Characteristics of glycyl-L-proline transport in intestinal brush-border membrane vesicles.
A proton-peptide symport mechanism has been postulated for transport of dipeptides in rabbit intestinal and renal brush-border membrane vesicles (BBMV). We have investigated the effects of a transmembrane potential (in mouse) and an inwardly directed proton gradient (in mouse, rabbit, and human) on the transport of glycyl-L-proline in intestinal BBMV. Membrane potential alterations, induced by permeant anions or generated by a K+-diffusion potential in the presence of valinomycin, did not accelerate the uptake of glycyl-L-proline. In contrast, in parallel experiments the uptake of D-glucose, whose cotransport system is electrogenic, was markedly increased by an interior negative membrane potential. Thus the transport of glycyl-L-proline in mouse intestinal BBMV is not electrogenic. Further studies on the effect of a proton gradient (extravesicular pH 5.5; intravesicular pH 7.5) on transport of glycyl-L-proline revealed an absence of stimulation of glycyl-L-proline transport and lower uptake rates in the presence of a proton gradient. The simultaneous presence of an interior negative membrane potential and an inwardly directed proton gradient did not accelerate the transport of glycyl-L-proline. These results demonstrate that the transport of glycyl-L-proline in mouse intestinal BBMV is neither electrogenic nor energized by an inwardly directed proton gradient. Likewise, pH gradients do not stimulate glycyl-L-proline uptake in either rabbit or human BBMV.


Acute extrapyramidal syndromes in neuroleptic-treated elders: a pilot study.
The incidence, morbidity, and risk factors for acute extrapyramidal syndromes (EPS) such as akathisia and drug-induced parkinsonism (DIP) in neuroleptic-treated elders have not been systematically explored. This study presents data on 17 elderly patients who were prospectively examined for up to 4 weeks for acute EPS, functional and cognitive status, and behavioral disturbances. Seventy-one percent of subjects developed DIP, and 18% developed akathisia. Predictors of DIP included pre-neuroleptic treatment parkinsonian signs and neuroleptic dose, despite use of low doses of neuroleptics. Development of acute EPS was associated with failure to improve behaviorally. New-onset urinary incontinence was the most common functional abnormality.


A systematic search for the structures, stabilities, and electronic properties of bimetallic Ca₂-doped gold clusters: comparison with pure gold clusters.
The local meta-GGA exchange correlation density functional (TPSS) with a relativistic effective core potential was employed to systematically investigate the geometric structures, stabilities, and electronic properties of bimetallic Ca(2)Au( n ) (n = 1-9) and pure gold Au( n ) (n ≤ 11) clusters. The optimized geometries show that the most stable isomers for Ca(2)Au( n ) clusters have 3D structure when n > 2, and that one Au atom capping the Ca(2)Au( n-1) structure for different-sized Ca(2)Au( n ) (n = 1-9) clusters is the dominant growth pattern. The average atomic binding energies and second-order difference in energies show that the Ca(2)Au(4) isomer is the most stable among the Ca(2)Au( n ) clusters. The same pronounced even-odd alternations are found in the HOMO-LUMO gaps, VIPs, and hardnesses. The polarizabilities of the Ca(2)Au( n ) clusters show an obvious local minimum at n = 4. Moreover, the inverse corrections to the polarizabilities versus the ionization potential and hardness were found for the gold clusters.


Pesticide occurrence in the waters of Júcar River, Spain from different farming landscapes.
A combined methodology to identify and quantify farming chemicals in the entire Júcar River basin has been developed. The procedure consisted of the application of environmental forensic criteria associating laboratory analytical samples, cartographic analysis using Geographical Information Systems (GIS) and synthetic statistical analysis. Sampling involved the collection of 15 samples in surface waters distributed alongside the Júcar River and its two main tributaries (Cabriel and Magro Rivers). The analytical procedure involves generic sample extraction and selective determination of up to 50 target pesticides by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Geographical analysis was performed by mixing both sampling points with analytical results and land use-cover layers for the year 2011. PCA and descriptive statistical analysis was further performed combining land use/cover information and pesticides results to determine correlation between dominant agricultural practices (irrigation and rain fed farming) and location of sampling points. Out of 50 pesticides, 20 were identified and 18 presented concentrations higher than the limits of quantification in surface waters, with a large dispersion in concentrations: from 0.05ng/L (terbuthylazine-2 hydroxy) to 222.45ng/L (imazalil). Statistical analyses reveals that there is a correlation between the percentage of land devoted to irrigation farming, whereas correlations are weaker when analysing the relationship of pesticides in rain fed dominated areas.


On the design of zinc-finger models with cyclic peptides bearing a linear tail.
Cyclic peptides with a linear tail (CPLT) have been successfully used to model two zinc fingers (ZFs) adopting the treble-clef- and loosened zinc-ribbon folds. In this article, we examine the factors that may influence the design of such ZF models: mutations in the sequence, size of the cycle, and size of the tail. For this purpose, several peptides derived from the CPLT-based models of the treble-clef- and loosened zinc-ribbon ZF were synthesized and studied. CPLT-based models appear to be robust toward mutations, accommodate various cycle sizes, and are sensible to the size of the linking region of the tail located between the cycle and the coordinating amino acids. Based on these criteria, we describe the design of a new CPLT-based model for the zinc-ribbon ZFs, LZR , and compare it to a linear analogue, LZR(lin) . The model complex Zn⋅LZR is able to fold correctly around the metal ion contrary to Zn⋅LZR(lin) , suggesting that CPLT-based models are more likely to yield structurally meaningful models of ZF sites than linear peptide models. Finally, we draw some rules that could allow the design of new CPLT-based metallopeptides with a controlled fold.


Catching eyes: effects of social and nonsocial cues on attention capture.
Direct eye contact and motion onset are two powerful cues that capture attention. In the present study, we combined direct gaze with the sudden onset of motion to determine whether these cues have independent or shared influences. Participants identified targets presented randomly on one of four faces. Initially, two faces depicted direct gaze, and two faces depicted averted gaze. Simultaneously with or 900 ms before target presentation, one face with averted gaze switched to direct gaze, and one face with direct gaze switched to averted gaze. When gaze transitions and target presentation were simultaneous, the greatest response-time facilitation occurred at the location of the sudden onset of direct gaze. When target presentation was delayed, direct-gaze cues maintained a facilitatory influence, whereas motion cues induced an inhibitory influence. These findings reveal that gaze cues and motion cues at the same location influence information processing via independent and concurrently acting social and nonsocial attention channels.


An audit of caesarean sections for very low birth weight babies.
This study reviewed caesarean sections for very low birth weight babies in a tertiary referral maternity hospital. Maternal and neonatal complications were recorded and classified according to uterine incision type. We reviewed medical records of 89 women over a period of 2 years. The indication for the caesarean section influenced the type of uterine incision made (p = 0.004). Women who had antepartum haemorrhage were more likely to need a vertical incision. There was also a higher incidence of vertical incisions for gestations <28 weeks (p = 0.029). Surprisingly, when the computerised discharge summaries were reviewed retrospectively, all the vertical uterine incisions were recorded as lower segment caesarean sections. This would have a clinical impact on those women in future pregnancies, especially in a highly mobile population.


Ibuprofen results in alterations of human fetal testis development.
Among pregnant women ibuprofen is one of the most frequently used pharmaceutical compounds with up to 28% reporting use. Regardless of this, it remains unknown whether ibuprofen could act as an endocrine disruptor as reported for fellow analgesics paracetamol and aspirin. To investigate this, we exposed human fetal testes (7-17 gestational weeks (GW)) to ibuprofen using ex vivo culture and xenograft systems. Ibuprofen suppressed testosterone and Leydig cell hormone INSL3 during culture of 8-9 GW fetal testes with concomitant reduction in expression of the steroidogenic enzymes CYP11A1, CYP17A1 and HSD17B3, and of INSL3. Testosterone was not suppressed in testes from fetuses younger than 8 GW, older than 10-12 GW, or in second trimester xenografted testes (14-17 GW). Ex vivo, ibuprofen also affected Sertoli cell by suppressing AMH production and mRNA expression of AMH, SOX9, DHH, and COL2A1. While PGE2 production was suppressed by ibuprofen, PGD2 production was not. Germ cell transcripts POU5F1, TFAP2C, LIN28A, ALPP and KIT were also reduced by ibuprofen. We conclude that, at concentrations relevant to human exposure and within a particular narrow 'early window' of sensitivity within first trimester, ibuprofen causes direct endocrine disturbances in the human fetal testis and alteration of the germ cell biology.


Levels of cholesterol in small LDL particles predict atherosclerosis progression and incident CHD in the HDL-Atherosclerosis Treatment Study (HATS).
Test whether angiographically-documented changes in percent stenosis and clinical endpoints (coronary-related deaths, myocardial infarctions, stroke, revascularization for worsening ischemia) in the HDL-Atherosclerosis Treatment Study (HATS) were attributable to specific LDL-subclasses. Gradient gel electrophoresis of on-study LDL-subclass cholesterol concentrations were measured in 32 placebo, 33 simvastatin-niacin, 38 antioxidant, and 39 simvastatin-niacin & antioxidant treated participants. The prespecified primary end point was the mean change per patient from the initial arteriogram to the final arteriogram in the percent stenosis caused by the most severe lesion in each of the nine proximal coronary segments. The change in the percent stenosis of the most severe proximal lesions increased in association with higher concentrations of the small LDL subfractions LDL-IIIb (24.2-24.6 nm) and LDL-IVa (23.3-24.1 nm) before (both P = 0.002) and after (P = 0.01 and P = 0.03 respectively) adjustment for treatment group and on-study HDL-cholesterol, LDL-cholesterol, and triglyceride concentrations. The associations appeared specific to lesions with <30% baseline stenosis. When adjusted for age, sex, baseline BMI and cigarette use, the odds for primary clinical endpoints (death from coronary causes, nonfatal myocardial infarction, stroke, or revascularization for worsening ischemia) were significantly greater in subjects with higher on-study LDL-IIIb levels both before (P = 0.01) and after (P = 0.03) adjustment for treatment group and the standard lipid values. Plasma LDL-IIIb cholesterol concentrations were related to changes in coronary artery stenosis and cardiovascular events in patients with coronary artery disease and low HDL-cholesterol. ClinicalTrials.gov NCT00000553.


Comparison of several sequence-based association methods in pedigrees.
Genome-wide association studies are very powerful in determining the genetic variants affecting complex diseases. Most of the available methods are very useful in detecting association between common variants and complex diseases. Recently, methods to detect rare variants in association with complex diseases have been developed with the increasingly available sequencing data from next-generation sequencing. In this paper, we evaluate and compare several of these recent methods for performing statistical association using whole genome sequencing data in pedigrees. Specifically, functional principal component analysis (FPCA), extended combined multivariate and collapsing (CMC) method for families, a generalized T(2) method, and chi-square minimum approach were compared by analyzing all the genetic variants, common and rare, of both the real data set and the simulated data set provided as part of Genetic Analysis Workshop 18.


Role of perfusion medium in rewarming machine perfusion from hypo- to normothermia.
Gradual warming up of cold stored organ grafts using a controlled machine perfusion protocol facilitates restitution of cellular homeostasis and mitigates rewarming injury by adapted increase of temperature and metabolism. The aim of the present study was to compare intra- and extracellular type perfusion media for the use in machine perfusion-assisted rewarming from hypo- to normothermia. Rat livers were retrieved 20 min after cardiac arrest. After 18 h of cold storage (CS) with or without additional 2 h of rewarming machine perfusion from 8°C up to 35°C with either diluted Steen solution or with Belzer MPS, liver functional parameters were evaluated by an established ex vivo reperfusion system. Rewarming machine perfusion with either solution significantly improved graft performance upon reperfusion in terms of increased bile production, less enzyme release, and reduced lipid peroxidation compared to CS alone. Cellular apoptosis (release of caspase-cleaved keratin 18) and release of tumor necrosis factor were only reduced significantly after machine perfusion with Belzer MPS. Histological evaluation did not disclose any major morphological damage in any of the groups. Within the limitation of our model, the use of Belzer MPS seems to be an at least adequate alternative to a normothermic medium like Steen solution for rewarming machine perfusion of cold liver grafts.


Deltoid ligament injury and repair.
The deltoid ligament is the primary stabilizer of the medial side of the ankle joint. It is a complex structure with an origin at the medial malleolus from where it spreads fan shaped distally with an insertion into the medial side of the talus, calcaneus and navicular bone. This chapter gives an overview of the anatomy, function, and pathology of the deltoid ligament.The deltoid ligament can become insufficient as a result of an ankle injury or prolonged strain. In the acute setting, deltoid insufficiency often coincides with multi ligament injury the ankle joint; syndesmosis injury, or ankle fractures. Management in the acute phase remains a subject of debate. Some orthopedic surgeons have a tendency towards repair, whereas most trauma surgeons often treat the deltoid nonoperatively. In the chronic setting the ligament complex is often elongated as a result of prolonged strain. It often coexists with a hindfoot valgus, as is the case in planovalgus feet. In such a case a realignment procedure should be combined with the deltoid repair.


Synergism Effect of the Essential Oil from Ocimum basilicum var. Maria Bonita and Its Major Components with Fluconazole and Its Influence on Ergosterol Biosynthesis.
The aim of this study was to evaluate the activity of the EO and its major components of Ocimum basilicum var. Maria Bonita, a genetically improved cultivar, against the fluconazole sensitive and resistant strains of Candida albicans and Cryptococcus neoformans. Geraniol presented better results than the EO, with a low MIC (76 μg/mL against C. neoformans and 152 μg/mL against both Candida strains). The combination of EO, linalool, or geraniol with fluconazole enhanced their antifungal activity, especially against the resistant strain (MIC reduced to 156, 197, and 38 μg/mL, resp.). The ergosterol assay showed that subinhibitory concentrations of the substances were able to reduce the amount of sterol extracted. The substances tested were able to reduce the capsule size which suggests they have an important mechanism of action. Transmission electron microscopy demonstrated cell wall destruction of C. neoformans after treatment with subinhibitory concentrations. In C. albicans ultrastructure alterations such as irregularities in the membrane, presence of vesicles, and cell wall thickening were observed. The biofilm formation was inhibited in both C. albicans strains at MIC and twice MIC. These results provide further support for the use of O. basilicum EO and its major components as a potential source of antifungal agents.


The Impact on Mental Health of Losing an Only Child and the Influence of Social Support and Resilience.
The number of parents who have lost their only child (PLOCs) has increased annually with the implementation of the birth control policy in mainland China. This study aimed to investigate the mental health status of PLOCs and the influence of social support and resilience. Study 1 recruited 100 PLOCs and 88 nonbereaved parents, and compared differences in depression, anxiety, and loneliness. Study 2 investigated the influence of social support and resilience on the mental health of PLOCs via a mediating model. Results indicate that PLOCs reported more anxiety and depression symptoms than nonbereaved counterparts. Perceived close family support, objective support, and resilience negatively predicted anxiety and depression. In addition, perceived close family support was found to influence mental health via resilience. The current findings reveal that losing an only child has long-term negative impacts on the mental health of PLOCs. However, perceived close family support and objective support can protect their mental health either directly or indirectly via resilience.


In Vitro Interactions of Epacadostat and its Major Metabolites with Human Efflux and Uptake Transporters: Implications for Pharmacokinetics and Drug Interactions.
Epacadostat (EPAC) is a first-in-class, orally active inhibitor of the enzyme indoleamine 2,3-dioxygenase 1 and has demonstrated promising clinical activity. In humans, three major plasma metabolites have been identified: M9 (a glucuronide-conjugate), M11 (a gut microbiota metabolite), and M12 (a secondary metabolite formed from M11). It is proposed, based on the human pharmacokinetics of EPAC, that the biliary excretion of M9, the most abundant metabolite, leads to the enterohepatic circulation of EPAC. Using various in vitro systems, we evaluated in the present study the vitro interactions of EPAC and its major metabolites with major drug transporters involved in drug absorption and disposition. EPAC is a substrate for efflux transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), but it is not a substrate for hepatic uptake transporters [organic anion transporting polypeptides OATP1B1 and OATP1B3]. The low permeability of M9 suggests an essential role for transporters in its disposition. M9 is likely excreted from hepatocytes into bile via multidrug resistance-associated protein 2 (MRP2) and BCRP, excreted into blood via MRP3, and transported from blood back into hepatocytes via OATP1B1 and OATP1B3. M11 and M12 are not substrates for P-gp, OATP1B1 or OATP1B3, and M11, but not M12, is a substrate for BCRP. With respect to inhibition of drug transporters, the potential of EPAC, M9, M11, and M12 to cause clinical drug-drug interactions via inhibition of P-gp, BCRP, OATP1B1, OATP1B3, OAT1, OAT3, or organic cation transporter 2 was estimated to be low. The current investigation underlines the importance of metabolite-transporter interactions in the disposition of clinically relevant metabolites, which may have implications for the pharmacokinetics and drug interactions of parent drugs.


An epidemiological study on vaginitis in 6,150 women of reproductive age in Shanghai.
The aim of the present study was to determine the prevalence and risk factors for vaginitis, the proportion of pathogens, and cognition of reproductive age patients on the harmful effects of vaginitis, its risk factors, and treatment. This retrospective study enrolled 6,150 patients admitted to the Shanghai Jinshan Central Hospital from 2011 to 2015 with a chief complaint of abnormal vaginal discharge. A questionnaire was designed to survey the cognition of patients on the harmful effects of vaginitis. Routine gynecological examinations and laboratory tests were performed and the risk factors for contracting vaginitis were analyzed by multifactor logistic regression analysis. The positive pathogen rate was 65.63% (4,036/6,150). Trichomonas infections were diagnosed in 1,416 (35.08%) cases including 761 (18.86%) cases of single trichomonas infections, which was significantly higher than the proportion of any other single pathogen infection (P<0.05). From 2011 to 2015, trichomoniasis and chlamydia infections decreased, but bacteria, candida and mycoplasma infections increased. The questionnaire survey showed a low cognition level on iatrogenic and mother-to-child transmission of vaginal infections as well as the risk of ectopic pregnancy and infertility, and on how to prevent vaginal infections. Logistic multifactor regression analysis revealed that advanced age, a low educational level, farmers, childbearing history and a low income were the risk factors for vaginitis. Women of reproductive age showed a high rate of vaginal infections and more attention should be paid to women with a low education level and income to reduce the incidence of vaginal infections in this population.


Common Antacid Medication-Ranitidine Causing a Rare Serious Adverse Effect.
Ranitidine is a widely used over-the-counter antacid medication, and is generally very well tolerated. To our knowledge, anaphylaxis secondary to ranitidine is exceedingly rare, and has only been reported in a few case reports. We present a patient who developed an anaphylactic reaction after one tablespoon of ranitidine. The goal of this manuscript is to add to the paucity of literature of this rare but life-threatening adverse effect of a commonly used medication.


Proliferative verrucous leukoplakia may initially mimic lichenoid reactions.
Proliferative verrucous leukoplakia is an intriguing disease, which occurs particularly in women aged greater than 60 years, is not associated with tobacco and alcohol, and has a high risk of recurrence and malignant transformation. Although it is well known that the typical presentation is characterized by multifocal and verrucous white lesions, there is no description that its initial clinical presentation may simulate a lichenoid reaction.


Ecological analysis of associations between groundwater quality and hypertension and cardiovascular disease in rural Saskatchewan, Canada using Bayesian hierarchical models and administrative health data.
Associations between groundwater quality and the prevalence of hypertension and ischemic heart disease were investigated in rural areas of the Canadian province of Saskatchewan. The partially ecological study was analyzed using Bayesian hierarchical models to account for spatial variability in risk. Exposure measures and health outcomes were estimated based on previously collected water quality surveillance data from public water supplies and private wells and administrative health data. Water quality exposures for each study region were estimated by applying geostatistical techniques to arsenic concentrations and principal component (PC) scores. The PC scores summarized groups of parameters measuring either health standards or aesthetic objectives described by the province. Generalized linear mixed models with a log link assessed associations between water quality and observed count of health outcomes relative to the expected value. The Bayesian models contained uncorrelated and spatially correlated random effects for each geographic region. Effect estimates were controlled for sex and age by stratification of case and expected case counts, for smoking by inclusion of sex- and age-specific prevalence of chronic obstructive pulmonary disease as a surrogate covariate, and for education and income by use of census data. There was no evidence for associations between groundwater arsenic concentrations in public or private water supplies and increased risk of hypertension or cardiovascular disease. An increase in the second aesthetic objectives PC score from public supplies was associated with a protective effect against ischemic heart disease. This PC value summarized hardness and magnesium Similarly, an increase in the second aesthetic objectives PC in private supplies was associated with decreased prevalence of hypertension. The results of this study are consistent with others demonstrating a relationship between elevated hardness and magnesium concentrations in drinking water and reduced risk of hypertension and cardiovascular disease. Further investigation is warranted with individual exposure history, particularly with respect to the potential beneficial effect of hard water on the prevalence of hypertension and cardiovascular disease.


Phase-Separation-Induced Anomalous Stiffening, Toughening, and Self-Healing of Polyacrylamide Gels.
Novel, tough, strong, and self-healable poly-acrylamide (PAAm) gels are fabricated by inducing an appropriate phase-separation structure using a poor solvent. The phase separation induces a gel-glass-like transition of the PAAm gels, providing the gels an anomalously high modulus (211 MPa), fracture stress (7.13 MPa), and fracture energy (4.16 × 10(4) J m(-2)), while keeping a high solvent content (≈60 vol%).


Effect of Khat chewing on the bioavailability of ampicillin and amoxycillin.
The study examined the effect of Khat chewing on ampicillin and amoxycillin bioavailability following the administration of a 500 mg single dose of each antibiotic at different times relative to Khat chewing. Using a urinary excretion method the bioavailabilities of ampicillin and amoxycillin were determined in eight healthy adult male Yemeni volunteers. The extent and rate of ampicillin bioavailability were reduced significantly by Khat chewing except when administered 2 h after the Khat chewing session. However, the bioavailability of amoxycillin was only significantly reduced when the antibiotic was taken midway through the Khat chewing session. It was concluded that the two antibiotics, particularly ampicillin, should be taken 2 h after Khat chewing.


Numb positively regulates autophagic flux via regulating lysosomal function.
Autophagy is a lysosome-dependent catabolic process involving in the degradation and recycling of unnecessary or damaged proteins and organelles. Emerging evidence indicates that autophagy dysfunction is closely related to various human diseases including cancer, aging, myopathies and neurodegenerative disorders. Here, using genetic knockdown, we uncover the role of Numb, an endocytic adaptor protein, in regulating the late steps of autophagy. We found that Numb depletion led to the accumulation of autophagic vacuole, as verified by RFP-LC3 staining combined with transmission electron microscopy. Further investigation indicated that Numb depletion impaired autophagic degradation through inhibiting the activities of lysosomal enzymes (Cathepsin D, β-glucuronidase and β-glucosidase). Moreover, Numb depletion induced elevation of lysosomal pH values and decrease of glycosylated lysosome-associated membrane proteins. We further observed that Rab7 activity was inhibited in Numb-depleted cells. Together, our findings revealed a novel function of Numb and its likely mechanism in regulation of autophagy events.


Isolation of a Cationic Platinum(II) σ-Silane Complex.
The platinum complex [Pt(It Bui Pr')(It Bui Pr)][BArF ] interacts with tertiary silanes to form stable (<0 °C) mononuclear PtII σ-SiH complexes [Pt(It Bui Pr')(It Bui Pr)(η1 -HSiR3 )][BArF ]. These compounds have been fully characterized, including X-ray diffraction methods, as the first examples for platinum. DFT calculations (including electronic topological analysis) support the interpretation of the coordination as an unusual η1 -SiH. However, the energies required for achieving a η2 -SiH mode are rather low, and is consistent with the propensity of these derivatives to undergo Si-H cleavage leading to the more stable silyl species [Pt(SiR3 )(It Bui Pr)2 ][BArF ] at room temperature.


Neutrophil CD64 expression: distinguishing acute inflammatory autoimmune disease from systemic infections.
Common bacterial and opportunistic infections are a major cause of mortality in patients who are immunosuppressed owing to treatment with corticosteroids or cytotoxic drugs. Common laboratory tests for infection lack sensitivity and specificity. One of the new generation of tests to detect early systemic infections measures the up regulation of an Fc receptor (Fcgamma R1, or CD64) on neutrophils. The Fc receptors on white blood cells are very important for effective phagocytosis of bacteria and are up regulated during an infection. To measure the clinical usefulness of quantitative CD64 measurements to differentiate between systemic infection and active autoimmune inflammation in an ongoing study. Patients with systemic infection (n=27), active autoimmune inflammatory disease (n=44), vasculitis (n=5), and controls (n=20) were studied for neutrophil CD64 expression using monoclonal antibodies and flow cytometry. The median (interquartile range (IQR)) CD64 expression in patients with active inflammatory disease and systemic infection was 907.5 (586-1550) and 3647 (2380-6642), respectively (p<0.0001). The median (IQR) CD64 expression in control patients (osteoarthritis and fibromyalgia) was 505 (359-599). The sensitivity and specificity of CD64 expression on neutrophils to diagnose systemic infection (using a cut off value of 2000) was 85% and 91%, respectively. These results indicate that quantitative measurement of CD64 can distinguish between systemic infection and the flare of autoimmune diseases.


Myocardial viability in coronary artery chronic total occlusion.
Coronary artery chronic total occlusion (CTO) has rapidly become a popular target of percutaneous coronary intervention (PCI). Technical and technological advances required for approaching these anatomically complex and challenging lesions have progressed at an extraordinary pace and have led to amazing success rates. Patient selection, however, has primarily focused on patient symptoms, lesion characteristics, as well as the state of collateral circulation. Multiple national and international registries have been established to follow the progress of percutaneous CTO recanalization and have provided valuable information. Concern, however, exists that this challenging procedure will become the "standard of care" before its effectiveness and appropriateness is tested in prospective controlled trials. This manuscript reviews the current state of patient selection and the need for careful assessment of the presence and extent of myocardial viability prior to lengthy, resource-intensive, and potentially high-risk procedures.


Performance of Four Transport and Storage Systems for Molecular Detection of Multidrug-Resistant Tuberculosis.
Detection of drug-resistant tuberculosis is essential for the control of the disease but it is often hampered by the limitation of transport and storage of samples from remote locations to the reference laboratory. We performed a retrospective field study to evaluate the performance of four supports enabling the transport and storage of samples to be used for molecular detection of drug resistance using the GenoType MTBDRplus. Two hundred Mycobacterium tuberculosis strains were selected and spotted on slides, FTA cards, GenoCards, and in ethanol. GenoType MTBDRplus was subsequently performed with the DNA extracted from these supports. Sensitivity and specificity were calculated and compared to the results obtained by drug susceptibility testing. For all supports, the overall sensitivity and specificity for detection of resistance to RIF was between 95% and 100%, and for INH between 95% and 98%. The four transport and storage supports showed a good sensitivity and specificity for the detection of resistance to RIF and INH in M. tuberculosis strains using the GenoType MTBDRplus. These supports can be maintained at room temperature and could represent an important alternative cost-effective method useful for rapid molecular detection of drug-resistant TB in low-resource settings.


Characterization of chronic lung allograft dysfunction phenotypes using spectral and intrabreath oscillometry.
Background: Chronic lung allograft dysfunction (CLAD) is the major cause of death beyond 2 years after lung transplantation and develops in 50% of all patients by 5 years post-transplant. CLAD is diagnosed on the basis of a sustained drop of 20% for at least 3 months in the forced expiratory volume (FEV1), compared to the best baseline value achieved post-transplant. CLAD presents as two main phenotypes: bronchiolitis obliterans syndrome (BOS) is more common and has better prognosis than restrictive allograft syndrome (RAS). Respiratory oscillometry is a different modality of lung function testing that is highly sensitive to lung mechanics. The current study investigated whether spectral and intrabreath oscillometry can differentiate between CLAD-free, BOS- and RAS-CLAD at CLAD onset, i.e., at the time of the initial 20% drop in the FEV1. Methods: A retrospective, cross-sectional analysis of 263 double lung transplant recipients who underwent paired testing with oscillometry and spirometry at the Toronto General Pulmonary Function Laboratory from 2017 to 2022 was conducted. All pulmonary function testing and CLAD diagnostics were performed following international guidelines. Statistical analysis was conducted using multiple comparisons. Findings: The RAS (n = 6) spectral oscillometry pattern differs from CLAD-free (n = 225) by right-ward shift of reactance curve similar to idiopathic pulmonary fibrosis whereas BOS (n = 32) has a pattern similar to obstructive lung disease. Significant differences were found in most spectral and intrabreath parameters between BOS, RAS, and time-matched CLAD-free patients. Post-hoc analysis revealed these differences were primarily driven by BOS instead of RAS. While no differences were found between CLAD-free and RAS patients with regards to spectral oscillometry, the intrabreath metric of reactance at end-inspiration (XeI) was significantly different (p < 0.05). BOS and RAS were differentiated by spectral oscillometry measure R5, and intrabreath resistance at end expiration, ReE (p < 0.05 for both). Conclusion: Both spectral and intrabreath oscillometry can differentiate BOS-CLAD from CLAD-free states while intrabreath oscillometry, specifically XeI, can uniquely distinguish RAS-CLAD from CLAD-free. Spectral and intrabreath oscillometry offer complementary information regarding lung mechanics in CLAD patients to help distinguish the two phenotypes and could prove useful in prognostication.


A review of the potential mechanisms for the lowering of colorectal oncogenesis by butyrate.
Colorectal cancer (CRC) is a leading cause of preventable cancer deaths worldwide, with dietary factors being recognised as key risk modifiers. Foods containing dietary fibre are protective to a degree that the World Cancer Research Fund classifies the evidence supporting their consumption as 'convincing'. The mechanisms by which fibre components protect against CRC remain poorly understood, especially their interactions with the gut microbiome. Fibre is a composite of indigestible plant polysaccharides and it is emerging that fermentable fibres, including resistant starch (RS), are particularly important. RS fermentation induces SCFA production, in particular, relatively high butyrate levels, and in vitro studies have shown that this acid has strong anti-tumorigenic properties. Butyrate inhibits proliferation and induces apoptosis of CRC cell lines at physiological concentrations. These effects are attributed to butyrate's ability to alter gene transcription by inhibiting histone deacetylase activity. However, the more recent discovery of G-protein coupled receptors that bind butyrate and other SCFA and data obtained from proteomic and genomic experiments suggest that alternative pathways are involved. Here, we review the mechanisms involved in butyrate-induced apoptosis in CRC cells and, additionally, the potential role this SCFA may play in mediating key processes in tumorigenesis including genomic instability, inflammation and cell energy metabolism. This discussion may help to inform the development of strategies to lower CRC risk at the individual and population levels.


Associations between age-related hearing loss, cognitive decline, and depression in Chinese centenarians and oldest-old adults.
Age-related hearing loss (ARHL) and age-related cognitive decline (ARCD) are leading causes of disability in older adults. ARHL may increase ARCD risk and cause depression development. This study aimed to explore the associations of ARHL with ARCD and depression in Chinese centenarians and oldest-old adults. A household survey was conducted on 859 centenarians and oldest-old adults residing in 16 cities and counties in China. Basic information was collected using interview questionnaires, physical examinations, and blood tests conducted by systematically trained local doctors and nurses. In total, 501 (58.3%), 649 (75.6%), and 211 (24.6%) participants had ARHL, ARCD, and depression, respectively. The prevalence of ARCD and depression was significantly higher in participants with ARHL than in those without ARHL (all p < 0.05). Participants with ARHL had significantly lower Mini-Mental State Examination (MMSE) scores indicative of more cognitive decline, and significantly higher 15-item version of the Geriatric Depression Scale (GDS-15) scores suggesting greater levels of depression, than those without ARHL (all p < 0.05). Multivariate logistic regression analyses (Stepwise) indicated that ARHL was significantly and positively associated with ARCD [odds ratio (OR): 1.594, 95% confidence interval (CI): 1.132, 2.245] and depression (OR: 1.623, 95% CI: 1.139, 2.314; all p < 0.05). Multivariate linear regression analyses (Stepwise) indicated that ARHL was significantly and inversely associated with MMSE scores (B: -2.520, 95% CI: -3.356, -1.684) and significantly and positively associated with GDS-15 scores (B: 0.713, 95% CI: 0.328, 1.098; all p < 0.05). ARHL is independently associated with ARCD and depression in Chinese centenarians and oldest-old adults.


Contraceptive efficacy and safety of a low-dose oral contraceptive, (0.03 mg ethinyl oestradiol and 2 mg chlormadinone acetate) Belara, over three medication cycles.
To describe the modulation of ovarian function during three medication cycles with 0.03 mg ethinyl oestradiol (EE) and 2 mg chlormadinone acetate (CMA), leading to inhibition of conception in healthy women. Phase II, single-centre, open, non-controlled trial. The main outcome measure was inhibition of ovarian activity, assessed by frequent monitoring of the presence, size and persistence of follicle-like structures using ultrasonography. Secondary parameters included: cervical reaction score (CRS-probability of fertilization), endometrial thickness (probability of nidation), and serum levels of the sex hormones oestradiol, progesterone, luteinizing hormone and follicle stimulating hormone. Safety was primarily assessed by monitoring the occurrence of adverse events. Thirty-three subjects were eligible for the trial and were included in the efficacy assessment (per protocol analysis, PPA). All subjects ovulated during the pretreatment cycle, but none during the three medication cycles. Follicular growth was profoundly suppressed during the medication phase, with residual ovarian activity occurring in only 12/83 (14.5%) treatment cycles. The CRS was negative during each medication cycle and endometrial thickness was suppressed on each medication day, with median values of 4.0-6.0 mm. EE/ CMA was well tolerated, with few adverse events reported; most were typically cycle-related and included headache, breast discomfort, nausea and vomiting. During the administration of EE/CMA follicular development, cervical reaction and endometrial thickness are profoundly suppressed, resulting in unfavourable conditions for fertilization, implantation and, thus, pregnancy.


Gainsharing Strategies, Physician Champions, Getting Physician Buy In.
As healthcare spending continues to outpace economic growth, legislators and healthcare economists have explored many processes aimed at improving efficiency and reducing waste. Gainsharing or the general concept that organizations and their employees can work together to continually improve outcomes at reduced expenditures in exchange for a portion of the savings has been shown to be effective within the healthcare system. Although gainsharing principles may be applicable to healthcare organizations and their physician partners, specific parameters should be followed when implementing these arrangements. This article will discuss 10 gainsharing strategies aimed at properly aligning healthcare organizations and physicians, which if followed will ensure the successful implementation of gainsharing initiatives.


Bacteriology of diabetic foot ulcers.
Diabetic foot ulcerations exhibit a wide range of the bacterial spectrum. A long-standing question is whether any particular bacterium or class of bacteria is responsible for the more involved ulcers. A review of such cases at Sheridan Park Hospital reveals that there may be factors other than bacterial type that may account for the virulence of diabetic ulcers. Multifactorial causes host a vital role in this common, but potentially serious, podiatric problem.


Combined orthogeriatric care in the management of hip fractures: a prospective study.
To evaluate the efficacy of combined care between orthopaedic surgeons and geriatricians in the management of patients with fractured necks of femur. A prospective study of the admissions to a district general hospital with hip fractures was carried out over a 5-year period. In the years 1992-1994, medical problems in this patient group were managed by a consultation-only service. At the end of 1994, a consultant geriatrician was appointed to manage these patients jointly with the orthopaedic surgeons, and the study was then carried through until the end of 1996. Information about the patients from admission to discharge or death was gathered prospectively using a proforma for the 3 years prior to orthogeriatric care, and the 2 years after. Main outcome measures were mortality, length of stay and discharge destination. These were compared for the two periods--pre- and post-orthogeriatric care. No significant differences were noted in mortality, length of stay or discharge destination. Combined orthogeriatric care according to our model did not have an impact on our chosen outcome measures.


Abdominal trauma surgery during recent US combat operations from 2002 to 2016.
Abdominal surgery constitutes approximately 13% of surgical procedures performed for combat injuries. This study examines the frequencies and type of abdominal surgical procedures performed during recent US Military operations. A retrospective analysis of the Department of Defense Trauma Registry was performed for all Role 2 (R2) and Role 3 (R3) medical treatment facilities (MTFs), from January 2002 to May 2016. The 273 International Classification of Diseases, Ninth Revision, Clinical Modification procedure codes that were identified as abdominal surgical procedures were stratified into 24 groups based on anatomic and functional classifications and then grouped by whether they were laparoscopic. Procedure grouping and categorization were determined, and adjudicated if necessary, by subject matter experts. Data analysis used Stata version 14 (College Station, TX). A total of 26,548 abdominal surgical procedures were identified at R2 and R3 MTFs. The majority of abdominal surgical procedures were reported at R3 facilities. The largest procedure group at both R2 and R3 MTFs were procedures involving the bowel. There were 18 laparoscopic procedures reported (R2: 4 procedures, R3: 14 procedures). Laparotomy not otherwise specified was the second largest procedure group at both R2 (1,060 [24.55%]) and R3 (4,935 [22.2%]) MTFs. Abdominal caseload was variable over the 15-year study period. Surgical skills such as open laparotomy and procedures involving the bowel are crucial in war surgery. The abundance of laparotomy not otherwise specified may reflect inadequate documentation, or the plethora of second- and third-look operations and washouts performed for complex abdominal injuries. Traditional elective general surgical cases (gallbladder, hernia) were relatively infrequent. Laparoscopy was almost nonexistent. Open abdominal surgical skills therefore remain a necessity for the deployed US Military General Surgeons; this is at odds with the shifting paradigm from open to laparoscopic skills in stateside civilian and military hospitals. Epidemiologic study, level III.


Redox-active alkylsulfones as precursors for alkyl radicals under photoredox catalysis.
A method for generating alkyl radicals using visible-light photoredox catalysis is described. This procedure was found to present an efficient means to access a diverse collection of 1°, 2°, and 3° alkyl radicals through the single-electron transfer of sulfones under mild reaction conditions. These alkyl radicals generated via the reductive desulfonylation of readily synthesized and stable alkylsulfones were engaged to forge C-C bonds. A detailed study was also carried out to shed light on the mechanism.


Long-Term Temporospatial Complementary Relationship between Degradation and Bone Regeneration of Mg-Al Alloy.
The utilization of guided tissue regeneration membranes is a significant approach for enhancing bone tissue growth in areas with bone defects. Biodegradable magnesium alloys are increasingly being used as guided tissue regeneration membranes due to their outstanding osteogenic properties. However, the degradation rates of magnesium alloy bone implants documented in the literature tend to be rapid. Moreover, many studies focus only on the initial 3-month period post-implantation, limiting their applicability and impeding clinical adoption. Furthermore, scant attention has been given to the interplay between the degradation of magnesium alloy implants and the adjacent tissues. To address these gaps, this study employs a well-studied magnesium-aluminum (Mg-Al) alloy membrane with a slow degradation rate. This membrane is implanted into rat skull bone defects and monitored over an extended period of up to 48 weeks. Observations are conducted at various intervals (2, 4, 8, 12, 24, and 48 weeks) following the implantation. Assessment of degradation behavior and tissue regeneration response is carried out using histological sections, micro-CT scans, and scanning electron microscopy (SEM). The findings reveal that the magnesium alloy membranes demonstrate remarkable biocompatibility and osteogenic capability over the entire observation duration. Specifically, the Mg-Al alloy membranes sustain their structural integrity for 8 weeks. Notably, their osteogenic ability is further enhanced as a corrosion product layer forms during the later stages of implantation. Additionally, our in vitro experiments employing extracts from the magnesium alloy display a significant osteogenic effect, accompanied by a notable increase in the expression of osteogenic-related genes. Collectively, these results strongly indicate the substantial potential of Mg-Al alloy membranes in the context of guided tissue regeneration.


Psychosocial interventions for infertile couples: a critical review.
This critical review aims to identify, summarize and critically appraise the current literature evaluating the effectiveness of psychosocial interventions to improve infertile couples' well-being. It also aims to identify the design implications of effective psychosocial interventions for the management of psychosocial distress in infertile couples, especially culturally specific interventions for Chinese infertile couples. Directions for future research are discussed. Infertility is a life crisis affecting 15% of couples in most countries. The affected couples experience considerable psychological distress and impaired interpersonal relationships. Assisted reproductive technologies offer couples hope for pregnancy, but pose an unbearable psychological burden. Psychosocial interventions have been developed to offer support; however, their effectiveness has been inconsistent. A thorough analysis of the literatures on the topic of psychosocial interventions for infertile couples. A systematic search of MEDLINE, CINAHL, PsycINFO, British Nursing Index and GoogleScholar from 2003-2015 was conducted to identify English language articles with the keywords 'psychosocial intervention' and 'infertility'. Two authors assessed all of the identified articles independently for inclusion in the review. Twelve studies were included in the review: seven were interventional studies and five were review studies. The findings indicated that the psychosocial interventions in general improved psychological outcomes, marital relationships and pregnancy rates among infertile couples. Psychosocial interventions should be incorporated into routine practice for infertile couples to provide timely support and counselling. The implications of the review findings for the effective design of psychosocial interventions, including the content, format, duration and intervener for clinical practice are discussed. In confirming the efficacy of such intervention design, randomized controlled trials are needed to compare the interventions and usual care at clinical setting. Longitudinal design is also needed to examine the long-term effects of psychosocial interventions in infertile couples' well-being.


Longitudinal follow-up of 100 patients at risk of intrauterine growth retardation: comparison of diagnosis in two periods.
The concept of low birth weight includes two different entities: prematurity and intrauterine growth retardation. Both of them are major public health problems, because they increase perinatal morbidity and mortality Early diagnosis of IUGR leads to adequate decisions, making possible a reduction in perinatal morbidity and mortality. In order to make an early diagnosis of IUGR, clinical methods have proven to be insufficient. Ultrasonography is an important aid to this diagnosis, introducing the measurement of fetal diameters and perimeters. This study, designed to compare both methods, was carried out in at the Antoine Béclère Hospital, Clamart, France. Data processing was done in CLAP-PAHO/WHO. In the first period, retrospective analyses of 116 clinical histories with IUGR were performed. In this study, only fetal diameters were used and the accuracy of clinical and ultrasonographic diagnosis was evaluated. In the second period a prospective longitudinal follow-up study of 100 pregnant women at risk of developing IUGR was carried out. Clinical diagnosis was also evaluated, and compared to the ultrasonographic approach. The parameters used were the fetal diameters and perimeters (head and abdominal perimeters, and their relationship). Sensitivity, specificity and predictive values of the ultrasonic parameters were calculated (table I). The clinical and ultrasonographic diagnosis of both periods were compared with the purpose to analyze the effect of the measurement of fetal perimeters in the diagnostic accuracy. Newborns of the 100 patients in the prospective study were classified into two groups according to birth weight.(ABSTRACT TRUNCATED AT 250 WORDS)


Frontal Examination of the Distal Nail Unit.
Clinical findings in many nail disorders are not usually pathognomonic. An accurate diagnosis therefore relies on inspection of the nail unit from different angles. We review clinical features of different nail disorders that can be observed during frontal examination of the distal edge of the nail plate and the hyponychium and correlate these with features observed when the nail is viewed from above. Frontal examination of the distal nail unit can help establish a clinical diagnosis in routine practice.


Decrease of fractional flow reserve shortly after percutaneous coronary intervention.
The aim of the present study was to quantitatively assess the physiological acute recoil after percutaneous coronary intervention (PCI), and to determine the relation between it and target lesion revascularization (TLR) in the chronic phase. This study evaluated 76 patients who underwent elective PCI between May 1997 and December 2001: plain old balloon angioplasty (POBA) in 50 patients and bare metal stent implantation in 26 patients. Fractional flow reserve (FFR) was measured immediately (FFR0m) and 15 min (FFR15m) after the final dilation, and the difference (dif-FFR) was calculated. In POBA patients with TLR, FFR15m was significantly low (0.79+/-0.05 vs 0.87 +/-0.08, p<0.001) and dif-FFR was significantly high (0.06+/-0.04 vs -0.01+/-0.04, p<0.001) compared with the patients without TLR. The patients with a larger dif-FFR value (> or =0.05) had a higher rate of TLR (92%). Dif-FFR was the strongest independent predictor of TLR. The changes in FFR during the time course shortly after coronary intervention can be detected and a decrease in the first 15 min after PCI is associated with a higher rate of TLR.


TREX1 degrades the 3' end of the small DNA oligonucleotide products of nucleotide excision repair in human cells.
The nucleotide excision repair (NER) machinery removes UV photoproducts from DNA in the form of small, excised damage-containing DNA oligonucleotides (sedDNAs) ∼30 nt in length. How cells process and degrade these byproducts of DNA repair is not known. Using a small scale RNA interference screen in UV-irradiated human cells, we identified TREX1 as a major regulator of sedDNA abundance. Knockdown of TREX1 increased the level of sedDNAs containing the two major UV photoproducts and their association with the NER proteins TFIIH and RPA. Overexpression of wild-type but not nuclease-inactive TREX1 significantly diminished sedDNA levels, and studies with purified recombinant TREX1 showed that the enzyme efficiently degrades DNA located 3' of the UV photoproduct in the sedDNA. Knockdown or overexpression of TREX1 did not impact the overall rate of UV photoproduct removal from genomic DNA or cell survival, which indicates that TREX1 function in sedDNA degradation does not impact NER efficiency. Taken together, these results indicate a previously unknown role for TREX1 in promoting the degradation of the sedDNA products of the repair reaction. Because TREX1 mutations and inefficient DNA degradation impact inflammatory and immune signaling pathways, the regulation of sedDNA degradation by TREX1 may contribute to photosensitive skin disorders.


Can the uptake of breast screening by Asian women be increased? A randomized controlled trial of a linkworker intervention.
This study investigates the effectiveness of a linkworker intervention, giving encouragement and explanations about breast screening, on the subsequent attendance for screening by 'Asian' women. The control group received no visits. The study population comprised all women with Asian names, from a batch of general practices where high proportions of patients were Asian, who were invited for screening. It was found that 59 per cent of the intervention group could be contacted by linkworkers. No difference in attendance was found between the intervention and control groups (49 per cent and 47 per cent). Twenty-five per cent of women were permanently or temporarily not resident at the invitation address. Attendance for screening was related to length of stay in the United Kingdom. This type of intervention was not a successful strategy for promoting uptake by Asian women, and indicates that it is essential to evaluate rigorously projects with such objectives.


Exercise in neuromuscular disease.
In this review, the authors present an overview of the role of exercise in neuromuscular disease (NMD). The authors demonstrate that despite the different pathologies in NMDs, exercise is beneficial, whether aerobic/endurance or strength/resistive training. The authors analyze methodological flaws of existing studies and suggest improvements for future trial protocols. Finally, we discuss specialized exercise training of specific muscles, as well as new technologies adapted from other neurologic disorders, including body-weight-supported treadmill ambulation, robotic-assisted gait training, and neuromuscular electrical stimulation.


Estradiol modulates density of putative 'oxytocin receptors' in discrete rat brain regions.
Previous studies have provided evidence for a discrete localization of two types of vasopressin (AVP)-labeled binding sites in the rat brain, i.e., regions labeled preferentially with AVP (putative AVP receptors) and regions labeled with AVP as well as oxytocin (OT). The latter binding sites are considered here as putative OT receptors. In the present study the effect of estradiol on the number of these putative receptor sites for OT and AVP was investigated in rat brain after daily subcutaneous administration of the steroid (10 micrograms/100 g body weight) to ovariectomized rats. Specific binding of [3H]-OT and [3H]-AVP was determined after in vitro incubation of frozen brain sections, autoradiography and quantitation of the images with computer-assisted densitometry. Estradiol increased the number of OT receptors at least 4-fold in the ventromedial nucleus of the hypothalamus, regions of the olfactory tubercle, the nucleus accumbens and occasionally in the organum vasculosum laminae terminalis. A smaller increase (two-fold) was noted in the central amygdala, while a tendency to a decrease in OT receptor number was noted in the olfactory nucleus and the ventral subiculum. Estradiol treatment permitted an estimation of binding constants of [3H]-OT-binding to a membrane fraction of microdissected ventromedial hypothalamic region (Kd: 1.3 nM, Bmax: 19.9 fmol/mg protein). The number of putative AVP receptors in the lateral septum and in the nucleus tractus solitarii was not affected by estradiol. In conclusion, the OT receptor system is subject to modulation by estradiol in some discrete brain regions, but not in others.(ABSTRACT TRUNCATED AT 250 WORDS)


Silver nanoparticles loaded on lactose/alginate: in situ synthesis, catalytic degradation, and pH-dependent antibacterial activity.
We present the in situ synthesis of silver nanoparticles (AgNPs) through ionotropic gelation utilizing the biodegradable saccharides lactose (Lac) and alginate (Alg). The lactose reduced silver ions to form AgNPs. The crystallite structure of the nanocomposite AgNPs@Lac/Alg, with a mean size of 4-6 nm, was confirmed by analytical techniques. The nanocomposite exhibited high catalytic performance in degrading the pollutants methyl orange and rhodamine B. The antibacterial activity of the nanocomposite is pH-dependent, related to the alterations in surface properties of the nanocomposite at different pH values. At pH 6, the nanocomposite demonstrated the highest antibacterial activity. These findings suggest that this nanocomposite has the potential to be tailored for specific applications in environmental and medicinal treatments, making it a highly promising material.


Dehydropolymerization of 1,1-dihydrotetraphenylsilole and 1,1-dihydrotetraphenylgermole to optoelectronic copolymers catalyzed by colloidal silver nanoparticles.
The co-dehydrocoupling at ambient air atmosphere of 1,1-dihydrotetraphenylsilole 1 and 1,1-dihydrotetraphenylgermole 2 (9:1 mole ratio) with 2 mol% of AgNO3 in toluene at 90 degrees C produces optoelectronic poly(silole-co-germole)s 3 in high yield. The copolymer mainly has Si-Si bonds (and Si-Ge/Ge-Ge bonds in minor) along with the small portion of Si-O/Ge-O bonds in the polymer backbone chain. While Ag2SO4 is also a good catalyst as AgNO3 for the co-dehydrocoupling, AgI is a moderate catalyst. However, CP2Co, Cp2Ni, Cp2ZrCl2/Red-Al, AgX (X = F, Cl, Br) and AgI@MWCNT do not show appreciable catalytic activity. The silver complexes (AgNO3, Ag2SO4, AgI) transformed to colloidal silver nanoparticles during the catalytic reaction. The co-dehydrocoupling of 1 and 2 with AgNO3 even at dry nitrogen atmosphere is occurred, supporting that the oxidation of NO3- ion to NO2 is only the possible oxygen source, but not from the adventitious moisture in air. All cyclodextrins (sigma, beta, and gamma forms) considerably deteriorated the co-dehydrocoupling of 1 and 2 probably by forming toluene-insoluble inclusion complexes and by encapsulating SiH2 moiety. The resulting copolymer emits green light at 521 nm and is electroluminescent at 523 nm, which is similar to the polysilole.


Amplitude death in complex networks induced by environment.
We present a mechanism for amplitude death in coupled nonlinear dynamical systems on a complex network having interactions with a common environment like external system. We develop a general stability analysis that is valid for any network topology and obtain the threshold values of coupling constants for the onset of amplitude death. An important outcome of our study is a universal relation between the critical coupling strength and the largest nonzero eigenvalue of the coupling matrix. Our results are fully supported by the detailed numerical analysis for different network topologies.


Elevated Expression of Vacuolar Nickel Transporter Gene IREG2 Is Associated With Reduced Root-to-Shoot Nickel Translocation in Noccaea japonica.
A number of metal hyperaccumulator plants, including nickel (Ni) hyperaccumulators, have been identified in the genus Noccaea. The ability to accumulate Ni in shoots varies widely among species and ecotypes in this genus; however, little is known about the molecular mechanisms underlying this intra- and inter-specific variation. Here, in hydroponic culture, we compared Ni accumulation patterns between Noccaea japonica, which originated in Ni-enriched serpentine soils in Mt. Yubari (Hokkaido, Japan), and Noccaea caerulescens ecotype Ganges, which originated in zinc/lead-mine soils in Southern France. Both Noccaea species showed extremely high Ni tolerance compared with that of the non-accumulator Arabidopsis thaliana. But, following treatment with 200 μM Ni, N. caerulescens showed leaf chlorosis, whereas N. japonica did not show any stress symptoms. Shoot Ni concentration was higher in N. caerulescens than in N. japonica; this difference was due to higher efficiency of root-to-shoot Ni translocation in N. caerulescens than N. japonica. It is known that the vacuole Ni transporter IREG2 suppresses Ni translocation from roots to shoots by sequestering Ni in the root vacuoles. The expression level of the IREG2 gene in the roots of N. japonica was 10-fold that in the roots of N. caerulescens. Moreover, the copy number of IREG2 per genome was higher in N. japonica than in N. caerulescens, suggesting that IREG2 expression is elevated by gene multiplication in N. japonica. The heterologous expression of IREG2 of N. japonica and N. caerulescens in yeast and A. thaliana confirmed that both IREG2 genes encode functional vacuole Ni transporters. Taking these results together, we hypothesize that the elevation of IREG2 expression by gene multiplication causes the lower root-to-shoot Ni translocation in N. japonica.


Thymopoiesis and regulatory T cells in healthy children and adolescents.
The purpose of this study was to investigate the association between T cell receptor excision circle levels in peripheral blood mononuclear cells and regulatory T cells that co-express CD25 and Foxp3 in healthy children and adolescents of different ages. The quantification of signal-joint T-cell receptor excision circle levels in the genomic DNA of peripheral blood mononuclear cells was performed using real-time quantitative PCR. The analysis of CD4, CD8, CD25, and Foxp3 expression was performed using flow cytometry. Ninety-five healthy controls (46 females and 49 males) ranging in age from 1 to 18 years were analyzed. The mean T-cell receptor excision circle count in all individuals was 89.095 ± 36.790 T-cell receptor excision circles per microgram of DNA. There was an inverse correlation between T-cell receptor excision circles counts and age (r = -0.846; p<0.001) as well as between the proportion of CD4(+)CD25(+)Foxp3(+) T cells and age (r = -0.467; p = 0.04). In addition, we observed a positive correlation between the amount of CD4(+)CD25(+)Foxp3(+) T cells and the amount of T-cell receptor excision circles per microgram of DNA in individuals of all ages (r = -0.529; p = 0.02). In this study, we observed a decrease in the thymic function with age based on the fact that the level of T-cell receptor excision circles in the peripheral blood positively correlated with the proportion of regulatory T cells in healthy children and adolescents. These findings indicate that although T-cell receptor excision circles and regulatory T cells levels decrease with age, homeostasis of the immune system and relative regulatory T cells population levels are maintained in the peripheral blood.


Pretreatment of Root Dentin Using Photon-Induced Photoacoustic Streaming, Photodynamic Therapy, and Riboflavin with EDTA as a Final Irrigant to Improve Bond Integrity of Glass Fiber Post.
Objective: To evaluate the outcome of post space disinfection using Er,Cr:YSGG laser (ECYL), riboflavin photosensitizer (RFP), and photon-induced photoacoustic streaming (PIPS) along with ethylene diamine tetra acetic acid (EDTA) as final irrigant on the bond values of glass fiber post (GFP) to the canal wall. Materials and methods: Forty human mandibular premolars were subjected to root canal treatment after decoronation till the cementoenamel junction. Post space was prepared using a Gates-Glidden drill leaving 4 mm of gutta perch at the apical third of the root section. Random allocation of samples was performed into four groups based on the post space disinfection (n = 10 each): Group 1: 1% RFP and 17% EDTA, group 2: 5.25% sodium hypochlorite (NaOCl) and 17% EDTA (control), group 3: PIPS and 17% EDTA, and group 4: ECYL and 17% EDTA. GFP was luted using Rely X Unicem. A universal testing machine and stereomicroscope were used to assess the push-out bond strength (PBS) and failure mode, respectively. Analysis of variance determined the PBS amid different experimental groups at three root levels. Multiple group comparison using means of tested groups was identified using post hoc Tukey. Results: The coronal third of group 2 (5.25% NaOCl +17% EDTA) demonstrated the highest PBS (8.83 ± 0.11 MPa). However, the lowest bond integrity (4.15 ± 0.52 MPa) was displayed in an apical third of group 1 (RFP +17% EDTA). The intergroup comparison revealed that 5.25% NaOCl +17% EDTA at all three levels demonstrated comparable outcomes of PBS with PIPS +17% EDTA and ECYL +17% EDTA specimens (p > 0.05). However, riboflavin +17% EDTA demonstrated the lowest bond strength (p < 0.05). Conclusions: Er,Cr: YSGG and PIPS in combination with 17% EDTA demonstrated comparable outcomes of bond score with those of conventional gold standard irrigation regime 5.25% NaOCl.


Substituent effects on the photophysical properties of pterin derivatives in acidic and alkaline aqueous solutions.
Pterins are heterocyclic compounds with important biological functions, and most of them may exist in two acid-base forms in the pH range between 3 and 13 in aqueous solution. In this work, the photophysical properties of acid and basic forms of six compounds of the pterin family (6-hydroxymethylpterin [HPT], 6-methylpterin [MPT], 6,7-dimethylpterin [DPT], rhamnopterin [RPT], N-methylfolic acid [MFA], and pteroic acid [PA]) have been studied. The effects of the chemical nature of the substituents at position 6 of the pterin moiety and the effects of the pH on the absorption and emission properties are analyzed. The fluorescence characteristics (spectra, quantum yields, lifetimes) of these compounds have been investigated using the single-photon-counting technique. Results obtained for pterin derivatives containing small substituents with 1 carbon atom (HPT, MPT, DPT) and short hydrocarbon chain (4 carbon atoms) (RPT) are different from those found for pterin derivatives containing a p-aminobenzoic acid (PABA) moiety in the substituent (MFA and PA). Fluorescence quantum yields (Phi(F)) of the first group of compounds are relatively high (>/=0.4), whereas MFA and PA exhibit very small Phi(F) values (</=0.01).


Cerebral and functional aging: first results on prevalence and incidence of the Paquid cohort.
Paquid is an interdisciplinary study designed to investigate cerebral and functional aging. A cohort of 3,777 community residents living in two administrative areas of South-Western France was selected. A standardized questionnaire was administered at home by trained psychologists. The same procedure was applied one and three years after the baseline data collection. The identification of demented subjects was made with a two-step procedure. The first step is a systematic screening by the psychologists using the DSM-III criteria for dementia. Subjects who fulfilled the DSM-III criteria were examined by a neurologist. Diagnosis of dementia is confirmed according to the NINCDS-ADRDA criteria. The Paquid cohort is complemented by a random sample of 357 institutionalized subjects. First results of prevalence and incidence rates show an exponential increase of dementia with age.


Genetic dissection of type 1 diabetes susceptibility gene, Idd3, by ancestral haplotype congenic mapping.
One of the strongest non-MHC susceptibility genes for type 1 diabetes, Idd3, has been mapped to a 0.15-cM segment of chromosome 3, where a strong candidate gene, Il2, encoding cytokine IL2, is located. To prove that the NOD allele of Il2 is responsible for the Idd3 effect, it is necessary to find a recombinant chromosome with the NOD allele of Il2, but with different flanking markers from NOD mice, and to demonstrate that NOD mouse strains that are congenic for the recombinant Il2 region develop type 1 diabetes with similar incidence and age at onset of the disease. As a first step in this approach, we searched for recombinant Il2 region in NOD-related strains derived from the same outbred colony, Jcl:ICR. The same Il2 allele as is found in the NOD mouse was found in four out of seven NOD-related strains, indicating that the NOD allele of Il2 is common in NOD-related strains. One of these strains, IIS, was found to have a recombinant Il2 region with the same Il2 allele as the NOD, but different alleles at flanking markers from the NOD mouse. A preliminary study on a NOD strain congenic for the Il2 region of IIS has shown that the Il2 region of IIS confers susceptibility to type 1 diabetes, suggesting that Il2 may be responsible for the Idd3 effect.


Is the interchromosomal effect present in embryos derived from Robertsonian and reciprocal translocation carriers particularly focusing on chromosome 10 rearrangements?
The aim of this study was to analyse the possible occurrence of the interchromosomal effect (ICE) in human preimplantation embryos obtained from Robertsonian and reciprocal translocation carriers focusing on ones with chromosome 10 rearrangements who were undergoing preimplantation genetic diagnosis (PGD) and to investigate whether offering aneuploidy screening would be beneficial to these patients. Cleavage stage embryos from translocation carriers undergoing PGD were biopsied. Multicolour fluorescence in situ hybridisation for the chromosomes involved in the translocation in addition to nine more chromosomes (13, 15, 16, 17, 18, 21, 22, X and Y) was used in the analysis. The control group involved embryos obtained from age-matched patients undergoing preimplantation genetic screening (PGS). Cumulative aneuploidy rate in embryos derived from both Robertsonian and reciprocal translocation carriers was found to be similar with the control group. Therefore no ICE was observed in cleavage stage embryos obtained from these carriers. More than half of the embryos with chromosome 10 rearrangements had aneuploidy for which an increased aneuploidy rate was more apparent in male carriers. Thus, it is possible that there is a risk of ICE in reciprocal carriers with chromosome 10 rearrangements. This study showed that there is no ICE in embryos derived from Robertsonian and reciprocal translocation carriers. However high rates of aneuploidy in structurally normal chromosomes were detected in embryos derived from these carriers and thus aneuploidy screening in addition to PGD may increase the pregnancy rates of these patients.


ABCG1 and ABCG4 are coexpressed in neurons and astrocytes of the CNS and regulate cholesterol homeostasis through SREBP-2.
Here, we describe the initial characterization of Abcg4(-/-) mice and identify overlapping functions of ABCG4 and ABCG1 in the brain. Histological examination of tissues from Abcg4(+/-)/nlsLacZ and Abcg1(+/-)/nlsLacZ mice demonstrates that coexpression of Abcg4 and Abcg1 is restricted to neurons and astrocytes of the central nervous system (CNS). Interestingly, Abcg4 mRNA is undetectable outside the CNS, in contrast with the broad tissue and cellular expression of Abcg1. We also used primary astrocytes, microglia, neurons, and macrophages to demonstrate that the expression of Abcg1, but not Abcg4, is induced after the activation of liver X receptor. Cellular localization studies demonstrated that both proteins reside in RhoB-positive endocytic vesicle membranes. Furthermore, overexpression of either ABCG1 or ABCG4 increased the processing of sterol-regulatory element binding protein 2 (SREBP-2) to the transcriptionally active protein, thus accounting for the observed increase in the expression of SREBP-2 target genes and cholesterol synthesis. Consistent with these latter results, we show that the expression levels of the same SREBP-2 target genes are repressed in the brains of Abcg1(-/-) and, to a lesser extent, Abcg4(-/-) mice. Based on the results of the current study, we propose that ABCG1 and ABCG4 mediate the intracellular vesicular transport of cholesterol/sterols within both neurons and astrocytes to regulate cholesterol transport in the brain.


Van der Waals density functional for layered structures.
To understand sparse systems, we must account for both strong local atom bonds and weak nonlocal van der Waals forces between atoms separated by empty space. A fully nonlocal functional form [Phys. Rev. B 62, 6997 (2000)]] of density-functional theory (DFT) is applied here to the layered systems graphite, boron nitride, and molybdenum sulfide to compute bond lengths, binding energies, and compressibilities. These key examples show that the DFT with the generalized-gradient approximation does not apply for calculating properties of sparse matter, while use of the fully nonlocal version appears to be one way to proceed.


Non-native heme-histidine ligation promotes microsecond time scale secondary structure formation in reduced horse heart cytochrome c.
Previous far-UV time-resolved optical rotatory dispersion (TRORD) studies of the sub-millisecond (burst) phase of secondary structure formation in horse and tuna cytochromes c after photoreduction in denaturant suggested that the non-native His18-Fe-His33 heme ligation dominant in the unfolded horse protein facilitated this fast folding better than did the His18-Fe-His26 coordination dominant in tuna [Chen, E., Goldbeck, R.A., and Kliger, D.S. (2003) J. Phys. Chem. A 107, 8149-8155; Chen, E., Goldbeck, R.A., and Kliger, D.S. (2004) J. Am. Chem. Soc. 126, 11175-11181]. Whether His18-Fe-His33 coordination actually facilitates fast secondary structure formation or just slows folding less than His18-Fe-His26 coordination is probed by examining the double histidine mutant H26QH33N of horse heart cytochrome c. The fast folding phase is absent in H26QH33N, indicating that His18-Fe-His33 misligation does promote fast secondary structure formation, as does His18-Fe-His26 to a lesser extent. His33 may be better able to facilitate folding because it is not as constrained by hydrogen bonding interactions in the denatured state as is His26. A greater flexibility, not only because of weakened or disrupted Van der Waals interactions in the presence of guanidine hydrochloride (GuHCl) but also because of its position relative to His18, may allow His33 to ligate to the heme group more easily than His26. These results are discussed along with the results of far-UV CD and Soret and visible region MCD measurements, which were performed to probe heme ligation in H26QH33N and to understand how GuHCl affects its folding stability and cooperativity.


Fertility preservation during cancer treatment: The Korean Society for Fertility Preservation clinical guidelines.
While many fertility preservation (FP) options now exist for reproductive-aged cancer patients, access to these services continues to be limited. A comprehensive FP program should be organized to serve oncofertility patients effectively. Also, much effort is needed from various individuals-patients, specialists from various fields, and consultants-to facilitate FP in a timely manner. Various challenges still exist in improving access to FP programs. To improve access to FP treatment, it is important to educate oncologists and patients via electronic tools and to actively navigate patients through the system. Reproductive endocrinology practices that receive oncofertility referrals must be equipped to provide a full range of options on short notice. A multidisciplinary team approach is required, involving physicians, nurses, mental health professionals, office staff, and laboratory personnel. The bottom line of FP patient care is to understand the true nature of each patient's specific situation and to develop a patient flow system that will help build a successful FP program. Expanding the patient flow system to all comprehensive cancer centers will ensure that all patients are provided with adequate information regarding their fertility, regardless of geography.


8-Nitro-quinoline.
The molecule of the title compound, C(9)H(6)N(2)O(2), is almost planar, with a dihedral angle of 3.0 (9)° between the pyridine and benzene rings.


Nurses' Experiences of Caring for Patients with Different Cultures in Mashhad, Iran.
Mashhad is a center of diverse cultures, where many local and foreign cultures live together in its context. One of the main needs of a society with cultural diversity is transcultural care of patients. Hence, the present study took the first step for care of culturally diversified and minority patients in Mashhad. This research has been conducted to explore the nurses' experience of caring from patients with different cultures. This study is a qualitative research using phenomenological hermeneutics approach. The participations include nurses who have been working 5 or less than 5 years in the hospitals affiliated to Medical University of Mashhad. They were selected using purposeful sampling method. For data collection, semi-structured, in-depth interview was used. For data analysis, interpretation method was used. The interviews continued until saturation of data was obtained. Data analysis resulted in extraction of 4 themes including ethnocentrism, contradicting perceptions of care, it is not our fault, and lack of cultural knowledge. The experience of nurses in taking care of patients with other cultures showed that minorities and small cultures have been neglected in Mashhad and hospitalization of such people in hospitals and other clinics is not specific. We recommend that an educational curriculum about transcultural care should be added to nursing courses. Also, necessary equipment and facilities should be considered and prepared for culturally different patients in hospitals.


Understanding grapevine-microbiome interactions: implications for viticulture industry.
Until recently, the analysis of complex communities such as that of the grapevine-microbe holobiont has been limited by the fact that most microbes are not culturable under laboratory conditions (less than 1%). However, metagenomics, the study of the genetic material recovered directly from environmental samples without the need for enrichment or of culturing, has led to open an unprecedented era in the field of microbiology. Importantly, this technological advance has now become so pervasive that it is being regularly applied to explore soils and plants of agricultural interest. Interestingly, many large companies are taking notice, with significant financial investment being used to exploring ways to manipulate the productivity, disease resistance and stress tolerance for crops by influencing the microbiome. To understand which microbes one needs to manipulate to influence this valuable characteristics, we need to sequence the microbiome and capture the genetic and hence functional metabolic information contained therein. For viticulture and other agricultural fields where the crop is also associated to particular flavor properties that may also be manipulated, understanding how the bacteria, fungi and viruses influence the development and hence chemical makeup of the crop is essential.


Gastric cancer management: Kinases as a target therapy.
The molecular diagnostics revolution has reshaped the practice of oncology by facilitating the identification of genetic, epigenetic and proteomic modifications correlated with cancer, thus delineating 'oncomaps' for various cancer types. These advances have enhanced our understanding of gastric cancer, one of the most fatal diseases worldwide, and culminated in the approval of novel molecular therapies such as trastuzumab. Gastric tumours display recurrent aberrations in key kinase oncogenes such as Her2, epidermal growth factor receptor (EGFR), PI3K, mTOR or c-Met, suggesting that these receptors are amenable to inhibition using specific drug agents. In this review, we examine the mutational landscape of gastric cancer, the use of kinase inhibitors as targeted therapies in gastric tumours and the clinical trials underway for novel inhibitors, highlighting successes, failures and future directions.


A hazard-based approach to modelling the effects of online shopping on intershopping duration.
Despite growing prevalence of online shopping, its impacts on mobility are poorly understood. This partially results from the lack of sufficiently detailed data. In this paper we address this gap using consumer panel data, a new dataset for this context. We analyse one year long longitudinal grocery shopping purchase data from London shoppers to investigate the effects of online shopping on overall shopping activity patterns and personal trips. We characterise the temporal structure of shopping demand by means of the duration between shopping episodes using hazard-based duration models. These models have been used to study inter-shopping spells for traditional shopping in the literature, however effects of online shopping were not considered. Here, we differentiate between shopping events and shopping trips. The former refers to all types of shopping activity including both online and in-store, while the latter is restricted to physical shopping trips. Separate models were estimated for each and results suggest potential substitution effects between online and in-store in the context of grocery shopping. We find that having shopped online since the last shopping trip significantly reduces the likelihood of a physical shopping trip. We do not observe the same effect for inter-event durations. Hence, shopping online does not have a significant effect on overall shopping activity frequency, yet affects shopping trip rates. This is a key finding and suggests potential substitution between online shopping and physical trips to the store. Additional insights on which factors, including basket size and demographics, affect inter-shopping durations are also drawn.


IGF/IGFBP axis in cartilage and bone in osteoarthritis pathogenesis.
In the context of joint biology, insulin-like growth factor-1 (IGF-1) is the most likely candidate to affect the anabolism of cartilage matrix molecules. Mechanisms for controlling the effects of IGF-1 include alterations in the level of this growth factor, its receptor and/or the IGF-1 affinity or availability to its receptor. Disturbance of any one of the above elements may induce a disregulation of the mechanisms involved in the local control of joint tissue integrity. This review focuses on recent studies of the IGF system, and the potential relevance of these results to in vivo effects in osteoarthritic (OA) tissues. It has been shown that, although the IGF-1's expression and synthesis are increased in OA cartilage, chondrocytes are hyporesponsive to IGF-1 stimulation. This phenomenon appears to be related, at least in part, to an increased level of IGF-binding proteins (IGFBP). The IGFBP have a high affinity for IGF-1, and appear to be important biomodulators for IGF action. Though to date seven IGFBP have been cloned and sequenced, disregulation in IGFBP-3 and -4 appears instrumental to arthritic disorders. Proteolytic activity directed against IGFBP has been found in both cartilage and bone; this activity appears to belong to serine- and/or metallo-proteases families. It has been suggested that a thickening of the subchondral bone participates in OA pathophysiology, and that IGF-1 production by bone and/or subchondral bone cells may contribute to these changes. An abnormal regulation of subchondral bone formation via an increase in the local activation of IGF-1 in bone cells, possibly via abnormal IGFBP synthesis due to aberrant PA/plasmin regulation of the IGF-I/IGFBP system, is believed to be a plausible hypothesis.


Provider Health and Wellness.
Provider health and wellness is a significant issue and can impact patient care, including patient satisfaction, quality of care, medical errors, malpractice risk, as well as provider and office staff turnover and early retirement. Health and wellness encompasses various areas including burnout, depression, divorce, and suicide and affects providers of all specialties and at all levels of training. Providers deal with many everyday stresses, including electronic health records, office politics, insurance and billing issues, dissatisfied patients, and their own personal and family issues. Approximately half of all physicians suffer from burnout, and the rate of burnout among physicians of all specialties is increasing. An important first step in dealing with burnout is recognition and then seeking assistance. Strategies to prevent and treat burnout include increasing provider resiliency as well as implementing practical changes in the everyday practice of medicine. There is currently very little data regarding health and wellness specifically in the field of allergy and immunology, and studies are necessary to determine the prevalence of burnout and related issues in this field. Many medical specialties as well as state and national medical associations have health and wellness committees and other resources, which are essential for providers. Health and wellness programs should be introduced early in a provider's training and continued throughout a provider's career.


Corneal staining patterns in vernal keratoconjunctivitis: the new VKC-CLEK scoring scale.
To propose a new scoring system in the assessment of ocular surface epithelial damage in vernal keratoconjunctivitis (VKC). 25 consecutive patients with VKC (50 eyes) were evaluated using the Quality of Life in children with VKC (QUICK) questionnaire and objective clinical measures: fluorescein and lissamine green staining and cornea confocal microscopy (Heidelberg Retina Tomography 3). Oxford, Van Bljsterweld and a new system, the VKC-Collaborative Longitudinal Evaluation of Keratoconus study (CLEK) (VKC-CLEK) scores, were used to evaluate the epithelial damage after staining. Mean Oxford and VKC-CLEK scores were significantly different after fluorescein staining (P<0.001), but significantly correlated (P<0.001; r=0.649). The same data were obtained comparing Van Bljsterweld and VKC-CLEK after lissamine green staining (P<0.001; r=0.760). In patient with limbal VKC, a statistically significant difference was found comparing new VKC-CLEK scores and Oxford or Van Bljsterweld scores (P<0.001), but not in tarsal VKC. A statistically superior concordance was found between QUICK and VKC-CLEK scores compared with standard staining scores values (P<0.001). Oxford and Van Bijsterveld scores are not adequate for the evaluation of the epithelial damage in patients with limbal VKC because the staining patterns considered for these tests do not correspond to the staining patterns in patients with VKC. We propose a new scoring system, VKC-CLEK, to better evaluate both limbal and tarsal epithelial damage in patients with VKC.


Hearing From You: Design Thinking in Audiological Research.
The purpose of this article is to describe the emerging use of design thinking methodologies in hearing health care research using a participatory action approach with a consumer and community involvement panel, audiologists, and adults with hearing loss. Two connected hearing health care projects that adopted design thinking principles are presented here as case studies. Case 1 investigated the applicability and acceptability of smart voice assistant technology as post-hearing aid fitting support. Case 2 investigated the feasibility of providing support for new adult patients with hearing loss before they attend their hearing assessment appointment. The design thinking process provided a flexible structure in which researchers were able to empathize with stakeholders, define their unmet needs, and ideate potential connected hearing health care solutions to develop and evaluate prototypes in clinical and home settings. Utilizing a needs-based, collaborative design thinking approach to conduct development in hearing health care research is a viable and novel option to produce innovative, relevant, and translational hearing health solutions that address stakeholder needs.


Supratentorial cavernous malformations adjacent to the corticospinal tract: surgical outcomes and predictive value of diffusion tensor imaging findings.
OBJECTIVE Diffusion tensor imaging (DTI) findings may facilitate clinical decision making in patients with supratentorial cavernous malformations adjacent to the corticospinal tract (CST-CMs). The objective of this study was to determine the predictive value of preoperative DTI findings for surgical outcomes in patients with CST-CMs. METHODS A prospectively maintained database of patients with CM referred to the authors' hospital between September 2012 and October 2015 was reviewed to identify all consecutive surgically treated patients with CST-CM. All patients had undergone sagittal T1-weighted anatomical imaging and DTI before surgery. Both DTI findings and clinical characteristics of the patients and lesions were analyzed with respect to surgery-related motor deficits. DTI findings included lesion-to-CST distance (LCD) and the alteration (i.e., deviation, interruption, or degeneration due to the CM) of CST on preoperative DTI images. Surgery-related motor deficits at 1 week and the last clinic visit (≥ 3 months) after surgery were defined as short-term and long-term deficits, respectively. Preoperative and final modified Rankin Scale scores were also analyzed to identify the surgical outcomes in these patients. RESULTS A total of 56 patients with 56 CST-CMs were included in this study. The mean LCD was 3.9 ± 3.2 mm, and alterations of the CST were detected in 20 (36.7%) patients. One week after surgery, 21 (37.5%) patients had short-term surgery-related motor deficits, but only 14 (25.0%) patients had long term deficits at the last clinical visit. The mean patient follow-up was 14.7 ± 10.1 months. The difference between preoperative and final modified Rankin Scale scores was not statistically significant (p = 0.490). Multivariate analysis showed that both short-term (p < 0.001) and long-term (p = 0.002) surgery-related motor deficits were significantly associated with LCD. Receiver operating characteristic (ROC) curve results were as follows: for short-term surgery-related motor deficits, the area under the ROC curve (AUC) was 0.860, and the cutoff point was LCD = 2.55 mm; for long-term deficits, the AUC was 0.894, and the cutoff point was LCD = 2.30 mm. Both univariate (p = 0.012) and multivariate (p = 0.049) analyses revealed that CST alteration on preoperative DTI was significantly correlated with short-term surgery-related motor deficits. On univariate analysis, deep location of the CST-CMs was significantly correlated with long-term motor deficits (p = 0.016). Deep location of the CST-CMs had a trend toward significance with long-term motor deficits on the multivariate analysis (p = 0.060). CONCLUSIONS To facilitate clinical practice, the authors propose that 3.00 mm (2.55 to ∼3.00 mm) may be the safe LCD for surgery in patients with CST-CMs. A CST alteration on preoperative DTI and a deep location of the CST-CM may be risk factors for short- and long-term surgery-related motor deficits, respectively. A randomized controlled trial is needed to demonstrate the predictive value of preoperative DTI findings on surgical outcomes in patients with CST-CMs in future studies.


Cramped synchronized general movements in preterm infants as an early marker for cerebral palsy.
To ascertain whether specific abnormalities (ie, cramped synchronized general movements [GMs]) can predict cerebral palsy and the severity of later motor impairment in preterm infants affected by brain lesions. Traditional neurological examination was performed, and GMs were serially videotaped and blindly observed for 84 preterm infants with ultrasound abnormalities from birth until 56 to 60 weeks' postmenstrual age. The developmental course of GM abnormalities was compared with brain ultrasound findings alone and with findings from neurological examination, in relation to the patient's outcome at age 2 to 3 years. Infants with consistent or predominant (33 cases) cramped synchronized GMs developed cerebral palsy. The earlier cramped synchronized GMs were observed, the worse was the neurological outcome. Transient cramped synchronized character GMs (8 cases) were followed by mild cerebral palsy (fidgety movements were absent) or normal development (fidgety movements were present). Consistently normal GMs (13 cases) and poor repertoire GMs (30 cases) either lead to normal outcomes (84%) or cerebral palsy with mild motor impairment (16%). Observation of GMs was 100% sensitive, and the specificity of the cramped synchronized GMs was 92.5% to 100% throughout the age range, which is much higher than the specificity of neurological examination. Consistent and predominant cramped synchronized GMs specifically predict cerebral palsy. The earlier this characteristic appears, the worse is the later impairment.


Reductive biotransformation by wild type and mutant strains of Saccharomyces cerevisiae in aqueous-organic solvent biphasic systems.
Whole cells of Saccharomyces cerevisiae analyzed the conversion of benzaldehyde to benzyl alcohol in aqueous-organic biphasic media. Reaction rate increased dramatically as moisture content of the solvent was increased in the range 0% to 2%. The highest biotransformation rates were observed when hexane was used as organic solvent. Benzaldehyde was also converted to benzyl alcohol by a cell-free crude extract in biphasic systems containing hexane, although the rate of product formation was much lower. Mutant strains of S. cerevisiae lacking some or all of the ADH isoenzymes, ADH I, II, and III, manifested similar rates for bioconversion of benzaldehyde to benzyl alcohol in both aqueous and two-phase systems. In general, conversion rates observed in aqueous media were 2 to 3 times higher than those observed in hexane containing 2% moisture.


Energetic costs of cellular and therapeutic control of stochastic mitochondrial DNA populations.
The dynamics of the cellular proportion of mutant mtDNA molecules is crucial for mitochondrial diseases. Cellular populations of mitochondria are under homeostatic control, but the details of the control mechanisms involved remain elusive. Here, we use stochastic modelling to derive general results for the impact of cellular control on mtDNA populations, the cost to the cell of different mtDNA states, and the optimisation of therapeutic control of mtDNA populations. This formalism yields a wealth of biological results, including that an increasing mtDNA variance can increase the energetic cost of maintaining a tissue, that intermediate levels of heteroplasmy can be more detrimental than homoplasmy even for a dysfunctional mutant, that heteroplasmy distribution (not mean alone) is crucial for the success of gene therapies, and that long-term rather than short intense gene therapies are more likely to beneficially impact mtDNA populations.


The role of alpha1- and beta-adrenoceptors in initiation and development of thermoregulatory reactions during fast and slow cooling.
Ionophoretic application of alpha1- and beta-adrenoceptor blockers into the skin produces no effect on the parameters of thermal homeostasis under thermoneutral conditions. alpha1-Adrenoblocker verapamil inhibits cold shivering during fast and slow cold exposure; it elevates the temperature threshold and moderates the vasoconstrictor response during rapid cooling. These changes are accompanied by a compensatory decrease in the threshold and stimulation of non-shivering thermogenesis. Application of non-selective beta-blocker propranolol had no effect on the temperature thresholds of the thermoregulatory reactions, but augmented the maximum amplitude of shivering during both cooling protocols, thereby compensating the decrease in non-shivering thermogenesis. In the whole organism, block of one type adrenoceptors during cold exposure is accompanied by activation of the compensatory mechanisms mediated by adrenoceptors of the other type.