in Almeria, a county hospital which has 165 beds. The hospital authorities defined those medications which were chosen to be prepared in a centralized unit in the Pharmacy Service of the hospital and they drew up a list/guide of their corresponding conservation conditions. The authorities determined the time which nursing personnel in the various hospital units would employ in the elaboration of these medications and compared that with the time employed in the Pharmacy Service.


Effectiveness of daily versus non-daily granulocyte colony-stimulating factors in patients with solid tumours undergoing chemotherapy: a multivariate analysis of data from current practice.
We conducted a multicentre, retrospective, observational study including patients with solid tumours (excluding breast cancer) that received granulocyte colony-stimulating factors (G-CSF) and chemotherapy. We investigated the effectiveness of daily vs. non-daily G-CSFs (pegfilgrastim) adjusting by potential confounders. The study included 391 patients (211 daily G-CSF; 180 pegfilgrastim), from whom 47.3% received primary prophylaxis (PP) (57.8% pegfilgrastim), 26.3% secondary prophylaxis (SP: initiation after cycle 1 and no reactive treatment in any cycle) (51.5% pegfilgrastim) and 26.3% reactive treatment (19.4% pegfilgrastim). Only 42.2% of patients with daily G-CSF and 46.2% with pegfilgrastim initiated prophylaxis within 72 h after chemotherapy, and only 10.5% of patients with daily G-CSF received it for ≥ 7 days. In the multivariate models, daily G-CSF was associated with higher risk of grade 3-4 neutropenia (G3-4N) vs. pegfilgrastim [odds ratio (OR): 1.73, 95% confidence interval (CI): 1.004-2.97]. Relative to SP, PP protected against G3-4N (OR for SP vs. PP: 6.0, 95%CI: 3.2-11.4) and febrile neutropenia (OR: 3.1, 95%CI: 1.1-8.8), and was associated to less chemotherapy dose delays and reductions (OR for relative dose intensity <85% for SP vs. PP: 3.1, 95%CI: 1.7-5.4) and higher response rate (OR: 2.1, 95%CI: 1.2-3.7). Data suggest that pegfilgrastim, compared with a daily G-CSF, and PP, compared with SP, could be more effective in preventing neutropenia and its related events in the clinical practice.


Staphylococcus lugdunensis: an emerging cause of ventriculoperitoneal shunt infections.
Staphylococcus lugdunensis, a coagulase-negative staphylococcus first described in 1988, has gained recognition as an organism with considerable pathogenic capability in adults. In contrast to the indolent presentation characteristic of other coagulase-negative staphylococci, S. lugdunensis infections resemble the aggressive behavior of Staphylococcus aureus. Although the organism has been isolated from a wide variety of infections in adults, it is a very rare cause of pediatric infections. We describe the first two pediatric patients who developed ventriculoperitoneal shunt infections caused by S. lugdunensis. These cases suggest that coagulase-negative staphylococci should be identified to the species level and that, if S. lugdunensis is identified, greater morbidity compared to that associated with other coagulase-negative staphylococcal shunt infections should be anticipated. A longer course of therapy is recommended for S. lugdunensis infections.


Portomesenteric venous thrombosis: A rare but probably under-reported complication of laparoscopic surgery: A case series.
Portomesenteric venous thrombosis (PMVT) is a rare but well-reported complication following laparoscopic surgery. We present three cases of PMVT following laparoscopic surgery. Our first case is a 71-year-old morbidly obese woman admitted for elective laparoscopic giant hiatus hernia (LGHH) repair. Post-operatively, she developed multi-organ dysfunction and computed tomography scan revealed portal venous gas and extensive small bowel infarct. The second patient is a 51-year-old man with known previous deep venous thrombosis who also had elective LGHH repair. He presented 8 weeks post-operatively with severe abdominal pain and required major bowel resection. Our third case is an 86-year-old woman who developed worsening abdominal tenderness 3 days after laparoscopic right hemicolectomy for adenocarcinoma and was diagnosed with an incidental finding of thrombus in the portal vein. She did not require further surgical intervention. The current guidelines for thromboprophylaxis follow-up in this patient group may not be adequate for the patients at risk. Hence, we propose prolonged period of thromboprophylaxis in the patients undergoing major laparoscopic surgery.


[Central action of a new cholinesterase reactivator, diethyxime].
In anesthetized cats, whose peripheral muscarinic-cholinorecptors are blocked by m-cholinolytics (benzilyl choline) failing to penetrate into the brain, the cholinesterases reactivator diethyxime debars the centrally caused fall of the arterial pressure produced by armine, an inhibitor of cholinesterases readily gaining access into the brain. Diethyxime is also capable of abolishing the depression of the phrenic nerve action potentials produced by armine. Dipyroxime-a quaternary diethyxime analogue and also a quaternary cholinesterase reactivator fails to produce such an effect.


Arachidonic Acid, but Not Omega-3 Index, Relates to the Prevalence and Progression of Abdominal Aortic Aneurysm in a Population-Based Study of Danish Men.
Animal models support dietary omega-3 fatty acids protection against abdominal aortic aneurysm (AAA), but clinical data are scarce. The sum of red blood cell proportions of the omega-3 eicosapentaenoic and docosahexaenoic acids, known as omega-3 index, is a valid surrogate for long-term omega-3 intake. We investigated the association between the omega-3 index and the prevalence and progression of AAA. We also investigated associations between AAA and arachidonic acid, an omega-6 fatty acid that is a substrate for proinflammatory lipid mediators. We obtained blood samples from 498 AAA patients (maximal aortic diameter ≥30 mm) within a population-based ultrasound-screening trial in men and from 199 age-matched controls who screened negative. We determined the fatty acids of red blood cells by gas chromatography. During a median follow-up of 4.85 years, 141 AAA patients reached criteria for vascular surgical repair. Participants were high consumers of omega-3 (average omega-3 index: 7.6%). No significant associations were found for omega-3 index. In contrast, arachidonic acid in AAA patients was higher than in controls (P<0.001), and individuals in the upper tertile of arachidonic acid at baseline had higher probability of having AAA (odds ratio: 1.309; 95% confidence interval, 1.021-1.678; P=0.033). AAA patients at the upper tertile of arachidonic acid at baseline had a 54% higher risk of needing surgical repair during follow-up (hazard ratio: 1.544; 95% confidence interval, 1.127-2.114; P=0.007). Omega-3 index is unrelated to men with AAA from a country in which fish consumption is customarily high. Arachidonic acid is associated with AAA presence and progression. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00662480.


Cytoprotective effect of polysaccharide isolated from different mushrooms against 7-ketocholesterol induced damage in mouse liver cell line (BNL CL. 2).
Cytoprotective ability of polysaccharides isolated from different edible mushrooms was investigated on the 7-ketocholesterol-induced damaged cell line. Polysaccharide extracts from six different edible mushrooms-Flammulina velutipes, Peurotus ostreatus, Lentinus edodes, Agrocybe aegerita, Agaricus blazei, and Cordyceps militaris- were prepared by hot water extraction and alcohol precipitation. Cytoprotective ability was evaluated by measuring the viable cells of the normal embryonic liver cell line (BNL CL. 2) in the presence of 7-ketocholesterol. At 80 microg/mL of 7-ketocholesterol, cytotoxicity was very high with a loss of 98% of viable cells after 20 h of incubation. With the addition of 200 microg/mL of each polysaccharide isolate to the cell line containing 80 microg/mL of 7-ketocholesterol, polysaccharide isolates from both Flammulina velutipes and Peurotus ostreatus could significantly inhibit the 7-ketochoelsterol-induced cytotoxicity in the cells. But other polysaccharide isolates were not effective in inhibiting cell damage caused by the oxLDL-induced cytotoxicity.


Decision rules for subgroup selection based on a predictive biomarker.
When investigating a new therapy, there is often some plausibility that the treatment is more efficient (or efficient only) in a subgroup as compared to the total patient population. In this situation, the target population for the proof of efficacy is commonly selected in a data-dependent way, for example, based on the results of a pilot study or a planned interim analysis. The performance of the applied selection rule is crucial for the success of a clinical trial or even a drug development program. We consider the situation in which the selection of the patient population is based on a biomarker and where the diagnostic that evaluates the biomarker may be perfect, that is, with 100% sensitivity and specificity, or not. We develop methods that allow an evaluation of the operational characteristics of rules for selecting the target population, thus enabling the choice of an appropriate strategy. Especially, the proposed procedures can be used to calculate the sample size required to achieve a specified selection probability. Furthermore, we derive optimal selection rules by modeling the uncertainty about parameters by prior distributions. Throughout, there is a strong impact of sensitivity and specificity of the biomarker on the results. It is therefore essential to evaluate the rules for patient selection before applying them, thereby bearing in mind that the diagnostic that evaluates the applied biomarker may be imperfect.


The Impact of a Non-Compete Clause on Patient Care and Orthopaedic Surgeons in the State of Louisiana: Afraid of a Little Competition?
Non-compete clauses (NCC) are commonly required for physicians practicing in an employed model. With growing pressures driving surgeons to practice in an employed model instead of physician-led practices, the purpose of this survey was to determine the impact of NCCs on orthopaedic surgeons and their patients in Louisiana. A voluntary, single-mode online survey containing 23 questions was created using the Qualtrics XM Platform (Qualtrics, Provo, UT) and distributed to 259 orthopaedic surgeons who are members of the Louisiana Orthopaedic Association. Survey questions assessed the prevalence and details of existing NCCs and perceptions of their impact on surgeons' practice, patients, and personal life. 117 members responded (response rate: 45.2%), of which 91 (77.8%) finished the survey. Nearly half (44%) of respondents had an expired or active NCC in their contract. Most (84.3%) believed NCCs give employers unfair leverage during contract negotiations. NCCs have deterred or would deter 71.4% of respondents from accepting another job offer. Respondents believed NCCs negatively impact patients, including forcing patients to drive long distances to maintain continuity of care (64.4%) and forcing surgeons to abandon their patients if they seek new employment (76.7%). Many respondents reported NCCs also exert significant detrimental effects on their personal life, including mandatory relocation of their family (67.0%). Nearly all (97.8%) believed such clauses have become unreasonable over the last decade with the rise of large hospital conglomerates. Most surgeons (83.7%) believed that removal of NCCs from all orthopaedic surgeons' contracts would improve the overall healthcare of orthopaedic patients in Louisiana. Perceptions of NCCs were overwhelmingly negative among orthopaedic surgeons in Louisiana. Such clauses give employers an unfair advantage during contract negotiations and exert a significant detrimental impact on surgeons and their patients. While NCCs may be reasonable in the business sector and other professions, it is unclear how such clauses benefit surgeons or improve patient care and may be detrimental to both. Cross-sectional Survey.


Epithelial cell specific Raptor is required for initiation of type 2 mucosal immunity in small intestine.
Intestinal tuft cells are one of 4 secretory cell linages in the small intestine and the source of IL-25, a critical initiator of the type 2 immune response to parasite infection. When Raptor, a critical scaffold protein for mammalian target of rapamycin complex 1 (mTORC1), was acutely deleted in intestinal epithelium via Tamoxifen injection in Tritrichomonas muris (Tm) infected mice, tuft cells, IL-25 in epithelium and IL-13 in the mesenchyme were significantly reduced, but Tm burden was not affected. When Tm infected mice were treated with rapamycin, DCLK1 and IL-25 expression in enterocytes and IL-13 expression in mesenchyme were diminished. After massive small bowel resection, tuft cells and Tm were diminished due to the diet used postoperatively. The elimination of Tm and subsequent re-infection of mice with Tm led to type 2 immune response only in WT, but Tm colonization in both WT and Raptor deficient mice. When intestinal organoids were stimulated with IL-4, tuft cells and IL-25 were induced in both WT and Raptor deficient organoids. In summary, our study reveals that enterocyte specific Raptor is required for initiating a type 2 immune response which appears to function through the regulation of mTORC1 activity.


Polyphenols from flowers of Magnolia coco and their anti-glycation effects.
We investigated the inhibitory effects of several plant extracts on advanced glycation end-products (AGEs) formation. Among tested samples, the flower extract of Magnolia coco showed significant inhibition of AGE formation. We isolated and characterized procyanidin oligomer and four other compounds from the flowers, and evaluated their inhibitory effects on AGE formation and the AGE-derived crosslink-cleaving activity of the isolated compounds.


Cryptococcal meningitis due to Cryptococcus neoformans genotype AFLP1/VNI in Iran: a review of the literature.
Cryptococcal meningitis is the most important opportunistic fungal infection with a high mortality in HIV-patients in less developed regions. Here, we report a case of cryptococcal meningitis in a 49-year-old HIV-positive female due to Cryptococcus neoformans (serotype A, mating-type alpha, genotype AFLP1/VNI) in Sari, Iran. In vitro antifungal susceptibility tests showed MICs of isavuconazole (0.016 μg ml(-1) ), voriconazole (0.031 μg ml(-1) ), posaconazole (0.031 μg ml(-1) ), itraconazole (0.063 μg ml(-1) ), amphotericin B (0.125 μg ml(-1) ) and fluconazole (8 μg ml(-1) ). Despite immediate antifungal therapy, the patient died 4 days later due to respiratory failure. Cryptococcal infections have been infrequently reported from Iran and therefore we analysed all published cases of cryptococcosis in Iran since the first reported case from 1969.


A nucleotide-binding domain of porcine liver annexin VI. Proteolysis of annexin VI labelled with 8-azido-ATP, purification by affinity chromatography on ATP-agarose, and fluorescence studies.
Porcine liver annexin VI (AnxVI) of Mr 68.000 is an ATP-binding protein as evidenced by specific and saturable UV-dependent labelling with 8-azido-[gamma-32P]ATP or the fluorescent analog of ATP, 2'-(or 3')-O-(2,4,6-trinitrophenyl)adenosine triphosphate and by binding of AnxVI to ATP-agarose. These characteristics of purified AnxVI were used to identify and characterize preliminary nucleotide-binding domain of the protein. AnxVI labelled with 8-azido-ATP was subjected to limited proteolysis and the proteolytic fragments of AnxVI that retained the covalently-bound nucleotide were separated by means of gel electrophoresis and visualized by exposure of the gel to a phosphor storage screen. It was found that the AnxVI proteolytic fragments of Mr 34-36.000 and smaller retained the nucleotide. In a reciprocal experiment, AnxVI was digested with proteolytic enzymes and in an ATP eluate from an ATP-agarose column protein fragments of similar Mr to these labelled with 8-azido-ATP were identified. The extent of AnxVI labelling with 8-azido-ATP and the distribution of proteolytic fragments varied upon calcium concentration. These results lead to the conclusion that there is a nucleotide-binding domain within the AnxVI molecule that is functionally similar to the nucleotide-binding domains of other nucleotide-binding proteins. The nucleotide-binding domain is located close to the tryptophan residue 343 of AnxVI and in close vicinity to the Ca2+- and phospholipid-binding sites of the protein. This is confirmed by the observation that the tryptophan fluorescence intensity of AnxVI decreases in the presence of a fluorescence analog of ATP in a calcium-dependent manner, due to the quenching properties of the nucleotide and/or fluorescence energy transfer from AnxVI tryptophan to fluorophore. Both processes were modulated by the presence of phospholipid molecules.


Current methodology to assess bioequivalence of levothyroxine sodium products is inadequate.
Levothyroxine sodium is a drug with a narrow therapeutic index for which an individual patient must have his or her dose carefully titrated to achieve the necessary therapeutic effect. In addition, exogenous levothyroxine cannot be distinguished from the endogenously produced hormone. Since 2004, generic formulations have been approved for the most frequently prescribed brands of levothyroxine sodium. This review examines the methodology and statistical acceptance criteria and summarizes findings of a previously published relative bioavailability study that brings into question the use of standard criteria to assess bioequivalence of levothyroxine sodium. The key findings reviewed were the following: (1) in the absence of baseline correction for endogenous T4 levels, products that differed by as much as 25% to 33% would be declared bioequivalent; (2) the use of baseline correction reduced the likelihood of declaring products bioequivalent when they actually differed by 25% to 33%; (3) even with baseline correction, products that differed by 12.5% would be declared bioequivalent; and (4) there was evidence of significant carryover from one dosing period to the next even with washout periods of up to 53 days. In conclusion, the current recommended methodology in the United States to assess bioequivalence for levothyroxine sodium products is inadequate to differentiate products that differ by 12.5%, a clinically relevant difference. Recommendations are made for modifications to the criteria that could improve the likelihood that products that differ by a clinically significant amount in their bioavailability would not be accepted as bioequivalent.


Erythema formation in magnesium-deficient albino rats. A non-invasive model for the screening of anti-inflammatory agents and oral mineral supplements.
The enteral bioavailability of magnesium firmly bound to a fire-proof, inert SiO2-Al2O3 matrix (ground magnesia boats) was studied in magnesium-deficient albino Sprague-Dawley rats, with and without blocking gastric hydrochloric acid secretion with omeprazole. Magnesium was absorbed, although to a small degree, also at anacidity. Pronounced erythema, developing after only some days in hypomagnesemic hypercalcemic rats, are proposed as a non-invasive model for the screening of antiinflammatory substances. Using this model significant protective effects were proven for cromoglycate, polyenthylene glycol 400, and omeprazole; the latter, however, seems more likely to act via a magnesium-sparing mechanism.


Acute coronary syndrome in aortic infective endocarditis.
A 34-year-old man was presented with aortic infective endocarditis and acute coronary syndrome due to an extrinsic coronary compression due to periannular complications.


Management of carcinoma of the esophagus: the role of radiotherapy.
This is an analysis of treatment results over a 23-year period in 241 patients with carcinoma of the esophagus. The treatment for unresectable patients was external beam radiotherapy (EBRT) alone (mean dose 55 Gy) in 137 (57%) combined with brachytherapy (mean dose 50 + 40 Gy) in 46 (19%), and chemotherapy alone in 3 (1%) patients. In the 55 resectable patients, treatment was resection alone in 9 (4%), and combined with radiotherapy (mean dose 43 Gy) in 46 (19%) patients. The 1-, 2-, and 5-year survival for the 241 patients was 36, 15, and 5%, respectively (median 38 weeks). The 5-year survival was 18% for radiotherapy (RT)-surgery (S) patients, 11% for EBRT with brachytherapy, 2% for EBRT alone, and 0% for patients who had S alone, p less than 0.001. Survival correlated well with initial performance status, treatment, stage of disease, tumor size, radiation dose, and degree of response, p less than 0.001, but not with tumor location in the esophagus and patients' race and sex, p = 0.44. Serious complications occurred in 5 (2%) patients treated with RT alone and in 4 (7%) patients treated with S alone or combined with RT. The leading cause of death was persistent or recurrent tumor in the chest found in 39% patients.


Analysis of serum and cerebrospinal fluid in clinically normal adult miniature donkeys.
To establish reference intervals for serum and cerebrospinal fluid (CSF) parameters in clinically healthy adult miniature donkeys. Experiments were conducted on 10 female and 10 male clinically normal adult miniature donkeys, randomly selected from five herds. Lumbosacral CSF collection was performed with the sedated donkey in the standing position. Cell analysis was performed immediately after the samples were collected. Blood samples were obtained from the jugular vein immediately after CSF sample collection. Sodium, potassium, glucose, urea nitrogen, total protein, calcium, chloride, phosphorous and magnesium concentrations were measured in CSF and serum samples. A paired t-test was used to compare mean values between female and male donkeys. The CSF was uniformly clear, colourless and free from flocculent material, with a specific gravity of 1.002. The range of total nucleated cell counts was 2-4 cells/μL. The differential white cell count comprised only small lymphocytes. No erythrocytes or polymorphonuclear cells were observed on cytological examination. Reference values were obtained for biochemical analysis of serum and CSF. Gender had no effect on any variables measured in serum or CSF (p>0.05). CSF analysis can provide important information in addition to that gained by clinical examination. CSF analysis has not previously been performed in miniature donkeys; this is the first report on the subject. In the present study, reference intervals for total nucleated cell count, total protein, glucose, urea nitrogen, sodium, potassium, chloride, calcium, phosphorous and magnesium concentrations of serum and CSF were determined for male and female miniature donkeys.


Association Between Korean-Style Balanced Diet and Risk of Abdominal Obesity in Korean Adults: An Analysis Using KNHANES-VI (2013-2016).
Abdominal obesity is a critical factor for metabolic diseases, and specific eating patterns such as the Mediterranean diet help prevent metabolic diseases. This study aimed to investigate the association between the modified Korean health eating index (MKHEI), including a Korean-balanced diet, and abdominal obesity risk according to genders in adults aged 20-64 years (4,886 males and 7,431 females), using the Korea National Health and Nutrition Examination Survey VI (2013-2016). Adjusted means and 95% confidence intervals of MKHEI scores and nutrient intake estimated using the 24-h recall method were calculated according to abdominal obesity (waist circumference ≥90 cm for men and ≥85 cm for women) after adjusting for age, residence area, region, education, income, drinking status, smoking status, marital status, and exercise. Adjusted odds ratios (ORs) for abdominal obesity were measured according to MKHEI tertiles using logistic regression analysis while controlling for covariates. Individuals aged >50 years, married, below high school, lower-income, heavy alcohol drinkers, past and current smokers, and males living in the southern areas had a higher risk of abdominal obesity. In both genders, the scores of all MKHEI components were lower in the abdominal obesity group (n = 2,895) than in the control group (n = 9,422). Further, the scores of fruits with and without fruit juice and those of beans, including fermented beans, were lower in the abdominal obesity group only in females but not in males. Further, the scores of fast foods were higher in the abdominal obesity group than in the control group only in females. After adjusting for covariates, the adjusted OR for abdominal obesity was inversely associated with Korean balanced diet (KBD) related to KHEI scores. Unlike KBD, MKHEI of Western-style diet was not associated with abdominal obesity in either gender. In conclusion, KBD can lower the risk of abdominal obesity in females and should thus be recommended to prevent abdominal obesity.


A review of a priori regression models for warfarin maintenance dose prediction.
A number of a priori warfarin dosing algorithms, derived using linear regression methods, have been proposed. Although these dosing algorithms may have been validated using patients derived from the same centre, rarely have they been validated using a patient cohort recruited from another centre. In order to undertake external validation, two cohorts were utilised. One cohort formed by patients from a prospective trial and the second formed by patients in the control arm of the EU-PACT trial. Of these, 641 patients were identified as having attained stable dosing and formed the dataset used for validation. Predicted maintenance doses from six criterion fulfilling regression models were then compared to individual patient stable warfarin dose. Predictive ability was assessed with reference to several statistics including the R-square and mean absolute error. The six regression models explained different amounts of variability in the stable maintenance warfarin dose requirements of the patients in the two validation cohorts; adjusted R-squared values ranged from 24.2% to 68.6%. An overview of the summary statistics demonstrated that no one dosing algorithm could be considered optimal. The larger validation cohort from the prospective trial produced more consistent statistics across the six dosing algorithms. The study found that all the regression models performed worse in the validation cohort when compared to the derivation cohort. Further, there was little difference between regression models that contained pharmacogenetic coefficients and algorithms containing just non-pharmacogenetic coefficients. The inconsistency of results between the validation cohorts suggests that unaccounted population specific factors cause variability in dosing algorithm performance. Better methods for dosing that take into account inter- and intra-individual variability, at the initiation and maintenance phases of warfarin treatment, are needed.


Silicon nanowires: electron holography studies of doped p-n junctions and biased Schottky barriers.
We report an in situ examination of individual Si p-n junction nanowires (NWs) using off-axis electron holography (EH) during transmission electron microscopy. The SiNWs were synthesized by chemical vapor deposition with an axial dopant profile from n- to p-type, and then placed inside the transmission electron microscope as a cantilever geometry in contact with a movable Pt probe for in situ biasing measurements during simultaneous EH observations. The phase shift from EH indicates the potential shift between the p- and n-segments to be 1.03 ± 0.17 V due to the built-in voltage. The I-V characteristics of a single SiNW indicate the formation of a Schottky barrier between the NW tip and the movable Pt contact. EH observations show a strong concentration of electric field at this contact, preventing a change in the Si energy bands in the p-n junction region due to the applied bias.


All-Arthroscopic Triangular Fibrocartilage Complex Ligamentoplasty: Technique and Results.
Objective The aim of the study is to describe the modified all-arthroscopic technique for triangular fibrocartilage complex (TFCC) ligamentoplasty in chronic injuries of the TFCC with distal radioulnar joint (DRUJ) instability, and to present the results obtained. Methods A prospective study was conducted including 11 consecutive patients with chronic TFCC injury with DRUJ instability who underwent an all-arthroscopic TFCC ligamentoplasty. During follow-up, the range of joint motion, grip strength, pain according to the visual analog scale (VAS), functional outcomes according to the Mayo Wrist Score (MWS), and the QuickDASH Score were measured, and any complications and necessary reinterventions were recorded Results We analyzed 11 patients with distal radioulnar ligament injury treated using the all-arthroscopic ligamentoplasty technique. Mean follow-up was 31.5 ± 4.4 (range 12-58) months. The technique presented achieved DRUJ stability in 100% of cases at 12 months. Grip strength and pain, showed a statistically significant improvement between the preoperative score and the two postoperative assessments. Functional assessment using the QuickDASH score and the MWS also improved significantly. Conclusion The all-arthroscopic technique for the reconstruction of irreparable peripheral TFCC tears is a reliable technique, intended not only to minimize the surgical trauma to reduce postoperative pain and to facilitate rehabilitation, but also to improve both the quality of the reconstruction and the functional outcome.


Proline Increases Pigment Production to Improve Oxidative Stress Tolerance and Biocontrol Ability of Metschnikowia citriensis.
Utilizing antagonistic yeasts is a promising approach for managing postharvest decay of fruits. However, it is well established that various severe stresses encountered in the environment and production process cause the intracellular reactive oxygen species (ROS) accumulation in yeast cells, resulting in cell damage and loss of vitality. Here, proline has been shown to function as a cell protectant and inducer of biofilm formation able to increase the oxidative stress tolerance and the biocontrol ability of the antagonistic yeast Metschnikowia citriensis. Addition of proline to M. citriensis cells induced a significant rise in superoxide dismutase (SOD) and catalase (CAT) activity in the early and late stages of oxidative stress, respectively, and increased the maroon pigment production that directly reduced intracellular iron content and indirectly diminished intracellular ROS levels and thus inhibited ROS- and iron-induced apoptosis. Treating cells with iron chelator tropolone yielded similar results. Pigment production induced by proline also enhanced the capability of biofilm formation of M. citriensis. These results suggested an important role for pigment of M. citriensis in response to oxidative stress. The abilities of proline to scavenge intracellular ROS and inhibit apoptosis, increase pigment production, and promote biofilm formation contribute to the improvements in oxidative stress tolerance and biocontrol efficacy of M. citriensis.


Composition, morphology, and growth of clusters in a gas of particles with random interactions.
We use Langevin dynamics simulations to study the growth kinetics and the steady-state properties of condensed clusters in a dilute two-dimensional system of particles that are all different (APD) in the sense that each particle is characterized by a randomly chosen interaction parameter. The growth exponents, the transition temperatures, and the steady-state properties of the clusters and of the surrounding gas phase are obtained and compared with those of one-component systems. We investigate the fractionation phenomenon, i.e., how particles of different identities are distributed between the coexisting mother (gas) and daughter (clusters) phases. We study the local organization of particles inside clusters, according to their identity-neighbourhood identity ordering (NIO)-and compare the results with those of previous studies of NIO in dense APD systems.


Smartphone-Enabled Detection Strategies for Portable PCR-Based Diagnostics.
Incredible progress continues to be made toward development of low-cost nucleic acid-based diagnostic solutions suitable for deployment in resource-limited settings. Detection components play a vitally important role in these systems, but have proven challenging to adapt for operation in a portable format. Here we describe efforts aimed at leveraging the capabilities of consumer-class smartphones as a convenient platform to enable detection of nucleic acid products associated with DNA amplification via the polymerase chain reaction (PCR). First, we show how fluorescence-based detection can be incorporated into a portable convective thermocycling system controlled by a smartphone app. Raw images captured by the phone's camera are processed to yield real-time amplification data comparable to benchtop instruments. Next, we leverage smartphone imaging to achieve label-free detection of PCR products by monitoring changes in electrochemical reactivity of embedded metal electrodes as the target DNA concentration increases during replication. These advancements make it possible to construct rugged inexpensive nucleic acid detection components that can be readily embedded in a variety of portable bioanalysis instruments.


Influence of dietary conjugated linoleic acid on growth, meat quality, lipogenesis, plasma leptin and physiological variables of lipid metabolism in rabbits.
We investigated the effects of conjugated linoleic acid (CLA) supplementation on growth, feed efficiency, carcass characteristics, meat quality, lipogenesis, and lipid metabolism in rabbits. One hundred forty-four New Zealand White rabbits, half males, half females, age 55 d, mean 1.8 kg BW, were randomly assigned to three weight- and sex-balanced feeding groups in which conventional pelleted diets were supplemented with 0, 0.25, or 0.5% of a CLA preparation. The CLA preparation contained 65% CLA isomers. Twelve rabbits (six males and six females from each group) were slaughtered at each of three slaughtering trials (2.5, 2.8, and 3.1 kg BW, or 76, 90, and 104 d of age). Conjugated linoleic acid supplementation did not influence growth performance (P > or = 0.05) or carcass characteristics but reduced perirenal fat at heavier slaughtering weights (P = 0.09 at 2.8 kg BW; P < 0.01 at 3.1 kg BW). Conjugated linoleic acid reduced acetyl-CoA-carboxylase (CBX) activity in liver (P < 0.05) and adipose tissues (P < 0.01) but did not influence malic enzyme (ME) or glucose-6-phosphate dehydrogenase activity. Significant differences were found between sex in interscapular fat (P < 0.05) for CBX, in perirenal (P < 0.01) and interscapular (P < 0.05) fat for ME, and a tendency (P = 0.070) in liver for glucose-6-phosphate dehydrogenase. The oxidative stability of longissimus lumborum muscle was increased at the higher level of supplementation (P < 0.05). Conjugated linoleic acid reduced (P < 0.05) triglycerides and total cholesterol in plasma with a trend to increased serum leptin (P = 0.06). Plasma triglycerides were higher in males than females (P < 0.01) and plasma leptin tended to be higher in females (2.57 vs. 2.13 ng/ml, P = 0.06). It is concluded that dietary CLA reduced carcass fat in rabbits slaughtered at 2.8 kg or above and altered lipid metabolism to produce lower concentrations of serum triglycerides and total cholesterol and higher concentrations of leptin.


Improving the frequency precision of oscillators by synchronization.
Improving the frequency precision by synchronizing a lattice of N oscillators with disparate frequencies is studied in the phase reduction limit. In the general case where the coupling is not purely dissipative the synchronized state consists of targetlike waves radiating from a local source, which is a region of higher-frequency oscillators. In this state the improvement of the frequency precision is shown to be independent of N for large N, but instead depends on the disorder and reflects the dependence of the frequency of the synchronized state on just those oscillators in the source region of the waves. These results are obtained by a mapping of the nonlinear phase dynamics onto the linear Anderson problem of the quantum mechanics of electrons on a random lattice in the tight-binding approximation.


Agency and the Calibration of Motivated Behavior.
The controllability of positive or negative environmental events has long been recognized as a critical factor determining their impact on an organism. In studies across species, controllable and uncontrollable reinforcement have been found to yield divergent effects on subsequent behavior. Here we present a model of the organizing influence of control, or a lack thereof, on the behavioral repertoire. We propose that individuals derive a generalizable estimate of agency from controllable and uncontrollable outcomes, which serves to calibrate their behavioral strategies in a manner that is most likely to be adaptive given their prior experience.


[Study on human UDP-glucuronosyltransferase (UGT) isoforms involved in in vitro metabolism of trans-resveratrol].
To study major human UGT isoforms involved in trans-resveratrol (TR) phase II metabolism. trans-resveratrol and 12 major human UGT isoforms were incubated in vitro and then glucuronic acid metabolites were determined by HPLC-MS, in order to preliminarily analyze the structure and observe the effect of different UGT isoforms on the generation rate of glucuronic acid metabolites. In in vitro metabolic system, two metabolites-4'-O-monoglucuronide resveratrol (M-1) and 3-0-monoglucuronide resveratrol (M-2)-were generated from trans-resveratrol after being catalyzed by UGT. During the cause, generation of M-1 and M-2 were catalyzed by UGT1A1, UGT1A3, 1A8, 1A9 andlA10, whereas only UGT1A6 and 1A7 contributed to the forma-tion of M-2. Both the formation rate of M-1 and M-2 catalyzed by UGT1A1, 1A10 and the formation of M-2 catalyzed by UGT1A8 slowed down with the increasing concentration of substrates, causing the phenomenon of "substrate inhibition". UGT1A1, 1A8, 1A9, 1A10 get involved in the formation of M-1, and of them UGTIA9 is the most important contributor. UGT1A3 also makes small contribution to the formation of M-1 and M-2, while other UGT isoforms show hardly any reaction with the trans-resveratrol phase II metabolites.


Bis(mu-6-hydroxypicolinato)-mu-oxo-bis[dipyridinemanganese(III)] monohydrate.
The title compound, [Mn2(mu-O)(C6H3NO3)2(C5H5N)4].H2O, was isolated from the reaction of 2,6-pyridinedicarboxylic acid with [Mn12O12(CH3COO)16(H2O)4] in pyridine. The dimanganese complex has twofold symmetry; the MnIII atoms are bridged by one oxo and two amidate ligands and show compressed octahedral Jahn-Teller distortion. The molecular packing comprises a three-dimensional structure constructed by means of extensive intermolecular interactions, including three kinds of hydrogen bonds and pi-pi interactions.


Determination of benzotriazole and benzothiazole derivatives in tea beverages by deep eutectic solvent-based ultrasound-assisted liquid-phase microextraction and ultrahigh-performance liquid chromatography-high resolution mass spectrometry.
Benzotriazole (BTRs) and benzothiazole (BTHs) derivatives are a group of high production volume chemicals with emerging health concern, which found in tea beverages raising potential risks for food safety and human health. The present work describes a simple method using a "green" deep eutectic solvent (DES) based-ultrasound-assisted liquid-phase microextraction (UALPME) to rapidly extract BTRs and BTHs from tea beverages, and then applying UHPLC-electrospray ionization (+)-quadrupole time-of-flight mass spectrometry for detection and quantification. To overcome the challenges related to different experimental conditions, a Factorial Multilevel Categoric Design and a Face Centered Central Composite Design were applied to screen and optimize the parameters for the DES-UALPME procedure, respectively. After optimization, the method was validated and shown to possess low limits of quantification (LOQs; 1.5-12 ng mL-1), high precision (3-13%), and satisfactory accuracy (65-107%). The developed method was then successfully applied for the analysis of some selected BTRs and BTHs in tea beverages.


Saffman-Taylor instability of viscoelastic fluids: from viscous fingering to elastic fractures.
We study the linear stability of an air front pushing on a viscoelastic upper convected Mawxell fluid inside a Hele-Shaw cell. Both theory and experiments involving several viscoelastic fluids prove that a unique dimensionless time parameter lambda[over] controls all elastic effects. For small values of lambda[over], Newtonian behavior dominates, while for higher values of lambda[over] viscoelastic effects appear. We show that the linear growth rate of a small initial perturbation diverges for a critical value lambda[over]=lambda(c)[over] approximately 10. Experiments prove that this divergence is associated to a fracturelike pattern instability of the interface. We conclude that the observed fractures come from the Saffman-Taylor instability and that they directly emerge from the linear regime of it.


PET in Benign Bone Marrow Disorders.
This review aims to describe the current status of benign bone marrow (BM) imaging using PET. BM imaging is important as the BM is not only involved in poiesis of different vital cell lines and can be affected by primary BM disorders, but it is also frequently affected by several extramedullary diseases. Indications for the use of PET in benign BM disorders are the detection of extramedullary hematopoiesis, evaluation of patients with a discrepancy between BM histology and clinical status, visualizing BM infarctions, location of the optimal site for BM biopsy, diagnosing and staging of other hematological BM disorders, evaluation of radiotherapy effect on BM, and evaluation of BM transplantation. The 3'-18F-fluoro-3'-deoxy-L-thymidine (FLT) and 2-18F-2-deoxy-D-glucose (FDG) are the current main PET tracers to image BM physiology and pathology. FLT is a DNA synthesis-related tracer that can be used effectively in primary BM disorders in both diagnosis and monitoring treatment response, for example, in aplastic anemia. In secondary benign BM disorders, FDG-PET reveals that the prevalence of BM involvement in several benign diseases is more common than thought before. Novel PET tracers, such as the proliferation marker 4DST and hypoxia markers FAZA, MISO, and ATSM, are promising to visualize (benign) BM pathology more specifically. PET/MRI using innovative MRI sequences is promising to improve BM imaging in the near future. Additional trials are recommended to evaluate possible clinical applications of these newer tracers and new applications of PET/MRI in daily practice. This should be followed by updated guidelines on the use of PET in benign BM diseases.


[The Bolsa Família cash transfer program and food and nutrition security in Brazil: a critical review of the literature].
To critically review studies evaluating the impact of Bolsa Família (PBF), a federal cash transfer program, for food and nutrition security in Brazil. The Cochrane Library, LILACS, Medline and SciELO databases were searched, as well as public organization websites. All studies based on primary data were selected. The following were excluded: studies using secondary data, review articles, studies that did now allow the establishment of associations between PBF and food and nutrition security, as well as studies evaluating food security strictly in sanitary terms. Ten studies were included. Of these, five concluded that PBF had a positive impact on the food and nutrition security of participating families. Three studies observed an increase in the consumption of foods with higher calorie content and less nutritional value. This change in dietary habits is a risk factor for the development of overweight, obesity, and noncommunicable chronic diseases. The guarantee of food and nutrition security requires programs that focus on both malnutrition and overweight and obesity. Cash transfer programs such as the PBF can contribute more effectively to the nutritional well-being of participants if they are combined with other types of interventions, such as actions to promote healthy eating.


Physical activity for pregnant women.
Essential facts The UK's chief medical officers (CMOs) have published new advice on physical exercise for pregnant women in the form of an infographic. It is aimed at providing midwives, nurses, GPs, obstetricians and gynaecologists, as well as leisure sector professionals, with the latest evidence on physical activity during pregnancy.


Melanoma associated retinopathy and how to understand the electroretinogram.
Melanoma associated retinopathy is a rare paraneoplastic complication of metastatic cutaneous malignant melanoma. It may present years after the original diagnosis of melanoma. Here we describe a patient with this condition who presented with persistent photopsias and visual loss. We will discuss the electroretinographic findings and their utility.


Pharmacodynamic and pharmacokinetic studies on prizidilol and nipradilol (K-351), antihypertensive drugs with combined vasodilator and beta-adrenoceptor blocking actions, in rabbits.
Effects of prizidilol and nipradilol (K-351), beta-adrenoceptor antagonists with vasodilator action, on blood pressure and heart rate were studied in normotensive conscious rabbits after i.v. administration. In addition, we investigated relationships between plasma drug concentrations and beta-adrenoceptor blocking activity as estimated by the inhibition of isoproterenol-induced tachycardia and vasodilator activity as assessed by the inhibition of pressor response to angiotensin II (ANG II). Prizidilol (4 mg/kg) produced a significant and sustained fall in blood pressure and a slight increase in heart rate, while hydralazine (2 mg/kg) caused the same degree of hypotension and a marked tachycardia. Nipradilol (1 mg/kg) caused a significant reduction of resting heart rate, but had no significant effect on blood pressure. Propranolol (1 mg/kg) did not affect resting blood pressure and heart rate. Hypertensive response to ANG II was significantly attenuated only by hydralazine. Isoproterenol-induced tachycardia was significantly suppressed by prizidilol, nipradilol and propranolol. Good correlations were observed between beta-adrenoceptor blocking activity and plasma drug concentrations. These data suggest that prizidilol has an advantage over hydralazine to induce less tachycardia, but still may cause a certain degree of increase in heart rate. Nipradilol has a more potent beta-adrenoceptor blocking action than propranolol, while its vasodilator action is not obvious, at least in rabbits. Plasma concentrations of prizidilol and nipradilol are good indicators for beta-adrenoceptor blocking activity, but not for vasodilator activity.


Phototaxis and chemotaxis of brown algal swarmers.
Brown algae exhibit three patterns of sexual reproduction: isogamy, anisogamy, and oogamy. Unicellular swarmers including gametes and zoospores bear two heterogenous flagella, an anterior flagellum with mastigonemes (fine tripartite hairs) and a posterior one. In seawater, these flagellates usually receive physico-chemical signals for finding partners and good habitats. It is well known that brown algal swarmers change their swimming direction depending on blue light (phototaxis), and male gametes do so, based on the sex pheromones from female gametes (chemotaxis). In recent years, the comparative analysis of chemotaxis in isogamy, anisogamy, and oogamy has been conducted. In this paper, we focused on the phototaxis and chemotaxis of brown algal gametes comparing the current knowledge with our recent studies.


Psychosocial treatment of phobia and panic disorders.
Intervention packages combining cognitive restructuring techniques and exposure exercises have become the psychosocial treatments of choice for panic, agoraphobia, and social phobia. Exposure and related desensitization techniques are the treatment of choice for all variants of simple phobia. Combining psychotropic medication and cognitive-behavior therapy suggests strategies that offer new opportunities for increasing the number of individuals with anxiety disorders who can be effectively treated with a biobehavioral approach.


Reliability of visual and instrumental color matching.
The aim of this investigation was to evaluate intra-rater and inter-rater reliability of visual and instrumental shade matching. Forty individuals with normal color perception participated in this study. The right maxillary central incisor of a teaching model was prepared and restored with 10 feldspathic all-ceramic crowns of different shades. A shade matching session consisted of the observer (rater) visually selecting the best match by using VITA classical A1-D4 (VC) and VITA Toothguide 3D Master (3D) shade guides and the VITA Easyshade Advance intraoral spectrophotometer (ES) to obtain both VC and 3D matches. Three shade matching sessions were held with 4 to 6 weeks between sessions. Intra-rater reliability was assessed based on the percentage of agreement for the three sessions for the same observer, whereas the inter-rater reliability was calculated as mean percentage of agreement between different observers. The Fleiss' Kappa statistical analysis was used to evaluate visual inter-rater reliability. The mean intra-rater reliability for the visual shade selection was 64(11) for VC and 48(10) for 3D. The corresponding ES values were 96(4) for both VC and 3D. The percentages of observers who matched the same shade with VC and 3D were 55(10) and 43(12), respectively, while corresponding ES values were 88(8) for VC and 92(4) for 3D. The results for visual shade matching exhibited a high to moderate level of inconsistency for both intra-rater and inter-rater comparisons. The VITA Easyshade Advance intraoral spectrophotometer exhibited significantly better reliability compared with visual shade selection. This study evaluates the ability of observers to consistently match the same shade visually and with a dental spectrophotometer in different sessions. The intra-rater and inter-rater reliability (agreement of repeated shade matching) of visual and instrumental tooth color matching strongly suggest the use of color matching instruments as a supplementary tool in everyday dental practice to enhance the esthetic outcome.


Construction and engineering of positive feedback loops.
Artificial positive feedback loops (PFLs) have been used as genetic amplifiers for enhancing the responses of weak promoters and in the creation of eukaryotic gene switches. Here we describe the construction and directed evolution of two PFLs based on the LuxR transcriptional activator and its cognate promoter, P luxI . The wild-type PFLs are completely activated by 10 nM of 3-oxo-hexanoyl-homoserine lactone (OHHL). Directed evolution of LuxR increased the sensitivity of the feedback loops, resulting in systems that are completely activated at OHHL concentrations of 5 nM, or approximately 3 molecules per cell. The responses of the PFLs can also be modulated by adjusting inducer concentrations. These highly sensitive yet regulatable PFLs can be used to construct larger artificial genetic networks to gain understanding of the design principles of complex biological systems and are expected to find various applications in industrial fermentation and gene therapy.


Research on the Forward Solving Method of Defect Leakage Signal Based on the Non-Uniform Magnetic Charge Model.
Pipeline magnetic flux leakage inspection is widely used in the evaluation of material defect detection due to its advantages of having no coupling agent and easy implementation. The quantification of defect size is an important part of magnetic flux leakage testing. Defects of different geometrical dimensions produce signal waveforms with different characteristics after excitation. The key to achieving defect quantification is an accurate description of the relationship between the magnetic leakage signal and the size. In this paper, a calculation model for solving the defect leakage field based on the non-uniform magnetic charge distribution of magnetic dipoles is developed. Based on the traditional uniformly distributed magnetic charge model, the magnetic charge density distribution model is improved. Considering the variation of magnetic charge density with different depth positions, the triaxial signal characteristics of the defect are obtained by vector synthesis calculation. Simultaneous design of excitation pulling experiment. The leakage field distribution of rectangular defects with different geometries is analyzed. The experimental results show that the change in defect size will have an impact on the area of the defect leakage field distribution, and the larger the length and wider the width of the defect, the more sensitive the impact on the leakage field distribution. The solution model is consistent with the experimentally obtained leakage signal distribution law, and the model is a practical guide by which to improve the quality of defect evaluation.


Surgical placement of left ventricular lead for cardiac resynchronisation therapy after failure of percutaneous attempt.
Cardiac resynchronisation therapy has been shown to be an effective treatment to improve functional status and prolong survival of patients in advanced chronic heart failure. This study assessed the surgical outcomes of left anterior mini-thoracotomy for the implantation of left ventricular epicardial pacing leads in cardiac resynchronisation therapy. Our study consisted of 30 consecutive patients who underwent cardiac resynchronisation therapy with a left thoracotomy between November 2010 and April 2012 in our clinic. Postoperative follow up included the assessment of New York Heart Association (NYHA) functional class, electrocardiography and echocardiography. There were 22 male and eight female patients with a mean age of 68 ± 5.04 years. All patients were in NYHA class III or IV. Pre-procedure mean left ventricular ejection fraction was 28.1 ± 4.5% and post-procedural ejection fraction improved to 31.7 ± 5.1%. The pre-operative QRS duration changed from 171.7 ± 10.8 to 156.2 ± 4.4 ms after the operation. Also there was a significant reduction in left ventricular end-diastolic dimension from 6.98 ± 0.8 to 6.72 ± 0.8 mm (p < 0 .05), but no change in left ventricular end-systolic dimension and severity of mitral regurgitation. All patients had successful surgical left ventricular lead placement. There was no procedure-related mortality. The mean follow-up time was 40.4 months. Surgical epicardial left ventricular lead placement procedure is a safe and effective technique in patients with a failed percutaneous attempt.