[Use of the mucoregulator ascoril for respiratory diseases].
The paper deals with the use of the combined mucoregulatory drug ascoril in pulmonological care. Due to its multicomponent composition, the drug has mucoregulatory properties that combine a bronchodilator effect and an ability to dilute sputum and to synthesize the surfactant. The mechanism of action of each ascoril component is analyzed; the results of basic experimental and clinical studies on the use of the drug are given. A wide range of indications, such as respiratory system diseases, for ascoril use is demonstrated.


Engineering protein farnesyltransferase for enzymatic protein labeling applications.
Creating covalent protein conjugates is an active area of research due to the wide range of uses for protein conjugates spanning everything from biological studies to protein therapeutics. Protein Farnesyltransferase (PFTase) has been used for the creation of site-specific protein conjugates, and a number of PFTase substrates have been developed to facilitate that work. PFTase is an effective catalyst for protein modification because it transfers Farnesyl diphosphate (FPP) analogues to protein substrates on a cysteine four residues from the C-terminus. While much work has been done to synthesize various FPP analogues, there are few reports investigating how mutations in PFTase alter the kinetics with these unnatural analogues. Herein we examined how different mutations within the PFTase active site alter the kinetics of the PFTase reaction with a series of large FPP analogues. We found that mutating either a single tryptophan or tyrosine residue to alanine results in greatly improved catalytic parameters, particularly in kcat. Mutation of tryptophan 102β to alanine caused a 4-fold increase in kcat and a 10-fold decrease in KM for a benzaldehyde-containing FPP analogue resulting in an overall 40-fold increase in catalytic efficiency. Similarly, mutation of tyrosine 205β to alanine caused a 25-fold increase in kcat and a 10-fold decrease in KM for a coumarin-containing analogue leading to a 300-fold increase in catalytic efficiency. Smaller but significant changes in catalytic parameters were also obtained for cyclo-octene- and NBD-containing FPP analogues. The latter compound was used to create a fluorescently labeled form of Ciliary Neurotrophic Factor (CNTF), a protein of therapeutic importance. Additionally, computational modeling was performed to study how the large non-natural isoprenoid analogues can fit into the active sites enlarged via mutagenesis. Overall, these results demonstrate that PFTase can be improved via mutagenesis in ways that will be useful for protein engineering and the creation of site-specific protein conjugates.


Trend in HIV incidence in a cohort of homosexual men in Sydney: data from the Health in Men Study.
To determine the incidence of HIV seroconversion in a community-based cohort of homosexual men in Sydney from 2002 to 2006. Participants were recruited between 2001 and 2004 from community-based events and venues. They were tested for HIV annually at follow-up interviews. Each year, the study database was matched against the national HIV register to identify additional HIV seroconversions among men lost to active follow up. The trend in HIV incidence over time was examined using Cox regression. Among 1426 participants, 52 cases of HIV seroconversion were identified between 2002 and 2006, an incidence of 0.87 per 100 person-years (95% CI: 0.65-1.14). HIV incidence varied from 1.67 per 100 person-years in 2002 to 0.39 in 2006 (P trend = 0.282). The median age of HIV seroconversion was 36.9 years, ranging from 22 to 63 years. In this community-based cohort of highly sexually active homosexual men in Sydney, HIV incidence was close to 1% each year and declined non-significantly between 2002 and 2006. These data are consistent with surveillance data suggesting no increase in recent HIV incidence in homosexual men in New South Wales.


Genomic profiles associated with early micrometastasis in lung cancer: relevance of 4q deletion.
Bone marrow is a common homing organ for early disseminated tumor cells (DTC) and their presence can predict the subsequent occurrence of overt metastasis and survival in lung cancer. It is still unclear whether the shedding of DTC from the primary tumor is a random process or a selective release driven by a specific genomic pattern. DTCs were identified in bone marrow from lung cancer patients by an immunocytochemical cytokeratin assay. Genomic aberrations and expression profiles of the respective primary tumors were assessed by microarrays and fluorescence in situ hybridization analyses. The most significant results were validated on an independent set of primary lung tumors and brain metastases. Combination of DNA copy number profiles (array comparative genomic hybridization) with gene expression profiles identified five chromosomal regions differentiating bone marrow-negative from bone marrow-positive patients (4q12-q32, 10p12-p11, 10q21-q22, 17q21, and 20q11-q13). Copy number changes of 4q12-q32 were the most prominent finding, containing the highest number of differentially expressed genes irrespective of chromosomal size (P=0.018). Fluorescence in situ hybridization analyses on further primary lung tumor samples confirmed the association between loss of 4q and bone marrow-positive status. In bone marrow-positive patients, 4q was frequently lost (37% versus 7%), whereas gains could be commonly found among bone marrow-negative patients (7% versus 17%). The same loss was also found to be common in brain metastases from both small and non-small cell lung cancer patients (39%). Thus, our data indicate, for the first time, that early hematogenous dissemination of tumor cells might be driven by a specific pattern of genomic changes.


"You rise up and then you start pulling people up with you": Patient experiences with a peer-delivered behavioral activation intervention to support methadone treatment.
Although medications for opioid use disorder (MOUD) are efficacious treatments for opioid use disorder, retention remains low. Peer recovery specialists (PRSs), individuals with lived substance use and recovery experience, may be particularly well-suited to support patients receiving MOUD. While PRSs are rarely trained in evidence-based behavioral interventions other than motivational interviewing, preliminary evidence suggests that peers can deliver brief behavioral interventions, such as behavioral activation, with efficacy and fidelity. This qualitative study sought to explore patient perspectives on receiving an adapted PRS-delivered behavioral activation intervention (Peer Activate) to support patients receiving methadone treatment. The sample (N = 26) included patients recently starting or demonstrating challenges with adherence at a community-based methadone treatment program who received the Peer Activate intervention in a pilot trial. Participants were invited to participate in in-depth, semi-structured interviews at study completion or discontinuation, assessing perceived acceptability and feasibility of Peer Activate, and stigma-related barriers. Interview transcripts were coded using codebook/template thematic analysis. Analysis revealed the importance of two areas to promote intervention acceptability: 1) connection with intervention content and skill building, and 2) valued PRS-specific qualities. Intervention flexibility was found to promote feasibility of the intervention in the context of chaotic and challenging life circumstances. Additionally, participants described stigma towards substance use and methadone treatment as potential barriers to engaging in methadone treatment. Results support the acceptability and feasibility to patients of this PRS-delivered behavioral activation intervention in the context of outpatient MOUD treatment among a low-income, majority racially minoritized patient population. Future intervention adaptation and implementation should focus on incorporating content related to relationships and interpersonal skills; balancing behavioral intervention content with system navigation support; maintaining flexibility; and further investigation of the impact of individual PRS attributes, including shared lived experiences, on intervention acceptability and shifts in stigma.


The dysplastic pulmonary valve: echocardiographic features and results of balloon dilatation.
The feasibility of using balloon dilatation to relieve stenosis caused by dysplasia of the pulmonary valve was assessed in seven patients (five female, mean age two years) with angiographically confirmed dysplasia who were identified among 38 patients with pulmonary valve stenosis selected for balloon dilatation over a two year period. The clinical features in three patients were consistent with Noonan's syndrome. In all patients the gradient across the valve was assessed by cross sectional echocardiography and Doppler echocardiography before cardiac catheterisation. Balloon dilatation was performed by conventional techniques. In one patient, who had balloon dilatation in the operating room before surgical valvectomy, the diameter of the valve orifice increased from 3 mm to 10 mm. Inspection showed a tear along the anterior commissure. The mean (SD) pressure gradients between the right ventricle and pulmonary artery before and immediately after dilatation in five patients were not significantly different (58 (28) and 47 (12) mm Hg) respectively. There was no overall significant change in the degree of stenosis when four of these patients were examined by Doppler echocardiography six months after operation (44 (17) mm Hg), although one patient (case 5) did show a significant reduction in gradient. This patient had angiographic and echocardiographic features of dysplasia and commissural fusion. Several echographic features were common to all patients and distinguished them from cases of typical pulmonary valve stenosis. These were: pronounced thickening of leaflets; leaflet immobility in diastole and systole; no dilatation of the sinuses of Valsalva in diastole, and supra-annular narrowing. These poor results of balloon dilatation suggest that commissural fusion is not an important mechanism for causing stenosis in the dysplastic pulmonary valve. When dysplasia of the pulmonary valve is identified clinically and echocardiographically, balloon dilatation is unlikely to improve haemodynamic function; it should be attempted if commissural fusion is present.


The portal of geriatrics online education: a 21st-century resource for teaching geriatrics.
The way students are taught and evaluated is changing, with greater emphasis on flexible, individualized, learner-centered education, including the use of technology. The goal of assessment is also shifting from what students know to how they perform in practice settings. Developing educational materials for teaching in these ways is time-consuming and can be expensive. The Portal of Geriatrics Online Education (POGOe) was developed to aid educators in meeting these needs and become quicker, better-prepared teachers of geriatrics. POGOe contains more than 950 geriatrics educational materials that faculty at 45% of allopathic and 7% of osteopathic U.S. medical schools and the Centers for Geriatric Nursing Excellence have created. These materials include various instructional and assessment methodologies, including virtual and standardized patients, games, tutorials, case-based teaching, self-directed learning, and traditional lectures. Materials with common goals and resource types are available as selected educational series. Learner assessments comprise approximately 10% of the educational materials. POGOe also includes libraries of videos, images, and questions extracted from its educational materials to encourage educators to repurpose content components to create new resources and to align their teaching better with their learners' needs. Web-Geriatric Education Modules, a peer-reviewed online modular curriculum for medical students, is a prime example of this repurposing. The existence of a robust compendium of instructional and assessment materials allows educators to concentrate more on improving learner performance in practice and not simply on knowledge acquisition. It also makes it easier for nongeriatricians to teach the care of older adults in their respective disciplines.


The Numbers of Animals Used in Mexico for Scientific and Educational Purposes.
In Mexico, there are no official public and reliably reported data on the total number and species of non-human animals used for scientific purposes. The aim of the current study was to calculate the total numbers of animals used for scientific and educational purposes in Mexico, from January 2015 to October 2021, based on data requested from the National Institute of Transparency, Access to Information and Protection of Personal Data (INAI, in Spanish). In this period, authorised laboratory animal facilities reported the use of 5,437,263 animals for scientific and educational purposes. However, these data should be viewed with caution, since there is no official register of all Mexican institutions that use animals for these purposes. The use of various species of different taxonomic groups was reported, including mammals, birds, reptiles, amphibians, fish and invertebrates. The main scientific purposes of this animal use were: technological development; innovation; laboratory testing; production of biologicals; quality control; diagnostic purposes; basic and applied research; and education. A robust system for the licensing and approval of animal use, as well as a means to ensure compliance with the relevant regulations, are both urgently required. In addition, in order to regulate animal use, monitor animal care and protect their welfare, the creation of a publicly accessible national database that records the number and species of the animals used is imperative.


[Preparation optimization of extract of Moringa oleifera leaves and its immune regulation effect on immunosuppressed mice].
With total flavonoid content and dry extract yield as the observation indexes, the optimal extraction conditions of Moringa oleifera leaves were determined by using single factor test and orthogonal test, and cyclophosphamide modeling method was used to establish immunosuppressed mice models, so as to investigate the effects of M. oleifera leaves extract on immune regulation in mice. The results showed that the optimal preparation conditions were as follows: extraction with 70% ethanol, material-liquid ratio 1:15, extraction temperature 80 °C, three times, 1.5 hours for each time. Under these conditions, the content of total flavonoids from M. oleifera leaves was 15.64 mg·g⁻¹, which can significantly enhance macrophage phagocytosis and immune organ index, promote the synthesis of serum immunoglobulin IgG and hemolysin, and decrease AST activity, with regulation effect on immune dysfunction.


Placental protein 21. Localization in human placenta and concentrations in the body fluids of men and nonpregnant and pregnant women.
The immunohistochemical localization of placental protein 21 (PP21) was marked in the syncytial brush border and basal membrane during the 1st and 2nd trimesters of pregnancy and also in the chorionic epithelial brush border and basement membrane at term. A weaker stain was found in the cell membranes of amniotic epithelial and chorionic trophoblast cells. Neither heparin nor changes in temperature significantly influenced PP21 concentration. Relatively high serum PP21 concentrations were measured during the follicular and luteal phases in healthy nonpregnant women and in healthy men whose seminal plasma also showed a high PP21 concentration. Serum PP21 levels in normal pregnancy rose from a median of 29.1 ng/ml at 6-7 weeks of gestation to 82.0 ng/ml at 36-37 weeks of gestation. Although maternal urine showed low PP21 levels during pregnancy, amniotic fluid PP21 levels were higher at 7-21 weeks of gestation than at term. Cord blood sera showed almost the same PP21 concentration as maternal sera, but retroplacental blood showed much higher levels. Maternal serum PP21 levels in hydatidiform mole patients did not differ from the normal pregnancy range, although their molar vesicular fluids contained higher PP21 concentrations. These results suggest an extraplacental source for PP21.


Practices and perspectives on building integrated data repositories: results from a 2010 CTSA survey.
Clinical integrated data repositories (IDRs) are poised to become a foundational element of biomedical and translational research by providing the coordinated data sources necessary to conduct retrospective analytic research and to identify and recruit prospective research subjects. The Clinical and Translational Science Award (CTSA) consortium's Informatics IDR Group conducted a survey of 2010 consortium members to evaluate recent trends in IDR implementation and use to support research between 2008 and 2010. A web-based survey based in part on a prior 2008 survey was developed and deployed to 46 national CTSA centers. A total of 35 separate organizations completed the survey (74%), representing 28 CTSAs and the National Institutes of Health Clinical Center. Survey results suggest that individual organizations are progressing in their approaches to the development, management, and use of IDRs as a means to support a broad array of research. We describe the major trends and emerging practices below.


The AMPK family member Snf1 protects Saccharomyces cerevisiae cells upon glutathione oxidation.
The AMPK/Snf1 kinase has a central role in carbon metabolism homeostasis in Saccharomyces cerevisiae. In this study, we show that Snf1 activity, which requires phosphorylation of the Thr210 residue, is needed for protection against selenite toxicity. Such protection involves the Elm1 kinase, which acts upstream of Snf1 to activate it. Basal Snf1 activity is sufficient for the defense against selenite, although Snf1 Thr210 phosphorylation levels become increased at advanced treatment times, probably by inhibition of the Snf1 dephosphorylation function of the Reg1 phosphatase. Contrary to glucose deprivation, Snf1 remains cytosolic during selenite treatment, and the protective function of the kinase does not require its known nuclear effectors. Upon selenite treatment, a null snf1 mutant displays higher levels of oxidized versus reduced glutathione compared to wild type cells, and its hypersensitivity to the agent is rescued by overexpression of the glutathione reductase gene GLR1. In the presence of agents such as diethyl maleate or diamide, which cause alterations in glutathione redox homeostasis by increasing the levels of oxidized glutathione, yeast cells also require Snf1 in an Elm1-dependent manner for growth. These observations demonstrate a role of Snf1 to protect yeast cells in situations where glutathione-dependent redox homeostasis is altered to a more oxidant intracellular environment and associates AMPK to responses against oxidative stress.


Receiving the Unwanted Gift: Infection Transmission through Organ Transplantation.
Infections are common in the general U.S. population, so it is inevitable that some persons with a potentially transmissible disease will become organ donors. There are numerous reports of viral, parasitic, fungal, and bacterial transmission through transplantation. At the same time, immunosuppression increases the risk of infection in organ recipients, so attribution of infectious diseases to the transplanted organ is often difficult. Review of the English-language literature. The Organ Procurement and Transplantation Network states that all potential deceased organ donors must be assessed for conditions that may influence donor acceptance. The infections most often transmitted knowingly to organ recipients are cytomegalovirus and hepatitis C virus. There was a 43% increase in the number of potential donor-derived transmission events between 2012 and 2013, but this affected only 3% of transplants; and the patterns of unexpected infection transmissions have remained fairly constant. The 2013 recognition of a case of raccoon rabies in a kidney recipient brought the risk of untested pathogens back into the general discussion of disease transmission. Also, unexpected transmissions of parasitic infection have resulted in highly visible recipient deaths. Organ transplantation has been an enormous advance in the treatment of chronic diseases, but the risk of unanticipated disease transmission has been gaining attention. The task for the organ donation community is to assess risk of transmission of clinically relevant diseases accurately without substantially diminishing organ availability.


Foraging niche shift maintains breeding parameters of a colonial waterbird during range expansion.
Relating the effects of foraging niche variation to reproductive dynamics is critical to understand species response to environmental change. We examined foraging niche variations of the slender-billed gull (Chroicocephalus genei), a nomadic colonial waterbird species during its range expansion along the French Mediterranean coast over a 16-year period (1998-2013). We investigated whether range expansion was associated with a change in chick diet, breeding success, and chicks body condition. We also examined whether breeding success and chicks body condition were explained by diet and colonial characteristics (number of pairs, laying phenology, habitat, and locality). Diet was characterized using dual-stable isotopic proxies (δ 13C and δ 15N) of feather keratin from 331 individuals subsampled from a total of 4,154 chicks ringed and measured at 18 different colonies. δ 13C decreased and δ 15N increased significantly during range expansion suggesting that chicks were fed from preys of increasing trophic level found in the less salty habitat colonized by the end of the study period. Niche shift occurred without significant change of niche width which did not vary among periods, habitats, or localities either. Breeding success and chick body condition showed no consistent trends over years. Breeding success tended to increase with decreasing δ 13C at the colony level while there was no relationship between stable isotope signatures and chick body condition. Overall, our results suggest that even if range expansion is associated with foraging niche shift toward the colonization of less salty and more brackish habitats, the shift had marginal effect on the breeding parameters of the Slender-billed gull. Niche width appears as an asset of this species, which likely explains its ability to rapidly colonize new locations.


DNA damage triggers p21WAF1-dependent Emi1 down-regulation that maintains G2 arrest.
Several regulatory proteins control cell cycle progression. These include Emi1, an anaphase-promoting complex (APC) inhibitor whose destruction controls progression through mitosis to G1, and p21(WAF1), a cyclin-dependent kinase (CDK) inhibitor activated by DNA damage. We have analyzed the role of p21(WAF1) in G2-M phase checkpoint control and in prevention of polyploidy after DNA damage. After DNA damage, p21(+/+) cells stably arrest in G2, whereas p21(-/-) cells ultimately progress into mitosis. We report that p21 down-regulates Emi1 in cells arrested in G2 by DNA damage. This down-regulation contributes to APC activation and results in the degradation of key mitotic proteins including cyclins A2 and B1 in p21(+/+) cells. Inactivation of APC in irradiated p21(+/+) cells can overcome the G2 arrest. siRNA-mediated Emi1 down-regulation prevents irradiated p21(-/-) cells from entering mitosis, whereas concomitant down-regulation of APC activity counteracts this effect. Our results demonstrate that Emi1 down-regulation and APC activation leads to stable p21-dependent G2 arrest after DNA damage. This is the first demonstration that Emi1 regulation plays a role in the G2 DNA damage checkpoint. Further, our work identifies a new p21-dependent mechanism to maintain G2 arrest after DNA damage.


Cardiovascular and muscular adaptations to combined endurance and strength training in elderly women.
Twenty-one women aged 60-75 years were examined to determine whether combined endurance and strength training resulted in greater increase in peak oxygen consumption, sub-maximal time to fatigue, cardiac output, stroke volume, and leg extension load when compared to endurance training alone. Subjects in both the endurance training (E) and endurance and strength (E & S) groups trained 3 days a week, for 12 weeks, at an intensity of 70-80% Vo2 peak for 30 min on a cycle ergometer. Subjects in the E & S groups also used resistance equipment to train the knee extensors. The workload for resistance training was based on an initial assessment of 10 repetitions maximum (10 RM), with 80% of that value used for training, three times weekly. Peak oxygen consumption increased to an average of 24.8 and 29.9% in the E and E & S groups, respectively, with no difference between groups. Subjects in the E & S and E groups significantly increased sub-maximal endurance time by 396 and 165%, respectively. Cardiac output, stroke volume, and arteriovenous oxygen difference at 80% peak VO2 were unchanged by either of the training methods. A needle biopsy was taken from the vastus lateralis before and after 12 weeks of training. Chi-square analysis of fibre area data showed an increase in the frequency of larger type I fibres in the post-training data from the E & S group, but an increase in the frequency of smaller fibres in the E group post-training; however, mean fibre area was not significantly changed by training. These data suggest that greater improvements in sub-maximal time to fatigue and strength is achieved when resistance training is added to an aerobic training programme in healthy elderly women.


Effects of extracellular cations on translation in poliovirus-infected cells.
The effect of pH and different concentrations of added monovalent and divalent cations on translation in poliovirus-infected HeLa cells has been examined. A strong effect on protein synthesis was observed when the concentration of sodium ions was modified. If cells were placed in a hypotonic medium after virus adsorption, no shut-off of cellular translation took place, nor were viral proteins synthesized. An increase in the multiplicity of infection partially overcame this effect. Reversal of the shut-off of cellular translation and inhibition of viral protein synthesis was achieved when cells were placed in hypotonic medium 2 h after infection. Modification of divalent cations (calcium or magnesium) had little or no effect on the pattern of translation. On the other hand, acidic pH (below 6) inhibited both cellular and viral protein synthesis, whereas basic pH had no influence. During infection the synthesis of poliovirus proteins reached a maximum at about 4 to 6 h and then declined. This inhibition of viral translation was partially prevented if cells were placed in a medium containing a high concentration of potassium although the cytopathic effect was prevented. These results indicate that viral protein synthesis and the cytopathic effect were, to a large extent, influenced by the external monovalent ion concentration.


A comparison study on effects of polyglycerols on physical properties of alginate films.
The water solubility and brittleness of unplasticized sodium alginate (SA) films hinder their widely application. Glycerol (GLY), the most commonly used plasticizer, is compatible with alginate due to the formation of hydrogen bonding owing to the hydroxyl functional groups. However, GLY is a small water-soluble molecule, and the resulting leaching problem may lead to decline in mechanical properties of SA films. Aimed at better plasticizers for alginate (ALG) films, this work focuses on the effects of polymerization degree of polyglycerol on physical properties of ALG films. The cross-sectional morphology, crystallinity, mechanical and thermal properties, water solubility, water content and barrier property of ALG films plasticized with GLY, triglycerol (TG) and decaglycerol (DG) were characterized and discussed. Results illustrated that owing to the long molecular chains of TG and DG and their strong interactions with ALG matrix, the plasticized films possessed better mechanical properties, higher water content and lower water solubility. Moreover, it was worth mentioning that even after water treatment, the mechanical properties of ALG-TG and ALG-DG films were superior than that plasticized with GLY. The results of this study were believed to provide particular insights into the plasticization mechanism and the improvement in performance of SA films in packaging applications.


Trends in dementia diagnosis rates in UK ethnic groups: analysis of UK primary care data.
We compared incidence of dementia diagnosis by white, black, and Asian ethnic groups and estimated the proportion of UK white and black people developing dementia in 2015 who had a diagnosis for the first time in a UK-wide study. We analyzed primary care electronic health records from The Health Improvement Network database between 2007 and 2015 and compared incidence of dementia diagnosis to dementia incidence from community cohort studies. The study sample comprised of 2,511,681 individuals aged 50-105 years who did not have a dementia diagnosis prior to the start of follow-up. A total of 66,083 individuals had a dementia diagnosis (4.87/1,000 person-years at risk, 95% CI 4.83-4.90); this incidence increased from 3.75 to 5.65/1,000 person-years at risk between 2007 and 2015. Compared with white women, the incidence of dementia diagnosis was 18% lower among Asian women (adjusted incidence rate ratio (IRR) 0.82, 95% CI 0.72-0.95) and 25% higher among black women (IRR 1.25, 95% CI 1.07-1.46). For men, incidence of dementia diagnosis was 28% higher in the black ethnic group (IRR 1.28, 95% CI 1.08-1.50) and 12% lower in the Asian ethnic group (IRR 0.88, 95% CI 0.76-1.01) relative to the white ethnic group. Based on diagnosis incidence in The Health Improvement Network data and projections of incidence from community cohort studies, we estimated that 42% of black men developing dementia in 2015 were diagnosed compared with 53% of white men. People from the black ethnic group had a higher incidence of dementia diagnosis and those from the Asian ethnic group had lower incidence compared with the white ethnic group. We estimated that black men developing dementia were less likely than white men to have a diagnosis of dementia, indicating that the increased risk of dementia diagnosis reported in the black ethnic group might underestimate the higher risk of dementia in this group. It is unclear whether the lower incidence of dementia diagnosis in the Asian ethnic group reflects lower community incidence or underdiagnosis. A cohort study to determine this is needed.


Developmental expression of voltage-gated potassium channel beta subunits.
Expression of potassium channel beta subunits (Kvbeta) was determined in the developing mouse CNS using an antiserum against an amino acid sequence present in the C-terminus of Kvbeta1, Kvbeta2, and Kvbeta3. Using the anti-Kvbeta antiserum, we determined that Kvbeta expression is restricted to the spinal cord and dorsal root ganglia in the embryonic CNS. At birth, Kvbeta expression is detected in brainstem and midbrain nuclei, but was not detected in the hippocampus, cerebellum or cerebral cortex. During the first postnatal week, Kvbeta expression is present in hippocampal and cortical pyramidal cells and in cerebellar Purkinje cells. Expression of Kvbeta subunits reaches adult levels by the third postnatal week in all of the brain regions examined. A rabbit antiserum directed against a unique peptide sequence in the N-terminus of the Kvbeta1 protein demonstrates that this subunit displays a novel expression pattern in the developing mouse brain. Kvbeta1 expression is high at birth in all brain regions examined and decreases with age. In contrast, Kvbeta2 expression is low at birth and increases with age to reach adult levels by the third postnatal week. These findings support the notion that the differential regulation of distinct potassium channel beta subunits, in the developing mouse nervous system, may confer the functional diversity required to mediate both neuronal survival and maturation.


Opening Editorial: CPD and Lifelong Learning: a call for an evidence based discussion.
This article was migrated. The article was marked as recommended. Globalization of Continuing Professional Development (CPD) is driven by shared educational principles and management trends that facilitate international standards in CPD. These are enforced through instructional design, clinical teaching and assessment methods based on education theory, effective communication skills, and CPD systems strengthening medical education global principles. The growing interest in recognizing CPD and in globalizing CPD accreditation standards has prompted several collaborative international initiatives which include the promotion of national CPD accreditation systems, international collaborations and partnerships, publications of research data and the mutual recognition of international CPD systems and programs.


Expression and localization of NOX2 and NOX4 in primary human endothelial cells.
Reactive oxygen species (ROS) control the integrity of the vascular endothelium. Our laboratory has recently shown that transduction of human umbilical vein endothelial cells (HUVECs) with an active variant of the small GTPase Rac promotes the production of ROS, ROS-dependent activation of p38 mitogen-activated protein kinase, and loss of vascular/endothelial-cadherin-mediated cell-cell adhesion. Here we show that HUVECs express mRNAs for NOX2 as well as NOX4 mRNA, but not for NOX1 or NOX3. Interestingly, NOX4 was expressed at 100-fold higher levels compared with NOX2. NOX4-green fluorescent protein largely localizes to an intracellular compartment that costained with a marker for the endoplasmic reticulum, and its distribution did not overlap with lysosomes, Weibel-Palade bodies, or mitochondria. The NOX2-regulatory proteins p47(phox) and p67(phox) associated with the actin cytoskeleton and were found in cell protrusions and membrane ruffles, colocalizing with Rac1. This translocation to the cell periphery was promoted by tumor necrosis factor (TNF)-alpha. Finally, scavenging of ROS was found to impair TNF-alpha-induced cytoskeletal rearrangements and the formation of a confluent endothelial monolayer. Together, these data prove the differential mRNA expression of NOX family members in human endothelium and indicate that these NOX proteins and their regulators may be involved in the control of endothelial cell spreading, motility, and cell-cell adhesion.


Postural neurocognitive and neuronal activated cerebral blood flow deficits in young chronic fatigue syndrome patients with postural tachycardia syndrome.
Neurocognition is impaired in chronic fatigue syndrome (CFS). We propose that the impairment relates to postural cerebral hemodynamics. Twenty-five CFS subjects and twenty control subjects underwent incremental upright tilt at 0, 15, 30, 45, 60, and 75° with continuous measurement of arterial blood pressure and cerebral blood flow velocity (CBFV). We used an n-back task with n ranging from 0 to 4 (increased n = increased task difficulty) to test working memory and information processing. We measured n-back outcomes by the number of correct answers and by reaction time. We measured CBFV, critical closing pressure (CCP), and CBFV altered by neuronal activity (activated CBFV) during each n value and every tilt angle using transcranial Doppler ultrasound. N-back outcome in control subjects decreased with n valve but was independent of tilt angle. N-back outcome in CFS subjects decreased with n value but deteriorated as orthostasis progressed. Absolute mean CBFV was slightly less than in control subjects in CFS subject at each angle. Activated CBFV in control subjects was independent of tilt angle and increased with n value. In contrast, activated CBFV averaged 0 in CFS subjects, decreased with angle, and was less than in control subjects. CCP was increased in CFS subjects, suggesting increased vasomotor tone and decreased metabolic control of CBFV. CCP did not change with orthostasis in CFS subjects but decreased monotonically in control subjects, consistent with vasodilation as compensation for the orthostatic reduction of cerebral perfusion pressure. Increasing orthostatic stress impairs neurocognition in CFS subjects. CBFV activation, normally tightly linked to cognitive neuronal activity, is unrelated to cognitive performance in CFS subjects; the increased CCP and vasomotor tone may indicate an uncoupling of the neurovascular unit during orthostasis.


The University of North Carolina Pain Center. I. Organization and function.
The University of North Carolina Comprehensive Pain Center, which has been in existence since 1972, is a pain evaluation, treatment and research program based upon individual diagnosis, comprehensive evaluation, and individualized therapy. This is done within the framework of a concurrent program involving anesthesiologists, oral surgeons, neurosurgeons, psychiatrists, physicians from family medicine, clinical psychologists, social workers and specialized nurses. The Center is organized in both the inpatient and outpatient modes. This presentation will briefly describe the operation of the Pain Center and discuss plans for future expansion.


Hepatocellular carcinoma coexisted with second malignancy--a study of 13 cases from a consecutive 440 autopsy cases of HCC.
In a consecutive 440 autopsy cases of hepatocellular carcinoma (HCC), 13 patients (2.95%) were found to have a second primary malignant tumor. All of the patients were male. The age ranged from 40 to 69 years old. (mean: 56.5) Peak incidence occurred in the seventh decade. The associated neoplasms included 4 cases of colorectal adenocarcinoma, 2 cases of thyroid cancer, 2 cases of retroperitoneal sarcomas, 1 case of pancreatic adenocarcinoma, 1 case of esophageal squamous cell carcinoma, 1 case of common bile duct adenocarcinoma, 1 case of renal cell carcinoma, and 1 case of prostatic adenocarcinoma. The organ most commonly involved was large bowel (4 cases). Epithelial origin neoplasms comprised the vast majority (84.6%). Of the 13 cases, 2 associated malignancies existed metachronously, 4 and 5 years before HCC. The others were found at the same time as HCC. The clinical and pathological observations included age, sex, serum alpha-fetoprotein (AFP), serum hepatitis B surface antigen (HBsAg), cirrhosis, gross and histologic appearance. The above presentations were similar in cases with and without second malignancy. We failed to find any factor that was possibly related to the etiology of the second neoplasm. Much more such cases are needed for further evaluation.


N-terminal truncation mutations of adenomatous polyposis coli are associated with primary cilia defects.
Adenomatous polyposis coli (APC) gene is a tumor suppressor gene and its truncated mutations cause a few cilia-related diseases such as Gardner's syndrome. However, little is known about the mechanism that links APC mutations and cilia disorder. APC mutations lead to the expression of N-terminal fragments, which have dominant effects in tumors owing to loss of the C-terminal region or a gain of function. The present study investigated the impact of tumor-associated N-terminal APC fragments on primary cilia assembly and the possible molecular mechanism involved. We discovered that expression of tumor-associated N-terminal APC fragments (APC-N, APC-N1, APC-N2, and APC-N3, which contain amino acids 1-1018, 1-448, 449-781, and 782-1018 respectively), resulted in primary cilia defects. We found that a β-catenin/PI3K/AKT/GSK-3β feedback signal cascade is responsible for causing N-terminal APC fragment-induced cilia defects. In this cascade, dysfunctions of both β-catenin and GSK-3β were involved in the up-regulation of HDAC6 and subsequent decreased acetylated tubulin levels, which thereby led to cilia defects. These data suggest a mechanism for linking N-terminal APC fragments and cilia loss, thus accelerating our understanding of human cilia-related diseases such as Gardner's syndrome and their cause due to APC mutations.


Repeat revascularization versus nephrectomy in the treatment of recurrent renovascular hypertension.
Between 1960 and 1983, 38 patients underwent multiple operations for treatment of recurrent renovascular hypertension. There were 23 women and 15 men who ranged in age from eight to 69 years old (a mean of 48.5 years). The cause of hypertension requiring repeat operation was determined roentgenographically, three patients had new disease of the contralateral nonoperated renal artery, 21 patients had a new lesion of the ipsilateral (previously operated) renal artery and 14 patients had new lesions of both the previously operated and nonoperated renal arteries. Thirty patients underwent a secondary unilateral operation and eight had a bilateral operation. Sixteen patients had unilateral renal artery revascularization, 14 had unilateral nephrectomy, three had bilateral revascularization and five had unilateral revascularization with contralateral nephrectomy. There were three operative deaths (an operative mortality of 7.9 per cent). At hospital dismissal, 30 of 35 patients were improved. Follow-up study ranged from seven months to 23 years (a mean of 7.2 years). There were eight (22.9 per cent) late deaths. Secondary revascularization alone produced improvement in 77 per cent. Nephrectomy alone produced improvement in 80 per cent. We conclude that secondary revascularization is the treatment of choice in patients with recurrent renal artery stenosis. Nephrectomy should be reserved for patients who cannot undergo a revascularization procedure for technical or medical reasons.


A prospective trial of magnetic resonance-guided focused ultrasound thalamotomy for essential tremor: Results at the 2-year follow-up.
Magnetic resonance guided focused ultrasound (MRgFUS) has recently been investigated as a new treatment modality for essential tremor (ET), but the durability of the procedure has not yet been evaluated. This study reports results at a 2- year follow-up after MRgFUS thalamotomy for ET. A total of 76 patients with moderate-to-severe ET, who had not responded to at least two trials of medical therapy, were enrolled in the original randomized study of unilateral thalamotomy and evaluated using the clinical rating scale for tremor. Sixty-seven of the patients continued in the open-label extension phase of the study with monitoring for 2 years. Nine patients were excluded by 2 years, for example, because of alternative therapy such as deep brain stimulation (n = 3) or inadequate thermal lesioning (n = 1). However, all patients in each follow-up period were analyzed. Mean hand tremor score at baseline (19.8 ± 4.9; 76 patients) improved by 55% at 6 months (8.6 ± 4.5; 75 patients). The improvement in tremor score from baseline was durable at 1 year (53%; 8.9 ± 4.8; 70 patients) and at 2 years (56%; 8.8 ± 5.0; 67 patients). Similarly, the disability score at baseline (16.4 ± 4.5; 76 patients) improved by 64% at 6 months (5.4 ± 4.7; 75 patients). This improvement was also sustained at 1 year (5.4 ± 5.3; 70 patients) and at 2 years (6.5 ± 5.0; 67 patients). Paresthesias and gait disturbances were the most common adverse effects at 1 year-each observed in 10 patients with an additional 5 patients experiencing neurological adverse effects. None of the adverse events worsened over the period of follow-up, and 2 of these resolved. There were no new delayed complications at 2 years. Tremor suppression after MRgFUS thalamotomy for ET is stably maintained at 2 years. Latent or delayed complications do not develop after treatment. Ann Neurol 2018;83:107-114.


A flexible model based on piecewise linear approximation for the analysis of left truncated right censored data with covariates, and applications to Worcester Heart Attack Study data and Channing House data.
Left truncated right censored (LTRC) data arise quite commonly from survival studies. In this article, a model based on piecewise linear approximation is proposed for the analysis of LTRC data with covariates. Specifically, the model involves a piecewise linear approximation for the cumulative baseline hazard function of the proportional hazards model. The principal advantage of the proposed model is that it does not depend on restrictive parametric assumptions while being flexible and data-driven. Likelihood inference for the model is developed. Through detailed simulation studies, the robustness property of the model is studied by fitting it to LTRC data generated from different processes covering a wide range of lifetime distributions. A sensitivity analysis is also carried out by fitting the model to LTRC data generated from a process with a piecewise constant baseline hazard. It is observed that the performance of the model is quite satisfactory in all those cases. Analyses of two real LTRC datasets by using the model are provided as illustrative examples. Applications of the model in some practical prediction issues are discussed. In summary, the proposed model provides a comprehensive and flexible approach to model a general structure for LTRC lifetime data.


Assessing speech at three years of age in the cleft palate population: a scoping review of assessment practices.
There is no consensus in the UK regarding the types of speech samples or parameters of speech that should be assessed at 3 years of age in children with cleft palate ± cleft lip (CP±L), despite cleft units routinely assessing speech at this age. The standardization of assessment practices would facilitate comparisons of outcomes across UK cleft units; earlier identification of speech impairments-which could support more timely treatments; and more reliable recording of therapy impacts and surgical interventions. To explore assessment practices used to assess speech in 3-year-old children with CP±L, including speech parameters, methods of assessment and the nature of the speech sample used. A broad examination of the literature was undertaken through the use of a scoping review conducted in accordance with Joanna Briggs Institute guidelines. Search terms were generated from a preliminary search and then used in the main search (Medline, CINAHL, Embase, AMED and PsycINFO). A combination of approaches (medical, linguistic, developmental and functional) is required to assess CP±L speech at age 3. A developmental approach is recommended at this age, considering the complexity of speech profiles at age 3, in which typically developing speech processes may occur alongside cleft speech characteristics. A combined measure for both nasal emission and turbulence, and an overall measure for velopharyngeal function for speech, show potential for assessment at this age. Categorical ordinal scales are frequently used; the use of continuous scales has yet to be fully explored at age 3. Although single-word assessments, including a subset of words developed for cross-linguistic comparisons, are frequently used, more than one type of speech sample may be needed to assess speech at this age validly. The lack of consensus regarding speech samples highlights a need for further research into the types of speech samples 3-year-olds can complete; the impact of incomplete speech samples on outcome measures (particularly relevant at this age when children may be less able to complete a full sample); the impact of different speech samples on the validity of assessments; and the reliability of listener judgements. Whilst a medical model and linguistic approaches are often central in assessments of age-3 cleft speech, this review highlights the importance of developmental and functional approaches to assessment. Cross-linguistic single-word assessments show potential, and would facilitate the comparison of UK speech outcomes with other countries. Further research should explore the impact of different speech samples and rating scales on assessment validity and listener reliability.


Synthesis, characterization of dihydrolipoic acid capped gold nanoparticles, and functionalization by the electroluminescent luminol.
The use of gold nanoparticles as biological probes requires the improvement of colloidal stability. Dihydrolipoic acid (DHLA), a dithiol obtained by the reduction of thioctic acid, appears therefore very attractive for the stabilization and the further functionalization of gold nanoparticles because DHLA is characterized by a carboxylic acid group and two thiol functions. The ionizable carboxylic acid groups ensure, for pH > or = 8, the water solubility of DHLA-capped gold (Au@DHLA) nanoparticles, prepared by the Brust protocol, and the stability of the resulting colloid by electrostatic repulsions. Moreover almost all DHLA, adsorbed onto gold, adopts a conformation allowing their immobilization by both sulfur ends. It is proved by sulfur K-edge X-ray absorption near edge structure spectroscopy, which appears as an appropriate tool for determining the chemical form of sulfur atoms present in the organic monolayer. Such a grafting renders the DHLA monolayers more resistant to displacement by dithiothreitol than mercaptoundecanoic acid monolayers. The presence of DHLA on gold particles allows their functionalization by the electroluminescent luminol through amine coupling reactions assisted by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide. As a luminol-functionalized particle is nine times as bright as a single luminol molecule, the use of the particles as a biological probe with a lower threshold of detection is envisaged.


Analysis of Corneal Densitometry and Endothelial Cell Function in Fuchs Uveitis Syndrome.
To evaluate corneal densitometry and endothelial cell properties in patients with unilateral Fuchs uveitis syndrome (FUS), and to compare results with unaffected contralateral eyes and healthy control subjects. A total of 90 participants were included in this prospective cross-sectional study. Forty-five affected eyes of patients with FUS were regarded as group 1 (FUSa), 45 fellow eyes were regarded as group 2 (FUSf), and 45 healthy-control eyes were regarded as group 3. Corneal densitometry was measured with densitometry software of Scheimpflug Corneal Topography (Pentacam HR, Oculus GmbH, Wetzlar, Germany), whereas endothelial cell measurement was evaluated with specular microscopy (Tomey, EM4000, GmbH, Germany). The mean corneal densitometry values were higher in the midstromal (zones; 2-6, 6-10 mm), posterior (all zones), and total thickness (zones; 2-6, 6-10 mm) layers in the FUSa compared with FUSf and control eyes (P<0.05 for all comparisons). The mean values of average cell area and cell size characteristics (minimum, maximum, SD, and coefficient of variation) were higher; endothelial cell density and percentage of hexagonal cells were lower in the FUSa than in the other two groups (P<0.05 for all comparisons). There was a significantly strong correlation between specular microscopy parameters and posterior corneal densitometry values in the FUSa group. Impairment of endothelial cell function in affected eyes of patients with FUS resulted in increased values of corneal densitometry, especially posterior layer.


Antibodies to cellular antigens in Sjögren's syndrome.
An extract of human lymphocytes from continous cell culture was used as the antigen source to detect antibodies in sera of patients with Sjögren's syndrome (SS). Using double diffusion in agarose, 85 per cent of a selected group of patients had precepating antibodies. Three precipitating antigen-antibody systems were detected and were shown to be different from those described previously in othe systemic rheumatic diseases. The SS precipitating antibodies were temporarily classified as precipitins, A, B, and C. SS patinets with sicca syndrome but without clinical rheumatoid arthritis had precipitin systems A and/or B, and SS patients with associated rheumatoid arthritis had precipitin system C. Serum reactants were demonstrated by immuno-electrophoresis to migrate in the gamma globulin region. The precipitating activity of the serum factors was not destroyed by treatment with 2-mercaptoethanol and was not removed by absorption of rheumatoid factor from the sera. The reactivity of the lympuocyte antigens was destroyed by treatment with trypsin but not by deoxyribonuclease or ribonuclease.


Epigallocatechin gallate upregulates NRF2 to prevent diabetic nephropathy via disabling KEAP1.
Epigallocatechin gallate (EGCG) is the most abundant and effective green tea catechin and has been reported to attenuate diabetic nephropathy (DN). However, the mechanism by which EGCG ameliorates DN, till now, has remained unclear. EGCG is known as a potent activator of nuclear factor erythroid 2-related factor 2 (NRF2), which plays a key role in cellular defense against diabetes-induced oxidative stress and in the prevention of DN. In the present study, we tested whether NRF2 is required for EGCG protection against DN. Therefore, C57BL/6 wild type (WT) and Nrf2 knockout mice were induced to diabetes by streptozotocin, in the presence or absence of a 24-week treatment with EGCG. In the WT mice, EGCG activated Nrf2 expression and function without altering the expression of Kelch-like ECH-associated protein 1 (Keap1). Diabetes-induced renal oxidative damage, inflammation, fibrosis and albuminuria were significantly prevented by EGCG. Notably, deletion of the Nrf2 gene completely abrogated these actions of EGCG. To further determine the effect of EGCG on KEAP1/NRF2 signaling, mouse mesangial cells were treated with high glucose, in the presence of both Keap1 siRNA and EGCG. Interestingly, EGCG failed to enhance NRF2 signaling and alleviate oxidative, inflammatory and fibrotic indicators, in the presence of Keap1 siRNA. The present study demonstrated, for the first time, that NRF2 plays a critical role in EGCG protection against DN. Other findings indicated that inactivation of KEAP1 protein by EGCG may mediate EGCG function in activating NRF2.


Unique and conserved features of floral evocation in legumes.
Legumes, with their unique ability to fix atmospheric nitrogen, play a vital role in ensuring future food security and mitigating the effects of climate change because they use less fossil energy and produce less greenhouse gases compared with N-fertilized systems. Grain legumes are second only to cereal crops as a source of human and animal food, and they contribute approximately one third of the protein consumed by the human population. The productivity of seed crops, such as grain legumes, is dependent on flowering. Despite the genetic variation and importance of flowering in legume production, studies of the molecular pathways that control flowering in legumes are limited. Recent advances in genomics have revealed that legume flowering pathways are divergent from those of such model species as Arabidopsis thaliana. Here, we discuss the current understanding of flowering time regulation in legumes and highlight the unique and conserved features of floral evocation in legumes.


Epidemiology and Predictors of Orbital Fractures in Children.
Data regarding clinical predictors of orbital fractures in children are limited. We sought to describe the epidemiology of pediatric orbital fractures and identify the signs and symptoms of orbital fractures in children. We performed a retrospective cohort study of children younger than 22 years who underwent a facial or orbital computed tomography (CT) scan to evaluate for orbital fracture. We included patients presenting to an emergency department of a tertiary care children's hospital between January 2009 and May 2013. The presence of an orbital fracture was assessed using the final interpretation of the CT by an attending radiologist in the electronic medical record. Among 326 children who underwent facial or orbital CT during the study period, 133 (41%) had an orbital fracture. The presence of nausea or vomiting, orbital tenderness, swelling, or ecchymosis and limitation of extraocular movement were each associated with the presence of an orbital fracture (P < 0.05 for each). Twenty-two children (6.7% of cohort and 16.5% of children with orbital fractures) underwent surgical repair for an orbital fracture. In the absence of orbital tenderness, swelling, or ecchymosis, there was 1 child with an orbital fracture who underwent operative intervention. Fewer than half of children undergoing CT have an orbital fracture identified, and fewer than 7% have a fracture that requires operative intervention. In the absence of orbital tenderness, swelling, or ecchymosis, only 1 child had an orbital fracture requiring surgical repair.


Estimating the incidence of dementia from two-phase sampling with non-ignorable missing data.
Two-phase sampling designs have been used in the field of psychiatry to estimate prevalence and incidence of a rare disease such as dementia and Alzheimer's disease. In a longitudinal study on dementia, since the repeated two-phase sampling is conducted several years after the baseline wave, some subjects may die before the follow-up wave, thus their disease status prior to death is missing. There are reasons to suggest that the missing due to death is non-ignorable. Estimation of disease incidence from longitudinal dementia study has to appropriately adjust for data missing by death as well as the sampling design used at each study wave. In this paper we adopt a selection model approach to model the missing data by death and use a likelihood approach to derive incidence estimates. A modified EM algorithm is used to deal with data from sampling selection. The non-parametric jack-knife variance estimator is used to derive variance estimates for the model parameters and the incidence estimates. The proposed approaches are applied to data from the Indianapolis-Ibadan Dementia Study.


Does visual impairment lead to additional disability in adults with intellectual disabilities?
This study addresses the question to what extent visual impairment leads to additional disability in adults with intellectual disabilities (ID). In a multi-centre cross-sectional study of 269 adults with mild to profound ID, social and behavioural functioning was assessed with observant-based questionnaires, prior to expert assessment of visual function. With linear regression analysis the percentage of variance, explained by levels of visual function, was calculated for the total population and per ID level. A total of 107/269 participants were visually impaired or blind (WHO criteria). On top of the decrease by ID visual impairment significantly decreased daily living skills, communication & language, recognition/communication. Visual impairment did not cause more self-absorbed and withdrawn behaviour or anxiety. Peculiar looking habits correlated with visual impairment and not with ID. In the groups with moderate and severe ID this effect seems stronger than in the group with profound ID. Although ID alone impairs daily functioning, visual impairment diminishes the daily functioning even more. Timely detection and treatment or rehabilitation of visual impairment may positively influence daily functioning, language development, initiative and persistence, social skills, communication skills and insecure movement.


Primary Care Providers' Information Needs for Prescribing Adolescents HIV Pre-Exposure Prophylaxis.
Although knowledge is a salient determinant in primary care providers (PCPs) prescribing HIV pre-exposure prophylaxis (PrEP) to adolescents, we know little about what information PCPs want about PrEP. We conducted an online mixed-method study to explore the PrEP information needs of a national sample of 351 PCPs. We analyzed data with deductive content analysis and compared themes between respondents who were aware and not aware of PrEP, knowledgeable and not knowledgeable of the prescribing guidelines, and prescribed and never prescribed PrEP to an adolescent. PCPs who were unknowledgeable about PrEP and never prescribed PrEP to an adolescent mentioned manufacturing information, indications and dosing, and contraindications and adverse reactions more so than PCPs who were aware of and prescribed PrEP. A better understanding of the information needs of PCPs could inform provider education interventions. Future research must examine the facilitators and barriers to integrating PrEP information into medical education and clinical settings.


Contrast enhancement in atherosclerosis development in a mouse model: in vivo results at 2 Tesla.
To develop an MRI method for the evaluation of contrast enhancement in early atherosclerotic plaque development in the abdominal aorta of a mouse model. Male apoE-/- mice from three groups, respectively 4 (n = 6), 8 (n = 11) and 16 (n = 4) weeks were included. Axial T1 spin echo images of the abdominal aorta were obtained above and below the renal arteries (90 microm spatial resolution) before and over 1 h after the injection of a macromolecular contrast agent. Signal enhancement was measured in the vessel wall and compared to histological features. Maximal arterial wall signal enhancement was obtained from 16 to 32 min post injection. During this time, the signal-to-noise ratio increased by a factor up to 1.7 in 16 week mice and 2.7 and 2.4 in 8 and 4 weeks mice, respectively. The enhancement of the arterial wall appeared less pronounced in the oldest mice, 16 weeks old, exhibiting more advanced lesions. Using a macromolecular gadolinium agent, contrast uptake in atherogenesis varies with lesion stage and may be related to vessel-wall permeability. Dynamic contrast-enhanced MRI may be useful to evaluate the atherosclerotic plaque activity in mice.


Inference of Internal Stress in a Cell Monolayer.
We combine traction force data with Bayesian inversion to obtain an absolute estimate of the internal stress field of a cell monolayer. The method, Bayesian inversion stress microscopy, is validated using numerical simulations performed in a wide range of conditions. It is robust to changes in each ingredient of the underlying statistical model. Importantly, its accuracy does not depend on the rheology of the tissue. We apply Bayesian inversion stress microscopy to experimental traction force data measured in a narrow ring of cohesive epithelial cells, and check that the inferred stress field coincides with that obtained by direct spatial integration of the traction force data in this quasi one-dimensional geometry.


Properties of ribbon and non-ribbon release from rod photoreceptors revealed by visualizing individual synaptic vesicles.
Vesicle release from rod photoreceptors is regulated by Ca(2+) entry through L-type channels located near synaptic ribbons. We characterized sites and kinetics of vesicle release in salamander rods by using total internal reflection fluorescence microscopy to visualize fusion of individual synaptic vesicles. A small number of vesicles were loaded by brief incubation with FM1-43 or a dextran-conjugated, pH-sensitive form of rhodamine, pHrodo. Labeled organelles matched the diffraction-limited size of fluorescent microspheres and disappeared rapidly during stimulation. Consistent with fusion, depolarization-evoked vesicle disappearance paralleled electrophysiological release kinetics and was blocked by inhibiting Ca(2+) influx. Rods maintained tonic release at resting membrane potentials near those in darkness, causing depletion of membrane-associated vesicles unless Ca(2+) entry was inhibited. This depletion of release sites implies that sustained release may be rate limited by vesicle delivery. During depolarizing stimulation, newly appearing vesicles approached the membrane at ∼800 nm/s, where they paused for ∼60 ms before fusion. With fusion, vesicles advanced ∼18 nm closer to the membrane. Release events were concentrated near ribbons, but lengthy depolarization also triggered release from more distant non-ribbon sites. Consistent with greater contributions from non-ribbon sites during lengthier depolarization, damaging the ribbon by fluorophore-assisted laser inactivation (FALI) of Ribeye caused only weak inhibition of exocytotic capacitance increases evoked by 200-ms depolarizing test steps, whereas FALI more strongly inhibited capacitance increases evoked by 25 ms steps. Amplifying release by use of non-ribbon sites when rods are depolarized in darkness may improve detection of decrements in release when they hyperpolarize to light.


Modulation by calcium of gamma-aminobutyric acid (GABA) binding to GABAA and GABAB recognition sites in rat brain. Involvement of different mechanisms.
Calcium modulates sodium-independent binding of gamma-aminobutyric acid (GABA) to GABAA and GABAB recognition sites located in synaptic membranes of rat brain. At 37 degrees the binding of [3H]GABA to the GABAB recognition site is dramatically stimulated by Ca2+ with an EC50 (half-saturation constant) of congruent to 10 microns, whereas the binding to the GABAA recognition site is only slightly, but significantly, potentiated by Ca2+ with an EC50 of congruent to 0.1-1.0 micron. The effect of calcium on GABAA recognition sites requires a temperature of 37 degrees and the presence of calmodulin. Only GABAA recognition sites are linked to benzodiazepine recognition sites, and the interaction between these sites is modulated by Ca2+ at physiological ion concentrations. When free Ca2+ in the assay medium is below 10 nM, only one population of low-affinity GABAA recognition sites can be measured; however, when free Ca2+ is at the micromolar level, or if diazepam is present, a high affinity-binding site appears in addition to the pre-existing low-affinity component. On the basis of affinity there is a single population of GABAB bindings sites, but the number of sites is about 90% greater at 37 degrees than at 4 degrees. This temperature-dependent increase in the number of GABAB recognition sites is calmodulin-independent, and data with leupeptin, hemin, and antipain suggest that this temperature-dependent increase in GABAB sites might involve the activity of Ca2+-dependent protease(s).


Biometric Screening and Future Employer Medical Costs: Is It Worth It to Know?
To study the relationship between a biometric wellness data and future/actual medical costs. A relationship between total cholesterol to high density lipoprotein ratio, blood pressure, and blood glucose and medical costs, based on analysis of claims data, was explored in 1834 employees that had both wellness program biometric and claims data in 2016. Increased total cholesterol to HDL ratio is strongly associated with increased average costs (P < 0.01). Similarly, an increased glucose level is strongly associated with increased average costs (P = 0.001). There was no evidence of a relationship between elevated blood pressure and higher costs. By investing in an employer-sponsored biometric screening of full cholesterol and glucose profiles, medium-sized employers can identify high-risk employees who are expected to incur significantly higher healthcare costs, as compared with low-risk level employees, and improve treatment outcomes.


Evolving Choice Inconsistencies in Choice of Prescription Drug Insurance.
We study choice over prescription insurance plans by the elderly using government administrative data to evaluate how these choices evolve over time. We find large "foregone savings" from not choosing the lowest cost plan that has grown over time. We develop a structural framework to decompose the changes in "foregone welfare" from inconsistent choices into choice set changes and choice function changes from a fixed choice set. We find that foregone welfare increases over time due primarily to changes in plan characteristics such as premiums and out-of-pocket costs; we estimate little learning at either the individual or cohort level.


Incorporation of chlorogenic acids in coffee brew melanoidins.
The incorporation of chlorogenic acids (CGAs) and their subunits quinic and caffeic acids (QA and CA) in coffee brew melanoidins was studied. Fractions with different molecular weights, ionic charges, and ethanol solubilities were isolated from coffee brew. Fractions were saponified, and the released QA and CA were quantified. For all melanoidin fractions, it was found that more QA than CA was released. QA levels correlated with melanoidin levels, indicating that QA is incorporated in melanoidins. The QA level was correlated with increasing ionic charge of the melanoidin populations, suggesting that QA may contribute to the negative charge and consequently is, most likely, not linked via its carboxyl group. The QA level correlated with the phenolic acid group level, as determined by Folin-Ciocalteu, indicating that QA was incorporated to a similar extent as the polyphenolic moiety from CGA. The QA and CA released from brew fractions by enzymes confirmed the incorporation of intact CGAs. Intact CGAs are proposed to be incorporated in melanoidins upon roasting via CA through mainly nonester linkages. This complex can be written as Mel=CA-QA, in which Mel represents the melanoidin backbone, =CA represents CA nonester-linked to the melanoidin backbone, and -QA represents QA ester-linked to CA. Additionally, a total of 12% of QA was identified in coffee brew, whereas only 6% was reported in the literature so far. The relevance of the additional QA on coffee brew stability is discussed.


Clinical presentation of Crohn's disease. association between familial disease, smoking, disease phenotype, extraintestinal manifestations and need for surgery.
Recent molecular data suggest that genetic factors may underlie the disease heterogeneity observed in Crohn's disease (CD). It was also suggested that familial inflammatory bowel disease (IBD) is a homogenous subgroup, phenotypically different from sporadic disease. Our aim was to determine the clinical presentation in a large CD population. 564 CD patients (m/f: 278/286, age: 37.4 (SD 12.7) yrs, duration: 8.4 (7.1) yrs) were included. Disease phenotype was determined according to Vienna classification. Familial disease, extraintestinal manifestations (EIM), need for surgery and smoking habits were also analyzed. Familial IBD was present in 73 (12.9%) patients. Age at onset and presence of EIMs was associated with familial disease. Penetrating (44.6% vs. <10 yrs: 29.1%, P<0.0001) and ileocolonic disease (54.4% vs. 42.8%, P=0.03) were more common in patients with a disease duration of > or =10 yrs. In a logistic regression model female gender, colonic/ileocolonic location, smoking and familial IBD were independent risk factors for EIMs, while ileal and non-inflammatory disease increased the risk for resections. Smoking was also associated with frequent relapses. Familial IBD was associated with the presence of EIMs, while ileal involvement and noninflammatory behavior independently increased the risk for surgery. Since penetrating and extensive disease was more frequent in patients with longer disease duration our data support a possible change in location and behavior during the course of disease.


The impact of making vaccines thermostable in Niger's vaccine supply chain.
Determine the effects on the vaccine cold chain of making different types of World Health Organization (WHO) Expanded Program on Immunizations (EPI) vaccines thermostable. Utilizing a detailed computational, discrete-event simulation model of the Niger vaccine supply chain, we simulated the impact of making different combinations of the six current EPI vaccines thermostable. Making any EPI vaccine thermostable relieved existing supply chain bottlenecks (especially at the lowest levels), increased vaccine availability of all EPI vaccines, and decreased cold storage and transport capacity utilization. By far, the most substantial impact came from making the pentavalent vaccine thermostable, increasing its own vaccine availability from 87% to 97% and the vaccine availabilities of all other remaining non-thermostable EPI vaccines to over 93%. By contrast, making each of the other vaccines thermostable had considerably less effect on the remaining vaccines, failing to increase the vaccine availabilities of other vaccines to more than 89%. Making tetanus toxoid vaccine along with the pentavalent thermostable further increased the vaccine availability of all EPI vaccines by at least 1-2%. Our study shows the potential benefits of making any of Niger's EPI vaccines thermostable and therefore supports further development of thermostable vaccines. Eliminating the need for refrigerators and freezers should not necessarily be the only benefit and goal of vaccine thermostability. Rather, making even a single vaccine (or some subset of the vaccines) thermostable could free up significant cold storage space for other vaccines, and thereby help alleviate supply chain bottlenecks that occur throughout the world.


Failure of anterior cingulate activation and connectivity with the amygdala during implicit regulation of emotional processing in generalized anxiety disorder.
Clinical data suggest that abnormalities in the regulation of emotional processing contribute to the pathophysiology of generalized anxiety disorder, yet these abnormalities remain poorly understood at the neurobiological level. The authors recently reported that in healthy volunteers the pregenual anterior cingulate regulates emotional conflict on a trial-by-trial basis by dampening activity in the amygdala. The authors also showed that this process is specific to the regulation of emotional, compared to nonemotional, conflict. Here the authors examined whether this form of noninstructed emotion regulation is perturbed in generalized anxiety disorder. Seventeen patients with generalized anxiety disorder and 24 healthy comparison subjects underwent functional MRI while performing an emotional conflict task that involved categorizing facial affect while ignoring overlaid affect label words. Behavioral and neural measures were used to compare trial-by-trial changes in conflict regulation. Comparison subjects effectively regulated emotional conflict from trial to trial, even though they were unaware of having done so. By contrast, patients with generalized anxiety disorder were completely unable to regulate emotional conflict and failed to engage the pregenual anterior cingulate in ways that would dampen amygdalar activity. Moreover, performance and brain activation were correlated with symptoms and could be used to accurately classify the two groups. These data demonstrate that patients with generalized anxiety disorder show significant deficits in the noninstructed and spontaneous regulation of emotional processing. Conceptualization of anxiety as importantly involving abnormalities in emotion regulation, particularly a type occurring outside of awareness, may open up avenues for novel treatments, such as by targeting the medial prefrontal cortex.


Structured report improves radiology residents' performance in reporting chest high-resolution computed tomography: a study in patients with connective tissue disease.
PURPOSE To evaluate the performance of radiology residents (RRs) when using a dedicated structured report (SR) template for chest HRCT in patients with suspected connective tissue disease-interstitial lung disease (CTD-ILD), compared to the traditional narrative report (NR). METHODS We retrospectively evaluated 50 HRCT exams in patients with suspected CTD-ILD. A chest-devoted radiologist reported all the HRCT exams as the reference standard, pointing out pulmonary fibrosis findings (i.e., honeycombing, traction bronchiectasis, reticulation, and volume loss), presence and pattern of ILD, and possible other diagnoses. We divided four RRs into two groups according to their expertise level. In each group, RRs reported all HRCT examinations alternatively with NR or SR, noting each report's reporting time. The Cohen's Kappa, Wilcoxon, and McNemar tests were used for statistical analysis. RESULTS Regarding the pulmonary fibrosis findings, we found higher agreement between RRs and the reference standard reader when using SR than NR, regardless of their expertise level, except for volume loss.RRs' accuracy for "other diagnosis" was higher when using SR than NR, moving from 0.48 to 0.66 in the novel group (p = 0.035) and from 0.44 to 0.80 in the expertise group (p < 0.001). No differences in accuracy were found between ILD presence and ILD pattern. The reporting time was significantly lower (p = 0.001) when using SR than NR. CONCLUSION SR is of value in increasing the reporting of critical chest HRCT findings in the complex CTD-ILD scenario and should be used early and systematically during the residency.


Design, implementation, and preliminary in-vivo assessment of a high-CMRR low-NEF wireless EEG miniaturized platform.
This work presents the design, manufacture, test, and preliminary in-vivo assessment of the proof-of-concept of a miniaturized wireless platform for acquiring electroencephalography signals, where the input stage is a high-CMRR current-efficiency custom-made integrated neural preamplifier.Clinical relevance- Small, low-power consumption, wireless, wearable devices for chronically monitoring EEG recordings may contribute to the diagnosis of transient neurological events, the characterization and potential forecasting of epileptic seizures, and provide signals for controlling prosthetic and aid devices.


Retinal imaging in human autopsy eyes using a custom optical coherence tomography periscope.
Age-related macular degeneration (AMD) is a major cause of vision loss in the elderly. To better study the pathobiology of AMD, postmortem eyes offer an excellent opportunity to correlate optical coherence tomography (OCT) imaging characteristics with histopathology. However, postmortem eyes from autopsy present challenges to standard OCT imaging including opaque anterior segment structures and standard of care autopsy processing resulting in oblique views to the macula. To overcome these challenges, we report a custom periscope attached by a standard mount to an OCT sample arm and demonstrate high quality macular OCT acquisitions in autopsy-processed eyes.


Review of smoking cessation research among Asian Americans: the state of the research.
The purpose of this paper is to provide an analytic review of population-based efforts to measure smoking prevalence levels among Asian Americans, and peer-reviewed smoking cessation research targeting Asian Americans. The heterogeneity of Asian Americans has hindered precise determinations of their smoking prevalence and has contributed to the difficulty of implementing standardized smoking cessation interventions. First, we reviewed abstracts of published articles accessible through PUBMED between 1995 and 2005 as well as other reports accessible to the authors to ascertain tobacco control interventions focusing on any Asian American population and the available data sources of Asian Americans' tobacco use. Only two clusters of controlled studies and one uncontrolled smoking cessation intervention study focused on Asian Americans have been published in the peer-reviewed literature. These studies had various degrees of success in cessation. Second, we compiled a list of data sources that contain tobacco use information for Asian Americans in California. These sources could potentially be used to shed light on the strategies of cessation intervention for this group. Community-based trial on tobacco cessation is lacking for Asian Americans even though some of the subgroups bear the heavy burden of smoking. Various survey data that have Asian American tobacco use information should be thoroughly analyzed and the results appropriately interpreted as the basis of intervention for this community. We concluded with three specific recommendations for further research on smoking cessation intervention research focused on Asian Americans.


Effect of seasonal variation on hospital admission due to cardiovascular disease - findings from an observational study in a divisional hospital in Bangladesh.
Seasonal variation in the hospital admission due to cardiovascular disease (CVDs) has been widely reported. However, very limited data on Bangladesh is available regarding this matter. The aim of the current study was to investigate the effect of seasonal variation on hospital admission due to CVDs in a leading hospital of Bangladesh. Over a period of two years (from May 2010 to April 2012), the number of patients hospitalized due to various CVDs and number of death among these hospitalized patients were recorded on a day-to-day basis. The data were recorded according to the chief reason of hospital admission such as myocardial infarction or MI (acute, old and non-ST elevation), unstable angina (UA), exaggeration of stable angina, acute left ventricular failure (LVF), cardiomyopathy (ischemic and dilated) or heart failure, syncope and arrhythmia. The data were cumulated and analyzed on month-wise and season-wise manner. A total of 8371 patients were admitted over the study period (5909 male and 2462 female; M/F ratio - 2.4:1). The highest number of patients were admitted during winter (n = 2839, 33.9%) and lowest during summer (n = 1648, 19.7%). The hospital admission was also significantly higher in winter compared to other seasons (p-value versus summer, autumn and spring was 0.018, 0.020 and 0.023 respectively). Acute MI (n = 2374), Acute LVF (n = 1582) and UA (n = 1277) were the top three reasons for hospitalization. Number of death also significantly higher in winter compared to other seasons (p-value versus summer, winter and spring was 0.044, 0.050 and 0.014 respectively). A seasonal variation in the hospital admission due to CVDs with a peak in winter was clearly demonstrated in the study. These data could be useful to improve causative prevention measures, therapeutic management, and educational strategies.


Directed transdifferentiation of Müller glial cells to photoreceptors using the sonic hedgehog signaling pathway agonist purmorphamine.
Specification of distinct cell types from Müller glial cells is key to the potential application of endogenous repair in retinal regeneration. Sonic hedgehog (SHH) has been established as a potent mitogen for rat Müller glial cells, which also induces Müller glial cells to dedifferentiate and adopt the phenotype of rod photoreceptors. The present study investigated the effects of purmorphamine, a small molecule that activates the SHH‑pathway, in the proliferation, dedifferentiation and transdifferentiation of Müller glial cells, as determined by several methods including immunofluorescence, polymerase chain reaction and western blotting. It was demonstrated that it may be able to replace SHH for the regeneration of retinal neurons. Purmorphamine was revealed to stimulate the proliferation of Müller glial cells by increasing the expression of cyclin D1 and cyclin D3. In addition, purmorphamine‑treated Müller glial cells were induced to dedifferentiate by inducing the expression of progenitor‑specific markers; subsequently differentiating into rod‑like photoreceptors. Intraocular injection of purmorphamine promoted the activation of Müller glial cells, and in turn, the production of rod‑like photoreceptors in acute damaged retina. These results suggested that the endogenous neurogenic capacity of retinal Müller glial cells may be enhanced by this small molecular agonist of the SHH signaling pathway.


Infectious complications and outcomes in children supported with left ventricular assist devices.
Infectious complications constitute a major cause of morbidity and death in adult patients supported with left ventricular assist devices (VADs). The incidence and patient outcomes related to infectious complications in pediatric patients on VAD support remain largely unknown. The aim of this study was to determine the incidence of infection among pediatric VAD recipients and to characterize the microbiology, associated risk factors, and clinical outcome. We conducted a retrospective record review of all patients undergoing VAD support for ≥2 weeks at Texas Children's Hospital from June 1999 to December 2011. Infections were categorized as VAD-specific, VAD-related, or non-VAD-related using the International Society for Heart and Lung Transplantation (ISHLT) definitions for VAD infections. Fifty-two VADs were implanted in 51 patients; of these, 35 patients (69%) had 92 infections while receiving VAD support. These included 10 VAD-specific infections, 23 VAD-related infections, and 59 non-VAD infections. The overall rate of VAD infections (specific + related) was 8/1,000 days of VAD support. The most common pathogens were Staphylococcus aureus, coagulase-negative staphylococci, Pseudomonas aeruginosa, and Candida spp. Of 8 deaths that occurred during VAD support, 3 (37.5%) were directly related to infections. Continuous-flow VAD (p = 0.0427) and prior cardiac transplantation with rejection (p = 0.0191) were significantly associated with development of VAD infections. Infectious complications are common in pediatric patients undergoing VAD support. VAD infections do not prevent successful cardiac transplantation in children.


Adulthood consumption of preserved and nonpreserved vegetables and the risk of nasopharyngeal carcinoma: a systematic review.
The incidence rates of nasopharyngeal carcinoma (NPC) are dramatically higher in certain regions of Asia compared to the rest of the world. Few risk factors for NPC are known; however, in contrast to the hypothesized health benefits of nonpreserved vegetables, it is thought that preserved vegetable intake may play a role in contributing to the higher incidence of NPC in high-risk regions. Therefore, the purpose of this study was to systematically review the epidemiologic evidence on the associations between adulthood intake of preserved and nonpreserved vegetables and NPC risk. A search of the epidemiological literature from 1966 to 2004 was performed using several bibliographic databases, including PubMed and the Chinese Biomedical Literature Database System. There were no language restrictions. Meta-analysis was conducted to obtain pooled odds ratios (ORs) for the highest-versus-lowest categories of preserved and nonpreserved vegetable intake. A total of 16 case-control studies were identified in the search. Results showed that highest-versus-lowest preserved vegetable intake was associated with a 2-fold increase in the risk of NPC (Random Effects Odds Ratio (RE OR) 2.04; 95% Confidence Limits (CL) 1.43, 2.92). Conversely, high nonpreserved vegetable intake was associated with 36% decrease in the risk of NPC (RE OR 0.64; 95% CL 0.48, 0.85). Findings for both preserved and nonpreserved vegetables were consistent across vegetable type and by country of study. Further research in high-risk areas to gain insight into the risk associated with preserved vegetables and protection associated with nonpreserved vegetables may advance understanding of NPC and yield clues for prevention.


Large Bulk Piezophotovoltaic Effect of Monolayer 2H-MoS2.
The bulk photovoltaic effect in noncentrosymmetric materials is an intriguing physical phenomenon that holds potential for high-efficiency energy harvesting. Here, we study the shift current bulk photovoltaic effect in the transition-metal dichalcogenide MoS2. We present a simple automated method to guide materials design and use it to uncover a distortion to monolayer 2H-MoS2 that dramatically enhances the integrated shift current. Using this distortion, we show that overlap in the Brillouin zone of the distributions of the shift vector (a quantity measuring the net displacement in real space of coherent wave packets during excitation) and the transition intensity is crucial for increasing the shift current. The distortion pattern is related to the material polarization and can be realized through an applied electric field via the converse piezoelectric effect. This finding suggests an additional method for engineering the shift current response of materials to augment previously reported methods using mechanical strain.


Glucose homeostasis in Egyptian children and adolescents with β-Thalassemia major: Relationship to oxidative stress.
Oxidative stress in children with β-thalassemia may contribute to shortened life span of erythrocytes and endocrinal abnormalities. This study was aimed to evaluate glucose homeostasis in Egyptian children and adolescents with β-thalassemia major and its relation to oxidative stress. Sixty children and adolescents with β-thalassemia major were studied in comparison to 30 healthy age and sex-matched subjects. Detailed medical history, thorough clinical examination, and laboratory assessment of oral glucose tolerance test (OGTT), serum ferritin, alanine transferase (ALT), fasting insulin levels, plasma malondialdehyde (MDA) as oxidant marker and serum total antioxidants capacity (TAC) were performed. Patients were divided into two groups according to the presence of abnormal OGTT. The prevalence of diabetes was 5% (3 of 60) and impaired glucose tolerance test (IGT) was 8% (5 of 60). Fasting blood glucose, 2-hour post-load plasma glucose, serum ferritin, ALT, fasting insulin level, homeostatic model assessment for insulin resistance index (HOMA-IR) and MDA levels were significantly elevated while TAC level was significantly decreased in thalassemic patients compared with healthy controls (P < 0.001 for each). The difference was more evident in patients with abnormal OGTT than those with normal oral glucose tolerance (P < 0.001 for each). We also observed that thalassemic patients not receiving or on irregular chelation therapy had significantly higher fasting, 2-h post-load plasma glucose, serum ferritin, ALT, fasting insulin, HOMA-IR, oxidative stress markers OSI and MDA levels and significantly lower TAC compared with either those on regular chelation or controls. HOMA-IR was positively correlated with age, serum ferritin, ALT, MDA, and negatively correlated with TAC. The development of abnormal glucose tolerance in Egyptian children and adolescents with β--thalassemia is associated with alteration in oxidant-antioxidant status and increase in insulin resistance. 1- Glucose tolerance tests, HOMA-IR, and MDA should be an integral part of the long-term follow-up of children and adolescents with β-thalassemia major. 2- Regular iron chelation and antioxidant therapy should be advised for thalassemic patients to improve glucose hemostasis.


Lifestyle and behavioral modifications made by patients with interstitial cystitis.
Interstitial cystitis/bladder pain syndrome (IC/BPS) negatively affects the quality of life. In this study, we investigated the lifestyle behavioral changes patients with IC/BPS make to cope with their symptoms. This prospective study was conducted between August 2018 and June 2019. All patients had a primary symptom of suprapubic pain with a full bladder and other lower urinary tract symptoms for more than 6 weeks as well as cystoscopic findings. All participants completed our self-developed questionnaire, which included informations about their living and work environment, occupational garments, dietary habits, and personal habits. Continuous variables were compared using an independent sample t test, and categorical variables were compared using a chi-square test. We recruited 86 patients with IC/BPS and age-matched 86 controls without IC/BPS. In our study, patients with IC/BPS had more cranberry intake (45.34% vs. 5.81%, P < 0.05) than non-IC/BPS controls; the IC/BPS group had decreased consumption of coffee and spicy food; and wore less makeup or special work garments. In conclusion, patients with IC/BPS tend to make several lifestyle behavioral changes to cope with their symptoms.


Lipid domains in the endocytic pathway.
Whereas endosomes connect with both exocytic and endocytic organelle via extensive lipid and protein traffic, each endosome has a distinct lipid and protein composition. Recent observations suggest that different lipid membrane domains exist even in the same endosome. These lipid domains, together with low pH milieu, may present a variety of micro-environments to cargo molecules. Evidence is accumulating which suggests that the alteration of these lipid microdomains may be involved in a number of pathological conditions.


Generation of propagation-invariant and intensity-controlled dark hollow beams by a refractive beam shaping system.
Dark hollow beams (DHBs) have great potential in the applications of optical manipulation, and the generation of DHBs is still a challenging and rewarding issue. In this paper, we present a beam shaping system for generating DHBs. The proposed system is composed of a freeform lens array and a non-classical zoom system which has a constant focal length but various image locations. The DHBs with a well-controlled intensity profile generated by the proposed system is not sensitive to the change of the intensity distribution of the incident beam, which allows flexible choices of light sources. Moreover, the annular pattern produced by the DHB remains unchanged when the image plane is moved a long distance of 17mm, and the energy efficiency of the beam shaping system is greater than 90% when Fresnel loss is considered. The proposed beam shaping system endows the generated DHBs with new properties and may have great potential in the field of optical tweezers and atom guides.


Photodynamic Therapy Is Effective Against Candida auris Biofilms.
Fungal infections are increasing in prevalence worldwide. The paucity of available antifungal drug classes, combined with the increased occurrence of multidrug resistance in fungi, has led to new clinical challenges in the treatment of fungal infections. Candida auris is a recently emerged multidrug resistant human fungal pathogen that has become a worldwide public health threat. C. auris clinical isolates are often resistant to one or more antifungal drug classes, and thus, there is a high unmet medical need for the development of new therapeutic strategies effective against C. auris. Additionally, C. auris possesses several virulence traits, including the ability to form biofilms, further contributing to its drug resistance, and complicating the treatment of C. auris infections. Here we assessed red, green, and blue visible lights alone and in combination with photosensitizing compounds for their efficacies against C. auris biofilms. We found that (1) blue light inhibited and disrupted C. auris biofilms on its own and that the addition of photosensitizing compounds improved its antibiofilm potential; (2) red light inhibited and disrupted C. auris biofilms, but only in combination with photosensitizing compounds; and (3) green light inhibited C. auris biofilms in combination with photosensitizing compounds, but had no effects on disrupting C. auris biofilms. Taken together, our findings suggest that photodynamic therapy could be an effective non-drug therapeutic strategy against multidrug resistant C. auris biofilm infections.


Genomic positions of co-expressed genes: echoes of chromosome organisation in gene expression data.
The relationships between gene expression and nuclear structure, chromosome territories in particular, are currently being elucidated experimentally. Each chromosome occupies an individual, spatially-limited space with a preferential position relative to the nuclear centre that may be specific to the cell and tissue type. We sought to discover whether patterns in gene expression databases might exist that would mirror prevailing or recurring nuclear structure patterns, chromosome territory interactions in particular. We used human gene expression datasets, both from a tissue expression atlas and from a large set including diverse types of perturbations. We identified groups of positional gene clusters over-represented in gene expression clusters. We show that some pairs of chromosomes and pairs of 10 Mbp long chromosome regions are significantly enriched in the expression clusters. The functions of genes involved in inter-chromosome co-expression relationships are non-random and predominantly related to cell-cell communication and reaction to external stimuli. We suggest that inter-chromosomal gene co-expression can be interpreted in the context of nuclear structure, and that even expression datasets that include very diverse conditions and cell types show consistent relationships.


Safety and Efficacy of Treatment for Scolios Is Secondary to Spinal Muscular Atrophy Fused to Lumbar 5 Level.
Patients with spinal muscular atrophy (SMA) usually have progressive scoliosis. Although fusion of the sacrum or pelvis has been recommended for correcting pelvic obliquity (PO), the procedure is invasive. This study determined as to whether performing instrumentation to the fifth lumbar vertebra (L5) is safe and effective for scoliosis in patients with SMA. Twelve patients with SMA underwent posterior spinal fusion and stopping instrumentation at the L5 level. We evaluated age at surgery, the duration of surgery, blood loss, complications, preoperative and postoperative Cobb angles, and PO. The mean age at surgery was 11.4 years; the mean duration of surgery was 319 minutes, and the mean blood loss was 1170 mL. The Cobb angle improved from 97.3° to 39.1° at 1 month postoperatively (correction rate, 60.9%) and to 42.3° at the final follow-up. PO was corrected from 27.8° to 13.1° at 1 month postoperatively (correction rate, 51.7%) and to 19.8° at the final follow-up. No complications were reported. All patients showed improvement in low back pain, with reduced difficulty while sitting. However, >10% correction loss of PO was observed in 6 patients with high preoperative PO. The correction rate of scoliosis in SMA patients with posterior spinal fusion and instrumentation to the L5 level was acceptable, and no complications occurred. Scoliosis associated with SMA was more rigid and severer than scoliosis associated with Duchenne muscular dystrophy. Correction rates of the Cobb angle and PO in SMA patients with instrumentation to L5 were similar to those in SMA patients with instrumentation to the sacrum or pelvis. Correction loss of PO was greater in patients with high preoperative PO than in those with low preoperative PO. Instrumentation and fusion to L5 for scoliosis in patients with SMA seems safe and effective, except in cases of high preoperative PO.