Fluid characteristics of benign ovarian cysts: correlation with recurrence after puncture.
To determine whether concentrations of gonadal steroids and fibrinolytic indices in fluid from benign ovarian cysts can discriminate between functional and neoplastic cysts and predict recurrence after ultrasound-guided puncture. Concentrations of gonadal steroids and components of the plasminogen-activating system were measured in cyst fluid obtained at ultrasound-guided puncture of 96 ovarian cysts and were related to subsequent cyst recurrence. In 83 patients who had surgery for benign ovarian cysts, components of the plasminogen-activating system in the cyst fluid were correlated with the histopathologic diagnosis. Higher levels of plasminogen activators and lower levels of inhibitors were found in those 54 cysts that recurred after puncture and in cysts with low levels (below 2000 pmol/L) of estradiol (E2). This enzyme-inhibitor balance resulted in high fibrinolytic activity. In contrast, cysts with high E2 levels (above 2000 pmol/L) had lower levels of activators, higher levels of inhibitors, and virtually no fibrinolytic activity. A high E2 concentration in cyst fluid was the single best predictor of no recurrence after puncture. Sixteen of 18 cysts in postmenopausal women recurred, and all had low levels of E2. However, an index based on cyst fluid volume and concentrations of E2 and urokinase predicted recurrence even better. A high concentration of urokinase in the fluid correlated with neoplastic histology of the cysts obtained at laparotomy. The fluid content of ovarian steroids and plasminogen activators and inhibitors is related to histopathology and recurrence after puncture of benign ovarian cysts. Puncture and assay of these components may minimize surgery on functional cysts.


Methodology for labeling proteins and peptides with lead-212 (212Pb).
Alpha particles possess an exquisite degree of cytotoxicity when employed for targeted α-particle therapy (TAT) or radioimmunotherapy (RIT). (212)Pb, which acts as an in vivo generator of the α-emitting nuclide (212)Bi has shown great promise in pre-clinical studies when used to label the HER2 binding antibody, trastuzumab. Currently, the first RIT clinical trial employing (212)Pb radiolabeled trastuzumab is in progress. This report provides detailed current protocol operations and steps that were generated for use in the clinical trial as well as the relevant pre-clinical experimentation, and describes in detail the labeling of proteins or peptides with (212)Pb as provided via a (224)Ra based generator system. (212)Pb was eluted from the (224)Ra/(212)Pb generator using hydrochloric acid (2M). The generator eluate was evaporated and digested with nitric acid (8M) followed by extraction of the (212)Pb with dilute nitric acid (0.1M). The dilute nitric acid solution of (212)Pb was used to label the immunoconjugate Trastuzumab-TCMC (2-(4-isothiocyanatobenzyl-1,4,7,10-tetraaza-1,4,7,10,tetra-(2-carbamonylmethyl)-cyclododecane) at pH5.5. Elution of (212)Pb from the generator was efficient yielding>90% of available (212)Pb. Trastuzumab-TCMC was efficiently labeled with a radiochemical yield of 94% ± 4% (n=7) by ITLC and an isolated yield of 73% ± 3% (n=7). The results show the feasibility of generating radioimmunoconjugates and peptide conjugates for use as in vivo α generator systems in the clinic. The technology holds promise in applications involving the treatment of minimal disease such as micrometastases and residual tumor after surgical debulking, hematological cancers, infections, and compartmental cancers, such as ovarian cancer.


Identification of progression markers in B-CLL by gene expression profiling.
B-cell chronic lymphocytic leukemia is a heterogeneous disease with a pronounced variation in the clinical course. With the purpose of identifying genes that could be related to disease progression, we have performed gene expression profiling on B-CLL patients with an indolent disease and patients with a progressive disease with need for therapy. we applied the Affymetrix GeneChip technique to 11 B-CLL patients with stable and 10 patients with clinically progressive disease. Supervised and unsupervised clustering methods with different algorithms were used to identify genes that tend to give a distinction between stable and progressive disease. The supervised learning procedures identified groups of genes with a combined power to discriminate samples from progressive and stable disease with 70-90% accuracy. The gene for protein phosphatase 2 regulatory subunit B' (B56) gamma isoform (PPP2R5C) and the gene for retinoblastoma-like 2 (p130) (RBL2) were included among the best discriminators; both genes were downregulated in progressive as compared to stable B-CLL. In a hierarchical clustering analysis based on gene expression pattern three clinical subcategories could be identified: one with a more severe clinical outcome, a second one with good prognosis, and a third one that was intermediate between the other two groups. Our application of microarray analysis on a clinically well defined material has identified a number of genes with combined expression patterns related to stable or progressive disease in general. Unsupervised clustering suggested the existence of subclasses of samples in the progressive group that may be identifiable through gene expression patterns.


Some variability factors in the cytomorphological analysis of frozen bull semen.
Frozen bull semen was analyzed after fixation with glutaraldehyde (0.2% sol. in PBS) by clear field microscopy (after staining with Rose Bengal and Victoria blue B), phase contrast microscopy and differential-interference-contrast microscopy performed by two observers who analysed sets of 100 and 200 spermatozoa. The results obtained with phase-contrast microscopy did not differ significantly from those obtained using interference contrast microscopy, performed by two observers on sets on 100 and 200 spermatozoa, concerning the following sperm abnormalities: abnormal detached heads, acrosome ruptures, tail abnormalities and total abnormalities. In view of the importance of extending the evaluation of sperm cytomorphology among artificial insemination centres, and the fact the phase-contrast microscopy system is less expensive than a differential-interference-contrast system and easier to operate, the authors recommend the use of phase-contrast microscopy for the routine study of sperm cytomorphology.


Sodium handling in congenitally hypothyroid neonates.
Early observations emphasized the possible development of hyponatraemia in hypothyroid children and adults, but recently this has been questioned. To investigate whether hyponatraemia develops in hypothyroid status by examining sodium handling in screening-detected neonates and infants with congenital hypothyroidism (CH). Serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), sodium (Na), creatinine (Cr), urinary Na, Cr, fractional sodium excretion rate (FENa) and other chemicals were measured before and after L-thyroxine (LT4) replacement therapy in 32 screening-detected CH neonates (11M, 21F) and 16 age-matched control neonates. No cases of hyponatraemia were found in the 32 CH neonates. Their serum Na concentrations (139.1 +/- 1.5 mmol/L, ranging from 136 to 142 mmol/L, median 139 mmol/L) were not statistically different from those of 16 control neonates (139.3 +/- 1.3 mmol/L, ranging from 137 to 142 mmol/L, median 139 mmol/L). No correlation was found between serum levels of TSH and FT4 and serum Na or FENa. No significant changes were found in serum Na concentrations in hypothyroid neonates two months after LT4 replacement therapy. The serum Na concentration (139.1 +/- 0.3 mmol/L, n = 25) before treatment did not change statistically (138.9 +/- 0.2 mmol/L, n = 25) two months after LT4 replacement therapy. As seen in various earlier reports, hyponatraemia can occur in hypothyroid patients, but no causal relationship exists between them. When hyponatraemia is detected in hypothyroid children, it does not seem to be directly related to lack of thyroid hormones and therefore other possible causes should be sought.


Baclofen and Alcohol-Dependent Patients: A Real Risk of Severe Self-Poisoning.
Baclofen is often prescribed in high doses to fight cravings experienced by alcohol-dependent patients. Such an increase in the availability of baclofen is concerning. This study aimed to determine the change in number and profile of self-poisoning with baclofen over time, as baclofen has become increasingly popular, in order to describe the severity of self-poisoning with baclofen and to focus on co-existing alcohol use disorders, and psychiatric illnesses determine predictors of severity. This was a retrospective study of self-poisoning with baclofen as reported by the western France Poison Control Center (PCC), which represents a population of more than 12 million people from January 2008 to March 2014. One hundred and eleven cases of self-poisoning with baclofen were reported to the western France PCC (62 males and 49 females; average age 39 ± 12). Poisoning severities were as follows: 'null' (nine cases), 'minor' (37 cases), 'moderate' (19 cases) and 'high' (46 cases, including four deaths). The most frequently reported symptoms were neurological (45%) and cardiovascular (27%). The severity was significantly associated with psychiatric disorders (OR = 2.9; p = 0.03). Baclofen, prescribed in high doses, may lead to severe poisoning, particularly in patients with psychiatric illnesses. Authorities should put forward a new policy for prescribing the drug as a treatment for alcohol dependence.


VUV-VIS FT spectroscopy of the rare 13C18O isotopologue of carbon monoxide: Analysis of the A1Π(v = 1) multiply-perturbed level.
Ro-vibronic spectra of the 13C18O carbon monoxide isotopologue were obtained with (i) emission spectroscopy in the visible region using a Bruker IFS 125HR spectrometer (University of Rzeszów) and (ii) vacuum-ultraviolet absorption spectroscopy using the wave-front-division spectrometer on the DESIRS beamline of the SOLEIL synchrotron. A deperturbation analysis of the 13C18O A1Π(v = 1) level was conducted from 598 observed transitions from the B1Σ+ - A1Π(0, 1), C1Σ+ - A1Π(0, 1), A1Π - X1Σ+(1, 0), B1Σ+ - X1Σ+(0, 0), C1Σ+ - X1Σ+(0, 0), I1Σ- - X1Σ+(2, 0) bands and five further nominally forbidden bands. An effective Hamiltonian and term-value fitting analysis was implemented. Consequently, 135 parameters were floated: 23 molecular parameters, including molecular constants for A1Π(v = 1), I1Σ-(v = 2), d3Δ(v = 6), e3Σ-(v = 3) and D1Δ(v = 1); rotation-electronic (L-uncoupling) mixing of A1Π(v = 1) ∼ [D1Δ(v = 1), I1Σ-(v = 1), I1Σ-(v = 2)] and spin-orbit interaction parameters for A1Π(v = 1) ∼ [d3Δ(v = 6), e3Σ-(v = 3), a'3Σ+(v = 11)]; the spin-orbit/spin-electronic/L-uncoupling a3Π(v = 12) ∼ d3Δ(v = 5) and spin-orbit a3Π(v = 12) ∼ [D1Δ(v = 1), I1Σ-(v = 2)] perturbation parameters; as well as 112 ro-vibronic term values of B1Σ+(v = 0) up to J = 50 and C1Σ+(v = 0) up to J = 60. The significant, indirect a3Π(v = 12) ∼ [e3Σ-(v = 2, 3), d3Δ(v = 5, 6)] ∼ A1Π(v = 1) spin-orbit/spin-electronic/L-uncoupling interaction and a3Π(v = 12) ∼ [I1Σ-(v = 2), D1Δ(v = 1)] ∼ A1Π(v = 1) spin-orbit/L-uncoupling interaction were detected and analysed. Thus, this study, using modern experimental methods and deperturbation analysis, leads to a much improved description in terms of molecular constants and interaction parameters, compared to previous studies of the A1Π(v = 1) energy region in the 13C18O isotopologue. This research is a continuation of the studies on the A1Π state and its numerous perturbers in the CO isotopologues made by our team.


Associations between frequency of food shopping at different store types and diet and weight outcomes: findings from the NEWPATH study.
The present study aimed to: (i) examine associations between food store patronage and diet and weight-related outcomes; and (ii) explore consumer motivations for visiting different types of food store. A stratified probability sample of residents completed household and individual-level surveys in 2009/2010 on food purchasing patterns and motivations, dietary intake, waist circumference (WC), weight and height. Diet quality was calculated using the Healthy Eating Index for Canada from a subset of participants (n 1362). Generalized estimating equations were created in 2015 to examine how frequency of patronizing different types of food store was associated with diet quality, intake of fruits and vegetable, mean intake of energy (kcal) sodium and saturated fat, WC and BMI. Three mid-sized urban municipalities in Ontario, Canada. A representative sample of residents (n 4574). Participants who shopped frequently at food co-ops had significantly better diet quality (β=5·3; 99 % CI 0·3, 10·2) than those who did not. BMI and WC were significantly lower among those who frequently shopped at specialty shops (BMI, β=-2·1; 99 % CI -3·0, -1·1; WC, β=-4·8; 99 % CI -7·0, -2·5) and farmers' markets (BMI, β=-1·4; 99 % CI -2·3, -0·5; WC, β=-3·8; 99 % CI -6·0, -1·6) compared with those who did not. Relative importance of reasons for food outlet selection differed by large (price, food quality) v. small (proximity, convenient hours) shopping trip and by outlet type. Findings contribute to our understanding of food store selection and have implications for potentially relevant retail food intervention settings.


Expression and role of p75 interleukin 2 receptor on human monocytes.
We investigated the expression of IL-2R subunits in human monocytes using the TU27 mAb, which recognizes the p75 chain, and anti-Tac mAb, which recognizes the p55 moiety of the IL-2R. We found that p75 but not p55 is constitutively expressed in more than 90% of fresh human monocytes. Antibody to p75, but not to p55, inhibited the activation of monocytes to a cytotoxic stage induced by IL-2 but did not block IFN-gamma-induced cytotoxicity. Our data demonstrate that the p75 chain is expressed on human monocytes and is involved in the activation of monocytes by IL-2.


High-resolution computed tomography evaluation of airway distensibility in asthmatic and healthy subjects.
Airway-wall remodelling may result in reduced airway distensibility in bronchial asthma. This study evaluated the baseline airway calibre and distensibility in asthmatic patients by means of high-resolution computed tomography (HRCT). We studied seven patients (two men, age range 36-69 years) with chronic asthma [forced expiratory volume in the first second (FEV(1)) range: 30%-87% of predicted; FEV1/forced vital capacity (FVC) range 48%-75% of predicted) under stable clinical conditions and six healthy control subjects (three men, age range 29-50 years). In all subjects, HRCT scanning, at suspended end-expiratory volume, was performed at rest and during ventilation with 6 and 12 cmH(2)O by nasal insufflation with continuous positive airway pressure (nCPAP), both at baseline and after inhalation of 200 mug oxitropium bromide metered dose inhaler (MDI). External and lumen diameter (mm) of the right apical upper lobe bronchus were measured in all HRCT scans. In asthmatics, 12 cmH(2)O insufflation significantly changed baseline lumen (3.3+/-0.7 mm vs. 3.8+/-0.6 mm; p<0.01) and external diameter (6.2+/-0.9 mm vs. 6.7+/-0.8 mm; p<0.05), whereas in healthy controls, both 6 and 12 cmH(2)O insufflation significantly changed baseline lumen diameter (4.0+/-1.6 mm vs. 4.8+/-1.6 mm and 4.7+/-1.7 mm; p<0.01). In asthmatic patients, oxitropium bromide inhalation significantly changed baseline lumen diameter (3.3+/-0.7 mm vs. 4.4+/-0.6 mm; p<0.05), whereas the application of 6 or 12 cmH(2)O insufflation did not modify any bronchial diameters. In healthy controls, oxitropium bromide inhalation significantly changed baseline lumen diameter (4.0+/-.6 mm vs. 5+/-1.5 mm; p<0.05). The application of 12 cmH(2)O but not of 6 cmH(2)O induced a significant change in lumen diameter (5.0+/-1.5 mm vs. 6,0+/-1.6 mm; p<0.05). Our results show that airway distensibility in asthmatic patients, as assessed by HRCT, can differ compared with that of healthy controls. HRCT can provide useful information on airway distensibility.


ESSENCE-Q: Slavic language versions for developmental screening in young children.
The Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations - Questionnaire (ESSENCE-Q) was developed as a brief screener to identify children with developmental concerns who might have neurodevelopmental disorders (NDDs). This study aimed to translate the ESSENCE-Q into south Slavic languages, namely, Bosnian, Bulgarian, Croatian, Macedonian, Montenegrin, Serbian, and Slovenian, and to evaluate its psychometric properties for screening purposes in clinical settings. In the study, the ESSENCE-Q was completed for 251 "typically developing" children and 200 children with 1 or more diagnosed NDDs, all aged 1-6 years. Internal consistency and construct validity were tested first, followed by generating receiver operating characteristic curves and the area under the curve. Optimal cutoff values were then explored. The Cronbach's α coefficients were 0.91, 0.88, and 0.86 for ESSENCE-Q parent-completed form, and the telephone and direct interview forms administered by trained nurse or specialist, respectively. The 3 versions produced area under the curve values (95% confidence interval): 0.96 (0.93-0.99), 0.91 (0.86-0.95), and 0.91 (0.86-0.97), respectively. An optimal cutoff for ESSENCE-Q parent-completed form was found to be ≥3 points, while for the telephone and direct interviews, it was ≥5 points. We found adequate measurement properties of the south Slavic languages versions of the ESSENCE-Q as a screener for NDDs in clinical settings. This study provided additional data supporting sound psychometric properties of the ESSENCE-Q.


Microalgae from the Selenastraceae as emerging candidates for biodiesel production: a mini review.
Over the years, microalgae have been identified to be a potential source of commercially important products such as pigments, polysaccharides, polyunsaturated fatty acids and in particular, biofuels. Current demands for sustainable fuel sources and bioproducts has led to an extensive search for promising strains of microalgae for large scale cultivation. Prospective strains identified for these purposes were among others, mainly from the genera Hematococcus, Dunaliella, Botryococcus, Chlorella, Scenedesmus and Nannochloropsis. Recently, microalgae from the Selenastraceae emerged as potential candidates for biodiesel production. Strains from the Selenastraceae such as Monoraphidium sp. FXY-10, M. contortum SAG 47.80, Ankistrodesmus sp. SP2-15 and M. minutum were high biomass and lipid producers when cultivated under optimal conditions. A number of Selenastraceae strains were also reported to be suitable for cultivation in wastewater. This review highlights recent reports on potential strains from the Selenastraceae for biodiesel production and contrasts their biomass productivity, lipid productivity as well as fatty acid profile. Cultivation strategies employed to enhance their biomass and lipid productivity as well as to reduce feedstock cost are also discussed in this paper.


Leucocytes mediate the hCG-induced increase in testicular venular permeability.
Human chorionic gonadotrophin (hCG) treatment of adult male rats induces microvascular changes in the testis consisting of abolished vasomotion, an accumulation of leucocytes in postcapillary venules and increased vascular permeability. To study the role of leucocytes, rats were made leucopenic with a specific antineutrophil serum (ANS). Testicular interstitial fluid volume was decreased in leucopenic rats. Leucopenic rats also failed to show an hCG-induced increase in venular permeability as in saline-treated rats. The normally pulsatile blood flow pattern (vasomotion) persisted in leucopenic rats but was abolished after hCG treatment both in saline-treated and leucopenic rats. Plasma testosterone concentration after hCG treatment was not affected by elimination of circulating polymorphonuclear (PMN) leucocytes. It is concluded that PMN leucocytes mediate in part the hCG-induced increase in testicular venular permeability but not the hCG-induced inhibition of vasomotion.


The role of mitochondrial glycerol-3-phosphate acyltransferase-1 in regulating lipid and glucose homeostasis in high-fat diet fed mice.
Glycerol-3-phosphate acyltransferase (GPAT) is involved in triacylglycerol (TAG) and phospholipid synthesis, catalyzing the first committed step. In order to further investigate the in vivo importance of the dominating mitochondrial variant, GPAT1, a novel GPAT1(-/-) mouse model was generated and studied. Female GPAT1(-/-) mice had reduced body weight-gain and adiposity when fed chow diet compared with littermate wild-type controls. Furthermore, GPAT1(-/-) females on chow diet showed decreased liver TAG content, plasma cholesterol and TAG levels and increased ex vivo liver fatty acid oxidation and plasma ketone bodies. However, these beneficial effects were abolished and the glucose tolerance tended to be impaired when GPAT1(-/-) females were fed a long-term high-fat diet (HFD). GPAT1-deficiency was not associated with altered whole body energy expenditure or respiratory exchange ratio. In addition, there were no changes in male GPAT1(-/-) mice fed either diet except for increased plasma ketone bodies on chow diet, indicating a gender-specific phenotype. Thus, GPAT1-deficiency does not protect against HFD-induced obesity, hepatic steatosis or whole body glucose intolerance.


Malignant cells, directors of the malignant process: role of transforming growth factor-beta.
Malignant cells survive and thrive by expressing growth and invasion 'programs' that many normal cell types recognize and respond to in 'programmed' patterns. An early event in the molecular evolution of many malignancies loss of response to growth control by transforming growth factor-beta (TGF-beta) frequently due to mutation in the type I or type II TGF-beta receptor or a Smad protein. The malignant cells secrete TFG-beta that acts on the host to suppress antitumor immune responses, to enhance extracellular matrix production and to augment angiogenesis. These activities resemble those induced by TGF-beta during embryonic development and account in part for the 'de-differentiated' nature of malignant disease. Clinically, TGF-beta1 is often elevated in the plasma of breast cancer patients, lung cancer patients, hepatocellular carcinoma patients, and prostate cancer patients. Preclinically, several breast cancer models and prostate cancer models in vivo have demonstrated a connection between TGF-beta expression and increased tumorigenicity, increased invasion and drug resistance. In other diseases such as colon, gastric, endometrial, ovarian, and cervical cancers and gliomas and melanoma, loss of response to TGF-beta as a growth inhibitor and increased expression of TGF-beta have been associated with malignant conversion and progression. Elevated levels of TGF-beta are measurable in nude mice bearing a wide variety of human tumor xenografts; thus, these tumor models may serve as useful mimics of the human disease with respect to the TGF-beta pathway. Cancer cure may be approached by blocking several of the major normal pathways used for tumor growth and survival in combination with cytotoxic therapies.


Interaction of zinc with cadmium and copper on ossification of embryonic chick bone in tissue culture.
Histological changes are shown of ossification induced by a simultaneous exposure to zinc and cadmium or to zinc and copper using embryonic chick femur in a culture system. Cadmium caused an atrophic change of the osseous tissue in the absence of zinc but caused an osteomalacic change with a partial degenerative change in the presence of zinc after a 6-day culture. Copper caused an atrophic change in the absence or presence of zinc. These observations were partly supported by the fact that the diaphysial calcium content was significantly decreased by zinc alone, and the decrease was unaffected by cadmium or copper. Zinc significantly decreased cadmium accumulation but not copper accumulation in the diaphysis. Thus, in spite of the inhibitory effect on calcification, zinc prevented a decrease in bone matrix formation caused by cadmium but not that by copper. Exposure of chick femur culture to zinc and cadmium induced changes consistent with osteomalacia, i.e., decreased mineralization of bone, with or without suppression of matrix formation. Exposure to zinc and copper, however, induced changes consistent with osteoporosis, i.e., decreased mineralization and matrix formation.


Urgent bedside endoscopy for clinically significant upper gastrointestinal hemorrhage after admission to the intensive care unit.
To investigate the sources of hemorrhage and use of endoscopic hemostasis in patients with clinically significant upper gastrointestinal (UGI) hemorrhage after admission to the intensive care unit (ICU). Prospective study, 123 beds of ICU in a 1,629-bed medical center. Of the 9,512 consecutive admissions over a 2-year period 105 UGI hemorrhage patients underwent urgent bedside UGI endoscopy. We compared two groups of these patients, one receiving and the other not receiving endoscopic hemostasis. Ulcers with profusely bleeding stigmata occurred in 31 patients (29.5%), ulcers with clean bases or firmly adherent blood clots in 27 (25.7%), stress-related mucosal diseases in 23 (21.9%), esophageal varices in 5 (4.8%), malignancy in 4 (3.8%), and no detectable bleeding site in 15 (14.3%). Endoscopic hemostasis was attempted in 34 patients (32.4%). Primary hemostasis for them was achieved in 67.6% and the rebleeding rate was 30.4%. In-hospital mortality rate was 77.1% and death related to hemorrhage 6.2%. Length of ICU stay before endoscopic diagnosis was significantly shorter in those who underwent endoscopic hemostasis than those who did not (28.2+/-26.3 vs. 41.2+/-57.5 days). Endoscopic hemostasis may be more beneficial when the period between ICU admission and development of hemorrhage is shorter. Bleeders can be more readily identified and controlled endoscopically in such patients. A significant proportion of bleeding sites cannot be identified by UGI endoscopy. It may indicate higher risk of small bowel hemorrhage in these critically ill patients.


The anabolic effect of human PTH (1-34) on bone formation is blunted when bone resorption is inhibited by the bisphosphonate tiludronate--is activated resorption a prerequisite for the in vivo effect of PTH on formation in a remodeling system?
Parathyroid hormone (PTH) and its (1-34) fragment are stimulators of bone turnover that have an anabolic effect increasing trabecular bone mass when administered intermittently by daily subcutaneous injections. Its clinical use in osteoporosis, however, has been limited by the concomitant increased bone resorption and deleterious effect on cortical bone. To evaluate if a treatment combining PTH and a potent inhibitor of bone resorption would retain the anabolic effect of PTH without increasing bone resorption, we analyzed the effects of PTH (1-34) (500 IU/d) with or without the bisphosphonate tiludronate (1 mg/kg per day) for 3 months on biochemical and histological indices of bone turnover in old female sheep, an animal model which has a slow bone remodeling activity that resembles the one of elderly women. As expected, PTH (1-34) induced a significant increase of urinary pyridinoline and hydroxyproline (reflecting bone resorption), and of serum osteocalcin and alkaline phosphatase (reflecting bone formation), that were consistent with an increase of resorption and tetracycline-based formation of bone measured on iliac crest biopsy. In contrast, all biochemical and histological indices of bone turnover were decreased in sheep receiving tiludronate, a potent inhibitor of bone resorption. Surprisingly, in the combined therapy group, biochemical and histological indices of both resorption and formation did not differ from the control groups. Thus, the model of old sheep, which closely resembles the situation in old human, shows that the anabolic effect of PTH on bone is not maintained when PTH is coadministered with a bisphosphonate, in marked contrast to results noted in the growing rat.(ABSTRACT TRUNCATED AT 250 WORDS)


Reversible electrical breakdown of lipid bilayer membranes: a charge-pulse relaxation study.
Charge-pulse experiments were performed with lipid bilayer membranes from oxidized cholesterol/n-decane at relatively high voltages (several hundred mV). The membranes show an irreversible mechanical rupture if the membrane is charged to voltages on the order of 300 mV. In the case of the mechanical rupture, the voltage across the membrane needs about 50-200 musec to decay completely to zero. At much higher voltages, applied to the membrane by charge pulses of about 500 nsec duration, a decrease of the specific resistance of the membranes by nine orders of magnitude is observed (from 10(8) to 0.1 omega cm2), which is correlated with the reversible electrical breakdown of the lipid bilayer membrane. Due to the high conductance increase (breakdown) of the bilayer it is not possible to charge the membrane to a larger value than the critical potential difference Vc. For 1 M alkali ion chlorides Vc was about 1 V. The temperature dependence of the electrical breakdown voltage Vc is comparable to that being observed with cell membranes. Vc decreases between 2 and 48 degrees C from 1.5 to 0.6 V in the presence of 1 M KCl. Breakdown experiments were also performed with lipid bilayer membrane composed of other lipids. The fast decay of the voltage (current) in the 100-nsec range after application of a charge pulse was very similar in these experiments compared with experiments with membranes made from oxidized cholesterol. However, the membranes made from other lipids show a mechanical breakdown after the electrical breakdown, whereas with one single membrane from oxidized cholesterol more than twenty reproducible breakdown experiments could be repeated without a visible disturbance of the membrane stability. The reversible electrical breakdown of the membrane is discussed in terms of both compression of the membrane (electromechanical model) and ion movement through the membrane induced by high electric field strength (Born energy).


Postcoital Hemorrhage of a Recurrent Seminal Vesicle Cyst Requiring Embolization.
Herein is a case of a 23-year-old man with recurrence of a seminal vesicle cyst after percutaneous drainage and laparoscopic excision complicated by hemorrhage requiring embolization. He presented to the emergency department for pain after ejaculation. Computed tomographic scan of his pelvis revealed extravasation of contrast near his cyst and pelvic fluid collection suspicious for a hematoma. The patient had steadily decreasing hemoglobin and hematocrit levels. An interventional radiologist performed an embolization of the left seminal vesicle cystic arteries. Hemoglobin and hematocrit values improved and he was discharged. Hemorrhage resolved with embolization procedure and pain dissipated over the course of follow up care.


Dispersive solid-phase extraction based on MoS2/carbon dot composite combined with HPLC to determine brominated flame retardants in water.
The method based on the dispersive solid-phase extraction (DSPE) by novel molybdenum disulfide modified with carbon dot (MoS2/CD) composite combined with high-performance liquid chromatography (HPLC) was developed for the determination of three brominated flame retardants (BFRs), including tetrabromobisphenol A (TBBPA), tetrabromobisphenol A bisallylether (TBBPA-BAE), and tetrabromobisphenol A bis(2,3-dibromopropyl ether) (TBBPA-BDBPE). Owing to the stacked planar structure and large surface area of MoS2, a large number of CDs can be easily loaded on the surface of MoS2. Benefiting from good dispersing capability of MoS2, similar density with analytes, and hydrogen bonds between CDs and the target analytes, the CDs on the surface of MoS2 as sorbent for the DSPE procedure exhibited good extraction performance. Under optimal conditions, application of the developed method to analyze BFRs from real water samples resulted in good recovery values ranging from 80 to 91% with relative standard deviation (RSD) values lower than 6.5%. Limits of detection (LODs) were in the range of 0.01-0.06 μg/L. The result above showed that the method has potential for the extraction and detection of trace-level BFRs from real water sample. Graphical abstract Owing to the stacked planar structure and large surface area of MoS2, a large number of CDs can be easily loaded on the surface of MoS2. Benefiting from good dispersing capability of MoS2, similar density with analytes, and hydrogen bonds between CDs and the target analytes, the prepared MoS2/CD composites as sorbent for the DSPE procedure exhibited good extraction performance. Accordingly, the extraction yield of BFRs was improved, which was favorable to its accurate determination in sample.


Infrared. An unseen and unnecessary hazard in ophthalmic devices.
The concept of instrument-induced light damage to the retina is well established. Many have argued that ultraviolet (UV) energy is overwhelmingly responsible and that longer wavelength infrared (IR) energy causes thermal change and plays a minimal role. We suggest that infrared may play a primary role in instrument-induced damage. We measured the radiometric and photometric outputs from commonly used ophthalmic devices in normal use and in IR-blocked conditions. We found IR output to represent a significant portion of the total irradiation produced by these instruments. Infrared was easily and inexpensively minimized without compromising usable visible light in these instruments using an efficient IR filter. The instruments' incandescent lamps, glass envelopes, and optics are poor UV emitters or transmitters. Manufacturers' data do not indicate UV emission. Evidence for UV blocking and IR transmission by the intraocular media is presented.


Enriched environment preconditioning induced brain ischemic tolerance without reducing infarct volume and edema: the possible role of enrichment-related physical activity increase.
External stimuli, including environmental enrichment (EE) and physical activity, have been shown to significantly facilitate recovery from brain injury. However, whether EE can be used as a preconditioning method to induce cerebral ischemic tolerance has never been investigated. Furthermore, whether, and to what extent, such environmental stimuli regulate physical activity to promote neuroprotection is largely unclear. To examine the neuroprotective effects of pre-ischemic EE (PIEE) and to investigate the relationship between these effects and EE-induced physical activity, we tested neurobehavioral and morphological recovery of rats following transient focal cerebral ischemia. Our study showed that PIEE improved the recovery of motor function, spatial learning and memory without reduction in brain edema or infarct volume. We also found that PIEE robustly increased the level of physical activity of rats that positively correlated with the extent of neurobehavioral recovery. Our results suggest that PIEE may induce brain ischemic tolerance through, at least partially, increasing physical activity.


Effect of stimulation and antagonism of interleukin-1 signaling on preterm delivery in mice.
Transgenic mice that overexpress the interleukin-1 receptor antagonist (IL-1ra), an endogenous competitive inhibitor of interleukin-1 (IL-1) signaling, were used to test whether blockade of IL-1 can prevent bacterially induced preterm delivery in a validated murine model. These IL-1ra transgenic mice have been shown previously to be protected from lethal endotoxin shock. In a series of four separate experiments, 201 female wild-type and transgenic mice on day 14.5 of a 19-20 day gestation underwent intrauterine injection with either 0.5-20 microg of recombinant human IL-1beta (rhIL-1beta) or 10(5)-10(8) heat-killed Escherichia coli organisms. Fetuses were either all wild-type, all transgenic, or of mixed genotype (see below). Preterm delivery and maternal survival rates were recorded. IL-1ra protein levels were determined by enzyme-linked immunosorbent assay (ELISA). Intrauterine administration of IL-1beta induced preterm delivery in a dose-dependent manner and did not cause other adverse maternal effects. In bacterially inoculated mice, neither maternal nor fetal carriage of the IL-1ra overexpression transgene affected preterm delivery rates. Fetal carriage of the IL-1ra transgene did not up-regulate IL-1ra protein levels in maternal or fetal tissues. Although intrauterine IL-1 exposure is sufficient for induction of preterm delivery, it was not possible to prevent bacterially induced preterm birth using the IL-1ra transgene. This may be either because the timing or magnitude of IL-1ra up-regulation in transgenic mice was insufficient to block IL-1's interaction with its receptor, or because bacterially induced labor in this model does not depend on IL-1 signaling alone.


Preserved proinsulin production in homozygous protein tyrosine phosphatase nonreceptor type 22 C1858T variant type 1 diabetes: a possible explanation for absence of overt ketoacidosis despite omission of exogenous insulin.
To report a postulated mechanism for resistance to overt ketoacidosis due to prolonged insulin omission in a severely hyperglycemic woman with a 14-year history of autoimmune type 1 diabetes (T1D). History, physical examination, laboratory testing, and genotyping were performed. We also review the medical literature pertinent to this patient's phenotype and genotype. Proinsulin levels remained within the normal range (suppressed with hypoglycemia) despite simultaneous almost unmeasurable C-peptide levels during hyperglycemia. We confirmed a homozygous (TT) variant of protein tyrosine phosphatase nonreceptor type 22 (PTPN22) 1858T, a T1D susceptibility gene associated with higher proinsulin levels. The extraordinarily preserved proinsulin biological activity may explain the unusual resistance to overt ketoacidosis despite omission of exogenous insulin administration for extended periods of time. The role of the associated PTPN22 1858TT variant remains speculative.


Surgical strategy for atrioventricular septal defect and tetralogy of Fallot or double-outlet right ventricle.
Tetralogy of Fallot, or double-outlet right ventricle with atrioventricular (AV) septal defect (TOF/DORV-AVSD), is rare, with limited long-term data available. We report our institutional experience and outcome over a 50-year period. From January 1961 to January 2011, 73 patients (50 males [68%]), with a mean age of 6.8 ± 4.4 years (range, 1 month to 35 years), underwent surgical repair of TOF/DORV-AVSD. Symptoms included cyanosis in 50 (69%) and heart failure in 12 (17%). Down syndrome was present in 25 (34%). Rastelli type A, B, and C was seen in 12%, 7%, and 81% of patients, respectively. Moderate or more common AV valve (AVV) regurgitation was present in 40%. Forty-nine patients (67%) had previous palliation, including 36 with a systemic-to-pulmonary arterial shunt. Surgical management included two-ventricle complete repair (CR) in 35 (48%) and single-ventricle (SV) palliation in 38 (52%). Overall, early mortality was 31% for CR and 34% for SV; after 1990, mortality was 6% for CR and 14% for SV. Repair before 1990 (p = 0.008) and the presence of significant common AVV regurgitation (p = 0.016) were univariate risk factors for early death in both groups. Median follow-up was 9.8 years (maximum, 32 years). Late mortality rate was 12% in CR (n = 6) and 18% (n = 9) in SV (p = 0.95). The presence of significant right AVV regurgitation was associated with late death (p = 0.02). Overall survival at 1, 5, and 15 years was 92%, 77%, and 77% in CR, and 83%, 79%, 70% in SV (p = 0.9). Freedom from reoperation at 1, 5, and 15 years was 95%, 85%, 67% in CR and 96%, 91%, 82% in SV (p = 0.1). Reoperations were most common for right ventricular outflow tract pathology, Fontan revision, and AVV intervention. Right AVV regurgitation (p = 0.018) and repair before 1990 (p = 0.041) were risk factors for late reoperation in both groups. Complete repair of TOF/DORV-AVSD is standard of care and associated with low early mortality rate in the current era, with reasonable long-term outcome. SV palliation continues to have significant risk. The presence of AVV regurgitation is a significant risk factor for death and reoperation.


Effects of polyol excipient stability during storage and use on the quality of biopharmaceutical formulations.
Biopharmaceuticals are formulated using a variety of excipients to maintain their storage stability. However, some excipients are prone to degradation during repeated use and/or improper storage, and the impurities generated by their degradation are easily overlooked by end users and are usually not strictly monitored, affecting the stability of biopharmaceuticals. In this study, we evaluated the degradation profile of polyol excipient glycerol during repeated use and improper storage and identified an unprecedented cyclic ketal impurity using gas chromatography with mass spectrometry (GC-MS). The other polyol excipient, mannitol, was much more stable than glycerol. The effects of degraded glycerol and mannitol on the stability of the model biopharmaceutical pentapeptide, thymopentin, were also evaluated. The thymopentin content was only 66.4% in the thymopentin formulations with degraded glycerol, compared to 95.8% in other formulations after the stress test. Most glycerol impurities (i.e., aldehydes and ketones) reacted with thymopentin, affecting the stability of thymopentin formulations. In conclusion, this work suggests that more attention should be paid to the quality changes of excipients during repeated use and storage. Additional testing of excipient stability under real or accelerated conditions by manufacturers would help avoid unexpected and painful results.


Guidelines for the Evaluation of Pulmonary Nodules Detected Incidentally or by Screening: A Survey of Radiologist Awareness, Agreement, and Adherence From the Watch the Spot Trial.
The aim of this study was to examine radiologists' beliefs about existing guidelines for pulmonary nodule evaluation. A self-administered survey was developed to ascertain awareness of, agreement with, and adherence to published guidelines, including those from the Fleischner Society and the Lung CT Screening Reporting and Data System (Lung-RADS™). Surveys were distributed to 514 radiologists at 13 health care systems that are participating in a large, pragmatic trial of pulmonary nodule evaluation. Prespecified comparisons were made among groups defined by type of health system, years of experience, reader volume, and study arm. The response rate was 26.3%. Respondents were most familiar with guidelines from Fleischner (94%) and Lung-RADS (71%). For both incidental and screening-detected nodules, self-reported adherence to preferred guidelines was very high (97% and 94%, respectively), and most respondents believed that the benefits of adherence outweigh the harms (81% and 74%, respectively). Underlying evidence was thought to be high in quality by 68% of respondents for screening-detected nodules and 41% for incidental nodules. Approximately 70% of respondents believed that the frequency of recommended follow-up was "just right" for both guidelines. Radiologists who practice in nonintegrated health care systems were more likely to believe that the evidence was high in quality (79.5% versus 57.1%) and that the benefits of adherence outweigh the harms (85.1% versus 67.5%). Low-volume readers had lower awareness and self-reported adherence than higher volume readers. Radiologists reported high levels of familiarity and agreement with and adherence to guidelines for pulmonary nodule evaluation, but many overestimated the quality of evidence in support of the recommendations.


Aggregation kinetics of polystyrene nanoplastics in gastric environments: Effects of plastic properties, solution conditions, and gastric constituents.
Nanoplastics are inevitably ingested into human gastric environment, wherein their aggregation kinetics and interactions with gastric constituents remain unclear. This study investigated the early-stage (20 min) and long-term (1-6 h) aggregation kinetics of four commonly-found polystyrene nanoplastics (PSNPs) including NP100 (100-nm), A-NP100 (100-nm, amino-modified), C-NP100 (100-nm, carboxyl-modified), and NP500 (500-nm) under gastric conditions. Five simulated human gastric fluids (SGFs) including SGF1-3 (0-3.2 g/L pepsin and 34.2 mM NaCl), SGF4 (400 mM glycine), and SGF5 (nine constituents), three pH (2, fasted state; 3.5, late-fed state; and 5, early-fed state), and 1-100 mg/L PSNPs were examined. Aggregation rates ranked NP100 > A-NP100 ≈ C-NP100 > NP500, SGF5 > SGF4 > SGF3 > SGF2 > SGF1, and pH 2 > 3.5 > 5. Increasing PSNP concentration enhanced aggregation rate up to 13.82 nm/s. Aggregation behavior generally followed the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. Pepsin, glycine, and proteose-peptone strongly influenced PSNP stability via electrostatic interaction and steric hindrance imparted by protein corona. Freundlich isotherm suggested that PSNPs adsorbed organic constituents following lysozyme > porcine bile > proteose-peptone > pepsin > glycine > D-glucose, inducing changes in constituent structure and PSNP properties. These findings provide insights on the transport of nanoplastics in the gastric environments.


The detection of antibody to virus-infection associated (VIA) antigen in various species of African wildlife following natural and experimental infection with foot and mouth disease virus.
The double immuno-diffusion (DID) test has been applied to detect antibody to VIA antigen in sera from various species of African wild ungulates. In conjunction with the serum neutralisation (SN) test it can be used to decide the degree of risk of movement of animals to other countries free from foot and mouth disease (FMD). The value of the test in assessing the history of infection is limited by its relatively low sensitivity and specificity in respect of virus type.


Functional analysis of recombinant calreticulin fragment 39-272: implications for immunobiological activities of calreticulin in health and disease.
Although calreticulin (CRT) is a major Ca(2+)-binding luminal resident protein, it can also appear on the surface of various types of cells and it functions as an immunopotentiating molecule. However, molecular mechanisms underlying the potent immunobiological activity of cell surface CRT are still unclear. In the present study, a recombinant fragment (rCRT/39-272) covering the lectin-like N domain and partial P domain of murine CRT has been expressed in Escherichia coli. The affinity-purified rCRT/39-272 assembles into homodimers and oligomers in solution and exhibits high binding affinity to various glycans, including carrageenan, alginic acids, and hyaluronic acids. Functionally, rCRT/39-272 is capable of driving the activation and maturation of B cells and cytokine production by macrophages in a TLR-4-dependent manner in vitro. It specifically binds recombinant mouse CD14, but not BAFFR and CD40. It is also able to trigger Ig class switching by B cells in the absence of T cell help both in vitro and in vivo. Furthermore, this fragment of CRT exhibits strong adjuvanticity when conjugated to polysaccharides or expressed as part of a fusion protein. Soluble CRT can be detected in the sera of patients with rheumatoid arthritis or systemic lupus erythematosus, but not in healthy subjects. We argue that CRT, either on the membrane surface of cells or in soluble form, is a potent stimulatory molecule to B cells and macrophages via the TLR-4/CD14 pathway and plays important roles in the pathogenesis of autoimmune diseases.


Reactions of AlH(3) x NMe(3) with nitriles: structural characterization and substitution reactions of hexameric aluminum imides.
The reaction of AlH(3).NMe(3) with RCN proceeds with the evolution of trimethylamine and affords (HAINCH(2)R)(6) (R = Ph (1), p-MeC(6)H(4) (2), p-CF(3)C(6)H(4) (3)). Compounds 1 and 3 are characterized by single-crystal structural analysis. Compound 1 reacts with Me(3)SiBr as well as with PhC[triple bond]CH to give (XAINCH(2)Ph)(6) (X = Br (4), PhC[triple bond]C (5)). Structural data and other characterization data of compounds 4 and 5 show that all the hydridic hydrogen atoms in 1 have been replaced by bromine atoms and PhC[triple bond]C groups, respectively. Compounds 1-5 are potential precursors for the preparation of aluminum nitride. Crystals of 1 are rhombohedral, space group R3 macro, with a = 15.7457(13) A, b = 15.7457(13) A, c = 14.949(2) A, V = 3209.8(5) A(3), and Z = 3. Crystals of 3.(3)/(4)C(7)H(8) are triclinic, space group P1 macro, with a = 17.527(11) A, b = 18.894(12) A, c = 19.246(15) A, alpha = 96.11(7) degrees, beta = 102.23(4) degrees, gamma = 106.79(3) degrees, V = 5867(7) A(3), and Z = 4. Compound 4 crystallizes in the monoclinic space group P2(1)/c, with a = 14.175(4) A, b = 16.678(5) A, c = 10.731(3) A, beta = 106.82(2) degrees, V = 2428.6(11) A(3), and Z = 2. Compound 5. C(7)H(8) crystallizes in the monoclinic space group C2/c, with a = 25.842(5) A, b = 15.443(3) A, c = 20.699(4) A, beta = 105.88(3) degrees, V = 7945(3) A(3), and Z = 4.


Linalool and cineole type glucosides from Cunila spicata.
The leaves of Cunila spicata yielded a monoterpenetriol and six glycosidic terpenoids derived from linalool, hydroxylated linalool and 1,8-cineole: 3,7-dimethyl-oct-1-ene-3,6,7-triol, linalool-O-beta-D-glucopyranoside, 3,7 dimethyl-octa-1,6-diene-3,8-diol-3-O-beta-D-glucopyranoside as well as 3,7-dimethyl-octa-1,5-diene-3,7-diol-3-O-beta-D-glucopyranoside, 3,7-dimethyl-octa-1,7-diene-3,6-diol-7-O-beta-D-glucopyranoside, 3,7- dimethyl-oct-1-ene-3,6,7-triol-6-O-beta-D-glucopyranoside and (1S,4R,6R)-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-O-beta- glucopyranoside. The structures of the glucosides were established by chemical and spectroscopic methods especially high field NMR techniques.


Development of hyporesponsiveness to augmentation of natural killer cell activity after multiple doses of maleic anhydride divinyl ether: association with decreased numbers of large granular lymphocytes.
A single injection of mice with maleic anhydride divinyl ether (MVE-2) resulted in significantly augmented natural killer (NK) activity. However, multiple injections with MVE-2 led to a hyporesponsive to boosting of NK activity. Stimulation of prostaglandin E secretion of induction of suppressor macrophages (M phi) or lymphocytes were shown not to be responsible for the depressed NK cell responses. Rather the hyporesponsiveness to NK boosting was associated with a decreased number of large granular lymphocytes (LGLs). Percoll discontinuous-density-gradient studies showed that the augmented NK activity of spleen cells after a single injection with MVE-2 was associated with an increase in the percentage of LGLs in the lower-density fractions (Fraction 1 and 2). In contrast, the NK activity and percentage of LGLs in the lower-density fractions were markedly decreased after multiple injections with MVE-2. Polyinosinic: polycytidylic acid stabilized with poly(L-lysine) in carboxymethylcellulose, another BRM capable of augmenting NK activity, was able to substantially augment NK activity in mice hyporesponsive to MVE-2 and this was accompanied by an increase in the percentage of LGLs in the lower-density Percoll fractions.


[Caudal regression sequence: clinical-radiological case].
Caudal regression syndrome is an uncommon congenital malformation that includes a wide spectrum of clinical presentations. Characterised by caudal musculoskeletal compromise, it can be associated to neurological, gastrointestinal, renal and genitourinary defects. Although the specific aetiology has not been clarified, it has been associated with the presence of maternal diabetes and mutations in homeobox gene HBLX9. Its diagnosis is based on a good prenatal ultrasound detection, detailed physical examination, and post-natal imaging study using radiography and magnetic resonance. Caudal regression syndrome requires multidisciplinary management, and it seems that good metabolic control of gestational diabetes constitutes the best preventive measure available. We present the clinical case and images of a male term newborn, born to a pregestational diabetic mother with poor metabolic control and a prenatal ultrasound diagnosis of lumbar spine, iliac bones and lower limbs malformation. Born in good conditions, the diagnosis was confirmed using X-rays and magnetic resonance.


Chronic exposure to 2.9 mT, 40 Hz magnetic field reduces melatonin concentrations in humans.
Diurnal rhythm of serum melatonin concentrations was estimated in 12 men with low back pain syndrome before and after exposure to a very low-frequency magnetic field (2.9 mT, 40 Hz, square wave, bipolar). Patients were exposed to the magnetic field for 3 weeks (20 min per day, 5 days per week) either in the morning (at 10:00 hr) or in the late afternoon (at 18:00 hr). Significant depression in nocturnal melatonin rise was observed regardless of the time of exposure. This phenomenon was characteristic for all the subjects, although the percent of inhibition of melatonin secretion varied among the studied individuals.


Point-of-Care Ultrasound Fracture-Physis Distance Association with Salter-Harris II Fractures of the Distal Radius in Children: The "POCUS 1-cm Rule".
Salter-Harris II fractures of the distal radius can result in serious complications. The aim of this study was to measure the fracture-physis distance using point-of-care ultrasound (POCUS) to determine whether a certain distance is associated with Salter-Harris II fractures, compared with other fracture types, in a cohort of children with X-ray-identified distal radius fractures. Participants were from a parent diagnostic study conducted in an Australian tertiary pediatric emergency department, which prospectively evaluated the diagnosis of pediatric distal forearm fractures using POCUS compared against X-ray. Nurse practitioners, who underwent 2 h of training, administered a six-view POCUS protocol in clinically non-angulated pediatric forearm injuries prior to X-ray. This was a secondary analysis of data from the parent study. The 122 participants with X-ray-identified distal radius fractures from the parent study had their POCUS images interpreted by two emergency physician sonologists, who measured the fracture-physis distance. The median and maximum fracture-physis distances for Salter-Harris II fractures (n = 19) were 8.00 and 9.85 mm, whereas minimum and median distances for incomplete fractures (n = 22) were 10.20 and 15.98 mm, and those for complete fractures (n = 9) were 10.85 and 12.85 mm. Buckle fracture (n = 72) distances ranged from 4.35 to 26.55 mm, with a median of 13.65 mm. In children diagnosed with a distal radius fracture on X-ray, a fracture-physis distance cutoff of 1 cm differentiated Salter-Harris II fractures from other cortical breach fracture types, but not buckle fractures. Although this exploratory study suggests the "POCUS 1-cm rule" could be used as a secondary sign to augment the diagnosis of Salter-Harris II distal radius fractures using POCUS, further research is required to validate this measurement prospectively.


Integration of black phosphorus and hollow-core anti-resonant fiber enables two-order magnitude enhancement of sensitivity for bisphenol A detection.
Hollow core anti-resonant fiber (HARF) has found a handful applications in optical communications, nonlinear optics and high power delivery. The intrinsic property of the fiber also renders it an ideal candidate for biosensing, which has not been explored intensively. Herein, we demonstrate an optical fiber sensing platform, taking advantages of the state-of-the-art HARF technology and superior physicochemical properties of 2D material black phosphorus, for ultra-sensitive detection of bisphenol A (BPA) in blood and environmental samples. The specially designed HARF can not only achieve broadband transmission of light, but also confine light in the low refractive-index liquid core, ensuring maximum overlap of light and liquid core. Modification of the inner surface of HARF with 2D black phosphorus nanoflakes functionalized with fluorescently labeled BPA-specific aptamer provides a smart sensing interface enabling highly selective detection of BPA via measuring the fluorescence. The limit of detection is 1.69pM, which is more than two orders of magnitude enhancement compared to the conventional plate assay. The proposed assay is not interfered with the BPA analogues BPB and BPS. The long optical path with tight optical confinement greatly enhances the analyte-light interaction and improves the sensitivity of the sensing platform. The proposed sensing platform can be further developed for versatile applications.


Intra- and Intersexual Mate Competition in Two Cultures : A Comparison of Women's Response to Mate Competition with Women and Gender-Nonbinary Males in Samoa and among the Istmo Zapotec.
The present study examined women's mate competition tactics in response to female and feminine-male rivals in two cultures in which competition against both occurs. In Samoa and the Istmo Zapotec (Southern Mexico), women not only compete with other women (intrasexually) but also compete with rival feminine males (intersexually) in order to access/retain the same masculine men as sexual/romantic partners. Using a mixed-method paradigm, women were asked about their experiences of intra- and intersexual mate competition, and these narratives were recorded. The tactics reportedly employed by participants, and those attributed to mate competitors, were categorized according to established taxonomies of mate competition tactics, and their frequencies compared. Within-culture, the likelihood that participant women had ever experienced intra- and intersexual mate competition did not differ. Furthermore, participants reported a similar pattern of behavioral tactics whether their rival was another woman or a feminine male. These included benefit provisioning tactics during mate acquisition and cost-inflicting tactics during mate retention. Similarly, the mate competition tactics attributed to rival women and rival feminine males bore a striking resemblance, focused on enticing target men. Results highlight the mate competition tactics employed by women outside of a Euro-American context, and the way cultural factors impact mating landscapes presumed to be exclusively heterosexual. The presence of feminine males, alongside masculine men's willingness to engage in sexual activity with them, induces women in such cultures to compete intersexually in comparable ways to intrasexual competition with rival women.


Identification of a putative binding site critical for general anesthetic activation of TRPA1.
General anesthetics suppress CNS activity by modulating the function of membrane ion channels, in particular, by enhancing activity of GABAA receptors. In contrast, several volatile (isoflurane, desflurane) and i.v. (propofol) general anesthetics excite peripheral sensory nerves to cause pain and irritation upon administration. These noxious anesthetics activate transient receptor potential ankyrin repeat 1 (TRPA1), a major nociceptive ion channel, but the underlying mechanisms and site of action are unknown. Here we exploit the observation that pungent anesthetics activate mammalian but not Drosophila TRPA1. Analysis of chimeric Drosophila and mouse TRPA1 channels reveal a critical role for the fifth transmembrane domain (S5) in sensing anesthetics. Interestingly, we show that anesthetics share with the antagonist A-967079 a potential binding pocket lined by residues in the S5, S6, and the first pore helix; isoflurane competitively disrupts A-967079 antagonism, and introducing these mammalian TRPA1 residues into dTRPA1 recapitulates anesthetic agonism. Furthermore, molecular modeling predicts that isoflurane and propofol bind to this pocket by forming H-bond and halogen-bond interactions with Ser-876, Met-915, and Met-956. Mutagenizing Met-915 or Met-956 selectively abolishes activation by isoflurane and propofol without affecting actions of A-967079 or the agonist, menthol. Thus, our combined experimental and computational results reveal the potential binding mode of noxious general anesthetics at TRPA1. These data may provide a structural basis for designing drugs to counter the noxious and vasorelaxant properties of general anesthetics and may prove useful in understanding effects of anesthetics on related ion channels.


Clade-related phenotypic switching among fluconazole resistant Candida albicans isolates.
C. albicans undergoes phenotypic switchng, a putative virulence trait assisting the organism to adapt to different environments. Although this switching has been studied among C. albicans isolates, not much is known about the process among various C. albicans clades (a group of genetic variants within a single species). To determine whether phenotypic switching among fluconazole resistant C. albicans isolates is clade-related. Fifteen fluconazole resistant C. albicans isolates from different clades were studied. Phenotypic switching was determined by a method previously described. Switching behaviour and different colony morphologies among different clades were compared. Phenotypic switching was observed in all clades, with clade SA exhibiting the most switching (75%), and clade NG the east (5.6%). Stipple was the most dominant phenotype observed in all clades (p = 0.024), occurring mostly in clade SA (35%). Irregular wrinkle phenotype was dominant in clade SA (62%). Phenotypic switching was clade-related. Highest switching in clade SA isolates suggests better survival un der adverse conditions. Stipple and irregular wrinkle phenotypes among clade SA isolates need to be studied further.


Continuity-based model interfacing for plant-wide simulation: a general approach.
In plant-wide simulation studies of wastewater treatment facilities, often existing models from different origin need to be coupled. However, as these submodels are likely to contain different state variables, their coupling is not straightforward. The continuity-based interfacing method (CBIM) provides a general framework to construct model interfaces for models of wastewater systems, taking into account conservation principles. In this contribution, the CBIM approach is applied to study the effect of sludge digestion reject water treatment with a SHARON-Anammox process on a plant-wide scale. Separate models were available for the SHARON process and for the Anammox process. The Benchmark simulation model no. 2 (BSM2) is used to simulate the behaviour of the complete WWTP including sludge digestion. The CBIM approach is followed to develop three different model interfaces. At the same time, the generally applicable CBIM approach was further refined and particular issues when coupling models in which pH is considered as a state variable, are pointed out.


TRP channels and STIM/ORAI proteins: sensors and effectors of cancer and stroma cell migration.
Cancer cells are strongly influenced by host cells within the tumour stroma and vice versa. This leads to the development of a tumour microenvironment with distinct physical and chemical properties that are permissive for tumour progression. The ability to migrate plays a central role in this mutual interaction. Migration of cancer cells is considered as a prerequisite for tumour metastasis and the migration of host stromal cells is required for reaching the tumour site. Increasing evidence suggests that transient receptor potential (TRP) channels and STIM/ORAI proteins affect key calcium-dependent mechanisms implicated in both cancer and stroma cell migration. These include, among others, cytoskeletal remodelling, growth factor/cytokine signalling and production, and adaptation to tumour microenvironmental properties such as hypoxia and oxidative stress. In this review, we will summarize the current knowledge regarding TRP channels and STIM/ORAI proteins in cancer and stroma cell migration. We focus on how TRP channel or STIM/ORAI-mediated Ca(2+) signalling directly or indirectly influences cancer and stroma cell migration by affecting the above listed mechanisms. This article is part of a themed section on Cytoskeleton, Extracellular Matrix, Cell Migration, Wound Healing and Related Topics. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-24.


Small bowel bypass as treatment for functional gastric obstruction.
Multiple bariatric operations performed on the same patient can cause loss of normal peristaltic function of the stomach. Bariatric revisions, especially when combined with previous truncal vagotomy, can lead to functional gastric obstruction. These patients complain of severe nausea and intractable vomiting. This can cause excessive weight loss and malnutrition, requiring at times total parenteral nutrition (TPN) or forms of enteral feeding. These patients frequently require a total or subtotal gastric resection with an esophago-jejunal anastomosis to relieve symptoms. We present two patients with a functional gastric obstruction treated by a small bowel bypass, which successfully relieved all symptoms of obstruction and allowed normal food intake.


EPR monitoring of wound oxygenation as a biomarker of response to gene therapy encoding hCAP-18/LL37 peptide.
To investigate the value of electron paramagnetic resonance oximetry to follow oxygenation in wounds treated by a plasmid-encoding host defense peptide hCAP-18/LL37. Flaps were created on diabetic mice (7- or 12-week-old db/db mice) presenting different levels of microangiopathy. The hCAP-18/LL37-encoding plasmids were administered in wounds by electroporation. Low-frequency electron paramagnetic resonance oximetry using lithium phthalocyanine as the oxygen sensor was used to monitor wound oxygenation in flaps during the healing process. Flaps were analyzed by immunohistochemistry to assess hypoxia and cell proliferation. Kinetics of closure was also assessed in excisional skin wounds. A reoxygenation of the flap was observed during the healing process in the 7-week-old db/db treated mice, but not in the untreated mice and the 12-week-old mice. Histological studies demonstrated less hypoxic regions and higher proportion of proliferating cells in hCAP-18/LL37-treated flaps in the 7-week-old db/db treated mice compared with untreated mice. Consistently, the kinetics of excisional wound closure was improved by hCAP-18/LL37 treatment in the 7-week-old db/db but not in the 12-week-old mice. Oxygenation measured by electron paramagnetic resonance oximetry is a promising biomarker of response to treatments designed to modulate wound oxygenation. Magn Reson Med 79:3267-3273, 2018. © 2017 International Society for Magnetic Resonance in Medicine.


Are avian intrapulmonary CO2 receptors chemically modulated mechanoreceptors or chemoreceptors?
Openings of paleopulmonic parabronchi in paralyzed, unidirectionally ventilated geese were photographed through small holes in the birds' mediodorsal secondary bronchi during single-unit recording from intrapulmonary CO2 receptors. Changes in the discharge frequency of the receptors as fractional CO2 concentration of ventilating gas was alternated between 0 and 0.05 were compared with the changes in cross-sectional areas of randomly selected parabronchial lumina. Intrapulmonary CO2 receptors, similar to those found in other avian species, are also present in geese. Changes in intrapulmonary CO2 concentration greatly influenced the discharge of these receptors but did not induce movement of parabronchial smooth muscle in this region of the lung. If most of the receptors are located in the paleopulmonic parabronchi, as currently appears to be the case, we must conclude that changes in receptor discharge in response to changes in intrapulmonary CO2 concentration do not result from mechanical distortion of the receptors induced by smooth muscle contraction; intrapulmonary CO2 receptors appear to be true chemoreceptors.


Actions of interleukin-4 on prostaglandin biosynthesis at the chorion-decidual interface.
We determined the effects of interleukin-4 on chorion and decidual prostaglandin production. Chorion and decidual cells from term placentas were grown to confluence. Cells were then incubated with interleukin-4 either alone or with other known stimulants of prostaglandin production: interleukin-1 beta, epidermal growth factor, ionomycin, or phorbol 12-myristate 13-acetate. Prostaglandin E2 production was determined with a specific radioimmunoassay. Interleukin-4 alone stimulated prostaglandin E2 production in chorion and decidual cells. Interleukin-4 significantly enhanced the stimulatory actions of phorbol 12-myristate 13-acetate, ionomycin, and epidermal growth factor but not interleukin-1 beta on prostaglandin E2 production. Interleukin-4 stimulates prostaglandin E2 production by chorion and decidual cells. These data suggest that interleukin-4 production by immune effector cells in gestational tissues may contribute to the pathophysiologic features of preterm labor.


Temporal changes in pollen flow and neighbourhood structure in a population of Saxifraga hirculus L.
The population are of flowering shoots of the perennial herb, Saxifraga hirculus, reaches a max. of 134 m2 and an overall density of flowers/m2 of 11.4. The flower is mainly visited by a syrphid sp., Eurimyia lineata, and to a lesser extent by another syrphid Neoscia tenur, a moth, Zygaena trifolii, and a fungus gnat, Asindulum nigrum. The distribution of the interfloral flight distance is leptokurtic. The mean flight distance of the visitors is 101 cm. 10% of the flights are much longer (2-8 m: cross-flower patch, and about 20 m: cross-population flights). If they are not included, the mean of flights (<1.7 m) becomes 28 cm. These flights become shorter with increasing flower density. The visitors do not have a nearest-neighbour foraging pattern. They visit on average the 8th nearest neighbour. The distribution of flight directions is uniform. Seed dispersal distances have a leptokurtic distribution and a mean dispersal distance of 13 cm. The ecological neighbourhood area is 66.4 m2 and 64.9 m2 assuming normality and allowing for leptokurtosis. Z. trifolii with its large proportion of long flights increases the size of the neighbourhood area considerably. The mean flight distance (<1.7 m) is correlated with neighbourhood area. The evolutionary impact of moths and butterflies to plant population structure is stressed.


[A morphological and morphometric study of the testicle in the rat vasectomized by electrocautery technics].
To evaluate the influence of vasectomy by different fulguration methods on the rat testicular structure. Experimental vasectomy was performed in Wistar rats by means of the Shapiro and Silber, and the Schmidt cauterization techniques. The animals were orchidectomized between 7 days and 9 months following vasectomy. A morphological and morphometric study of the rat testes was performed. We have observed that both cauterization techniques do not produce sequelae in the rat testicular structure and its morphology is compatible with the normal. The morphometric study showed that both techniques produced a significant decrease (p > 0.05) of the area occupied by seminiferous epithelium within one month post-vasectomy; however, these values returned to normal three months thereafter. Vasectomy by different fulguration methods does not change the rat testicular structure.


Cardiac biomarkers, electrolytes, and other analytes in collapsed marathon runners: implications for the evaluation of runners following competition.
We measured analytes in collapsed Boston Marathon runners to compare with changes in asymptomatic runners. Of collapsed runners at the 2007 marathon, 18.2% had a measurable cardiac troponin T (cTnT) value with a mean postrace level of 0.017 ng/mL (0.017 microg/L; SD, 0.02 ng/mL [0.02 microg/L]). Three subjects had cTnT values above the cutoff (0.10 ng/mL [0.10 microg/L]) typically used for the diagnosis of acute myocardial infarction. The mean and median N-terminal pro-B-type natriuretic peptide levels were 73 ng/L (SD, 77.3 ng/L) and 54.3 ng/L (interquartile range, 22.8-87.3 ng/L), respectively, in collapsed runners. Only 4.9% had values more than the age-specific normal value (<125 ng/L for subjects younger than 75 years). In collapsed subjects at the 2006 marathon, 18.0% had an abnormal sodium value, including 18 cases of hypernatremia and 7 cases of hyponatremia. The ionized calcium level was low in 49% of subjects, and the ionized magnesium level was low in 19.5% and elevated in 1 subject. The blood lactate level was elevated in 95% of subjects. The frequency of elevated postrace cTnT levels in collapsed athletes after endurance exercise is similar to that in asymptomatic runners. Other metabolic abnormalities, including hypernatremia, hyponatremia, low ionized calcium and magnesium levels, and lactic acidosis may contribute to muscle fatigue and collapse.


Changes in urinary catecholamines in response to noise exposure in workers at Sarcheshmeh Copper Complex, Kerman, Iran.
Noise is one of the most harmful agents in the workplace. In addition to the adverse effects of noise on the auditory system, as a stressor it may cause increased blood pressure, cardiovascular disease, anxiety, and impaired secretion of hormones. The purpose of this study was to evaluate changes in urinary catecholamines in workers exposed to industrial noise. This is an experimental study of the workers at the smelter section of Sarcheshmeh Copper Industries done on two separate days. During the first day, urine samples from 20 workers who did not use any hearing protection device, were collected during an 8-h work shift and on the second day the same was done but they were asked to use earplugs. Also 20 people were selected as a control group from people who were not exposed to noise at work. Urinary catecholamine levels were measured with ELISA kits. The mean urinary epinephrine and norepinephrine levels in the workers (without earplugs) was respectively 8.69 and 35.56 μg/8h on the first day and on the second day (with earplugs) dropped to 6.45 and 30.95 μg/8h. Noise reduction by earplugs led to almost significant reductions in urinary epinephrine (p = 0.05) and significant reductions in norepinephrine (p = 0.02). The results showed that with noise reduction the urinary excretion of stress hormones, especially norepinephrine significantly decreases and workers are probably less prone to stress-related disorders.


Impurity-Mediated Early Condensation of a Charge Density Wave in an Atomic Wire Array.
We directly show how impurity atoms induce the condensation of a representative electronic phase, the charge density wave (CDW) phase, in atomic scale with scanning tunneling microscopy. Oxygen impurity atoms on the self-assembled metallic atomic wire array on a silicon crystal condense the CDW locally above the pristine transition temperature. More interestingly, the CDW along the wires is induced not by a single atomic impurity but by the cooperation of multiple impurities. First-principles calculations disclose the mechanism of the cooperation as the coherent superposition of the local lattice strain induced by impurities, stressing the coupled electronic and lattice degrees of freedom for the CDW. This opens the possibility of the strain engineering over electronic phases of atomic-scale systems.


Competitive electrochemical immunosensor for the detection of unfolded p53 protein in blood as biomarker for Alzheimer's disease.
Alzheimer's disease is one of the most common causes of dementia nowadays, and its prevalence increases over time. Because of this and the difficulty of its diagnosis, accurate methods for the analysis of specific biomarkers for an early diagnosis of this disease are much needed. Recently, the levels of unfolded isoform of the multifunctional protein p53 in plasma have been proved to increase selectively in Alzheimer's Disease patients in comparison with healthy subjects, thus entering the list of biomarkers that can be used for the diagnosis of this illness. We present here the development of an electrochemical immunosensor based on nanostructured screen-printed carbon electrodes for the quantification of unfolded p53 in plasma samples. The sensor shows a suitable linear range (from 2 to 50 nM) for its application in real blood samples and a very low limit of detection (0.05 nM). The concentration of unfolded p53 has been accurately detected in plasma of elderly people in healthy conditions, subjects with mild cognitive impairment (MCI) and Alzheimer's Disease (AD) subjects, obtaining results with no significant differences to those provided by an ELISA assay. These results support the possibility of measuring unfolded p53 levels with a cheap, simple and miniaturized device with a promising future for point-of-care applications in the early diagnosis of Alzheimer's dementia.


Interleukin-4 overcomes the negative influence of cyclic AMP accumulation on antigen receptor stimulated B lymphocytes.
Activation of protein kinase A (PKA) in B lymphocytes prior to the ligation of the B cell antigen receptor (BCR) results in a profound inhibition of BCR induced proliferation. The major effect of increased PKA activity in B lymphocytes was the induction of apoptosis leading to a reduced BCR induced growth response. The growth promoting cytokine IL-4 rescued B lymphocytes from PKA mediated negative effects. IL-4 protected BCR stimulated cells from PKA mediated inhibition primarily by preventing apoptosis and growth arrest. PKA-activation caused a downregulation of anti-IgM induced expression of Bcl-xL protein, that was restored by IL-4. Previous studies have shown that PKA-activation blocks BCR induced phospholipase Cgamma-activation and calcium mobilization. IL-4 was unable to overcome the block in anti-IgM mediated calcium mobilization due to PKA-activation. B cell apoptosis induced by PKA-activation was also seen in CD72 stimulated cells, although CD72 mediated B-lymphocyte proliferation was not affected. PKA mediated block in phospholipase gamma-activation and calcium mobilization were not due to alterations in the activation of tyrosine kinases lyn, blk and syk. Moreover, BCR mediated tyrosine phosphorylation of PLC gamma2 and CD19 were also unaffected by cAMP accumulation. These observations are in contrast to the ability of PKA to drastically reduce the activity of ZAP-70 and syk in T lymphocytes and neutrophils, respectively. The IL-4 mediated protection appears to be due to a change in late events in BCR signaling, which are important for Bcl-xL expression.


Oscillating spatial structures of a tissue.
We present a simple mathematical model for the self-controlled growth of a tissue giving rise to an oscillating tissue size under certain conditions. The control is brought about by two substances (two inhibitors or one inhibitor and one nutrient) which influence the cell kinetics locally. The inhibitors are produced by the tissue itself (whereas the nutrient comes from outside but is consumed by the tissue which produces the same effect). Both diffuse freely throughout the tissue, and thus realize a communication between different parts of the tissue. In any case the tissue approaches a self-maintaining space-time structure with properties depending on the parameters of proliferation, death and inhibiting control. We discuss the conditions for this structure not to be time-independent but oscillating.


SARS: just another viral acronym?
Recent observations and experimental evidence have purported that a virus causes SARS, but such viruses have been isolated in only less than half of SARS patients in some studies and virologist Vincent Plummer of Winnipeg's National Microbiology Laboratory found that indeed 1 in 5 perfectly healthy Canadians with a history of recent travel to Asia had the virus. Therefore SARS microbiologic origins remain unclear. Outbreaks of multi-drug resistant (MDR) tuberculosis and the atypical mycobacteria simulate SARS on clinical, radiologic, epidemiologic, and diagnostic laboratory grounds and it is only logical then to include them in the differential to find a definitive cause and cure for SARS.


Crossing relationships among ancient and experimental sunflower hybrid lineages.
Reproductive barrier formation between newly derived hybrid taxa and their parental species represents a major evolutionary hurdle. Here, I examine the development of a sterility barrier during hybrid speciation by examining the fertility of progeny from all combinations of crosses involving three experimentally synthesized sunflower hybrid lineages, their natural hybrid counterpart, Helianthus anomalus, and their parents, H. annuus and H. petiolaris. Crosses between the parental species and H. anomalus generated almost completely sterile offspring (pollen viability < 5%; seed set < 1%). A fairly strong sterility barrier also has developed between three hybrid lineages and both parental species (pollen viability 11.1-41.6%; seed set 0.84-20.1%). In contrast, the three hybrid lineages are almost fully interfertile (pollen viabilities 83.1-88.6%; seed set 72.1-75.3%), as predicted by molecular mapping studies that indicate they have converged on a similar set of gene combinations and chromosomal rearrangements. A modest decline in compability is observed in crosses between the three hybrid lineages and H. anomalus (pollen viabilities 64.1-70.7%; seed set 37-43%), a result that agrees well with prior data demonstrating significant congruence between the genomes of the natural and experimental hybrid lineages. These observations not only indicate that reproductive isolation can arise as a by-product of fertility selection in hybrid populations, but also testify to the repeatability of this mode of speciation.


Differences in mucus-stimulating serum fractions of cystic fibrosis patients and controls.
In nature, the urn cell complexes which swim in the coelomic fluid of the marine invertebrate, Sipunculus nudus, produce "tails" of mucus in response to bacterial pathogens. Since they produce measurable tails of mucus in vitro, suspensions of urn cell complexes provide a bioassay for mucus-stimulating substances (MSS) in biological fluids, including several human body fluids. Heat-activated seawater dilutions of human serum contain MSS. Serum from 87 cystic fibrosis (CF) homozygotes, 60 obligate heterozygotes, and 45 controls were fractionated on a Sephadex G-200 gel filtration column. After subsequent heating for 4 min at 85 degrees C, the fractions of all normal sera showed two characteristic peaks of MSS activity. The pattern differed in heated serum fractions of CF patients, in that the second peak was lacking in 59% of individual tests. The pattern was intermediate in heterozygote sera. Of the 36 CF serum fractions which did have two peaks of activity, 89% had the predominant activity in peak 1. The frequency of single peaks of activity increased with patient age, from 33% in those under 10 years to 75% in those over 16. The molecular weight of peak 1 is about 75,000 daltons, of peak 2 about 30,000. One may speculate that the frequent lack of peak 2 serum components may be associated with the inability of most CF patients to produce normal mucus following respiratory infection.


Comparative study of the neuronal populations containing beta-endorphin, corticotropin and dopamine in the arcuate nucleus of the rat hypothalamus.
Neurons simultaneously immunoreactive with anti-beta-endorphin and anti-(17-39) corticotropin (anti(17-39) ACTH) have been detected in the arcuate and ventromedial nuclei of the hypothalamus of colchicine-treated rats. These neurons are different from those fluorescent with the Falck and Hillarp technique. These results show that in the arcuate nucleus, immunoreactive ACTH and beta-endorphine are stored in the same neurons which are different from dopamine-containing neurons.


Immunogenicity and safety of a fully liquid aluminum phosphate adjuvanted Haemophilus influenzae type b PRP-CRM197-conjugate vaccine in healthy Japanese children: A phase III, randomized, observer-blind, multicenter, parallel-group study.
Broad use of monovalent Haemophilus influenzae type b (Hib) conjugate vaccines based on the capsular polysaccharide polyribosyl-ribitol phosphate (PRP), has significantly reduced invasive Hib disease burden in children worldwide, particularly in children aged <1year. In Japan, PRP conjugated to tetanus toxoid (PRP-T) vaccine has been widely used since the initiation of public funding programs followed by a routine vaccination designation in 2013. We compared the immunogenicity and safety of PRP conjugated to a non-toxic diphtheria toxin mutant (PRP-CRM197) vaccine with the PRP-T vaccine when administered subcutaneously to healthy Japanese children in a phase III study. Additionally, we evaluated the immunogenicity and safety profiles of a diphtheria-tetanus acellular pertussis (DTaP) combination vaccine when concomitantly administered with either PRP-CRM197 or PRP-T vaccines. The primary endpoint was the "long-term seroprotection rate", defined as the group proportion with anti-PRP antibody titers ⩾1.0μg/mL, after the primary series. Long-term seroprotection rates were 99.3% in the PRP-CRM197 group and 95.6% in the PRP-T group. The intergroup difference (PRP-CRM197 group - PRP-T group) was 3.7% (95% confidence interval: 0.099-7.336), demonstrating that PRP-CRM197 vaccine was non-inferior to PRP-T vaccine (p<0.0001). Furthermore, the "short-term seroprotection rate" (anti-PRP antibody titer ⩾0.15μg/mL) before booster vaccination was higher in the PRP-CRM197 group than in PRP-T. Concomitant administration of PRP-CRM197 vaccine with DTaP vaccine showed no differences in terms of immunogenicity compared with concomitant vaccination with PRP-T vaccine and DTaP vaccine. Although CRM197 vaccine had higher local reactogenicity, overall, both Hib vaccines had acceptable safety and tolerability profiles. The immunogenicity of PRP-CRM197 vaccine administered subcutaneously as a three-dose primary series in children followed by a booster vaccination 1year after the primary series induced protective levels of Hib antibodies with no safety or tolerability concerns. Registered on ClinicalTrials.gov: NCT01379846.


Macrophages support pathological erythropoiesis in polycythemia vera and β-thalassemia.
Regulation of erythropoiesis is achieved by the integration of distinct signals. Among them, macrophages are emerging as erythropoietin-complementary regulators of erythroid development, particularly under stress conditions. We investigated the contribution of macrophages to physiological and pathological conditions of enhanced erythropoiesis. We used mouse models of induced anemia, polycythemia vera and β-thalassemia in which macrophages were chemically depleted. Our data indicate that macrophages contribute decisively to recovery from induced anemia, as well as the pathological progression of polycythemia vera and β-thalassemia, by modulating erythroid proliferation and differentiation. We validated these observations in primary human cultures, showing a direct impact of macrophages on the proliferation and enucleation of erythroblasts from healthy individuals and patients with polycythemia vera or β-thalassemia. The contribution of macrophages to stress and pathological erythropoiesis, which we have termed stress erythropoiesis macrophage-supporting activity, may have therapeutic implications.


Relationship between susceptibility to antimicrobials and virulence factors in paediatric Escherichia coli isolates.
The in vitro susceptibilities to several antibiotics of 136 Escherichia coli strains containing virulence factors isolated from children with urinary tract infection were analysed. Escherichia coli strains were analysed by multiplex polymerase chain reaction for genes encoding the following virulence factors: pyelonephritis-associated pili (pap); S fimbriae (sfa); afimbrial adhesin I (afaI); haemolysin (hly); cytotoxic necrotizing factor I (cnfI); and aerobactin (aer). It was observed that the virulence genes increased antibiotic resistance of resistant strains and increased the sensitivity of susceptible strains.


Prevalence of HBsAg and anti-HBs among delivering women.
A survey of 2,500 delivering women revealed a 7.6% incidence of past infection with hepatitis B virus (HBV) (HBsAg or anti-HBs). Only 5.9% of the anti-HBs-positive mothers had a possible history of parenteral exposure to hepatitis B and none of the 55 HBsAg carriers had such a history. The findings suggest that HBV is endemic and that it is probably spread in part by nonparenteral means. The high rates of HBsAg and anti-HBs point to the possible preventive value of routine screenings for this system among pregnant women.


Synthesis of prenylated flavonols and their potents as estrogen receptor modulator.
Prenylated flavonols are known as phytoestrogen and have good bioactivties. However, their abundances in nature are pretty low. It is required to find an efficient synthesis technique. Icariin is a prenylated flavonol glycoside with low cost. It can be used to synthesize different prenylated flavonols. A combination of cellulase and trifluoacetic acid hydrolysis could effectively remove rhamnose and glucose from icariin. Icaritin, anhydroicaritin and wushanicaritin were the leading prenylated flavonol products. Their affinities to estrogen receptors α and β were predicted by docking study. The weak affinity of wushanicaritin indicated that prenyl hydroxylation impaired its affinity to estrogen receptor β. The prenyl cyclization led to a loss of affinity to both receptors. The interactions between icaritin and ligand binding cavity of estrogen receptor β were simulated. π-π stacking and hydrophobic forces were predicted to be the dominant interactions positioning icaritin, which induced the helix (H12) forming an activated conformation.


Video fluoroscopy for evaluating adenoid hypertrophy in children.
Adenoid hypertrophy is a common cause of upper airway obstruction in children. Traditionally, adenoid size has been evaluated using a conventional lateral skull film. Flexible endoscopy is now the gold standard for the evaluation of the upper airway. Children need to be cooperative in order to complete a videonasopharyngoscopy examination, which is not always possible. The purpose of this paper is to determine the sensitivity and specificity of lateral video fluoroscopy for assessing adenoid size compared to conventional lateral skull films with videonasopharyngoscopy as the gold standard. Twenty pediatric patients with adenoid hypertrophy demonstrated by videonasopharyngoscopy, and 20 control patients without adenoid hypertrophy were assessed with video fluoroscopy and lateral skull radiograph. Two independent examiners evaluated all studies. Specificity, sensitivity, and predictive values were obtained for findings on video fluoroscopy and lateral skull film. Video fluoroscopy showed 100% sensitivity, and 90% specificity for the diagnosis of adenoid hypertrophy. Lateral skull films showed 70% sensitivity, and 55% specificity. A Spearman correlation coefficient demonstrated a significant correlation (P<0.05) between findings on video fluoroscopy and videonasopharyngoscopy. In contrast, there was a no significant correlation (P>0.05) between lateral skull films and videonasopharyngoscopy. Video fluoroscopy appears to be a safe and reliable procedure for assessing adenoid hypertrophy in children.


Wastewater preinteraction accelerates the photoaging of disposable box-derived polystyrene microplastics in water.
Before being discharged into natural environment, almost all of microplastics (MPs) interact with wastewater constituents in wastewater treatment plants (WWTPs). This study investigated the photoaging of disposable box-derived polystyrene (PS) mediated by real wastewater by simulating the case flowing from WWTPs to natural water. Results showed that wastewater influent pretreatment significantly enhanced the photoaging of PSMPs through the sorption of wastewater constituents, e.g., 2.02 times of increase in photooxidation after 30 d of ultraviolet irradiation. Fulvic acid was identified as the leading contributor for the enhancing effect of wastewater relative to other wastewater constituents such as Cl, CO32-, NO3- and clay particles. In-depth mechanism analysis showed that the observed enhancement was critically controlled by the photosensitization effect of wastewater itself and the enhanced utilization of PSMPs for ultraviolet energy. Specifically, various sorbed wastewater constituents can not only generate higher concentrations of •OH and O2⋅- than clean MPs without constituents, but also reinforce the utilization of PSMPs for light energy due to the increased dispersion in solution by increasing hydrophilicity and surface charges. Also, the light-shielding effect was induced by wastewater, but was less important. This study bridges wastewater source and MP aging and fate and suggests the shortened lifetime of (micro)plastic samples via WWTP input to deepen our understanding of MP pollution in the environment.


Agaricus blazei Murill as an efficient hepatoprotective and antioxidant agent against CCl4-induced liver injury in rats.
Agaricus blazei Murill is one of the very popular edible medicinal mushrooms. The present study investigated the protective effect of this biologically active mushroom on the tissue peroxidative damage and abnormal antioxidant levels in carbon tetrachloride induced hepatotoxicity in male albino rats. Male albino rats of Sprague-Dawley strain weighting (120-150 g) were categorized into five groups. The first group served as the normal control, the second and the third groups were treated with Agaricus blazei Mushroom extract and carbon tetrachloride dose, respectively. Fourth group (protective group) was first treated with Agaricus blazei Mushroom extract followed by carbon tetrachloride treatment and fifth (therapeutic group) with carbon tetrachloride first followed by Agaricus blazei Mushroom treatment. The wet fruiting bodies of mushroom Agaricus blazei Murill, crushed and suspended in distilled water was administered orally to the treated groups of male albino rats. The activities of various enzymes (aspartate and alanine transaminase, lactate dehydrogenase, glutathione reductase), levels of non-enzymatic antioxidants (glutathione, vitamin C, vitamin E) and level of lipid peroxidation (malondialdehyde) were determined in the serum of all the experimental animals. Decrease in all the enzymes and non-enzymatic antioxidant, along with an increase in the lipid peroxidative index (malondialdehyde) was found in all the carbon tetrachloride treated rats as compared with normal controls. Also increase level of non-enzymatic antioxidant along with the decrease level in malondialdehyde was found in all experimental animals which were treated with Agaricus blazei Mushroom extract as compared with normal controls. The findings indicate that the extract of Agaricus blazei Murill can protect the liver against carbon tetrachloride induced oxidative damage in rats and is an efficient hepatoprotective and antioxidant agent against carbon tetrachloride induced liver injury.


The interspecific variations in molecular responses to various doses of heat and cold stress: The case of cereal aphids.
Insects are currently subjected to unprecedented thermal stress due to recent increases in the frequency and amplitude of temperature extremes. Understanding molecular responses to thermal stress is critically important to appreciate how species react to thermal stress. Three co-occurring cosmopolitan species are found within the guild of cereal aphids: Sitobion avenae, Ropalosiphum padi and Metopolophium dirhodum. Earlier reports have shown that increasing frequency of temperature extremes causes a shift in dominant species within guilds of cereal aphids by differently altering the population's growth. We hypothesize that a differential molecular response to stress among species may partially explain these changes. Heat shock proteins (HSPs) are molecular chaperones well known to play an important role in protecting against the adverse effects of thermal stress. However, few studies on molecular chaperones have been conducted in cereal aphids. In this study, we compared the heat and cold tolerance between three aphid species by measuring the median lethal time (Lt50) and examined the expression profiles of seven hsp genes after exposures to comparable thermal injury levels and also after same exposure durations. Results showed that R. padi survived comparatively better at high temperatures than the two other species but was more cold-sensitive. Hsp genes were induced more strongly by heat than cold stress. Hsp70A was the most strongly up-regulated gene in response to both heat and cold stress. R. padi had more heat inducible genes and significantly higher mRNA levels of hsp70A, hsp10, hsp60 and hsp90 than the other two species. Hsps ceased to be expressed at 37 °C in M. dirhodum and S. avenae while expression was maintained in R. padi. In contrast, M. dirhodum was more cold tolerant and had more cold inducible genes than the others. These results confirm species-specific differences in molecular stress responses and suggest that differences in induced expression of hsps may be related to species' thermal tolerance, thus causing the changes in the relative abundance.


Myelolipoma of adrenal.
A case of a forty-six-year-old woman with an adrenal myelolipoma on the left side is reported. The presenting complaint was pain, and investigation revealed a large, relatively avascular nonfunctioning tumor of the left adrenal. This rare (ninth reported instance of surgical removal) tumor is briefly reviewed.