Impact of Left Atrial Appendage Exclusion on Cardiovascular Outcomes in Patients With Atrial Fibrillation Undergoing Coronary Artery Bypass Grafting (From the National Inpatient Sample Database).
Left atrial appendage (LAA) exclusion is performed by some surgeons in patients with atrial fibrillation (AF) who undergo coronary artery bypass grafting (CABG). However, the available evidence regarding the efficacy and safety of this procedure remains mixed. We queried the Nationwide Inpatient Survey Database for the 10-year period from 2004 to 2013. Using International Classification of Diseases, Ninth Edition, Clinical Modification diagnosis codes, we identified patients who had a diagnosis of AF and underwent a primary procedure of CABG with or without LAA exclusion. We then performed a 1:5 matching based on the CHA2DS2VASc score between patients who got LAA exclusion and those who did not (control group). The primary outcome was the incidence of in-hospital cerebrovascular events, whereas the secondary outcomes included in-hospital bleeding events, pericardial effusion, cardiac tamponade, postoperative shock, and mortality. Our analysis included a total of 15,114 patients. Patients who underwent LAA exclusion had significantly less incidence of cerebrovascular events (2.0% vs 3.1%, p = 0.002). However, LAA exclusion group had higher incidences of bleeding events (36.4% vs 21.3%, p <0.001), pericardial effusion (2.7% vs 1.2%, p <0.001), cardiac tamponade (0.6% vs 0.2%, p <0.001), and postoperative shock (1.2% vs 0.4%, p <0.001). LAA exclusion was associated with higher in-hospital mortality (1.6% vs 0.3%, p <0.001). Multivariate regression analysis showed that LAA exclusion was significantly associated with lower cerebrovascular accident events and higher in-hospital mortality. In conclusion, LAA exclusion in patients with AF undergoing CABG might be associated with a lower incidence of in-hospital cerebrovascular events. This benefit is offset by a higher incidence of higher bleeding events, pericardial effusion, cardiac tamponade, postoperative shock, and in-hospital mortality.


[An analysis of the decision process in the pharmacological treatment of a patient with chronic heart failure by means of a therapy management information system: the experience of the Montescano Heart Failure Unit].
A computer-based system integrated into the hospital information system for the pharmacological management of the chronic heart-failure patients admitted to the heart-failure unit of Montescano is presented. The major aims of the system involved monitoring the patients' treatment history and the related therapeutic decision-making. The treatment history of the first 151 consecutive CHF patients admitted after the system implementation is examined. The prescribed drug doses at admission and at discharge are compared, as well as the differences in etiology and NYHA class between patients discharged with or without each drug. Several considerations can be drawn from this analysis. First of all, in heart failure patients the choice of drugs is limited and optimal treatment is a result of individualized dosages. Secondly, time and trials are necessary to obtain optimal treatment. Consequently, continuity of care and in- and out-hospital networks are advisable. Third, a computer-based system offers advantages not only for the pharmacological management itself, but also for improving the quality of care through continuous analysis of the decision-making process.


Utility of probability scores for the diagnosis of pulmonary embolism in patients with SARS-CoV-2 infection: A systematic review.
Clinical prediction models determine the pre-test probability of pulmonary embolism (PE) and assess the need for tests for these patients. Coronavirus infection is associated with a greater risk of PE, increasing its severity and conferring a worse prognosis. The pathogenesis of PE appears to be different in patients with and without SARS-CoV-2 infection. This systematic review aims to discover the utility of probability models developed for PE in patients with COVID-19 by reviewing the available literature. A literature search on the PubMed, Scopus, and EMBASE databases was carried out. All studies that reported data on the use of clinical prediction models for PE in patients with COVID-19 were included. Study quality was assessed using the Newcastle-Ottawa scale for non-randomized studies. Thirteen studies that evaluated five prediction models (Wells score, Geneva score, YEARS algorithm, and PERC and PEGeD clinical decision rules) were included. The different scales were used in 1,187 patients with COVID-19. Overall, the models showed limited predictive ability. The two-level Wells score with low (or unlikely) clinical probability in combination with a D-dimer level <3000ng/mL or a normal bedside lung ultrasound showed an adequate correlation for ruling out PE. Our systematic review suggests that the clinical prediction models available for PE that were developed in the general population are not applicable to patients with COVID-19. Therefore, their use is in clinical practice as the only diagnostic screening tool is not recommended. New clinical probability models for PE that are validated in these patients are needed.


Maternal complications of pregnancy increase beyond 40 weeks of gestation in low-risk women.
We sought to determine when rates of maternal pregnancy complications increase for low-risk nulliparous and multiparous women at term. We designed a retrospective cohort study of low-risk women delivered beyond 37 weeks gestational age from 1976 to 2001. Rates of mode of delivery and maternal complications of labor and delivery were examined by gestational age with both bivariate and multivariate analyses. Statistical significance was designated by P<0.05. We found that among the 32,828 low-risk women who delivered at 37 completed weeks and beyond, the rates of primary cesarean delivery, operative vaginal delivery, third- or fourth-degree perineal lacerations, and chorioamnionitis all increased at 40 weeks of gestation (P<0.001), and the rate of postpartum hemorrhage increased at 41 weeks of gestation (P<0.001). These increases of rates of complications were larger and increased at an earlier gestational age among nulliparous women. We found that the risk of maternal complications for otherwise low risk nulliparous and multiparous women increased as pregnancy progressed beyond 40 weeks of gestation. Counseling of women who progress past their EDC should include comparing the risks of induction of labor to that of expectant management.


Therapeutic drug monitoring of psychotropic medications.
Therapeutic drug monitoring (TDM) of a number of psychotropic medications has proven to be of value, enabling minimization of the limitations of considerable genetic variability in their metabolism and the high rates of poor compliance with many psychiatric disorders. Therapeutic ranges have been established for lithium, some of the tricyclic antidepressants, and clozapine. TDM has also been shown to be useful in avoiding toxicity (as many psychotropics have narrow therapeutic indices), particularly that due to interactions with other compounds.


RNA polymerase II association with the phosphoenolpyruvate carboxykinase (PEPCK) promoter is reduced in vitamin A-deficient mice.
Phosphoenolpyruvate carboxykinase (PEPCK) gene expression is decreased in vitamin A-deficient (VAD) mice. However, the underlying molecular mechanism at the PEPCK promoter that contributes to this alteration in gene expression remains unexplained and thus serves as the basis for our investigation in this report. Using liver from vitamin A-sufficient (VAS) and VAD mice in the chromatin immunoprecipitation (ChIP) assay, we determined that histones H3 and H4 were in the acetylated or active state in VAS mice at each of the three retinoic acid response elements (RARE1, RARE2 and RARE3) of the PEPCK promoter. The same acetylation pattern was seen in VAD mice, but with relatively lower levels of acetylated H3 and H4 bound at the region encompassing PEPCK RARE1/RARE2. In ChIP assays conducted with an antibody to RNA polymerase II (RNA Pol II), the association of RNA Pol II with PEPCK RARE1/RARE2 was significantly decreased in vitamin A deficiency. The reduction in RNA Pol II association is indicative of an interruption in the direct interactions of RNA Pol II with the PEPCK promoter, with general transcription factors and/or with coregulator molecules that contribute to the activation of the PEPCK gene. These results increase our understanding of the molecular basis for decreased PEPCK gene expression in VAD mice in vivo and offer additional insight into the regulation of other retinoid-responsive genes.


Systemic effects of neem on western flower thrips, Frankliniella occidentalis (Thysanoptera: Thripidae).
The systemic effects of neem on the western flower thrips, Frankliniella occidentalis (Pergande), were investigated in laboratory trials using green bean, Phaseolus vulgaris L., in arena and microcosm experiments. In arena experiments, systemic effects of neem against western flower thrips larvae on primary bean leaves were observed with maximum corrected mortality of 50.6%. In microcosm experiments using bean seedlings, higher efficacy in the control of western flower thrips were observed with soil applications of neem on a substrate mixture (i.e., Fruhstorfer Erde, Type P, and sand) in a 1:1 ratio (93% corrected mortality) compared with application on the commercial substrate only (76% corrected mortality). However, longer persistence of neem was observed with soil application on the commercial substrate, which showed effects against thrips for up to 6 d after application. In addition to systemic effects observed on all foliage-feeding stages of western flower thrips, mortality on contact and repellent effects were observed on soil-inhabiting stages after soil applications of neem. Finally, bean seedlings grown from seeds pregerminated for 3 d in neem emulsion were also toxic to western flower thrips.


Use and Validation of the AUA/SUO Risk Grouping for Nonmuscle Invasive Bladder Cancer in a Contemporary Cohort.
We applied nonmuscle invasive bladder cancer AUA (American Urological Association)/SUO (Society of Urologic Oncology) guidelines for risk stratification and analyzed predictors of recurrence and progression. We retrospectively reviewed the records of 398 patients with nonmuscle invasive bladder cancer treated between 2001 and 2017. Descriptive statistics were used to compare AUA/SUO risk groups. Predictors of recurrence and progression were determined by multivariable regression. Kaplan-Meier analysis was done, a Cox proportional hazards regression model was created and time dependent AUCs were calculated to determine progression-free and recurrence-free survival by risk group. Median followup was 37 months (95% CI 35-42). Of the patients 92% underwent bacillus Calmette-Guérin induction and 46% received at least 1 course of maintenance treatment. Of the patients 11.5% were at low, 32.5% were at intermediate and 55.8% were at high risk. In patients at low, intermediate and high risk the 5-year progression-free survival rate was 93%, 74% and 54%, and the 5-year recurrence-free survival rate was 43%, 33% and 23%, respectively. Kaplan-Meier analysis was done to stratify high grade Ta 3 cm or less tumor recurrence-free and progression-free survival in the intermediate vs the high risk group. Relative to low risk, classification as intermediate and as high risk was an independent predictor of progression (HR 9.7, 95% CI 2.23-42.0, p <0.01, and HR 36, 95% CI 8.16-159, p <0.001, respectively). Recurrence was more likely in patients at high risk than in those at low risk (HR 2.03, 95% CI 1.11-3.71, p=0.022). For recurrence and progression the 1-year AUC was 0.60 (95% CI 0.546-0.656) and 0.68 (95% CI 0.622-0.732), respectively. The AUA/SUO nonmuscle invasive bladder cancer risk classification system appropriately stratifies patients based on the likelihood of recurrence and progression. It should be used at diagnosis to counsel patients and guide therapy.


Effectiveness of circumferential endoscopic mucosal resection with a novel tissue-anchoring device.
To evaluate the efficacy of circumferential endoscopic mucosal resection (EMR) with a tissue-anchoring device in comparison to forceps precut EMR and conventional endoscopic submucosal dissection (ESD). The study was designed as a prospective, randomized, ex vivo study. Fresh ex vivo specimens were harvested from adult white Yorkshire pigs weighing 30-50 kg. Seventy-five standardized, artificial lesions measuring 3 cm × 3 cm were created by methylene blue tattoo at the greater curvature in fresh ex vivo stomachs using the EASIE-R simulator platform (Endosim LLC, Berlin, MA, United States). The three advanced endoscopists performed the three resection techniques such as circumferential EMR using the tissue-anchoring device (TA-EMR), forceps precut EMR (FP-EMR), and endoscopic submucosal dissection. The endoscopists and the type of cutting methods were determined randomly by grouped randomized selection. The resection bed was grossly inspected to determine whether the lesion was resected "en-bloc" (defined as no remaining mucosal tattoo remaining on specimen). The resection bed was also probed for evidence of perforation. The procedural time of circumferential resection, submucosal dissection, and injection frequency were recorded by an independent observer. All 75 created lesions were successfully resected by three advanced endoscopists using the three techniques. The mean ± SD size of resected specimens (long axis) were 39.5 ± 5.6 mm, 36.5 ± 7.3 mm, and 44.6 ± 5.6 mm for TA-EMR, FP-EMR, and ESD respectively. The overall mean dissection time of both the TA-EMR and FP-EMR was significant shorter than ESD (TA-EMR: 5.1 ± 3.3 min, FP-EMR: 3.5 ± 2.0 min vs ESD: 15.8 ± 9.5 min, P < 0.001, P < 0.001). The overall mean total procedure time of both the tissue-anchoring and forceps circumferential EMR was significantly shorter than ESD (TA-EMR: 17.5 ± 6.0 min, FP-EMR: 16.6 ± 6.6 min vs ESD: 28.6 ± 13.9 min, P < 0.001, P < 0.001). The en-bloc resection rate of ESD was 100% (25/25) and the en-bloc resection rate of the TA-EMR (84.0%, 21/25) was higher than for the FP-EMR (60.0%, 15/25), yet not statistically significant (P = 0.18). The perforation rate of each technique was 8.0% (2/25). TA-EMR appears to be quicker than ESD, and there was a trend towards improved en bloc resection rate with the TA-EMR when compared to the FP-EMR.


Reentry into the cell cycle of differentiated skeletal myocytes.
The activation of muscle-specific myosin synthesis and its relationship to withdrawal from the cell cycle have been examined in cycle-synchronized myoblasts under growth-restrictive, fusion-impermissive (low Ca2+) culture conditions. Under these conditions, embryonic quail skeletal myoblasts, collected in mitosis by mechanical shake-off, complete one normal cycle and arrest in G1. The presence of skeletal muscle myosin is first detected, by indirect immunofluorescence, 8 hr into this protracted G1. Within the next 10-11 hr the percentage myosin positive (Myo+) cells increases with good synchrony, reaching approximately 95%. Refeeding with a proliferation--stimulating, low Ca2+ medium when approximately 50% of the cells are Myo+ induces reentry into S. Applying a 15-min pulse with [3H]TdR immediately preceding fixation at regular intervals following refeeding, cells can be detected which are Myo+ and whose nuclei have incorporated [3H]TdR. The numbers of such doubly labeled cells are small but consistent with the fraction of cells in S (by time-lapse analysis) at the postfeeding times sampled. These cinematographic studies also indicate that progression to mitosis following stimulation occurs slowly and asynchronously. The kinetics of progression of the stimulated cells suggest that they reenter S from a different compartment in G1 than do log-phase myoblasts. We conclude that in fusion-blocked quail myocytes irreversible withdrawal from the cell cycle is neither an obligate precondition for, nor an immediate consequence of the activation of the muscle-specific contractile gene set.


Characterization of Alzheimer's Disease Using Ultra-high b-values Apparent Diffusion Coefficient and Diffusion Kurtosis Imaging.
The aim of the study is to investigate the diffusion characteristics of Alzheimer's disease (AD) patients using an ultra-high b-values apparent diffusion coefficient (ADC_uh) and diffusion kurtosis imaging (DKI). A total of 31 AD patients and 20 healthy controls (HC) who underwent both MRI examination and clinical assessment were included in this study. Diffusion weighted imaging (DWI) was acquired with 14 b-values in the range of 0 and 5000 s/mm2. Diffusivity was analyzed in selected regions, including the amygdala (AMY), hippocampus (HIP), thalamus (THA), caudate (CAU), globus pallidus (GPA), lateral ventricles (LVe), white matter (WM) of the frontal lobe (FL), WM of the temporal lobe (TL), WM of the parietal lobe (PL) and centrum semiovale (CS). The mean, median, skewness and kurtosis of the conventional apparent diffusion coefficient (ADC), DKI (including two variables, Dapp and Kapp) and ADC_uh values were calculated for these selected regions. Compared to the HC group, the ADC values of AD group were significantly higher in the right HIP and right PL (WM), while the ADC_uh values of the AD group increased significantly in the WM of the bilateral TL and right CS. In the AD group, the Kapp values in the bilateral LVe, bilateral PL/left TL (WM) and right CS were lower than those in the HC group, while the Dapp value of the right PL (WM) increased. The ADC_uh value of the right TL was negatively correlated with MMSE (mean, r=-0.420, p=0.019). The ADC value and Dapp value have the same regions correlated with MMSE. Compared with the ADC_uh, combining ADC_uh and ADC parameters will result in a higher AUC (0.894, 95%CI=0.803-0.984, p=0.022). Comparing to ADC or DKI, ADC_uh has no significant difference in the detectability of AD, but ADC_uh can better reflect characteristic alternation in unconventional brain regions of AD patients.


NVP-BEZ235, a dual pan class I PI3 kinase and mTOR inhibitor, promotes osteogenic differentiation in human mesenchymal stromal cells.
Osteoblasts are bone-forming cells derived from mesenchymal stromal cells (MSCs) that reside within the bone marrow. In response to a variety of factors, MSCs proliferate and differentiate into mature, functional osteoblasts. Several studies have shown previously that suppression of the PI3K and mTOR signaling pathways in these cells strongly promotes osteogenic differentiation, which suggests that inhibitors of these pathways may be useful as anabolic bone agents. In this study we examined the effect of BEZ235, a newly developed dual PI3K and mTOR inhibitor currently in phase I-II clinical trials for advanced solid tumors, on osteogenic differentiation and function using primary MSC cultures. Under osteoinductive conditions, BEZ235 strongly promotes osteogenic differentiation, as evidenced by an increase in mineralized matrix production, an upregulation of genes involved in osteogenesis, including bone morphogenetic proteins (BMP2, -4, and -6) and transforming growth factor β1 (TGF-β1) superfamily members (TGFB1, TGFB2, and INHBE), and increased activation of SMAD signaling molecules. In addition, BEZ235 enhances de novo bone formation in calvarial organotypic cultures. Using pharmacologic inhibitors to delineate mechanism, our studies reveal that suppression of mTOR and, to a much lesser extent PI3K p110α, mediates the osteogenic effects of BEZ235. As confirmation, shRNA-mediated knockdown of mTOR enhances osteogenic differentiation and function in SAOS-2 osteoblast-like cells. Taken together, our findings suggest that BEZ235 may be useful in treating PI3K/mTOR-dependent tumors associated with bone loss, such as the hematologic malignancy multiple myeloma.


Full-vectorial whispering-gallery-mode cavity analysis.
We present a full-vectorial three-dimensional whispering-gallery-mode microcavity analysis technique. With this technique, optical properties such as resonance wavelength, quality factor, and electromagnetic field distribution of a microcavity in the presence of individual nanoparticle adsorption can be simulated with high accuracy, even in the presence of field distortion from plasmon effects at a wavelength close to plasmon resonance. This formulation is applicable to a wide variety of whispering-gallery related problems, such as waveguide to cavity coupling and full wave propagation analysis of a general whispering-gallery-mode microcavity where axisymmetry along the azimuthal direction is not required.


Impact of prenatal haemodynamic and functional abnormalities in Ebstein's anomaly on survival.
Predicting outcomes of foetuses with Ebstein's anomaly and tricuspid valve dysplasia continues to be challenging. Limited data exist on the prognostic significance of prenatal haemodynamic and functional parameters in this population. Our aim was to investigate the prognostic significance of haemodynamic and ventricular functional parameters in addition to associated morphometric parameters in patients with Ebstein's anomaly. We reviewed medical records of foetuses with Ebstein's anomaly and tricuspid valve dysplasia at All Children's Hospital Johns Hopkins Medicine and Johns Hopkins University between 2005 and 2012. The main outcome was survival past 30 days from birth; participants who died in utero or <30 days after birth were considered non-survivors. There were 13 survivors and seven non-survivors. We found that participants with abnormal right ventricular function predicted by low tricuspid regurgitation velocity (<2.3 m/second) (p=0.012) and low estimated right ventricular pressure (<24 mmHg) (p=0.029), a low (<7) cardiovascular profile score (p=0.029) and high (>0.53) cardiothoracic ratio (p=0.008) at the first foetal echocardiogram were less likely to survive. In addition, participants with a fossa ovalis/atrial septal length ratio <0.36 at the last foetal echocardiogram (p=0.051) were more likely to die, albeit of borderline statistical significance. Low tricuspid regurgitation velocity and low right ventricular estimated pressure, or a low cardiovascular profile score could be potential prognostic factors for Ebstein's anomaly and tricuspid valve dysplasia. However, future larger prospective studies are needed to confirm these initial findings.


[Psychiatric provisions for patients in departments for treatment of acute poisoning from the standpoint of manpower standards].
The results of a study carried out at basic health service institutions in 7 cities of the country and dealing with the forms, occurrence, character and duration of psychopathological symptoms in patients with acute poisonings are presented. The annual scope and expenses of a psychiatrist's consultative work at a specialized division are determined. It was found desirable to have one staff psychiatrist per each 50 patients treated at the division. The initial prerequisites and method of calculating that rate are described.


Catabolic pathways for streptokinase, plasmin, and streptokinase activator complex in mice. In vivo reaction of plasminogen activator with alpha 2-macroglobulin.
The catabolic pathways of streptokinase, plasmin, and activator complex prepared with human plasminogen were studied in mice. (125)I-streptokinase clearance occurred in the liver and was 50% complete in 15 min. Incubation with mouse plasma had no effect on the streptokinase clearance rate. Complexes of plasmin and alpha(2)-plasmin inhibitor were eliminated from the plasma by a specific and saturable pathway. Competition experiments demonstrated that this pathway is responsible for the clearance of injected plasmin. Streptokinase-plasminogen activator complex formed with either (125)I-plasminogen or (125)I-streptokinase cleared in the liver at a significantly faster rate than either of the uncomplexed proteins (50% clearance in <3 min). Streptokinase incubated with human plasma also demonstrated this accelerated clearance. p-Nitrophenyl-p'-guanidinobenzoate-HCl or pancreatic trypsin inhibitor-treated complex cleared slowly compared with untreated complex independent of which protein was radiolabeled. Significant competition for clearance was demonstrated between alpha(2)-macroglobulin-trypsin and activator complex only when the plasmin(ogen) was the radiolabeled moiety. Large molar excesses of alpha(2)-plasmin inhibitor-plasmin failed to retard the clearance of activator complex. Hepatic binding of streptokinase-plasmin, in liver perfusion experiments, was dependent upon prior incubation with plasma (8-10% uptake compared to a background of approximately 2.5%). Substitution of human alpha(2)-macroglobulin for plasma also resulted in binding when the incubation was performed for 10 min at 37 degrees C (7.5%). Electrophoresis experiments confirmed the transfer of 0.8 mol plasmin/mol alpha(2)-macroglobulin when activator complex was incubated at 37 degrees C with alpha(2)-macroglobulin for 40 min. Streptokinase transfer from activator complex to alpha(2)-macroglobulin was negligible. The in vivo clearance of activator complex is proposed to involve active attack of the complex on the alpha(2)-macroglobulin "bait region," resulting in facilitated plasmin transfer. Dissociated streptokinase is rapidly bound and cleared by sites in the liver.


Adolescent-parent interactions in middle-class African American families: longitudinal change and contextual variations.
Family interactions were examined longitudinally over 2 years in 79 middle-class African American families with early adolescents. Mothers and adolescents (as well as fathers and adolescents and triads in 2-parent families) were videotaped discussing a conflict for 10 min. A macro-coding system (J. G. Smetana, J. Yau, A. Restrepo, & J. L. Braeges, 1991) was modified to be culturally sensitive to African American families. Interaction ratings were reduced, through principal-components analyses, into composite variables. After control for family income, mothers' communication in triadic interactions became less positive over time. Both mothers' and fathers' communication was more positive in dyadic than triadic interactions. In triadic interactions, mothers validated sons more than daughters, and in dyadic interactions with either parent, boys were more receptive to parents than were girls. Findings extend previous research on adolescent-parent relationships to African American families.


[The role of clinical autopsy in monitoring the quality of the clinical diagnosis in an emergency department].
A total of 61 autopsies performed in patients died in emergency department of a university hospital were retrospectively analysed and the findings were compared with clinical diagnoses. Sensitivity and specificity of the clinical diagnoses and the correction of medical procedures were measured. The influence of age and sex of patients was analyzed using Fisher's exact test and chi-square-test. The most common causes of death were cardiovascular diseases (52.46%). Autopsy showed unexpected major findings in 44.26% of cases. Major discrepancies between the autopsy reports and the clinical diagnoses, were present in 26.22% of all cases. Absolute concordance between clinical and autopsy diagnoses was obtained in 44.26% of cases. The major sensitivity of clinical diagnosis was found in cerebrovascular disorders (100%), upper digestive hemorrhage (100%), and acute myocardial infarction (82.35%). The lowest sensitivity was found in malignant tumors (16.66%), hemorrhagic pancreatitis (0%) and bowel infarction (0%). The patient cares were correct in 68.85% of cases. No statistically significant differences were observed in relation to age and sex. We concluded that autopsy is a useful method for evaluate diagnostic procedures and quality of medical cares in emergency departments.


Immunohistochemistry of pulmonary surfactant-associated protein A in acute respiratory distress syndrome.
Acute respiratory distress syndrome (ARDS) is a fatal complication in severe traumas and diseases. Although the contribution of pulmonary surfactant abnormality to the pathogenesis of ARDS has been clinically fairly well investigated, the histopathological evidence has not been established. The aim of this study was to clarify the immunohistochemical distribution of surfactant-associated protein A (SP-A) for early diagnosis of ARDS with special regard to hyaline membrane (HM) formation. Two-hundred-and-ten autopsy cases of prolonged death from various traumas and diseases were investigated. ARDS were observed in 23 cases, showing speckled SP-A immunostaining. During the early, exudative phase of ARDS, characteristic SP-A distribution showed intense staining in the intra-alveolar massive aggregates and thick 'peeling'-like substances accompanied with a lot of granular staining. During the proliferative phase, localized accumulation of granular SP-A and macrophages containing dense granular SP-A became predominant. During the final fibrotic phase, SP-A staining in HMs became weak, and disseminated granular staining was observed in the alveolar spaces. These findings provide morphological evidence of the increase of SP-A during the early phase of ARDS, including some molecular alteration and its decrease during the late phase. Characteristic SP-A distribution in the exudative phase appeared to be especially useful for early histopathological diagnosis of respiratory distress, even prior to the appearance of typical HMs.


Acoustic multipath arrivals in the horizontal plane due to approaching nonlinear internal waves.
Simultaneous measurements of acoustic wave transmissions and a nonlinear internal wave packet approaching an along-shelf acoustic path during the Shallow Water 2006 experiment are reported. The incoming internal wave packet acts as a moving frontal layer reflecting (or refracting) sound in the horizontal plane. Received acoustic signals are filtered into acoustic normal mode arrivals. It is shown that a horizontal multipath interference is produced. This has previously been called a horizontal Lloyd's mirror. The interference between the direct path and the refracted path depends on the mode number and frequency of the acoustic signal. A mechanism for the multipath interference is shown. Preliminary modeling results of this dynamic interaction using vertical modes and horizontal parabolic equation models are in good agreement with the observed data.


Comparison of culture and the antigenemia assay for detection of cytomegalovirus in blood specimens submitted to a reference laboratory.
We compared the antigenemia assay (AA) with tandem shell vial cultures (SVCs) and tube cultures (TCs) for detection of cytomegalovirus (CMV) in 343 blood specimens. For 249 specimens, the AA was performed in duplicate with two different commercially available monoclonal antibody reagents (Biotest Diagnostic Corporation and Argene Biosoft). Specimens considered true positives were positive in either culture system or both AAs. Only specimens which were negative in both cultures and positive in a single AA were tested retrospectively with a CMV PCR assay. CMV recovery rates were also calculated to determine if increased specimen age resulted in decreased positivity. CMV recovery rates for the AA and the combination of both cultures were 20.0 and 5.0% at 3 to 18 h, 20.2 and 14.0% at 18 to 35 h, 12.5 and 7.8% at 36 to 52 h, and 18.8 and 6.3% at 64 to 75 h, respectively. The sensitivities and specificities of the Biotest AA, the Argene AA, SVC, and TC were 84.4 and 100.0, 100.0 and 99.6, 44.4 and 100.0, and 46.0 and 100.0%, respectively. The AA was significantly more sensitive than either culture method alone and was also more sensitive than the two culture methods used in tandem (the tandem culture sensitivity was 63.5%); the Argene AA identified more positives than the Biotest AA.


Molten globules, entropy-driven conformational change and protein folding.
The exquisite side chain close-packing in the protein core and at binding interfaces has prompted a conviction that packing selectivity is the primary mechanism for molecular recognition in folding and/or binding reactions. Contrary to this view, molten globule proteins can adopt native topology and bind targets tightly and specifically in the absence of side chain close-packing. The molten globule is a highly dynamic form with native-like secondary structure and a loose protein core that admits solvent. The related (but still controversial) dry molten globule is an expanded form of the native protein with largely intact topology but a tighter protein core that excludes solvent. Neither form retains side chain close-packing, and therefore both structure and function must result from other factors, assuming that the reality of the dry molten globule is accepted. This simplifying realization calls for a re-evaluation of established models.


Cryobiopsy with endobronchial ultrasonography using a guide sheath for peripheral pulmonary lesions and DNA analysis by next generation sequencing and rapid on-site evaluation.
The purpose of this study was to evaluate the diagnostic accuracy of Cryo with endobronchial ultrasonography using a guide sheath (EBUS-GS) for peripheral pulmonary lesions (PPLs) to assess the volume of specimen, determine DNA sequencing analysis, and evaluate the utility of rapid on-site evaluation (ROSE). Out of 30 patients assessed for eligibility, 23 were enrolled in this prospective study. The histological diagnostic yield of Cryo was evaluated and the volume was compared to that of trans-bronchial biopsy (TBB). DNA analysis of Cryo was performed using next generation sequencing (NGS). ROSE was compared with the final diagnosis. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy rate was 85%, 100%, 100%, 50%, 87% for Cryo and 80%, 100%, 100%, 42.9%, 82.6% for TBB, respectively. The mean volume was 0.078 cm3 for Cryo and 0.003 cm3 for TBB (p < 0.0001). All Cryo specimens provided sufficient quantity and quality of DNA for analysis by NGS. ROSE had a high sensitivity (70%), specificity (100%), PPV (100%), and diagnostic accuracy (73.9%). There were no clinically serious adverse events except mild bleeding in 4 cases. Cryo with EBUS-GS for PPLs is a safe and potentially useful diagnostic strategy. It has a high diagnostic yield, and provides significantly larger specimens than TBB. It also provides high quantity and quality of DNA for NGS and high concordance rate between ROSE and the final diagnosis.


[Chemical composition of human milk. Influence of the nutritional status of the nursing mother].
The chemical composition of human milk obtained from 16 underweight women and 25 controls collected at four, eight and 12 weeks of lactation, was determined in order to assess the effect of maternal nutrition upon milk quality. No meaningful differences were observed for protein, lactose, energy, calcium, iron and copper contents. The values obtained are comparable to those reported in the literature from developed countries. As to Zn content, both groups exhibited decreased values with time, with significant higher values for the controls at the 12th week of observation. Magnesium showed exactly the opposite behavior. On the basis of the present study, it is concluded that maternal nutrition does not condition important changes in the chemical composition of human milk. The authors propose the application of comparable methodologic and analytical criteria, in order to achieve a more complete understanding of the relationships between maternal nutrition and lactation.


Mannose-centered aromatic galactoclusters inhibit the biofilm formation of Pseudomonas aeruginosa.
Pseudomonas aeruginosa (PA) is a major public health care issue due to its ability to develop antibiotic resistance mainly through adhesion and biofilm formation. Therefore, targeting the bacterial molecular arsenal involved in its adhesion and the formation of its biofilm appears as a promising tool against this pathogen. The galactose-binding LecA (or PA-IL) has been described as one of the PA virulence factors involved in these processes. Herein, the affinity of three tetravalent mannose-centered galactoclusters toward LecA was evaluated with five different bioanalytical methods: HIA, ELLA, SPR, ITC and DNA-based glycoarray. Inhibitory potential towards biofilms was then assessed for the two glycoclusters with highest affinity towards LecA (Kd values of 157 and 194 nM from ITC measurements). An inhibition of biofilm formation of 40% was found for these galactoclusters at 10 μM concentration. Applications of these macromolecules in anti-bacterial therapy are therefore possible through an anti-adhesive strategy.


Visceral Adiposity Index is not Superior over Anthropometric Parameters with regards to Inflammation in Healthy Adolescent Girls.
Better than simple anthropometric parameters, the visceral adiposity index (VAI) has recently been proposed as a predictor of cardiometabolic risk in adults. However, there are conflicting results on the associations of these parameters in children and adolescents. Therefore, we aimed to estimate this potential relationship between VAI, anthropometric parameters (i.e., body mass index [BMI], waist circumference [WC], and waist-to-height ratio [WHtR], respectively), and inflammation as measured by high-sensitivity C-reactive protein (hs-CRP) levels in a cohort of adolescent girls. A total of 90 adolescent girls from 16 to 19 years old were included in cross-sectional study. Anthropometric and biochemical parameters (glucose, lipid parameters, and hsCRP) were measured. The VAI, derived from anthropometric and lipid parameters, calculated {[WC/36.58 + (1.89 × BMI)] × (triglycerides/0.81) × (1.52/HDL-cholesterol)} was calculated. A comparison of the receiver operating characteristic (ROC) curves showed that all the curves for the anthropometric parameters (e.g., BMI, WC, WHtR) had excellent discriminatory capability with regard to inflammation level status (low vs. high level) and significantly larger areas under the curve (AUC = 0.885, AUC = 0.863, AUC = 0.860, respectively; P < 0.001) than the ROC curve for VAI did (AUC = 0.686; P = 0.021). Visceral adiposity index is not superior over anthropometric parameters in relation to inflammation as measured by high sensitivity C-reactive protein in adolescent girls.


Risk of Chronic Kidney Disease in Brushite Stone Formers Compared With Idiopathic Calcium Oxalate Stone Formers.
To study brushite stone formers (BSFs) change in renal function and overall risk of progression to chronic kidney disease (CKD) over time. A retrospective review of all patients with urolithiasis on stone analysis was performed from 1995 to 2003. Stones were classified as brushite if they had at least 10% brushite composition on analysis. Patients with a minimum of 6 years of clinical follow-up were included in the study. BSFs were matched 1:3 to idiopathic calcium oxalate stone formers (CaOx SF) over the same time period. Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease equation. CKD was classified according to the National Kidney Foundation definition, with grade 3 defined as <60 mL/min/1.73 m2. We identified 20 BSFs who met the inclusion criteria and matched to 60 CaOx SFs. Pure brushite stones were identified in 13 (65%) patients and 17 (85%) had >50% brushite composition. The median patient age (48 vs 47 years, P = .82) and baseline eGFR were not different between BSF and CaOx SF (74 vs 69 mL/min/1.73 m2, P = .68). No patients had stage IV or higher CKD in either group. At median follow-up of 13.6 years, both eGFR (78 vs 74 mL/min/1.73 m2, P = .61) and change in eGFR (0.31 vs 3.2 mL/min/1.73 m2, P = .92) were similar between groups despite the BSF having a higher stone recurrence rate (80% vs 42%, P = .003). No brushite patients experienced a change in CKD stage. BSFs were not shown to be at increased clinical risk of CKD compared with CaOx SFs at long-term follow-up despite more frequent stone recurrence.


The elaborate route for UDP-arabinose delivery into the Golgi of plants.
In plants, L-arabinose (Ara) is a key component of cell wall polymers, glycoproteins, as well as flavonoids, and signaling peptides. Whereas the majority of Ara found in plant glycans occurs as a furanose ring (Araf), the activated precursor has a pyranose ring configuration (UDP-Arap). The biosynthesis of UDP-Arap mainly occurs via the epimerization of UDP-xylose (UDP-Xyl) in the Golgi lumen. Given that the predominant Ara form found in plants is Araf, UDP-Arap must exit the Golgi to be interconverted into UDP-Araf by UDP-Ara mutases that are located outside on the cytosolic surface of the Golgi. Subsequently, UDP-Araf must be transported back into the lumen. This step is vital because glycosyltransferases, the enzymes mediating the glycosylation reactions, are located within the Golgi lumen, and UDP-Arap, synthesized within the Golgi, is not their preferred substrate. Thus, the transport of UDP-Araf into the Golgi is a prerequisite. Although this step is critical for cell wall biosynthesis and the glycosylation of proteins and signaling peptides, the identification of these transporters has remained elusive. In this study, we present data demonstrating the identification and characterization of a family of Golgi-localized UDP-Araf transporters in Arabidopsis The application of a proteoliposome-based transport assay revealed that four members of the nucleotide sugar transporter (NST) family can efficiently transport UDP-Araf in vitro. Subsequent analysis of mutant lines affected in the function of these NSTs confirmed their role as UDP-Araf transporters in vivo.


Emergent dynamics of spatio-temporal chaos in a heterogeneous excitable medium.
Self-organized activation patterns in excitable media such as spiral waves and spatio-temporal chaos underlie dangerous cardiac arrhythmias. While the interaction of single spiral waves with different types of heterogeneity has been studied extensively, the effect of heterogeneity on fully developed spatio-temporal chaos remains poorly understood. We investigate how the complexity and stability properties of spatio-temporal chaos in the Bär-Eiswirth model of excitable media depend on the heterogeneity of the underlying medium. We employ different measures characterizing the chaoticity of the system and find that the spatial arrangement of multiple discrete lower excitability regions has a strong impact on the complexity of the dynamics. Varying the number, shape, and spatial arrangement of the heterogeneities, we observe strong emergent effects ranging from increases in chaoticity to the complete cessation of chaos, contrasting the expectation from the homogeneous behavior. The implications of our findings for the development and treatment of arrhythmias in the heterogeneous cardiac muscle are discussed.


[Variability of the quantitative and qualitative traits of Aedes dorsalis mosquitoes from larval cultures of varying densities].
Larvae of Aedes dorsalis Mg. were maintained at the density of 0.05 and 0.5 spec./ml. It was noted that mosquitoes from overpopulated cultures grew smaller in size. The wings became shorter and more narrow by 4 to 6%. The wing reduction occurred on account of its distal elements (veins r3 and m2). Despite the decrease in the value of characters their variability decreased too, having increased only for wing width and vein mcu. In overpopulated cultures the wing length connection with veins r3 and m2 grew weaker in males while in females only such tendency was observed. Wing bilateral asymmetry was noted: left wing of females became wider and those of males wider and shorter. Analysis of variability of qualitative wing characters, which were singled out according to the venation pattern, has shown that of 9 studied characters only two depended on density (arrangement of corners of radial and medial vectors) and only in females. The role of such wing changes for swarming, active escaping from danger, direction and distance of flight of mosquitoes is discussed.


Negatively co-operative ligand binding.
Simple systems are considered in which the binding of a ligand at a single site exhibits a doubly sigmoid curve when saturation is plotted against the logarithm of ligand concentration, i.e. where a fraction of the site exhibits one dissociation constant and the rest exhibits another. The condition for this to occur is that the ligand should also combine at another site on the binding molecule with comparable affinity and that the binding at one site should markedly lower affinity at the other. The protonation of simple compounds such as cysteine and 3-hydroxypyridine is taken as an example of this process and the equations derived are also applied to the binding of substrates to enzymes.


Helical conformation of alkanes in a hydrophobic cavitand.
Alkanes adopt extended conformations in solution that minimize steric interactions and maximize surface area. Folding can reduce the amount of hydrophobic surface exposed to solvent, but sterically unfavorable gauche interactions result. However, we found that the alkyl chains of two common surfactants in aqueous solution adopt helical conformations when bound within a synthetic receptor. The receptor recognizes the helical alkane better than the extended conformation, even though 2 to 3 kilocalories per mole of strain is introduced. The proper filling of space and burial of hydrophobic surface drive the molecular recognition between the receptor and the coiled alkane.


Internal jugular vein thrombosis after ovarian stimulation.
Thromboembolic events are serious, but fortunately rare, complications following ovarian stimulation for IVF. Here, we report a case of internal jugular vein thrombosis after ovarian stimulation with gonadotrophins. Most of the cases of thrombosis are late complications of ovarian hyperstimulation syndrome (OHSS) or hereditary hypercoagulability. Screening for these risk factors in our patient was negative. The patient was successfully treated with low molecular weight heparin and a twin pregnancy is ongoing.


Comparison between low-dose, high-sort and high-dose, low-sort semen on conception and calf sex ratio in Jersey heifers and cows.
The objective of this clinical trial was to compare conception and newborn calf sex ratios among Jersey heifers and lactating cows inseminated with either standard sex-sorted semen (low-dose, high-sort; LDHS) containing 2.1 × 10(6) sorted sperm at 90% purity or high-dose, low-sort (HDLS) semen containing 10 × 10(6) sorted sperm at 75% purity. After a specified voluntary waiting period (VWP), female subjects, consisting of nulliparous heifers (VWP 10 mo of age) and lactating cows (VWP 50d in milk), received their first service and were systematically allocated to each treatment group in the order in which they presented for artificial insemination (AI). Females were bred to the same sire and type of sex-sorted semen for up to 2 additional services. Animals that were not pregnant after 3 breeding attempts were excluded. A total of 1,846 services were performed on 1,011 eligible females (LDHS; n=494, HDLS; n=517), which consisted of 516 nulliparous heifers and 495 lactating cows. Study groups were comparable with respect to the mean age at first AI for nulliparous heifers and the mean days in milk at first AI for parous cows. Insemination with HDLS semen did not result in a higher proportion of pregnancies per AI (P/AI) compared with LDHS semen for either nulliparous heifers (P/AI=43 vs. 38%) or parous cows (P/AI=47 vs. 43%). Insemination of nulliparous heifers using HDLS resulted in a lower proportion of newborn female calves compared with those bred to LDHS (76% vs. 87%). Similarly, lactating cows bred to HDLS gave birth to a lower proportion of newborn female calves compared with those bred to LDHS (79 vs. 90%). The odds ratio for a female calf to be born to an animal inseminated with HDLS compared with LDHS was 0.32 for nulliparous heifers and 0.19 for parous cows. Overall, the use of HDLS resulted in fewer females compared with LDHS, which may be explained by the lower concentration of X-bearing spermatozoa in HDLS compared with LDHS.


Pestle-pounding and nut-cracking by wild chimpanzees at Kpala, Liberia.
Bossou in Guinea is one of the longitudinal study sites of wild chimpanzees, and is located only a few kilometers away from the national border between Guinea and Liberia. The forests in the area spread over the national border of Guinea, and the Bossou chimpanzees have been found to use the neighboring Liberian forest. Local assistants and I started surveying these forests in Liberia, and found that additional groups of chimpanzees lived in Nimba County, Liberia. The present study reports tool use behaviors by chimpanzees living in forests of the Kpala area in Nimba County. We directly observed pestle-pounding behavior, which had been confirmed only in the Bossou group of wild chimpanzees. Moreover, we heard sounds of nut-cracking, and successfully filmed chimpanzees cracking open oil palm nuts with stones. The uniqueness of stone-tool use behaviors has been emphasized with the group of chimpanzees that have been longitudinally studied at Bossou, but the behaviors probably have a wide distribution in this area. Emigrant chimpanzees are thought to contribute to the propagation of the cultural tool-use behaviors. It is also thought that, if the distantly located groups share similar cultural behaviors, there might be genetic exchange between them. Conservation efforts should be needed not only at Bossou, but also in a wider area including nonprotected forests beyond the national border.


Guideline-recommended vs high-dose long-term opioid therapy for chronic noncancer pain is associated with better health outcomes: data from a representative sample of the German population.
Recent evidence-based guidelines for long-term opioid therapy (LTOT) for chronic noncancer pain (CNCP) have defined daily morphine equivalent doses (MEQ/d) that require particular caution. The recommendation for a threshold MEQ/d is based on North American studies that have demonstrated negative health outcomes associated with high-dose LTOT for CNCP. We have conducted a retrospective cross-sectional study using an anonymized German health claims database, including 4,028,618 persons insured by 69 German statutory health insurances, representative of age and sex for the German population in 2014. Those receiving German guideline-recommended opioid treatments (dose <120 mg MEQ/d) for CNCP were compared with those receiving high-dose LTOT (≥120 mg MEQ/d) for selected health outcomes (risky opioid prescribing; hospital admissions due to diagnoses indicative of abuse/addiction of prescribed opioids; and health costs). The prevalence of LTOT for CNCP was 0.8%, with 9.9% receiving high-dose LTOT. Those receiving German guideline-recommended opioid treatments vs those receiving high-dose LTOT differed for the following parameters: risky opioid prescribing (combination with tranquilizers) (11.1% vs 14.3%; P < 0.001), hospital admissions because of mental and behavioral disorders due to alcohol, opioids, tranquilizers, multiple substances and intoxication by narcotic agents (1.6% vs 2.9%; P < 0.001), and total health costs (7259 vs 10,732 Euro; P < 0.001). The difference in annual costs between the 2 groups was largely due to differences in pharmaceutical costs in the outpatient setting (2282 vs 5402 &OV0556;; P < 0.001). These data confirm recommendations for a threshold MEQ/d for CNCP as recommended by recent opioid prescribing guidelines for CNCP.


Transbilayer movement of various phosphatidylcholine species in intact human erythrocytes.
Phosphatidylcholine specific phospholipid exchange protein was used to introduce (14C)-labeled phosphatidylcholine of different fatty acyl compositions into the intact human erythrocyte. Hydrolysis by a combination of phospholipase A2 and sphingomyelinase was applied to prove that originally all newly introduced phosphatidylcholine resided in the outer monolayer. Subsequently the erythrocytes were reincubated at 37 degrees C, and redistribution of the introduced (14C)phosphatidylcholine was monitored by applying the combination of phospholipases after different times of incubation. In the situation where 20% of the native erythrocyte phosphatidylcholine had been replaced by phosphatidylcholine from (14C)choline-labeled rat liver microsomal membranes, a slow translocation of the (14C)microsomal phosphatidylcholine was found, with a half-time of transbilayer equilibration of 10.8 hr. Furthermore, the transbilayer movement of probe amounts of (14C)dipalmitoyl-phosphatidylcholine, (14C)egg phosphatidylcholine and (14C)soybean phosphatidylcholine was studied under conditions whereby the fatty acyl composition of the bulk erythrocyte phosphatidylcholine remained unchanged. In correlation to the increasing unsaturation of the probe, half-times for the transbilayer equilibration were calculated to be 26.9, 12.8, and 8.1 hr, respectively.


Urine output on an intensive care unit: case-control study.
To compare urine output between junior doctors in an intensive care unit and the patients for whom they are responsible. Case-control study. General intensive care unit in a tertiary referral hospital. 18 junior doctors responsible for clerking patients on weekday day shifts in the unit from 23 March to 23 April 2009 volunteered as "cases." Controls were the patients in the unit clerked by those doctors. Exclusion criteria (for both groups) were pregnancy, baseline estimated glomerular filtration rate <15 ml/min/1.73 m(2), and renal replacement therapy. Oliguria (defined as mean urine output <0.5 ml/kg/hour over six or more hours of measurement) and urine output (in ml/kg/hour) as a continuous variable. Doctors were classed as oliguric and "at risk" of acute kidney injury on 19 (22%) of 87 shifts in which urine output was measured, and oliguric to the point of being "in injury" on one (1%) further shift. Data were available for 208 of 209 controls matched to cases in the data collection period; 13 of these were excluded because the control was receiving renal replacement therapy. Doctors were more likely to be oliguric than their patients (odds ratio 1.99, 95% confidence interval 1.08 to 3.68, P=0.03). For each additional 1 ml/kg/hour mean urine output, the odds ratio for being a case rather than a control was 0.27 (0.12 to 0.58, P=0.001). Mortality among doctors was astonishingly low, at 0% (0% to 18%). Managing our own fluid balance is more difficult than managing it in our patients. We should drink more water. Modifications to the criteria for acute kidney injury could be needed for the assessment of junior doctors in an intensive care unit.


Transshipment site selection using the AHP and TOPSIS approaches under fuzzy environment.
Site selection is an important issue in waste management. Selection of the appropriate solid waste site requires consideration of multiple alternative solutions and evaluation criteria because of system complexity. Evaluation procedures involve several objectives, and it is often necessary to compromise among possibly conflicting tangible and intangible factors. For these reasons, multiple criteria decision-making (MCDM) has been found to be a useful approach to solve this kind of problem. Different MCDM models have been applied to solve this problem. But most of them are basically mathematical and ignore qualitative and often subjective considerations. It is easier for a decision-maker to describe a value for an alternative by using linguistic terms. In the fuzzy-based method, the rating of each alternative is described using linguistic terms, which can also be expressed as triangular fuzzy numbers. Furthermore, there have not been any studies focused on the site selection in waste management using both fuzzy TOPSIS (technique for order preference by similarity to ideal solution) and AHP (analytical hierarchy process) techniques. In this paper, a fuzzy TOPSIS based methodology is applied to solve the solid waste transshipment site selection problem in Istanbul, Turkey. The criteria weights are calculated by using the AHP.


[Distribution of argyrophilic cells in the lungs of human fetuses].
Lungs of the human fetuses have been investigated at the age of 11, 18, 22 and 25 weeks. General histological staining methods and silver nitrate impregnation of the sections after Grimelius have been applied. Single argyrophile endocrinic cells (apudocytes) are revealed in the fetal lungs during all the time investigated. Groups of the argyrophilic cells--neuroepithelial bodies (NEB)--appear later and in small quantity. The quantity of the apudocytes and NEB gradually increases, especially noticeably in the distal parts of the bronchial tree. The number of the apudocytes increases during the canalicular stage of the pulmonary development. The endocrinic apparatus of the human lungs is forming in connection with development of the airy pathways, respiratory part and intraorganic vascular system.


New efficient ruthenium sensitizers with unsymmetrical indeno[1,2-b]thiophene or a fused dithiophene ligand for dye-sensitized solar cells.
Two novel ruthenium sensitizers containing unsymmetrical indeno[1,2-b]thiophene or a fused dithiophene unit in the ancillary ligand have been designed and synthesized. The photovoltaic performance of JK-188 using an electrolyte consisting of 0.6 M 1,2-dimethyl-3-propylimidazolium iodide, 0.05 M I(2), 0.1 M LiI, 0.05 M guanidinium thiocyanate, and 0.5 M tert-butylpyridine in acetonitrile revealed a short-circuit photocurrent density of 18.60 mA/cm(2), an open-circuit voltage of 0.72 V, and a fill factor of 0.71, yielding an overall conversion efficiency of 9.54%. The cell exhibits a remarkable stability under 1000 h of light soaking at 60 °C using a quasi-solid-state electrolyte consisting of 5 wt % poly(vinylidenefluoride-co-hexafluoropropylene), 0.6 M 1-propyl-2,3-dimethylimidazolium iodide, 0.5 M N-methylbenzimidazole, and 0.1 M I(2) in 3-methoxypropionitrile, retaining 97% of the initial efficiency (7.38%).


Metabolic Acidosis in CKD: Core Curriculum 2019.
Maintenance of normal acid-base homeostasis is one of the most important kidney functions. In chronic kidney disease, the capacity of the kidneys to excrete the daily acid load as ammonium and titratable acid is impaired, resulting in acid retention and metabolic acidosis. The prevalence of metabolic acidosis increases with declining glomerular filtration rate. Metabolic acidosis is associated with several clinically important complications, including chronic kidney disease progression, bone demineralization, skeletal muscle catabolism, and mortality. To mitigate these adverse consequences, clinical practice guidelines suggest treating metabolic acidosis with oral alkali in patients with chronic kidney disease. However, large clinical trials to determine the efficacy and safety of correcting metabolic acidosis with oral alkali in patients with chronic kidney disease have yet to be conducted. In this Core Curriculum article, established and emerging concepts regarding kidney acid-base regulation and the pathogenesis, risk factors, diagnosis, and management of metabolic acidosis in chronic kidney disease are discussed.


Nutrition in chronic pancreatitis.
The pancreas is a major player in nutrient digestion. In chronic pancreatitis both exocrine and endocrine insufficiency may develop leading to malnutrition over time. Maldigestion is often a late complication of chronic pancreatic and depends on the severity of the underlying disease. The severity of malnutrition is correlated with two major factors: (1) malabsorption and depletion of nutrients (e.g., alcoholism and pain) causes impaired nutritional status; and (2) increased metabolic activity due to the severity of the disease. Nutritional deficiencies negatively affect outcome if they are not treated. Nutritional assessment and the clinical severity of the disease are important for planning any nutritional intervention. Good nutritional practice includes screening to identify patients at risk, followed by a thoroughly nutritional assessment and nutrition plan for risk patients. Treatment should be multidisciplinary and the mainstay of treatment is abstinence from alcohol, pain treatment, dietary modifications and pancreatic enzyme supplementation. To achieve energy-end protein requirements, oral supplementation might be beneficial. Enteral nutrition may be used when patients do not have sufficient calorie intake as in pylero-duodenal-stenosis, inflammation or prior to surgery and can be necessary if weight loss continues. Parenteral nutrition is very seldom used in patients with chronic pancreatitis and should only be used in case of GI-tract obstruction or as a supplement to enteral nutrition.


The fountain effect of ice-like water across nanotubes at room temperature.
The well-known fountain effect of superfluid helium can directly convert heat to mechanical work by the transport of the superfluid across narrow channels under a temperature difference. But it is regarded as a unique feature of superfluids, only occurring below the temperature of 2.17 K. Here we report a peculiar fountain effect of ice-like water across nanotubes at room temperature. Based on molecular simulations, we observed fascinating ultrafast fountain flow across nanotubes from the cold side to the hot side under a small temperature difference, due to the near-dissipationless nature of ice-like ordered water inside the nanotubes. Water molecules exhibit collective behavior and spontaneously convert thermal energy from the surrounding into directed motion without dissipation. A surprising pressure difference of up to 256 bar is generated from a temperature difference of 23 K, almost reaching the thermodynamic limit. This finding is anticipated to provide a new protocol for power harvesting devices, heat engines and nanomotors.


Time-dependent changes in the mouse hippocampal synaptic membrane proteome after contextual fear conditioning.
A change in efficacy of hippocampal synapses is critical for memory formation. So far, the molecular analysis of synapses during learning has focused on small groups of proteins, whereas the dynamic global changes at these synapses have remained unknown. Here, we analyzed the temporal changes of the mouse hippocampal synaptic membrane proteome 1 and 4 h after contextual fear learning, comparing two groups; (1) a fear memory forming "delayed-shock" group and (2) a fear memory-deficient "immediate-shock" group. No changes in protein expression were observed 1 h after conditioning between the two experimental groups. However, 423 proteins were significantly regulated 4 h later of which 164 proteins showed a temporal regulation after a delayed shock and 273 proteins after the stress of an immediate shock. From the proteins that were differentially regulated between the delayed- and the immediate-shock groups at 4 h, 48 proteins, most prominently representing endocytosis, (amphiphysin, dynamin, and synaptojanin1), glutamate signaling (glutamate [NMDA] receptor subunit epsilon-1, disks large homolog 3), and neurotransmitter metabolism (excitatory amino acid transporter 1, excitatory amino acid transporter 2, sodium- and chloride-dependent GABA transporter 3) were regulated in both protocols, but in opposite directions, pointing toward an interaction of learning and stress. Taken together, this data set yields novel insight into diverse and dynamic changes that take place at hippocampal synapses over the time course of contextual fear-memory learning.


Expression profiling of immune-related genes from Japanese flounder Paralichthys olivaceus kidney cells using cDNA microarrays.
A Japanese flounder Paralichthys olivaceus cDNA microarray containing 871 unique cDNAs including 91 putative immune-related genes from our EST studies was constructed and used to characterize of gene expression of in vitro grown kidney cells stimulated with mitogens such as ConA, PMA, LPS or infected with hirame rhabdovirus (HRV). The numbers of genes whose expressions were increased or decreased by these factors were: 17 by Con A, 139 by PMA, 76 by LPS and 182 by HRV infection. The treatment of Con A for 1 and 6h affected the expression of only a few of the immune-related genes. PMA down-regulated far more genes than it up-regulated. Apoptosis-related factors, such as c-fos, NGF induced protein IB and NR13 genes, were among the genes whose expressions were induced by PMA. LPS induced the expression of inflammation-related genes, such as IL-1beta, monocyte chemotactic protein 1 and collagenase. The expressions of many genes were induced after 3h HRV infection but some of them were decreased to the basal level after 6h HRV infection. The expression of some genes of unknown function were induced or reduced by Con A, PMA or LPS or by HRV infection in different time periods. From all of the gene expression profiling in this study, we could get lots of information about the dynamic changes in the gene expression of the kidney cells under different stress or stimulations.


Lateralized cognitive processes and lateralized task control in the human brain.
The principles underlying human hemispheric specialization are poorly understood. We used functional magnetic resonance imaging of letter and visuospatial decision tasks with identical word stimuli to address two unresolved problems. First, hemispheric specialization depended on the nature of the task rather than on the nature of the stimulus. Second, analysis of frontal candidate regions for cognitive control showed increased coupling between left anterior cingulate cortex (ACC) and left inferior frontal gyrus during letter decisions, whereas right ACC showed enhanced coupling with right parietal areas during visuospatial decisions. Cognitive control is thus localized in the same hemisphere as task execution.


Caring for depression in the dying is complex and challenging - survey of palliative physicians.
Depression is prevalent in people with very poor prognoses (days to weeks). Clinical practices and perceptions of palliative physicians towards depression care have not been characterised in this setting. The objective of this study was to characterise current palliative clinicians' reported practices and perceptions in depression screening, assessment and management in the very poor prognosis setting. In this cross-sectional cohort study, 72 palliative physicians and 32 psychiatrists were recruited from Australian and New Zealand Society of Palliative Medicine and Royal Australian and New Zealand College of Psychiatrists between February and July 2020 using a 23-item anonymous online survey. Only palliative physicians results were reported due to poor psychiatry representation. Palliative physicians perceived depression care in this setting to be complex and challenging. 40.0% reported screening for depression. All experienced uncertainty when assessing depression aetiology. Approaches to somatic symptom assessment varied. Physicians were generally less likely to intervene for depression than in the better prognosis setting. Most reported barriers to care included the perceived lack of rapidly effective therapeutic options (77.3%), concerns of patient burden and intolerance (71.2%), and the complexity in diagnostic differentiation (53.0%). 66.7% desired better collaboration between palliative care and psychiatry. Palliative physicians perceived depression care in patients with very poor prognoses to be complex and challenging. The lack of screening, variations in assessment approaches, and the reduced likelihood of intervening in comparison to the better prognosis setting necessitate better collaboration between palliative care and psychiatry in service delivery, training and research.


Comparison of potential risk factors for medication errors with and without patient harm.
To compare determinants for medication errors leading to patient harm with determinants for medication errors without patient harm. A two-way case-control design was used to identify determinants for medication errors without harm (substudy 1) and determinants for medication errors causing harm (substudy 2). Data of patients admitted to five internal medicine wards of two Dutch hospitals during 5 months were collected prospectively by chart review. Medication errors were detected and classified by two pharmacists. Consensus between five pharmacists was reached on the causal relationship between medication errors and patient harm. Data analysis was performed by multivariate logistic regression. We included 7286 medication orders, of which 3315 without errors (controls), and 5622 medication errors without harm (cases substudy 1) and 102 medication errors causing harm (cases substudy 2) were identified. Hospital, ward and the therapeutic class anti-infectives were associated with both medication errors without harm (hospital odds ratio (OR) 1.40; 95% confidence interval (CI) 1.21-1.63), TweeSteden hospital (TSh) geriatrics OR 2.03; 95% CI 1.73-2.38, TSh general internal medicine OR 1.44; 95% CI 1.23-1.69 and anti-infectives OR 1.28; 95% CI 1.06-1.56) and medication errors with harm (hospital OR 4.91; 95% CI 3.02-7.79, TSh geriatrics OR 5.76; 95% CI 2.52-13.15, TSh general internal medicine OR 6.51; 95% CI 2.82-15.02 and anti-infectives OR 4.20; 95% CI 2.24-7.90). This study shows that organisational determinants (hospital, ward) are comparable for medication errors with and without harm. For conclusions on patient- and medication-related determinants studies with larger sample sizes are needed.


Risk factors for noncompliance in a colposcopy clinic.
To evaluate demographic characteristics as risk factors for noncompliance with colposcopy clinic follow-up. A retrospective, case-control study was performed on patients evaluated in the Women & Infants' Hospital colposcopy clinic between January 1, 1992, and December 31, 1993. Data extracted from chart review included demographic characteristics, insurance status, smoking status, cytologic and histologic grade treatment received, number of appointments kept and missed, number of attempts to contact the patient and degree of compliance with colposcopy follow-up. A scoring system was created to assess a patient's level of compliance by evaluating the number of appointments kept and missed. After review of the first 80 patients, a noncompliance rate of 23% was determined based on our scoring system. A total of 86 noncompliant patients were then compared to 93 compliant patients. Women who were noncompliant with follow-up were more likely to be on Medicaid or to have no insurance when compared to compliant patients (odds ratio [OR] = 2.4, confidence interval [CI] .85, 6.7), but this difference did not reach statistical significance (P = .07). Noncompliant patients were less likely to have high grade lesions than compliant patients (OR = .34; CI .13, .85; P = .01). Patients with lower grade lesions may be more likely to be noncompliant with recommended follow-up than patients with high grade lesions. This association may be due to a reduced emphasis on follow-up and patient education in women with low grade lesions. Increased educational efforts should be made to attempt to reduce high rates of noncompliance in this group of women.


Human mitochondrial DNA is extensively methylated in a non-CpG context.
Mitochondrial dysfunction plays critical roles in cancer development and related therapeutic response; however, exact molecular mechanisms remain unclear. Recently, alongside the discovery of mitochondrial-specific DNA methyltransferases, global and site-specific methylation of the mitochondrial genome has been described. Investigation of any functional consequences however remains unclear and debated due to insufficient evidence of the quantitative degree and frequency of mitochondrial DNA (mtDNA) methylation. This study uses WGBS to provide the first quantitative report of mtDNA methylation at single base pair resolution. The data show that mitochondrial genomes are extensively methylated predominantly at non-CpG sites. Importantly, these methylation patterns display notable differences between normal and cancer cells. Furthermore, knockdown of DNA methyltransferase enzymes resulted in a marked global reduction of mtDNA methylation levels, indicating these enzymes may be associated with the establishment and/or maintenance of mtDNA methylation. DNMT3B knockdown cells displayed a comparatively pronounced global reduction in mtDNA methylation with concomitant increases in gene expression, suggesting a potential functional link between methylation and gene expression. Together these results demonstrate reproducible, non-random methylation patterns of mtDNA and challenge the notion that mtDNA is lowly methylated. This study discusses key differences in methodology that suggest future investigations must allow for techniques that assess both CpG and non-CpG methylation.


INTEGRATING PROSTATE SPECIFIC ANTIGEN DENSITY BIOMARKER INTO DEEP LEARNING PROSTATE MRI LESION SEGMENTATION MODELS.
Prostate cancer lesion segmentation in multi-parametric magnetic resonance imaging (mpMRI) is crucial for pre-biopsy diagnosis and targeted biopsy guidance. Deep convolution neural networks have been widely utilized for lesion segmentation. However, these methods fail to achieve a high Dice coefficient because of the large variations in lesion size and location within the gland. To address this problem, we integrate the clinically-meaningful prostate specific antigen density (PSAD) biomarker into the deep learning model using feature-wise transformations to condition the features in latent space, and thus control the size of lesion prediction. We tested our models on a public dataset with 214 annotated mpMRI scans and compared the segmentation performance to a baseline 3D U-Net model. Results demonstrate that integrating the PSAD biomarker significantly improves segmentation performance in both Dice coefficient and centroid distance metric.


Wound care management: tracheostomy and gastrostomy.
Percutaneous dilatational tracheostomy (PDT) and percutaneous endoscopic gastrostomy (PEG) tube placements are routine procedures performed in the intensive care units (ICUs). They are performed to facilitate care and promote healing. They also help prevent complications from prolonged endotracheal intubation and malnutrition. In most cases, both are performed simultaneously. Physicians performing them require knowledge of local anatomy, tissue and vascular relationships, along with advance bronchoscopy and endoscopy skills. Although PDTs and PEGs are considered relatively low-risk procedures, operators need to have the knowledge and skill to recognize and prevent adverse outcomes. Current published literature on post-procedural care and stoma wound management was reviewed. Available recommendations for the routine care of tracheostomy and PEG tubes are included in this review. Signs and symptoms of early PDT- and PEG-related complications and their management are discussed in detail. These include hemorrhage, infection, accidental decannulation, tube obstruction, clogging, and dislodgement. Rare, life-threatening complications are also discussed. Multidisciplinary teams are needed for improved patient care, and members should be aware of all pertinent care aspects and potential complications related to PDT and PEG placement. Each institute is strongly encouraged to have detailed protocols to standardize care. This review provides a state-of-the-art guidance on the care of patients with tracheostomies and gastrostomies specifically in the ICU setting.


The plant oncogene rolC is responsible for the release of cytokinins from glucoside conjugates.
The rolC gene of Agrobacterium rhizogenes, which drastically affects growth and development of transgenic plants, codes for a cytokinin-beta-glucosidase. Indeed, rolC protein expressed in Escherichia coli as a fusion protein hydrolyses cytokinin glucosides, thus liberating free cytokinins. Furthermore, beta-glucosidase activity present in E. coli extracts expressing the rolC protein was inhibited by affinity-purified antibodies specific for the rolC protein. Finally, rolC proteins expressed in transgenic plants were shown to be responsible for cytokinin-beta-glucosidase activity. Morphological and phytohormonal analysis, performed on transgenic plants that are somatic mosaics for the expression of the rolC gene, extend and confirm our interpretation that the developmental, physiological and morphological alterations caused by rolC expression in transgenic plants are primarily due to a modification of the cytokinin balance. These observations shed new light on the control of growth and differentiation in plants by growth factors.


Concurrent laparoscopic totally extraperitoneal inguinal hernia repair and transurethral resection of prostate: Breaking with convention - A retrospective study.
This study aimed to evaluate concurrent laparoscopic totally extraperitoneal (TEP) inguinal hernia repair and transurethral resection of the prostate (TURP) with determination of outcomes. This retrospective study was conducted at our hospital, from June 2011 to June 2020. Over 9 years, 17 patients with co-existing uncomplicated unilateral or bilateral inguinal hernia (primary/recurrent) and significant benign prostatic hypertrophy were operated in the same sitting. The following outcomes were compared: duration of the surgery, conversion to open hernia surgery, intraoperative and post-operative complications, duration of hospital stay, recurrence, time taken to resume normal activity and cost of the treatment. This study included 17 patients with a mean age of 65 years (range of 50-87 years). The average time taken for the surgery was 115 min with no conversion to open hernia repair. The mean post-operative stay was 3.7 days. There were four patients (23.5%) with seromas identified at day 10, only two remained at 6 weeks and none at 12 weeks. None had significant bleeding intraoperatively or postoperatively. There was no superficial or deep wound infection (including mesh infection). There was no recurrence of inguinal hernia. Two patients (11.7%) developed post-TURP urethral stricture and underwent cystoscopic stricturoplasty, 3 and 2.5 months after the initial procedure. The time taken to resume normal activity was 7 (±1) days. The hospital cost is reduced by 25% as compared to the sum of costs when both the operations are done separately. Concurrent TEP inguinal hernia repair and TURP is a practical, safe and cost-effective procedure.


Aquatic toxicity of magnesium sulfate, and the influence of calcium, in very low ionic concentration water.
The toxicity of magnesium sulfate (MgSO(4)), and the influence of calcium (Ca), were assessed in very soft freshwater (natural Magela Creek water [NMCW]) using six freshwater species (Chlorella sp., Lemna aequinoctialis, Amerianna cumingi, Moinodaphnia macleayi, Hydra viridissima, and Mogurnda mogurnda). The study involved five stages: toxicity of MgSO(4) in NMCW, determination of the toxic ion, influence of Ca on Mg toxicity, toxicity of MgSO(4) at an Mg:Ca mass ratio of 9:1, and derivation of water quality guideline values for Mg. The toxicity of MgSO(4) was higher than previously reported, with chronic median inhibition concentration (IC50)/acute median lethal concentration (LC50) values ranging from 4 to 1,215 mg/L, as Mg. Experiments exposing the 3 most sensitive species (L. aequinoctialis, H. viridissima, and A. cumingi) to Na(2)SO(4) and MgCl(2) confirmed that Mg was the toxic ion. Additionally, Ca was shown to have an ameliorative effect on Mg toxicity. For L. aequinoctialis and H. viridissima, Mg toxicity at the IC50 concentration was eliminated at Mg:Ca (mass) ratios of < or =10:1 and < or =9:1, respectively. For A. cumingi, a 10 to 30% effect persisted at the IC50 concentration at Mg:Ca ratios <9:1. The toxicity of MgSO(4) in NMCW at a constant Mg:Ca ratio of 9:1 was lower than at background Ca, with chronic IC50/acute LC50 values from 96 to 4,054 mg/L, as Mg. Water quality guideline values for Mg (to protect 99% of species) at Mg:Ca mass ratios of >9:1 and < or =9:1 were 0.8 and 2.5 mg/L, respectively. Magnesium can be toxic at concentrations approaching natural background levels, but toxicity is dependent on Ca concentrations, with exposure in very low ionic concentration, Ca-deficient waters posing the greatest risk to aquatic life.


Mammalian ecology and epidemiology of zoonoses.
Insufficient use has been made of ecological data concerning potential hosts in studies to determine the life cycles of zoonotic parasites and pathogens. Factors such as the geographical distribution of hosts, the altitudes at which they live, their affinities for specific habitats, their vertical distribution within the habitat, and the periodicity of their activities have bearing on the hosts' predisposition to involvement in disease cycles. Diets and feeding habits may determine the likelihood of acquiring infection. Reproductive characteristics determine whether a species is suitable as a reservoir or as an amplifying host. Behavioral factors, such as selection of a particular kind of nest site, may also predispose the involvement of the host with parasites and pathogens. Behavior patterns may determine the maximum population densities of hosts. Estimates of population sizes, of relative abundances of species, and of the involvement of species in disease cycles may be strongly influenced by the collecting and sampling methods that are used and also by the behavioral response of the mammals toward collecting devices, such as traps.


Eosinophils altered phenotypically and primed by culture with granulocyte/macrophage colony-stimulating factor and 3T3 fibroblasts generate leukotriene C4 in response to FMLP.
Normodense eosinophils failed to generate leukotriene C4 (LTC4) in response to incremental concentrations of FMLP but did produce LTC4 when stimulated with calcium ionophore A23187. Normodense eosinophils, maintained in culture with 10(-11) M granulocyte/macrophage colony-stimulating factor (GM-CSF) in the presence of 3T3 fibroblasts, became responsive to transmembrane stimulation with FMLP by day 4 with a maximal effect by day 7. After 7 d of culture, hypodense eosinophils stimulated with 2 x 10(-7) M FMLP generated 26 ng LTC4/10(6) cells, and LTC4 biosynthesis was blocked by N-tertbutoxy-carbonyl-L-methionyl-L-leucyl-L-phenylalanine (N-t-BOC-MLP). Neither calcium ionophore stimulation of LTC4 from endogenous arachidonic acid nor substrate-initiated production of LTC4 from incorporated LTA4 changed when eosinophils were cocultured with GM-CSF and 3T3 fibroblasts. Furthermore, when incubated with 10(-6) M FMLP, normodense eosinophils generated no net superoxide measured by the reduction of cytochrome c, whereas replicate eosinophils cultured for 7 d with 10(-11) M GM-CSF and 3T3 fibroblasts reduced a net of 17 nmol of cytochrome c/10(6) cells. These studies suggest that primed and phenotypically altered eosinophils present at an extravascular site may exert pathobiologic effects by responding to soluble ligands in the tissues.


[The contribution of ethnography to knowledge on socio-cultural codes related to localized cutaneous leishmaniasis in a health education program in Venezuela].
This article presents the experience with the validation of the ethnographic methodology as an alternative for an objective and timely approach to the construction of socio-cultural scenarios in communities affected by cutaneous leishmaniasis in Venezuela. It begins with a brief presentation on the resurgence of leishmaniasis in the Americas as a whole and in Venezuela in the context of social inequalities. It proceeds with a review of the role of health education in programs to control endemic diseases. It then highlights the role of ethnography in the construction of rationality in daily life, its meanings, and interpretation by persons with the disease in order to elaborate permanent and sustainable health education programs. The methodology was validated using a figure in which an analysis was performed of the clinical and epidemiological history normally used to gather information on the disease. Among the main findings was the inadequacy of the clinical history design for obtaining information on socio-cultural factors linked to the disease, expressed by specific geographic territories with the support of georeferencing.


[Electromyography in children with polymyositis (author's transl)].
Findings of repeat electromyography (EMG) in 15 children with polymyositis or dermatomyositis are reported. The data classically provided by EMG in these conditions is recalled. Emphasis is put on the contribution of stimulodetection to the diagnosis of primary disease of the muscle. With this procedure, EMG showed myogenic signs in all patients, at the first examination. Electrical anomalies are widespread from the start. A long-term study in 12 patients shows that electrical anomalies remain present long after clinical recovery. EMG disturbances are the last anomalies to disappear. EMG returns to normal when recovery is longstanding. EMG signs reappear if relapse occurs.


A Within-Subject Comparison of Bimodal Hearing, Bilateral Cochlear Implantation, and Bilateral Cochlear Implantation With Bilateral Hearing Preservation: High-Performing Patients.
To compare speech understanding with bimodal hearing and bilateral cochlear implants (CIs). Within-subjects, repeated-measures. Speech understanding was assessed in the following conditions: unilateral hearing aid (HA) in the non-implanted ear, unilateral CI, bimodal (CI + HA), and bilateral CI. In addition, three participants had bilateral hearing preservation and were also tested with bilateral CIs and bilateral HAs (BiBi). Tertiary academic CI center. Eight adult sequential bilateral recipients who, despite achieving incredibly high performance with the first CI, self-selected for bilateral cochlear implantation. Bilateral cochlear implantation. Speech understanding for the adult minimum speech test battery as well as sentences in semidiffuse noise using the R-SPACE system. Bilateral CIs afforded significant individual improvement in a complex listening environment even for individuals demonstrating near perfect sentence scores with both the first CI alone as well as the bimodal condition. The 3 BiBi participants demonstrated additional significant benefit over the bilateral CI condition-presumably because of the availability of interaural time difference cues. These data suggest that, for noisy environments, adding a second implant can significantly improve speech understanding-even for high-performing unilateral CI with bimodal hearing. In diffuse noise conditions, bilateral acoustic hearing can yield even greater benefits beyond that offered by bilateral implantation.


Assessment of bone biopsy needles for sample size, specimen quality and ease of use.
To assess whether there are significant differences in ease of use and quality of samples among several bone biopsy needles currently available. Eight commonly used, commercially available bone biopsy needles of different gauges were evaluated. Each needle was used to obtain five consecutive samples from a lamb lumbar pedicle. Subjective assessment of ease of needle use, ease of sample removal from the needle and sample quality, before and after fixation, was graded on a 5-point scale. The number of attempts necessary to reach a 1 cm depth was recorded. Each biopsy specimen was measured in the gross state and after fixation. The RADI Bonopty 15 g and Kendall Monoject J-type 11 g needles were rated the easiest to use, while the Parallax Core-Assure 11 g and the Bard Ostycut 16 g were rated the most difficult. Parallax Core-Assure and Kendall Monoject needles had the highest quality specimen in the gross state; Cook Elson/Ackerman 14 g and Bard Ostycut 16 g needles yielded the lowest. The MD Tech without Trap-Lok 11 g needle had the highest quality core after fixation, while the Bard Ostycut 16 g had the lowest. There was a significant difference in pre-fixation sample length between needles (P<0.0001), despite acquiring all cores to a standard 1 cm depth. Core length and width decrease in size by an average of 28% and 42% after fixation. Bone biopsy needles vary significantly in performance. Detailed knowledge of the strengths and weaknesses of different needles is important to make an appropriate selection for each individual's practice.


Lipid Metabolism and Cancer Immunotherapy: Immunosuppressive Myeloid Cells at the Crossroad.
Cancer progression generates a chronic inflammatory state that dramatically influences hematopoiesis, originating different subsets of immune cells that can exert pro- or anti-tumor roles. Commitment towards one of these opposing phenotypes is driven by inflammatory and metabolic stimuli derived from the tumor-microenvironment (TME). Current immunotherapy protocols are based on the reprogramming of both specific and innate immune responses, in order to boost the intrinsic anti-tumoral activity of both compartments. Growing pre-clinical and clinical evidence highlights the key role of metabolism as a major influence on both immune and clinical responses of cancer patients. Indeed, nutrient competition (i.e., amino acids, glucose, fatty acids) between proliferating cancer cells and immune cells, together with inflammatory mediators, drastically affect the functionality of innate and adaptive immune cells, as well as their functional cross-talk. This review discusses new advances on the complex interplay between cancer-related inflammation, myeloid cell differentiation and lipid metabolism, highlighting the therapeutic potential of metabolic interventions as modulators of anticancer immune responses and catalysts of anticancer immunotherapy.


Schistosoma haematobium infection in workers returning from Africa to China.
Schistosoma haematobium infection is mainly associated with urinary schistosomiasis. Here, we describe two cases of S haematobium infection in workers returning to China from Tanzania and Angola. They had hematuria and were misdiagnosed as having tuberculosis or tumor of the bladder. The diagnosis was established by discovery of eggs in the urine.


Percutaneous Zenith endografting for abdominal aortic aneurysms.
A completely percutaneous approach to infrarenal abdominal aortic aneurysm (AAA) endografting has the theoretic benefits of being minimally invasive and more expedient. Our goal was to demonstrate the utility of this approach using a suprarenal fixation device and a suture-mediated closure system. We conducted a single-institution, retrospective review of 14 patients who underwent percutaneous AAA repair with the Zenith device between August 2003 and March 2007. Immediate and delayed access-related outcomes were examined over a mean follow-up of 12.1+/-2.0 months. Mean AAA size was 5.6 cm. Immediate arterial closure and technical success rate was 96% (27/28 vessels). One immediate hemostatic failure required open surgical repair. Over follow-up, one vessel required operative repair for new-onset claudication. No other immediate or delayed complications (thrombosis, pseudoaneurysm, infection, or deep venous thrombosis) were detected. A percutaneous approach for the treatment of AAA has several advantages over femoral artery cutdown but also has its own unique set of risks in the immediate and late postoperative period. Ultimately, the "preclose technique" can be safely applied for the Zenith device despite its large-bore delivery system.


Targeted impairment of thymidine kinase 2 expression in cells induces mitochondrial DNA depletion and reveals molecular mechanisms of compensation of mitochondrial respiratory activity.
The mitochondrial DNA (mtDNA) depletion syndrome comprises a clinically heterogeneous group of diseases characterized by reductions of the mtDNA abundance, without associated point mutations or rearrangements. We have developed the first in vitro model to study of mtDNA depletion due to reduced mitochondrial thymidine kinase 2 gene (TK2) expression in order to understand the molecular mechanisms involved in mtDNA depletion syndrome due to TK2 mutations. Small interfering RNA targeting TK2 mRNA was used to decrease TK2 expression in Ost TK1(-) cells, a cell line devoid of endogenous thymidine kinase 1 (TK1). Stable TK2-deficient cell lines showed a reduction of TK2 levels close to 80%. In quiescent conditions, TK2-deficient cells showed severe mtDNA depletion, also close to 80% the control levels. However, TK2-deficient clones showed increased cytochrome c oxidase activity, higher cytochrome c oxidase subunit I transcript levels and higher subunit II protein expression respect to control cells. No alterations of the deoxynucleotide pools were found, whereas a reduction in the expression of genes involved in nucleoside/nucleotide homeostasis (human equilibrative nucleoside transporter 1, thymidine phosphorylase) and mtDNA maintenance (DNA-polymerase γ, mitochondrial transcription factor A) was observed. Our findings highlight the importance of cellular compensatory mechanisms that enhance the expression of respiratory components to ensure respiratory activity despite profound depletion in mtDNA levels.


Expression and significance of E-cadherin and β-catenins in pituitary adenoma.
This study used immunohistochemical methods for detecting the expression of E-cadherin and β-catenin in pituitary adenoma. Specimens were collected from 91 cases. EnVision was used for immunohistochemical staining. The results were graded depending on the staining intensity and range. Associations between E-cadherin and β-catenin expression and tumor subtype, invasiveness, and postoperative recurrence were investigated. There was a significant downregulation of E-cadherin and β-catenin in growth hormone (GH)-type tumors when compared with prolactin-type tumors (u(c) = 2.693 and 2.109, respectively; P < .05). E-cadherin and β-catenin were downregulated in invasive pituitary adenomas (u(c) = 3.563 and 4.166, respectively; P < .05) and in clinically recurring pituitary adenomas (u(c) = 2.871 and 3.866, respectively; P < .05). There was no difference in the percentage of invasive prolactin and GH secreting tumors (28.57% and 22.86%, respectively; P > .05). The expression of E-cadherin and β-catenin in pituitary adenoma was significantly downregulated and related to subtype, invasiveness, and postoperative recurrence.


Trends in medical spending by age, 1963-2000.
We combine household surveys and total spending data to analyze trends in medical spending from 1963 to 2000. During this nearly forty-year period, spending grew fastest among the elderly. Per person spending among the elderly grew rapidly from 1963 to 1987, but this trend then reversed during the next decade, reflecting reforms to Medicare's physician and hospital payment systems. Prescription drug spending growth accelerated throughout the time period; it grew fastest among the nonelderly, for whom prescription drug insurance coverage is most extensive.


Childhood blindness in Lebanon.
A survey in the Lebanese schools for the blind revealed that 77% of childhood blindness in the country was genetically determined. Two thirds of the hereditary blindness cases were due to autosomal recessive conditions; the high frequency of consanguineous marriages in Lebanon was the underlying cause of this finding. There is marked similarity in the etiology of childhood blindness in Cyprus and Lebanon, for both countries are somewhere between the highly developed countries.


An investigation of the correspondence between psychological problems diagnosed by GPs and those subsequently targeted for treatment by clinical psychologists.
1. To observe the level of concordance between problems identified by GPs in the referral letter, and primary treatment targets identified by Clinical Psychologists following assessment within an NHS Clinical Psychology Department. 2. To examine whether concordance between GP and Psychologist varies for different psychological problem areas. 3. To examine whether concordance between GP and Psychologist varies with time spent on the waiting list. A retrospective review, and classification, of GP referral letters and Psychologists treatment targets. A Department of Clinical Psychology based in Scotland. Sixty five GPs based across fifteen GP practices refer to the department. Four hundred and one patients consecutively referred by GPs to the Department of Clinical Psychology between April 1 1996 and March 31 1998, and subsequently assessed by one of the qualified Clinical Psychologists. Two hundred and seventy three cases were female (68.08%), 128 male (31.92%). Overall agreement between GP referred problem and Psychologist treatment target, coded in terms of EPPIC 'reasons for care' categories, was 'fair', and observed for 59.6% of cases. High agreement for eating disorders, moderate agreement for anxiety and depression, and low agreement for relationship/social problems was observed. Analysis indicated one third of anxiety referrals and one half of depression referrals were treated differently. Agreement levels were high for short waiting times, and lower for long waiting times, although findings for intermediate waiting times were mixed. Moderate agreement levels between GP and Clinical Psychologist in cases initially referred for anxiety and depression replicate previous findings. Low levels of agreement for relationship/social problems were not anticipated. The implications of results for future research and service provision are outlined.