Emotional experience in patients with advanced Alzheimer's disease from the perspective of families, professional caregivers, physicians, and scientists.
The objective of this qualitative study was to gain insight into families' and professionals' understanding of the emotional experience in patients with advanced Alzheimer's disease. A total of ten focus group interviews were carried out with 63 participants (relatives n = 20; caregivers n = 17; physicians n = 12; scientists n = 14) recruited using purposive sampling strategies. Each focus group was audiotaped, transcribed and analysed using the method of structured qualitative content analysis. Study findings show that for all groups with the exception of relatives, emotionality is one of the most important characteristics retained despite the illness. Indicators are patient's continued ability to produce emotional signals, be responsive to others, and retain emotional information despite memory loss. In the spectrum of emotions, professional caregivers emphasize positive emotional states more strongly than physicians or scientists. In contrast, relatives emphasize the loss of emotional experience. Critical indicators denying subjective emotional experience are impairment of (autobiographical) memory (especially the non-recognition of relatives), the reduction of means of verbal expression with simultaneous uncertainty in interpreting nonverbal expression as well as the perceived discrepancy between present emotional experience and behaviour and that of the premorbid personality. When relatives anchor on the premorbid personality, the perceived discontinuity of emotional reactions to stimuli triggering an emotional response in contrast to their own expectations gives rise to an extremely ambiguous situation. Training programmes should be developed for families to help them comprehend and respond to nonverbal emotional expression.


Identification of the crayfish plague fungus Aphanomyces astaci by polymerase chain reaction and restriction enzyme analysis.
To characterise the DNA of the crayfish plague fungus Aphanomyces astaci, Saprolegniales (Oomycetes), primers were developed to amplify a 1050bp segment of the 28S rDNA region. Restriction enzymes were applied to the amplicon obtained, to distinguish A. astaci from 12 fungal species belonging also to the Saprolegniales and five more distantly related fungi. Most of the fungal species included in the study are either known parasites of freshwater crayfish cuticle or can be found in their natural environment. A. astaci DNA was distinguishable from the DNA of other fungal species tested by using the primers developed plus restriction enzymes AluI, HindIII and AvaI. Prior to this study, methods for A. astaci-species determination, e.g. spore production and infection experiments, required a protracted period to yield results; the method described in this study is quicker.


Characterization of metal kinetics and bioavailability using diffusive gradients in thin films technique in sediments of Taihu Lake, China.
For an improved understanding of the metal behavior between the sediment and overlaying water of Taihu Lake, the technique of diffusive gradients in thin films (DGT) was used to characterize the DGT measured concentration in sediments and release kinetics of Cr, Ni, Cu, Zn, Cd and Pb in representative lake parts. Spatially, the DGT-measured concentration of heavy metals showed that Zn, Cu, Ni, Cr, and Pb had higher concentrations in the northern lake than in the eastern Lake Taihu. The order of the release flux for the studied metals from sediments to overlaying water was Zn>Cu>Ni, Cr>Pb>Cd (p<0.05). DGT devices were deployed over a series of time (0.5, 1, 2, 4, 8, 12, 24 and 48 h) in sediment cores from the two typical lake parts (northwest algae dominant area and southeast macrophyte dominant area) to explore the dynamics in the sediment/DGT system, and the best fitted regression model was selected to characterize the release of metals in the two lake parts. The fitted results showed that the equilibration time of the metal release was approximately 24h and Zn had a higher release capacity than other metals. Further analyses indicated that significant correlation existed between the DGT-measured metal concentrations in sediments and metal concentrations in lake organisms (r=0.943 and 0.996 for zoobenthos and coilia ectenes, p<0.05), suggesting that DGT technique is more effective to predict the metal bioavailability in lake sediments.


NMDA receptor-dependent synaptic plasticity in dorsal and intermediate hippocampus exhibits distinct frequency-dependent profiles.
The hippocampus may be functionally differentiated along its dorsoventral axis. In contrast to the wealth of data available on synaptic plasticity mechanisms in the dorsal hippocampus, little is known about synaptic plasticity processes in the intermediate hippocampus. Behavioral data suggest that this structure may play a distinct role in learning and memory. Here, we compared amplitudes, frequency-dependency and persistency of long-term potentiation (LTP) and long-term depression (LTD) in the dorsal (DDG) and intermediate dentate gyrus (IDG). In freely moving rats, high-frequency stimulation (HFS) at 200 Hz (10 burst of 15 stimuli) elicited LTP of similar magnitude in both structures that persisted for over 24 h. The intermediate dentate gyrus is more likely to exhibit persistent LTP than its dorsal counterpart, however: HFS at 200 Hz (3 or 1 burst(s)) or 100 Hz elicited short-term potentiation (STP) in DDG, unlike in the IDG, where LTP could be recorded for at least 4 h. Whereas low frequency stimulation (LFS) at 1 Hz elicited long-lasting LTD (>24 h) in the DDG, it had no significant effect on fEPSP profile in the IDG. LFS at 2 Hz elicited short-term depression in DDG and had no effect in IDG. LTP in both IDG and DDG required activation of N-methyl-D-aspartate receptors. Paired-pulse and input-output responses differed in IDG and DDG. Our data suggest that afferent input from the entorhinal cortex generates a different response profile in the dorsal vs. intermediate DG, which may in turn relate to their postulated distinct roles in synaptic information processing and memory formation. This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'.


Multi-parameter optimization of the capacitance of Carbon Xerogel catalyzed by NaOH for application in supercapacitors and capacitive deionization systems.
Carbon Xerogel is an economic choice of material for electrodes with applications in Electric Double Layer Capacitors (EDLCs) and Capacitive DeIonization systems (CDI, particularly for desalination). The objective here is to optimize Carbon Xerogel's performance, specifically its capacitance, through multi-parameter optimization using Response Surface Methodology (RSM). We choose NaOH as the catalyst and select as the optimization parameters (i) the pH of the initial Resorcinol-Formaldehyde-Catalyst (RFC) solution, (ii) Reactants to Liquid mass ratio (R/L) of the RFC solution, and (iii) the Pyrolysis Temperature (PT). For a selected range of these three parameters, we obtain an optimum capacitance of Carbon Xerogel equal to 37.6 F/g with optimized parameters PT = 800, R/L = 30% and pH = 5.7. Through comparing Carbon Xerogel samples synthesized with Na2CO3 versus NaOH as the catalyst, we show that the capacitance not only depends on the pH of the initial RFC solution, but also is a strong function of the catalyst material.


Trends in the Average Age of Quitting Among U.S. Adult Cigarette Smokers.
Quitting smoking at any age confers health benefits. However, studies have suggested that quitting by age 35 years leads to mortality rates similar to never smokers. This study assessed whether the mean and median ages of past-year quitting and prevalence of past-year quit attempts and successful quitting by age group changed over time. Data came from 113,599 adult cigarette smokers participating in the 1997-2012 National Health Interview Survey, an annual, cross-sectional household survey of U.S. adults aged ≥18 years. Mean and median ages of past-year successful abstinence (quit 6-12 months) were computed. Orthogonal polynomial logistic regression models tested for trends in quit attempts and successful quitting. Data were analyzed in 2014. The average age of quitting (40.0 years in 1997-1998, 39.5 years in 2011-2012, p=0.80) and median age of quitting (35.9 years in 1997-1998, 36.9 years in 2011-2012, p=0.62) did not change over time. During 1997-2012, the percentage of smokers making a past-year quit attempt increased among those aged 25-34, 35-44, and 45-64 years; the percentage of smokers who reported quitting successfully increased among those aged 25-34 and 35-44 years (p<0.001). Although the average age of quitting did not change over time, increases in past-year quit attempts and successful quitting occurred among adults aged 25-44 years. Proven population-level interventions--including price increases, mass media campaigns, comprehensive smoke-free policies, and health systems interventions--should be continued to further increase cessation, particularly among younger adults.


Chemotherapy of carcinoma of renal pelvis: preliminary report.
Seven patients with metastatic and/or recurrent transitional cell carcinoma of the renal pelvis treated with systemic chemotherapy are evaluated. The median age of the patients was fifty-five; 6 were men, 6 of the tumors were histologic grade III and Stage C at the time of nephroureterectomy. Most of the patients presented with a large recurrent mass at the original site of surgery in addition to bone and/or pulmonary metastases. Four patients were treated with CISCA combination chemotherapy (cis-platinum, cyclophosphamide, and doxorubicin), and responded with 1 partial remission, 1 less than partial remission, and 2 symptomatic improvement. Two patients were treated with FAM combination chemotherapy (5-fluorouracil, doxorubicin, and mitomycin C) and demonstrated an objective response. One patient had a less than partial remission (30 per cent) and the second patient a partial remission. The seventh patient was treated with alternating courses of CISCA and FAM and thus far has received 8 courses and is in complete remission. The median survival time of the 7 patients is seven months (range four to fourteen months). Transitional cell carcinoma of the renal pelvis is responsive to chemotherapy; therefore, trials are indicated.


Epithelial downgrowth as a complication of toxic anterior segment syndrome.
We present a case of epithelial downgrowth that arose within 1 month of routine clear corneal phacoemulsification. The case was complicated by unexplained total corneal edema from the first postoperative day. Histological analysis following penetrating keratoplasty showed complete endothelial cell loss and an epithelial cyst on the internal surface of Descemet's membrane.


Heritability of Human Plasma N-Glycome.
The N-glycosylation profile of total human plasma proteins could be a useful biomarker for various pathological states. Reliable high-throughput methods for such profiling have been developed. However, studies of relative importance of genetic and environmental factors in regulating plasma N-glycome are scarce. The aim of our study was to determine the role of genetic factors in phenotypic variation of plasma N-glycan profile through the estimates of its heritability. Thirty-nine total plasma N-glycome traits were analyzed in 2816 individuals from the TwinsUK data set. For the majority of the traits, high heritability estimates (>50%) were obtained pointing at a significant contribution of genetic factors in plasma N-glycome variation, especially for glycans mostly attached to immunoglobulins. We have also found several structures with higher environmental contribution to their variation.


Design, synthesis and biological evaluation of peptide derivatives of L-dopa as anti-parkinsonian agents.
A series of dipeptide derivatives of L-dopa were synthesized and investigated for their pharmacological activity using the unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rat as an experimental model of Parkinson's disease. Among them, (S)-isopropyl 2-(2-amino-2-methylpropanamido)-3-(3,4-dihydroxyphenyl)propanoate (4 g) was found to be the most active compound, with 106% AUC activity and 149% peak activity of L-dopa after oral administration.


Intestinal detoxification time of hand-foot-and-mouth disease in children with EV71 infection and the related factors.
Hand-foot-and-mouth disease (HFMD) is a common pediatric infectious disease caused by a variety of intestinal viruses. Enterovirus 71 (EV71) is the primary pathogen that might cause severe symptoms and even death in children with HFMD. This study aimed to investigate the intestinal detoxification time of HFMD children with EV71 infection and its related factors. Sixty-five HFMD children with EV71 infection were followed up. Their stool samples were collected once every 4 to 7 days. Viral nucleic acids were detected by fluorescent polymerase chain reaction until the results became negative. The positive rates of viral nucleic acids were analyzed by the Kaplan-Meier method. The Log-rank test and Cox-Mantel test were used to analyze factors affecting the HFMD children with EV71 infection. On the 2nd, 4th, 6th and 10th week, the positive rates of viral nucleic acids in stool samples of the 65 children were 94.6%, 48.1%, 17.2% and 0, respectively. Univariate analysis showed that the intestinal detoxification time of the children were related to gender, pre-admission disease course, severity of disease, and use of steroids or gamma globulin (P<0.05). Multivariate analysis showed that the severity of disease was an independent factor affecting the intestinal detoxification time (P<0.05), with a relative risk of 2.418. The longest intestinal detoxification time of HFMD children with EV71 infection was 10 weeks. The severity of disease was an important factor affecting the intestinal detoxification time of HFMD children with EV71 infection. Severe HFMD children with EV71 infection had a longer intestinal detoxification time.


Identification of Human Neuronal Protein Complexes Reveals Biochemical Activities and Convergent Mechanisms of Action in Autism Spectrum Disorders.
The prevalence of autism spectrum disorders (ASDs) is rapidly growing, yet its molecular basis is poorly understood. We used a systems approach in which ASD candidate genes were mapped onto the ubiquitous human protein complexes and the resulting complexes were characterized. The studies revealed the role of histone deacetylases (HDAC1/2) in regulating the expression of ASD orthologs in the embryonic mouse brain. Proteome-wide screens for the co-complexed subunits with HDAC1 and six other key ASD proteins in neuronal cells revealed a protein interaction network, which displayed preferential expression in fetal brain development, exhibited increased deleterious mutations in ASD cases, and were strongly regulated by FMRP and MECP2 causal for Fragile X and Rett syndromes, respectively. Overall, our study reveals molecular components in ASD, suggests a shared mechanism between the syndromic and idiopathic forms of ASDs, and provides a systems framework for analyzing complex human diseases.


Ophthalmologist Turnover in the United States: Analysis of Workforce Changes from 2014 through 2021.
Physician turnover is costly to health care systems and affects patient experience due to discontinuity of care. This study aimed to assess the frequency of turnover by ophthalmologists and identify physician and practice characteristics associated with turnover. Retrospective cross-sectional study. Actively practicing United States ophthalmologists included in the Centers for Medicare and Medicaid Services Physician Compare and Physician and Other Supplier Public Use File between 2014 and 2021. We collected data for each ophthalmologist that was associated with practice/institution and then calculated the rate of turnover both annually in each year window and cumulatively as the total proportion from 2014 to 2021. Multivariable logistic regression analysis was used to identify physician and practice characteristics associated with turnover. We also evaluated turnover characteristics surrounding the Coronavirus disease 2019 (COVID-19) pandemic. Ophthalmologist turnover, defined as a change of an ophthalmologist's National Provider Identifier practice affiliation from one year to the next. Of 13 264 ophthalmologists affiliated with 3306 unique practices, 34.1% separated from at least 1 practice between 2014 and 2021. Annual turnover ranged from 3.7% (2017) to 19.4% (2018), with an average rate of 9.4%. Factors associated with increased turnover included solo practice (adjusted odds ratio [aOR], 9.59), university affiliation (aOR, 1.55), practice location in the Northeast (aOR, 1.39), and practice size of 2 to 4 members (aOR, 1.21; P < 0.05 for all). Factors associated with decreased turnover included male gender (aOR, 0.87) and more than 5 years of practice: 6 to 10 years (aOR, 0.63), 11 to 19 years (aOR, 0.54), 20 to 29 years (aOR, 0.36), and ≥ 30 years (aOR, 0.18; P < 0.05 for all). In the initial year (2020) of the COVID-19 pandemic, annual turnover increased from 7.8% to 11.0%, then decreased to 8.7% in the postvaccine period (2021). One-third of United States ophthalmologists separated from at least 1 practice from 2014 through 2021. Turnover patterns differed by various physician and practice characteristics, which may be used to develop future strategies for workforce stability. Because administrative data cannot solely determine reasons for turnover, further investigation is warranted given the potential clinical and financial implications. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.


Prognostic significance of Epstein-Barr virus DNA detection in pretreatment serum in diffuse large B-cell lymphoma.
It is still a matter of debate whether detection of Epstein-Barr virus (EBV) DNA in pretreatment serum has clinical implications for diffuse large B-cell lymphoma. For this study, we measured EBV DNA load in pretreatment serum from 127 diffuse large B-cell lymphoma patients without any underlying immunodeficiency to evaluate its effects on clinical manifestations and prognosis. Anthracycline-based chemotherapy in combination with rituximab was given as initial therapy for 119 patients (94%). Epstein-Barr virus DNA was detected in 15 patients (12%), who were older (P = 0.005) and tended to be at a more advanced disease stage (P = 0.053). They showed significantly worse progression-free survival (PFS) and overall survival (OS) than other patients (P < 0.001 each). This effect remained significant (P = 0.004 and P = 0.027, respectively) after adjustment for age, lactate dehydrogenase, performance status, stage, and extranodal sites. The status of EBV-encoded small RNA in situ hybridization was known for 123 patients; 6 of 8 positive patients (75%) and 9 of 115 negative patients (8%) had detectable EBV DNA in pretreatment serum. While patients positive for EBV-encoded small RNA had significantly worse PFS and OS than negative patients (P = 0.001 and P = 0.029, respectively), EBV DNA detection in pretreatment serum was associated with poorer PFS and OS even for the 115 patients negative for EBV-encoded small RNA (P < 0.001 each). These findings suggest that EBV DNA detection in pretreatment serum may have an adverse prognostic impact for patients with diffuse large B-cell lymphoma.


Effect of geometry on drug release from 3D printed tablets.
The aim of this work was to explore the feasibility of combining hot melt extrusion (HME) with 3D printing (3DP) technology, with a view to producing different shaped tablets which would be otherwise difficult to produce using traditional methods. A filament extruder was used to obtain approx. 4% paracetamol loaded filaments of polyvinyl alcohol with characteristics suitable for use in fused-deposition modelling 3DP. Five different tablet geometries were successfully 3D-printed-cube, pyramid, cylinder, sphere and torus. The printing process did not affect the stability of the drug. Drug release from the tablets was not dependent on the surface area but instead on surface area to volume ratio, indicating the influence that geometrical shape has on drug release. An erosion-mediated process controlled drug release. This work has demonstrated the potential of 3DP to manufacture tablet shapes of different geometries, many of which would be challenging to manufacture by powder compaction.


Recovery of hemoglobin mass after blood donation.
Blood donation plays an important role in every health care system. Measurement of hemoglobin (Hb) concentration or hematocrit to assess hematologic recovery after donation may not adequately reflect the true amount of blood as they are affected by plasma volume fluctuations. Instead, total Hb mass (tHb) is the variable of choice and can be determined in routine clinical practice. Therefore, the purpose was to investigate the recovery of tHb after standard blood donation. The optimized CO rebreathing method was used for evaluation of tHb before and after 1-unit (erythrocyte concentrate) standard blood donation in 29 male volunteers (30 +/- 10 years, 181 +/- 7 cm, 76.6 +/- 11.2 kg). Subsequently, tHb measurements were performed in regular intervals until one of two termination criteria was met. After donation of approximately 550 mL of whole blood, the lost amount of tHb of 75 +/- 15 g (8.8 +/- 1.9%) was recovered after a mean of 36 +/- 11 days (range, 20-59 days). The results of this study confirm the minimal, recommended donation intervals (56 days for men) as adequate when, for the first time, judged upon by tHb as a direct marker of hematologic recovery.


An NADH-induced conformational change that mediates the sequential 3 beta-hydroxysteroid dehydrogenase/isomerase activities is supported by affinity labeling and the time-dependent activation of isomerase.
3 beta-Hydroxysteroid dehydrogenase (3 beta-HSD) and steroid delta-isomerase were copurified as a single protein from human placental microsomes. Because NADH is an essential activator of isomerase (Kact = 2.4 microM, Vmax = 0.6 mumol/min/mg), the affinity alkylating nucleotide, 8-[(4-bromo-2,3-dioxobutyl)thio]adenosine 5'-diphosphate (8-BDB-TADP), was synthesized. 8-BDB-TADP activates isomerase (Kact = 338 microM, Vmax = 2.1 mumol/min/mg) prior to inactivating the enzyme. The inactivation kinetics for isomerase fit the Kitz and Wilson model for time-dependent, irreversible inhibition by 8-BDB-TADP (KI = 314 microM, first order maximal rate constant kobs = 7.8 x 10(-3) s-1). NADH (50 microM) significantly protects isomerase from inactivation by 8-BDB-TADP (100 microM). The isomerase activity is inactivated more rapidly by 8-BDB-TADP as the concentration of the affinity alkylator increases from 67 microM (t1/2 = 8.4 min) to 500 microM (t1/2 = 2.4 min). In sharp contrast, the 3 beta-HSD activity is inactivated more slowly as the concentration of 8-BDB-TADP increases from 67 microM (t1/2 = 4.8 min) to 500 microM (t1/2 = 60.0 min). We hypothesized that the paradoxical kinetics of 3 beta-HSD inactivation is a consequence of the activation of isomerase by 8-BDB-TADP via a nucleotide-induced shift in enzyme conformation. Biophysical support for an NADH-induced conformational change was obtained using stopped-flow fluorescence spectroscopy. The binding of NADH (10 microM) quenches the intrinsic fluorescence of the enzyme protein in a time-dependent manner (rate constant kapp = 8.1 x 10(-3) s-1, t1/2 = 85 s). A time lag is also observed for the activation of isomerase by NADH. This combination of affinity labeling and biophysical data using nucleotide derivatives supports our model for the sequential reaction mechanism; the cofactor product of the 3 beta-HSD reaction, NADH, activates isomerase by inducing a conformational change in the single, bifunctional enzyme protein.


Temperature-sensitive polioviruses containing mutations in RNA polymerase.
Site-directed mutagenesis was performed to change the wild-type residue (asparagine) to aspartate, histidine, or tyrosine at amino acid 424 of the poliovirus RNA polymerase, 3Dpol. The mutations were introduced into plasmids containing full-length viral cDNA and plasmids which direct the expression of 3Dpol in Escherichia coli. Mutant viruses, recovered after transfection of HeLa cells with RNA transcripts of the full-length clones, produced small plaques at 32 degrees. In addition, the plaquing efficiency was decreased for all three mutants at 37 degrees, compared to 32 degrees. The polyprotein processing of all mutant viruses was normal at the temperatures tested, suggesting that the mutant plaque phenotypes were not due to incorrect processing of viral proteins. Analyses of viral RNA synthesis in infected cells and of the polymerase activities of mutant enzymes produced in E. coli suggested the following: (1) The his424 mutant enzyme appeared to be defective in the initiation of plus-strand RNA synthesis in HeLa cells. (2) The asp424 mutant enzyme appeared unable to assume proper conformation for active polymerase function when synthesized at 37 degrees. (3) The tyr424 mutant enzyme was totally inactive when synthesized in E. coli at 37 degrees.


Hybrid superconductor-quantum dot devices.
Advances in nanofabrication techniques have made it possible to make devices in which superconducting electrodes are connected to non-superconducting nanostructures such as quantum dots. The properties of these hybrid devices result from a combination of a macroscopic quantum phenomenon involving large numbers of electrons (superconductivity) and the ability to control single electrons, offered by quantum dots. Here we review research into electron transport and other fundamental processes that have been studied in these devices. We also describe potential applications, such as a transistor in which the direction of a supercurrent can be reversed by adding just one electron to a quantum dot.


The preoperative evaluation of the child with epilepsy.
This article reviews the preoperative evaluation of the child with intractable epilepsy. The importance of the history and the clinical manifestations of the seizures, and the results of electrophysiology, neurophysiology, and neuroimaging studies are discussed.


The T1150A cancer mutant of the protein lysine dimethyltransferase NSD2 can introduce H3K36 trimethylation.
Protein lysine methyltransferases (PKMTs) play essential roles in gene expression regulation and cancer development. Somatic mutations in PKMTs are frequently observed in cancer cells. In biochemical experiments, we show here that the NSD1 mutations Y1971C, R2017Q, and R2017L observed mostly in solid cancers are catalytically inactive suggesting that NSD1 acts as a tumor suppressor gene in these tumors. In contrast, the frequently observed T1150A in NSD2 and its T2029A counterpart in NSD1, both observed in leukemia, are hyperactive and introduce up to three methyl groups in H3K36 in biochemical and cellular assays, while wildtype NSD2 and NSD1 only introduce up to two methyl groups. In Molecular Dynamics simulations, we determined key mechanistic and structural features controlling the product specificity of this class of enzymes. Simulations with NSD2 revealed that H3K36me3 formation is possible due to an enlarged active site pocket of T1150A and loss of direct contacts of T1150 to critical residues which regulate the product specificity of NSD2. Bioinformatic analyses of published data suggested that the generation of H3K36me3 by NSD2 T1150A could alter gene regulation by antagonizing H3K27me3 finally leading to the upregulation of oncogenes.


Evaluation of thermal cycling and mechanical loading on bond strength of a self-etching primer system to dentin.
The aim of this study was to evaluate the in vitro durability and fracture modes of the tooth-resin interface following thermal cycling, fatigue load cycling (FLC) and micro-tensile bond strength testing (MTBS). Twenty-four human molars were divided into two groups. In group A, coronal dentin was ground flat with #600-grit SiC paper, Clearfil Linerbond.2V (LB.2V) adhesive was applied and a crown fabricated with Clearfil AP-X resin composite. Samples were loaded in the FLC simulator and thermal cycle device. In group B, Class I cavities were prepared with a diamond bur and the cavity restored with LB.2V/AP-X. Samples were simultaneously subjected to FLC and thermal cycling. After storage of the specimens in water for 1 week, MTBS tests were performed, and fracture modes examined by SEM. For group A, MTBS were approximately 40 MPa with cohesive failures in the bonding resin of all specimens. Neither thermal nor mechanical stressing altered bond strengths on flat dentin surfaces. In group B, MTBS in the unstressed control group was 21 MPa with cohesive failures in the resin. As both thermal and mechanical stresses increased, there was a significant decrease in bond strength (16 MPa, P<0.05) and the fractures were seen in the resin-dentin interface and hybrid layer. Surface preparation, C-factor, cavity depth, the dentin substrate and character of the smear layer strongly influence the bond strength values after thermal and fatigue loading. The FLC simulator in combination with MTBS testing provides meaningful in vitro evaluation of dentin bonding durability.


99mTc particle perfusion/99mTc aerosol ventilation imaging using a subtraction technique in suspected pulmonary embolism.
It is generally acknowledged that ventilation-perfusion mismatch is diagnostic of pulmonary embolism. Lung ventilation imaging with radioactive gases is a good method for the detection of pulmonary embolism, but it is not in widespread use because of the limited availability of 81mKr gas and the poor physical properties of 133Xe. Aerosols have been proposed, instead of gases for use in lung ventilation imaging. As perfusion and ventilation distributions may change very rapidly, the two imaging procedures should be done in rapid succession. The cheapest way to perform the combined perfusion-ventilation (Q/V) imaging is to use 99mTc-labelled macroaggregates and aerosols. In our method the perfusion imaging was done first, immediately followed by the ventilation imaging with 99mTc-labelled aerosols. A computer program was used to subtract the contribution of the perfusion from the combined Q/V image so that the pure ventilation image alone was obtained. The method was tested in 41 patients with suspected pulmonary embolism.


Quantitative diagnosis of stress-induced myocardial ischemia using analysis of contrast echocardiographic parametric perfusion images.
Parametric imaging of myocardial perfusion provides useful visual information for the diagnosis of coronary artery disease (CAD). We developed a technique for automated detection of perfusion defects based on quantitative analysis of parametric perfusion images and validated it against coronary angiography. Contrast-enhanced, apical 2-, 3- and 4-chamber images were obtained at rest and with dipyridamole in 34 patients with suspected CAD. Images were analyzed to generate parametric perfusion images of the standard contrast-replenishment model parameters A, beta and A.beta. Each parametric image was divided into six segments, and mean parameter value (MPV) was calculated for each segment. Segmental MPV ratio between stress and rest was defined as a flow reserve index (FRI). Receiver operating characteristics (ROC) analysis was used in a Study group (N=17) to optimize FRI threshold and the minimal number of abnormal segments per vascular territory (LAD and non-LAD), required for automated detection of stress-induced perfusion defects. The optimized detection algorithm was then tested prospectively in the remaining 17 patients (Test group). LAD and non-LAD stenosis >70% was found in 19 and 17 patients, respectively. In the Study group, FRI threshold was: LAD=0.95 and non-LAD=0.68, minimal number of abnormal segments was four and two, correspondingly. Sensitivity, specificity and accuracy in the Test group were: 75%, 67% and 71% in the LAD, and 75%, 75% and 75% in the non-LAD territories. Automated quantitative analysis of contrast echocardiographic parametric perfusion images is feasible and may aid in the objective detection of CAD.


Surface modification of electrospun silk/AMOX/PVA nanofibers by dielectric barrier discharge plasma: physiochemical properties, drug delivery and in-vitro biocompatibility.
The naturally obtained protein Bombyxmori silk is a biocompatible polymer with excellent mechanical properties and have the potential in controlled drug delivery applications. In this work, we have demonstrated dielectric barrier discharge (DBD) oxygen (O2) plasma surface modified electrospun Bombyxmori silk/Amoxicillin hydrochloride trihydrate (AMOX)/polyvinyl alcohol (PVA) nanofibers for drug release applications with controlled plasma treatment duration (1-10 min). The findings indicate that plasma treated electrospun nanofibers for 1-3 min exhibited significant enhancement in tensile strength, Young's modulus, wettability and surface energy. The plasma treated electrospun nanofibers for 1-5 min showed remarkable increase in AMOX released rate, whereas the electrospun nanofibers treated with plasma irradiation beyond 5 min showed only marginal increase. Moreover, the plasma treated nanofibers also exhibited good antibacterial activity against both E. coli (gram negative) and S. aureus (gram positive) bacteria. The untreated and the plasma treated silk/AMOX/PVA electrospun nanofibers for 1-3 min showed enhanced viability of primary adipose derived mesenchymal stem cells (ADMSCs) growth on them and much less hemolysis activity (< 5%). The in vitro biocompatibility of various electrospun nanofibers were further corroborated by live/dead imaging and cytoskeletal architecture assessment demonstrating enhanced cell adhesion and spreading on the plasma treated nanofibers for 1-3 min. The findings of the present study suggest that the silk/AMOX/PVA electrospun nanofibers with plasma treatment (1-3 min) due to their enhanced drug release ability and biocompatibility can be used as potential wound dressing applications.


Gene expression and functional characterization of serum amyloid P component 2 in rock bream, Oplegnathus fasciatus.
Mammalian serum amyloid P component (SAP) recognizes a wide range of exogenous pathogenic substances and activates a complementary pathway leading to pathogen clearance. To determine the potential roles of SAP in the fish immune system, SAP (RbSAP2) gene was cloned from ESTs analysis of rock bream (Oplegnathus fasciatus), which consisted of a signal peptide and pentraxin domain. Phylogenetic analysis revealed that the RbSAP2 gene was classified with other known fish SAPs. RbSAP2 was highly expressed in the liver of healthy rock bream. Overall, pathogen exposure led to an induction of RbSAP2 in the liver and spleen, although this effect was not observed in the spleen following infection with Edwardsiella tarda. A high concentration of recombinant RbSAP2 (rRbSAP2) showed lower growth Streptococcus iniae than control in the absence of Ca(2+), whereas E. tarda growth was decreased by high concentration of rRbSAP in the presence of the Ca(2+). These results suggest that RbSAP plays an important role in the immune response against invading pathogens.


Clinical benefit of joint distraction in the treatment of ankle osteoarthritis.
Irrespective of underlying mechanisms, the structural changes after joint distraction and the efficacy during several years validate the concept of joint distraction in the treatment of osteoarthritis. Therefore, joint distraction in the case of severe ankle osteoarthritis at relatively young age may be a treatment of choice. In the light of increased aging, and the limited life span of an endoprosthesis, evaluation of joint distraction in the case of knee and hip osteoarthritis is justified.


Adenoid cystic carcinoma of the Bartholin's gland: report of two cases and review of the literature.
Adenoid cystic carcinoma (ACC) of the Bartholin's gland is a rare malignancy of the female genital tract and there have been 62 cases of ACC of the Bartholin's gland in the literature. Two cases of ACC of the Bartholin's gland are reported. There is no consensus on optimal treatment of ACC of the Bartholin's gland. Most commonly, wide local excision and radical vulvectomy with or without lymph node dissection, are performed. More long-term follow up is recommended to evaluate optimal primary treatment and roles of radiotherapy and chemotherapy because ACC of the Bartholin's gland recurs and metastasizes long after primary treatment.


Managing poorly performing clinicians: health care providers' willingness to pay for independent help.
To determine the willingness to pay (WTP) of senior managers in the UK National Health Service (NHS) for services to help manage performance concerns with doctors, dentists and pharmacists. A discrete choice experiment (DCE) was used to elicit senior managers' preferences for a support service to help manage clinical performance concerns. The DCE was based on: a literature review; interviews with support service providers and clinical professional bodies; and discussion groups with managers. From the DCE responses, we estimate marginal WTP for aspects of support services. 451 NHS managers completed the DCE questionnaire. NHS managers are willing to pay for: advice, 'facilitation', and behavioural, health, clinical and organisational assessments. Telephone advice with written confirmation was valued most highly. NHS managers were willing to pay £161.56 (CI: £160.81-£162.32) per year per whole time equivalent doctor, dentist or pharmacist, for support to help manage clinical performance concerns. Marginal WTP varied across respondent subgroups but was always positive. Health care managers valued help in managing the clinicians' performance, and were willing to pay for it from their organisations' limited funds. Their WTP exceeds the current cost of a UK body providing similar support. Establishing a central body to provide such services across a health care system, with the associated economies of scale including cumulative experience, is an option that policy makers should consider seriously.


Cognitive performance and cognitive workload in multiple sclerosis: Two different constructs of cognitive functioning?
Cognitive impairment in individuals with Multiple Sclerosis (iwMS) is traditionally diagnosed using performance measures on cognitive tests. Yet, performance on cognitive tests does not convey the amount of mental effort or cognitive workload it takes to complete the task. The main aim was to evaluate whether cognitive performance and cognitive workload are two different constructs of cognitive functioning in iwMS. IwMS were categorized into cognitive impairments (iwMS+, n = 10) and no cognitive impairments (iwMS-, n = 12) using their performance on Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). Their scores on BICAMS, Stroop, and trail making tests were compared to age- and education-matched controls (n = 22). Cognitive workload was assessed using the self-reported NASA Task Load Index and the Index of Cognitive Activity, derived from pupillary response. IwMS+ performed worse on most cognitive tests compared to iwMS- and controls. However, iwMS+ did not report or exhibit greater cognitive workload compared to the other groups. Potential confounding variables, such as sex, use of antidepressants, and symptoms of depression, fatigue, and dysautonomia did not influence the lack of correlation between cognitive performance and cognitive workload in all three groups. Cognitive performance and cognitive workload seem to measure different cognitive constructs of cognitive functioning in MS. Our results suggest that iwMS+ do not show effective allocation of cognitive resources to compensate for deteriorated performance in cognitive tests.


Behavioural Tracking and Profiling Studies Involving Objective Data Derived from Online Operators: A Review of the Evidence.
Studies involving the analysis of objective data from online operators attempt to address common concerns about biases in self-report research. This paper surveys the progress in this area of research over the last 15 years. The findings highlight many areas of achievement, including: the development of a set of behavioural markers that reliably differentiate variations in gambler risk. Online gamblers can be grouped into clusters based on the intensity and frequency of gambling; behavioural variability; or, signs of over-commitment (e.g., deposit frequency or expenditure patterns). Behavioural indicators have also been successfully used to predict proxies of harm such as self-exclusion or account closures. However, relatively few studies have combined objective data with self-report data to achieve independent validation of the risk-status of gamblers. Evidence also supports the potential value of short-term responsible gambling interventions involving the use of voluntary and mandatory limits, messages and behavioural feedback. Less work has, on the other hand, addressed the comparative risk of different online gambling products. The findings suggest the need for further validation of findings against independent measures of gambling risk; consistent definitions of indicators; a greater focus on the differentiation of product risk; and, on the long-term impact of RG interventions.


Improvement of the Cd and Zn phytoremediation efficiency of rice (Oryza sativa) through the inoculation of a metal-resistant PGPR strain.
Cadmium (Cd) and zinc (Zn) in contaminated soil inhibit rice yield and produce toxic effects on human body through rice accumulation. Plant growth promoting rhizobacteria (PGPR) assisted phytoremediation is an effective ecological measure to improve the remediation efficiency of heavy metal contaminated soil. The purpose of this study was to investigate the efficiency of the combination of rice and Cd/Zn-tolerant PGPR strain Bacillus sp. ZC3-2-1 for the remediation of Cd-Zn contaminated soil. Moreover, the effects of inoculations on rhizosphere bacterial communities and ion homeostasis of rice under Cd-Zn exposure will also be explored. The results showed that compared with the treatment without inoculation, ZC3-2-1 decreased the bioavailable Cd and Zn concentrations in soil by 39.3% and 32.0%, respectively, and increase the phytoextraction of Cd2+ and Zn2+ by rice to 48.2% and 8.0%, respectively. This inoculation process significantly increased the rice biomass, resulting that the contents of Cd2+ and Zn2+ per biomass unit of rice didn't change significantly. This fact meant that ZC3-2-1 could improve the phytoremediation efficiency of Cd-Zn contaminated soil by promoting the phytoextraction and immobilization of the metal, while might not affect the crop food safety. Besides, through regulation of the Na+ and Mg2+ concentration in rice, ZC3-2-1 played a positive role in maintaining ion homeostasis which was disrupted by Zn or Cd. Moreover, ZC3-2-1 could modulate the beneficial bacterial communities in rice rhizosphere soil, and then enhanced Cd-Zn immobilization and enzyme activities in soil, leading to the enhancement of rice growth and phytoremediation efficiency. Above all, this study provided novel insights into developing an efficient phytoremediation system and safe production of rice in Cd-Zn contaminated soil with the application of Bacillus sp. ZC3-2-1, as well as advance our understanding of the principles of rhizosphere bacterial community assemble and maintaining ion homeostasis in rice during this phytoremediation process.


Author Correction: Pre-existing immunity to SARS-CoV-2: the knowns and unknowns.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Ultrasonography for inguinal hernias in boys.
History taking and physical examination alone no longer meet the surgeon's need in the diagnosis of inguinal hernia. Ultrasonography (US) provides a good and safe diagnostic tool for inguinal hernias in boys. From 1995 to 1997, 244 boys with inguinal hernias (41 bilateral and 203 unilateral), received preoperative US on both groins to confirm the diagnosis. Those with positive US findings, such as viscera or fluid in inguinal canal or widening of the internal inguinal ring, underwent surgery. The accuracy of diagnosis with US and clinical assessment were 97.9% and 84%, respectively. More than 95% of widening of internal inguinal rings (>4 mm) proved to be hernias. There were two direct inguinal hernias and two femoral hernias, which were misdiagnosed by clinical examination, but proved to be diagnosed correctly by US. US serves as a noninvasive and highly accurate diagnostic tool for inguinal hernias in boys. Using 4 mm as the upper limit of the normal diameter of the internal inguinal ring, an occult inguinal hernia can be easily detected before surgery.


Pathways of pyrimidine salvage in Pseudomonas and former Pseudomonas: detection of recycling enzymes using high-performance liquid chromatography.
Pyrimidine salvage pathways are vital for all bacteria in that they share in the synthesis of RNA with the biosynthetic pathway in pyrimidine prototrophs, while supplying all pyrimidine requirements in pyrimidine auxotrophs. Salvage enzymes that constitute the pyrimidine salvage pathways were studied in 13 members of Pseudomonas and former pseudomonads. Because it has been established that all Pseudomonas lack the enzyme uridine/cytidine kinase (Udk) and all contain uracil phosphoribosyl transferase (Upp), these two enzymes were not included in this experimental work. The enzymes assayed were: cytosine deaminase [Cod: cytosine + H2O --> uracil + NH3], cytidine deaminase [Cdd: cytidine + H2O --> uridine + NH3], uridine phosphorylase [Udp: uridine + Pi <--> uracil + ribose - 1 - P], nucleoside hydrolase [Nuh: purine/pyrimidine nucleoside + H2O --> purine/pyrimidine base + ribose], uridine hydrolase [Udh: uridine/cytidine + H2O --> uracil/cytosine + ribose]. The assay work generated five different Pyrimidine Salvage Groups (PSG) designated PSG1 - PSG5 based on the presence or absence of the five enzymes. These enzymes were assayed using reverse phase high-performance liquid chromatography techniques routinely carried out in our laboratory. Escherichia coli was included as a standard, which contains all seven of the above enzymes.


Crystal structures of monomeric actin bound to cytochalasin D.
The fungal toxin cytochalasin D (CD) interferes with the normal dynamics of the actin cytoskeleton by binding to the barbed end of actin filaments. Despite its widespread use as a tool for studying actin-mediated processes, the exact location and nature of its binding to actin have not been previously determined. Here we describe two crystal structures of an expressed monomeric actin in complex with CD: one obtained by soaking preformed actin crystals with CD, and the other obtained by cocrystallization. The binding site for CD, in the hydrophobic cleft between actin subdomains 1 and 3, is the same in the two structures. Polar and hydrophobic contacts play equally important roles in CD binding, and six hydrogen bonds stabilize the actin-CD complex. Many unrelated actin-binding proteins and marine toxins target this cleft and the hydrophobic pocket at the front end of the cleft (viewing actin with subdomain 2 in the upper right corner). CD differs in that it binds to the back half of the cleft. The ability of CD to induce actin dimer formation and actin-catalyzed ATP hydrolysis may be related to its unique binding site and the necessity to fit its bulky macrocycle into this cleft. Contacts with residues lining this cleft appear to be crucial to capping and/or severing. The cocrystallized actin-CD structure also revealed changes in actin conformation. An approximately 6 degrees rotation of the smaller actin domain (subdomains 1 and 2) with respect to the larger domain (subdomains 3 and 4) results in small changes in crystal packing that allow the D-loop to adopt an extended loop structure instead of being disordered, as it is in most crystal structures of actin. We speculate that these changes represent a potential conformation that the actin monomer can adopt on the pathway to polymerization or in the filament.


Establishment of a multifunctional impact system and a study of a pancreatic trauma model in rats based on controlling the injury area.
At present, basic scientific research on pancreatic trauma is rare due to the lack of ideal animal models and modeling equipment for pancreatic trauma. Therefore, we intend to develop a multifunctional impact system with simple operation, diverse impact and accurate measurement and to establish a rat pancreatic trauma model based on injury area control by using the system. The impactor was designed based on the convenience of the impact energy acquisition, the diversity of the impact operation, and the precision of the impact strength parameter measurement by the team. The efficacy and stability/repeatability of the impactor were preliminarily evaluated. An impact head with different impact areas (3 cm2 and 6 cm2) of the impactor was used to squeeze the rat pancreas in the abdomen to form different injury areas under a pressure of 400 kPa. The efficacy features of this trauma model were evaluated by detecting the outcomes of pathology and biochemistry at 24 h after injury in the two groups. Furthermore, these changes were also evaluated at 6 h, 24 h, 48 h and 72 h after injury in the 3 cm2 trauma group. Multifunctional impactors were successfully explored. The impact force was continuously adjustable with a range of 0-200 kg. The compression and extrusion stress ranges were continuously adjustable from 0 to 100 kg. System adjustment verified that the impactor had fine efficacy (P < 0.05) and stability/repeatability (P > 0.05). Compared with the control group, rats in the pancreatic trauma group with different injury areas exhibited obvious injuries (P < 0.05), and compared with the 3 cm2 trauma group, the 6 cm2 trauma group exhibited the more severe injury (P < 0.05). After modeling, the injury characteristics at different time points showed stable differences(P < 0.05). A rat pancreatic trauma model based on injury area control was successfully established using the impactor developed in this study. This model is simple, effective, controllable, and suitable for animal experimental research on pancreatic trauma.


Ovarian mucinous neoplasms, intestinal type, in premenopausal patients, develop in abnormal ovaries.
Although several studies have addressed different aspects of mucinous neoplasms arising in the ovary, such as their clinicopathologic features, immunohistochemical profile, and molecular characteristics, no study has presented an analysis of the ovarian tissue where these neoplasms arise. In this study, we included 196 cases of intestinal-type ovarian mucinous neoplasms in premenopausal patients. Our main goal was to perform a rigorous examination of the ovarian tissue surrounding these neoplasms. We also reviewed the clinicopathologic features of these cases. For comparison, the background ovarian tissue in 85 cases of ovarian serous neoplasm and in 29 cases of metastatic neoplasms to the ovary, as well as 57 normal ovaries, was examined. All the patients in this study, which included those with mucinous and with serous neoplasms primary in the ovary, those with metastatic tumors to the ovaries, and those with normal ovaries, were also premenopausal. Patients affected by ovarian mucinous neoplasms ranged in age from 13 to 52 years (median = 36 years). Nulligravidity was seen in 50%, 32%, and 22% of patients with mucinous carcinomas, mucinous borderline neoplasms, and mucinous cystadenomas, respectively. Ovarian mucinous intestinal neoplasms arise in abnormal ovaries characterized by two important features: (1) an abnormal ovarian cortex, seen in 95% of the cases, which is hypocellular or with no distinction between the cellular cortex and medulla, and (2) a remarkable paucity of primordial follicles. The abnormalities detected in the background ovarian tissue might provide insights into the tumorigenesis of these neoplasms and might facilitate their distinction from metastasis to the ovary, in premenopausal patients.


Vascular morphometric changes after radioactive stent implantation: a dose-response analysis.
The goal of this study was to evaluate the dose-dependency of morphometric changes in the coronary arterial wall after radioactive stenting. Radioactive stents have been found to reduce intrastent intimal hyperplasia (IIH) but lead to a characteristic type of restenosis occurring predominantly at the stent edges. Fifteen patients underwent intravascular ultrasound (IVUS) examination after implantation of a P-32 radioactive stent and at the six-month follow-up. The post-stent IVUS measurements on seven predefined locations of each lesion were subjected to a computer algorithm for the development of dose-volume histograms (DVH). Thus, we derived the radiation doses delivered to at least 10% and 90% of the adventitia (DV10, DV90). The IIH and vascular remodeling at follow-up were correlated with the doses in each segment. The IIH was most pronounced at the stent edges and lowest in the stent-body, whereas we detected a significant expansive remodeling within the stent body. The delivered doses correlated with a decreased IIH (r = 0.52, p < 0.001 for DV10 and r = 0.62, p < 0.001 for DV90) and with expansive remodeling (r = 0.48, p = 0.009 for DV10 and r = 0.50, p = 0.006 for DV90). A DV10 >90 Gy or a DV90 >15 Gy reduced IIH and induced expansive remodeling. Plaque growth was not reduced by radioactive stents. The DVH analysis reveals a dose-dependent increase of external elastic lamina area behind radioactive stents, whereas plaque growth is not reduced but inverted into an outward direction from the stent. A DV10 >90 Gy or a DV90 >15 Gy results in a beneficial long-term outcome after radioactive stenting.


The effect of heat on lung diffusing capacity for carbon monoxide (DLCO) during cycling exercise.
This study aimed to quantify the combined effects of heat exposure and exercise of increasing intensity on pulmonary blood flow using lung diffusing capacity for carbon monoxide (DLCO) as an indirect measure. We hypothesized that, during exercise in the heat, the well-documented increase in skin blood flow for thermoregulation would lead to alterations in pulmonary blood flow and a subsequent fall in DLCO versus a thermoneutral condition. Nine healthy subjects (4 F/5 M, 20-45 years, VO2max 46.7 ± 5.8 mL/kg/min) completed three 15-min stages including rest and during cycling at 20 and 40% of maximum workload (Wmax) in either thermoneutral (TN; 22.2 ± 0.6 °C) or heat (HT; 39.4 ± 0.4 °C) conditions. DLCO, minute ventilation (VE), oxygen consumption ([Formula: see text]), heart rate (HR), and core (TC) and skin temperature (Tsk) were measured. DLCO showed a significant interaction between exercise intensity and heat (P = 0.019); post hoc testing revealed that DLCO was higher at 40% of Wmax in HT vs. TN (53.2 ± 10.6 vs 50.0 ± 10.3 mL/min/mmHg, P = 0.003) only. VE and [Formula: see text] showed no difference in HT vs. TN. HR was higher in HT vs. TN (P < 0.001). TC and Tsk showed a significant interaction between temperature and intensity (P < 0.05). The unexpected increase in DLCO during exercise in HT vs. TN conditions suggests a larger lung surface area for gas exchange, perhaps due to increased pulmonary capillary recruitment and/or distension secondary to a higher cardiac output (Q) in the heat. This study furthers our understanding of how heat exposure might impact pulmonary blood flow, specifically as assessed via DLCO.


Pyrethroid resistance in African anopheline mosquitoes: what are the implications for malaria control?
The use of pyrethroid insecticides in malaria vector control has increased dramatically in the past decade through the scale up of insecticide treated net distribution programmes and indoor residual spraying campaigns. Inevitably, the major malaria vectors have developed resistance to these insecticides and the resistance alleles are spreading at an exceptionally rapid rate throughout Africa. Although substantial progress has been made on understanding the causes of pyrethroid resistance, remarkably few studies have focused on the epidemiological impact of resistance on current malaria control activities. As we move into the malaria eradication era, it is vital that the implications of insecticide resistance are understood and strategies to mitigate these effects are implemented.


What Factors Determine the Patients' Choice in Finding Their Office Urologist?
The present study aimed to investigate how patients identify a quality urologist in primary health care and how they determine and evaluate their provider's qualities before their first examination. A specific questionnaire (The ESUO Questionnaire) was prepared to describe the domains that influence the patient's evaluation and summarize the urologist related characteristics and behaviours that the patients estimate are more important. A total of 335 patients, over 18 years of age, presented in primary healthcare urology practice, completed the survey. The participants were divided into three age groups; 18-39 years of age (111 patients), 40-59 years of age (111 patients) and 113 patients 60 years of age and older. The majority of patients (68.4%) selected that the urologist must be efficient and well trained. This attitude was primarily expressed in patients ≥60 years of age. Individuals under 60 years old stated that they expect a detailed examination and that the patient should be the urologist's priority. The majority of the patients evaluates friends or family's proposals concerning the urologist's quality primarily and believes that there is at least good quality of urological health care. Most patients evaluate primarily the effectiveness of the care they receive instead of the urologist's personality traits or personal relationships.


Seasonal changes in the precision of the circadian clock of a tropical bat under natural photoperiod.
The emergence and returning activity patterns of a colony of microchiropteran bats Hipposideros speoris, under natural light-dark cycles keep pace with the timings of sunset and sunrise respectively. The onset of emergence flight occurred at different environmental twilight intensities which vary over the seasons. The seasonal changes of phase relationship between the onset and end of flight activity to sunset and sunrise respectively are discussed. As a result ψ-onset, ψ-end, and ψ-midpoint all undergo marked seasonal variations and the values obtained are well in accordance with the seasonal rule of Aschoff. The changes in the timing of onset and end of activity reflect the changes in the duration of activity time of the colony. The activity time is positively correlated with the duration of night time. The possible involvement of the 'non-parametric' action on the entrainment of this colony is briefly discussed.


Encapsulation of charge-diffuse peralkylated onium cations in the cavity of cucurbit[7]uril.
Cucurbit[7]uril binds, with considerable size selectivity, NR(4)(+), PR(4)(+), and SR(3)(+) cations (R=Me, Et, (n)Pr, (n)Bu), with the smaller guests inside its cavity, rather than at the carbonyl-lined portals.


Kinetic and mechanistic studies of blue tetrazolium reaction with phenylhydrazines.
The reaction kinetics of blue tetrazolium with selected arylhydrazines were investigated under pseudo-first-order conditions. The reaction rate constants were obtained at various temperatures, and the enthalpy (8.4-11.2 kcal/mole) and entropy (-38--45 eu) of activations were calculated. A Hammett plot yielded a straight line with a slope of 0.52. The reaction was inhibited by atmospheric oxygen and iodine. A free radical mechanism is presented.


Fibroblast to substratum contacts mediated by the different forms of fibronectin.
Highly purified preparations of fibronectin from bovine or hamster plasma and conditioned medium or urea extracts of BHK cells facilitate spreading of BHK cells to plastic surfaces. The different forms of fibronectin have very similar specific activities.


Integrated transcriptome and proteome analysis the molecular mechanisms of nutritional quality in 'Chenggu-32' and 'Koroneiki' olives fruits (Olea europaea L.).
In this work, integrated transcriptome and proteome to offer a new insight of the molecular mechanisms linked to the nutritional quality of Koroneiki and Chenggu-32 by RNA sequencing and 4D Label-free quantitative proteomics technology. Physical and chemical properties studies showed that the main nutrient content of Koroneiki was significantly higher than Chenggu-32, proved the quality of Koroneiki was better. Compared to Koroneiki, there were differences in expression levels of 10,115 genes and 723 proteins in Chenggu-32, mainly related to enzymes in lipid metabolism and lipid biosynthesis. Through the joint analysis of transcriptome and proteome, it was found that the differentially expressed genes and differentially expressed proteins on the association were mainly enriched in starch and sucrose metabolism and α-linolenic acid metabolism pathways, indicated that the nutritional quality of olive fruits was related to the two metabolic pathways. The results of this study identified key genes and proteins related to nutrient metabolism and accumulation in olive fruits, provided transcriptomic and proteomic information for the molecular mechanism of nutritional changes in olive fruit, it helps to develop higher quality olive trees.


Patterns of avian nest predators and a brood parasite among restored riparian habitats in agricultural watersheds.
In fragmented edge-dominated landscapes, nest predation and brood parasitism may reduce avian reproductive success and, ultimately, populations of some passerine species. In the fragmented agroecosystem of northwest Mississippi, placement of drop-pipe structures has been used as a restoration technique for abating gully erosion along stream banks. These actions have formed small herbaceous and woody habitat extensions into former agricultural lands. We quantified species relative abundances, species richness, and evenness of avian nest predators and a brood parasite within four categories of constructed habitat resulting from drop-pipe installation. Differences in the abundance of two nest predators, cotton mouse (Peromyscus gossypinus) and blue jay (Cyanocitta cristata), were observed among constructed habitats. However, relative abundances of other predators such as common grackle (Quiscalus quiscula), American crow (Corvus brachyrhynchos), and hispid cotton rat (Sigmodon hispidus), and the obligate brood parasite brown-headed cowbird (Molothrus ater) did not differ among four habitat categories. Although species richness, abundance, and evenness of potential nest predators were generally similar among the constructed habitats, predator species composition varied, suggesting that these habitats supported different predator communities. This difference is important because as each predator species is added to or deleted from the community, variation may occur in the framework of prey search methods, predator strategies, and potentially overall predation pressure. We suggest that land managers using drop-pipes as part of stream restoration projects allow for the development of the constructed habitat with the largest area and greatest vegetative structure.


Cerebral hemodynamics and incident depression: the Rotterdam Study.
According to the vascular depression hypothesis, subclinical cerebrovascular disease can cause depression in older adults. To test this hypothesis, several cross-sectional studies have assessed structural brain parameters, but few have examined hemodynamic alterations in the brain. From the Rotterdam Study, we studied a cohort of 1494 participants (65+ years of age) free of depression, dementia, and stroke at baseline. In the middle cerebral artery blood flow velocities and vasomotor reactivity were measured with transcranial Doppler ultrasonography. All participants were repeatedly assessed for depressive symptoms with Centre for Epidemiological Studies-Depression scale (CES-D). Participants with depressive symptoms (CES-D ≥16) had a semi-structured interview, to classify the depression according to DSM-IV criteria. All analyses were adjusted for sociodemographic data, vascular risk factors, and incident stroke. Lower peak-systolic, end-diastolic, and mean blood flow velocities at baseline were associated with higher CES-D scale scores at follow-up. Mean blood flow velocity predicted incident depressive symptoms (odds ratio [OR]: .74, 95% confidence interval [CI]: .60-.91, p = .004) and depressive disorders (OR: .83, 95% CI: .69-.98, p = .032), whereas decreased baseline vasomotor reactivity predicted incident depressive disorders only (OR: .66, 95% CI: .53-.83, p < .001). Lower blood flow velocity, indicating reduced cerebral metabolism, predicted depressive symptoms and depressive disorders. Reduced vasomotor reactivity, which might indicate cerebral microangiopathy, predicted depressive disorders only, in healthy older adults. These findings provide prospective evidence for vascular depression hypothesis.


Direct Delivery of Apatite Nanoparticle-Encapsulated siRNA Targeting TIMP-1 for Intractable Abnormal Scars.
Hypertrophic scars (HSs) and keloids are histologically characterized by excessive extracellular matrix (ECM) deposition. ECM deposition depends on the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteases (TIMPs). TIMP-1 has been linked to ECM degradation and is therefore a promising therapeutic strategy. In this study, we generated super carbonate apatite (sCA) nanoparticle-encapsulated TIMP-1 small interfering RNA (siRNA) (siTIMP1) preparations and examined the effect of local injections on mouse HSs and on ex vivo-cultured keloids. The sCA-siTIMP1 injections significantly reduced scar formation, scar cross-sectional areas, collagen densities, and collagen types I and III levels in the lesions. None of the mice died or exhibited abnormal endpoints. Apatite accumulation was not detected in the other organs. In an ex vivo keloid tissue culture system, sCA-siTIMP1 injections reduced the thickness and complexity of collagen bundles. Our results showed that topical sCA-siTIMP1 injections during mechanical stress-induced HS development reduced scar size. When keloids were injected three times with sCA-siTIMP1 during 6 days, keloidal collagen levels decreased substantially. Accordingly, sCA-siRNA delivery may be an effective approach for keloid treatment, and further investigations are needed to enable its practical use.


Alternating Facial Palsy- Decoding the Enigma.
Facial palsy is a neurological emergency with a wide spectrum of aetiologies. The term 'alternating facial palsy', a very rare presentation, refers to facial paralysis, the onset of which occurs at different points in time on both sides of the face. It can occur in systemic vasculitis, trauma, tumours and infectious diseases. We report the case of a middle-aged female who presented with complaints of alternating facial palsy and the diligent journey that we took to finally reach a diagnosis of Lyme neuroborreliosis.


[Effects of social support on well-being of demented nursing home residents. The Käferberg Visitation Study].
Relatives and caregivers of patients with dementia are often insecure about the impact of their efforts. This study examines whether and to what extent social support in the form of regular visits is increasing the well-being of demented aged. A field experiment with slightly to seriously demented institutionalized aged persons (MMS 5-25) was carried out to assess the effect of increased social support upon their well-being. Voluntary helpers, who were willing to visit their patients on a regular basis, were recruited by appeals at the senior university and by advertisements. The volunteers were trained to deal with the demented and were looked after regularly. The test subjects were randomly assigned to one of two test groups. The first group was visited regularly for ten weeks, whereas the second group served as a control group. The participants of the experimental group received a visiting card with a photo of the volunteer and the next appointment date to remember their visitors and to increase the effect of predictability. The effect of visits on the well-being of the institutionalized aged persons was significantly positive (F(1,39) = 11.16, p < 0.002). The psychological, physiological and social well-being of the participants was improved. Additionally, visits moderated the pain resulting from physical illness and seemed to decrease the effects of mental decline on their performance. Furthermore, it was most impressive to find that the demented aged really took notice of the visits and seemed to remember them in one way or an other. The study pointed out that demented aged persons are still very sensitive in an emotional respect and that they are still able to give astonishing good and differentiated information about their feelings even in an advanced state of dementia. Even the volunteers gained from their visits, which was shown by their higher well-being after their visits.


Is early laparoscopic cholecystectomy a safe procedure in patients when the duration of acute cholecystitis is more than three days?
The role of laparoscopic cholecystectomy for patients with acute cholecystitis and symptoms for >3 days is debated. Our purpose was to compare the results of laparoscopic cholecystectomy in patients with acute cholecystitis and symptoms for ≤ 3 days and >3 days. Sixty patients with acute cholecystitis had a laparoscopic cholecystectomy performed by the same surgeon. There were 39 patients in the short group (symptoms ≤ 3 days) and 21 patients in the long group (symptoms >3 days). Demographic data, surgical findings and clinical results were analyzed. There were no significant differences in age, gender, comorbidities, abnormal liver function tests, white bile, gallbladder empyema, blood loss, conversion rate, postoperative hospital stay or complication rates between the groups. The mean duration of acute cholecystitis was 1.9 days in the short group and 5.3 days in the long group (p<0.0001). The long group had a longer operating time (p=0.004) and a higher rate of subhepatic drains (p=0.014). Laparoscopic cholecystectomy is a safe and feasible procedure for patients with acute cholecystitis when the duration of symptoms is >3 days, however, a higher conversion rate is seen for acute chronic cholecystitis.


Ruxolitinib treatment for myelofibrosis: Efficacy and tolerability in routine practice.
Ruxolitinib has been shown in two randomized clinical trials to be effective in alleviating systemic symptoms and reducing spleen size in patients with myelofibrosis (MF). We retrospectively evaluated efficacy and tolerability of ruxolitinib in a cohort of unselected MF patients treated in routine clinical practice. One hundred and two patients who began ruxolitinib therapy were identified in 13 participating centers. Ninety three of the patients receiving ruxolitinib for at least 3 months were evaluated for treatment efficacy and toxicity. Median age at ruxolitinib initiation was 67 years. Indications for treatment were constitutional symptoms (15%), symptomatic splenomegaly (6%) or both (76%). Two patients received ruxolitinib for other indications. The median initial ruxolitinib dose was 30mg/day. Median duration of therapy was 11 months. Eighty two patients (88.2%) responded to therapy, 76 (84.4%) patients had improvement in constitutional symptoms and 60 patients (70.6%) had reduction in spleen length. While on ruxolitinib, 30% of patients had grade 3-4 anemia and 12.9% of patients had grade 3-4 thrombocytopenia. Thirteen patients (14%) discontinued therapy. This analysis of a cohort of MF patients treated with ruxolitinib in routine clinical practice demonstrates the efficacy and tolerability of this drug outside of a highly monitored clinical trial setting.


Inspiratory-modulated neurons of the rostrolateral pons: effects of pulmonary afferent input.
In decerebrate, paralyzed cats ventilated with a cycle-triggered pump, firing of inspiratory (I) and I-modulated neurons in the pontine respiratory group was markedly increased by withholding lung inflation, indicating strong inhibition by lung afferents. Spectral analysis showed that only a small minority of I-modulated neurons had high-frequency oscillations (HFO), in contrast to medullary I neurons, indicating that the pontine neurons are not closely linked to medullary I networks.


The one-two punch of alcoholism: role of central amygdala dynorphins/kappa-opioid receptors.
The dynorphin (DYN)/kappa-opioid receptor (KOR) system undergoes neuroadaptations following chronic alcohol exposure that promote excessive operant self-administration and negative affective-like states; however, the exact mechanisms are unknown. The present studies tested the hypothesis that an upregulated DYN/KOR system mediates excessive alcohol self-administration that occurs during withdrawal in alcohol-dependent rats by assessing DYN A peptide expression and KOR function, in combination with site-specific pharmacologic manipulations. Male Wistar rats were trained to self-administer alcohol using operant behavioral strategies and subjected to intermittent alcohol vapor or air exposure. Changes in self-administration were assessed by pharmacologic challenges during acute withdrawal. In addition, 22-kHz ultrasonic vocalizations were utilized to measure negative affective-like states. Immunohistochemical techniques assessed DYN A peptide expression and [(35)S]GTPγS coupling assays were performed to assess KOR function. Alcohol-dependent rats displayed increased alcohol self-administration, negative affective-like behavior, DYN A-like immunoreactivity, and KOR signaling in the amygdala compared with nondependent control rats. Site-specific infusions of a KOR antagonist selectively attenuated self-administration in dependent rats, whereas a mu-opioid receptor/delta-opioid receptor antagonist cocktail selectively reduced self-administration in nondependent rats. A mu-opioid receptor antagonist/partial KOR agonist attenuated self-administration in both cohorts. Increased DYN A and increased KOR signaling could set the stage for a one-two punch during withdrawal that drives excessive alcohol consumption in alcohol dependence. Importantly, intracentral nucleus of the amygdala pharmacologic challenges functionally confirmed a DYN/KOR system involvement in the escalated alcohol self-administration. Together, the DYN/KOR system is heavily dysregulated in alcohol dependence and contributes to the excessive alcohol consumption during withdrawal.


Soluble HLA-DR serum levels are associated with smoking but not with acute coronary syndrome.
Elevated soluble HLA-DR (sHLA-DR) serum levels have been reported in HLA class II-associated inflammatory disorders. We have previously shown that the HLA class II allele HLA-DRB1*01 may predispose to acute coronary syndromes (ACS). To our knowledge, sHLA-DR serum levels have not been studied in ACS. sHLA-DR serum levels were measured in 477 ACS patients as cases and 475 area- and sex-matched controls by sandwich enzyme-linked immunosorbent assay. Binary logistic regression and ordinal logistic regression analyses adjusted for clinical parameters were conducted to evaluate the associations of sHLA-DR levels. ACS patients had lower sHLA-DR serum levels compared to controls (OR = 0.837; 95% CI = 0.704-0.994; p = 0.043). After adjustment for smoking status, this association was no longer significant. This was explained by the notion that current smoking was inversely associated with sHLA-DR levels both in cases (OR = 0.592; 95% CI = 0.553-0.908; p = 0.016) and in controls (OR = 0.356; 95% CI = 0.226-0.563; p = 0.000010). A similar effect was not seen with other cardiovascular risk factors. The results indicate, for the first time, that lower sHLA-DR levels are associated with smoking, but not with ACS. This is an important finding because previous studies of sHLA-DR have not accounted for the possible associations between smoking and sHLA-DR levels. Further studies are required to confirm these novel results and explore the mechanisms behind the observed associations.


Development of instrumentation and fluorochromes for automated multiparameter analysis of cells.
We have developed and interfaced to a computer an automated instrument (the AMAC III) which is designed to observe simultaneously several physical parameters of cells. Typical parameters include electronic cell volume (Coulter effect), RF amplitude (opacity), multiwavelength fluorescence of cytological stains, and cell light-scattering. The use of a new ultraviolet laser combined with a holographic grating spectrograph promises to increase the number of fluorescing species that can be detected simultaneously. This number can be further increased by use of special rare-earth-based fluorochromes, that emit well-defined, spectrally distinct peaks.


Simulation studies, 3D QSAR and molecular docking on a point mutation of protein kinase B with flavonoids targeting ovarian Cancer.
Ovarian cancer is the world's dreaded disease and its prevalence is expanding globally. The study of integrated molecular networks is crucial for the basic mechanism of cancer cells and their progression. During the present investigation, we have examined different flavonoids that target protein kinases B (AKT1) protein which exerts their anticancer efficiency intriguing the role in cross-talk cell signalling, by metabolic processes through in-silico approaches. Molecular dynamics simulation (MDS) was performed to analyze and evaluate the stability of the complexes under physiological conditions and the results were congruent with molecular docking. This investigation revealed the effect of a point mutation (W80R), considered based on their frequency of occurrence, with AKT1 protein. The ligand with high docking scores and favourable behaviour on dynamic simulations are proposed as potential W80R inhibitors. A virtual screening analysis was performed with 12,000 flavonoids satisfying Lipinski's rule of five according to which drug-likeness is predicted based on its pharmacological and biological properties to be active and taken orally. The pharmacokinetic ADME (adsorption, digestion, metabolism, and excretion) studies featured drug-likeness. Subsequently, a statistically significant 3D-QSAR model of high correlation coefficient (R2) with 0.822 and cross-validation coefficient (Q2) with 0.6132 at 4 component PLS (partial least square) were used to verify the accuracy of the models. Taxifolin holds good interactions with the binding domain of W80R, highest Glide score of - 9.63 kcal/mol with OH of GLU234 and H bond ASP274 and LEU156 amino acid residues and one pi-cation interaction and one hydrophobic bond with LYS276. Natural compounds have always been a richest source of active compounds with a wide variety of structures, therefore, these compounds showed a special inspiration for medical chemists. The present study has aimed molecular docking and molecular dynamics simulation studies on taxifolin targeting W80R mutant protein of protein kinase B/serine- threonine kinase/AKT1 (EC:126.96.36.199) protein of ovarian cancer for designing therapeutic intervention. The expected result supported the molecular cause in a mutant form which resulted in a gain of ovarian cancer. Here we discussed validations computationally and yet experimental evaluation or in vivo studies are endorsed for further study. Several of these compounds should become the next marvels for early detection of ovarian cancer.


Identical reactivity of monoclonal antibodies HNK-1 and NC-1: conservation in vertebrates on cells derived from the neural primordium and on some leukocytes.
NC-1 and HNK-1, two mouse monoclonal antibodies raised against quail ciliary ganglion and a human leukemic cell-line, respectively, were found to display the same pattern of reactivity. Species investigated included human, rodents, birds and amphibians. In 1- to 3-day-old avian embryos, migrating crest cells are stained, whereas in older animals neuroepithelial cells and neurons are labelled. Staining with fluorescein isothiocyanate-conjugated NC-1 is blocked by preincubation with HNK-1. In immunoblot analyses both antibodies recognize the same pattern of bands which are different in central and peripheral nervous systems and vary during development. Thus, HNK-1/NC-1 provides a useful tool for investigating the ontogeny of neural and lymphocytic cells carrying this determinant, which, in view of its high degree of conservation during vertebrate evolution, may play an important part within the haematopoietic and nervous systems.


Intimate interactions of enteropathogenic Escherichia coli at the host cell surface.
Unlike many gastrointestinal pathogens, enteropathogenic Escherichia coli orchestrates the modulation of host cellular and immune responses from the exterior of the infected cell, chiefly via the secreted and translocated components of a type III secretion system. Close inspection of these enteropathogenic Escherichia coli proteins and the interactions they mediate provides an increasingly coherent picture of the pathogenic mechanisms that enteropathogenic Escherichia coli uses to exploit its host.


Soft X-ray angle-resolved photoemission with micro-positioning techniques for metallic V₂O₃.
Soft X-ray angle-resolved photoemission has been performed for metallic V2O3. By combining a microfocus beam (40 µm × 65 µm) and micro-positioning techniques with a long-working-distance microscope, it has been possible to observe band dispersions from tiny cleavage surfaces with a typical size of several tens of µm. The photoemission spectra show a clear position dependence, reflecting the morphology of the cleaved sample surface. By selecting high-quality flat regions on the sample surface, it has been possible to perform band mapping using both photon-energy and polar-angle dependences, opening the door to three-dimensional angle-resolved photoemission spectroscopy for typical three-dimensional correlated materials where large cleavage planes are rarely obtained.


Physiotherapy Regimens in Esophagectomy and Gastrectomy: a Systematic Review and Meta-Analysis.
Esophageal and gastric cancer surgery are associated with considerable morbidity, specifically postoperative pulmonary complications (PPCs), potentially accentuated by underlying challenges with malnutrition and cachexia affecting respiratory muscle mass. Physiotherapy regimens aim to increase the respiratory muscle strength and may prevent postoperative morbidity. The aim of this study was to assess the impact of physiotherapy regimens in patients treated with esophagectomy or gastrectomy. An electronic database search was performed in the MEDLINE, EMBASE, CENTRAL, CINAHL and Pedro databases. A meta-analysis was performed to assess the impact of physiotherapy on the functional capacity, incidence of PPCs and postoperative morbidity, in-hospital mortality rate, length of hospital stay (LOS) and health-related quality of life (HRQoL). Seven randomized controlled trials (RCTs) and seven cohort studies assessing prehabilitation totaling 960 patients, and five RCTs and five cohort studies assessing peri- or postoperative physiotherapy with 703 total patients, were included. Prehabilitation resulted in a lower incidence of postoperative pneumonia and morbidity (Clavien-Dindo score ≥ II). No difference was observed in functional exercise capacity and in-hospital mortality following prehabilitation. Meanwhile, peri- or postoperative rehabilitation resulted in a lower incidence of pneumonia, shorter LOS, and better HRQoL scores for dyspnea and physical functioning, while no differences were found for the QoL summary score, global health status, fatigue, and pain scores. This meta-analysis suggests that implementing an exercise intervention may be beneficial in both the preoperative and peri- or postoperative periods. Further investigation is needed to understand the mechanism through which exercise interventions improve clinical outcomes and which patient subgroup will gain the maximal benefit.


Changing concepts in the treatment of nonseminomatous germ cell tumors of the testis.
The development of effective chemotherapy for advanced nonseminomatous germ cell tumors of the testis has changed dramatically the outlook for this once uniformly fatal disease. We reviewed our experience with changing modalities of therapy during a 7-year period in the treatment of 152 patients with all stages of testis tumor. Survival rates have increased from 84 per cent for patients with stage A, B1 or B2 tumors treated with sandwich irradiation therapy and retroperitoneal lymph node dissection to 100 per cent for patients with node dissection with or without chemotherapy. Survival rates continuously free of disease for patients with advanced (stage B3 or C) disease have increased from 53 per cent in 1975 to 1977 to 82 per cent by the addition of platinum-based polychemotherapy and judicious lymphadenectomy. A unified plan of management for patients with low stage and advanced stage nonseminomatous testicular tumors has evolved.


Improved indirect instantaneous torque control based torque sharing function approach of SRM drives in EVs using hybrid technique.
This manuscript proposes an improved indirect instantaneous torque control (IITC) based torque sharing function (TSF) method of switched reluctance motor (SRM) drives in electric vehicles (EVs) using a hybrid system. The proposed hybrid techniques are joint performance of both Reptile Search Algorithm (RSA) and Honey Badger Algorithm (HBA), hence it is named as Enhanced RSA (ERSA) method. Here, an IITC method of SRMs for EVs is utilized. It achieves the requirements of the vehicle, like minimum torque ripple, improved speed range, high effectiveness, and maximal torque per ampere (MTPA). To precisely specify the switched reluctance motor and its magnetic features are measured by the proposed method. The modified Torque sharing function compensates the torque error along with incoming phase, which contains the minimal rate of change of flux linkage. Finally, the ERSA method is implemented to define the best control parameters. Then, the proposed ERSA system is performed on the MATLAB platform and the performance is compared to different existing systems. The MSE for case 1 and case 2 using proposed system attains 0.01093 and 0.01095. The voltage deviation for case 1 and case 2 using proposed system reaches 5 and 5. The power factor for case 1 and case 2 reaches a value of 50 and 40 using the proposed system.


Enantioselective metabolism of novel chiral insecticide Paichongding by human cytochrome P450 3A4: A computational insight.
As a novel chiral neonicotinoid insecticide, Paichongding (IPP) has been widely applied in agriculture due to its excellent insecticidal activity. However, the enantioselective metabolism of IPP stereoisomers (5R7R-IPP, 5S7S-IPP, 5R7S-IPP, and 5S7R-IPP) mediated by enzymes in non-target organisms, especially the cytochrome P450s (CYPs), remains unknown. To address this knowledge gap, we developed an integrated computational framework to elucidate the binding interactions and enantioselective metabolism of IPP stereoisomers in human CYP3A4. The results reveal that 5R7R-IPP shows much stronger binding affinity to CYP3A4 than 5S7S-IPP, while enantiomers 5R7S-IPP and 5S7R-IPP have no essential difference in their binding potential, owing to their specific interactions with key CYP3A4 residues. Although enantiomers 5R7R-IPP and 5S7S-IPP feature distinct binding modes resulting from the chiral differences, their transformation activities are slightly different, with C5 and C13 being the primary metabolic sites, respectively. In contrast, CYP3A4 preferably metabolizes 5R7S-IPP over 5S7R-IPP. The metabolism of epimers 5R7R-IPP and 5R7S-IPP share C5-hydroxylation routes due to the conserved 5R-conformaitons, but differ with the transformation routes at C11/C13 and C3 sites. The 7R-chirality of 5S7R-IPP significantly reduces the metabolic potency compared to 5S7S-IPP. CYP3A4-catalyzed hydroxylation and desaturation of IPP stereoisomers generate various chiral metabolites, with C5- and C13-hydroxyIPPs further transforming into depropylated products. Furthermore, the toxicity assessment reveals that IPP, along with the majority of its hydroxylated, desaturated, and depropylated metabolites, can potentially induce adverse effects on human health, specifically hepatotoxicity, respiratory toxicity, and carcinogenicity. This study provides valuable insights into the enantioselective fate of chiral IPP metabolism by CYP3A4, and the identified metabolites can serve as potential biomarkers for monitoring IPP exposure and associated health risk in human body.


Encapsulating Metal Nanoparticles into a Layered Zeolite Precursor with Surface Silanol Nests Enhances Sintering Resistance.
Supported metal nanoparticles are used as heterogeneous catalysts but often deactivated due to sintering at high temperatures. Confining metal species into a porous matrix reduces sintering, yet supports rarely provide additional stabilization. Here, we used the silanol-rich layered zeolite IPC-1P to stabilize ultra-small Rh nanoparticles. By adjusting the IPC-1P interlayer space through swelling, we prepared various architectures, including microporous and disordered mesoporous. In situ scanning transmission electron microscopy confirmed that Rh nanoparticles are resistant to sintering at high temperature (750 °C, 6 hrs). Rh clusters strongly bind to surface silanol quadruplets at IPC-1P layers by hydrogen transfer to clusters, while high silanol density hinders their migration based on density functional theory calculations. Ultimately, combining swelling with long-chain surfactant and utilizing metal-silanol interactions resulted in a novel, catalytically active material-Rh@IPC_C22.


The effect of extremely low-frequency magnetic field on motor activity of rats in the open field.
Exposure to extremely low-frequency magnetic field (ELF-MF, 50 Hz, 0.5 mT) for seven days did not change spontaneous motor activity of rats in the open field compared to sham-exposed animals. Pre-exposure to ELF-MF decreased locomotor and stereotypic activity induced by amphetamine (1.5 mg/kg body weight) and accordingly increased the resting time compared to sham-exposed and amphetamine-treated rats. Vertical activity (rearing) of these two groups was similar. Our results indicate that ELF-MF has different effects on some parameters of amphetamine-induced motor activity, probably due to brain region-specific effects on catecholaminergic systems responsible for movement control.


Sequence analysis of both genome segments of three Croatian infectious bursal disease field viruses.
In order to determine the mutations responsible for virulence, three Croatian field infectious bursal disease viruses (IBDV), designated Cro-Ig/02, Cro-Po/00, and Cro-Pa/98 were characterized. Coding regions of both genomic segments were sequenced, and the nucleotide and deduced amino acid sequences were compared with previously reported full-length sequenced IBDV strains. Phylogenetic analysis, based on the nucleotide and deduced amino acid sequences of polyprotein and VP1, was performed. Eight characteristic amino acid residues, that were common to very virulent (vv) IBDV, were detected on polyprotein: 222A, 256I, 294I, 451L, 685N, 715S, 751D, and 1005A. All eight were found in Cro-Ig/02 and Cro-Po/00. C-Pa/98 had all the characteristics of an attenuated strain, except for glutamine on residue 253, which is common for vv, classical virulent, and variant strains. Between less virulent and vvIBDV, three substitutions were found on VP5: 49 G --> R, 79 --> F, and 137 R --> W. In VP1, there were nine characteristic amino acid residues common to vvwIBDV: 146D, 147N, 242E, 390M, 393D, 511S, 562P, 687P, and 695R. All nine residues were found in A-Ig/02, and eight were found in B-Po/00, which had isoleucine on residue 390. Based on our analyses, isolates Cro-Ig/02 and Cro-Po/00 were classified with vv IBDV strains. C-Pa/98 shared all characteristic amino acid residues with attenuated and classical virulence strains, so it was classified with those.


Treatment of a torqued hematosalpinx in the thirteenth week of pregnancy using gasless laparoscopy.
Laparotomy and carbon dioxide laparoscopy are relatively traumatic and high-risk operations for patients. They may have negative effects on pregnancy, especially in advanced pregnancy. Gasless laparoscopy was performed on torqued hematosalpinx in a woman in the thirteenth week of pregnancy. After salpingectomy, the pregnancy proceeded normally.


Biosynthesis of Cd-bound phytochelatins by Phaeodactylum tricornutum and their speciation by size-exclusion chromatography and ion-pair chromatography coupled to ICP-MS.
Cd-bound phytochelatins (Cd-PCs) have been synthesised by incubation of Phaeodactylum tricornutum cell cultures with Cd and purified by size-exclusion chromatography-UV-Vis. These complexes, which were identified in previous work, have now been used as model substances to develop and optimise ion-pair chromatography (IPC) coupled to inductively coupled plasma-mass spectrometry (ICP-MS) for analysis of Cd-PCs. Subsequent analysis of samples taken from Silene vulgaris plants cultivated under heavy metal stress conditions revealed Cd signals but no Cd-PC signals. By use of isotopically enriched (116)Cd-PCs the sample preparation steps were verified to determine the stability of the analytes. We observed species transformation between Cd-PCs and other unidentified Cd complexes. Consequently, the kinetic and thermodynamic lability of Cd-PCs are decisive factors in their detection.


Voiding urosonography with ultrasonography contrast medium in children.
Voiding urosonography (VUS) with ultrasonography contrast medium is a new modality in the detection of vesicoureteral reflux (VUR) in children. The purpose of this study was to evaluate the diagnostic accuracy of VUS compared with voiding cystourethrography (VCUG) in the detection of VUR. One hundred and eighteen patients, aged 3 weeks to 16 years, with 234 ureterorenal units, were investigated by VUS with ultrasonography contrast medium and radiographic VCUG in one session. The indications were predominantly urinary tract infection and follow-up of previously detected VUR. During the sonographic examination, the bladder was filled with saline solution and an ultrasonography contrast medium (Levovist) was administered through a catheter. Reflux was diagnosed when echogenic bubbles were observed in the ureter or in the renal pelvis. Afterwards, conventional VCUG was performed. Concordant findings were obtained in 210 of 224 ureterorenal units (93.7%). Reflux was excluded by both methods in 174 units (77.7%). With the VCUG as the reference, the sensitivity of VUS was 90%, the specificity 94.6%, the positive predictive value 78.3%, and the negative predictive value 97.8%. The accuracy was 93.7%. In conclusion, VUS with ultrasonography contrast medium is a reliable diagnostic tool for the detection of VUR in children.


The Use of Physiotherapy among Patients with Subacromial Impingement Syndrome: Impact of Sex, Socio-Demographic and Clinical Factors.
Physiotherapy with exercises is generally recommended in the treatment of patients with subacromial impingement syndrome (SIS). We aimed to investigate the use of physiotherapy in patients with SIS in Danish hospital settings as part of initial non-surgical treatment and after SIS-related surgery and to evaluate to which extent sex, socio-demographic and clinical factors predict the use of physiotherapy. Using national health registers, we identified 57,311 patients who had a first hospital contact with a diagnosis of ICD-10, groups M75.1-75.9, 1 July 2007 to 30 June 2011. Records of physiotherapy were extracted within 52 weeks after first contact (or until surgery), and for surgically treated patients within 26 weeks after surgery. Predictors of the use of physiotherapy after first contact and after surgery were analysed as time-to-event. Within 52 weeks after first contact, 43% of the patients had physiotherapy and 30% underwent surgery. Within 26 weeks after surgery, 80% had a record of physiotherapy. After first contact and after surgery, exercise was part of physiotherapy in 65% and 84% of the patients, respectively. A public hospital contact, physiotherapy before hospital contact, administrative region, female sex, a diagnosis of other or unspecified disorders (M75.8-M75.9), and surgical procedure predicted higher use of physiotherapy. Low education level predicted slightly lower use of physiotherapy after first contact, but not after surgery. In patients with SIS in Danish hospital settings, physiotherapy was more often used after surgery than as part of initial non-surgical treatment. The use of physiotherapy was less common among men than women, whereas unequal use of physiotherapy in relation to education level was not noticeable. The use of physiotherapy with exercises in initial non-surgical treatment was relatively limited.


Genetic diversity and genetic structure of an endangered species, Trillium tschonoskii.
The genetic diversity and genetic structure of Trillium tschonoskii (Maxim) were investigated using amplified fragment length polymorphism markers. Eight primer combinations were carried out on 105 different individuals sampled from seven populations. Of the 619 discernible DNA fragments generated, 169 (27.3%) were polymorphic. The percentage of polymorphic bands within populations ranged from 4.52 to 10.50. Genetic diversity (H(E)) within populations ranged from 0.0130 to 0.0379, averaging 0.0536 at the species level. Genetic differentiation among populations was detected based on Nei's genetic diversity analysis (53.03%) and analysis of molecular variance (AMOVA) (52.43%). AMOVA indicated significant genetic differentiation among populations (52.43% of the variance) and within populations (47.57% of the variance) (p < 0.0002). Gene flow was low (0.4429) among populations. Species breeding system and limited gene flow among populations are plausible reasons for the high genetic differentiation observed for this species. We propose an appropriate strategy for conserving the genetic resources of T. tschonoskii in China.