A novel mitochondrial G8313A mutation associated with prominent initial gastrointestinal symptoms and progressive encephaloneuropathy.
We describe a childhood mitochondrial disorder in which the clinical symptoms began and remained confined to the gastrointestinal (GI) system during the first 4 y. Seizures heralded the onset of progressive encephalopathy at age 7. Peripheral neuropathy, retinitis pigmentosa, and neural deafness developed subsequently. Laboratory investigations disclosed elevated levels of plasma lactate, and a muscle biopsy revealed ragged red fibers lacking cytochrome c oxidase activity and diminished levels of respiratory chain enzyme complexes. Molecular genetic tests failed to show any of the previously reported pathogenic mitochondrial DNA (mtDNA) mutations. We therefore screened the whole mitochondrial genome by coupling restriction digestions with single-strand conformational polymorphism (SSCP) patterns. We identified a unique SSCP in the segment that encompassed the tRNA(Lys) gene, and direct sequencing of this segment revealed a G-->A transition at an evolutionarily conserved nucleotide at mtDNA position 8313. This G8313A transition was heteroplasmic in muscle and fibroblasts of the patient, but was absent in the white blood cells and platelets from his maternal relatives. This report illustrates how GI symptoms can be the initial manifestation in a mitochondrial disorder and suggests that mitochondrial dysfunction should be considered in differentials of unexplained chronic GI symptoms, especially when lactic acidosis or other unrelated clinical signs or symptoms are present.


[Effect of normobaric hypoxia and physical load on the functional indices of cardiorespiratory system in overweight people].
Changes in the cardiorespiratory function in obese persons exposed to different combinations of normobaric hypoxia and physical exercise were studied. The results show a positive effect of combined use of normobaric hypoxic exercise on functional reserves of cardiorespiratory system, physical performance and aerobic potentialities in obese patients. The highest effect is achieved in combination of physical exercise with hypoxic gas mixtures breathing.


Alteration in Melanin Content in Retinal Pigment Epithelial Cells upon Hydroquinone Exposure.
Abnormal pigmentation or depigmentation of the retinal pigment epithelium (RPE) is a precursor to neovascular age-related macular degeneration (nAMD). In this study, we evaluated the effects of hydroquinone (HQ), the most potent reductant in cigarette smoke, on the melanin production in RPE cells. Induced pluripotent stem cell (iPS)-derived RPE and adult retinal pigment epithelial (ARPE-19) cells were cultured with HQ. Real-time reverse transcription polymerase chain reaction revealed that the expression of melanin-related genes decreased due to the addition of HQ for 1 day. Enzyme-linked immunosorbent immunoassay showed that the concentration of melanin significantly decreased due to the addition of HQ for 24 h. A suspension of RPE cells with HQ for 24 h was prepared, and the absorbance was measured. The absorbance decreased particularly under blue light, suggesting that blue light may reach the choroid and cause choroidal inflammation. Additionally, melanin levels significantly decreased due to the addition of HQ for 1 week. After blue light irradiation on the RPE with HQ for 1 week, the vascular endothelial growth factor in the medium was significantly higher in the HQ group than in the control group. HQ-induced changes in melanin production may be responsible for the uneven pigmentation of the RPE, and these changes may cause nAMD.


Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease.
CREB-binding protein and p300 function as transcriptional coactivators in the regulation of gene expression through various signal-transduction pathways. Both are potent histone acetyl transferases. A certain level of CREB-binding protein is essential for normal development, since inactivation of one allele causes Rubinstein-Taybi syndrome (RSTS). There is a direct link between loss of acetyl transferase activity and RSTS, which indicates that the disorder is caused by aberrant chromatin regulation. We screened the entire CREB-binding protein gene (CBP) for mutations in patients with RSTS by using methods that find point mutations and larger rearrangements. In 92 patients, we were able to identify a total of 36 mutations in CBP. By using multiple ligation-dependent probe amplification, we found not only several deletions but also the first reported intragenic duplication in a patient with RSTS. We extended the search for mutations to the EP300 gene and showed that mutations in EP300 also cause this disorder. These are the first mutations identified in EP300 for a congenital disorder.


Self-fluorescent antibiotic MoOx-hydroxyapatite: a nano-theranostic platform for bone infection therapies.
Nowadays, the repair of large-size bone defects represents a huge medical challenge. A line of attack is the construction of advanced biomaterials having multifunctional properties. In this work, we show the creation of biocompatible MoOx-hydroxyapatite nanoparticles (nano-HA/MoOx) that simultaneously exhibit self-activated fluorescence and antibiotic skills. Along this text, we demonstrate that the insertion of molybdenum, an essential trace element, into the non-stoichiometric calcium deficient hydroxyapatite lattice generates intrinsic electronic point defects that exacerbate its epifluorescence blue emission and provokes new red emissions, preserving, always, its bioactivity. Furthermore, these point defects, acting as electron acceptors, stimulate the materials' biological redox status and promote the death of pathogen microorganisms after their direct contact. A putative mechanism, by which bacteria lose electrons from their metabolic circuit that alter the function of their cytoplasmic membrane and potentially die, agrees with our results. Our findings highlight the importance of tuning the electronic communications between biomaterial interfaces and biological units, and support the use of self-fluorescent MoOx-hydroxyapatite nanoparticles as fundamental building blocks for new real-time imaging platforms against bone infection.


MATI: An efficient algorithm for influence maximization in social networks.
Influence maximization has attracted a lot of attention due to its numerous applications, including diffusion of social movements, the spread of news, viral marketing and outbreak of diseases. The objective is to discover a group of users that are able to maximize the spread of influence across a network. The greedy algorithm gives a solution to the Influence Maximization problem while having a good approximation ratio. Nevertheless it does not scale well for large scale datasets. In this paper, we propose Matrix Influence, MATI, an efficient algorithm that can be used under both the Linear Threshold and Independent Cascade diffusion models. MATI is based on the precalculation of the influence by taking advantage of the simple paths in the node's neighborhood. An extensive empirical analysis has been performed on multiple real-world datasets showing that MATI has competitive performance when compared to other well-known algorithms with regards to running time and expected influence spread.


Impact of targeted PPARγ disruption on bone remodeling.
Peroxisome proliferator-activated receptor gamma (PPARγ), known as the master regulator of adipogenesis, has been regarded as a promising target for new anti-osteoporosis therapy due to its role in regulating bone marrow mesenchymal stem/progenitor cell (BMSC) lineage commitment. However, the precise mechanism underlying PPARγ regulation of bone is not clear as a bone-specific PPARγ conditional knockout (cKO) study has not been conducted and evidence showed that deletion of PPARγ in other tissues also have profound effect on bone. In this study, we show that mice deficiency of PPARγ in cells expressing a 3.6 kb type I collagen promoter fragment (PPAR(fl/fl):Col3.6-Cre) exhibits a moderate, site-dependent bone mass phenotype. In vitro studies showed that adipogenesis is abolished completely and osteoblastogenesis increased significantly in both primary bone marrow culture and the BMSCs isolated from PPARγ cKO mice. Histology and histomorphometry studies revealed significant increases in the numbers of osteoblasts and surface in the PPARγ cKO mice. Finally, we found that neither the differentiation nor the function of osteoclasts was affected in the PPARγ cKO mice. Together, our studies indicate that PPARγ plays an important role in bone remodeling by increasing the abundance of osteoblasts for repair, but not during skeletal development.


The etiology of treatment-related lymphopenia in patients with malignant gliomas: modeling radiation dose to circulating lymphocytes explains clinical observations and suggests methods of modifying the impact of radiation on immune cells.
Severe treatment-related lymphopenia (TRL) occurs in 40% of patients with high grade gliomas (HGG) receiving glucocorticoids, temozolomide, and radiation. This occurs following radiation, persists for months, and is associated with reduced survival. As all three treatment modalities are lymphotoxic, this study was conducted to estimate the radiation dose that lymphocytes receive passing through the radiation field and if this could explain the observed TRL. A typical glioblastoma plan (8-cm tumor, 60 Gy/30 fractions) was constructed using the Pinnacle™ radiation planning system. Radiation doses to circulating cells (DCC) were analyzed using MatLab™. The primary endpoints were mean DCC and percent of circulating cells receiving ≥0.5 Gy. The model was also used to study how changes in target volumes (PTV), dose rates, and delivery techniques affect DCC. The modeling determined that while a single radiation fraction delivered 0.5 Gy to 5% of circulating cells, after 30 fractions 99% of circulating blood had received ≥0.5 Gy. The mean DCC was 2.2 Gy and was similar for IMRT, 3D-conformal techniques, and different dose rates. Major changes in PTV size affected mean DCC and percent of circulating cells receiving ≥0.5 Gy. Standard treatment plans for brain tumors deliver potentially lymphotoxic radiation doses to the entire circulating blood pool. Altering dose rates or delivery techniques are unlikely to significantly affect DCC by the end of treatment. Novel approaches are needed to limit radiation to circulating lymphocytes given the association of lymphopenia with poorer survival in patients with HGG.


Histochemical fiber composition of lumbar back muscles in the rabbit.
The present study of the back muscles of the rabbit, using enzyme histochemical techniques and stereological methods, was undertaken with the view to gaining a better understanding of the fiber-type make-up of the lumbar musculature of this animal. The muscles considered were the multifidus, sacrospinalis and the intertransversarii between levels L5 and L6. Gross examination reveals that the multifidus and the sacrospinalis form the bulk of the lumbar musculature and that these muscles appear white. Between and deep to these two muscles are the red intertransversarii. Histochemically the multifidus and the sacrospinalis are also similar in their fiber-type composition, mostly types IIA and IIB and the percentage of connective tissue that they contain. The intertransversarii, in contrast, are for all practical purposes composed of only type-I fibers. The intertransversarii contain significantly more connective tissue than the other two muscles. It may be concluded that the bulk of the lumbar musculature of the rabbit is phasic while the intertransversarii, containing only type-I fibers and a high percentage of connective tissue, are postural muscles.


Molecular mechanisms of chromium in alleviating insulin resistance.
Type 2 diabetes is often associated with obesity, dyslipidemia and cardiovascular anomalies and is a major health problem approaching global epidemic proportions. Insulin resistance, a prediabetic condition, precedes the onset of frank type 2 diabetes and offers potential avenues for early intervention to treat the disease. Although lifestyle modifications and exercise can reduce the incidence of diabetes, compliance has proved to be difficult, warranting pharmacological interventions. However, most of the currently available drugs that improve insulin sensitivity have adverse effects. Therefore, attractive strategies to alleviate insulin resistance include dietary supplements. One such supplement is chromium, which has been shown to reduce insulin resistance in some, but not all, studies. Furthermore, the molecular mechanisms of chromium in alleviating insulin resistance remain elusive. This review examines emerging reports on the effect of chromium, as well as molecular and cellular mechanisms by which chromium may provide beneficial effects in alleviating insulin resistance.


LIMD2 is the Signature of Cell Aging-immune/inflammation in Acute Myocardial Infarction.
Acute myocardial infarction (AMI) is an age-dependent cardiovascular disease in which cell aging, immunity, and inflammatory factors alter the course; however, cell aging-immune/inflammation signatures in AMI have not been investigated. Based on the GEO database to obtain microRNA (miRNA) sequencing, mRNA sequencing and single-cell sequencing data, and utilizing the Seurat package to identify AMI-associated cellular subpopulations. Subsequently, differentially expressed miRNAs and mRNAs were screened to establish a network of competing endogenous RNAs (ceRNAs). Senescence and immunity scores were calculated by single sample gene set enrichment analysis (ssGSEA), ESTIMATE and CIBERSORT algorithms, and the Hmisc package was used to screen for genes with the highest correlation with senescence and immunity scores. Finally, protein-protein interaction (PPI) and molecular docking analyses were performed to predict potential therapeutic agents for the treatment of AMI. Four cell types (Macrophage, Fibroblast, Endothelial cells, CD8 T cells) were identified in AMI, and CD8 T cells exhibited the lowest cell aging activity. A ceRNA network of miRNAs-mNRA interactions was established based on the overlapping genes in differentially expressed miRNAs (DEmiRNAs) target genes and differentially expressed mRNAs (DEmRNAs). Twenty-four marker genes of CD8 T cells were observed. LIMD2 was identified as cell aging-immune/inflammation-related hub gene in AMI. This study also identified a potential therapeutic network of DB03276-LIMD2-AMI, which showed excellent and stable binding status between DB03276-LIMD2. This study identified LIMD2 as a cell aging-immune/inflammation-related hub gene. The understanding of the pathogenesis and therapeutic mechanisms of AMI was enriched by the ceRNA network and DB03276-LIMD2-LAMI therapeutic network.


Characterization of the UVA protection provided by avobenzone, zinc oxide, and titanium dioxide in broad-spectrum sunscreen products.
Solar UV radiation (UVR) is composed of UVB (290-320 nm) and UVA (320-400 nm) wavelengths. Only two sunscreen active ingredients approved in the US, avobenzone (butylmethoxydibenzoylmethane) and zinc oxide (ZnO), provide true broad-spectrum protection against UVA wavelengths >360 nm. Although effective against shorter UVR wavelengths <360 nm, titanium dioxide (TiO(2)) is also often believed to confer broad-spectrum protection and is substituted for ZnO or avobenzone. To sustain its absorption capacity within a sunscreen film during UVR exposure, avobenzone needs to be formulated into sunscreen products using sound formulation strategies. To characterize the efficacy of avobenzone, ZnO, and TiO(2) in terms of their abilities to provide broad UVA protection and to demonstrate the effectiveness of the different formulation strategies used today to maintain the efficacy of avobenzone even during prolonged exposures to UVR. UVA efficacy was assessed by measuring absorbance profiles in vitro using Vitro Skin® (IMS Inc., Orange, CT, USA) as an inert substrate and by determining UVA protection factors (PFA) on human skin. The impact of avobenzone loss on sun protection factor (SPF) and PFA values was evaluated by serially reducing avobenzone concentrations in an otherwise photostable product. The photostabilizing influence of specific formulation ingredients was monitored by measuring the extent to which they prevented UVR-induced degradation of avobenzone, whereas photostability of commercial sunscreen products was quantified by measuring the percentage change in absorbance within the UVB and UVA spectral regions following irradiation of thin product films on inert substrates. Model formulations containing 3% avobenzone or 5% ZnO provided superior attenuation of UVA wavelengths >360 nm compared with formulas containing 5% TiO(2). Additionally, sunscreen products of similar SPF containing avobenzone or ZnO exhibited significantly higher PFA values than those containing TiO(2). The addition of photostabilized avobenzone or ZnO increased PFA values nearly 3-fold, whereas the addition of TiO(2) increased PFA values only modestly. Judicious selection of sunscreen actives alone or in combination with extra stabilizing agents maintained the photostability of avobenzone in formulations to deliver sustained broad-spectrum absorbance during 4 hours of exposure to UVR. Small losses (<20%) of avobenzone did not significantly reduce a product's protective effects as measured by SPF and PFA values on human skin. TiO(2) provided neither the same level of UVA attenuation nor the same degree of UVA protection on human skin as did products containing photostabilized avobenzone or ZnO. Hence, TiO(2) cannot be considered a substitute for avobenzone or ZnO in providing high levels of UVA protection to human skin. Use of proper formulation strategies can ensure that avobenzone losses are minimized to the extent that they have no impact on a product's ability to deliver sustained protection, even over periods of prolonged exposure to UVR.


The Cultural Relevance of Mindfulness Meditation as a Health Intervention for African Americans: Implications for Reducing Stress-Related Health Disparities.
African Americans experience a disproportionate rate of stress-related health conditions compared to European Americans. Mindfulness meditation has been shown to be effective for managing stress and various stress-related health conditions. This study explored the cultural relevance of mindfulness meditation training for African Americans adults. Fifteen African American adults with past or current experience with mindfulness meditation training were interviewed. Participants felt that mindfulness meditation helped them with enhanced stress management, direct health improvement, and enhanced self-awareness and purposefulness. They felt that they would recommend it and that other African Americans would be open to the practice but suggested that its presentation may need to be adapted. They suggested emphasizing the health benefits, connecting it to familiar spiritual ideology and cultural practices, supplementing the reading material with African American writers, increasing communication (education, instructor availability, "buddy system," etc.), and including African Americans as instructors and participants. By implementing minor adaptations that enhance cultural relevance, mindfulness meditation can be a beneficial therapeutic intervention for this population.


An improved phase shift reconstruction algorithm of fringe scanning technique for X-ray microscopy.
The X-ray phase imaging method has been applied to observe soft biological tissues, and it is possible to image the soft tissues by using the benefit of the so-called "Talbot effect" by an X-ray grating. One type of the X-ray phase imaging method was reported by combining an X-ray imaging microscope equipped by a Fresnel zone plate with a phase grating. Using the fringe scanning technique, a high-precision phase shift image could be obtained by displacing the grating step by step and measuring dozens of sample images. The number of the images was selected to reduce the error caused by the non-sinusoidal component of the Talbot self-image at the imaging plane. A larger number suppressed the error more but increased radiation exposure and required higher mechanical stability of equipment. In this paper, we analyze the approximation error of fringe scanning technique for the X-ray microscopy which uses just one grating and proposes an improved algorithm. We compute the approximation error by iteration and substitute that into the process of reconstruction of phase shift. This procedure will suppress the error even with few sample images. The results of simulation experiments show that the precision of phase shift image reconstructed by the proposed algorithm with 4 sample images is almost the same as that reconstructed by the conventional algorithm with 40 sample images. We also have succeeded in the experiment with real data.


Estimation of weighted log partial area under the ROC curve and its application to MicroRNA expression data.
MicroRNAs (miRNAs) are short non-coding RNAs that play critical roles in numerous cellular processes through post-transcriptional functions. The aberrant role of miRNAs has been reported in a number of diseases. A robust computational method is vital to discover novel miRNAs where level of noise varies dramatically across the different miRNAs. In this paper, we propose a flexible rank-based procedure for estimating a weighted log partial area under the receiver operating characteristic (ROC) curve statistic for selecting differentially expressed miRNAs. The statistic combines results taking partial area under the curve (pAUC) and their corresponding variance. The proposed method does not involve complicated formulas and does not require advanced programming skills. Two real datasets are analyzed to illustrate the method and a simulation study is carried out to assess the performance of different miRNA ranking statistics. We conclude that the proposed method offers robust results with large samples for miRNA expression data, and the method can be used as an alternative analytical tool for identifying a list of target miRNAs for further biological and clinical investigation.


Refinement of the Interprofessional Socialization and Valuing Scale (ISVS-21) and Development of 9-Item Equivalent Versions.
Measures of interprofessional (IP) socialization are needed to capture the role of interprofessional education in preparing students and health practitioners to function as part of IP health care teams. The aims of this study were to refine a previously published version of the Interprofessional Socialization and Valuing Scale (the ISVS-24) and create two shorter equivalent forms to be used in pre-post studies. A graded response model was used to identify ISVS items in a practitioner data set (n = 345), with validation (measure invariance) conducted using a separate student sample (n = 341). Analyses indicated a unidimensional 21-item version with excellent measurement properties, Cronbach alpha of 0.988, 95% confidence interval (CI) 0.985-0.991. There was evidence of measure invariance, as there was excellent agreement of the factor scores for the practitioner and student data, intraclass correlation coefficient = 0.993, 95% CI 0.991-0.994. This indicates that the ISVS-21 measures IP socialization consistently across groups. Two 9-item equivalent versions for pre-post use were developed, with excellent agreement between the two forms. The student score agreement for the two item sets was excellent: intraclass correlation coefficient = 0.970, 95% CI 0.963-0.976. The ISVS-21 is a refined measure to assess existing levels of IP socialization in practitioners and students, and relate IP socialization to other important constructs such as IP collaboration and the development of an IP identity. The equivalent versions can be used to assess change in IP socialization as a result of interprofessional education.


Nanometer-scale water- and proton-diffusion heterogeneities across water channels in polymer electrolyte membranes.
Nafion, the most widely used polymer for electrolyte membranes (PEMs) in fuel cells, consists of a fluorocarbon backbone and acidic groups that, upon hydration, swell to form percolated channels through which water and ions diffuse. Although the effects of the channel structures and the acidic groups on water/ion transport have been studied before, the surface chemistry or the spatially heterogeneous diffusivity across water channels has never been shown to directly influence water/ion transport. By the use of molecular spin probes that are selectively partitioned into heterogeneous regions of the PEM and Overhauser dynamic nuclear polarization relaxometry, this study reveals that both water and proton diffusivity are significantly faster near the fluorocarbon and the acidic groups lining the water channels than within the water channels. The concept that surface chemistry at the (sub)nanometer scale dictates water and proton diffusivity invokes a new design principle for PEMs.


Calmodulin is essential for cardiac IKS channel gating and assembly: impaired function in long-QT mutations.
The slow IKS K+ channel plays a major role in repolarizing the cardiac action potential and consists of the assembly of KCNQ1 and KCNE1 subunits. Mutations in either KCNQ1 or KCNE1 genes produce the long-QT syndrome, a life-threatening ventricular arrhythmia. Here, we show that long-QT mutations located in the KCNQ1 C terminus impair calmodulin (CaM) binding, which affects both channel gating and assembly. The mutations produce a voltage-dependent macroscopic inactivation and dramatically alter channel assembly. KCNE1 forms a ternary complex with wild-type KCNQ1 and Ca(2+)-CaM that prevents inactivation, facilitates channel assembly, and mediates a Ca(2+)-sensitive increase of IKS-current, with a considerable Ca(2+)-dependent left-shift of the voltage-dependence of activation. Coexpression of KCNQ1 or IKS channels with a Ca(2+)-insensitive CaM mutant markedly suppresses the currents and produces a right shift in the voltage-dependence of channel activation. KCNE1 association to KCNQ1 long-QT mutants significantly improves mutant channel expression and prevents macroscopic inactivation. However, the marked right shift in channel activation and the subsequent decrease in current amplitude cannot restore normal levels of IKS channel activity. Our data indicate that in healthy individuals, CaM binding to KCNQ1 is essential for correct channel folding and assembly and for conferring Ca(2+)-sensitive IKS-current stimulation, which increases the cardiac repolarization reserve and hence prevents the risk of ventricular arrhythmias.


The severity of trauma determines the immune response to PF4/heparin and the frequency of heparin-induced thrombocytopenia.
Heparin can induce heparin-induced thrombocytopenia (HIT). The combined effect of type of surgery (major vs minor) and heparin on this prothrombotic immune reaction to platelet factor 4 (PF4)/heparin was analyzed. In a randomized, double-blind study, trauma patients receiving low-molecular-weight (LMWH) or unfractionated heparin (UFH) for thrombosis prophylaxis were assessed for PF4/heparin-antibody seroconversion, HIT, and thrombosis according to type of surgery. The risk for seroconversion was higher than major versus minor surgery odds ratio, 7.98 [95% confidence interval, 2.06-31.00], P = .003, controlled for potential confounders, as was the risk for HIT (2.2% [95% confidence interval, 0.3%-4.1%] vs 0.0%, P = .010). During LMWH compared with UFH thromboprophylaxis, HIT (1 of 298 vs 4 of 316; P = .370) and PF4/heparin seroconversion (1.7% vs 6.6%; P = .002) were less frequent, driven by differences in patients undergoing major surgery (incidence of HIT: LMWH 0.8% vs UFH 4.0%; P = .180; seroconversion rates: 4.0% vs 17.0%; P = .001). After minor surgery, no case of HIT occurred. The severity of trauma and the need for major surgery strongly influence the risk of an anti-PF4/heparin immune response, which is then increased by UFH. In major trauma certoparin may be safer than UFH because it induces HIT-antibody seroconversion, and the corresponding risk of HIT, less frequently.


[Chimeric hepatitis B core antigen particles as a presentation system of foreign protein epitopes].
The paper presents data available in the literature and the author's own experimental findings as to the construction of chimeric hepatitis B core antigen (HBcAg) particles. The problems associated with the design of hybrid HBcAg particles and the ways of solving arising problems are considered. Data from studies of the antigen and immunogenic properties of hybrid HBcAg particles.


Prediction and prevention system for Severe Acute Respiratory Syndrome CoronaVirus 2 infection by preempting the onset of a cough.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is fast becoming one of the most significant infections worldwide. Of all the causes of SARS-CoV-2 infection, airborne-droplet infection via coughing is the most common. Therefore, if predicting the onset of a cough and preventing infection were possible, it would have a globally positive impact. Here, we describe a new prediction and prevention system for SARS-CoV-2 infection. Usually, air is inhaled prior to coughing, and the cough, which contains droplets of the virus, then occurs during acute exhalation. Therefore, if we can predict the onset of a cough, we can prevent the spread of SARS-CoV-2. At Tohoku University, a diagnosis system for evaluating swallowing motions and peripheral circulation has already been developed, and our prediction system can be integrated into this system. Using three-dimensional human body imaging, we developed a prediction system for preempting the onset of a cough. If we can predict the onset a cough, we can prevent the spread of SARS-CoV-2 infection, by decreasing the shower of virally active airborne droplets. Here, we describe the newly developed prediction and prevention system for SARS-CoV-2 infection that preempts the onset of a cough.Clinical Relevance- If predicting the onset of a cough and preventing infection were possible, it would have a globally positive impact. Here, we describe the newly developed prediction and prevention system for SARS-CoV-2 infection.


Poor prognoses of open globe injuries with concomitant orbital fractures.
Orbital trauma, particularly with open globe injury, can have a wide range of visual outcomes, which can be difficult to predict at presentation. Clinical features on presentation may provide insight into visual prognosis. We hypothesized that patients with open globe injuries and concomitant orbital fractures have poorer visual outcomes than patients without orbital fractures. We reviewed the charts of 77 patients with isolated open globe injuries (OG) and 76 patients with open globe injuries and concomitant orbital fractures (OGOF). Multivariate regression analysis was performed to assess the relative influence of individual presenting historical and clinical features on visual outcome. OGOF patients were more likely to have sustained blunt trauma than a sharp, penetrating injury compared to OG patients. Ocular wound locations were more posterior and likely to involve multiple zones in OGOF compared to OG patients. Among OGOF patients, orbital floor fractures were the most common and roof fractures were the least common, but the latter was associated with presenting NLP vision and multiple zone involvement. The presence of an orbital fracture independently increased the odds of subsequent evisceration/enucleation (OR: 4.6, 95% CI 1.3-20.1, p = .0246) and NLP vision (OR: 6.81, 95% CI 2.42-21.85, p = .0005) when controlling for zone, mechanism of injury, uveal prolapse and demographic variables. The presence of an orbital fracture independently confers a worse visual and ocular prognosis in patients with open globe injuries. Patients with open globe injuries in this category should be appropriately counseled.


Hydrophobicity of proteins and interfaces: insights from density fluctuations.
Macroscopic characterizations of hydrophobicity (e.g., contact angle measurements) do not extend to the surfaces of proteins and nanoparticles. Molecular measures of hydrophobicity of such surfaces need to account for the behavior of hydration water. Theory and state-of-the-art simulations suggest that water density fluctuations provide such a measure; fluctuations are enhanced near hydrophobic surfaces and quenched with increasing surface hydrophilicity. Fluctuations affect conformational equilibria and dynamics of molecules at interfaces. Enhanced fluctuations are reflected in enhanced cavity formation, more favorable binding of hydrophobic solutes, increased compressibility of hydration water, and enhanced water-water correlations at hydrophobic surfaces. These density fluctuation-based measures can be used to develop practical methods to map the hydrophobicity/philicity of heterogeneous surfaces including those of proteins. They highlight that the hydrophobicity of a group is context dependent and is significantly affected by its environment (e.g., chemistry and topography) and especially by confinement. The ability to include information about hydration water in mapping hydrophobicity is expected to significantly impact our understanding of protein-protein interactions as well as improve drug design and discovery methods and bioseparation processes.


General practitioners' preferences for managing insomnia and opportunities for reducing hypnotic prescribing.
Insomnia and sleep problems are common with many sufferers seeking medical help from general practitioners (GPs) whose clinical response is limited, often involving prescription of hypnotic drugs. The case for improving the quality of care for patients with insomnia is compelling but there is little evidence about how better care could be achieved in a primary care setting. The aim of this study was to investigate GPs' management preferences for sleep problems and their awareness and perception of opportunities for improving care as well as reducing the use of benzodiazepines and Z drugs. Cross-sectional survey of GPs using a self-administered postal questionnaire in 2005 to all GPs in West Lincolnshire Primary Care Trust Lincolnshire, UK. A total of 84 of 107 (78.5%) questionnaires sent to GP principals were returned after one reminder. Respondents favoured Z drugs over benzodiazepines for the majority of indications. Respondent attitudes to benzodiazepines and Z drugs were generally negative whereas they were positive towards initiatives to reduce hypnotic prescribing through personal guidance, awareness-raising strategies and organizational interventions. GPs were negative in attitude towards hypnotics and positive towards reducing prescribing for sleep problems. They need to develop resources and better strategies for assessment and non-pharmacological management of patients presenting with insomnia for the first time as well as those on long-term hypnotics. The feasibility and effectiveness of psychosocial interventions tailored to patient and service needs in primary care setting should be evaluated systematically seeking to understand potential clinical benefits as well as potential undesirable effects of service changes.


Robot-Assisted Parathyroidectomy Using Indocyanine Green (ICG) Fluorescence in Primary Hyperparathyroidism.
Background and Objectives: Surgical treatment for primary hyperparathyroidism (PHPT) has evolved from bilateral exploration through a long transcervical incision to focused parathyroidectomy with a minimal incision above the pathologic gland. Recently, endoscopic or robot-assisted parathyroid surgery without direct neck incision has been introduced. The aim of this study was to investigate the effectiveness of indocyanine green (ICG) fluorescence as a new method for the visual identification of abnormal hyperfunctioning parathyroid glands in robot-assisted parathyroidectomy using FireflyTM technology. We also aimed to conduct a comparative analysis between robot-assisted parathyroidectomy and conventional focused parathyroidectomy in order to identify clinical differences between the two surgical approaches. Materials and Methods: A total of 37 patients with PHPT underwent parathyroidectomy at a single university hospital between September 2018 and December 2022. Thirty-one patients underwent open focused parathyroidectomy (open group), and six patients underwent robot-assisted parathyroidectomy (robot group). Pre-operative localization via parathyroid SPECT-CT and an intraoperative parathyroid hormone (IOPTH) assay were used to successfully remove the pathologic parathyroid in both groups. ICG was administered only in the robot group. Results: Pathologic parathyroid showed a persistent fluorescence pattern under near-infrared vision. After the removal of the fluorescent parathyroid gland, IOPTH was normalized in all six patients in the robot group. However, the open group showed shorter hospital stays (1.8 ± 1.2 vs. 3.0 ± 0.0 days, p < 0.001) and shorter operation times (91.1 ± 69.1 vs. 152.5 ± 23.6 min, p = 0.001) than the robot group. After 6 months of surgery, PTH, calcium, and ionized calcium levels were all normalized without significant differences between the groups. Conclusions: Robot-assisted parathyroidectomy using ICG is helpful for the visual identification of the pathologic parathyroid gland. The advantage of robot parathyroidectomy is a better cosmetic outcome. However, it still does not show better clinical outcomes than conventional open focused parathyroidectomy.


Communication between healthcare providers and communicatively-vulnerable patients with associated health outcomes: A scoping review of knowledge syntheses.
Summarize literature on provider-patient communication linked to health outcomes in communicatively-vulnerable patient populations. Scoping review of reviews: systematically searched six databases. systematic searches and syntheses of literature; one or more providers and communicatively-vulnerable patients; synchronous in-person communication; intermediate or health outcome linked to communication. The search yielded 14,615 citations; 47 reviews - with wide range of providers, communication vulnerabilities, communication practices, and health outcomes - met inclusion criteria. Methodology included qualitative, quantitative, and mixed approaches. Quality ranged from very low to high. Six categories of communication practices linked to health outcomes were identified: 1) motivation-based; 2) accommodation of language, culture, gender, sexual identity, and other concordance with the patient; 3) cultural adaptations of interventions; 4) use of interpreters; 5) other provider-patient communication practices; 6) patient communication practices. Communication practices were studied in a wide range of providers, with common themes regarding best practices. A unique finding is the role of the patient's communication practices. The specificity of communication practices studied is heterogeneous, with many reviews providing insufficient details. Motivation-based practices and culturally- and linguistically-appropriate care have impacts on patient outcomes across a range of settings with different professions and communicatively-vulnerable groups.


The effect of programs to improve oral hygiene outcomes for older residents in long-term care: a systematic review.
Nurses have a critical role in promoting oral health in dependent older adults residing in long-term care or having extended hospital stays. Strategies aimed at improving the quality of oral hygiene care nurses provide may contribute to better oral hygiene outcomes. The purpose of this systematic review was to examine the effect of intervention programs designed to enhance the ability of nurses or those to whom they delegate care to improve oral hygiene outcomes in frail older adults. Studies reported an educational program, either alone or augmented in some way. The study interventions consisted of: (a) single in-service education sessions; (b) single in-service education sessions supplemented by a "train-the-trainer" approach; and (c) education sessions supplemented with ongoing active involvement of a dental hygienist. None of the approaches emerged as being desirable over the others, as methodologically strong studies with good intervention integrity were lacking, and a variety of oral health outcomes were used to measure effectiveness of the interventions, making comparisons across studies difficult.


Role of Endoscopic Ultrasound Elastography Strain Histograms in the Evaluation of Patients with Pancreatic Masses.
The Endoscopic Ultrasound (EUS) quantitative elastography strain ratio (SR) and strain histogram (SH) methods for noninvasive pancreatic masses differentiation have been recently developed. The aim of this research was to investigate the accuracy of the diagnostic differentiation methods for patients with pancreatic masses, based on the EUS SR and SH. This is a prospective study involving 100 cases with pancreatic masses. Patients were classified into 2 groups: group that was diagnosed with pancreatic malignancy with positive histopathology by biopsy obtained by fine-needle aspiration or postoperative pathology (72 patients) and the group diagnosed with pancreatitis with negative pathology and follow-up for at least 1 year (28 patients). Based on the ROC curve, the cut-off point for Mode 1 was set at 97. Values under it showed the presence of malignant pancreatic masses. Mode 1 achieved a sensitivity of 89% and a specificity of 43% with an overall accuracy of 76%. The predictive positive value was 70%, and the predictive negative value was 60%. The cut-off point for SR was set at 3.04, and the values were equal or above the suggested pancreatic malignancy. The SR achieved a sensitivity of 95.83%, a specificity of 61%, with an overall accuracy of 86%. The predictive positive and negative values were 86.2% and 85%, respectively. Mode 1 SH showed good sensitivity in the identification of pancreatic malignant tumors but were disappointingly of low specificity. Higher sensitivity, specificity, and overall accuracy were obtained by using the SR.


Retinal evaluation and treatment after refractive corneal surgery.
Refractive corneal surgery (a collective term used to describe a variety of surgical procedures that alter the refractive status of the eye through the surgical modification of corneal curvature) shows promise for use in situations where current methods of optical correction do not meet the patient's needs. This article reviews our experiences with the retinal evaluation of patients who have undergone corneal refractive surgery and offers recommendations for the treatment of retinal pathology after such surgery.


When is gender accessed? A study of paraphasias in Hebrew anomia.
This study explored access to grammatical gender during naming in Hebrew. Studies of anomia and tip-of-the-tongue states (TOT) found that speakers of various languages (Italian, Spanish, German, Dutch) have information about the grammatical gender of words they fail to retrieve. In Hebrew, on the other hand, a TOT study found that Hebrew speakers could not provide gender information. To test access to gender in single words in Hebrew we used an implicit measure--the analysis of paraphasias of anomic patients with respect to whether or not they preserved the grammatical gender of the target word. The rationale behind this measure was that when a paraphasia is created, it generally conforms to the partial knowledge the speaker has on the target word. If speakers have gender knowledge when they fail to name, they should produce paraphasias that match their partial information, and thus match the gender of the target. Such gender preservation in paraphasias was found in German for individuals with anomia, and in Arabic, French and German for slips of the tongue. Participants were 22 Hebrew-speaking aphasic patients with phonological, semantic or conceptual anomia, who produced 532 paraphasias. None of the participants showed gender preservation in their paraphasias. Even phonological anomics, who have access to semantic information, did not preserve grammatical gender in a single-word naming task. We suggest that this difference between Hebrew and previously studied languages relates to the fact that in Hebrew bare nouns are allowed, and therefore gender is not accessed in single-word naming, whereas in languages in which a noun should be produced as a full NP (with a determiner or case-marking for example) gender has to be accessed even in single-word tasks. We propose a hypothesis according to which gender is accessed if and only if the noun is incorporated into a syntactic tree (or a chunk of a tree) that includes an agreement phrase.


Label-Free Discrimination of Rhizobial Bacteroids and Mutants by Single-Cell Raman Microspectroscopy.
Symbiotic rhizobia in legumes account for a large portion of nitrogen fixation in the biosphere. Nitrogen fixation is an energy-demanding process requiring tight control of metabolism and redox state. It is of great interest to understand the bacteroid differentiation process and the roles of energy storage molecules, such as glycogen and polyhydroxybutyrate (PHB), in maintaining the Rhizobium-legume symbioses. Traditional biochemical assays for checking phenotypic changes of mutants require a large volume of starting materials, which is difficult for unculturable, terminally differentiated bacteroids. Here we present a label-free technique that allows the identification and characterization of phenotypic changes of bacteria at the single-cell level. This work demonstrates the application of single-cell Raman spectra (SCRS) to differentiate Rhizobium leguminosarum bv. viciae wild-type and mutants under different conditions. We found symbiotically differentiated bacteroids and free-living bacteria differed primarily at a Raman biomarker, cytochrome c, corresponding to a bacteroid-specific terminal oxidase. We demonstrated that, for the first time, SCRS were able to link phenotypic changes and specific genetic mutants, in this case, single and double mutations in synthesis of carbon storage molecules glycogen and polyhydroxybutyrate (PHB). By analyzing SCRS of these mutants, it provides insights into metabolite production and carbon regulatory network of rhizobia.


Identification of facilitators and barriers to home dialysis selection by canadian adults with ESRD.
Home dialysis (home HD or home PD) remains underutilized in most jurisdictions. Physicians, advanced-practice nurses, and policy makers working with chronic kidney disease populations can provide insights into patient, healthcare professional, and system-level barriers to home dialysis selection by suitable patients. We used in-depth interviews, with a purposive sampling strategy until informational redundancy was achieved, to elicit barriers and facilitators to home dialysis selection from thirteen informants. We triangulated these data against qualitative data collected in a related survey of nephrologist attitudes. We used a modified grounded theory approach to construct a taxonomy of barriers and facilitators. Informants included nephrologists (n = 11), an advanced-practice nurse, and a health administrator with a provincial renal care organization. We constructed separate taxonomies of barriers and related facilitators that were specific to PD, specific to home HD, and common to both. We distinguished between factors favoring, modifiable factors opposing, and nonmodifiable factors opposing home dialysis selection. Several major themes emerged, including: medical factors, home physical environment, psychological and cognitive factors (knowledge, attitudes, coping styles), social factors (supports, lifestyle), dialysis program, local hospital or regional factors (expertise, resources, local culture), healthcare professional-related factors (knowledge, attitudes, reimbursement), health system-related factors (funding models), and exogenous factors (late referral, technology). We identified several modifiable practices at the level of patient, healthcare professional, dialysis facility, and healthcare system to increase appropriate use of home dialysis. We discuss potential facilitating factors, knowledge gaps, and priorities for future research, and propose potential applications for this novel taxonomy of determinants of dialysis modality choice.


Potential Role of Neuroprotective Agents in the Treatment of Patients with Acute Ischemic Stroke.
Currently, intravenous recombinant tissue plasminogen activator is the only US Food and Drug Administration-approved therapy for acute ischemic stroke. Although efficacious, its usefulness is limited, mainly because of the very limited time window for its administration. Neuroprotective treatments are therapies that block the cellular, biochemical, and metabolic elaboration of injury during or after exposure to ischemia, and have a potential role in ameliorating brain injury in patients with acute ischemic stroke. More than 50 neuroprotective agents have reached randomized human clinical trials in focal ischemic stroke, but none have been unequivocally proven efficacious, despite successful preceding animal studies. The failed neuroprotective trials of the past have greatly increased understanding of the fundamental biology of ischemic brain injury and have laid a strong foundation for future advance. Moreover, the recent favorable results of human clinical trials of hypothermia in human cardiac arrest and global brain ischemia have validated the general concept of neuroprotection for ischemic brain injury. Recent innovations in strategies of preclinical drug development and clinical trial design that rectify past defects hold great promise for neuroprotective investigation, including novel approaches to accelerating time to initiation of experimental treatment, use of outcome measures sensitive to treatment effects, and trial testing of combination therapies rather than single agents alone. Although no neuroprotective agent is of proven benefit for focal ischemic stroke, several currently available interventions have shown promising results in preliminary trials and may be considered for cautious, off-label use in acute stroke, including hypothermia, magnesium sulfate, citicoline, albumin, and erythropoietin. Overall, the prospects for safe and effective neuroprotective therapies to improve stroke outcome remain promising.


[Application of preparation endotelon in complex treatment of chronic arterial insufficiency of lower extremities].
The results of treatment of 43 patients with chronic ischemia of extremities with application of preparation endotelon were summarized. Stable positive effect, preserved during 2-4 month was noted in 34 patients. Lowering of regional venous pressure, at average for the first week by (1.3 +/- 0.31) kPa, or (10 +/- 2.3) mm Hg, was observed after the first course of treatment conduction.


MicroRNA-297b-5p/3p target Mllt3/Af9 to suppress lymphoma cell proliferation, migration and invasion in vitro and tumor growth in nude mice.
Mllt3/Af9 is a proto-oncogene capable of deregulating the expression of genes critical for leukemia. However, the regulation of its expression remains incompletely elucidated. Herein, we show that the microRNAs miR-297b-5p/3p are capable of regulating Mllt3/Af9 expression negatively by binding to its 3'-untranslated region. Overexpression of miR-297b-5p/3p also led to altered expression of p27(Kip1) and proliferating cell nuclear antigen, abnormal cell cycle arrest, decreased cell proliferation, migration and invasion in vitro in cell cultures, and suppressed xenograft tumor growth in vivo in the nude mouse. These data demonstrate that miR-297b-5p/3p and Mllt3/Af9 might be critical regulators of lymphoma cell proliferation or carcinogenesis. Together our findings suggest that miR-297b-5p/3p might be useful molecular targets for diagnosis or treatment of cancers associated with abnormal expression of Mllt3/Af9.


Informing evaluation of a smartphone application for people with acquired brain injury: a stakeholder engagement study.
Brain in Hand is a smartphone application (app) that allows users to create structured diaries with problems and solutions, attach reminders, record task completion and has a symptom monitoring system. Brain in Hand was designed to support people with psychological problems, and encourage behaviour monitoring and change. The aim of this paper is to describe the process of exploring the barriers and enablers for the uptake and use of Brain in Hand in clinical practice, identify potential adaptations of the app for use with people with acquired brain injury (ABI), and determine whether the behaviour change wheel can be used as a model for engagement. We identified stakeholders: ABI survivors and carers, National Health Service and private healthcare professionals, and engaged with them via focus groups, conference presentations, small group discussions, and through questionnaires. The results were evaluated using the behaviour change wheel and descriptive statistics of questionnaire responses. We engaged with 20 ABI survivors, 5 carers, 25 professionals, 41 questionnaires were completed by stakeholders. Comments made during group discussions were supported by questionnaire results. Enablers included smartphone competency (capability), personalisation of app (opportunity), and identifying perceived need (motivation). Barriers included a physical and cognitive inability to use smartphone (capability), potential cost and reliability of technology (opportunity), and no desire to use technology or change from existing strategies (motivation). The stakeholders identified potential uses and changes to the app, which were not easily mapped onto the behaviour change wheel, e.g. monitoring fatigue levels, method of logging task completion, and editing the diary on their smartphone. The study identified that both ABI survivors and therapists could see a use for Brain in Hand, but wanted users to be able to personalise it themselves to address individual user needs, e.g. monitoring activity levels. The behaviour change wheel is a useful tool when designing and evaluating engagement activities as it addresses most aspects of implementation, however additional categories may be needed to explore the specific features of assistive technology interventions, e.g. technical functions.


Renal excretion of cimetidine.
The renal excretion and certain pharmacokinetic properties of cimetidine were studied in anesthetized rats undergoing moderate osmotic diuresis. When cimetidine concentrations in plasma (Pcim) were low, ca. 2 micrograms/ml, the clearance of cimetidine (Ccim) was 2.64-fold greater than the glomerular filtration rate (GFR). Ccim was lower at higher concentrations, e.g., at ca. 200 micrograms/ml, Ccim/GFR was 1.24. When animals with low Pcim were alkalotic (bicarbonate infusion), Ccim/GFR was 1.82 (different from control, P less than 0.01). In nonalkalotic animals, Ccim/GFR was not influenced by changes in urine flow rate. High levels of Pcim completely blocked net secretion of the cation, tetraethylammonium ion, but did not inhibit the secretion of the anion p-aminohippurate. The half-time of cimetidine in plasma was 43 to 49 min. The apparent volume of distribution was 3.6-fold greater than estimated total body water. We conclude that cimetidine is secreted by the renal organic cation transport mechanism and that it probably undergoes passive reabsorption (nonionic diffusion) to a modest extent when the urine is alkaline. The relatively long half-life of the drug in the body, despite its very high renal clearance, is attributable to the large volume of distribution.


mRNA isoform diversity can obscure detection of miRNA-mediated control of translation.
Reporter-based studies support inhibition of translation at the level of initiation as a substantial component of the miRNA mechanism, yet recent global analyses have suggested that they predominantly act through decreasing target mRNA stability. Cells commonly coexpress several processing isoforms of an mRNA, which may also differ in their regulatory untranslated regions (UTR). In particular, cancer cells are known to express high levels of short 3' UTR isoforms that evade miRNA-mediated regulation, whereas longer 3' UTRs predominate in nontransformed cells. To test whether mRNA isoform diversity can obscure detection of miRNA-mediated control at the level of translation, we assayed the responses of 11 endogenous let-7 targets to inactivation of this miRNA in HeLa cells, an intensively studied model system. We show that translational regulation in many cases appears to be modest when measuring the composite polysome profile of all extant isoforms of a given mRNA by density ultracentrifugation. In contrast, we saw clear effects at the level of translation initiation for multiple examples when selectively profiling mRNA isoforms carrying the 5' or 3' untranslated regions that were actually permissive to let-7 action, or when let-7 and a second targeting miRNA were jointly manipulated. Altogether, these results highlight a caveat to the mechanistic interpretation of data from global miRNA target analyses in transformed cells. Importantly, they reaffirm the importance of translational control as part of the miRNA mechanism in animal cells.


Students' Use of Optional Online Reviews and Its Relationship to Summative Assessment Outcomes in Introductory Biology.
Retrieval practice has been shown to produce significant enhancements in student learning of course information, but the extent to which students make use of retrieval to learn information on their own is unclear. In the current study, students in a large introductory biology course were provided with optional online review questions that could be accessed as Test questions (requiring students to answer the questions before receiving feedback) or as Read questions (providing students with the question and correct answer up-front). Students more often chose to access the questions as Test compared with Read, and students who used the Test questions scored significantly higher on subsequent exams compared with students who used Read questions or did not access the questions at all. Following an in-class presentation of superior exam performance following use of the Test questions, student use of Test questions increased significantly for the remainder of the term. These results suggest that practice questions can be an effective tool for enhancing student achievement in biology and that informing students about performance-based outcomes coincides with increased use of retrieval practice.


Gramene: a growing plant comparative genomics resource.
Gramene (www.gramene.org) is a curated resource for genetic, genomic and comparative genomics data for the major crop species, including rice, maize, wheat and many other plant (mainly grass) species. Gramene is an open-source project. All data and software are freely downloadable through the ftp site (ftp.gramene.org/pub/gramene) and available for use without restriction. Gramene's core data types include genome assembly and annotations, other DNA/mRNA sequences, genetic and physical maps/markers, genes, quantitative trait loci (QTLs), proteins, ontologies, literature and comparative mappings. Since our last NAR publication 2 years ago, we have updated these data types to include new datasets and new connections among them. Completely new features include rice pathways for functional annotation of rice genes; genetic diversity data from rice, maize and wheat to show genetic variations among different germplasms; large-scale genome comparisons among Oryza sativa and its wild relatives for evolutionary studies; and the creation of orthologous gene sets and phylogenetic trees among rice, Arabidopsis thaliana, maize, poplar and several animal species (for reference purpose). We have significantly improved the web interface in order to provide a more user-friendly browsing experience, including a dropdown navigation menu system, unified web page for markers, genes, QTLs and proteins, and enhanced quick search functions.


Evidence of a common founder for SCA12 in the Indian population.
Spinocerebellar ataxia type 12 (SCA12) is an autosomal dominant cerebellar ataxia associated with the expansion of an unstable CAG repeat in the 5' region of the PPP2R2B gene on chromosome 5q31-5q32. We found that it accounts for approximately 16% (20/124) of all the autosomal dominant ataxia cases diagnosed in AIIMS, a major tertiary referral centre in North India. The length of the expanded allele in this population ranges from 51-69 CAG triplets. Interestingly, all the affected families belong to an endogamous population, which originated in the state of Haryana, India. We identified four novel SNPs and a dinucleotide marker spanning approximately 137 kb downstream of CAG repeat in the PPP2R2B gene. Analysis of 20 Indian SCA12 families and ethnically matched normal unrelated individuals revealed one haplotype to be significantly associated with the affected alleles (P= 0.000), clearly indicating the presence of a common founder for SCA12 in the Indian population. This haplotype was not shared by the American pedigree with SCA12. Therefore, the SCA12 expansion appears to have originated at least twice.


Characterization of a human 'midisatellite' sequence.
We have examined the structure and DNA sequence of a human genomic locus that consists of a large hypervariable region made up of repeats of a simple sequence. With several restriction enzymes, the locus shows many restriction fragments that vary quantitatively as well as qualitatively. Other restriction enzymes produce only a single, high-molecular-weight fragment at this locus. Almost all of the fragments are revealed with a simple sequence probe. Southern transfers of the high-molecular-weight restriction fragments produced by the restriction enzymes NotI and SfiI, resolved by pulsed-field gel electrophoresis, gave at most two fragments, demonstrated to be allelic, showing that the majority of the restriction fragments seen in the complex patterns are at a single locus. The estimated size of the region homologous to the probe varied from 250 to 500 kilobases. DNA sequencing indicated that the region consists of tandem repeats of a 40-base-pair sequence. Some homology was detected to the tandem repeating units of the insulin gene and the zetaglobin pseudogene hypervariable regions, and to the "minisatellite" DNA at the myoglobin locus.


Pre-admission antibiotics for suspected cases of meningococcal disease.
Meningococcal disease begins suddenly and death can follow within hours. Pre-admission antibiotic therapy aims to prevent delay in starting therapy that occurs if bacterial confirmation is sought before instituting therapy. To study the effectiveness and safety of pre-admission antibiotics versus no pre-admission antibiotics or placebo and of different pre-admission antibiotic regimens in decreasing mortality and morbidity in people suspected of meningococcal disease. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2007, Issue 1), MEDLINE (1966 to February 2007) and EMBASE (1980 to February 2007). We selected randomised controlled trials (RCTs) or quasi-RCTs, of all people with suspected meningococcal infection. We compared antibiotic treatment versus placebo or no intervention, or different antibiotic treatments administered before admission to hospital or confirmation of the diagnosis. Two author authors independently assessed quality and extracted data from included trials. We calculated the relative risk (RR) and 95% confidence interval (CI) for dichotomous data. As only one trial fulfilled inclusion criteria, data synthesis was not performed. No RCTs were found that compared pre-admission antibiotics versus no pre-admission antibiotics or placebo. One open-label RCT evaluated a single dose of intramuscular ceftriaxone versus a single dose of intramuscular long acting (oily) chloramphenicol. Interventions did not differ significantly in mortality (RR 1.2, 95% CI 0.5 to 2.6; N = 510; 349 confirmed meningococcal meningitis; 26 deaths), nor in proportions of survivors who developed neurological sequelae (RR 1.2, 95% CI 0.6 to 2.2; N = 488; 36 with neurological sequelae), or that were classified as clinical failures (RR 0.8, 95% CI 0.4 to 1.8; N = 488, 25 clinical failures). No adverse effects of treatment were seen. No data were available for our secondary outcomes. We found no reliable evidence to support or refute the use of pre-admission antibiotics for suspected cases of meningococcal disease. Evidence from one RCT-during an epidemic of meningococcal meningitis, indicated that single intramuscular injections of ceftriaxone and long-acting chloramphenicol were equally effective and safe in preventing mortality and morbidity. The choice between these antibiotics would be based on affordability, availability, and patterns of antibiotic resistance.Further RCTs comparing different pre-admission antibiotics, including penicillin, including participants with severe illness are ethically justifiable and are needed to provide reliable evidence to clinicians in differing clinical settings.


Emerging Ferret Diseases.
There are a number of newly described and emerging disease syndromes affecting the domestic ferret, and the purpose of this article is to make veterinarians aware of these diseases. A recently described systemic coronavirus infection appears to be a variant of the ferret enteric coronavirus and is currently termed "ferret infectious peritonitis." Disseminated immunopathologic myositis, aplastic anemia/bone marrow aplasia, acute hemorrhagic syndrome, and oral ulcerations are also described, although the exact etiologies for these diseases have yet to be determined. There appears to be at least 2 important amino acid metabolism deficiencies in ferrets: hindlimb weakness in older ferrets (L-carnitine) and cysteine urolithiasis. Ferrets have recently been found to be susceptible to H1N1 influenza, so knowledge regarding this zoonotic disease is essential for veterinarians working with these animals. A novel Mycoplasma spp. has also recently been identified in ferrets with chronic respiratory problems that originated from one breeding colony. Because these diseases are still being investigated, practitioners who treat a ferret patient exhibiting clinical signs consistent with any of the conditions mentioned are encouraged to contact people who are knowledgeable of that particular illness.


[X-Ray upper airway changes in individuals suffering from obstructive respiratory disorders during sleep].
Obstructive respiratory disorders during sleep present an important medical and social problem. Serious dysfunctions of cardiovascular, nervous, endocrine and other vital systems of the body reduce longevity and life quality. On the other hand, load nocturnal snore and abnormal diurnal sleepiness cause great damage to family life, reduce working capacity and induce accidents. X-ray visualization of the upper airways is essential in diagnosing obstructive upper airway states and selecting patients for surgical treatment. The paper presents the authors' own experience in using various X-ray diagnostic methods in patients with chronic snore and obstructive sleep apnea-hypopnea syndrome.


Intimate partner violence as a mechanism underlying the intergenerational transmission of maltreatment among economically disadvantaged mothers and their adolescent daughters.
Child maltreatment represents a pervasive societal problem. Exposure to maltreatment is predictive of maladjustment across development with enduring negative effects found in adulthood. Compelling evidence suggests that some parents with a history of child abuse and neglect are at elevated risk for the maltreatment of their own children. However, a dearth of research currently exists on mediated mechanisms that may underlie this continuity. Ecological and transactional theories of child maltreatment propose that child maltreatment is multiply determined by various risk factors that exist across different ecological systems. Intimate partner violence (IPV) often co-occurs with child maltreatment and may represent a pathway through which risk for child abuse and neglect is transmitted across generations within a family. Informed by theories on the intergenerational transmission of child maltreatment and utilizing a community-based, cross-sectional sample of 245 racially and ethnically diverse, low-income mothers and daughters, the objective of this study was to investigate IPV as a propagating process through which risk of child abuse and neglect is conferred from parent to child. We found evidence suggesting that mothers' history of maltreatment is associated with both their IPV involvement and their adolescent daughters' maltreatment victimization (with exposure to IPV as a maltreatment subtype excluded for clarity). Maternal IPV also partially accounted for the continuity of maltreatment victimization from mother to adolescent. A secondary analysis that included the adolescent's own engagement in dating violence provided compelling but preliminary evidence of the emergence of a similar pattern of relational violence, whereby adolescent girls with maltreatment histories were likewise involved in abusive intimate relationships. Future directions and clinical implications of these findings are discussed.


Surgical management of aortopulmonary window.
Aortopulmonary window is a rare congenital malformation involving a window-like communication between the ascending aorta and the pulmonary artery. Here, we present our experience regarding the surgical repair of an aortopulmonary window, and also assess the long-term outcome. Thirteen children with an aortopulmonary window associated with various congenital lesions underwent a repair of the defect. The age at operation ranged from 3 days to 1 year (median age, 19 days). The patient's weight ranged from 2.1 to 7.0 kg (mean weight, 3.6 kg). The associated lesions included an interrupted aortic arch (5 patients), a ventricular septal defect (2), an atrial septal defect (1), mitral valve regurgitation (1), and tricuspid atresia [Ic] with mitral valve regurgitation (1). The aortopulmonary window was repaired with a cardiopulmonary bypass in 11 patients, and 2 patients were ligated without a cardiopulmonary bypass. One patient associated with tricuspid atresia died (mortality rate of 7.7%). There has been no late death during a mean follow-up of 7 years and 3 months. The surgical results for an aortopulmonary window are encouraging, even if such patients are associated with major cardiac anomalies and an interrupted aortic arch. Most have shown a good long-term outcome.


[Diagnostic standard evaluation of Chinese medicine syndrome for coronary heart disease patients after percutaneous coronary intervention].
To evaluate the validity, reliability, and clinical applicability of Chinese medicine syndrome diagnostic standards for coronary heart disease (CHD) patients after percutaneous coronary intervention (PCI), which was established by expert consultation. A total of 1 050 CHD patients after PCI were recruited from 23 hospitals. The sensitivity, specificity, accuracy, positive likelihood ratio, and area under ROC curve were used to evaluate the validity of diagnostic standards for Chinese medical syndrome types. The observable agreement rate and Kappa value were used to evaluate the reliability. Positive predictive value and negative predictive value were used to evaluate the clinical applicability. The sensitivity, specificity, accuracy, positive likelihood ratio, area under ROC curve, observable agreement rate, Kappa value, positive predictive value, and negative predictive value of each Chinese medicine syndrome in CHD patients after PCI were as follows: 95.26%, 93.70%, 94.86%, 15.13, 0.924, 98.76%, 0.969, 97.76%, and 87.24% for blood stasis syndrome; 96.42%, 95.34%, 96.00%, 20.70, 0.957, 99.52%, 0.990, 97.02%, and 94.42% for qi deficiency syndrome; 88.19%, 96.46%, 94.19%, 24.89, 0.923, 96.67%, 0.915, 90.39%, and 95.58% for phlegm turbidity syndrome; 91.06%, 98.77%, 97.05%, 74.22, 0.950, 98.67%, 0.960, 95.54%, and 97.46% for cardiac blood stasis syndrome; 98.41%, 96.73%, 97.33%, 30.10, 0.976, 98.86%, 0.976, 94.40%, and 99.09% for qi deficiency blood stasis syndrome; 94.81%, 94.75%, 94.76%, 18.07, 0.948, 97.71%, 0.918, 72.73%, and 99.20% for phlegm-stasis stagnation syndrome. The validity, reliability, and clinical applicability of Chinese medicine syndrome diagnostic standards for CHD patients after PCI were rational and considerable in clinical practice.


Nonexercise Estimated Cardiorespiratory Fitness and All-Cancer Mortality: the NHANES III Study.
To examine the relationship between estimated cardiorespiratory fitness (eCRF) using nonexercise equations and all-cancer mortality in a representative sample of the US population. A total of 8506 study participants were derived from the Third National Health and Nutrition Examination Survey, conducted from October 18, 1988, to October 15, 1994. They were followed for all-cancer mortality. Participants' CRF was estimated from nonexercise models that were determined by age, body mass index, waist circumference, resting heart rate, physical activity status, and smoking status, and further grouped into quintiles. Hazard ratios (HRs) and 95% CIs were calculated from Cox proportional hazards models for the relationship between eCRF and all-cancer mortality. During a mean of 19.5 years of follow-up, 455 cancer deaths (263 men and 192 women) were registered. After adjustment for race/ethnicity, age, educational level, current smoking, hypertension, diabetes mellitus, and hypercholesterolemia, each 1-metabolic equivalent increase in eCRF was associated with 30% (95% CI, 24%-35%) and 27% (95% CI, 18%-36%) risk reduction for all-cancer mortality in men and women, respectively. When eCRF was categorized into quintiles, HRs (95% CIs) were 0.47 (0.24-0.95), 0.81 (0.46-1.44), 0.49 (0.26-0.93), and 0.57 (0.31-1.06) across incremental quintiles in women (quintile 1 was the reference group). However, none of the HRs reached statistical significance in men. The eCRF was inversely associated with all-cancer mortality in quintiles 2 and 4 in women. More research is needed to further understand the association between eCRF and all-cancer mortality in men.


[Chemical characterization of Brazilian oat genotypes].
The chemical composition of oats has been poorly studied in Brazil. Therefore, the objective of this study was to characterize the main chemical constituents of Brazilian oat cultivars. This knowledge is essential for the utilization of this cereal in balanced diets, specially for individuals with high blood cholesterol, where the beta-glucans contribute to it's reduction. The analyzed genotipes were recommended by the Brazilian Oat Research Commission. The cultivars studied (CTC3, UFRGS7, UFRGS14, UPF7 and UPF16) showed high levels of protein (16.8%), lipids (6.84%) and beta-glucans (4.89%). The aminoacid profil of these samples was limiting only for lyisine, threonine and isoleucine. The other aminoacids had similar values to those recommended by the FAO. It was observed that all the studied variables suffered changes according to the interactions between genotype, locality and year of production. Cultivars UFRGS14, UFRGS7 and UPF16 were differentiated for their high contents of protein, lipids and beta-glucans, respectively.


Chemiluminescence imaging ELISA using an imprinted polymer as the recognition element instead of an antibody.
An imaging assay analogous to competitive enzyme immunoassays has been developed using a molecularly imprinted polymer instead of an antibody. The antigen 2,4-dichlorophenoxyacetic acid (2,4-D) was labeled with tobacco peroxidase, and the chemiluminescence reaction of luminol was used for detection. Microtiter plates (96 or 384 wells) were coated with polymer microspheres imprinted with 2,4-D, which were fixed in place by using poly(vinyl alcohol) as glue. In a competitive mode, the analyte-peroxidase conjugate was incubated with the free analyte in the microtiter plate, after which the bound fraction of the conjugate was quantified. After addition of the chemiluminescent substrates, light emission was measured in a high-throughput imaging format with a CCD camera. Calibration curves corresponding to analyte concentrations ranging from 0.01 to 100 microg/mL were obtained.


Variation of PM2.5 and PM10 in emissions and chemical compositions in different seasons from a manure-belt laying hen house.
Particulate matter (PM) emissions from animal houses and the corresponding hazard have raised increasing attention during recent years. In this study, a large-scale manure-belt laying hen house located in Beijing, China was selected as the experimental site for the study of the emission rates (ER) and chemical compositions of PM2.5 and PM10 in 3 seasons, namely, summer, autumn, and winter, to investigate their possible influences on ambient air quality and human health. The results showed that the mean ER from the hen house in summer, autumn, and winter were 9.0 ± 1.7, 2.4 ± 0.7, and 1.9 ± 0.7 mg hen-1 d-1 for PM2.5 (P < 0.05), and 30.7 ± 1.1, 12.8 ± 1.5, and 10.9 ± 0.9 mg hen-1 d-1 for PM10 (P < 0.05), respectively. Moreover, large amounts of secondary inorganic aerosols (SIA) were observed inside the house in summer, accounting for 11.4 and 9.6% of indoor PM2.5 and PM10 mass, respectively, compared with the value of <1.4% in autumn and winter. Among the 31 detected elements in indoor PM, arsenic concentration exceeded the threshold set in legislation. Zn had a notably high concentration of 3,403 to 4,432 ng m-3 in indoor PM10, which was 28 to 71 times higher than that in ambient PM10. The findings suggest that the poultry-raising house emit PM2.5 and PM10 containing SIA and toxic heavy-metal elements such as As and Zn to the ambient with much more emissions in summer than in autumn and winter. Considering the increasing development of poultry-raising farming in China, the potential hazard derived from the exhaust of PM2.5 and PM10 should be focused on, especially during summer.


Rhenium-186 liposomes as convection-enhanced nanoparticle brachytherapy for treatment of glioblastoma.
Although external beam radiation is an essential component to the current standard treatment of primary brain tumors, its application is limited by toxicity at doses more than 80 Gy. Recent studies have suggested that brachytherapy with liposomally encapsulated radionuclides may be of benefit, and we have reported methods to markedly increase the specific activity of rhenium-186 ((186)Re)-liposomes. To better characterize the potential delivery, toxicity, and efficacy of the highly specific activity of (186)Re-liposomes, we evaluated their intracranial application by convection-enhanced delivery in an orthotopic U87 glioma rat model. After establishing an optimal volume of 25 µL, we observed focal activity confined to the site of injection over a 96-hour period. Doses of up to 1850 Gy were administered without overt clinical or microscopic evidence of toxicity. Animals treated with (186)Re-liposomes had a median survival of 126 days (95% confidence interval [CI], 78.4-173 days), compared with 49 days (95% CI, 44-53 days) for controls. Log-rank analysis between these 2 groups was highly significant (P = .0013) and was even higher when 100 Gy was used as a cutoff (P < .0001). Noninvasive luciferase imaging as a surrogate for tumor volume showed a statistically significant separation in bioluminescence by 11 days after 100 Gy or less treatment between the experimental group and the control animals (χ(2)[1, N= 19] = 4.8; P = .029). MRI also supported this difference in tumor size. Duplication of tumor volume differences and survival benefit was possible in a more invasive U251 orthotopic model, with clear separation in bioluminescence at 6 days after treatment (χ(2)[1, N= 9] = 4.7; P = .029); median survival in treated animals was not reached at 120 days because lack of mortality, and log-rank analysis of survival was highly significant (P = .0057). Analysis of tumors by histology revealed minimal areas of necrosis and gliosis. These results support the potential efficacy of the highly specific activity of brachytherapy by (186)Re-liposomes convection-enhanced delivery in glioma.


Growth of Salmonella enterica in foliar pesticide solutions and its survival during field production and postharvest handling of fresh market tomato.
To evaluate in vitro the growth kinetics of Salmonella enterica in pesticide solutions labelled for fresh market tomato and the effect of ag-chemical application with contaminated water to tomatoes during field production. The capacity of pesticide formulations in the survival of S. enterica was evaluated in vitro and on tomato surfaces during field production. Most pesticides had ability to maintain the growth of Salmonella, however, specific pesticides can also support its growth, which was also dependent on the water composition and temperature to which pesticide solutions were held. Salmonella applied to field grown tomatoes through pesticide application was able to survive up to 15 days in up to 80% of the collected samples, even more postharvest washing with sodium hypochlorite was insufficient to completely mitigate the presence of Salmonella on tomato surfaces. This study provides further evidence that pesticides may support the growth of Salmonella, if introduced with source water and may elevate risk during foliar contact application beyond that of the water source alone. The study points out the importance of the microbiological quality of foliar contact water as a critical point to prevent contamination of fruits and vegetables from early stages of field production.


Advances in microfluidics for environmental analysis.
During the past few years, a growing number of groups have recognized the utility of microfluidic devices for environmental analysis. Microfluidic devices offer a number of advantages and in many respects are ideally suited to environmental analyses. Challenges faced in environmental monitoring, including the ability to handle complex and highly variable sample matrices, lead to continued growth and research. Additionally, the need to operate for days to months in the field requires further development of robust, integrated microfluidic systems. This review examines recently published literature on the applications of microfluidic systems for environmental analysis and provides insight in the future direction of the field.


Accumulation of hypointense lesions ("black holes") on T1 spin-echo MRI correlates with disease progression in multiple sclerosis.
MRI findings are increasingly used as outcome measures in therapeutic trials in MS. The discrepancy between the extent of the lesions on conventional T2 images and the clinical condition of the patient is one of the problems encountered in such studies. This clinical-radiological paradox prevents the use of MRI data as surrogate markers of disability in MS. A recent pilot study suggested a relationship between hypointense lesions on T1 MRI and disability. To assess in more detail the correlation of changes in hypointense lesion load on T1-weighted spin-echo MR images ("black holes") with changes in disability in MS, we studied 46 patients with clinically definite MS at baseline and after a median follow-up of 40 months. There was a significant correlation between baseline disability and hypointense lesion load (Spearman rank correlation coefficient [SRCC] = 0.46, p = 0.001). In secondary progressive patients, the rate of accumulation of these "black holes" was significantly related to progression rate (SRCC = 0.81, p < 0.0001). We speculate that the appearance of hypointense lesions is the MRI equivalent of a failure of remission. Overall, T1 lesion load measurements correlated better with clinical assessments than T2 lesion load measurements. Quantification of hypointense lesion load on T1-weighted spin-echo MRI helps to resolve the clinical-radiological paradox between disability and MRI and has the potential to be a surrogate marker of disability in MS.


Controlled breathing protocols probe human autonomic cardiovascular rhythms.
The purpose of this study was to determine how breathing protocols requiring varying degrees of control affect cardiovascular dynamics. We measured inspiratory volume, end-tidal CO2, R-R interval, and arterial pressure spectral power in 10 volunteers who followed the following 5 breathing protocols: 1) uncontrolled breathing for 5 min; 2) stepwise frequency breathing (at 0.3, 0.25, 0.2, 0.15, 0.1, and 0.05 Hz for 2 min each); 3) stepwise frequency breathing as above, but with prescribed tidal volumes; 4) random-frequency breathing (approximately 0.5-0.05 Hz) for 6 min; and 5) fixed-frequency breathing (0.25 Hz) for 5 min. During stepwise breathing, R-R interval and arterial pressure spectral power increased as breathing frequency decreased. Control of inspired volume reduced R-R interval spectral power during 0.1 Hz breathing (P < 0.05). Stepwise and random-breathing protocols yielded comparable coherence and transfer functions between respiration and R-R intervals and systolic pressure and R-R intervals. Random- and fixed-frequency breathing reduced end-tidal CO2 modestly (P < 0.05). Our data suggest that stringent tidal volume control attenuates low-frequency R-R interval oscillations and that fixed- and random-rate breathing may decrease CO2 chemoreceptor stimulation. We conclude that autonomic rhythms measured during different breathing protocols have much in common but that a stepwise protocol without stringent control of inspired volume may allow for the most efficient assessment of short-term respiratory-mediated autonomic oscillations.


Dentine hypersensitivity--a review. Aetiology, symptoms and theories of pain production.
The exposure of cervical dentine has a multifactorial aetiology and pain may frequently be elicited by a number of stimuli. Management of the condition, dentine hypersensitivity, tends to be empirical because of the lack of knowledge concerning the mechanism of pain transmission through dentine. The pulpal changes associated with the condition and any modulating effect on symptoms are by no means clearly established. Evidence suggests that exposed dentine which is sensitive exhibits patent tubules. The question of how pain is initiated across the dentine has received considerable attention but still remains somewhat debatable. The literature reviewed indicates that, at most, nerve fibres only penetrate a limited distance along some dentinal tubules. The theories that either the odontoblasts and their processes act as dentinal receptors or the nerves in the pulp are the pain receptors, are discussed. Evidence for the stimulation of pulp nerve fibres by a hydrodynamic mechanism would appear the most likely mechanism. Nevertheless, whichever theory proves to be correct, occlusion of dentinal tubules would appear an essential prerequisite for an effective desensitising agent.


Analysis of CD44-containing lipid rafts: Recruitment of annexin II and stabilization by the actin cytoskeleton.
CD44, the major cell surface receptor for hyaluronic acid (HA), was shown to localize to detergent-resistant cholesterol-rich microdomains, called lipid rafts, in fibroblasts and blood cells. Here, we have investigated the molecular environment of CD44 within the plane of the basolateral membrane of polarized mammary epithelial cells. We show that CD44 partitions into lipid rafts that contain annexin II at their cytoplasmic face. Both CD44 and annexin II were released from these lipid rafts by sequestration of plasma membrane cholesterol. Partition of annexin II and CD44 to the same type of lipid rafts was demonstrated by cross-linking experiments in living cells. First, when CD44 was clustered at the cell surface by anti-CD44 antibodies, annexin II was recruited into the cytoplasmic leaflet of CD44 clusters. Second, the formation of intracellular, submembranous annexin II-p11 aggregates caused by expression of a trans-dominant mutant of annexin II resulted in coclustering of CD44. Moreover, a frequent redirection of actin bundles to these clusters was observed. These basolateral CD44/annexin II-lipid raft complexes were stabilized by addition of GTPgammaS or phalloidin in a semipermeabilized and cholesterol-depleted cell system. The low lateral mobility of CD44 in the plasma membrane, as assessed with fluorescent recovery after photobleaching (FRAP), was dependent on the presence of plasma membrane cholesterol and an intact actin cytoskeleton. Disruption of the actin cytoskeleton dramatically increased the fraction of CD44 which could be recovered from the light detergent-insoluble membrane fraction. Taken together, our data indicate that in mammary epithelial cells the vast majority of CD44 interacts with annexin II in lipid rafts in a cholesterol-dependent manner. These CD44-containing lipid microdomains interact with the underlying actin cytoskeleton.


Women Radiologists in the United States: results from the American College of Radiology's 2003 Survey.
To retrospectively evaluate data from the 2003 American College of Radiology (ACR) survey of diagnostic radiologists with regard to characteristics of women radiologists, their professional activities, and the practices in which they work. The authors analyzed nonindividually identified data from the ACR's 2003 Survey of Radiologists, a stratified random sample survey that guaranteed respondents confidentiality. A cover letter assured respondents that no individually identifiable information would be disseminated; to further enhance confidentiality, survey operations were conducted by a contractor rather than by the ACR itself. There was a 63% response rate, with a total of 1924 responses. Responses were weighted to make them representative of all radiologists in the United States. Two-tailed z tests of percentages and means and multiple regression analysis were used to compare information for women radiologists with that for men radiologists. Twenty-four percent of radiologists in training (residents and fellows) and 18% of posttraining, professionally active radiologists were women. Forty-one percent of posttraining, professionally active women were younger than 45 years in comparison with 29% of men (P = .004). Women radiologists were more likely to have fellowship training than men (69% vs 60%, P = .007), although they were less likely than men to have a subspecialty certificate (16% vs 27%, P < .001). Thirty-nine percent of women and 16% of men worked part-time (P < .001). Women were more concentrated in academia (22% vs 14%, P = .009) and breast imaging (27% vs 6%, P < .001) than their male peers but were underrepresented in interventional radiology (2% vs 13%, P < .001) and neuroradiology (3% vs 10%, P < .001). In situations where radiologists are likely to be practice owners, fewer women than men were owners (75% vs 91%) (P = .011). Women reported the same level of enjoyment of radiology as did men. Women radiologists differ from men in regard to age, fellowship training, full- versus part-time employment, academic versus nonacademic practice, subspecialty practice, and practice ownership.


Relationship of toxin production to species in the genus Aeromonas.
Ninety-five strains of Aeromonas were divided into three species--A. sobria, A. hydrophila and A. caviae--on the basis of results in 13 biochemical tests. The minimum number of tests necessary to distinguish these species was determined. Culture filtrate of the strains were tested for cytotoxin and cytotonin, haemolysin and protease. One filtrate with high-titre cytotoxin, haemolysin and protease activities was subjected to gel filtration on Sephadex G75 and isoelectric focussing. Of the five cell lines tested, Vero cells were most sensitive to the cytotoxin; no reproducible cytotonic effects were observed. The haemolysin effect appeared to be equivalent to cytotoxin. At least two distinct protease activities were found that might be responsible for the cytotonic effects described. Cytotoxin production was species related; it was present in A. sobria and A. hydrophila but not in A. caviae.


Protease pretreatment increases the efficacy of adenovirus-mediated gene therapy for the treatment of an experimental glioblastoma model.
Effective virus-mediated gene therapy for cancer will be facilitated by procedures that enhance the low level of gene transfer mediated by replication-deficient, recombinant viral vectors. We found recently that protease pretreatment of solid tumors is a useful strategy for enhancing virus-mediated gene transduction in vivo. In this study, we examined the potential of protease pretreatment to improve the efficacy of a gene therapy strategy for prodrug activation that depends on infection with a recombinant adenovirus encoding herpes simplex virus thymidine kinase (Ad-HSV-tk). Trypsin or a dissolved mixture of collagenase/dispase was inoculated into xenografts derived from the human glioblastoma multiforme-derived cell lines, U87 or U251. Ad-HSV-tk was administered 24 h after protease pretreatment, and animals were then treated for 10 days with ganciclovir (GCV). We found that protease pretreatment increased the efficacy of adenovirus mediated HSV-tk/GCV gene therapy in these experimental tumor models. Mice receiving Ad-HSV-tk/GCV after protease pretreatment demonstrated a significantly greater regression of tumors compared with those treated with Ad-HSV-tk/GCV alone. No adverse effects of protease pretreatment were observed. No signs of metastasis were seen either by histological inspection of lymph nodes or by a PCR-based analysis of selected mouse tissues to detect human tumor cells. Our findings indicate that protease pretreatment may be a useful strategy to enhance the efficacy of virus-mediated cancer gene therapy.


Posttransplant diastolic hypertension: associations with intragraft transforming growth factor-beta, endothelin, and renin transcription.
Diastolic hypertension after renal transplantation leads to significant chronic morbidity and mortality. Recently, calcineurin phosphatase inhibition by cyclosporine or tacrolimus has been postulated to lead to diastolic hypertension through the induction of transforming growth factor-beta (TGF-beta) and resultant endothelin-mediated renal arteriolar vasospasm. To investigate this hypothesis in humans, the allografts of 40 stable renal allograft recipients were biopsied 2 to 3 years after transplantation. Both cyclosporine and tacrolimus patients were included. Biopsies were divided and processed for histology and RNA extraction. RNA was then converted to cDNA and evaluated by semiquantitative polymerase chain reaction (actin-standardized, high-performance liquid chromatography-quantitated) for TGF-beta, endothelin, and renin transcription. Inflammatory cytokine gene transcription was also evaluated. Blood pressure was measured during the clinic check-in before biopsy. Variables were evaluated by Spearman rank correlation coefficient (rs) analysis. Diastolic hypertension was prevalent in the study population, with 40% of individuals having diastolic pressure >90 mmHg. TGF-beta and endothelin transcription were detected in 88% of biopsies studied, and renin transcription was detected in 91%. Intragraft transcription of TGF-beta (rs=0.61, P=0.0003) and endothelin (rs=0.43, P=0.0188) was strongly correlated with increasing transcription intragraft renin. In turn, renin transcription was strongly correlated with increasing diastolic blood pressure (rs=0.55, P=0.0015). Histological correlation of fibrosis score did not predict the degree of hypertension, nor did it correlate with TGF-beta transcription. Inflammatory cytokine transcription was not related to renin transcription or diastolic hypertension but was correlated with histological evidence of immune graft injury. These data support the hypothesis that posttransplant diastolic hypertension is a result of TGF-beta-induced, endothelin-mediated arteriolar vasoconstriction and subsequent activation of the renin-angiotensin pathway. These effects are independent of immune-mediated graft injury.


Impact of hypertension and diabetes on the onset of chronic kidney disease in a general Japanese population.
Hypertension (HT) and diabetes mellitus (DM) are both major risk factors for chronic kidney disease (CKD); however, few studies have examined the impacts of the combination of HT and DM on CKD development in general populations. We aimed to explore whether HT or DM contributes more to CKD development in a Japanese community. A total of 5823 individuals without a history of CKD who underwent specific health checkups in fiscal year 2013 were monitored until the end of March 2018. Participants were categorized as having neither HT nor DM (none group), either HT or DM, and both (HT + DM). We calculated the hazard ratios (HRs) for developing CKD in each category using Cox proportional hazards models after adjusting for age, dyslipidemia, smoking, and alcohol drinking and with the none group as the reference. We also estimated the population attributable fraction (PAF) for CKD development in populations with either HT or DM or both. During a mean follow-up of 3.0 years, 759 individuals developed CKD, with HRs of 1.56 with a 95% confidence interval (CI) [1.33, 1.83], 1.22 with a 95% CI [0.86, 1.75], and 2.83 with a 95% CI [2.22, 3.63] for the HT only, DM only and HT + DM categories, respectively. Sex-specific analysis showed similar findings. The PAFs for CKD (14.1% and 17.2% for men and women, respectively) were the highest among participants with HT only. We concluded that in this Japanese community, HT contributed more than DM to CKD development; hence, managing hypertension is important to prevent CKD as well as diabetes.