Synthesis, characterization and biological evaluation of indomethacin derived thioureas as purinergic (P2Y1, P2Y2, P2Y4, and P2Y6) receptor antagonists.
G-protein-coupled receptors for extracellular nucleotides are known as P2Y receptors and are made up of eight members that are encoded by distinct genes and can be classified into two classes based on their affinity for specific G-proteins. P2Y receptor modulators have been studied extensively, but only a few small-molecule P2Y receptor antagonists have been discovered so far and approved by drug agencies. Derivatives of indole carboxamide have been identified as P2Y12 and P2X7 antagonist, as a result, we developed and tested a series of indole derivatives4a-lhaving thiourea moiety as P2Y receptor antagonist by using a fluorescence-based assay to measure the inhibition of intracellular calcium release in 1321N1 astrocytoma cells that had been stably transfected with the P2Y1, P2Y2, P2Y4 and P2Y6 receptors. Most of the compounds exhibited moderate to excellent inhibition activity against P2Y1 receptor subtype. The series most potent compound, 4h exhibited an IC50 value of 0.36 ± 0.01 µM selectivity against other subtypes of P2Y receptor. To investigate the ligand-receptor interactions, the molecular docking studies were carried out. Compound 4h is the most potent P2Y1 receptor antagonist due to interaction with an important amino acid residue Pro105, in addition to Ile108, Phe119, and Leu102.


Backscattered light from the cornea before and after laser-assisted subepithelial keratectomy for myopia.
To study corneal backscatter changes after laser-assisted subepithelial keratectomy (LASEK) and to search for correlations between the changes in forward and backward corneal light scatter. Antwerp University Hospital, Edegem, Belgium. Prospective interventional case series. Corneal backscatter was determined with a commercial Scheimpflug device and purpose-written image-analysis software. The mean backscatter profile and gray value distributions of the images for a 1.0 mm zone around the corneal apex were obtained preoperatively and 6 months after LASEK for myopia. This was compared with forward light scatter (or straylight) using measurements obtained with the compensation comparison method. The study enrolled 80 eyes (40 patients; mean age 34.2 years ± 10.4 [SD]). Very strong correlations were found between the backscatter profiles of right eyes and left eyes preoperatively. Hence, only right eyes were used for further calculations. The epithelial-Bowman peak of the backscatter profile decreased significantly after LASEK (mean decrease -2.2 ± 4.7 grayscale units) (P=.002, paired t test), which corresponded to the ablation of Bowman layer. Significant changes in the gray-value distribution were observed postoperatively, corresponding to the decreases in the epithelium-Bowman peak. Forward light scatter decreased significantly after LASEK (mean decrease -0.10 ± 0.13) (P<.001); however, no significant correlation with corneal backscatter was observed. The anterior part of the corneal backscatter profile decreased significantly after LASEK. A significant reduction in forward light scatter was also seen, although it was not correlated to backward light scatter.


Poor Stability of Li2 CO3 in the Solid Electrolyte Interphase of a Lithium-Metal Anode Revealed by Cryo-Electron Microscopy.
The solid electrolyte interphase (SEI) dictates the cycling stability of lithium-metal batteries. Here, direct atomic imaging of the SEI's phase components and their spatial arrangement is achieved, using ultralow-dosage cryogenic transmission electron microscopy. The results show that, surprisingly, a lot of the deposited Li metal has amorphous atomic structure, likely due to carbon and oxygen impurities, and that crystalline lithium carbonate is not stable and readily decomposes when contacting the lithium metal. Lithium carbonate distributed in the outer SEI also continuously reacts with the electrolyte to produce gas, resulting in a dynamically evolving and porous SEI. Sulfur-containing additives cause the SEI to preferentially generate Li2 SO4 and overlithiated lithium sulfate and lithium oxide, which encapsulate lithium carbonate in the middle, limiting SEI thickening and enhancing battery life by a factor of ten. The spatial mapping of the SEI gradient amorphous (polymeric → inorganic → metallic) and crystalline phase components provides guidance for designing electrolyte additives.


Organization of the nervous system in Opisthorchis viverrini investigated by histochemical and immunohistochemical study.
The structure and organization of the nervous system has been documented for various helminth parasites. However, the neuroanatomy of the carcinogenic liver fluke, Opisthorchis viverrini has not been described. This study therefore investigated the organization of the nervous system of this fluke using cholinesterase activity, aminergic and peptidergic (FMRFamide-like peptides) immunostaining to tag major neural elements. The nervous system, as detected by acetylcholinesterase (AchE) reaction, was similar in newly excysted metacercariae, migrating juveniles and adult parasites. In these stages, there were three pairs (dorsal, ventral and lateral) of bilaterally symmetrical longitudinal nerve cords and two cerebral ganglia. The ventral nerve cords and the cerebral ganglia were well-developed and exhibited strong AchE reactivity, as well as aminergic and FMRFamide-like immunoreactivity. Numerous immunoreactive nerve cell bodies were observed around the inner surface of the ventral sucker. Fine FMRFamide-like peptides immunopositive nerve fiber was rarely observed. Overall, the organization of the nervous system of O. viverrini is similar to other trematodes.


Meta-analysis and machine learning-augmented mixed effects cohort analysis of improved diets among 5847 medical trainees, providers and patients.
We sought to produce the first meta-analysis (of medical trainee competency improvement in nutrition counseling) informing the first cohort study of patient diet improvement through medical trainees and providers counseling patients on nutrition. (Part A) A systematic review and meta-analysis informing (Part B) the intervention analysed in the world's largest prospective multi-centre cohort study on hands-on cooking and nutrition education for medical trainees, providers and patients. (A) Medical educational institutions. (B) Teaching kitchens. (A) Medical trainees. (B) Trainees, providers and patients. (A) Of the 212 citations identified (n 1698 trainees), eleven studies met inclusion criteria. The overall effect size was 9·80 (95 % CI (7·15, 12·45) and 95 % CI (6·87, 13·85); P < 0·001), comparable with the machine learning (ML)-augmented results. The number needed to treat for the top performing high-quality study was 12. (B) The hands-on cooking and nutrition education curriculum from the top performing study were applied for medical trainees and providers who subsequently taught patients in the same curriculum (n 5847). The intervention compared with standard medical care and education alone significantly increased the odds of superior diets (high/medium v. low Mediterranean diet adherence) for residents/fellows most (OR 10·79, 95 % CI (4·94, 23·58); P < 0·001) followed by students (OR 9·62, 95 % CI (5·92, 15·63); P < 0·001), providers (OR 5·19, 95 % CI (3·23, 8·32), P < 0·001) and patients (OR 2·48, 95 % CI (1·38, 4·45); P = 0·002), results consistent with those from ML. The current study suggests that medical trainees and providers can improve patients' diets with nutrition counseling in a manner that is clinically and cost effective and may simultaneously advance societal equity.


Melatonin alleviates imidacloprid phytotoxicity to cucumber (Cucumis sativus L.) through modulating redox homeostasis in plants and promoting its metabolism by enhancing glutathione dependent detoxification.
Melatonin (Mel), a powerful antioxidant that has the ability to regulate physiological and biochemical processes in plants under abiotic stresses. However, its roles in pesticide detoxification is poorly understood. Herein, selecting leaf spraying insecticide imidacloprid (IMD) as the model, we demonstrated the detoxification mechanism underlying root pretreatment of Mel on IMD in cucumber. IMD treatment affected the primary light conversion efficiency of photosystem II (Fv/Fm), reduced the quantum yield, and increased hydrogen peroxide and superoxide anions contents as well as the levels of membrane lipid peroxidation, indicating that excessive IMD treatment induces oxidative stress. Nonetheless, by increasing the appropriate levels of exogenous Mel, the photosynthesis of cucumber under IMD treatment reached the control levels, effectively removing reactive oxygen species. Furthermore, the content and ratio of ascorbate (AsA) and glutathione (GSH) were decreased under IMD treatment; Mel treatment enhanced the AsA/DHA and GSH/GSSG ratios, as well as the activities of MDHAR, DHAR and GR, suggesting that Mel could alleviate oxidative stress of cucumber treated with IMD by regulating the ascorbic acid-glutathione cycle. Importantly, IMD degradation rate and glutathione S-transferase (GST) activity increased after Mel treatment. The levels of transcripts encoding antioxidant enzymes GPX and GST (GST1,2 and 3) were also increased, indicating that Mel accelerated IMD degradation. These results suggest that Mel plays an important role in the detoxification of IMD by promoting GST activity and transcription and the AsA-GSH cycle, thus providing an approach for plants to reduce IMD residue through the plant's own detoxification mechanism.


Role of hip MR imaging in the management of sports-related injuries.
MR imaging is an invaluable method for the workup of a painful hip. It is showing increased sensitivity and specificity for many of the soft tissue and bony abnormalities of the hip, especially with the addition of intra-articular contrast(MR arthrography). Chondral injuries of the femoral head and acetabulum remain an area in MR imaging that should continue to improve with new gradient protocols.


Role of the lipoxygenase pathway in phenylephrine-induced vascular smooth muscle cell proliferation and migration.
We studied the effects of phenylephrine-stimulated proliferation and migration of vascular smooth muscle cells and the role of 12-lipoxygenase-mediated pathways under normal as well as high glucose conditions. Phenylephrine-induced increases in cellular proliferation and migration were attenuated by the specific 12-lipoxygenase inhibitor baicalein. In contrast, neither of the cyclo-oxygenase inhibitors, indomethacin or ibuprofen, had any effect. Direct addition of the 12-lipoxygenase product, 12-S-hydroxyeicosatetraenoic acid (12-HETE), increased the proliferation and migration of vascular smooth muscle cells treated with both phenylephrine and nordihydroguaiaretic acid. Furthermore, we observed that phenylephrine induced greater increases in the proliferation and migration of vascular smooth muscle cells and also that the 12-lipoxygenase inhibitor prevented the enhancement of proliferation and migration of vascular smooth muscle cells induced by phenylephrine in the presence of high glucose (25 mmol/l). These results suggest that 12-lipoxygenase activation plays a key role in phenylephrine-induced responses of vascular smooth muscle cells under normal and hyperglycemic conditions. 12-lipoxygenase may be a good pharmacological target for treatment of vascular disease of hypertension and diabetes mellitus.


ι-Carrageenan Tetrasaccharide from ι-Carrageenan Inhibits Islet β Cell Apoptosis Via the Upregulation of GLP-1 to Inhibit the Mitochondrial Apoptosis Pathway.
ι-Carrageenan performs diversified biological activities but has low bioavailability. ι-Carrageenan tetrasaccharide (ιCTs), a novel marine oligosaccharide prepared by the marine enzyme Cgi82A, was investigated for its effects on insulin resistance in high-fat and high-sucrose diet mice. Oral administration of ιCTs (ιCTs-L 30.0 mg/kg·bw, ιCTs-H 90.0 mg/kg·bw) decreased fasting blood glucose by 35.1% ± 1.41 (P < 0.01) and 27.4% ± 0.420 (P < 0.05), and enhanced glucose tolerance. Besides, ιCTs-L ameliorated islet vacuolization, decreased the β cell apoptosis by 21.8% ± 0.200 (P < 0.05), and promoted insulin secretion by 5.41% ± 0.0173 (P < 0.01) through pancreatic hematoxylin and eosin (H&E) staining, TUNEL staining, and insulin-glucagon immunostaining analysis. Interestingly, ιCTs-L and ιCTs-H treatment increased the incretin GLP-1 content in serum by 22.1% ± 0.402 (P < 0.01) and 10.7% ± 0.0935 (P < 0.05) respectively, through regulating the bile acid levels, which contributed to the inhibition of β cell apoptosis. Mechanically, ιCTs upregulated the expression of the GLP-1 receptor (GLP-1R) and protein kinase A (PKA) in the GLP-1/cAMP/PKA signaling pathway, and further inhibited the expression of cytochrome C and caspase 3 in the mitochondrial apoptotic pathway. In conclusion, this study suggested that ιCTs alleviated insulin resistance by GLP-1-mediated inhibition of β cell apoptosis and proposed a new strategy for developing potential functional foods that prevent insulin resistance.


Addition of Na2CO3 Improves the Shelf Life of Experimental 4-META Self-etch Primer.
The objective of this study was to assess the influence of the addition of Na2CO3 on the shelf life and bond strength of 4-META self-etch primer. Two 4-META self-etch primers were experimentally formulated with and without the addition of Na2CO3 (primer A and primer B, respectively). The primers were stored at 37°C for several periods of time after formulation. Clearfil SE Bond Primer (Kuraray Noritake Dental) was used as a control. A composite was bonded to bovine dentin using a combination of the primer and a bonding agent (Clearfil SE Bond), and the shear bond strengths were measured. Changes in the pH of the experimental primers were monitored and macroscopic observations were made as a function of the storage periods. With 0-day storage, the bond strength of primer A was equivalent to that of primer B and significantly lower than that of Clearfil SE Primer. The bond strengths of primer A were stable during 90-day storage; by contrast, the bond strengths of primer B significantly decreased during 7-day storage. primer A exhibited stable pH values during 180-day storage; primer B exhibited significantly lower pH than primer A with 0-day storage and discolored gelation during 7-day storage. By adding Na2CO3, the shelf life of the 4-META self-etch primer was obviously improved without significant deterioration in dentin bond strength. Adjusting the pH to around 4.5 was effective for obtaining sufficient bond strength and hydrolytic stability of the primer.


Carbon Nanodots-Embedded Pullulan Nanofibers for Sulfathiazole Removal from Wastewater Streams.
Carbon nanodots (CNDs)-embedded pullulan (PUL) nanofibers were developed and successfully applied for sulfathiazole (STZ) removal from wastewater streams for the first time. The CNDs were incorporated into PUL at 0.0%, 1.0%, 2.0%, and 3.0% (w/w) to produce M1, M2, M3, and M4 nanofibers (PUL-NFs), respectively. The produced PUL-NFs were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD), thermal gravimetric analysis (TGA) and Differential scanning calorimetry (DSC) and applied for STZ removal from aqueous solutions through pH, kinetics, and equilibrium batch sorption trials. A pH range of 4.0-6.0 was observed to be optimal for maximum STZ removal. Pseudo-second order, intraparticle diffusion, and Elovich models were suitably fitted to kinetics adsorption data (R2 = 0.82-0.99), whereas Dubinin-Radushkevich, Freundlich, and Langmuir isotherms were fitted to equilibrium adsorption data (R2= 0.88-0.99). STZ adsorption capacity of PUL-NFs improved as the amount of embedded CNDs increased. Maximum STZ adsorption capacities of the synthesized PUL-NFs were in the order of: M4 > M3 > M2 > M1 (133.68, 124.27, 93.09, and 35.04 mg g-1, respectively). Lewis acid-base reaction and π-π electron donor-acceptor interactions were the key STZ removal mechanisms under an acidic environment, whereas H-bonding and diffusion were key under a basic environment. Therefore, CNDs-embedded PUL-NFs could be employed as an environmentally friendly, efficient, and non-toxic adsorbent to remove STZ from wastewater streams.


Response to the Comment on "A Systematic Review and Meta-Analysis of Hospitalised Current Smokers and COVID-19".
This is a reply to the comment by Ivan Berlin and Daniel Thomas on our recently published work [...].


Blood salvage produces higher total blood product costs in single-level lumbar spine surgery.
Retrospective review. To determine the incremental cost-effectiveness of cell saver for single-level posterior lumbar decompression and fusion (PLDF). Intraoperative cell salvage is used during surgery to reduce the need for perioperative allogeneic blood transfusion. Although the use of cell saver may be beneficial in certain circumstances, its utility has not been clearly established for the common procedure of an adult single-level PLDF. Randomly selected adult patients treated with a single-level PLDF between July 2010 and June 2011 at a single institution were identified. Patients who had a combined anterior and posterior approach were excluded. The final study sample for analysis consisted of 180 patients. Hospital records were reviewed to determine whether: (1) cell saver was available during surgery, (2) recovered autologous blood was infused, and (3) the patient received intra- or postoperative allogeneic transfusions. Estimated blood loss, levels fused, volume(s) transfused, and all related complications were recorded. Costs included the cost of allogeneic blood transfusion, setting up the cell saver recovery system, and infusing autologous blood from cell saver, whereas effectiveness measures were allogeneic blood transfusions averted and quality adjusted life years. The incremental cost-effectiveness ratio was $55,538 per allogeneic transfusion averted, with a decrease in the transfusion rate from 40.0% to 38.7% associated with the cell saver approach. This translated into an incremental cost-effectiveness ratio of $5,555,380 per quality adjusted life years gained, which is well above the threshold for an intervention to be considered cost-effective ($100,000 per quality adjusted life years gained). The use of cell saver during a single-level PLDF does not significantly reduce the need for allogeneic blood transfusion and is not cost-effective. The high cost of cell saver in combination with the low complication rate of allogeneic blood transfusion, suggest that cell saver should not be used for single-level PLDF. Further studies are needed to evaluate the necessity for cell saver among other types of spinal surgery.


Infant behaviors are predictive of functional somatic symptoms at ages 5-7 years: results from the Copenhagen Child Cohort CCC2000.
To investigate infancy predictors of impairing functional somatic symptoms (FSS) at child ages 5-7 years with a focus on problems with feeding, sleep, and tactile reactivity. This study is part of a longitudinal birth cohort study, Copenhagen Child Cohort CCC2000. Child health, development, and functioning were assessed by community health nurses at 4 home visits from birth to age 10 months. FSS at ages 5-7 years were measured by the Soma Assessment Interview in 1327 children. Sociodemographic data and information on maternal psychiatric illness were obtained from the Danish National Registers. Multiple logistic regression analysis controlled for maternal psychiatric illness and annual household income revealed that combined infancy regulatory problems (ie, at least 2 of 3 problems of feeding, sleeping, or tactile reactivity during the first 10 months of living) predicted impairing FSS at 5-7 years (aOR = 2.9, 95% CI: 1.3-6.6). Maternal psychiatric illness during the child's first year of living was also associated with later child FSS (aOR = 7.1, 95% CI: 1.8-27.8). Regulatory problems may be an early marker of disturbed sensory reactivity in young children, which together with maternal psychiatric problems, point to possible early risk mechanisms of impairing FSS in childhood.


Enhancing the role of faith-based organizations to improve health: a commentary.
Researchers, policymakers, and community members increasingly recognize the potential to leverage faith-based organizations (FBOs) to improve health. This commentary complements Leyva and colleagues' article on whether and how members of FBOs view such a role. The commentary draws on our 13+ years operating a faith-based and community-based research organization, Faith Moves Mountains, in the Appalachian context. Issues to be addressed in the further development of faith-based health promotion include sustainability; adherence to the evidence-based operations of interventions, training, and privacy and protection protocols; and understanding the changing landscape of American public life.


Antenatal sonographic findings associated with unilateral pulmonary agenesis.
Unilateral pulmonary agenesis is a rare anomaly that has a relatively frequent association with other congenital malformations. Prognosis depends in part upon associated anomalies and whether the right or left lung is involved. The prenatal sonographic findings of this defect share some similarities with those of other intrathoracic lesions or congenital diaphragmatic hernia. Our patient had a twin gestation complicated by early discordant growth and hydramnios. The smaller fetus had cardiac dextroposition, abnormally echogenic left lung tissue, and a flattened but clearly visible left hemidiaphragm. No abdominal viscera were seen in the thoracic cavity. Postnatally, this infant was found to have agenesis of the right lung, a tracheoesophageal fistula, and pyloric stenosis. The diagnosis of unilateral pulmonary agenesis should be considered in a fetus with the sonographic findings of a shift of the mediastinal structures, echogenic lungs, and an intact diaphragm.


[Adenomyoma of the stomach (pancreatic heterotopia)--case report and review of the literature].
A case report is given of a patient, who harbored a gastric adenomyoma; this is a special form of heterotopic pancreatic tissue including excessive formation of smooth muscle tissue. Size and localization of the tumor were unusual in our case. The case presented is discussed taking into account the literature available.


The High Expression of Legumain in Canine Neoplasms: A Retrospective Analysis of 100 Cases.
Legumain, a novel asparaginyl endopeptidase, has been observed to be overexpressed in several types of human solid tumors. Elevated levels of legumain are found in human cancers, and this oncoprotein may facilitate tumor invasion and metastasis when overexpressed. These findings suggest that legumain plays a malignant role in cancer biology. However, currently, no publications have identified the role of legumain in the development of canine cancers. The present study first compared the expression patterns of legumain in paraffin-embedded canine tumor tissues, with those of normal tissues, by immunohistochemistry. A total of 100 canine tumor samples, including mast cell tumors, soft tissue sarcoma, hemangiosarcoma, lymphoma, mammary gland carcinoma, hepatoid gland tumor, squamous cell carcinoma, trichoblastoma, and melanoma were evaluated. Compared with the normal tissues, all tumor samples displayed high intensities of legumain expression. Mesenchymal-type tumors displayed immunoreactivity for legumain, with an average expression of 40.07% ± 1.70%, which was significantly lower than those of epithelial tumors and other types of tumors, which had median expressions of 49.12% ± 1.75% and 47.35% ± 2.71%, respectively (p < 0.05). These findings indicate that legumain has a high potential to be a candidate for distinguishing tumors from normal tissues. Although further studies on a larger number of cases are necessary to clarify the clinical application of legumain, the overexpression patterns of legumain in canine tumor tissues are reported, for the first time, in this study.


Occurrence of syphilis in the young patient who coinfected with human immunodeficiency virus: A dangerous combination case report.
Several complications can occur if syphilis is not treated at an early stage. Several developing countries recently remerged the high cases of syphilis with human immunodeficiency. We reported the case of 26-years-old male infected with syphilis with the human immunodeficiency virus (HIV). The patient sole and palm contain lesions. In our patient, HIV was diagnosed 2 years earlier in the prophylactic studies but had not taken any medical management. The penicillin G was taken to the patient to reverse the lesions, and it was successfully treated. The patient also was on antiretroviral therapy for the improvement in immune status. This case highlighted the importance of early management of any inflammatory cutaneous disease with HIV infections that can prevent the severity of the disease condition.


Approach to treatment of the patient with metabolic syndrome: lifestyle therapy.
The National Cholesterol Education Program's Adult Treatment Panel III definition of the metabolic syndrome identifies those at high risk for diabetes mellitus and/or a cardiac event by clustering a number of easily measured clinical findings, including abdominal obesity, elevated plasma levels of triglycerides, low plasma levels of high-density lipoprotein cholesterol, elevated fasting blood glucose, and elevated blood pressure. The presence of > or = 3 of these 5 risk factors justifies a diagnosis of the metabolic syndrome. This article focuses on root causes of the syndrome (atherogenic diet, sedentary lifestyle, and overweight/obesity) and highlights recent studies that demonstrate the effectiveness of therapeutic lifestyle changes in improving or preventing the components of the metabolic syndrome. We offer a practical approach with a focus that embraces not only patients, but also physicians and healthcare professionals as well as the larger healthcare system.


The MacNew heart disease health-related quality of life instrument: reference data for users.
To report reference data for the heart-specific MacNew Heart Disease Health-Related Quality of Life instrument. One thousand five hundred and six patients with myocardial infarction (n = 346), heart failure (n = 201), and ischaemic heart disease (IHD, n = 959) were surveyed 4 months after hospital discharge. Quality of life scores were determined, stratified by diagnostic category, age and sex. Changes in scores from 4 to 8 months post-discharge were calculated for a subset of 830 patients, stratified by age and sex. At 4 months there were no significant differences in scores between myocardial infarction and electively admitted IHD patients, however the scores of heart failure patients were significantly lower (indicating poorer quality of life) than those of patients with other diagnoses. There were few significant differences between age groups or sexes when comparing within diagnostic groups. Change from 4 to 8 months was not associated with diagnosis, age, or sex but was associated with events within the period (readmission or revascularisation). The change data suggest that a value of 0.5 may be a useful indicator of the minimal clinically important difference. These reference data will assist in sample size calculations and with comparison of results in other studies, and will be of use to researchers who are using or intending to use the MacNew instrument.


Both IL-1β and TNF-α regulate NGAL expression in polymorphonuclear granulocytes of chronic hemodialysis patients.
NGAL is involved in modulation of the inflammatory response and is found in the sera of uremic patients. We investigated whether hemodiafiltration (HDF) could influence the ability of polymorphonuclear granulocytes (PMGs) to release NGAL. The involvement of interleukin- (IL-)1β and tumor necrosis factor- (TNF-)α on NGAL release was evaluated. We studied end-stage renal disease (ESRD) patients at the start of dialysis (Pre-HDF) and at the end of treatment (Post-HDF) and 18 healthy subjects (HSs). Peripheral venous blood was taken from HDF patients at the start of dialysis and at the end of treatment. PMGs obtained from ESRD patients were hyporesponsive to LPS treatment, with respect to PMG from HS. IL-1β and TNF-α produced by PMG from post-HDF patients were higher than those obtained by PMG from pre-HDF. Neutralization of IL-1β, but not of TNF-α, determined a clear-cut production of NGAL in PMG from healthy donors. On the contrary, specific induction of NGAL in PMG from uremic patients was dependent on the presence in supernatants of IL-1β and TNF-α. Our data demonstrate that in PMG from healthy subjects, NGAL production was supported solely by IL-1β, whereas in PMG from HDF patients, NGAL production was supported by IL-1β, TNF-α.


Preparation of indoles via iron catalyzed direct oxidative coupling.
Iron-catalyzed aryl C-H and vinyl C-H bonds activation to give valuable substituted indole products was reported. The reaction shows high functional group tolerance.


Gastrointestinal transit and distribution of ranitidine in the rat.
Ranitidine gastrointestinal distribution was examined in the rat small intestine after oral administration to determine whether intestinal transit or secretion (exsorption) may influence the appearance of secondary peaks in ranitidine serum concentration-time profiles. Male Sprague-Dawley rats received ranitidine (50 mg/kg) by oral gavage, and the mass of ranitidine recovered in all small intestinal segments (approximately 12 cm each) was determined 30, 60, 90, or 120 min after administration. In a separate group of anesthetized rats, the small intestine was divided into two segments of equal length that were perfused with normal saline in a single-pass manner. Rats received an escalating, zero-order IV infusion of ranitidine for 30 min, and venous blood and intestinal effluent were collected over 90 min to quantitate ranitidine exsorption. Thirty min after oral administration, > 50% of the recovered ranitidine mass resided in the lower half of the small intestine in all rats. Ranitidine mass in 5 of 16 rats displayed a bimodal distribution with significant amounts of ranitidine recovered from the stomach 60 to 90 min after dosing. Ranitidine exsorption was more efficient from the lower jejunum and ileum than from the duodenum and upper jejunum. However, intestinal secretion of ranitidine was minor (5% of the IV dose). Ranitidine absorption from the lower ileum contributes significantly to systemic ranitidine concentrations before and during the time of the first concentration maximum. Separation of the drug mass into multiple boluses may contribute to secondary peaks in ranitidine concentration-time profiles. Exsorption did not contribute significantly to ranitidine distribution in the gastrointestinal tract.


The binding of cortisol to adrenal mitochondria.
Binding of tritiated cortisol to adrenal zona glomerulosa mitochondria was studied and compared with that of corticosterone. Cortisol was shown to bind specifically to the inner membrane of zona glomerulosa mitochondria. Corticosterone and cortisol had similar apparent association constants (Ka) and concentrations of binding sites. The methodology was validated by obtaining similar Ka from both binding plots and kinetic data. Cortisol binding was inhibited by pretreatment with sodium dithionite, and displaced by deoxycorticosterone, corticosterone, 18-hydroxy-corticosterone, 11 beta-hydroxy-18-ethynyl-progesterone and metyrapone, but not by cholesterol. These results suggest that cortisol and corticosterone bind to the same cytochrome P-450.


Clinical outcomes observation in stage IIB-IIIB cervical cancer treated by adjuvant surgery following concurrent chemoradiotherapy.
To explore the feasibility of adjuvant surgery following concurrent chemoradiation therapy (CCRT) in stage IIB-IIIB (according to FIGO staging of 2009) cervical cancer and analyze risk factors of recurrence after surgery. Forty-nine patients diagnosed with stage IIB-IIIB cervical cancer were reviewed retrospectively. We investigated the risk factors of recurrence after surgery using Chi-squared Test and further analyzed multiple factors affecting postoperative recurrence using the multi-factor logistic regression. Furthermore, the correlation of surgery outcomes (including operation time, bleeding, and hospitalization date and surgery complications) with the time which carried out between CCRT and completion surgery was analyzed. Tumor histology and residual tumor in the cervix were significantly associated with postoperative recurrence (P = 0.014 and P = 0.040, respectively). Logistic regression analysis demonstrated that the independent risk factors of postoperative recurrence were age and residual tumor in the cervix (P = 0.017 and P = 0.030, respectively). Complications (operation time, bleeding, hospitalization date) were compared between patients with an interval with radiotherapy less than 6 weeks and patients with an interval longer than 6 weeks. There were statistical differences in the amount of bleeding and postoperative complications between the two groups (P = 0.019 and P = 0.044, respectively). CCRT combined with surgery for stage IIB-IIIB cervical cancer was feasible, reduced the rate of postoperative recurrence and surgery complications were tolerated.


Usefulness of screening for Candida auris colonisation in international patients admitted to a large university hospital.
Candida auris is an emerging pathogen in health care-associated infections. In contrast to many other countries with rising numbers of C. auris, only seven cases have been reported in Germany from 2015 to 2017, mostly from patients who received prior medical treatment abroad. We therefore established a mandatory screening for C. auris colonisation at our tertiary care centre for all patients who were admitted as international patients or previously hospitalised in a foreign country within the past 6 months. Colonisation of patients was assessed using a previously established screening protocol for multidrug resistant bacteria. Since 2017, all screening samples were additionally analysed for C. auris using CHROMagar Candida (CHROMagar, Paris, France). Yeast isolates were identified using matrix-assisted laser ionisation time-of-flight (MALDI TOF), except for C. albicans (identified by the typical green colour on chromogenic agar). Data were analysed retrospectively. Our study cohort included 655 patients and an overall number of 1399 samples. Fifty-three patients were colonised with Candida species (C. albicans, n = 37; C. glabrata, n = 14; others n = 9). No case of C. auris was detected. Candida spp. were mainly detected from respiratory samples (5.4% positive) and gastrointestinal specimen (5.2%). Laboratory costs were 14,689 € and analyses resulted in 98.7 h of additional technician's work. No colonisation with C. auris was detected among patients with previous hospitalisation abroad. Universal C. auris screening of patients with any contact to foreign health care does not seem to be cost-effective in our setting and more targeted screening strategies have to be developed.


Polymeric metal-containing ionic liquid sorbent coating for the determination of amines using headspace solid-phase microextraction.
This study describes the design, synthesis, and application of polymeric ionic liquid sorbent coatings featuring nickel metal centers for the determination of volatile and semivolatile amines from water samples using headspace solid-phase microextraction. The examined polymeric ionic liquid (PIL) sorbent coatings were composed of two ionic liquid monomers (tetra(3-vinylimidazolium)nickel bis[(trifluoromethyl)sulfonyl]imide [Ni2+ (VIM)4 ] 2[NTf2 - ] and 1-vinyl-3-hexylimidazolium [HVIM+ ][NTf2 - ]), and an ionic liquid cross-linker (1,12-di(3-vinylimidazolium)dodecane [(VIM)2 C12 2+ ] 2[NTf2 - ]). With these ionic liquid monomers and cross-linkers, three different types of coatings were prepared: PIL 1 based on the neat [Ni2+ (VIM)4 ] 2[NTf2 - ] monomer, PIL 2 consisting of the [Ni2+ (VIM)4 ] 2[NTf2 - ] monomer with addition of cross-linker, and PIL 3 composed of the [HVIM+ ][NTf2 - ] monomer and cross-linker. Analytical performance of the prepared sorbent coatings using headspace solid-phase microextraction gas chromatography-mass spectrometry was compared with the polydimethylsiloxane and polyacrylate commercial coatings. The PIL 2 sorbent coating yielded the highest enrichment factors ranging from 5500 to over 160 000 for the target analytes. The developed headspace solid-phase microextraction gas chromatography-mass spectrometry method was applied for the analysis of real samples (the concentration of amines was 200 μg/L), producing relative recovery values in the range of 90.9-120.0% (PIL 1) and 83.0-122.7% (PIL 2) from tap water, and 84.8-112.4% (PIL 1) and 79.2-119.3% (PIL 2) from lake water.


The impact of CytoGam on cardiac transplant recipients with moderate hypogammaglobulinemia: a randomized single-center study.
We have previously shown that the preemptive use of cytomegalovirus (CMV) immunoglobulin (Ig) replacement (CytoGam) decreases the incidence of opportunistic infections in cardiac transplant recipients with severe hypogammaglobulinemia. However, the impact of Ig replacement in moderately hypogammaglobulinemic patients is unknown. Periodic monitoring of the IgG levels was done in 300 heart transplant recipients. Moderate hypogammaglobulinemia (IgG, 350-500 mg/dl) developed in 56 patients (18.6%). Thirty-three patients declined randomization but agreed to have their IgG levels monitored. Twenty-three patients were randomized to placebo (n = 10) or CytoGam (n = 13) at 105 +/- 63 days after transplantation. The baseline characteristics were similar. A significant reduction in CMV infection was noted in the CytoGam Group compared with the Placebo Group (15.4% [2/13] vs 60% [6/10], p = .039). Among patients who declined randomization, CMV infection developed in 13 (39.4%) of 33, and 6 (46.1%) of the 13 progressed to severe hypogammaglobulinemia. A trend for reduction in the average episodes of > or =grade 2 rejection during the 6-month period after randomization was noted in the CytoGam group (0.4 +/- 0.6 vs 1.4 +/- 1.3, p = 0.065). The preemptive use of CytoGam decreases the incidence of CMV infection in patients with moderate hypogammaglobulinemia. A larger randomized study is needed to substantiate these results.


Protective effects of esculentic acid against endotoxic shock in Kunming mice.
Esculentic acid (EA), a triterpene compound extracted from the root of Phytolacca esculenta (the Chinese name Shang Lu), has been widely used to therapy a variety of inflammatory diseases such as rheumatoid arthritis, edema, hepatitis and bronchitis. The present study was designed to investigate the protective effects of EA against LPS-induced endotoxic shock by the intraperitoneal injection of EA (1, 5 and 10 mg/kg) prior to LPS stimulation (1 mg/kg, i.p.). We examined the effects of EA on the survival rate of mice, inflammatory cytokine and pro-inflammatory mediator production, histopathological changes and protein expression of COX-2 in tissue sections from lung, liver and kidney. The results indicate that EA not only increases the survival rate of mice, but decreases the levels of TNF-α, IL-6, NO and PGE2 in serum or tissues, histopathological changes and COX-2 protein expression also. Furthermore, EA also increases the levels of anti-inflammatory cytokine IL-10 in serum. Overall, these data suggest that the protective effects of EA against LPS-induced endotoxic shock may be mediated, at least in part, by regulation the release of inflammatory cytokines and mediators, and protein expression of COX-2 in mice.


Prokaryotic rRNA-mRNA interactions are involved in all translation steps and shape bacterial transcripts.
The well-established Shine-Dalgarno model suggests that translation initiation in bacteria is regulated via base-pairing between ribosomal RNA (rRNA) and mRNA. We used novel computational analyses and modelling of 823 bacterial genomes coupled with experiments to demonstrate that rRNA-mRNA interactions are diverse and regulate all translation steps from pre-initiation to termination. Previous research has reported the significant influence of rRNA-mRNA interactions, mainly in the initiation phase of translation. The results reported in this paper suggest that, in addition to the rRNA-mRNA interactions near the start codon that trigger initiation in bacteria, rRNA-mRNA interactions affect all sub-stages of the translation process (pre-initiation, initiation, elongation, termination). As these interactions dictate translation efficiency, they serve as an evolutionary driving force for shaping transcripts in bacteria while considering trade-offs between the effects of different interactions across different transcript regions on translation efficacy and efficiency. We observed selection for strong interactions in regions where such interactions are likely to enhance initiation, regulate early elongation, and ensure translation termination fidelity. We discovered selection against strong interactions and for intermediate interactions in coding regions and presented evidence that these patterns maximize elongation efficiency while also enhancing initiation. These finding are relevant to all biomedical disciplines due to the centrality of the translation process and the effect of rRNA-mRNA interactions on transcript evolution.


Scutellariae radix extracts suppress ethanol-induced caspase-11 expression and cell death in N(2)a cells.
Scutellariae radix is a Chinese herbal medicine that has been used to treat disease conditions accompanying inflammation and oxidative stress. In the present study, we examined the effect of Scutellariae radix extracts during acute ethanol exposure in N(2)a neuroblastoma. The Scutellariae radix extracts effectively inhibited ethanol-induced apoptosis and caspase-3/-7 activation. Ethanol induced the expression of caspase-11 that has been known as a dual regulator of pathological apoptosis and inflammatory response. The ethanol-induced caspase-11 expression was suppressed by pretreatment of the Scutellariae radix extracts. Furthermore, the activation of caspase-3/-7 and apoptosis were significantly inhibited in caspase-11-/- mouse embryonic fibroblasts following ethanol treatment. These results suggest that caspase-11 has a regulatory role in ethanol-induced apoptosis, and the suppression of caspase-11 may be a mechanism by which Scutellariae radix exerts its cytoprotective effect.


Characterization of radioactive particles using non-destructive alpha spectrometry.
Spherical particles with known properties were used to demonstrate and test a novel software package known as AASIFIT, which is able to unfold complex alpha spectra. A unique feature of the program is that it uses simulated peak shapes in the fitting process. The experimental reference particles in the testing were artificially produced U particles of diameter 1.4microm and a nuclear bomb particle with a twenty-fold greater diameter, mainly composed of U and Pu dioxides. AASIFIT was used to determine the density of the U particles. In addition, the activities of (239+240)Pu and (241)Am were determined for the nuclear bomb particle and compared to earlier determinations in the literature. The results of this investigation demonstrated that the software can be used to estimate the properties of particles emitting alpha radiation. However, the composition and geometry of the investigated particles need to be known with good accuracy for reliable estimates. Furthermore, uncertainties in the stopping power data, especially for U and Pu, may have an influence on the results obtained from the software.


[Trichoteiromania].
The physical influences leading to traumatic hair injury may be the result of cosmetic treatments, may be accidental or self-inflicted. The most frequent cause of self-inflected hair loss is trichotillomania, in which the hair is plucked, while trichotemnomania, in which the hair is deliberately cut, is less frequent. Freyschmidt-Paul et al. proposed the term trichoteiromania for yet another type of artificial hair loss, which results from perpetual rubbing of the scalp with fracturing of the hair shafts. Four patients with trichoteiromania are further characterized on the basis of clinical, morphological and psychopathological criteria. In contrast to trichotillomania, trichoteiromania has no diagnostic histopathological features and has a normal trichogram. Traumatic changes to the hair shaft are more conspicuous, with splitting at the ends of the hairs, giving the impression of white tips. The underlying mental disorder varis among the patients, though scalp dysaesthesia, not explained through any specific dermatological disorder, is a common denominator in all cases. While trichotillomania is considered to be an obsessive-compulsive disorder, the underlying mental disorder in trichoteiromania represents a more heterogeneous group. Cooperation with the psychiatrist is indicated, as much as the management and prognosis of trichoteiromania will depend on recognition of the underlying mental disorder and its specific psychotherapeutic and pharmacological treatment.


Asthma, allergy, and sinopulmonary disease in pediatric condition falsification.
Reports of pediatric condition falsification (PCF) have noted, but not emphasized, exaggerated complaints of real and common illnesses. Among the most frequent chronic childhood illnesses are asthma, allergy, drug sensitivity, and ear and sinopulmonary infections. The most common pediatric surgery is the insertion of myringotomy tubes. A computer database of 104 PCF victims from 68 families spanning from 1974 to 1998 was searched for the frequency of these conditions. Outright falsification or extreme exaggeration of severity of asthma or allergies was noted in 52 children (50%), sinopulmonary infections in 50 (48%), and drug reactions or sensitivities in 30 (29%). Forty-five children (43%) had otolaryngologic surgery, including ear tubes. In all, 71 children (68%) had at least one of these conditions. Associated victim and perpetrator characteristics are described. Children with PCF are not only subjected to induced illnesses and excessive medical diagnostic and therapeutic efforts but also victimized b) the consequences of false and exaggerated complaints of common pediatric diseases.


The myoglobin of rodents Proechimys guairae (casiragua) and Mus musculus (house mouse).
The amino acid sequences of the myoglobins of two rodents, the casiragua and the house mouse, have been determined. The myoglobin of casiragua differs from that of viscacha (another hystricomorph) at 6 positions. Mouse myoglobin differs from that of mole-rat (another myomorph) at 17 positions, whereas casiragua and mouse differ at 22 positions. Mouse myoglobin possesses several features unique among all known myoglobins (Gly 31, Cys 66, Thr 74 and Glu 113) and one substitution unique among known mammalian myoglobins (Glu 53).


Towards objective evaluation of the skin aspect: principles and instrumentation.
The aim of this paper is to propose an objective procedure for the evaluation of the skin aspect. This work is based on light scattering phenomena and in-vivo measurements of the skin profile and of the skin Bi-directional Reflection Distribution Function (BRDF). We consider the basic mechanisms of light reflection and scattering by a surface to extract the key sur-face-parameters of aspect. It appears that the surface relief is determinant for the local surface orientation while the light scattering properties of the skin are responsible for the visibility of that skin relief. The first part presents the principles of skin-image formation on the retina and de-scribes the actual roles of the BRDF and of the skin relief. The second part is dedicated to experimental measurements on the skin in vivo. The 3D relief is reconstructed by a fringe projection method and numerical processing. The angular distribution of light reflected by the skin is also measured by means of a different set-up. The knowledge of both the skin relief obtained by 3D optical profilometry and the skin scattering behavior measured for regularly distributed set angle values, allows an objective aspect evaluation as well as a prediction of the skin images that an observer will receive. This paper presents both the principles and instrumentation elements suitable for the setting up of an objective evaluation procedure of the skin aspect.


Cytochrome P4501A1 polymorphism is associated with susceptibility to acute lymphoblastic leukemia in adult Mexican patients.
We studied the role of cytochrome P4501A1 (CYP1A1 Val/Val) genotypes in the etiology of acute lymphoblastic leukemia (ALL) in adult Mexican patients. Distributions of CYP1A1 Val/Val genotypes in peripheral blood DNA samples from 136 healthy controls and 136 adult patients with ALL were evaluated. There was an increased frequency of the CYP1A1 Val/Val genotype among ALL patients, showing a significant association between this genotype and the risk of developing ALL.


Laparoscopic liver surgery for everyone: the hybrid method.
Minimally invasive techniques have been described recently for liver resections. We have developed a surgical approach to liver resection that combines the benefits of minimally invasive surgery with the safety of open liver resection. We have applied this hybrid approach to selected cases, and we feel that it can be adopted by most hepatobiliary surgeons, even those with minimal or no laparoscopic experience. Briefly, this technique consists of laparoscopic mobilization of the target liver lobe, followed by standard open liver resection through the extraction site. The required incisions parallel those needed for hand-assisted laparoscopic liver resections. We have compared these hybrid procedures with contemporaneous laparoscopic, hand-assisted, and open liver resections at our institution and have found that they compare favorably with minimally invasive procedures. A wider utilization of this approach by both general and hepatobiliary surgeons will result in a more generalized acceptance of minimally invasive liver resection that ultimately will advance the field and benefit patients in need of liver surgery.


Generalized tetanus in an elderly patient: A case report.
Tetanus is a rare disease caused by Clostridium tetani causing painful muscle spasms and respiratory failure. A patient from a rural part of the country presented with a nonhealing and increasingly painful penetrating wound. The patient had a purulent wound and later developed risus sardonicus and muscle spasms of tetanus and his blood culture grew the bacteria. His condition was later complicated by respiratory failure, sepsis, and multiorgan failure. He was managed in the ICU with Intravenous antibiotics, respiratory support with endotracheal Intubation and mechanical ventilation, Intravenous Immunoglobin, and multiple organ support. The patient was taken off the ICU by the family for financial reasons and ultimately succumbed to the illness. Tetanus, is a rare vaccine-preventable illness that is underreported. Spasms control and organ support is still the mainstay of treatment. Strict clinical vigilance is important for the early diagnosis and management of tetanus.


Frequency and implications of resetting and entrainment with right atrial stimulation in atrial flutter.
Thirty-three patients (24 with typical and 9 with atypical flutter-wave morphology) were studied to evaluate the incidence and implications of resetting and entrainment of atrial flutter with right atrial stimulation. Resetting with single extrastimulus was present in 23 cases (group A) and absent in 10 (group B). Most cases of reset flutter were typical (20 of 23). Fixed fusion indicative of entrainment was observed in all 29 cases with pacing trains. Groups A and B did not differ significantly in flutter cycle length (230 +/- 20 vs 223 +/- 19 ms), atrial functional refractory period (165 +/- 18 vs 167 +/- 22 ms) or longest paced cycle length producing entrainment (213 +/- 19 vs 210 +/- 19 ms). In contrast, the return cycle after the longest paced cycle length producing entrainment was significantly shorter in group A (228 +/- 27 vs 284 +/- 56 ms; p = 0.001). The return cycle in group A was virtually identical to the flutter cycle length, whereas in group B it was greater (p = 0.002 compared with group A). Resetting was more frequent in typical than atypical flutter (20 of 24 vs 3 of 9; p = 0.01). Both typical and atypical flutter can be transiently entrained by right atrial pacing. Lack of resetting and longer return cycle, suggesting a longer conduction time between the reentrant circuit and the stimulation site, were mostly observed in atypical flutter. The data suggest a different location for both types of flutter, and may have implications for ablation techniques. A more cautious approach, with more extensive mapping, appears appropriate for ablation attempts of atypical flutter.


Association between sense of coherence and oral health-related quality of life among toddlers.
To assess the relationship between sense of coherence (SOC) and oral health-related quality of life (OHRQoL) among children aged one to three years. A cross-sectional study was conducted with 276 mother-child pairs randomly selected from the city of Diamantina, Brazil. Information was obtained on socio-demographic factors. The short version of Antonovsky's sense of coherence scale (SOC 13) and the Early Childhood Oral Health Impact Scale (ECOHIS) were administered. The children were examined for dental caries. Statistical analysis involved descriptive statistics, the calculation of Spearman's correlation coefficients and adjusted Poisson regression models. SOC was significantly associated with the child's OHRQoL in the multivariate analysis. Children of mothers with high SOC (PR 0.96; 95%CI 0.93,0.98; p=0.045) had a lower prevalence of a negative impact on OHRQoL. Children with severe dental caries had a greater prevalence of a negative impact on OHRQoL (PR 2.53; 95%CI 1.77,3.62; p⟨0.001). Maternal SOC could be a psychosocial determinant of the OHRQoL of children aged one to three years. Severe dental caries was associated with poorer quality of life.


Impact of inter-subunit interactions on the dimeric arginine kinase activity and structural stability.
Arginine kinase (AK) is a key enzyme for cellular energy metabolism, catalyzing the reversible phosphoryl transfer from phosphoarginine to ADP in invertebrates. In this study, the inter-subunit hydrogen bonds between the Q53 and D200 and between D57 and D200 were disrupted to explore their roles in the activity and structural stability of Stichopus japonicus (S. japonicus) AK. Mutating Q53 and/or D57 to alanine (A) can cause pronounced loss of activity and substrate synergism, and cause distinct conformational changes. Spectroscopic experiments indicated that mutations destroying the inter-subunit hydrogen bonds impaired the structure of dimer AK, and resulted in a partially unfolded state. The inability to fold to the functional compact state made the mutants prone to be inactivated and aggregate under environmental stresses. Restoring hydrogen bonds in Q53E and D57E mutants could rescue the loss of activity and substrate synergism, and conformational changes. All those results suggested that the inter-subunit interactions played a key role in keeping the activity, substrate synergism and structural stability of dimer AK. The result herein may provide a clue in understanding the folding and self-assembly processes of oligomeric proteins.


Systematic tracing of nitrate sources in a complex river catchment: An integrated approach using stable isotopes and hydrological models.
Quantitative estimation for tracking the transport of various nitrate sources is required to effectively manage nitrate loading in complex river systems. In this study, we validated an integrated framework using field isotopic data (δ15NNO3 and δ18ONO3) of nitrates and hydrological modeling (hydrological simulation program FORTRAN; HSPF) to determine anthropogenic nitrate flux among different land-use types within a watershed. Nitrate isotopic compositions showed different ranges among four land-use types (4.9 to 15.5‰ for δ15NNO3, -4.9 to 12.1‰ for δ18ONO3), reflecting the different nitrate sources (sewage, synthetic fertilizer, effluent and soil) within watersheds. Based on the integration of HSPF modeling, we also found that total nitrate loads might be partially controlled by hydrological conditions such as water discharge (12,040.3-22,793.2 L/s) from upstream to downstream. Among the nitrate sources, the sewage transport showed unique enhancement near urban boundaries, along with an increase in total nitrate load (>193.5 NO3-N g/s km2) in downstream areas. In addition, the isotopic- and model-based nitrate fluxes showed good correlation for urban sources (R2=0.73, p < 0.05) but poor correlations for agriculture-dominated land use (R2=0.13, p > 0.05), reflecting the potential influence of surface runoff and ground infiltration into the watershed. Consequently, this research provided useful information to establish nitrogen management policy controlling point and non-point nitrate source loads in various land-use types for the restoration of water quality and aquatic ecosystem in the complex river system. Considering the recent increase in human activities near aquatic environments, this framework would be effective for individually estimating the quantitative contributions of anthropogenic nitrate sources transported along river-coastal systems.


Acute coronary syndrome in young males after a prolonged stay at high altitude.
The Indian population is predisposed to acute coronary syndrome at a younger age, but very few cases are reported at high altitude. Acute coronary syndrome is frequently associated with multiple cardiovascular risk factors. During management of seven young patients with acute coronary syndrome, it was found that none of them had conventional cardiovascular risk factors including recent physical exertion. It is a known fact that the risk of vascular thrombosis increases by 30 times in Indian soldiers after a long stay at high altitude. Therefore, it is necessary to carry out the tests for procoagulant markers to know whether the acute coronary syndrome was because of the prothrombotic state, and if yes, was high altitude responsible for the procoagulant state or whether the person per se had a procoagulant syndrome. With the absence of these tests at hospitals at high-altitude areas, it becomes difficult to ascertain the exact cause of acute coronary syndrome. This study highlights the importance of aggressively testing for procoagulant markers in young patients presenting with chest pain at high altitude, even in the absence of traditional risk factors.


Modified combined disc test (mCDT): a novel, labor-saving and 4 times cheaper method to differentiate Class A, B and D carbapenemase-producing Klebsiella species.
Carbapenemase-producing organisms have been an immense public health problem in recent years. Combined disc test (CDT) is a simple and widely used phenotypic method for carbapenemase detection, especially in developing countries. This study evaluates the performance of modified combined disc test (mCDT), a novel and 4 times cheaper method than CDT. In total, 572 (15.5%) Klebsiella spp. including 81 (14.2%) carbapenemase producers were isolated from 3993 clinical samples. Both mCDT and CDT showed similar sensitivity, specificity, positive predictive value, and negative predictive value for the differentiation of Class A, B, and D carbapenemase-producing Klebsiella spp.


Endosomal Sequestration of TLR4 Antibody Induces Myeloid-Derived Suppressor Cells and Reverses Acute Type 1 Diabetes.
We previously showed that treating NOD mice with an agonistic monoclonal anti-TLR4/MD2 antibody (TLR4-Ab) reversed acute type 1 diabetes (T1D). Here, we show that TLR4-Ab reverses T1D by induction of myeloid-derived suppressor cells (MDSCs). Unbiased gene expression analysis after TLR4-Ab treatment demonstrated upregulation of genes associated with CD11b+Ly6G+ myeloid cells and downregulation of T-cell genes. Further RNA sequencing of purified, TLR4-Ab-treated CD11b+ cells showed significant upregulation of genes associated with bone marrow-derived CD11b+ cells and innate immune system genes. TLR4-Ab significantly increased percentages and numbers of CD11b+ cells. TLR4-Ab-induced CD11b+ cells, derived ex vivo from TLR4-Ab-treated mice, suppress T cells, and TLR4-Ab-conditioned bone marrow cells suppress acute T1D when transferred into acutely diabetic mice. Thus, the TLR4-Ab-induced CD11b+ cells, by the currently accepted definition, are MDSCs able to reverse T1D. To understand the TLR4-Ab mechanism, we compared TLR4-Ab with TLR4 agonist lipopolysaccharide (LPS), which cannot reverse T1D. TLR4-Ab remains sequestered at least 48 times longer than LPS within early endosomes, alters TLR4 signaling, and downregulates inflammatory genes and proteins, including nuclear factor-κB. TLR4-Ab in the endosome, therefore, induces a sustained, attenuated inflammatory response, providing an ideal "second signal" for the activation/maturation of MDSCs that can reverse acute T1D.


SnapShot: Tumor evolution.
Understanding how tumors grow and evolve over time is crucial to help shed light on the underlying reasons why treatments fail and tumors metastasize. This SnapShot provides a brief introduction into the main concepts of tumor evolution. To view this SnapShot, open or download the PDF.


Elevated lactate dehydrogenase (LDH) can be a marker of immune suppression in cancer: Interplay between hematologic and solid neoplastic clones and their microenvironments.
Metabolism of neoplastic cells is shifted toward high glucose uptake and enhanced lactate production. Lactate dehydrogenase (LDH), which is comprised of two major subunits, LDH-A and LDH-B, reversibly catalyzes the conversion of pyruvate to lactate or lactate to pyruvate. LDH-A has a higher affinity for pyruvate and is a key enzyme in the glycolytic pathway. Elevated LDH is a negative prognostic biomarker not only because it is a key enzyme involved in cancer metabolism, but also because it allows neoplastic cells to suppress and evade the immune system by altering the tumor microenvironment. LDH-A alters the tumor microenvironment via increased production of lactate. This leads to enhancement of immune-suppressive cells, such as myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and dendritic cells (DCs); and inhibition of cytolytic cells, such as natural killer (NK) cells and cytotoxic T-lymphocytes (CTLs). By promoting immune-suppression in the tumor microenvironment, LDH-A is able to promote resistance to chemo/radio/targeted therapy. Here we discuss the evidence that LDH is both a metabolic and an immune surveillance prognostic biomarker and its elevation is harbinger of negative outcome in both solid and hematologic neoplasms.


Purification of mitochondrial DNA from total cellular DNA of small tissue samples.
A method is presented for the isolation of highly purified mitochondrial (mt)DNA from a crude DNA extract, making use of the different mobilities of covalently closed circular mtDNA vs. endonuclease-digested nuclear DNA in agarose gels. The preparation is virtually free of any contaminating linear DNA, as judged from its electron microscopic appearance, and can be used for further procedures such as polymerase chain reaction (PCR). Since isolation of mitochondria is not a prerequisite for this method, it can be applied to tissue samples in the mg range. In principle, the method can be applied to every eukaryotic species, provided a molecular hybridization probe is available which permits the position of mtDNA to be located in an agarose gel. This probe can be a cDNA, a DNA fragment generated by PCR, or mtDNA itself, if only the approximate size of the genome is known.


Calcium fluxes in internally dialyzed giant barnacle muscle fibers.
Calcium-45 fluxes have been examined in isolated giant barnacle muscle fibers subjected to internal solute control by means of "internal dialysis". The 45Ca efflux was dependent upon the concentrations of both total and ionized internal Ca (Ca2+ buffered with EGTA). With a total Ca concentration of 2.0 mM and a 1:2 Ca/EGTA ratio (nominal [Ca2+]i =0.13 muM), the Ca efflux averaged 1.2 pmoles/cm2 sec. Under identical conditions, the mean Ca influx was only 0.36 pmoles/cm2 sec. The Ca efflux may not be attributed to leak of the CaEGTA complex, since a 2.5-fold increase in the EGTA concentration (nominal [Ca2+]i=0.032 muM) reduced the 45Ca efflux by one-third. Furthermore, when EDTA was used to buffer the internal Ca concentration (in the absence of internal Mg), the steady efflux of 14C-EDTA was only about 10% of the 45Ca efflux (in parallel experiments). The timecourse of the 45Ca fluxes also appeared anomalous in the 45Ca influx reached a steady level much more rapidly than 45Ca efflux in fibers of comparable diameters. If the muscle fibers are treated as right circular cylinders, these data imply that the apparent diffusion coefficient for inwardly-moving Ca is much larger than for outwardly-moving Ca. In contrast to Ca efflux, the outward diffusion of 22Na, 14C-EDTA and 3H2O appears to be limited primarily by the permeability of the dialysis tube wall. Some, but not all, of the anomalous behavior of the Ca fluxes can be reconciled if the deep, branched infoldings of the barnacle muscle surface membrane are taken into account.


Cervicofacial flap for reconstruction of squamous cell carcinoma on the right cheek: A case report.
Reconstruction of the cheek to the lower eyelid can be performed with the use of a cervicofacial flap in patients that may not otherwise be able to sustain a long surgical procedure. In addition, the cervicofacial flap is superior in terms of color and texture match.


Hillslope terracing effects on the spatial variability of plant development as assessed by NDVI in vineyards of the Priorat region (NE Spain).
The availability of heavy machinery and the vineyard restructuring and conversion plans of the European Union Common Agricultural Policy (Commission Regulation EC no. 1227/2000 of 31 May 2000) have encouraged the restructuring of many vineyards on hillslopes of Mediterranean Europe, through the creation of terraces to favor the mechanization of agricultural work. Terrace construction requires cutting and filling operations that create soil spatial variability, which affects soil properties and plant development. In the present paper, we study the effects of hillslope terracing on the spatial variability of the normalized difference vegetation index (NDVI) in fields of the Priorat region (NE Spain) during 2004, 2005, and 2006. This index was computed from high-resolution remote sensing data (Quickbird-2). Detailed digital terrain models before and after terrace construction were used to assess the earth movements. The results indicate that terracing by heavy machinery induced high variability on the NDVI values over the years, showing significant differences as effect of the cut and fill operations.


Mathematical modeling and process analytical technology for continuous chromatography of biopharmaceutical products.
Chromatography is a widely used separation method that is inherently a batch operation. However, the demand for higher productivity and lower cost and labor has prompted industries such as the petrochemical and food industries to transition from batch to continuous chromatography. Growing market competition in the biopharmaceutical industry and the rise of novel biotherapeutics modalities have brought about promising continuous chromatography methods as well as next-generation tools to enable continuous operation in bioprocessing. While these continuous chromatography methods outperform their batch counterpart, their implementation presents challenges due to their greater complexity. This review discusses two key technologies that are essential for the implementation of continuous chromatography: mathematical modeling and novel process analytical technologies. Mechanistic-based models not only aid in process development and optimization but also allow for greater process control and automation.


First-in-Human Dose-Escalation Study of Cyclin-Dependent Kinase 9 Inhibitor VIP152 in Patients with Advanced Malignancies Shows Early Signs of Clinical Efficacy.
To report on the first-in-human phase I study of VIP152 (NCT02635672), a potent and highly selective cyclin-dependent kinase 9 (CDK9) inhibitor. Adults with solid tumors or aggressive non-Hodgkin lymphoma who were refractory to or had exhausted all available therapies received VIP152 monotherapy as a 30-minute intravenous, once-weekly infusion, as escalating doses (5, 10, 15, 22.5, or 30 mg in 21-day cycles) until the MTD was determined. Thirty-seven patients received ≥ 1 VIP152 dose, with 30 mg identified as the MTD based on dose-limiting toxicity of grade 3/4 neutropenia. The most common adverse events were nausea and vomiting (75.7% and 56.8%, respectively), all of grade 1/2 severity. Of the most common events, grade 3/4 events occurring in > 1 patient were neutropenia (22%), anemia (11%), abdominal pain (8%), increased alkaline phosphatase (8%), and hyponatremia (8%). Day 1 exposure for the MTD exceeded the predicted minimum therapeutic exposure and reproducibly achieved maximal pathway modulation; no accumulation occurred after multiple doses. Seven of 30 patients with solid tumors had stable disease (including 9.5 and 16.8 months in individual patients with pancreatic cancer and salivary gland cancer, respectively), and 2 of 7 patients with high-grade B-cell lymphoma with MYC and BCL2/BCL6 translocations (HGL) achieved durable complete metabolic remission (ongoing at study discontinuation, after 3.7 and 2.3 years of treatment). VIP152 monotherapy, administered intravenously once weekly, demonstrated a favorable safety profile and evidence of clinical benefit in patients with advanced HGL and solid tumors.


High-expression and characterization of a novel serine protease from Ornithinibacillus caprae L9T with eco-friendly applications.
In the current work, a novel thermophilic serine protease gene (P3862) from Ornithinibacillus caprae L9T was functionally expressed in Bacillus subtilis SCK6. The monomeric enzyme of about 29 kDa was purified to homogeneity with 43.91% of recovery and 2.81-folds of purification. Characterization of the purified protease revealed the optimum activity at pH 7 and 65 °C. The protease exhibited excellent activity and stability in the presence of Na+, Mg2+, Ca2+, ethanediol, n-hexane, Tween-20, Tween-80 and Triton X-100. P3862 displayed favorable caseinolytic activity, moderate keratinolytic activity but no collagenolytic activity. Besides, the homology model of P3862 possessed a globular configuration and characteristic of α/β hydrolase fold, and displayed stable interactions with casein, glycoprotein and keratin rather than collagen. Moreover, the crude enzyme could completely dehair goatskin within 6 h, resulting in decrease in BOD5, COD and TSS loads by 72.86, 74.07, and 73.79%, respectively, as compared with Na2S treatment. Biocatalytic applications revealed that it could effectively remove egg-stains from fabrics at 37 °C for 30 min with low supplementation (300 U/mL), and was able to degrade the feathers of duck and chicken. Overall, these outstanding properties make P3862 valuable in the development of environmentally friendly biotechnologies .


Diagnostic performance of HE4 and ROMA among Chinese women.
Human epididymis protein 4 (HE4) has been suggested as a new biomarker for the detection of ovarian cancer. Because there are few reports on HE4 in terms of ovarian cancer diagnosis in the Chinese population, we evaluated the diagnostic performances of HE4 and the ROMA in Chinese women with pelvic masses. The serum concentrations of CA 125 and HE4 in 318 Chinese women with pelvic masses (39 of which were ovarian cancers) were determined. For the discrimination of benign gynecological diseases from ovarian cancer, the sensitivity and specificity values were 87.2% and 75.8% for the ROMA and 51.3% and 97.3% for HE4. The ROMA also showed higher sensitivity than HE4 in both the early and advanced stages. In the ROC curve analysis, the AUC values for ROMA, HE4 and CA 125 were 0.927, 0.907 and 0.785, respectively. As a new tumor marker, HE4 shows high specificity and efficacy in the Chinese population, while the ROMA that combines HE4 and CA 125 shows high sensitivity and a high Youden's index. These markers should be extended to China since they have good diagnostic performances.


Group 2 innate lymphoid cells resolve neuroinflammation following cerebral ischaemia.
Acute brain ischaemia elicits pronounced inflammation, which aggravates neural injury. However, the mechanisms governing the resolution of acute neuroinflammation remain poorly understood. In contrast to regulatory T and B cells, group 2 innate lymphoid cells (ILC2s) are immunoregulatory cells that can be swiftly mobilised without antigen presentation; whether and how these ILC2s participate in central nervous system inflammation following brain ischaemia is still unknown. Leveraging brain tissues from patients who had an ischaemic stroke and a mouse model of focal ischaemia, we characterised the presence and cytokine release of brain-infiltrating ILC2s. The impact of ILC2s on neural injury was evaluated through antibody depletion and ILC2 adoptive transfer experiments. Using Rag2-/-γc-/- mice receiving passive transfer of IL-4-/- ILC2s, we further assessed the contribution of interleukin (IL)-4, produced by ILC2s, in ischaemic brain injury. We demonstrate that ILC2s accumulate in the areas surrounding the infarct in brain tissues of patients with cerebral ischaemia, as well as in mice subjected to focal cerebral ischaemia. Oligodendrocytes were a major source of IL-33, which contributed to ILC2s mobilisation. Adoptive transfer and expansion of ILC2s reduced brain infarction. Importantly, brain-infiltrating ILC2s reduced the magnitude of stroke injury severity through the production of IL-4. Our findings revealed that brain ischaemia mobilises ILC2s to curb neuroinflammation and brain injury, expanding the current understanding of inflammatory networks following stroke.


Periorbital edema as the presenting sign of dermatomyositis.
Periorbital edema can occur in dermatomyositis, which is characterized by symmetric macular erythema, Gottron's papules, Gottron's sign, periungual telangiectasia, heliotrope rash, and poikilodermatous macules on the shoulders, arms, or upper back (shawl sign). We report the case of an 81-year-old man with dramatic periorbital edema. It was not until he was hospitalized with dysphagia 6 months after developing the edema that the diagnosis of dermatomyositis was considered. Laboratory tests, skin biopsy, and electromyography resulted in a diagnosis of dermatomyositis. Periorbital edema may appear as the presenting cutaneous manifestation of dermatomyositis.


A morphometric and morphological analysis of the foramen magnum, hypoglossal canal and occipital condyles in a select South African population.
The foramen magnum is a centralised structure found at the base of the skull. This orifice is a passageway that allows secondary structures, such as the medulla oblongata and meninges, to pass through. The occipital condyles is a small structure on either side of the foramen magnum, forming the craniovertebral joint. The hypoglossal canal is an orifice located on the occipital canal, providing a passageway for hypoglossal nerves. The study aimed to document the morphology and morphometry of the foramen magnum, occipital condyles and hypoglossal canals within a South African population. Fifty skulls (n=50) were randomly selected from the Department of Clinical Anatomy, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal. This study investigated the morphological and morphometric parameters of the foramen magnum, occipital condyles and hypoglossal canal. The morphometric parameters were measured using a digital Vernier calliper. The data was statistically analysed using SPSS, and a p-value of <0.05 was deemed statistically significant. The mean length and width of the foramen magnum was found to be 35.19mm and 27.77mm, respectively. The mean index of the foramen magnum was 1.3, which indicated that the foramen magnum was predominantly oval-shaped within the selected sample. The occipital condyles have a mean length and width of 21.73mm and 12.87mm, respectively. Furthermore, the most prevalent shape of the occipital condyles was oval. The mean length and width of the hypoglossal canals were 5.14mm and 3.87mm, respectively. While the most prevalent shape of the hypoglossal canal was oval and round on the right and left sides, respectively. The findings of this study may assist in reducing the risk of injury and mortalities during trans-condylar approach procedures.


Role of Junction-Mediating and Regulatory Protein in the Pathogenesis of Glucocorticoid-Induced Endothelial Cell Lesions.
Nontraumatic osteonecrosis of the femoral head (ONFH) is one of the most common diseases in orthopaedics. The damage to vascular endothelial (VE) cells caused by glucocorticoids (GC) has been reported as a possible mechanism of pathogenesis for ONFH. Junction-mediating and regulatory protein (JMY), originally identified as a p53 coactivator, plays prominent roles in the DNA damage response and in cell motility. This study aimed to discover the role of JMY in the pathogenesis of GC-induced endothelial cell lesions. High-throughput RNA sequencing was performed to identify the differentially expressed genes between GC-treated human umbilical vein endothelial cells (HUVEC) and control cells. JMY knockdown and overexpressing HUVEC lines were treated with GC. Cell proliferation was examined with a survival cell count assay (Cell Counting Kit-8, CCK-8); cell apoptosis was measured by flow cytometry; a scarification assay was used to detect the capability of cell migration; a Transwell chamber assay was done to detect the cell motility . Differential expression of cell protein was detected by western blot. A total of 1561 differential genes were obtained through transcription sequencing, of which 789 mRNA were upregulated and 772 mRNA were downregulated in the GC-treated HUVEC compared with the control cells. CCK-8 assay results showed that: without GC treatment, overexpression or knockdown of JMY did not affect the proliferation activity of HUVEC. In the presence of GC treatment, the proliferation activity of HUVEC in the JMY knockdown group was significantly higher than that in the control group (P < 0.01). The proliferation activity of HUVEC in the overexpression JMY group was significantly lower than that in the control group (P < 0.01). The results of flow cytometry showed that without GC treatment, overexpression or knockdown of JMY did not affect the apoptosis proportion of HUVEC. With GC treatment, the apoptosis proportion of HUVEC in the JMY knockdown group was significantly lower than that in the control group (P < 0.01), and the apoptosis proportion of HUVEC in the overexpression JMY group was significantly higher than that in the control group (P < 0.01). Western blot results showed that with GC treatment, the JMY expression level of HUVEC increased with the reaction time. Moreover, the distribution of JMY was mainly concentrated in the nucleus. The expression level of Bax also increased with the reaction time. With GC treatment, overexpression of JMY could significantly increase the expression of Bax in HUVEC. JMY knockdown could reduce the expression of Bax in HUVEC. In the absence of GC treatment, HUVEC overexpression or knockdown of JMY did not affect the expression of Bax. The results of scarification and Transwell chamber assays showed that: without GC treatment, JMY knockdown could significantly decrease the cell motility and increase the expression level of VE-cadherin in HUVEC; with GC treatment, JMY knockdown in HUVEC had lower cell motility compared with the control group (P < 0.01). Glucocorticoids can induce the HUVEC apoptosis, and reduce its proliferation, cell motility. Our results mainly confirmed the role of JMY in the pathogenesis of GC-inducing lesions in HUVEC. GC act on HUVEC, inducing cell damage. Following the event of cell damage, JMY levels upregulate in the nucleus to induce transcription of Bax, triggering apoptosis. JMY can also regulate HUVEC motility via its regulation of VE-cadherin levels.


Riding the (mono)rails: the structure of catenated DNA-tracking proteins.
New evidence suggests that the 'sliding clamp' processivity factors of DNA polymerases can carry a variety of protein factors along the DNA 'track'. Recent information on the structure of these factors sheds light on how they slide on DNA and why they confer processivity.


Fura-2 diffusion and its use as an indicator of transient free calcium changes in single striated muscle cells.
Two questions bearing on the use of fura-2 to measure transient changes in intracellular Ca2+ concentration have been addressed. To investigate fura-2 intracellular binding, the amounts of fura-2 and [14C]glycine in Balanus nubilus myofibrillar bundles after loading were determined and their intracellular apparent diffusion constants measured. No significant fura-2 immobilisation occurs under the conditions used. The apparent diffusion constant for fura-2 in aqueous solution was determined. The relationship between half-time for relaxation of force and fura-2 fluorescence transients, and intracellular fura-2 concentration, in voltage-clamped single muscle fibres was examined. Significant buffering of the Ca2+ transient occurred at fura-2 concentrations above approximately 6 microM.


Neuronal hypertrophy in the human supraoptic and paraventricular nucleus in aging and Alzheimer's disease.
In the literature, activation of the hypothalamo-neurohypophyseal system (HNS) in normal aging has been demonstrated in rat and human. This activation might be secondary to an age-related decline in vasopressin binding sites in the kidney, or to cell loss in the supraoptic (SON) and paraventricular nuclei (PVN) and/or to an age-related decline in noradrenergic (NA) innervation of the hypothalamus. This study shows neuronal hypertrophy in SON and PVN in normal aging and an additional hypertrophy in Alzheimer's disease. No cell loss could be demonstrated in both conditions.


Haemoglobin C and haemoglobin O Arab-thalassaemia in families of Greek origin.
A case of Haemoglobin C trait and a family with Haemoglobin O Arab thalassaemia from Greece are described. Both Haemoglobin C and Haemoglobin O Arab were identified by peptide analysis.


Coordination Properties of Hydroxyisophthalic Acids: Topological Correlations, Synthesis, Structural Analysis, and Properties of New Complexes.
Hydroxyisophthalic acids are valuable polytopic ligands for the design of functional materials based on coordination polymers due to the variety of charges and coordination modes they possess. Herein, we describe the synthesis, thermal stability, nonlinear optical (NLO) and spectroscopic properties of five novel coordination compounds, [K2 L(H2 O)2 ], [MgL(H2 O)2 ] ⋅ 3H2 O, [CaL(H2 O)3 ], [SrL(H2 O)3 ] ⋅ H2 O, [BaL(H2 O)(H2 O)5 ], and one salt, (NH4 )2 L ⋅ 2H2 O, with 4,5,6-trihydroxyisophthalic acid (H2 L), which has not been tested in assembling crystalline coordination networks before. The peculiarities of the structural organization of the compounds were analyzed and compared with those for other hydroxyisophthalates. The coordination properties of hydroxyisophthalic acids were studied from the topological point of view, and a comparative topological analysis of coordination and H-bonded networks was performed. Structural correlations revealed in this study could be useful for the design of hydroxyisophthalate-based coordination networks, including porous metal-organic frameworks, proton conductors, and NLO materials.


PON1 Q192R polymorphism (rs662) is associated with childhood embryonal tumors.
Genetic susceptibility and environment exposures are associated risk factors in carcinogenesis. Gene polymorphisms that decrease the activity of detoxifying carcinogen substances may modify the effect of exposures. We investigated whether the polymorphisms PON1 rs662 (Q192R), and PON1 rs854560 (L55M) would be associated with embryonal tumors in Brazilian children. Blood samples from 163 children with embryonal tumors and 342 as control group were genotyped by TaqMAN real-time PCR assays. Logistic regression was used to evaluate the association between the polymorphisms of cases and controls groups, adjusted by skin color and age strata. When all tumors were taken together, the presence of the PON1 rs662 (Q192R) variant genotype (RR) was associated with an increased risk of developing embryonal tumors (OR = 2.80, 95 % CI 1.12-7.02). The presence of at least one variant PON1 rs662 R allele increased the risk of developing Wilms´ Tumor although without statistical power. However, it was observed a significant association of PON1 rs662 (Q192R) variant genotype (RR) with retinoblastoma (OR = 4.08, 95 % CI 1.13-14.97), whereas the PON1 rs854560 (L55M) polymorphism was not associated with any tumor. These results indicate that PON1 polymorphisms may have an influence on the risk of developing embryonal tumors.


Trypanosoma cruzi: antiprotozoal activity of parthenolide obtained from Tanacetum parthenium (L.) Schultz Bip. (Asteraceae, Compositae) against epimastigote and amastigote forms.
This study reports the activity of crude extracts, fractions and parthenolide (pure compound) obtained from Tanacetum parthenium against two forms of the parasite Trypanosoma cruzi. Feverfew is a traditional herbal medicine that has been used for the treatment of migraine, fever and arthritis. Activity against epimastigote forms was observed for crude extracts, fractions and parthenolide, and a progressive increase in the antitrypanosomal effect was observed in the course of the purification process. The pure compound showed IC50/96h and IC90/96h of 0.5 microg/ml and 1.25 microg/ml, respectively. The cytotoxic effect of parthenolide in LLMCK2 cells was 3.2 microg/ml (CC50/96h) and the selectivity index was 6.4. No hemolysis was detected for the pure compound. The internalization index of T. cruzi in LLMCK2 cells was reduced almost 51% at the concentration of 2 microg/ml of parthenolide, and 96.6% at 4 microg/ml. Scanning and transmission electron microscopy permitted observation of morphological modifications and ultrastructural alterations.


VEPH1 expression decreases vascularisation in ovarian cancer xenografts and inhibits VEGFA and IL8 expression through inhibition of AKT activation.
VEPH1 is amplified in several cancers including ovarian but its impact on tumour progression is unknown. Previous work has shown that VEPH1 inhibits TGFβ signalling while its Drosophila ortholog increases tissue growth, raising the possibility that VEPH1 could impact tumour growth or progression. A CRISPR approach was used to disrupt VEPH1 expression in ovarian cancer ES-2 cells, while VEPH1-negative SKOV3 cells were stably transfected with VEPH1 cDNA. The impact of altered VEPH1 expression was assessed using in vitro and in vivo assays and mechanistic studies were performed in vitro. VEPH1 expression in SKOV3 cells resulted in a reduced tumour growth rate associated with increased necrotic area, and decreased microvessel density and VEGF-A levels relative to tumours formed by mock-transfected cells. VEPH1 expression also decreased VEGFA and IL8 expression in SKOV3 cells and was associated with decreased activated AKT levels. These effects were not observed in ES-2 cells, which bear a BRAFV600E activating mutation that leads to constitutively increased IL8 and VEGFA expression. VEPH1 expression in SKOV3 ovarian cancer cells inhibits AKT activation to decrease VEGFA and IL8 expression, which leads to decreased tumour vascularisation and progression.


[Purple urine bag syndrome (PUBS): about two cases at the Regional University Hospital Center (CHUR) of Ouahigouya].
Purple urine bag syndrome (PUBS) is an uncommon complication of urinary tract infection. It mainly affects elderly patients with constipation, chronic urinary catheter and prolonged bed rest. Several bacteria belonging to two different groups, the group converting indoxyl urinary sulphate into indoxyl and the group alkalizing urine by the production of urease, are associated with it. We here report two cases of young patients aged 30 and 16 years, living in Burkina Faso, with uremic encephalopathy associated with severe infection and cloudy urine with purple urine bag. Unlike cases reported in the literature, our cases occurred two and four days after urinary catheterization and in young patients without constipation. Despite early antibiotic therapy, outcome was unfavorable in one patient.


[Splenogonadal fusion].
The splenogonadal fusion is a rare but benign anomaly. The diagnosis is usually given at operation or histologically after operation. In about 50% of the patients who undergo surgery for scrotal tumor, an unnecessary orchidectomy is performed due to clinical unawareness of this rare condition. A case of splenogonadal fusion belonging to the continuous type is presented to illustrate problems of this anomaly and point out the importance of intraoperative microscopic sections.


Visual quality assessment in patients with orange-tinted blue light-filtering and clear ultraviolet light-filtering intraocular lenses.
To evaluate potential differences in the quality of vision after implantation of a blue light-filtering intraocular lens (IOL) and an ultraviolet (UV) light-filtering IOL. Department of Ophthalmology, Ruhr-University, Bochum, Germany. Prospective randomized cohort study. Patients with age-related cataract had bilateral standardized small-incision Kelman phacoemulsification-based cataract surgery with implantation of a blue light-filtering IOL (Oculaid PC 440Y Orange Series) in 1 eye and a UV light-filtering IOL (Oculaid PC 430 Elite Series) in the other eye. Outcome measures included scotopic and photopic corrected distance visual acuity (CDVA) and photopic uncorrected distance visual acuity (UDVA), color discrimination, and contrast sensitivity with and without glare. A questionnaire was used to assess patient satisfaction. Postoperative follow-up visits were scheduled at 1, 3, and 6 months. Twenty-two patients (44 eyes) completed the study. There were no statistically significant differences in UDVA, CDVA, or contrast sensitivity with or without glare between the 2 IOL groups. Color discrimination was significantly decreased in eyes with blue light-filtering IOLs compared with UV light-filtering IOLs, except along the red-green axis (P=.118). No subjective differences in color or light perception were found. Both IOL types provided similar postoperative visual function except color perception, which was slightly better in eyes with a clear IOL. Although differences were not clinically significant, information about potential disturbances in color vision might be provided before implanting an orange blue light-filtering IOL. No author has a financial or proprietary interest in any material or method mentioned.


Why do children and adolescents with epilepsy disclose or not disclose their condition to their friends?
A diagnosis of epilepsy substantially influences the lives of affected children and adolescents, and concealing the diagnosis can generate additional stress. However, little is known about whether children and adolescents communicate their diagnosis to their friends. We performed a survey at two German university hospitals. Epilepsy patients aged 6-18 years were asked why they did or did not disclose their condition to their friends. A total of 101 patients (44 female, 57 male) were interviewed. Twenty-one (21%) informed all their friends about their epilepsy, 63 (62%) informed only certain friends, and 3 (3%) did not specify. Fourteen (14%) did not inform any friends. Their reasons for informing their friends were trust in friends (47/87; 54%); questions from friends, e.g., about missed school days (29/87; 33%); a wish for friends to be informed in case of an emergency (15/87; 17%); and a desire to live openly with the condition (8/87; 9%). The reasons for not informing friends were fear of stigmatization/shame (4/14; 29%), discouragement from parents (3/14; 21%), and a wish for confidentiality (3/14; 21%).Conclusion: Most children and adolescents inform their friends about their epilepsy. Fear of stigmatization is the main reason for not informing friends about this condition. What is Known • An epilepsy diagnosis is a life-changing event for affected children and adolescents. • Having to conceal the diagnosis can be very stressful. What is New • Most pediatric epilepsy patients informed at least some close friends about their diagnosis motivated by trust in friends; questions from friends, e.g., about missed school days; and a wish for friends to be informed in case of an emergency. • Fear of stigmatization/shame, discouragement from parents, and a wish for confidentiality were the motivations for concealing the disease.


Prolonged administration of maraviroc reactivates latent HIV in vivo but it does not prevent antiretroviral-free viral rebound.
Human immunodeficiency virus (HIV) remains incurable due to latent viral reservoirs established in non-activated CD4 T cells that cannot be eliminated via antiretroviral therapy. Current efforts to cure HIV are focused on identifying drugs that will induce viral gene expression in latently infected cells, commonly known as latency reversing agents (LRAs). Some drugs have been shown to reactivate latent HIV but do not cause a reduction in reservoir size. Therefore, finding new LRAs or new combinations or increasing the round of stimulations is needed to cure HIV. However, the effects of these drugs on viral rebound after prolonged treatment have not been evaluated. In a previous clinical trial, antiretroviral therapy intensification with maraviroc for 48 weeks caused an increase in residual viremia and episomal two LTR-DNA circles suggesting that maraviroc could reactivate latent HIV. We amended the initial clinical trial to explore additional virologic parameters in stored samples and to evaluate the time to viral rebound during analytical treatment interruption in three patients. Maraviroc induced an increase in cell-associated HIV RNA during the administration of the drug. However, there was a rapid rebound of viremia after antiretroviral therapy discontinuation. HIV-specific T cell response was slightly enhanced. These results show that maraviroc can reactivate latent HIV in vivo but further studies are required to efficiently reduce the reservoir size.


Management of superior sulcus tumors: experience with 139 cases treated by surgical resection.
The management of non-small cell carcinomas of the lung involving the superior sulcus remains controversial. The goal of this retrospective study was to evaluate the role of surgery, radiotherapy, and chemotherapy for the treatment of superior sulcus tumors, to define the best surgical approach for radical resection, and to identify factors influencing long-term survival. Between 1983 and 1999, 139 patients underwent surgical resection of superior sulcus tumors in seven thoracic surgery centers. According to the classification of the American Joint Committee, 51.1% of cancers were stage IIB, 13.7% stage IIIA, 32.4% stage IIIB, and 2.9% stage IV. The resections were performed with 74.1% using the posterior approach and 25.9% using an anterior approach. A lobectomy was accomplished in 69.8% of the cases and a wedge resection in 22.3%. Resection of a segment of vertebrae or subclavian artery was performed, respectively, in 19.4% and 18% of the cases. Resection was complete in 81.3% of cancers. The overall 5-year survival rate was 35%. Preoperative radiotherapy improved 5-year survival for stages IIB-IIIA. Surgical approach, postoperative radiotherapy, or chemotherapy did not change survival. The optimal treatment for superior sulcus tumors is complete surgical resection. The surgical approach (anterior/posterior) did not influence the 5-year survival rate. Preoperative radiotherapy should be recommended to improve outcome of patients with a superior sulcus tumor.


The Early Osteoarthritic Knee: Implications for Cartilage Repair.
Patients with early osteoarthritis (OA) have been reported to have inferior outcomes with an increased prevalence of early failure after cartilage procedures. The underlying reasons for this failure are likely multifactorial, including a chronic synovial and chondrogenic process, which is confounded by persistent muscle weakness and altered pain processing for those with increased preoperative symptom duration. Pain, radiographic changes, patient-reported outcomes, and macroscopic changes on arthroscopic evaluation or MRI can assist clinicians in identifying the early OA knee to both aid in clinical decision making and create realistic postoperative expectations for patients.


[Current status of Akt in non-small cell lung cancer].
Lung cancer is one of the most common malignant tumors in the world, but its pathogenesis has still been remaining confusing. As an important protein in several signaling pathways, Akt has been identified to play a major role in the growth, proliferation, apoptosis and invasion of tumor cells. This paper is to review the effects of Akt, together with PDK1, Raf-1 and p70S6K, which are upstream and downstream regulatory molecules of Akt, and provide a new basis for the pathogenesis of non-small cell lung cancer.