Physical properties of small water clusters in low and moderate electric fields.
Likely candidates for the lowest minima of water clusters (H(2)O)(N) for N ≤ 20 interacting with a uniform electric field strength in the range E ≤ 0.6 V/Å have been identified using basin-hopping global optimization. Two water-water model potentials were considered, namely TIP4P and the polarizable Dang-Chang potential. The two models produce some consistent results but also exhibit significant differences. The cluster internal energy and dipole moment indicate two varieties of topological transition in the structure of the global minimum as the field strength is increased. The first takes place at low field strengths (0.1 V/Å<E < 0.2 V/Å) and reorganizes the hydrogen-bonds to orient the water permanent dipoles along the field. The second type of transition occurs at larger field strengths (0.3 V/Å<E < 0.5 V/Å) and corresponds to an extensive structural reorganization, where several hydrogen-bonds break as the cluster stretches along the field direction, the larger clusters (N > 10) usually forming helical structures.


Optical Bloch oscillations of an Airy beam in a photonic lattice with a linear transverse index gradient.
We theoretically report the existence of optical Bloch oscillations (BO) of an Airy beam in a one-dimensional optically induced photonic lattice with a linear transverse index gradient. The Airy beam experiencing optical BO shows a more robust non-diffracting feature than its counterparts in free space or in a uniform photonic lattice. Interestingly, a periodical recurrence of Airy shape accompanied with constant alternation of its acceleration direction is also found during the BO. Furthermore, we demonstrate that the period and amplitude of BO of an Airy beam can be readily controlled over a wide range by varying the index gradient and/or the lattice period. Exploiting these features, we propose a scheme to rout an Airy beam to a predefined output channel without losing its characteristics by longitudinally modulating the transverse index gradient.


Evidence of enhanced serum amino acid profile but not appetite suppression by dietary glycomacropeptide (GMP): a comparison of dairy whey proteins.
There is evidence that high-protein foods increase satiety and may aid weight loss, yet little is known of differential effects of protein composition. The aim of the study was to compare the acute effects of 4 whey proteins on satiety and food intake and to evaluate possible relationships with postprandial serum amino acid concentrations. Isoenergetic high-protein shakes (∼1 MJ) containing 25 g whey protein were given to 18 lean male participants using a crossover design. Three protein fractions identified as satiating in a rat model, glycomacropeptide (GMP), beta-lactoglobulin (ß-lac), and colostrum whey protein concentrate (WPC), were compared with a WPC control. A standardized 2.5MJ breakfast was given at 0830 hours, followed by the preload beverages at 1130 hours. Participants rated appetite sensations using visual analogue scales (VAS) prior to the beverage (baseline, 0 minutes) and then at 15, 30, 45, 60, 90, 150, and 210 minutes. Energy and macronutrient intake was measured by covert weighing of an ad libitum lunch meal at 90 minutes. Repeat blood samples were collected via venous cannulation. Serum amino acid (a.a.) concentrations differed between whey fractions (p=0.012) and were higher following GMP compared to ß-lac (p=0.051) and colostrum WPC (p=0.044) but not the WPC control (p=0.20). There was no difference in VAS-rated hunger, satisfaction, or thoughts of food between whey fractions, but fullness did differ (p=0.032) and was highest following the ß-lac beverage. Energy intake was not suppressed relative to control by any of the 3 whey fractions. We conclude that total serum a.a. concentration was a poor indicator of satiety, with little evidence of differential satiety between these whey proteins other than a modest enhancement of fullness by ß-lac.


Infections of the urinary tract in women: a prospective, longitudinal study of 235 women observed for 1-19 years.
A prospective long-term study was conducted of 235 young to middle-aged women with past histories of and/or active infections of the urinary tract. The present report defines certain characteristics of the population and of the 1,018 confirmed infections of the urinary tract that occurred during observation periods ranging from 1.1 to 19.4 years (mean, 7.4 yr). The population could be divided into 3 groups: women with confirmed infections who did (Group 1, n = 19) or did not (Group 2, n = 191) receive courses of antimicrobial prophylaxis and those who did not have confirmed infections (Group 3, n = 25). The 3 groups differed significantly only in their mean infection rates per year (3.1, 0.8, and 0.0, respectively). The number of infections among individual women ranged from 0 to 42. The patterns of recurrent infections among individual women ranged widely and were not predictable. Clusters of infections occurred in 45.7% of the women and ranged in size from 2 to 12 infections per cluster. The proportions of different infecting organisms and clinical syndromes were similar to those reported by others. accounted for the great majority of infections. Eighty-five percent of the isolates of tested were serologically classified. A total of 50 different O groups were identified. Three (O4, O6, and O75) of the 131 potential O groups accounted for 49% of the isolates that could be classified. In each of the 4 clinical syndromes, these same 3 O groups were also the most frequently identified. The ability to classify serologically the infecting isolates of permitted a more complete definition of the complexity of patterns of recurrent infections among individual women. The findings in the present study are compared with those in the literature.


Relationship between inflammatory hepatic disease and inflammatory bowel disease, pancreatitis, and nephritis in cats.
To determine whether cats with inflammatory hepatic disease had concurrent inflammatory bowel disease (IBD), pancreatitis, or chronic interstitial nephritis. Prospective case series. 78 tissue sections of liver, intestine, pancreas, and kidney from cats that had previous necropsy examinations at the teaching hospital. We reviewed histologic sections of liver, intestine, pancreas, and kidney from cats that had previous necropsy examinations and determined the prevalence of lymphocytic portal hepatitis, cholangiohepatitis, IBD, pancreatitis, and chronic interstitial nephritis, and the relationship among them. 36 cats had lymphocytic portal hepatitis, 18 had cholangiohepatitis, and 24 did not have inflammatory hepatic disease. The prevalence of IBD (10/36; 28%) and pancreatitis (5/36; 14%) in cats with lymphocytic portal hepatitis was not significantly different from cats without inflammatory hepatic disease. The prevalence of IBD (15/18; 83%) and pancreatitis (9/18; 50%) was greater (P < 0.05) for cats with cholangiohepatitis, compared with cats without inflammatory hepatic disease. Thirty-nine percent of cats (7/18) with cholangiohepatitis had IBD and pancreatitis. Evidence of IBD in association with cholangiohepatitis was characterized by infiltration of lymphocytes and plasma cells into the lamina propria; however, neutrophilic infiltrates also were found in 6 of 15 (40%) cats with cholangiohepatitis. Pancreatitis was mild in all cats. Cats with a diagnosis of cholangiohepatitis should be evaluated for IBD and pancreatitis.


Glial Cell Calcium Signaling Mediates Capillary Regulation of Blood Flow in the Retina.
The brain is critically dependent on the regulation of blood flow to nourish active neurons. One widely held hypothesis of blood flow regulation holds that active neurons stimulate Ca(2+) increases in glial cells, triggering glial release of vasodilating agents. This hypothesis has been challenged, as arteriole dilation can occur in the absence of glial Ca(2+) signaling. We address this controversy by imaging glial Ca(2+) signaling and vessel dilation in the mouse retina. We find that sensory stimulation results in Ca(2+) increases in the glial endfeet contacting capillaries, but not arterioles, and that capillary dilations often follow spontaneous Ca(2+) signaling. In IP3R2(-/-) mice, where glial Ca(2+) signaling is reduced, light-evoked capillary, but not arteriole, dilation is abolished. The results show that, independent of arterioles, capillaries actively dilate and regulate blood flow. Furthermore, the results demonstrate that glial Ca(2+) signaling regulates capillary but not arteriole blood flow. We show that a Ca(2+)-dependent glial cell signaling mechanism is responsible for regulating capillary but not arteriole diameter. This finding resolves a long-standing controversy regarding the role of glial cells in regulating blood flow, demonstrating that glial Ca(2+) signaling is both necessary and sufficient to dilate capillaries. While the relative contributions of capillaries and arterioles to blood flow regulation remain unclear, elucidating the mechanisms that regulate capillary blood flow may ultimately lead to the development of therapies for treating diseases where blood flow regulation is disrupted, including Alzheimer's disease, stroke, and diabetic retinopathy. This finding may also aid in revealing the underlying neuronal activity that generates BOLD fMRI signals.


Hyponatremia in a hospital population.
The frequency, causes, and outcome of hyponatremia (plasma sodium less than 125 mmol/L), and the value of some routine investigations were studied during a six month period in a hospital population. The incidence and prevalence of hyponatremia were 1.5 and 2.6 per 100 patients per day, respectively. A majority of patients (75%) developed hyponatremia in the hospital. The commonest cause of hyponatremia was normovolemic hyponatremia (79 patients). Hypovolemic and hypervolemic hyponatremia were seen in 63 and 21 patients, respectively. Urine osmolality did not differ between the three groups, and was of little diagnostic value. The mortality in the hyponatremic patients was 41.7%.


Modeling of transient ultrasonic wave propagation using the distributed point.
Transient ultrasonic waves in a fluid medium generated by a flat circular and a point-focused transducer of finite size are modeled by the distributed point source method (DPSM). DPSM is a Green's-function-based semi-analytical mesh-free technique which is modified here to incorporate the transient loading from a finite-sized acoustic transducer. Conventional DPSM solves acoustic problems in steady-state frequency domain. Here, DPSM is extended to the time domain without the fast Fourier transform (FFT) but using the Green's function in the time domain. This modified method is denoted t-DPSM. Harmonic point sources of DPSM are replaced by time-dependent point sources in t-DPSM. Generated t-DPSM results are compared with the finite element (FE) results for both focused and flat circular transducers. The developed method is used to solve the transient problem of wave scattering by an air bubble in a fluid as the bubble is moved horizontally or vertically from the focal point of the focused transducer. The received energy signal is compared for different eccentricities.


[Mediastinal lymph node metastasis from esophageal carcinoma: CT assessment with pathologic correlation].
Computed tomographic (CT) scans were performed in 179 patients with esophageal carcinoma to evaluate mediastinal lymph node metastasis. Histopathologic findings were compared with CT findings in a total of 7,218 resected lymph nodes. First, the criterion for lymph node metastasis on CT scans was 10 mm or more in long transverse diameter. The overall sensitivity and positive predictive value (PPV) were 19% (60 of 317 nodes) and 33% (60 of 180 nodes), respectively. Analysis of each of the eight subgroups of mediastinal nodes revealed that the PPV was more than 70% in node Nos. 105, 108, 110, and 112. In other subgroups, however, the PPV was less than 60%. Sensitivity was less than 50% in all eight subgroups. Second, the criterion for metastasis was 10 mm or more in short transverse diameter. The overall sensitivity and PPV were 8% (26 of 317 nodes) and 63% (26 of 41 nodes), respectively. Analysis of subgroups showed that the PPV in No. 106 nodes increased to 92%. In No. 106 nodes, use of a 5 mm criterion in long transverse diameter increased sensitivity to only 55%. Of the 317 histopathologically proven metastatic lymph nodes, 90 nodes (28%) were 10 mm or more in size, 112 (35%) were 5-10 mm, and 115 (36%) were less than 5 mm. Of the 6,901 non-metastatic lymph nodes, 473 nodes (7%) were 10 mm or more in size. Small (less than 5 mm in size) metastatic nodes were present in all eight subgroups. Among No. 107 and 109 nodes, large (10 mm or more in size) nonmetastatic nodes were prominent, resulting in low sensitivity and PPV. We conclude that CT does not provide an accurate assessment of metastatic versus non-metastatic mediastinal lymph nodes in patients with esophageal carcinoma.


Contoured Harrington instrumentation in the treatment of unstable spinal fractures. The effect of supplementary sublaminar wires.
Twenty-nine patients with major fractures and fracture-dislocations of the thoracic and lumbar spine were treated by spinal fusion and contoured Harrington distraction instrumentation. Two groups of patients were identified. Group I (16 patients) had sublaminar wires. Group II (13 patients) had no wiring. Satisfactory alignment was achieved in all patients. There were several complications in both groups. None of the patients in Group I had postoperative cast immobilization. The addition of sublaminar wiring appears to eliminate the need for rigid external immobilization and is beneficial only for patients who cannot tolerate body casts. This technique is a disadvantage, however, when a short-length fusion is desired.


Translational demand is not a major source of plasmid-associated fitness costs.
Plasmids are key drivers of bacterial evolution because they are crucial agents for the horizontal transfer of adaptive traits, such as antibiotic resistance. Most plasmids entail a metabolic burden that reduces the fitness of their host if there is no selection for plasmid-encoded genes. It has been hypothesized that the translational demand imposed by plasmid-encoded genes is a major mechanism driving the fitness cost of plasmids. Plasmid-encoded genes typically present a different codon usage from host chromosomal genes. As a consequence, the translation of plasmid-encoded genes might sequestrate ribosomes on plasmid transcripts, overwhelming the translation machinery of the cell. However, the pervasiveness and origins of the translation-derived costs of plasmids are yet to be assessed. Here, we systematically altered translation efficiency in the host cell to disentangle the fitness effects produced by six natural antibiotic resistance plasmids. We show that limiting translation efficiency either by reducing the number of available ribosomes or their processivity does not increase plasmid costs. Overall, our results suggest that ribosomal paucity is not a major contributor to plasmid fitness costs. This article is part of the theme issue 'The secret lives of microbial mobile genetic elements'.


International migration and remittances to a Lebanese village.
"A number of hypotheses concerning remittances from foreign emigrants are developed and tested using questionnaire survey data from Lala, a Lebanese village. According to the theory, a rural family engages in an implicit insurance-type contract with the potential migrant because both are averse to risk.... Results from testing the hypotheses are somewhat consistent with the proposition that, after a period of adjustment, migrants do begin to remit, thereby providing their families with an insurance against the uncertainties of life in the country of origin. However, the level of remittances does not appear to depend on the potential to inherit from a family's wealth. Moreover, families do not seem to invest in their migrants so as to improve their farm lands and to undertake risky agricultural techniques. The long-term remittance commitment of migrants to their residual families suggests that migrants' altruism may be a more significant motivating factor than self-interest." (SUMMARY IN FRE)


Perchloroethylene: effects on body and organ weights and plasma butyrylcholinesterase activity in mice.
The effects of continuous and intermittent inhalation of perchloroethylene (PCE) on plasma butyrylcholinesterase (BuChE) activity, organ weights, liver morphology and motor activity in mice (strain NMRI) were tested. PCE exposure increased plasma BuChE activity in a time- and concentration dependent manner in both sexes. The increase was statistically significant at 37 p.p.m. in animals continuously exposed for 30 days. BuChE increased approximately 1.5 times in females and 2.5 times in males after 120 days exposure to 150 p.p.m. After rehabilitation of animals exposed for 30 days to 150 p.p.m., BuChE levels returned to normal. Liver weight also increased in a time and concentration dependent manner. Both sexes exhibited significant liver enlargement at 9 p.p.m. The increase was about 2.3 in females and 1.9 in males after continuous exposure to 150 p.p.m. for 120 days. After rehabilitation (120 days) of animals exposed to 150 p.p.m. for 30 days, a 10% increase still remained. A decrease in body weight gain was seen in both sexes after exposure to concentrations above 75 p.p.m. Female kidney weight was slightly increased. No clear effect on spleen weight could be detected. When the same time-weighted average concentration was used, intermittent exposure for 30 days had similar effects on liver weight and BuChE activity as continuous exposure, even when exposures lasted for only one hour per day. Liver cell morphology was changed after PCE exposure. The alterations could be observed already at 9 p.p.m. but disappeared after rehabilitation.


The Hybrid III upper and lower neck response in compressive loading scenarios with known human injury outcomes.
Physical biomechanical surrogates are critical for testing the efficacy of injury-mitigating safety strategies. The interpretation of measured Hybrid III neck loads in test scenarios resulting in compressive loading modes would be aided by a further understanding of the correlation between the mechanical responses in the Hybrid III neck and the probability of injury in the human cervical spine. The anthropomorphic test device (ATD) peak upper and lower neck responses were measured during dynamic compressive loading conditions comparable to those of postmortem human subject (PMHS) experiments. The peak ATD response could then be compared to the PMHS injury outcomes. A Hybrid III 50th percentile ATD head and neck assembly was tested under conditions matching those of male PMHS tests conducted on an inverted drop track. This includes variation in impact plate orientation (4 sagittal plane and 2 frontal plane orientations), impact plate surface friction, and ATD initial head/neck orientation. This unique matched data with known injury outcomes were used to evaluate existing ATD neck injury criteria. The Hybrid III ATD head and neck assembly was found to be robust and repeatable under severe loading conditions. The initial axial force response of the ATD head and neck is very comparable to PMHS experiments up to the point of PMHS cervical column buckle or material failure. An ATD lower neck peak compressive force as low as 6,290 N was associated with an unstable orthopedic cervical injury in a PMHS under equivalent impact conditions. ATD upper neck peak compressive force associated with a 5% probability of unstable cervical orthopedic injury ranged from as low as 3,708 to 3,877 N depending on the initial ATD neck angle. The correlation between peak ATD compressive neck response and PMHS test outcome in the current study resulted in a relationship between axial load and injury probability consistent with the current Hybrid III injury assessment reference values. The results add to the current understanding of cervical injury probability based on ATD neck compressive loading in that it is the only known study, in addition to Mertz et al. (1978), formulated directly from ATD compressive loading scenarios with known human injury outcomes.


Spatiotemporal EEG/MEG source analysis based on a parametric noise covariance model.
A method is described to incorporate the spatiotemporal noise covariance matrix into a spatiotemporal source analysis. The essential feature is that the estimation problem is split into two parts. First, a model is fitted to the observed noise covariance matrix. This model is a Kronecker product of a spatial and a temporal matrix. The spatial matrix models the spatial covariances by a function dependent on sensor distance. The temporal matrix models the temporal covariances as lag dependent. In the second part, sources are estimated given this noise model, which can be done very efficiently due to the Kronecker formulation. An application to real electroencephalogram (EEG) data shows that the noise model fits the data very well. Simulation results show that the resulting source estimates are more precise than those obtained from a standard analysis neglecting the noise covariance. In addition, the estimated standard errors of the source parameter estimates are far more precise than those obtained from a standard analysis. Finally, the source parameter standard errors are used to investigate the effects of temporal sampling. It is shown that increasing the sampling by a factor x, decreases the standard errors of all source parameters with the square root of x.


Detection of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli on flies at poultry farms.
In the Netherlands, extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli bacteria are highly prevalent in poultry, and chicken meat has been implicated as a source of ESBL-producing E. coli present in the human population. The current study describes the isolation of ESBL-producing E. coli from house flies and blow flies caught at two poultry farms, offering a potential alternative route of transmission of ESBL-producing E. coli from poultry to humans. Overall, 87 flies were analyzed in 19 pools. ESBL-producing E. coli bacteria were detected in two fly pools (10.5%): a pool of three blow flies from a broiler farm and a pool of eight house flies from a laying-hen farm. From each positive fly pool, six isolates were characterized and compared with isolates obtained from manure (n = 53) sampled at both farms and rinse water (n = 10) from the broiler farm. Among six fly isolates from the broiler farm, four different types were detected with respect to phylogenetic group, sequence type (ST), and ESBL genotype: A0/ST3519/SHV-12, A1/ST10/SHV-12, A1/ST58/SHV-12, and B1/ST448/CTX-M-1. These types, as well as six additional types, were also present in manure and/or rinse water at the same farm. At the laying-hen farm, all fly and manure isolates were identical, carrying blaTEM-52 in an A1/ST48 genetic background. The data imply that flies acquire ESBL-producing E. coli at poultry farms, warranting further evaluation of the contribution of flies to dissemination of ESBL-producing E. coli in the community.


Cystic tumors of the biliary tract: a complete excision is crucial.
Intrahepatic cystic tumors are rare liver tumors whose diagnosis is based on a wide range of imaging modalities. Surgical management and prognosis are not clearly defined. The medical records of patients with a diagnosis of intrahepatic cystic tumor managed in our unit were reviewed. Two patients were successfully treated by surgery. One of these two patients had to undergo a second laparotomy to obtain complete removal of the tumor. Another patient developed tumor recurrence after an incomplete incision of the cystic lesion previously performed abroad. She was referred to our unit but was deemed unresectable and therefore was referred for a liver transplantation. We report 3 cases of hepatic cystic tumors, showing some difficult issues related to the diagnosis and management of this condition and underlining the importance of performing a complete surgical excision to avoid early recurrence of the tumor.


Hyperhomocysteinemia and Lupus Nephritis.
Background In SLE, both disease-specific and traditional risk factors are important. Increased serum homocysteine levels are seen in approximately 15% of patients with systemic lupus erythematosus and are associated with an increased risk of atherothrombotic events in this population. The serum level of homocysteine in patients with lupus nephritis has not been well described. Methods We performed a retrospective review of patients who had both biopsy-proven lupus nephritis (class II-VI) and measured homocysteine levels during routine evaluation. Clinical and laboratory data were obtained from reviews of medical records. Results Of the 15 patients with lupus nephritis, 10 had elevated homocysteine levels. The ages ranged from 21-68 years and were predominately African-American females. There were three patients with class III, one with class III-V, two with class IV, and two with class V lupus nephritis. Two patients had more than one biopsy each, one with class III, IV-V, and one with III and IV. At the time, when the serum homocysteine level was measured, of the 10 patients with elevated homocysteine levels, five patients had positive anti-dsDNA, and four had hypocomplementemia predominately low C3 (three patients). All patients were on hydroxychloroquine. Conclusions This study demonstrates that patients with lupus nephritis are at a higher risk (66.6%) for developing elevated homocysteine levels.


Structural and functional basis for p38-MK2-activated Rsk signaling in toll-like receptor-stimulated dendritic cells.
Rsk kinases play important roles in several cellular processes such as proliferation, metabolism, and migration. Until recently, Rsk activation was thought to be exclusively initiated by Erk1/2, but in dendritic cells (DC) Rsk is also activated by p38 mitogen-activated protein (MAP) kinase via its downstream substrates, MK2/3. How and why this noncanonical configuration of the MAP kinase pathway is adopted by these key immune cells are not known. We demonstrate that the Erk1/2-activated C-terminal kinase domain of Rsk is dispensable for p38-MK2/3 activation and show that compared with fibroblasts, a greater fraction of p38 and MK2/3 is located in the cytosol of DC prior to stimulation, suggesting a partial explanation for the operation of the noncanonical pathway of Rsk activation in these cells. p38/MK2/3-activated Rsk phosphorylated downstream targets and is physiologically important because in plasmacytoid DC (pDC) stimulated with Toll-like receptor 7 (TLR7) agonists, Erk1/2 activation is very weak relative to p38. As a result, Rsk activation is entirely p38 dependent. We show that this unusual configuration of MAP kinase signaling contributes substantially to production of type I interferons, a hallmark of pDC activation.


A Label-free Time-resolved Luminescent Platform for Sensitive Endonuclease V Detection Based on Exonuclease III Regulated DNA-Tb3+ Luminescence.
Endonuclease V (EndoV) plays the important role of nucleotide excision repair (NER) in the maintenance of genomic stability. Highly sensitive detection of EndoV was achieved through an oligonucleotides sensitizing Tb3+ luminescent technique. We found that although both guanine-rich (G-rich) single-stranded DNA and dGMP could enhance the time-resolved luminescence of Tb3+, their efficiencies of enhancement were considerably different. Employing such interesting phenomenon, a label-free and time-resolved luminescent strategy for the sensitive detection of EndoV activity was developed based on DNA-enhanced time-resolved luminescence (TRL) of Tb3+. The EndoV was used to cut off the deoxyinosine site (dI) and convert the 3'-protruding termini to a recessed end, and Exonuclease III (Exo III) was used to enhance the signal contrast via digestion of G-rich DNA to dNTP. Combining with the natural advantages of the TRL, the proposed method exhibited a good linear response to EndoV ranging from 0.005 to 0.4 U/mL, with a low limit of detection of 0.005 U/mL.


Prevalence of malnutrition and vitamin A deficiency in the Diourbel, Fatick, and Kaolack regions of Senegal: feasibility of the method of impression cytology with transfer.
The evaluation of the prevalence of ophthalmological diseases and vitamin A deficiency in Senegalese preschool-aged children enabled us to confirm the method of impression cytology with transfer (ICT) and to assess the impact of ophthalmological diseases on the cytological appearance of conjunctival cells. A simplification of the ICT method consisted of transferring cells present on a strip of paper to a glass slide by finger pressure. Harris-Schorr staining of the sample papers confirmed the results obtained by the transfer. Inflammatory trachoma influenced the results of the test. This simple method will prove very helpful for detection of vitamin A deficiency in children in underdeveloped areas.


A Systematic Review of Computational Drug Discovery, Development, and Repurposing for Ebola Virus Disease Treatment.
Ebola virus disease (EVD) is a deadly global public health threat, with no currently approved treatments. Traditional drug discovery and development is too expensive and inefficient to react quickly to the threat. We review published research studies that utilize computational approaches to find or develop drugs that target the Ebola virus and synthesize its results. A variety of hypothesized and/or novel treatments are reported to have potential anti-Ebola activity. Approaches that utilize multi-targeting/polypharmacology have the most promise in treating EVD.


Effect of high dose inhaled beclomethasone dipropionate on carbohydrate and lipid metabolism in normal subjects.
The metabolic effects of four weeks' high dose inhaled beclomethasone dipropionate (500 micrograms twice daily) were studied in nine normal subjects with an open study design. No effect was found on fasting blood glucose concentration or glycosylated haemoglobin concentration. Peak blood glucose concentration 30 minutes after a 75 g oral glucose load was, however, significantly higher (7.1 (SEM 0.2) versus 6.7 (0.1) mmol/l, or 128 (3.6) v 121 (1.8) mg/100 ml). After treatment there was a 36% increase in fasting serum insulin concentration (7.6 (0.7) versus 5.6 (0.5) mU/l) and a 32% increase in the area under the serum insulin concentration curve after glucose challenge. High dose inhaled beclomethasone dipropionate treatment raised the fasting plasma cholesterol concentration (4.62 (0.25) v 4.16 (0.26) mmol/l, or 178 (9.7) v 161 (10.0) mg/100 ml) and high density lipoprotein cholesterol (1.19 (0.065) versus 0.97 (0.065) mmol/l, or 45 (2.5) v 37 (2.5) mg/100 ml). Fasting blood lactate and pyruvate concentrations were also significantly higher and blood glycerol lower. The findings indicate that high dose inhaled beclomethasone dipropionate may disturb both carbohydrate and lipid metabolism.


Full blockade of intestinal P-glycoprotein and extensive inhibition of blood-brain barrier P-glycoprotein by oral treatment of mice with PSC833.
Mice lacking mdr1-type P-glycoproteins (mdr1a/1b [-/-] mice) display large changes in the pharmacokinetics of digoxin and other drugs. Using the kinetics of digoxin in mdr1a/1b (-/-) mice as a model representing a complete block of P-glycoprotein activity, we investigated the activity and specificity of the reversal agent SDZ PSC833 in inhibiting mdr1-type P-glycoproteins in vivo. Oral PSC833 was coadministered with intravenous [3H]digoxin to wild-type and mdr1a/1b (-/-) mice. The direct excretion of [3H]digoxin mediated by P-glycoprotein in the intestinal mucosa of wild-type mice was abolished by administration of PSC833. Hepatobiliary excretion of [3H]digoxin was markedly decreased in both wild-type and mdr1a/1b (-/-) mice by PSC833, the latter effect indicating that in vivo, PSC833 inhibits not only mdr1-type P-glycoproteins, but also other drug transporters. Upon coadministration of PSC833, brain levels of [3H]digoxin in wild-type mice showed a large increase, approaching (but not equaling) the levels found in brains of PSC833-treated mdr1a/1b (-/-) mice. Thus, orally administered PSC833 can inhibit blood-brain barrier P-glycoprotein extensively, and intestinal P-glycoprotein completely. These profound pharmacokinetic effects of PSC833 treatment imply potential risks, but also promising pharmacological applications of the use of effective reversal agents.


Challenges of maintaining polio-free status of the European Region.
The European region, certified as polio free in 2002, had recent wild poliovirus (WPV) introductions, resulting in a major outbreak in Central Asian countries and Russia in 2010 and in current widespread WPV type 1 circulation in Israel, which endangered the polio-free status of the region. We assessed the data on the major determinants of poliovirus transmission risk (population immunity, surveillance, and outbreak preparedness) and reviewed current threats and measures implemented in response to recent WPV introductions. Despite high regional vaccination coverage and functioning surveillance, several countries in the region are at high or intermediate risk of poliovirus transmission. Coverage remains suboptimal in some countries, subnational geographic areas, and population groups, and surveillance (acute flaccid paralysis, enterovirus, and environmental) needs further strengthening. Supplementary immunization activities, which were instrumental in the rapid interruption of WPV1 circulation in 2010, should be implemented in high-risk countries to close population immunity gaps. National polio outbreak preparedness plans need strengthening. Immunization efforts to interrupt WPV transmission in Israel should continue. The European region has successfully maintained its polio-free status since 2002, but numerous challenges remain. Staying polio free will require continued coordinated efforts, political commitment and financial support from all countries.


Cellular localization of Na+/MYO-inositol co-transporter mRNA in the rat brain.
The distribution of Na+/MYO-inositol co-transporter (SMIT) mRNA in the rat brain was studied by in situ hybridization histochemistry. The highest levels of SMIT mRNA were observed in the choroid plexus. Intense hybridization signals were found in the pineal gland, the area postrema, the hippocampus, the locus coeruleus, the suprachiasmatic nucleus, the olfactory bulb and the Purkinje cell and granule cell layers of the cerebellum. Low to moderate levels of labelling were detected in almost all neurones and small glia-like cells throughout the brain. These results suggest that almost all cells in the brain possess an SMIT-mediated osmotic and ionic regulatory system, and uneven densities of positive SMIT mRNA signals may reflect the differences in sensitivity of the cells to osmotic and ionic changes and also reflect differences in permeability of capillaries.


Limits of computational biology.
Are we close to a complete inventory of living processes so that we might expect in the near future to reproduce every essential aspect necessary for life? Or are there mechanisms and processes in cells and organisms that are presently inaccessible to us? Here I argue that a close examination of a particularly well-understood system--that of Escherichia coli chemotaxis--shows we are still a long way from a complete description. There is a level of molecular uncertainty, particularly that responsible for fine-tuning and adaptation to myriad external conditions, which we presently cannot resolve or reproduce on a computer. Moreover, the same uncertainty exists for any process in any organism and is especially pronounced and important in higher animals such as humans. Embryonic development, tissue homeostasis, immune recognition, memory formation, and survival in the real world, all depend on vast numbers of subtle variations in cell chemistry most of which are presently unknown or only poorly characterized. Overcoming these limitations will require us to not only accumulate large quantities of highly detailed data but also develop new computational methods able to recapitulate the massively parallel processing of living cells.


The influence of fibrin polymerization and platelet-mediated contractile forces on citrated whole blood thromboelastography profile.
Thromboelastography analysis providing a global assessment of coagulation is gaining new interest in clinical practice. MinimalTF triggered whole blood thromboelastography provides a valuable tool for studying the kinetics of clot formation (expressed by the parameters R, K and alpha-angle) and the physical characteristics of the clot, such as its firmness and the elastic modulus shear (expressed by the parameters maximal amplitude MA and G). We studied the influence of fibrin polymerization and platelet functional status on each parameter of thromboelastographic trace obtained by minimalTF activation inWB by employing increasing concentrations of a fibrin polymerization inhibitors (the tetrapeptide Gly-Pro-Arg-Pro-OH.AcOH; Pefabloc-FG) and an inhibitor of actin polymerization (Cytochalasin D). Pefabloc-FG at concentrations higher than 5 mg/ml prolonged the R and K times and decreased the alpha-angle in a concentration-dependent manner but it did not modify MA and G parameters. At the concentration of 5 mg/ml, Pefabloc-FG completely inhibited clot formation. Cytochalasin D had no effect on R time but decreased the alpha-angle, MA and G parameters by reaching a plateau at the concentration of 5 microM. The effect of cytochalasin D was more pronounced on MA and G than on the alpha-angle. A combination of both Pefabloc-FG (0.5 mg/ml) and cytochalasin D (50 microM) significantly decreased alpha-angle compared to control as well as their single effect. However, G value was dramatically reduced in the presence of cytochalasin D exposure, without any additional effect when both inhibitors were combined. This study confirms the importance of fibrin polymerisation on the kinetics of thrombus formation and demonstrates the close association between the quality of the thrombus and the functional status of platelets. Normal platelet contractile forces are of major importance for the maximum amplitude of TEG which is related to the strength and elastic modulus of the thrombus.


Shared electronic care coordination systems following referral to hospice.
In Scotland, the Key Information Summary (KIS) enables health providers to access key patient information to guide decision-making out-of-hours. KISs are generated in primary care and rely on information from other teams, such as community specialist palliative care teams (CSPCTs), to keep them up-to-date. This study involved a service evaluation consisting of case note reviews of new referrals to a CSPCT and semi-structured interviews with palliative care community nurse specialists (CNSs) regarding their perspectives on KISs. Some 44 case notes were examined, and 77% of patients had a KIS on CSPCT referral. One-month post-referral, all those re-examined (n=17) had a KIS, and 59% KISs had been updated following CNS assessments. CNSs cited anticipatory care planning (ACP) as the most useful aspect of KIS, and the majority of CNSs said they would appreciate KIS editing access. A system allowing CNSs to update KISs would be acceptable to CNSs, as it could facilitate care co-ordination and potentially improve comprehensiveness of ACP information held in KISs.


Renal sympathetic denervation in therapy resistant hypertension - pathophysiological aspects and predictors for treatment success.
Many forms of human hypertension are associated with an increased systemic sympathetic activity. Especially the renal sympathetic nervous system has been found to play a prominent role in this context. Therefore, catheter-interventional renal sympathetic denervation (RDN) has been established as a treatment for patients suffering from therapy resistant hypertension in the past decade. The initial enthusiasm for this treatment was markedly dampened by the results of the Symplicity-HTN-3 trial, although the transferability of the results into clinical practice to date appears to be questionable. In contrast to the extensive use of RDN in treating hypertensive patients within or without clinical trial settings over the past years, its effects on the complex pathophysiological mechanisms underlying therapy resistant hypertension are only partly understood and are part of ongoing research. Effects of RDN have been described on many levels in human trials: From altered systemic sympathetic activity across cardiac and metabolic alterations down to changes in renal function. Most of these changes could sustainably change long-term morbidity and mortality of the treated patients, even if blood pressure remains unchanged. Furthermore, a number of promising predictors for a successful treatment with RDN have been identified recently and further trials are ongoing. This will certainly help to improve the preselection of potential candidates for RDN and thereby optimize treatment outcomes. This review summarizes important pathophysiologic effects of renal denervation and illustrates the currently known predictors for therapy success.


Mitochondrial localization of glucocortocoid receptor in glial (Müller) cells in the salamander retina.
Glucocorticoid hormones regulate the transcription of nuclear genes by way of their receptors. In addition, these hormones modulate mitochondrial gene transcription by mechanisms that remain poorly understood. Using immunofluorescence labeling in isolated Müller and photoreceptor cells and in intact salamander retina, we found that the glucocorticoid receptor (GR) is localized in both cell types. Confocal laser scanning microscopy and double staining with cytochrome oxidase (COX) showed that GR is localized in the mitochondria of Müller cells, but not in the mitochondria of photoreceptors. GR also colocalizes with glutamine synthetase (GS) in the cytoplasm of Müller cells. GR is also localized in the microvilli of the distal process of Müller cells and in the synaptic terminal of photoreceptors. Pre-incubation of Müller cells with 1 microM dexamethasone (DEX) for 7 h led to greater than 50% inhibition of the glutamate-induced increase in mitochondrial NADH. This late effect of glucocorticoids on glutamate metabolism could be ascribed, in part, to a direct action of steroid hormones on mitochondrial metabolism.


Retinal coenzyme Q in the bovine eye.
Coenzyme Q plays an integral role in oxygen metabolism and management, and there is a positive correlation between low tissue coenzyme Q concentrations and the progression of many degenerative diseases. Retinal oxidative damage plays a role in the pathogenesis of many degenerative eye diseases; nevertheless, despite the retina's high rate of oxygen metabolism, there is little data relating to retinal coenzyme Q concentrations. In this study, we quantified coenzyme Q in the model bovine eye and determined whether it could function as a retinal lipid antioxidant. We found that the neural retina's ubiquinone concentration exceeded those of the vitreous humor, lens, choroid, and extraocular muscle, but it was lower than those measured in heart, kidney, liver, and brain tissues. Ubiquinol was found to be as effective as vitamin E as a retinal lipid antioxidant. The overall relatively low levels of ubiquinone found in the retina, coupled with the retina's need for lipid antioxidants and oxidative metabolism, suggests that retinal function might be sensitive to changes in ubiquinone concentrations.


Extracorporal shock wave therapy for calcifying tendinitis of the shoulder.
During the past 2 years, 40 patients referred to the authors' hospital for persistent calcifying tendinitis of the shoulder were seen on prospective followup after undergoing a single extracorporal shock wave therapy. During a single therapy session, all patients received 1500 impulses of the energy density 0.28 mJ/mm2 in plexus anesthesia. Followup examinations were done at 6 and 24 weeks. In 62.5% of the patients partial or complete disintegration of the deposit was observed. Statistical analysis showed significant improvement both of subjective and objective criteria. According to the Constant score, 60% of the patients reached normal values, and 72.5% of the patients had no or only occasional discomfort. Only 6 patients (15%) reported no improvement at the 24-week followup.


Unique features of the trophoblast interferons.
The trophoblast interferons (IFN) are Type I IFN with about 50% amino acid sequence identity to the leukocyte IFN (IFN-alpha). They are the major secretory products of the trophoblast of ruminant ungulate species during pregnancy in the period immediately preceding attachment and implantation when they have been implicated in the phenomenon known as maternal recognition of pregnancy. The trophoblast IFN have antiviral and antiproliferative activities typical of other Type I IFN, but unlike IFN-alpha, -beta and -omega are poorly responsive to viral induction and have a highly restricted pattern of expression. Nevertheless, a recombinant bovine IFN-alpha can mimic many of the properties of the trophoblast IFN and has been used pharmacologically to improve pregnancy success in sheep. It still remains unclear, however, whether the trophoblast IFN have unique biological properties or whether they are unusual merely by virtue of the location, magnitude and temporal nature of their expression at a critical time during pregnancy.


Interprofessional Interactions and Competencies on Clinical Rotations: Preceptors' Perspectives of Student Experiences.
This study describes (1) preceptors' perceptions of interprofessional encounters that PA students had at clinical sites and (2) ways that the preceptors report evaluating the PA students' interprofessional practice skills. This study disseminated a single electronic survey of clinical preceptors who were affiliated with an accredited PA program. Descriptive statistics were used to analyze the results. Of 195 preceptors, 66 completed the survey. Practice specialties of respondents and nonrespondents were similar. Preceptors indicated that PA students had frequent interactions with a wide variety of health professionals and students. These interactions occurred with greater frequency in specialty settings and academic medical centers than in other settings. Preceptors reported that they assess interprofessional practice competencies, although many were not familiar with the definitions that the health care profession has endorsed. Findings suggest that educators may identify specific clinical sites or settings that are more optimal for interprofessional education interventions and that focused preceptor development may encourage deliberate assessment of students' interprofessional practice competencies.


Evaluation of a program to enhance young drivers' safety in Israel.
Young drivers in Israel, as in other parts of the world, are involved in car crashes more than any other age group. The graduated driver licensing system in Israel requires that all new drivers be accompanied by an experienced driver whenever they drive for the first 3 months after obtaining a driving license. In an effort to make the accompanied driving phase more effective, a novel program which targets both young drivers and their parents was initiated in 2005. The program administers a personal meeting with the young driver and the accompanying parent scheduled for the beginning of the accompanied driving phase. In this meeting guidance is given regarding best practices for undertaking the accompanied driving, as well as tips for dealing with in-vehicle parent-teen dynamics. Through 2008, almost 130,000 families of young drivers have participated in the program. In order to evaluate the effectiveness of the program, injury crash records of the young drivers who participated in the program were compared with those of all other young drivers that were licensed at the same time period. The results obtained indicate statistically significant lower crash records for young drivers that participated in the program. Limitations of the evaluation related to self-selection biases are discussed, and practical implications are suggested.


Effects of amlodipine on serum testosterone, testicular weight and gonado-somatic index in adult rats.
Calcium ions are vital in many biological processes including hormonal secretion, mitosis, reproduction, fertility and regulation of gene expression. Thus, calcium antagonists who are frequently prescribed for the cure of cardiovascular diseases may affect any of these physiological processes. This quasi experimental study was done at Army Medical College, Rawalpindi from October 2007 to March 2008. Thirty male Sprague Dawley rats, purchased from National Institute of Health, Islamabad were divided into group A (vehicle treated controls) and group B (amlodipine treated). After receiving drug treatment for 50 days, all the rats were sacrificed. Serum was stored to measure testosterone by enzyme immunoassay technique. The testes were removed for measuring absolute testicular weight and gonado-somatic index. Serum testosterone, absolute testicular weight and gonado-somatic index were found to be significantly reduced in amlodipine treated rats. These results suggest that long-term treatment with amlodipine might be associated with significant testicular regression and reduction in serum testosterone. Furthermore, since dihydopyridine antagonists are widely used in hypertension, our data may have some clinical implication in the management of infertility associated with hypertension.


Cambodia. MOE to introduce population education in three subjects.
Cambodia is currently undertaking reforms of its educational system both in structure and substance. Under these reforms, the Ministry of Education (MOE) is revising its curricula and textbooks in selective subjects. The government and UNFPA saw a timely opportunity to introduce population education concepts into three subjects, geography, home science, and moral education and civics from grades 7 to 12. To pave the way for this activity, the UNFPA and the government discussed the development of a pilot project that will concentrate first on the training of small numbers of professional educators and development of a first draft of curricula and textbooks including teacher's guides which could be tried out in this pilot stage and reproduced during the second phase. The project document has been prepared with the assistance of CST adviser on population education, Mr. Ansar Ali Khan, based in CST Bangkok, and is now under review.


Mechanism of aquaporin 4 (AQP 4) up-regulation in rat cerebral edema under hypobaric hypoxia and the preventative effect of puerarin.
We aim to investigate the mechanism of aquaporin 4 (AQP 4) up-regulation during high-altitude cerebral edema (HACE) in rats under hypobaric hypoxia and preventative effect of puerarin. Rats were exposed to a hypobaric chamber with or without the preventative treatment of puerarin or dexamethasone. Morriz water maze was used to evaluate the spatial memory injury. HE staining and W/D ratio were used to evaluate edema injury. Rat astrocytes and microglia were co-cultured under the condition of hypoxia with the administration of p38 inhibitor, NF-κB inhibitor or puerarin. Interleukin 6 (IL-6) and tumor necrosis factor α (TNF α) of cortex and culture supernatant were measured with ELISA. AQP4, phosphorylation of MAPKs, NF-κB pathway of cortex and astrocytes were measured by Western blot. Weakened spatial memory and cerebral edema were observed after hypobaric hypoxia exposure. AQP4, phosphorylation of NF-κB and MAPK signal pathway of cortex increased after hypoxia exposure and decreased with preventative treatment of puerarin. Hypoxia increased TNF-α and IL-6 levels in cortex and microglia and puerarin could prevent the increase of them. AQP4 of astrocytes increased after co-cultured with microglia when both were exposed to hypoxia. AQP4 showed a decrease after administered with p38 inhibitor, NF-κB inhibitor or puerarin. Hypoxia triggers inflammatory response, during which AQP4 of astrocytes can be up regulated through the release of TNF-α and IL-6 from microglia. Puerarin can exert a preventative effect on the increase of AQP4 through inhibiting the release of TNF-α and phosphorylation of NF-κB, MAPK pathway.


Non-additive QTL mapping of lactation traits in 124,000 cattle reveals novel recessive loci.
Deleterious recessive conditions have been primarily studied in the context of Mendelian diseases. Recently, several deleterious recessive mutations with large effects were discovered via non-additive genome-wide association studies (GWAS) of quantitative growth and developmental traits in cattle, which showed that quantitative traits can be used as proxies of genetic disorders when such traits are indicative of whole-animal health status. We reasoned that lactation traits in cattle might also reflect genetic disorders, given the increased energy demands of lactation and the substantial stresses imposed on the animal. In this study, we screened more than 124,000 cows for recessive effects based on lactation traits. We discovered five novel quantitative trait loci (QTL) that are associated with large recessive impacts on three milk yield traits, with these loci presenting missense variants in the DOCK8, IL4R, KIAA0556, and SLC25A4 genes or premature stop variants in the ITGAL, LRCH4, and RBM34 genes, as candidate causal mutations. For two milk composition traits, we identified several previously reported additive QTL that display small dominance effects. By contrasting results from milk yield and milk composition phenotypes, we note differing genetic architectures. Compared to milk composition phenotypes, milk yield phenotypes had lower heritabilities and were associated with fewer additive QTL but had a higher non-additive genetic variance and were associated with a higher proportion of loci exhibiting dominance. We identified large-effect recessive QTL which are segregating at surprisingly high frequencies in cattle. We speculate that the differences in genetic architecture between milk yield and milk composition phenotypes derive from underlying dissimilarities in the cellular and molecular representation of these traits, with yield phenotypes acting as a better proxy of underlying biological disorders through presentation of a larger number of major recessive impacts.


Design, synthesis, and molecular modeling of heterocyclic bioisostere as potent PDE4 inhibitors.
A new hybrid template was designed by combining the structural features of phosphodiesterase 4 (PDE4) inhibitors with several heterocyclic moieties which present an integral part in the skeleton of many apoptotic agents. Thirteen compounds of the synthesized hybrids displayed higher inhibitory activity against PDE4B than the reference drug, roflumilast. Further investigation indicated that compounds 13b and 20 arrested the cell cycle at the G2/M phase and the pre-G1 phase, and induced cell death by apoptosis of A549 cells in a caspase-dependent manner.


GnRH-induced gonadotrophin secretion in ovariectomized Booroola ewes with hypothalamic-pituitary disconnection.
To test whether the F gene-specific differences in the plasma concentrations of FSH and LH are due to differences in the pituitary responsiveness to exogenous GnRH, ovariectomized Booroola ewes with hypothalamic-pituitary disconnection (HPD-ovx) were treated with GnRH (250 ng i.v.) once every 2 h for up to 5 weeks. In Exp. 1, jugular venous blood was collected once weekly from 13 FF and 14 ++ HPD-ovx ewes for 6 weeks before GnRH treatment and every 2nd, 3rd or 6th day for 5 weeks during treatment. In Exp. 2, jugular venous blood was collected from another 8 FF and 7 ++ HPD-ovx ewes at 5- or 10-min intervals over 4 GnRH pulses (250 ng i.v. once every 2 h) on 3 separate occasions after the animals had been subjected to the GnRH pulse regimen for approximately 7 days beforehand. Also in Exp. 2, the animals were extensively sampled around a larger (10 micrograms) i.v. injection of GnRH and the pituitary FSH and LH contents assessed after the animals had been re-exposed to the once every 2 h GnRH (250 ng i.v.) pulse regimen for several days following the larger GnRH bolus. In Exp. 3 the distributions of mean plasma concentrations of FSH and LH in individual GnRH-treated HPD-ovx ewes were compared with those in ovariectomized and ovary-intact FF and ++ ewes. During the 6 weeks before GnRH treatment (Exp. 1), the plasma concentrations of FSH (approximately 1 ng/ml) and LH (less than or equal to 0.8 ng/ml) were not different between the genotypes. After GnRH treatment both the mean FSH and LH concentrations increased significantly (P less than 0.01) above basal values after 2 days with F gene-specific differences being noted for FSH but not LH (FSH; FF greater than ++; P less than 0.05). Thereafter, the mean FSH but not LH concentrations increased at a faster rate in FF than in ++ ewes with the overall mean FSH concentrations between the genotypes being significantly different (P less than 0.05). In Exp. 2 considerable between-animal variation in the pulsatile pattern of FSH but not LH concentrations was seen in ewes of both genotypes during GnRH treatment. The overall mean FSH concentrations were higher in FF than in ++ ewes (P less than 0.05) and the mean FSH response to each GnRH pulse was significantly higher in FF than in ++ ewes (P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)


Reset for systematic action: Removing VA barriers to housing and treatment for military veterans with sexual offenses.
Though the U.S. Department of Veterans Affairs (VA) provides housing, residential treatment, and mental health care to justice involved veterans, those with sexual offenses face daunting obstacles to securing such services, including exclusion from housing programs, and lack of mental health services to treat sexual deviancy disorders. The VA's strategy to date may reflect a large system's caution in systematically addressing a problem that involves a population with an even higher degree of stigma than homelessness. Failure to develop strategies to address this problem reflects the need for a VA system-wide, consistent, and effective approach across relevant domains that incorporate the current state of knowledge and practice. Since 2006, the VA's program serving justice system veterans has been highly effective in serving the reentry veteran population. The challenge of serving veterans with sex offenses can and must be met with a similar level of effectiveness. In this commentary, we propose that the VA, beginning with the Secretary, adopt a "reset" policy and programmatic action agenda to enhance access to housing and treatment for sexual deviancy disorders. We offer specific pathways for implementation. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Feasibility of reduction in use of the mouse bioassay: presence/absence screening for saxitoxin in frozen acidified mussel and oyster extracts from the coast of California with in vitro methods.
In the United States, the detection of paralytic shellfish poisoning (PSP) for regulatory purposes relies on the mouse bioassay (MBA). Using a saxitoxin presence/absence test could reduce animal usage significantly. Three in vitro methods, the RIDASCREEN Saxitoxin kit, MIST Alert, and a 5 h neuroblastoma assay, were evaluated in parallel with the MBA using 106 twice-frozen, acidified extracts from California-grown mussel and oyster tissues. For each assay, a cutoff point was established whereby data below or equal to that point were scored as negative and were assigned a score of zero. Data above the cutoff were considered positive and assigned a score of one. Pearson correlation coefficients were generated. The RIDASCREEN, MIST Alert, and neuroblastoma bioassay correlated to the MBA at 0.849, 0.853, and 0.832 when used for presence/absence detection. These data suggest that a reduction in MBA usage could be achieved in the surveillance of California-grown mussels and oysters for PSP-associated toxins. Correlation data between the in vitro assays, cost comparisons, and the potential for false negatives and false positives were examined. Implications of these methodologies in protecting public health are discussed.


Behavioural and neurocognitive implications of snoring and obstructive sleep apnoea in children: facts and theory.
The pathophysiology of obstructive sleep apnoea (OSA), a common condition in children, is poorly understood. While adenotonsillar hypertrophy is certainly a major contributor, other factors are needed for OSA to develop. OSA has been associated with substantial morbidities primarily affecting cardiovascular and neurobehavioural systems which may not be completely reversed with appropriate treatment. This paper reviews the available information and attempts to provide the rationale for early diagnosis and treatment of OSA in children.


Achieving high-efficiency emission depletion nanoscopy by employing cross relaxation in upconversion nanoparticles.
Stimulated emission depletion microscopy provides a powerful sub-diffraction imaging modality for life science studies. Conventionally, stimulated emission depletion requires a relatively high light intensity to obtain an adequate depletion efficiency through only light-matter interaction. Here we show efficient emission depletion for a class of lanthanide-doped upconversion nanoparticles with the assistance of interionic cross relaxation, which significantly lowers the laser intensity requirements of optical depletion. We demonstrate two-color super-resolution imaging using upconversion nanoparticles (resolution ~ 66 nm) with a single pair of excitation/depletion beams. In addition, we show super-resolution imaging of immunostained cytoskeleton structures of fixed cells (resolution ~ 82 nm) using upconversion nanoparticles. These achievements provide a new perspective for the development of photoswitchable luminescent probes and will broaden the applications of lanthanide-doped nanoparticles for sub-diffraction microscopic imaging.


[Differential diagnosis of uremic pseudoperitonitis and peritonitis in patients on renal replacement therapy].
To analyze serum concentration of β2-microglobulin (β2-MG) and C-reactive protein (CRP) in patients on renal replacement therapy for differential diagnosis of uremic pseudoperitonitis and peritonitis. The study included 76 patients on renal replacement therapy who admitted to the hospital with suspected peritonitis. The control group comprised 60 outpatients on renal replacement therapy. We excluded patients with suspected peritonitis who did not receive previous renal replacement therapy. In both groups, we analyzed serum concentration of β2-MG and CRP. Among patients with previous renal replacement therapy, the highest concentration of β2-MG was found in those with suspected uremic pseudoperitonitis, and the highest concentration of CRP was in patients with suspected peritonitis. There were no significant changes in serum concentrations of β2-MG and CRP in the control group.


Efficacy of the Danish epilepsy surgery programme.
Despite optimal medical treatment, approximately one-third of patients with epilepsy continue to have seizures. Epilepsy surgery is widely accepted as a therapeutic option in the selected subset of patients with drug-resistant focal epilepsy. Here, we report the results of the Danish epilepsy surgery programme from 2009 to 2014. A total of 169 consecutive patients, operated at Rigshospitalet, were included. Information was gathered from digital patient records. Before 1-year follow-up, two patients were lost to follow-up and three were referred to new surgery. The median years of drug resistance before operation were 11 years. At 1-year follow-up (n = 164), seizure outcomes were as follows: 65% Engel I (free from disabling seizures), 51% Engel IA (completely seizure free) and 9% Engel IV (no worthwhile improvement), and for patients operated in the medial temporal lobe (n = 114): 70% Engel I, 56% Engel IA, 5% Engel IV. The outcomes of the 53 patients needing intracranial EEG recording (ICR) were not significantly different from the patients only evaluated with surface EEG. None of the eight MRI-negative patients operated outside the medial temporal lobe after ICR were free of disabling seizures. 12% of MTLE patients developed de novo depression after epilepsy surgery despite good surgical outcome. Three patients required rehabilitation due to post-operative hemiplegia. The outcomes of the Danish epilepsy surgery programme align with international results found in recent meta-analyses. Serious complications to epilepsy surgery are seldom. In accordance with international recommendations, Danish drug-resistant patients should be referred to epilepsy surgery evaluation at an earlier stage of the disease.


The Legionella pneumophila effector DrrA is sufficient to stimulate SNARE-dependent membrane fusion.
The intracellular bacterial pathogen Legionella pneumophila subverts host membrane transport pathways to promote fusion of vesicles exiting the endoplasmic reticulum (ER) with the pathogen-containing vacuole. During infection there is noncanonical pairing of the SNARE protein Sec22b on ER-derived vesicles with plasma membrane (PM)-localized syntaxin proteins on the vacuole. We show that the L. pneumophila Rab1-targeting effector DrrA is sufficient to stimulate this noncanonical SNARE association and promote membrane fusion. DrrA activation of the Rab1 GTPase on PM-derived organelles stimulated the tethering of ER-derived vesicles with the PM-derived organelle, resulting in vesicle fusion through the pairing of Sec22b with the PM syntaxin proteins. Thus, the effector protein DrrA stimulates a host membrane transport pathway that enables ER-derived vesicles to remodel a PM-derived organelle, suggesting that Rab1 activation at the PM is sufficient to promote the recruitment and fusion of ER-derived vesicles.


The role of relationship quality and perceived partner responses with pain and disability in those with back pain.
The objectives of this study were to investigate the associations of key constructs of relationship quality (cohesion, consensus, and satisfaction) and perceived partner responses to pain behavior (e.g., solicitous and negative responses) with the outcomes of pain and disability in those with long-term low back pain, and to explore the role of the patient's depressive symptom mood state on those associations. Self-report questionnaires on pain intensity, disability, relationship quality, perceived partner reactions to pain, and depressive symptoms were collected from participants (N = 174) taking part in a longitudinal study on low back pain within a primary care sample. Participants reporting more consensus (e.g., agreement about sexual intimacy, level of affection) in their relationships had significantly higher pain intensity (P = 0.03), and solicitous partner responses (P = 0.04) were significantly positively associated with disability levels. However, the findings for pain intensity were only present in those with higher levels of depression, while the association of solicitous responses with disability was only significant in those with lower levels of depression, indicating a suppression effect of depression on pain and disability. Depressive symptoms play a significant role in determining the associations between relationship quality, perceived partner reactions, and pain and disability. The relationship construct of consensus and perceived solicitous responses were associated with pain and disability. These findings illustrate the importance of social context and patient mood state on the outcomes for those with low back pain.


Efficacy of praziquantel during the incubation and invasive phase of Schistosoma haematobium schistosomiasis in 18 travelers.
The efficacy of praziquantel started during the incubation period of schistosomiasis has not been studied. Eighteen tourists were infected by Schistosoma haematobium during summer 2003 after bathing once in the same cascade in Mali. We observed the efficacy of praziquantel given at different phases. They received praziquantel at the first consultation, from Days 10 to 15 after exposure in eight asymptomatic patients (Group 1), from Days 28 to 40 in 4 asymptomatic patients (Group 2), and from Days 20 to 39 in 6 patients with acute schistosomiasis (Group 3). All Group 1 patients developed acute schistosomiasis, compared with none of the Group 2 patients (P < 0.004). Among the 10 patients treated during the acute phase, clinical status deteriorated in four cases. Seventeen of the 18 patients developed chronic schistosomiasis. Early praziquantel treatment was thus less effective than later treatment in preventing acute schistosomiasis, while neither treatment effectively prevented chronic schistosomiasis.


Rapidly Enlarging Pediatric Cortical Ependymoma.
We report a 10-year-old boy with supratentorial cortical ependymoma that rapidly grew in the course of 3 years. He suffered generalized seizures when he was 5 years old; MRI showed a small cortical lesion in the right postcentral gyrus. MRI performed 2 years later revealed no changes. For the next 3 years he was free of seizures. However, at the age of 10 he again suffered generalized seizures and MRI disclosed a large parietal tumor. It was resected totally and he remains free of neurological deficits. The histopathological diagnosis was ependymoma. Pediatric supratentorial cortical ependymomas are extremely rare. We recommend including cortical ependymoma as a differential diagnosis in pediatric patients with cortical mass lesions presenting with seizures and careful follow-up even in the absence of symptoms because these tumors may progress.


Selective stimulation of pig radial nerve: comparison of 12-polar and 18-polar cuff electrodes.
Aiming at the development of an implantable neuroprosthesis for restoration of hand function in tetraplegic patients (C5/C6), we examined and compared the stimulation performance of two different neural electrode designs. Our studies on the radial nerve of adult pigs proved the feasibility of selective control of different forearm muscles by using only one multichannel nerve cuff electrode. The results gained by applying a 12-polar cuff electrode design were poor, while the potential of an 18-polar design was very encouraging.


Single-Incision Mini-Slings: Obturator Complex Pull-Out-Force Measurements.
To evaluate the different pull-out-force out of the obturator membrane and the obturator internus muscle of 2 mini-sling systems for stress urinary incontinence (SUI) treatment. In a prospective study, the pull-out-force measurements were performed on 8 female cadaver pelvises, both on the obturator membrane and internal muscle, using the force measurement device PCE-FM50 (PCE Instruments). Tested were the hooks of 2 on the market available mini-sling kits (MiniArc by American Medical System; Ajust by BARD Inc.). Connected to the force measurement device, the hooks were placed into the obturator membrane and the obturator internus muscle. Mean value and SD were documented. On the complete obturator complex, Ajust showed a significantly higher pull-out-force (2,561.75 ± 638.8 g) than did the MiniArc (1,780.69 ± 442.3 g), p = 0.025. No significant differences were performed on the obturator membrane. The Ajust mini-sling hook is, given the objective results, more stably attached to the obturator complex than the MiniArc. Yet, both systems are sufficiently attachable to the evaluated anatomic structures, fulfilling the needed requirements for their use in the treatment of SUI.


[International consensus for lung cancer treatment].
Lung cancer is classified into small cell lung cancer (SCLC) and non-SCLC (NSCLC) based on their clinical and biological characteristics. Chemotherapy is currently a primary treatment modality for SCLC, which is divided into two groups: limited and extensive stage. In the limited stage, radiotherapy is added to chemotherapy to improve the treatment result. In the extensive stage, only chemotherapy provides a survival benefit. In NSCLC, surgical resection is a main treatment modality in stage I, II, and some stage III patients. Other unresectable patients are treated by cisplatin-based chemotherapy and/or radiotherapy with limited benefit. Most of lung cancer patients need systemic therapy, so chemotherapy is important for its treatment. However, the agents which are commonly used for treatment of lung cancer are not sufficiently beneficial. Further improvement, including development of new anti-cancer agents, is expected.


Factors contributing to posttraumatic growth and its buffering effect in adult children of cancer patients undergoing treatment.
This study examined relationships among demographic, clinical, and psychosocial variables in adult children of cancer patients. Two hundred and fourteen participants completed measures of posttraumatic growth (PTG), distress, posttraumatic stress disorder (PTSD) symptoms, social support, and family functioning. Significant gender differences in all PTG dimensions were found, as well as associations among PTG, gender, parental dependency, distress, PTSD, and family functioning. Social support was not a mediator in the relationship between gender and PTG. Gender, education, disease duration, dependency, distress, and family flexibility predicted PTG. Finally, PTG had a moderating effect in the relationship between distress and PTSD/social support. These results may guide psychosocial interventions in this population.


Purification of fetal mouse hepatoblasts by magnetic beads coated with monoclonal anti-e-cadherin antibodies and their in vitro culture.
A simple, rapid, and reproducible method of fetal hepatoblast purification was established to investigate mechanisms controlling interactions between hepatoblasts and nonparenchymal cells during liver development. Because E-cadherin is exclusively expressed on the cell membrane of hepatoblasts, magnetic beads coated with monoclonal antibodies to an extracellular epitope of its molecule were used to purify hepatoblasts from a cell suspension prepared from 12.5-day fetal mouse livers. The purity and yield in the hepatoblast fraction prepared in our protocol were more than 90% and approximately 30%, respectively. The nonparenchymal fraction rarely contained hepatoblasts; the rate of hepatoblast contamination in this fraction was less than 1%. Separate cultures of these two fractions were compared with cocultures of both fractions. In culture of the hepatoblast fraction, hepatoblasts formed aggregates similar to a bunch of grapes via their loose adhesion, floating in the medium after 24 h, and dissociated into single cells from the aggregates after 120 h of culture. By contrast, in the mixed culture, the majority of hepatoblasts formed multicellular spheroids after 24 h, and these spheroids changed into monolayer cell sheets after 120 h of culture. The cells comprising these monolayer sheets abundantly expressed albumin and carbamoylphosphate synthase I. In the mixed culture, fibroblastic cells also proliferated extensively with spreading on glass slides and surrounded the hepatoblast or hepatocyte colonies. On the other hand, fibroblastic cells spreading on glass slides decreased gradually in cultures of the nonparenchymal cell fraction alone. These findings indicated that the coexistence of hepatoblasts and nonparenchymal cells may be essential for their mutual survival, proliferation, differentiation, and morphogenesis. The conditioned medium of fetal liver cell cultures could partially replace the effects of the nonparenchymal cells on hepatoblasts in vitro. Our isolation protocol for fetal mouse hepatoblasts using immunobeads can greatly facilitate studies on mechanisms of cell-cell interactions during liver development.


JAK3 and TYK2 Serve as Prognostic Biomarkers and Are Associated with Immune Infiltration in Stomach Adenocarcinoma.
Stomach adenocarcinoma (STAD) is one of the most common malignant tumors. The Janus kinases (JAKs) play a significant part in cellular biological process, inflammation, and immunity. The roles of JAKs in STAD are still not systematically described. A series of bioinformatics tools were used to clarify the role of JAKs in STAD. JAK3/TYK2 levels were significantly increased in STAD during subgroup analyses based on gender, tumor grade, cancer stages, and nodal metastasis status. STAD patients with high levels of JAK3/TYK2 had poor overall survival, postprogression survival, and first progression. Immune infiltration revealed a significant correlation between JAK3/TYK2 expression and the abundance of immune cells as well as immune biomarker expression in STAD. JAK3/TYK2 was associated with the adaptive immune response, chemokine signaling pathway, and JAK-STAT signaling pathway. JAK3 and TYK2 serve as prognostic biomarkers and are associated with immune infiltration in STAD.


Non-mastoidectomy Cochlear Implant Approaches: A Literature Review.
Introduction Posterior tympanotomy approach for cochlear implant (CI) surgery, has been the most commonly used worldwide with current 0.7% rate of facial nerve injury. Non-mastoidectomy CI approaches include the suprameatal approach (SMA) and its modifications, the transcanal approach and its modifications and the pericanal approach for electrode insertion. Objectives The objective of this study was to review the literature regarding non-mastoidectomy CI approaches. Data Synthesis A search was performed in the LILACS, MEDLINE, SciELO, PubMed databases and Cochrane Library in February 2015, and the key words used in the search were CI, SMA, transcanal approach, pericanal approach, or electrode extrusion. About 30 studies that met the criteria described in "Study Selection" were read in full. The studies showed 1014 patients that underwent CI by SMA or its modifications, 266 CI patients treated by transcanal approach or its modifications, and 15 patients implanted by the pericanal approach. Reported complication with SMA was 99 (9.8%) minor and 13 (1.3%) major. With transcanal, there were 24 complications; 19 (7.1%) minor and 5 (1.9%) major. No post-operative complication was reported in pericanal approach. Studies showed no reported facial nerve paresis or paralysis in all non-mastoidectomy approaches. Conclusion Complications rates with non-mastoidectomy approaches are similar to those found in the mastoidectomy approach. Thus, non-mastoidectomy approaches may be an alternative in cases where the conventional mastoidectomy approach is difficult to perform. It would be helpful for CI surgeons to become familiarized with these approaches.


Alcoholics Anonymous and the use of medications to prevent relapse: an anonymous survey of member attitudes.
The purpose of this study was to systematically assess the attitudes of Alcoholics Anonymous (AA) members toward the newer medications used to prevent relapse (e.g., naltrexone) and to assess their experiences with medication use, of any type, in AA. Using media solicitations and snowball sampling techniques, 277 AA members were surveyed anonymously about their attitudes toward use of medication for preventing relapse and their experiences with medication use of any type in AA. Over half the sample believed the use of relapse-preventing medication either was a good idea or might be a good idea. Only 17% believed an individual should not take it and only 12% would tell another member to stop taking it. Members attending relatively more meetings in the past 3 months had less favorable attitudes toward the medication. Almost a third (29%) reported personally experiencing some pressure to stop a medication (of any type). However, 69% of these continued taking the medication. The study did not find strong, widespread negative attitudes toward medication for preventing relapse among AA members. Nevertheless, some discouragement of medication use does occur in AA. Though most AA members apparently resist pressure to stop a medication, when medication is prescribed a need exists to integrate it within the philosophy of 12-step treatment programs.


Evaluating the Increased Burden of Cardiorespiratory Illness Visits to Adult Emergency Departments During Flu and Bronchiolitis Outbreaks in the Pediatric Population: Retrospective Multicentric Time Series Analysis.
Cardiorespiratory decompensation (CRD) visits have a profound effect on adult emergency departments (EDs). Respiratory pathogens like respiratory syncytial virus (RSV) and influenza virus are common reasons for increased activity in pediatric EDs and are associated with CRD in the adult population. Given the seasonal aspects of such challenging pathology, it would be advantageous to predict their variations. The goal of this study was to evaluate the increased burden of CRD in adult EDs during flu and bronchiolitis outbreaks in the pediatric population. An ecological study was conducted, based on admissions to the adult ED of the Centre Hospitalier Universitaire (CHU) of Grenoble and Saint Etienne from June 29, 2015 to March 22, 2020. The outbreak periods for bronchiolitis and flu in the pediatric population were defined with a decision-making support tool, PREDAFLU, used in the pediatric ED. A Kruskal-Wallis variance analysis and a Spearman monotone dependency were performed in order to study the relationship between the number of adult ED admissions for the International Classification of Diseases (ICD)-10 codes related to cardiorespiratory diagnoses and the presence of an epidemic outbreak as defined with PREDAFLU. The increase in visits to the adult ED for CRD and the bronchiolitis and flu outbreaks had a similar distribution pattern (CHU Saint Etienne: χ23=102.7, P<.001; CHU Grenoble: χ23=126.67, P<.001) and were quite dependent in both hospital settings (CHU Saint Etienne: Spearman ρ=0.64; CHU Grenoble: Spearman ρ=0.71). The increase in ED occupancy for these pathologies was also significantly related to the pediatric respiratory infection outbreaks. These 2 criteria gave an idea of the increased workload in the ED due to CRD during the bronchiolitis and flu outbreaks in the pediatric population. This study established that CRD visits and bed occupancy for adult EDs were significantly increased during bronchiolitis and pediatric influenza outbreaks. Therefore, a prediction tool for these outbreaks such as PREDAFLU can be used to provide early warnings of increased activity in adult EDs for CRD visits.


Expression of the iap gene coding for protein p60 of Listeria monocytogenes is controlled on the posttranscriptional level.
Expression of the iap gene of Listeria monocytogenes encoding a major extracellular protein (p60) was analyzed. Different start sites for transcription of the iap gene were identified by primer extension analysis in L. monocytogenes and in a recombinant Escherichia coli clone. The mutant RIII of L. monocytogenes represents a member of the frequently occurring L. monocytogenes R mutants, which form cell chains and produce greatly reduced amounts of p60. However, the concentrations of iap-specific mRNA were similar in mutant RIII and the wild-type strain. The introduction of additional copies of the iap gene from wild-type L. monocytogenes led to an equal increase of iap mRNA in both strains, but overexpression of protein p60 was only observed in the wild-type strain. The nucleotide sequences of both iap genes and their 5' noncoding regions were identical in all parts that are essential for efficient transcription of the iap gene, translation of the iap-specific mRNA, and transport of the p60 protein. These data suggest that the expression of the iap gene in L. monocytogenes is controlled on the posttranscriptional level by a specific factor that is defective in mutant RIII.


[Aging and exocrine pancreatic function evaluated by the recently standardized secretin test].
The authors studied the relationship between aging and exocrine pancreatic function by the secretin test which was recently standardized by the Japanese Society of Gastroenterology. Pancreatic juice was collected at 10 min intervals for 60 minutes after a bolus intravenous injection of secretin (Secrepan, Eisai Co., Ltd., 100 U/body) through a quadruple-lumen doudenal tube equipped with double balloons. Exocrine pancreatic function was evaluated by three parameters: secretory volume, maximal bicarbonate concentration or bicarbonate output, and enzyme (amylase and lipase) output. Control subjects consisted of 65 outpatients presenting with mild vague abdominal symptoms who fulfilled the following three criteria: 1) good general condition with no known diseases; 2) no abnormality in the liver, bile duct, pancreas, kidney and metabolism judged from blood chemistry, urine and stool analysis, upper GI series, abdominal ultrasonography (US), and endoscopic retrograde cholangiopancreatography (ERCP); 3) alcohol consumption less than 25 g/day. Control subjects were divided into three groups: 15 subjects below 40 years of age (group A), 32 subjects from 40 to 65 years (group B), and 18 subjects of 65 years and above (group C). Nineteen patient with chronic pancreatitis were also studied. The group C showed significantly lower values in secretory volume, bicarbonate output, and enzyme output than group A and B. Enzyme output showed a gradual decrease with aging. However, secretory volume and bicarbonate output showed a gentle convex curve with a peak around age 40 and a rather steep down-slope after late 50s. The degree of the decrease was significantly more marked in volume and bicarbonate output than in enzyme output in group C.(ABSTRACT TRUNCATED AT 250 WORDS)


Why medical students choose orthopedic surgery as a specialty?
Before the crisis announced the Moroccan surgery, the objectives of this study were to analyze the choice of specialties newly appointed to the internal review and the guidance of medical students and to determine the factors influencing this choice. Data on specialty choice students were analyzed and a questionnaire was offered to students of Morocco at the beginning of academic year 2013-20014 The form consisted of questions on the year of study. sex, professional guidelines and reasons for choice. candidates were male, the average age of our residents was 28 years. We also noted the importance of the passage as well as external service trauma. Care provided to patients, lifestyle and income reported by 85% of respondents to be the most important factors to pursue orthopedics as a career. The TR-Orth is now a specialty that responds to a positive choice. The choice of TR-Orth by students at the end of medical school curriculum is reinforced by teaching and practicing the specialty during the internship. The overall training is unsatisfactory overall. Students would deepen in some areas. This study confirms that there is currently a shift in trauma surgery, mostly induced by an a priori negative for particular workloads.


Menopause, insulin resistance, and risk factors for cardiovascular disease.
In this retrospective analysis of the European Group for the Study of Insulin Resistance database, a clamp data pooling project, a cardiovascular risk score (CVS) was assessed to verify whether hyperinsulinemia and/or insulin resistance were independent cardiovascular risk factors and to investigate how menopause affected CVS and insulin resistance. Information was obtained on whole-body glucose uptake (M), determined by the euglycemic hyperinsulinemic clamp technique, normalized by fat-free mass (FFM), and insulin concentration (I) at a steady state. Body composition was estimated using a labeled water technique or bioimpedance. Other parameters measured included blood pressure, lipid levels, and waist-to-hip ratio. CVS was computed using a structural equation model that included age, body mass index, blood lipids, and blood pressure. The study population included 523 normal and overweight patients. Women were grouped according to fertility status, and men, according to age (cutoff 50 y). M/kg(FFM)/I significantly decreased after menopause (12.41 +/- 3.40 vs 10.96 +/- 3.68; P < 0.01) and in men 50 years and older (11.39 +/- 3.47 vs 10.32 +/- 3.77 micromol x min(-1) x kg(-1) x microUI/mL; P < 0.02). CVS was lowest in fertile women (-0.414 +/- 0.57 vs 0.107 +/- 0.43; P < 0.0001) and highest in men 50 years and older (0.045 +/- 0.455 vs 0.257 +/- 0.51; P < 0.001). CVS significantly correlated with M/kg(FFM)/I in men 49 years and younger (r(o) = -0.27, P < 0.0001) and 50 years and older (r(o) = -0.38, P < 0.0001) and with fasting insulin in fertile women (r(o) = -0.29, P < 0.01) and in the other groups (r(o) ranging from 0.37 to 0.45, P < 0.0001). Menopause does not seem to strictly relate to a decrease in insulin sensitivity as postmenopausal women had the same insulin sensitivity as age-matched men. In the population studied, the best predictor of CVS was fasting insulin rather than insulin sensitivity.


Glioblastoma and malignant melanoma: Serendipitous or anticipated association?
We describe a patient who had primary glioblastoma (GB) and malignant melanoma (MM). A 78-year-old man presented with several weeks to months of history of gait disturbance, confusion, memory disturbance, and worsening speech. Imaging studies performed on admission revealed a large frontotemporal lobe mass associated with the surrounding zone of vasogenic edema. Given the patient's medical history of incomplete biopsy of a midback tumor performed three weeks before, the presumptive clinical diagnosis was metastatic MM. Pathological examination of frozen sections of fragmented specimens obtained at stereotactic biopsy performed on admission revealed a high-grade malignant neoplasm characterized by discohesive cells in a blue myxoid background and abundant foci of tumor necrosis. Given these features, in conjunction with the abovementioned pathological report, the frozen section diagnosis by the neuropathologist was "neoplasm identified, favor melanoma." Due to the paucity of lesional tissue, a limited immunohistochemistry performed on the permanent sections revealed positive staining of lesional cells for Sox10 alone using a multiplex MART1/Sox10 immunostain and S-100 protein, an immunohistochemical profile supporting the presumptive frozen section diagnosis. A tumor debulk procedure, performed two weeks later, revealed histopathologic features most compatible with GB, IDH wild-type. Thus, additional immunohistochemistry on the permanent sections revealed positive staining of glial fibrillary acidic protein (GFAP), Sox10, and S-100 protein as well as negative staining of gp100, a complex carbohydrate matrix protein in embryonic melanosomes, using a specific antibody HMB45. The concomitant occurrence of MM and GB in our patient underscores the association between these two entities. Our literature review suggests that the sporadic co-occurrence of these two conditions is likely not serendipitous.


Synergistic regulation of pulmonary beta-adrenergic receptors by glucocorticoids and interleukin-1.
Coculturing IM9 human lymphocytes and A549 human lung adenocarcinoma cells results in a 2-3-fold increase in the density of beta-adrenergic receptors in the latter, as quantified by 125I-cyanopindolol binding. Lymphocyte-conditioned medium (LCM) has the same effect, which is moderately sensitive to heat, is retained by ultrafiltration over a Mr 10,000 cut-off filter, and is reduced by trypsin treatment or by preincubation of lymphocytes with 0.3 micrograms/ml cycloheximide. Treatment of lung cells with cycloheximide also prevents the effect of LCM. Glucocorticoids, which also increase beta-receptor density in A549 cells, markedly potentiate the effect of LCM. Gel permeation high pressure liquid chromatography of LCM yields three peaks of biological activity with Mr 70,000, 35,000, and 15,000. Monocytic interleukin-1 (IL-1) mimics the effect of LCM in that it increases beta-receptor density in A549 cells (EC50 0.3 pM), and its effect is potentiated by cortisol. Recombinant IL-1 alpha is somewhat more potent than IL-1 beta, while interleukin-2 and interferon-alpha are ineffective. Tumor necrosis factor alpha causes a small increase in beta-receptors, which is not influenced by glucocorticoids. A polyclonal anti-IL-1 antibody inhibits the effect of IL-1 and the effect of the 15-kDa but not the 35- and 70-kDa fractions of LCM. The activity of the latter two fractions is also unaffected by anti-tumor necrosis factor alpha antibody. These results indicate that lymphocytes release protein factors including IL-1 that up-regulate pulmonary beta-adrenergic receptors by an action that involves protein synthesis. The possible relevance of this regulatory mechanism for the pathomechanism of certain respiratory diseases is discussed.


Human post-infection serological response to the spike and nucleocapsid proteins of SARS-CoV-2.
To inform seroepidemiological studies, we characterized the IgG- responses in COVID-19 patients against the two major SARS-CoV-2 viral proteins, spike (S) and nucleocapsid (N). We tested 70 COVID-19 sera collected up to 85 days post-symptom onset and 230 non-COVID-19 sera, including 27 SARS sera from 2003. Although the average SARS-CoV-2 S and N-IgG titers were comparable, N-responses were more variable among individuals. S- and N-assay specificity tested with non-COVID-19 sera were comparable at 97.5% and 97.0%, respectively. Therefore, S will make a better target due to its lower cross-reactive potential and its' more consistent frequency of detection compared to N.


Screening and diagnosis of congenital adrenal hyperplasia in Basilicata (Italy).
Research of the frequency of 21-OH enzyme deficiency, autosomal recessive disease, caused by aberrations in the short arm of chromosome 6 was performed in order to prevent CAH (Congenital Adrenal Hyperplasia) manifested by: 1) possible cerebral damage 2) errors of sex attribution 3) behavioral hyperandrogenism 4) metabolic damage. Radioimmunoassay was used where there is competition between a radioactive and a non-radioactive antigens for a fixed number of antibody binding sites. In an 18 month period of screening 6,000 newborns we found one positive case of CAH which we confirmed by dosaging steroids such as, 4-androstenedione, testosterone, ACTH, PRA and electrolytic activity on the serum. We ascertained that an incidence of 1:6,000 in a 18 month period is high enough to deserve attention.


A new technique for retrograde flexible ureteroscopy after Cohen cross-trigonal ureteral reimplantation.
Retrograde ureteral access after cross-trigonal ureteral reimplantation can be challenging. We present our experience with retrograde ureteral catheterization and flexible ureteroscopy after Cohen cross-trigonal reimplantation in patients presenting with ureteral stones. Cystoscopy is performed and a Tiemann ureteral catheter is inserted into the involved ureteral orifice. A retrograde ureterography is performed and hydrophilic guide wire is passed up to the kidney. A dual-lumen ureteral access sheath is then passed under x-ray control underneath the ureteral stone. The flexible ureterorenoscope is passed under x-ray control up to the stone which is then fragmented with a holmium laser. From June 2006 to June 2010, this technique was successful in 8 patients without acute or delayed sequelae. Where the endourological expertise is readily available, the ureter can be accessed retrogradely even after Cohen cross-trigonal ureteral reimplantation in a safe, straightforward and effective modality.


Exercise Intensity and Brain Plasticity: What's the Difference of Brain Structural and Functional Plasticity Characteristics Between Elite Aerobic and Anaerobic Athletes?
This study investigated the differences in morphometry and functional plasticity characteristics of the brain after long-term training of different intensities. Results showed that an aerobic group demonstrated higher gray matter volume in the cerebellum and temporal lobe, while an anaerobic group demonstrated higher gray matter volume in the region of basal ganglia. In addition, the aerobic group also showed significantly higher fractional amplitude of low-frequency fluctuation (fALFF) and degree centrality (DC) in the motor area of the frontal lobe and parietal lobe, and the frontal gyrus, respectively. At the same time, the anaerobic group demonstrated higher fALFF and DC in the cerebellum posterior lobe (family-wise error corrected, p < 0.01). These findings may further prove that different brain activation modes respond to different intensities of physical activity and may help to reveal the neural mechanisms that can classify athletes from different intensity sports.


Nuclear export of proteins and drug resistance in cancer.
The intracellular location of a protein is crucial to its normal functioning in a cell. Cancer cells utilize the normal processes of nuclear-cytoplasmic transport through the nuclear pore complex of a cell to effectively evade anti-neoplastic mechanisms. CRM1-mediated export is increased in various cancers. Proteins that are exported in cancer include tumor-suppressive proteins such as retinoblastoma, APC, p53, BRAC1, FOXO proteins, INI1/hSNF5, galectin-3, Bok, nucleophosmin, RASSF2, Merlin, p21(CIP), p27(KIP1), N-WASP/FAK, estradiol receptor and Tob, drug targets topoisomerase I and IIα and BCR-ABL, and the molecular chaperone protein Hsp90. Here, we review in detail the current processes and known structures involved in the export of a protein through the nuclear pore complex. We also discuss the export receptor molecule CRM1 and its binding to the leucine-rich nuclear export signal of the cargo protein and the formation of a nuclear export trimer with RanGTP. The therapeutic potential of various CRM1 inhibitors will be addressed, including leptomycin B, ratjadone, KOS-2464, and specific small molecule inhibitors of CRM1, N-azolylacrylate analogs, FOXO export inhibitors, valtrate, acetoxychavicol acetate, CBS9106, and SINE inhibitors. We will also discuss examples of how drug resistance may be reversed by targeting the exported proteins topoisomerase IIα, BCR-ABL, and galectin-3. As effective and less toxic CRM1 export inhibitors become available, they may be used as both single agents and in combination with current chemotherapeutic drugs. We believe that the future development of low-toxicity, small-molecule CRM1 inhibitors may provide a new approach to treating cancer.