Improving physician performance through peer comparison feedback.
A project to improve physician performance in colorectal cancer screening was evaluated as part of an ambulatory quality assurance program. A minimum standard was adopted requiring a digital examination and stool test for occult blood at annual check-ups of patients aged 40 years and older. During a 31/2-year period, three different intervention strategies for improved compliance with the standard were sequentially implemented and assessed: educational meeting, retrospective feedback of group compliance rate, and retrospective feedback of individual compliance rate compared with that of peers. A pretest/posttest design was employed in evaluating the first two intervention strategies. Neither strategy resulted in significant improvement in compliance. Monthly feedback of individual performance ranked with that of peers was then implemented in a randomized clinical trial utilizing a crossover design. During the first 6-month period, the physicians receiving feedback (group 1) improved from 66.0% to 79.9% (P less than 0.001), while the control group (group 2) also improved, from 67.5% to 76.6% (P less than 0.001), suggesting a spillover effect. During the second 6-month period, group 2 received feedback and group 1 did not. Group 1 stabilized at approximately 80% while group 2 continued to improve from 76.6% to 84.0% (P less than 0.001). Behavior changes persisted at 6 and 12 months after intervention.


The Early Tech Development Course: Experiential Commercialization Education for the Medical Academician.
Research produced by medical academicians holds promise for developing into biomedical innovations in therapeutics, devices, diagnostics, and health care information technology; however, the road to biomedical innovation is fraught with risk, including the challenge of moving from basic research insight onto a viable commercialization path. Compounding this challenge is the growing demand on medical academicians to be more productive in their clinical, teaching, and research duties within a resource-constrained environment. In 2014, the University of Michigan (UM) Medical School and College of Engineering codesigned and implemented an accelerated, biomedical-focused version of the National Science Foundation (NSF) Innovation Corps (I-Corps) program. The UM Early Tech Development (ETD) Course, designed for medical academicians exploring the commercial potential of early-stage ideas, covers the NSF I-Corps concept; supports the formation of teams of faculty, graduate, and medical students; and accommodates medical academicians' schedules. From 2014 to 2015, the ETD Course graduated 39 project teams from UM and other institutions. One-third of the teams have continued to pursue their projects, receiving additional funding, engaging industry partners, or enrolling in the NSF I-Corps program. The ETD Course, a potential pipeline to the NSF I-Corps program, captures a target audience of medical academicians and others in academic medicine. To better understand the long-term effects of the course and its relationship to the NSF I-Corps program, the authors will conduct a study on the careers of all ETD Course graduates, including those who have enrolled in NSF I-Corps versus those who have not.


Benign hepatic portal venous gas following blunt abdominal trauma.
A case of transient hepatic portal venous gas (HPVG) following blunt abdominal trauma is presented. No evidence of a serious mucosal breach or direct complication was seen. Benign forms of HPVG are being increasingly reported and must be considered in order to avoid unnecessary invasive procedures.


[Phenotypic and molecular genetic properties of Escherichia coli clinical strains isolated from patients with urological diseases].
Microbiological and molecular genetic characterization resistance profiles of Escherichia coli strains isolated in a pilot single-center clinical study from patients of the urological department in Yaroslavl in 2016-2017. Clinical strains of E. coli (n=18) were isolated from the urine of women aged 23-84 years. The mobility of bacteria, colicinogenicity, and sensitivity to lactobacilli antagonism, biofilm formation, and susceptibility to antimicrobials were evaluated. The antibiotic resistance genes were identified. The E. coli strains had a wide heterogeneity in mobility, colicinogenicity, and biofilm formation. They were sensitive to Lactobacillus acidophilus antagonism, as well as to nitrofurantoin, meropenem, fosfomycin and the main functional classes of disinfectants and antiseptics, but are resistant to beta-lactams, fluoroquinolones and aminoglycosides. The mcr-1 gene providing resistance to colistin was identified in two strains. Analysis of genetic antibiotic resistance determinants revealed the genetic diversity of clinical E. coli strains. The obtained data on the strain sensitivity to antibacterials and disinfectants can be used by clinicians in choosing the optimal antibiotic therapy and treatment of abiotic surfaces in urological departments.


[Indirect lymphography of sub-mental and sub-maxillary lymph nodes (author's transl)].
This report presents our observations in 81 cases; and we have used indirect lymphography only, we injected the contrast medium, lipiodole ultra fluide, intramuscularly to both sides of the tongue. The injection sites are first anaesthetized. The amount of contrast medium should not exceed 5 cc. It is injected in about 10 mn. The first radiological examination is performed 4, 8 and 12 hours after the injection. X-rays are taken using the occipitomental and also lower intraoral occlusal views. The following radiological studies are made after 24 and 48 hours. If necessary further x-rays can be taken as well.


Low-temperature growth and dye-sensitized solar cells applications of flower-shaped ZnO hexagonal nanorods.
Flower-shaped ZnO structures composed of hexagonal nanorods were grown in a large-quantity via simple aqueous solution process by using zinc nitrate as a source of zinc ions at low-temperature of approximately 85 degrees C. The as-grown flower-shaped ZnO structures composed of hexagonal nanorods were characterized in terms of their structural, optical and photovoltaic properties by using X-ray diffraction pattern (XRD), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), selected area electron diffraction (SAED) pattern, FTIR, UV-Vis and Raman-scattering spectroscopy. The detailed structural investigations confirmed that the as-synthesized products are well-crystalline and possessing wurtzite hexagonal phase. For the application point of view, the as-grown flower-shaped ZnO structures composed of hexagonal nanorods were used as photo-anode materials to fabricate the dye sensitized solar cells (DSSCs). An overall light to electricity conversion efficiency of 1.1% with a short-circuit current of 4.34 mA/cm2, open-circuit voltage of 0.554 V and fill factor of 0.45, were achieved for the fabricated solar cell based on flower-shaped ZnO structures composed of hexagonal nanorods.


Bone SPECT of the spine: a comparison of attenuation correction techniques.
Image artifacts from variable self-attenuation are recognized as major sources of diagnostic uncertainty in SPECT. For myocardial perfusion studies, an attenuation map is often obtained from a separate transmission study. However, for many applications such as bone SPECT, it has been believed to be unnecessary to obtain a transmission study to correct for the effects of attenuation. We have had significant success in clinical management of lower spine pain using bone SPECT. This success has led us to consider SPECT for the management of cervical spine pain. Cervical spine reconstructions without attenuation correction are difficult to interpret, because the high attenuation in the mandible and skull tends to decrease estimates of activity of the upper cervical spine, and the lower cervical/upper thoracic vertebrae are obscured by the shoulders. We present a technique that uses downscatter to provide attenuation correction for these acquisitions and compare it with other recognized attenuation correction techniques. An emission study is acquired using two windows: one for obtaining the photopeak data and another for obtaining the downscattered photons. A body outline is estimated from these datasets using a projection data thresholding method. From this outline, a uniform attenuation map is created using attenuation coefficients appropriate for 99mTc in water (0.154 cm(-1)). These maps are used in SPECT reconstruction using ordered-subset expectation maximization (OSEM). This method is compared with (a) no attenuation correction (NC), (b) conventional Chang attenuation correction based on the interactive determination of the body outline from the 99mTc emission photopeak data (ChangAC) and (c) OSEM correction using attenuation maps estimated with a line source and fanbeam collimators (transAC). Patient studies using scatterAC demonstrated a significant improvement in the uniformity of estimated cervical spine uptake in normal patients, compared with either NC or ChangAC. Results using scatterAC were similar to those of transAC. We also observed significant improvement in uniformity using scatterAC in SPECT of the lower back in obese patients, as well as the relative limitations of scatterAC versus nonuniform, transmission-based attenuation correction. Comparisons with reconstructions using transmission data for estimating attenuation demonstrate that reasonable quantitative accuracy can be obtained in SPECT of the cervical spine using this simple attenuation estimate. Both scatterAC and transAC appear to provide consistent and expected uniform spine uptake in the cervical spines of normal patients.


Conserved threonine 1505 in the catalytic domain stabilizes mouse DNA methyltransferase 1.
In mammals, DNA methyltransferase 1 (DNMT1) is responsible for propagating the DNA methylation pattern into the next generation through selective methylation of hemi-methylated CpG that emerges just after replication, a process known as maintenance methylation. The T1505, which is conserved among DNMT1s of vertebrates, in the catalytic domain of mouse DNMT1 forms the hydrogen bond with the W1512, which is also conserved among vertebrates and one of the essential residues in recognition of the 5-methylcytosine in hemi-methylated CpGs. However, importance of the hydrogen bond between T1505 and W1512 is unknown. In this study, we determined the crystal structure of mouse DNMT1(291-1620) that replaced T1505 with alanine (DNMT1(291-1620)T1505A) and examined its DNA methylation activity in vitro. Although the mutation lost the hydrogen bond between T1505 and W1512, the overall structure of DNMT1(291-1620)T1505A remained almost identical with that of the wild type. Structural stability and DNA methylation activity of DNMT1(291-1620)T1505A under physiological temperature were lower than those of DNMT1(291-1620). T1505 is crucial on the DNA methylation activity of DNMT1 through stabilizing its structure during ongoing round of DNA methylation.


Youth Perceptions of Parental Involvement and Monitoring, Discrepancies With Parental Perceptions, and Their Associations With First Cigarette Use in Black and White Girls.
Low parental involvement and monitoring are risk factors for adolescent cigarette use. Assessments of parental involvement and monitoring by youth and parents may capture an additional source of risk: differences in perceptions of these parenting behaviors. This study tested for unique contributions of youth-reported parental involvement and monitoring and youth-parent discrepancies in reporting to first cigarette use in girls. Data were drawn from interviews at ages 8-17 with 1,869 girls (57.3% Black, 42.7% White) and their primary caregivers (94% mothers) in the Pittsburgh Girls Study. Cox proportional hazards regression analyses were conducted to predict first cigarette use as a function of girls' reports of parental involvement and monitoring, magnitude and direction of youth-parent reporting discrepancies, and the interaction between them, adjusting for neighborhood, socioeconomic, and individual level factors. High magnitude of discrepancy in parental involvement reports (hazard ratio [HR] = 1.14, 95% confidence interval [CI] [1.03, 1.26]) and lower perceived parental involvement by girls (HR = 1.14, CI [1.03, 1.27]) were associated with an elevated risk for first cigarette use. Girls' reports of low parental monitoring also predicted first cigarette use (HR = 1.14, CI [1.06, 1.21]). Girls whose parents have limited awareness of their whereabouts and friends (i.e., low monitoring) are at an elevated risk for trying cigarettes, but parent-daughter differences in perceived awareness do not affect risk. By contrast, girls who perceive a lower degree of parental involvement than their parents do are at increased risk. Monitoring is one component of parenting that may reduce smoking risk; shared perspectives on the parent's level of involvement are similarly important.


Development and validation of a short form of the Fugl-Meyer motor scale in patients with stroke.
The 50-item Fugl-Meyer motor scale (FM) is commonly used in outcome studies. However, the lengthy administration time of the FM keeps it from being widely accepted for routine clinical use. We aimed to develop a short form of the FM (the S-FM) with sound psychometric properties for stroke patients. The FM was administered to 279 patients. It was then simplified based on expert opinions and the results of Rasch analysis. The psychometric properties (including Rasch reliability, concurrent validity, predictive validity, and responsiveness) of the S-FM were examined and were compared with those of the FM. The concurrent validity and responsiveness of the S-FM were further validated in a sample from the Netherlands. We selected 6 items for each subscale to construct a 12-item S-FM. The S-FM demonstrated high Rasch reliability, high concurrent validity with the original scale, moderate responsiveness, and moderate predictive validity with the comprehensive activities of daily living function. The S-FM also showed sufficient concurrent validity and responsiveness on the Dutch sample. Our results provide strong evidence that the psychometric properties of the S-FM are comparable with those of the FM. The S-FM contains only 12 items, making it a very efficient measure for assessing the motor function of stroke patients in both clinical and research settings.


Neuromuscular Electric Stimulation in Addition to Exercise Therapy in Patients with Lower Extremity Paresis Due to Acute Ischemic Stroke. A proof-of-concept randomised controlled trial.
Exercise therapy and neuromuscular electrical stimulation (NMES) during the initial 14 days after stroke may benefit recovery of gait. We aimed to determine whether poststroke NMES of vastus medial and tibial muscles during exercise therapy is more effective than exercise therapy alone. In this proof-of-concept randomised trial patients with first-ever acute ischemic stroke and a leg paresis (40-85 years of age) were randomised (1:1) to 10 min of daily NMES + exercise therapy or exercise therapy alone. Primary outcome was the between-group difference in change in 6 min Walk Test (6MWT) at 90 days post stroke estimated with a mixed regression model. Secondary outcomes included 10 m Walk Test, Fugl-Meyer Motor Assessment, Guralnik Timed Standing Balance, Sit to Stand, Timed Up and Go, EQ-5D-5L, Montreal Cognitive Assessment and Becks Depression Inventory. 50 stroke survivors (25 in each group) with a mean age of 67 years (range 43-83) were included. An insignificant between-group difference in change of 28.3 m (95%CI -16.0 to 72.6, p = 0.23, adjusted for baseline) in 6MWT at 90-days follow-up was found, in favour of the NMES group. All secondary outcomes showed no statistically significant between-group difference. The conclusion was that adding NMES to exercise therapy had no effect on poststroke walking distance measured by the 6 MWT or any of the secondary outcomes. In this proof-of-concept RCT, we demonstrated that NMES in addition to exercise therapy during the first 14 days after onset of ischemic stroke did not improve walking distance or any of the secondary outcomes. Future studies with a longer trial period, stratifying patients into subgroups with comparable patterns of expected spontaneous recovery - if possible within 48 h post stroke, and greater sample size, than in this study are suggestions of how rehabilitation research could go on exploring the potential for NMES as an amplifier in stroke recovery.


[Clinical and Ultrasonographic Characteristics of Women With Gestational Hypertension].
We studied clinical and ultrasonographic parameters in pregnant women - 183 with and 152 without gestational arterial hypertension (GAP). Characteristics of women with GAP were as follows: age 16-45 years, mean age 27.9+/-4.7 years, disease duration 8.8+/-4.0 weeks, mean systolic and diastolic blood pressure at initial examination 150.2+/-4.8 and 93.1+/-6 mm Hg, respectively. Results of this study allowed us to make the following conclusions. Social, historical, constitutional parameters can contribute to the development of hypertension during pregnancy. GAP is associated with development of hypertrophy of left ventricular myocardium and its subsequent remodeling, hypertrophy and dilatation of the right ventricle, i.e. formation of morphological substrate for heart failure. Dynamics of echocardiographic structural-geometrical parameters of pregnant women with GAP is related to type and degree of hypertension.


[Inhibition of bacterial adhesion of uropathogenic Escherichia coli strains by the urine of patients treated with nitroxoline].
The present study evaluates the effects of sub-inhibitory concentrations of nitroxoline, (oxyquinoline derivative) widely used in the treatment of uncomplicated, urinary tract infections, on the adherence of uropathogenic strains of Escherichia coli. These bacterial strains showed mannose sensitive and/or mannose resistant hemagglutinating activity (HA). In the presence of nitroxoline and at sub-MIC concentrations, inhibition of adherence is 90% (MIC/4), 87% (MIC/8), and 70% (MIC/16), whatever HA's are expressed by the E. coli strains. The inhibitory effect on adherence is also observed in the urine after oral administration of 400 mg of nitroxoline. The concentrations of nitroxoline in the urine are determined by microbiological assay (anti-bacterial activity) and by physico-chemical assay (total nitroxoline and free nitroxoline). The percentages of inhibition are related to the concentrations of free and conjugated nitroxoline. For a 1/16 dilution of urine, the inhibitory effect is 70% and 87% respectively 1 h 30 and 2 h 30 after oral administration of nitroxoline. After 5 h, a similar inhibitory effect is observed for a 1/2 dilution of urine. These results justify the performance of a clinical trial on the prophylaxis of recurrent urinary tract infections by nitroxoline.


[Consensus on clinical diagnosis, treatment, and prevention of chemotherapy-induced neutropenia in China (2023 edition)].
Chemotherapy-induced neutropenia (CIN) is a common hematological adverse events and dose-limiting toxicities of chemotherapy. CIN may lead to dose reduction and delay of chemotherapeutic agents, febrile neutropenia and severe infection, which results in increased treatment cost, reduced efficacy of chemotherapy, and even life-threatening morbidities. Assessment of risk of CIN, early detection of FN and infection, and proper prevention and treatment play a crucial role in reducing the occurrence of CIN-related morbidities, improving patient treatment safety and anticancer efficacy. Based on evidence and expert opinion, the expert committee of Chinese Anti-Cancer Association issued "the consensus on diagnosis and treatment of chemotherapy-induced neutropenia in China (2023 edition)", which is an update version of the 2019 edition, aiming to provide reference for the diagnosis and treatment of CIN for Chinese oncologists.


Learning epigenetic regulation from mycobacteria.
In a eukaryotic cell, the transcriptional fate of a gene is determined by the profile of the epigenetic modifications it is associated with and the conformation it adopts within the chromatin. Therefore, the function that a cell performs is dictated by the sum total of the chromatin organization and the associated epigenetic modifications of each individual gene in the genome (epigenome). As the function of a cell during development and differentiation is determined by its microenvironment, any factor that can alter this microenvironment should be able to alter the epigenome of a cell. In the study published in Nature Communications (Yaseen 2015 Nature Communications 6:8922 doi: 10.1038/ncomms9922), we show that pathogenic Mycobacterium tuberculosis has evolved strategies to exploit this pliability of the host epigenome for its own survival. We describe the identification of a methyltransferase from M. tuberculosis that functions to modulate the host epigenome by methylating a novel, non-canonical arginine, H3R42 in histone H3. In another study, we showed that the mycobacterial protein Rv2966c methylates cytosines present in non-CpG context within host genomic DNA upon infection. Proteins with ability to directly methylate host histones H3 at a novel lysine residue (H3K14) has also been identified from Legionella pnemophilia (RomA). All these studies indicate the use of non-canonical epigenetic mechanisms by pathogenic bacteria to hijack the host transcriptional machinery.


The MHF complex senses branched DNA by binding a pair of crossover DNA duplexes.
The conserved MHF1-MHF2 (MHF) complex functions in the activation of the Fanconi anaemia pathway of the DNA damage response, in regulating homologous recombination, and in DNA replication fork maintenance. MHF facilitates the processing of multiple types of branched DNAs by the DNA translocase FANCM. Here we report the crystal structure of a human MHF-DNA complex that reveals the DNA-binding mode of MHF. The structure suggests that MHF prefers branched DNA over double-stranded DNA because it engages two duplex arms. Biochemical analyses verify that MHF preferentially engages DNA forks or various four-way junctions independent of the junction-site structure. Furthermore, genetic experiments provide evidence that the observed DNA-binding interface of MHF is important for cellular resistance to DNA damage. These results offer insights into how the MHF complex recognizes branched DNA and stimulates FANCM activity at such a structure to promote genome maintenance.


Asthma--the problem and the paradox.
Asthma is a common condition world-wide. Recent data show an increase in prevalence in the United Kingdom, and there is disturbing evidence of increases in morbidity and mortality from asthma in many countries. The reasons for these increases are unclear, but they are occurring in the face of dramatic increases in the sales of potent anti-asthmatic medications, with a particular emphasis on the use of beta agonists and inhaled corticosteroids. Furthermore, despite much publicity and education, the management of acute severe asthma is variable and often ineffectual. Identification of the reasons for the epidemiological trends is essential. The development of new potent prophylactic agents for treatment will help; it is, however, incumbent on us to examine our current pharmacological approach to asthma and to re-evaluate the drugs currently available, both in terms of their clinical use and our understanding of their modes of action. Comparison of morbidity and mortality figures between countries, and relating these figures to what is known about the use of medication in those countries should help clarify and co-ordinate approaches to treatment, and dispel some of the therapeutic myths which have currency at present.


An interventional pilot study on obesity among low-income patients using a computer-based weight management module.
Primary care physicians infrequently address lifestyle modification with their obese patients, among whom those of lower economic means are disproportionately represented. To enhance patients' access to education on lifestyle modification, a clinic-based computer kiosk was installed at our residency clinic for the purpose of healthy lifestyle education. While posttest scores improved and were maintained after completion of lifestyle modification education, body mass index (BMI) was essentially unaffected. Computer-based education without intensive counseling on lifestyle modification appears ineffective in reducing BMI amongst obese patients of lower economic means. Accountable care organization-sponsored health coaching may represent a potential means by which intensive counseling is accomplished among such patients.


Characterization and Functional Analysis of the Poplar Pectate Lyase-Like Gene PtPL1-18 Reveal Its Role in the Development of Vascular Tissues.
Pectin is a major component of plant cell walls, and the structure of pectin impacts on the properties of wood. Although we know that pectate lyase (PL, EC 188.8.131.52) has a major influence on the structure of pectin, our knowledge of Pectate lyase-like genes (PLL) in tree species remains limited. To better understand the characteristics of PLL genes in trees and to identify novel PLL genes that are potentially involved in the development of wood, we performed comprehensive analyses of gene structures, phylogenetic relationships, chromosomal locations, gene duplication events, conserved protein motifs, and gene expression patterns of 30 PLLs in Populus trichocarpa (PtPL1s). We performed an in silico gene expression profiling and quantitative real-time PCR analysis and found that most of the PtPL1 genes from subgroups Ia and Ib were highly expressed in xylem. PtPL1-18 from subgroup Ia was preferentially expressed in developing primary xylem and in xylem cells that were developing secondary walls. Overexpression of PtPL1-18 in poplar reduced plant growth and xylem development. Reduced secondary cell wall thickening and irregular xylem cells were observed in the transgenic trees, probably due to their lower pectin content. Although pectin is not a major component of plant secondary cell walls, our results are consistent with the PtPL1 genes performing important functions during wood formation.


Lipid peroxidation in diabetic retinopathy.
Oxidative stress has been implicated in pathogenesis of diabetic retinopathy. It has been hypothesized that hyperglycaemia may damage vascular endothelium and retina by inducing the synthesis of oxidant reactive species. The aim of the present study was to estimate lipid peroxidation by detecting the concentration of malondialdehyde and 4-hydroxynonenal in diabetic patients with retinopathy, subjects without retinopathy and the reference group. Sixty-one patients were studied, including 30 patients with severe non-proliferative retinopathy in NIDDM and 31 diabetic patients without retinopathy. The reference group were 11 systemic healthy patients. Concentration of malondialdehyde and 4-hydroxynonenal was measured in plasma sample using a Lipid peroxidation Assay Kit (Calbiochem-Novabiochem Corp.). The concentration of lipid peroxidation products in patients with retinopathy was statistically significantly elevated in comparison to diabetic patients without retinopathy (p < 0.001) and the reference group (p < 0.001). We do not notice any significant differences in levels of MDA and 4-HNE between patients without diabetic retinopathy and the reference group. In view of our results we can conclude that oxidative stress is an important risk factor in the development of diabetic retinopathy.


Dissociation between the detection and perception of motion in Alzheimer's disease.
To better understand the damage to the motion pathway that occurs in senile dementia of the Alzheimer type (SDAT), we developed a system to assess separately the conscious perception and unconscious detection of motion in patients with SDAT. Motion perception thresholds were significantly elevated in SDAT (n = 9) compared with controls (n = 12), but motion detection thresholds were normal. This dissociation between the perception and detection of motion in early SDAT parallels histologic evidence of a disconnection between primary and association visual cortices. This disconnection may underlie the severe visual perception deficits seen in SDAT.


The training of New Jersey emergency service first responders in autism awareness.
This study investigated the extent and adequacy of training among New Jersey first responders (e.g., police, firefighters, emergency medical technicians) specifically as relates to a 2008 state law mandating that autism and hidden disability recognition and response training be conducted. The results show that a significant percentage of emergency service personnel have not completed the state mandated training. Recommendations for improving the training, such as by involving parents, advocates, and field and training personnel as a part of the training process, are discussed.


Switched Fuzzy-PD Control of Contact Forces in Robotic Microbiomanipulation.
Force sensing and control are of paramount importance in robotic micromanipulation. A contact force regulator capable of accurately applying mechanical stimuli to a live Drosophila larva could greatly facilitate mechanobiology research on Drosophila and may eventually lead to novel discoveries in mechanotransduction mechanisms of neuronal circuitries. In this paper, we present a novel contact force control scheme implemented in an automated Drosophila larvae micromanipulation system, featuring a switched fuzzy to proportional-differential (PD) controller and a noise-insensitive extended high gain observer (EHGO). The switched fuzzy-PD control law inherits the fast convergence of fuzzy control and overcomes its drawbacks such as large overshoot and steady-state oscillation. The noise-insensitive EHGO can reliably estimate system modeling errors and is robust to force measurement noises, which is advantageous over conventional high gain observers (sensitive to signal noises). Force control experiments show that, compared to a proportional-integral-differential (PID) controller, this new force control scheme significantly enhances the system dynamic performance in terms of rising time, overshoot, and oscillation. The developed robotic system and the force control scheme will be applied to mechanical stimulation and fluorescence imaging of Drosophila larvae for identifying new mechanotransduction mechanisms.


Thermal physics in carbon nanotube growth kinetics.
The growth of single wall carbon nanotubes (SWNTs) mediated by metal nanoparticles is considered within (i) the surface diffusion growth kinetics model coupled with (ii) a thermal model taking into account heat release of carbon adsorption-desorption on nanotube surface and carbon incorporation into the nanotube wall and (iii) carbon nanotube-inert gas collisional heat exchange. Numerical simulations performed together with analytical estimates reveal various temperature regimes occurring during SWNT growth. During the initial stage, which is characterized by SWNT lengths that are shorter than the surface diffusion length of carbon atoms adsorbed on the SWNT wall, the SWNT temperature remains constant and is significantly higher than that of the ambient gas. After this stage the SWNT temperature decreases towards that of gas and becomes nonuniformly distributed over the length of the SWNT. The rate of SWNT cooling depends on the SWNT-gas collisional energy transfer that, from molecular dynamics simulations, is seen to be efficient only in the SWNT radial direction. The decreasing SWNT temperature may lead to solidification of the catalytic metal nanoparticle terminating SWNT growth or triggering nucleation of a new carbon layer and growth of multiwall carbon nanotubes.


Expertise in psychotherapy: an elusive goal?
It has been argued that psychotherapy is a profession without any expertise (Shanteau, 1992). We examine the validity of this claim, reviewing the literature on expertise, clinical decision making, and psychotherapeutic outcome assessment, and find it a reasonable assessment. There is no demonstration of accuracy and skill that is associated with experience as a therapist. We posit that this absence of an expertise-experience relation is attributable to therapists' lack of access to quality outcome information regarding their interventions and an overreliance on fallible information-processing strategies even when such outcome information is available. The research on providing outcome feedback is reviewed, and although it does relate to client improvement, it has not been shown to be associated with any gains in therapist skill or expertise. We propose a model of outcome information usage and specific a priori hypothesis testing as a means of developing expertise. (PsycINFO Database Record (c) 2014 APA, all rights reserved).


Utilization of antihepatocyte clone OCH1E5 (Hep Par 1) in histological evaluation of liver tumors.
Diagnosis of hepatocellular carcinoma (HCC) is not always easy on simple hematoxylin and eosin (H&E) stain. The diagnostic problems arise when tumor shows pseudoglandular, pleomorphic or clear cell differentiation. Various tumors markers have been described with varying sensitivity and specificity. Monoclonal antibody Hep Par 1 (OCH1E5) which is specific for hepatocytes offers great help in separation of these tumors. The aim of the present study was to determine utility of Hep Par 1 (OCH1E5) in differentiating HCC from metastatic tumors and cholangiocarcinoma. Total of 62 cases of liver tumors obtained from biopsies, resected or autopsy specimens were included in the study. Slides having representative sections were subjected to immunohistochemistry with monoclonal antibody Hep Par 1 (Dako Corp) using avidin biotin technique with primary antibody dilution of 1:40. Adjacent nontumorous hepatocytes were taken as positive control. Slides were examined by experienced pathologist without any information of clinical or H&E diagnosis. Cases were considered positive for Hep Par 1 if tumor cells showed cytoplasmic brown colored granules. The intensity and distribution (diffuse/ focal) of immunoreactivity was noted. Subsequently immunohistochemistry results were correlated with histology and clinical diagnosis. Hep Par 1 antibody was positive in 26 (42 %) and negative in 36 (58 %) liver tumors. On correlating with H&E sections, out of 26 positive cases, 25 (89.2%) were HCC and one was the case of metastasis of mucin secreting adenocarcinoma. From 36 tumors with negative staining 3 were cases of HCC, 27 metastatic adenocarcinomas and 6 cholangiocarcinomas. Only one case of liver metastasis of mucin secreting adenocarcinoma showed positivity. None of the cases of cholangiocarcinoma showed positivity for Hep Par 1. The three HCCs which did not take up staining for Hep Par 1 were 2 cases of moderately differentiated HCC having pseudoglandular pattern and a case of well differentiated HCC with trabecular arrangement. In 11(44%) cases staining was diffuse while in 14 (56%) it was focal but intense. Hep Par 1 is a useful marker in differentiating HCC from metastaic tumors and cholangiocarcinoma with sensitivity and specificity of 89 % and 97 % respectively and positive predictive value of 96 %. However one should be aware of limitations of immunohistochemistry.


Clinical characteristics of allergic bronchopulmonary aspergillosis in patients with and without bronchiectasis.
Allergic bronchopulmonary aspergillosis (ABPA) is classified radiologically as serologic ABPA (ABPA-S) or ABPA with central bronchiectasis (ABPA-CB). This retrospective case series study aimed to describe and compare the clinical characteristics of both forms of ABPA. Patients with ABPA treated in the hospital between February 2011 and June 2019 were enrolled and were divided into ABPA-S and ABPA-CB groups based on whether their cases were complicated with central bronchiectasis. Demographic data, symptoms, laboratory values, comorbidities, and image findings were collected. ABPA-S patients were followed up retrospectively through medical records. Ninety-three (93) patients were enrolled, including 74 ABPA-CB patients and 19 ABPA-S patients. The most common predisposing condition was asthma (36.6%), with a median course of 30 years (IQR 13-42.5) prior to ABPA diagnosis. Patients of 54.8% had been misdiagnosed, with ABPA-S more likely than ABPA-CB to have been misdiagnosed as asthma (p < 0.01). Obstructive ventilation dysfunction and mixed ventilation dysfunction were found in 21 patients (22.6%) and 16 patients (17.2%), respectively. Compared with ABPA-S, ABPA-CB had a higher median blood eosinophil count (880 vs. 700 cells/μl), serum IgE (2957 vs. 2616 IU/ml), and Aspergillus fumigatus specific-IgE (20.6 vs. 7.31 kUA/L), although these findings were not statistically significant. Three ABPA-S patients developed bronchiectasis during follow-up and experienced relapses more than twice. Our findings suggested that the clinical characteristics between ABPA-CB and ABPA-S were mostly similar. ABPA-S had a relatively lower immunological activity level than ABPA-CB but was still immunologically active and could develop bronchiectasis.


Release of cationic polymer-DNA complexes from the endosome: A theoretical investigation of the proton sponge hypothesis.
Polyplexes are complexes composed of DNA and cationic polymers; they are promising transport vehicles for nonviral gene delivery. Cationic polymers that contain protonatable groups, such as polyethylenimine, have been suggested to trigger endosomal escape of polyplexes according to the "proton sponge hypothesis." Here, osmotic swelling is induced by a decrease in the endosomal pH value, leading to an accumulation of polymer charge accompanied by the influx of Cl(-) ions to maintain overall electroneutrality. We study a theoretical model of the proton sponge mechanism. The model is based on the familiar Poisson-Boltzmann approach, modified so as to account for the presence of ionizable polyelectrolytes within self-consistent field theory with assumed ground state dominance. We consider polyplexes, composed of fixed amounts of DNA and cationic polymer, to coexist with uncomplexed cationic polymer in an enclosing vesicle of fixed volume. For such a system, we calculate the increase in osmotic pressure upon moderately decreasing the pH value and relate that pressure to the rupture tension of the enclosing membrane. Our model predicts membrane rupture upon pH decrease only within a certain range of free polymer content in the vesicle. That range narrows with increasing amount of DNA. Consequently, there exists a maximal amount of DNA that can be incorporated into a vesicle while maintaining the ability of content release through the proton sponge mechanism.


Delimitation of the embryonic thermosensitive period for sex determination using an embryo growth model reveals a potential bias for sex ratio prediction in turtles.
The sexual phenotype of the gonad is dependent on incubation temperature in many turtles, all crocodilians, and some lepidosaurians. At hatching, identification of sexual phenotype is impossible without sacrificing the neonates. For this reason, a general method to infer sexual phenotype from incubation temperatures is needed. Temperature influences sex determination during a specific period of the embryonic development, starting when the gonad begins to form. At constant incubation temperatures, this thermosensitive period for sex determination (TSP) is located at the middle third of incubation duration (MTID). When temperature fluctuates, the position of the thermosensitive period for sex determination can be shifted from the MTID because embryo growth is affected by temperature. A method is proposed to locate the thermosensitive period for sex determination based on modelling the embryo growth, allowing its precise identification from a natural regime of temperatures. Results from natural nests and simulations show that the approximation of the thermosensitive period for sex determination to the middle third of incubation duration may create a quasi-systematic bias to lower temperatures when computing the average incubation temperature during this period and thus a male-bias for sex ratio estimate.


Chromatographic determination of the effect of storage on lycopene.
A reverse-phase high-performance liquid chromatography (HPLC) method for the determination of lycopene in an alkaline lipid phase is described, and pigment stability in stored tomato sausage is reported. To avoid and replace the use of nitrite, lycopene from tomato products is added to minced meat and a tomato sausage with natural color is produced. Tomato sausage with and without nitrite were smoked in a smoking compartment and stored (4 degrees C and 8 degrees C) for 25 and 17 days, respectively. Among other factors, the quality of the tomato sausage depends on stability of lycopene during process and storage. Lycopene, being lipophilic, is extracted together with the polar and neutral fat in food. Efforts to purify lycopene from the fatty content will result in loss of pigment. The triacylglycerides obstruct the detection of lycopene by spectrophotometry or by HPLC with diode-array detection. To solve this problem, the triacylglycerides are hydrolyzed to free fatty acids just before analyzing lycopene on a column tolerating alkaline samples. At the end of the storage, loss of pigment in the sausage without nitrite was 26% stored at 4 degrees C and 19% at 8 degrees C. Corresponding results for the sausage with nitrite added as well as tomato paste show the loss of pigment is 20% and 45%. For each type of fatty food extracted, it is important to minimize the use of alkaline solutions because the HPLC equipment may be susceptible to alkaline conditions.


Primary structure of porcine pepsin. I. Purification and placement of cyanogen bromide fragments and the amino acid sequence of fragment CB5.
Fragments resulting from the cyanogen bromide cleavage of reduced and aminoethylated porcine pepsin were purified. Only four of the five fragments theoretically present could be accounted for in major yield when the cyanogen bromide reaction was carried out at room temperature. The NH2-terminal fragment, CB2, contained an internal homoserine which was not cleaved to any significant extent. The amino acid sequence around this internal homoserine was determined by isolating and partially determining the sequence of an alpha-chymotryptic peptide. Cleavage at this methionine was increased by 50% when the cyanogen bromide reaction was carried out at 37 degrees. The NH2- and COOH-terminal sequences of five major fragments were determined. The placement of these fragments in the native pepsin molecule was demonstrated. The amino acid sequence of one of the fragments, CB5, was determined. This fragment contains 44 residues with an internal disulfide bridge. The COOH-terminal methionine of this fragment was connected to another 37-residue cyanogen bromide fragment of known sequence. Together these two fragments formed the COOH-terminal 81 residues of porcine pepsin.


Altered expression of chemokine receptor CXCR5 on T cells of myasthenia gravis patients.
Myasthenia gravis (MG) is characterized by the T cell-dependent production of anti-acetylcholine receptor (AChR) antibodies. The chemokine receptor CXCR5 regulates lymphocyte migration and is expressed on a subset of CD4+ T cells named follicular helper T cells (T(FH)), the key modulators of antibody production by B cells. We studied the frequency of CXCR5-positive lymphocytes in the peripheral blood of MG patients before and after therapy (thymectomy plus glucocorticoid). Before therapy, the MG patients showed a significantly higher frequency of CXCR5+ CD4+ T cells in the peripheral blood compared with the control group, while no significant difference in the percentages of CXCR5+ CD4+ T cells was observed between the patients of the hyperplasia group and those of the thymoma group. The CXCR5+ CD4+ T cell frequency correlated with the disease severity. The CXCR5+ CD4+ T cell frequency of MG patients positive for other autoantibodies together with anti-AChR antibodies was significantly higher than in those having only anti-AChR antibodies. After therapy, the CXCR5+ CD4+ T cell percentage decreased gradually to the control level with a significant inverse correlation between the CXCR5+ CD4+ T cell frequency and duration after the initiation of MG therapy. The CXCR5+ CD4+ T cell populations in the hyperplastic thymuses and thymomas were not significantly different from those in the control thymuses. These results suggest that CXCR5+ CD4+ T cells play an important role in the disease activity of MG and that some MG patients have a systemic abnormality in T cell-dependent antibody production.


Ventricular arrhythmias originating from the epicardial ventricular outflow tract complicated with peripartum cardiomyopathy.
We report two cases undergoing electrophysiological studies for ventricular arrhythmias (VAs) associated with peripartum cardiomyopathy. Those two cases demonstrated that subsequent pregnancies might result in deterioration of VAs even though they exhibit no symptoms of heart failure. Those findings may clinically impact the decision making when women with a history of peripartum cardiomyopathy desire to become pregnant again. The VA foci in both cases were determined or suggested to be in the epicardium of the ventricular outflow tract from the results of the catheter ablation and electrophysiological study. Therefore, catheter ablation of those VAs may be feasible but challenging.


Cellular mechanisms of brain state-dependent gain modulation in visual cortex.
Visual cortical neurons fire at higher rates to visual stimuli during locomotion than during immobility, while maintaining orientation selectivity. The mechanisms underlying this change in gain are not understood. We performed whole-cell recordings from layer 2/3 and layer 4 visual cortical excitatory neurons and from parvalbumin-positive and somatostatin-positive inhibitory neurons in mice that were free to rest or run on a spherical treadmill. We found that the membrane potential of all cell types became more depolarized and (with the exception of somatostatin-positive interneurons) less variable during locomotion. Cholinergic input was essential for maintaining the unimodal membrane potential distribution during immobility, whereas noradrenergic input was necessary for the tonic depolarization associated with locomotion. Our results provide a mechanism for how neuromodulation controls the gain and signal-to-noise ratio of visual cortical neurons during changes in the state of vigilance.


The role of the lateral hypothalamus and orexin in ingestive behavior: a model for the translation of past experience and sensed deficits into motivated behaviors.
The hypothalamus has been recognized for its involvement in both maintaining homeostasis and mediating motivated behaviors. The present article discusses a region of the hypothalamus known as the lateral hypothalamic area (LHA). It is proposed that brain nuclei within the LHA including the dorsal region of the lateral hypothalamus (LHAd) and perifornical area (PeF) provide a link between neural systems that regulate homeostasis and those that mediate appetitive motivated behaviors. Functional and immunohistochemical data indicate that the LHA promotes many motivated behaviors including food intake, water intake, salt intake, and sexual behavior. Anatomical tracing experiments demonstrate that the LHA is positioned to receive inputs from brain areas involved in regulating body fluid and energy homeostasis. Regions within the LHA send dense projections to the ventral tegmental area (VTA), providing a pathway for the LHA to influence dopaminergic systems generally recognized to be involved in motivated behaviors and their reinforcement. Furthermore, the LHA contains neurons that synthesize orexin/hypocretin, a neuropeptide that promotes many appetitive motivated behaviors. The LHA also receives inputs from brain areas involved in reward-related learning and orexin neuron activation can become conditioned to environmental stimuli that are associated with rewards. Therefore, it is hypothesized that the LHA integrates signaling from areas that regulate body fluid and energy balance and reward-related learning. In turn, this information is "fed into" mesolimbic circuitry to influence the performance of motivated behaviors. This hypothesis may foster experiments that will result in an improved understanding of LHA function. An improved understanding of LHA function may aid in treating disorders that are associated with an excess or impairment in the expression of ingestive behavior including obesity, anorexia, impairments in thirst, salt gluttony, and salt deficiency.


Dual diagnosis in elders discharged from a psychiatric hospital.
Recent evidence indicates persons 60 years and over experience significant alcohol and substance abuse problems. Since a combination of alcoholism and depression is likely to increase the relative rsk of suicide, it is important to examine the prevalence of dual diagnosis in older adults. The purpose of this study is to examine the prevalence and correlates of dual diagnosis in older psychiatric inpatient populations and compare our results with findings from studies of younger hospitalized dually diagnosed patients. A retrospective chart audit was performed on 101 elders who were discharged from three psychiatric hospitals. Clinical variables that were examined included length of hospital stay, psychiatric and medical diagnoses, medications and history of suicidal ideation or intent. The leading psychiatric disorder diagnosis for our sample of hospitalized psychiatric elders was depression. Over one-third (37.6%) had a substance abuse disorder in addition to a psychiatric disorder, and almost three-fourths (71%) of this 'dual diagnosis' group abused alcohol and 29% abused both alcohol and other substances. In addition, significantly more elders in the "dual diagnosis' group (17.7%) than in the group with only a mental disorder diagnosis (3.3%) made a suicide attempt prior to admission to the hospital. Because, affective disorders in conjunction with alcohol abuse are the most frequently found disorders in completed suicides, our findings have important relevance for the advocating of routine use of diagnostic assessment and screening for both substance abuse and mental disorders in this population.


Gemcitabine plus S-1 for metastatic pancreatic cancer.
To investigate the treatment effects of gemcitabine plus S-1 (GS) for metastatic pancreatic cancer in our institution.Data from 41 patients with metastatic pancreatic cancer treated with GS regimen in West China Hospital, Sichuan University were reviewed. The therapeutic efficacy and toxicity were evaluated. The influencing factors of progression-free survival (PFS) and overall survival (OS) were also explored.At the last follow-up, all patients had died. The objective response rate was 22.0% (9/41) and the disease control rate was 65.9% (27/41). The median PFS and OS times were 5.1 (range, 1.5-21) and 10.6 months (range, 1.5-40), respectively. The 0.5-, 1-, and 2-year OS rates were 65.9%, 41.5%, and 9.8%, respectively. In multivariate analysis, body mass index and carbohydrate antigen 19-9 change were the significant influencing factors of PFS, compared to tumor site and chemotherapy cycles for OS. The adverse effects were moderate and tolerable.The effects of GS for metastatic pancreatic cancer in our institution were good. The adverse effects were moderate and tolerable. However, further investigation in future prospective clinical studies is warranted.


Quantifying the impact of the COVID-19 pandemic on cancer center clinical trial operations.
Oncology clinical trials are complex, and the COVID-19 pandemic caused major disruptions in 2020. Using its networking and sharing of best practices, the Association of American Cancer Institutes, comprising 105 cancer centers, solicited a longitudinal series of voluntary surveys from members to assess how clinical trial office operations were affected. The surveys showed that centers were able to keep oncology trials available to patients while maintaining safety. Data were collected regarding interventional clinical trial accruals for the calendar years 2019, 2020, and 2021. Data demonstrated a sizeable decrease in interventional treatment trial accruals in both 2020 and 2021 compared with prepandemic figures in 2019. No cancer center reported an increase in interventional treatment trial accruals in 2020 compared with 2019, with most centers reporting a moderate decrease. In mid-2022, 15% of respondents reported an increasing trend, 31% reported no significant change, and 54% continued to report a decrease. The pandemic necessitated rapid adoption of trial operations, with the emergence of several best practices, including remote monitoring, remote consenting, electronic research charts, and work-from-home strategies for staff. The national infrastructure to conduct trials was significantly affected by the pandemic, with noteworthy resiliency, evidenced by improvements in efficiencies and patient-centered care delivery but with residual capacity challenges that will be evident for the foreseeable future.


The dynamic histopathologic spectrum of lung cancer.
The APUD concept has postulated that pulmonary carcinoids and small cell carcinomas arise from the neural crest. In development from hypothesis to tautology is traced, and evidence is presented that all pulmonary epithelial tumors arise from the primitive endoderm. Morphologic studies show that a dynamic spectrum exists. Not only do various cell types appear within a single section, but cell types may change from biopsy to autopsy with or without chemotherapy. The spectrum is sustained at the ultramicroscopic level in regard to organelles such as desmosomes, tonofibrils, and dense core granules. Secretory products such as ACTH and L-dopa decarboxylase also show that all lung cancers are related. Epidemiologic evidence indicates that small cell carcinomas in uranium miners occur after prolonged squamous cell dysplasia, and that carcinoids occur independently of external carcinogens, but show transitions to other tumors. Finally, experimental evidence indicates that the K cells, to which carcinoids are most closely related, are of local origin.


Subjective assessment of contact lens wear by army aircrew.
Because 23% of Army aviators are ametropic, contact lenses have drawn increased attention as a spectacle substitute to solve system compatibility problems. From November 1988 until October 1991, a series of contact lens research protocols were conducted to develop a comprehensive database on contact lens wear in varied environments. Questionnaires were used to assess suitability and acceptability of routine contact lens wear. Responses from 202 subjects were obtained from September 1989 through September 1991. The questions explored operational and safety of flight issues of contact lens wear. Subjects overwhelmingly approved of contact lens use in all settings: 95% expressed greater combat readiness and effectiveness with contact lenses, 98% felt contact lens use (and maintenance) in the cockpit had no adverse impact on safety of flight, and 98% endorsed the routine use of contact lenses. These data highlight Army aircrew acceptance of contact lens use.


Tribochemical reaction dynamics of molybdenum dithiocarbamate on nascent iron surface: a hybrid quantum chemical/classical molecular dynamics study.
Using a hybrid quantum chemical/classical molecular dynamics method, we have studied the tribochemical reaction dynamics of molybdenum dithiocarbamate (MoDTC), a commonly used friction modifier in automobile engine oils. MoDTC molecule adsorbed on rubbing nascent iron surface was situated. We firstly investigated the dynamic behavior of MoDTC molecule on the rubbing Fe(001) surface. During the friction simulation, the elongation of Mo-O bonds was observed, forming the Mo2S4 and thiocarbamic acid molecules. To unveil the detailed mechanism of this bond elongation, the electronic states of the MoDTC molecule and Fe(001) surface were computed, and the catalytic effects of Fe(001) surface to the molecule was found. We also found that extreme friction would influence the complete Mo-O bond dissociation. By using the hybrid quantum chemical/classical molecular dynamics method, we successfully simulated the tribochemical reaction dynamics of MoDTC as a friction modifier and obtained the influences of nascent iron surface and friction on its chemical reaction.


Excitonic structure and pumping power dependent emission blue-shift of type-II quantum dots.
In this work we study theoretically and experimentally the multi-particle structure of the so-called type-II quantum dots with spatially separated electrons and holes. Our calculations based on customarily developed full configuration interaction ap- proach reveal that exciton complexes containing holes interacting with two or more electrons exhibit fairly large antibinding energies. This effect is found to be the hallmark of the type-II confinement. In addition, an approximate self-consistent solution of the multi-exciton problem allows us to explain two pronounced phenomena: the blue-shift of the emission with pumping and the large inhomogeneous spectral broadening, both of those eluding explanation so far. The results are confirmed by detailed intensity and polarization resolved photoluminescence measurements on a number of type-II samples.


Burn injuries in Zaria: a one year prospective study.
Fifty three patients admitted for burn care during a 12 month period from September 1987 to August 1988 were prospectively studied. There were 36 males (60%) and 21 females (40%) with ages ranging from 3 months to 60 years. Children aged 0-4 constituted 40% but 32 (60%) were younger than 16 years. Flame burns affected 26 (49%) patients, scalds in 22 (12%), electrical burns affected four patients and chemical burn was in one. Scald was the commonest injury among children aged 0-4 (70%). Flame, affected 33% of those aged 16 and above. Clothing fire was the commonest flame injury and it was a cause of very extensive injury (mean % BSA 45). Kerosene burn, gas and clothing burns caused the most extensive injury with a mean % BSA 46, 41 and 45 respectively. The commonest complication was burn wound sepsis most frequently by a gram-negative bacilli (65.63%) of which Pseudomonas aeruginosa were that commonest organisms. Pseudomonas and Staphylococcus aureus were about same frequency. Duration of hospital stay ranged from 6 days to 300 days with a mean of 46.52 days. 8 patients absconded, two were transferred to a hospital near their home and 9 died, giving a mortality rate of 17%. Since burn injuries are largely preventable, it is important to define clearly the social, cultural and economic factors which contribute to burn causation in order to combat them effectively.


Vital volume increase versus clinical evaluation as the indication of additional radiofrequency ablation for benign thyroid nodule: a single center retrospective study.
Purpose: To compare results in patients treated with additional radiofrequency ablation (RFA) after clinical evaluation or vital volume (Va) increase.Methods: Forty patients with 42 benign thyroid nodules who underwent additional RFA were evaluated in this retrospective study. According to the different indication for additional RFA, 18 patients were divided into Vv increase group (V group) and 22 into clinical evaluation group (C group). Patients were followed up at 1, 3, 6, 12 months and every 12 months thereafter by conventional ultrasound (US), contrast-enhancement ultrasound (CEUS) and clinical evaluation. Volume, volume reduction rate (VRR), symptom score and cosmetic score were evaluated before treatment and each ablation.Results: After the first RFA, there were no statistically differences between two groups in volume, VRR, cosmetic and symptom scores. Compared with the first RFA, volume of all the patients after additional RFA decreased significantly (p < 0.001). In additional RFA, during a mean follow-up time of 10.15 ± 9.17 months, volume in V group was significantly smaller than in C group (2.84 ± 5.43 ml Vs 7.39 ± 13.01 ml, p = 0.046). VRR in V group was significantly larger than in C group (90.18 ± 12.74% Vs 75.66 ± 26.47%, p = 0.007) with significant improvement of cosmetic and symptom scores (p = 0.047; p = 0.030). No complications occurred after each session ablation.Conclusion: Vv increase was a more reliable indicator for additional RFA than clinical evaluation. Additional RFA performed after Vv increase was more effective with respect to volume reduction and improvement of clinical outcomes. Therefore, Vv increase should be set as an indication for additional RFA.


Role of microRNAs in the resistance of colorectal cancer to chemoradiotherapy.
Colorectal cancer (CRC) is among the main tumor-related causes of death worldwide. The fact that the majority of the patients develop resistance to chemoradiotherapy (CRT) is a major obstacle for the treatment of CRC. In order to develop more effective treatment strategies, it is crucial to elucidate the mechanisms underlying the development of resistance to CRT. Several studies have recently indicated the regulatory effects of microRNAs (miRNAs) in response to antitumor agents. For example, miR-34a attenuates the chemoresistance of colon cancer to 5-FU by inhibiting E2F3 and SIRT1. The miR-34a mimic MRX34 is the first synthetic miRNA to have been entered into clinical trials. miR-21 prevents tumor cell stemness, invasion and drug resistance, which are required for the development of CRC. These findings suggest that miRNAs represent a focus in the research of novel cancer treatments aimed at sensitizing cancer cells to chemotherapeutic drugs. The aim of the present study was to review the functions of miRNAs and investigate the roles of miRNAs in CRC radioresistance or chemoresistance. Furthermore, the potential of including miRNAs in therapeutic strategies and using them as molecular biomarkers for predicting radiosensitivity and chemosensitivity was discussed.


Tris(pyridyl)borates: an emergent class of versatile and robust polydentate ligands for catalysis and materials applications.
Tridentate ligands that incorporate pyridyl rather than pyrazolyl groups are emerging as an attractive class of "scorpionate"-type ligands with enhanced electron donation, increased stability, and divergent geometry at the metal centre relative to tris(pyrazolyl)borates originally introduced by Trofimenko. Following our initial reports, the tris(pyridyl)borate (Tpyb) ligand architecture has been adopted by several research groups in pursuit of functional metal complexes that offer new opportunities in catalysis and materials science. While earlier work had been focused on symmetric octahedral complexes, ML2, which are advantageous as highly robust building blocks in materials sciences, recently introduced new ligand designs provide access to heteroleptic metal complexes with vacant sites that lend themselves to applications in catalysis. Signficant progress has also been made in the post-complexation functionalization of these ligands via electrophilic and nucleophilic substitution reactions at the boron centres, opening up new routes for integration of Tpyb complexes with diverse functional materials while also raising interesting mechanistic questions.


Girdlestone's operation: a follow-up study.
A study was made of 43 patients (48 hips) operated for diseases of the hip using Girdlestone's method. The follow-up time ranged from 2.5 to 13 years. For assessment of the post-operative results the following parameters were taken into consideration: pain, range of movement, gait and the patient's opinion. These were studied separately and in relation to the type of disease, the patient's age, and the time which had elapsed since the operation. Pain decreased in a considerable number of patients and range of movement and gait improved. The patients were generally in favor of the operation, and felt it had had a beneficial effect on their condition.


Inversion Technique for the Removal of Partially Covered Self-Expandable Metallic Stents.
Partially covered self-expandable metallic stents (PCSEMS), although an effective treatment for anastomotic/staple line leaks and strictures, can be difficult to remove. This study examines the effectiveness of the inversion technique for the removal of PCSEMS in the treatment of leaks and strictures that occurred post-sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). Consecutive patients who underwent PCSEMS removal for a leak and/or stricture post-SG or RYGB between July 2013 and December 2016 at the Johns Hopkins Medical Institutions were reviewed. All PCSEMS removals were first attempted via the inversion technique, which involves grasping the distal end of the stent and inverting it through itself. Fourteen patients (four males) underwent PCSEMS removal via the inversion technique for an anastomotic/staple line leak (50%), stricture (29%) or both (21%) post-SG (79%) or RYGB (21%). Technical success (successful removal of the stent) was achieved in one endoscopic session for 13 of the 14 PCSEMS (93%). One PCSEMS required the use of the stent-in-stent technique for removal. The median dwell time was 47 days (range 5-72). A distal partial occlusion developed in five patients (35%) due to tissue overgrowth and one PCSEMS (7%) migrated, necessitating premature removal. Eight patients (57%) experienced clinical success at follow-up, and six patients (43%) required subsequent treatment due to persistence or recurrence of the pathology. The inversion technique is a safe, effective, and efficient method of removing PCSEMS placed to correct anastomotic/staple line leaks and strictures post-SG and RYGB.


Non-functional Pituitary Adenomas: Analysis of Delayed Diagnosis in Mexico.
Although tumors of the central nervous system (CNS) are rare, they can cause significant morbidity and mortality. The clinical presentation of patients with non-functional pituitary adenomas (NFPA) ranges from being completely asymptomatic to causing pituitary, hypothalamic, or visual dysfunction due to their large size. Patients usually arrive with large tumors at the time of diagnosis. Objectives: Try to describe the characteristics of NFPA and explain the causes of delayed diagnosis. Methods: We carried out a retrospective study including 58 patients with NFPA and analyzed the tumor volume at the time of diagnosis and its relationship with sociodemographic and health sector variables. Results: Low socioeconomic status (SES) was associated with high tumor volume (SES 1-2 of 17.4 cm3 vs 3-6 of 11.7 cm3, p=0.018), and the time between first consultation and diagnosis was longer in the public sector than in the private sector (13.5 months vs 5.1 months). The time between the first symptom and the first consultation was shorter when they had visual impairment than when they did not (4.1 vs 18.4 months, p=0.006). On the one hand, citizens should be made aware that a visual deficit should make them go to a medical check-up, and on the other hand, strengthen the health system so that they have the NFPA as a differential diagnosis in patients with some visual alteration. Socioeconomic inequality in our country undoubtedly puts the underprivileged at greater risk.


HLA gene and clinical study of insulin dependent diabetes mellitus (IDDM) in Chinese individuals.
The prevalence rate of diabetes in China was 0.67% in 1980. For the last ten years, the prevalence rate has increased 0.1% every year. The total number of diabetics in China is enormous, in the range of 12-15 million people; 10% have insulin dependent diabetes (IDDM) and 90% have non insulin dependent diabetes (NIDDM). 1) HLA Typing DR3 was statistically increased in Chinese IDDM patients; relative risk 7.89, Fisher's p 5.91 x 10-6 corrected p 4.14 x 10-6. DR3 is increased in most Caucasians and American Blacks, but not in Japanese individuals. 2) HLA-DQA1 and B1 alleles contribute to susceptibility to IDDM IDDM is strongly associated with the presence of arginine in position 52 of the DQ α chain and absence of aspartic acid in position 57 of the DQ β chain in Caucasians. To confirm this association in Chinese, extensive oligonucleotide dot blot hybridisation of PCR-amplified DQA1 and DQB1 genes were studied using samples from 48 IDDM patients and 46 healthy non diabetic control subjects. DQ α 52-Arg and DQ β 57-non-Asp are strongly associated with IDDM susceptibility as compared with controls (p < 0.001 and 0.006, respectively). DQ β 57-non-Asp homozygosity is associated with increased susceptibility to IDDM. DQ β 57-Asp homozygosity is associated with protection against IDDM; 14.6% of IDDM patients were homozygous for DQ β -Asp, compared with 0% of American patients; 22.9% of IDDM patients were homozygous for DQ β 57-nonAsp, compared with 96% of American diabetic subjects in a previous study. These results suggest that the effect of the DQ b 57-Asp variation on Chinese IDDM susceptibility is not as remarkable as in Caucasians, and there may be other alleles which contribute to IDDM susceptibility in Chinese individuals. 3) Familial Aggregation and HLA Typing of Pedigrees in IDDM In 280 cases with IDDM 1000 positive family histories of diabetes have been found to be present in 26.8% of IDDM probands. The prevalence of diabetes in relatives has been shown to be 68% in first degree relatives, 28% in second degree relatives and 4% in the third degree relatives. HLA data support the hypothesis that IDDM is a multigenic hereditary disorder. 4). Clinical Features of Microvascular Complications in Long Term IDDM One hundred sixty three individuals with IDDM of more than 10 years in duration were followed. Most complications were microvascular, such as proliferative retinopathy (39/163, 23.9%) and nephropathy (19/163, 11.7%). We have found that the development and degree of microvascular complications depend on the age of onset, diabetes duration and the long term glycaemic control. Especially, microvascular complications were found to be significantly influenced by glycaemic control in the first ten years after onset.


Periparturient dairy cows do not exhibit hepatic insulin resistance, yet adipose-specific insulin resistance occurs in cows prone to high weight loss.
The periparturient period in dairy cows is associated with alterations in insulin action in peripheral tissues; however, the molecular mechanism underlying this process is not completely understood. The objective was to examine the response to a glucose tolerance test (GTT) and to analyze insulin signaling in liver and adipose tissues in pre- and postpartum dairy cows. Liver and adipose tissue biopsies were taken before and after GTT, at 17d prepartum and again at 3 to 5d postpartum from 8 high-yielding Israeli Holstein dairy cows. Glucose clearance rate after GTT was similar pre- and postpartum. Basal insulin concentrations and the insulin response to GTT were approximately 4-fold higher prepartum than postpartum. In accordance, phosphorylation of the hepatic insulin receptor after GTT was higher prepartum than postpartum. Across periods, a positive correlation was observed between the basal and peak plasma insulin and phosphorylated insulin receptor after GTT in the liver. Hepatic phosphorylation of protein kinase B after GTT was elevated pre- and postpartum. Conversely, in adipose tissue, phosphorylation of protein kinase B after GTT pre- and postpartum was increased only in 4 out of 8 cows that lost less body weight postpartum. Our results demonstrate that hepatic insulin signaling is regulated by plasma insulin concentrations as part of the homeorhetic adjustments toward calving, and do not support a model of hepatic insulin resistance in periparturient cows. Nevertheless, we suggest that specific insulin resistance in adipose tissue occurs pre- and postpartum only in cows prone to high weight loss. The different responses among these cows imply that genetic background may affect insulin responsiveness in adipose tissue pre- and postpartum.


Preserving a sense of wonder: the integration of an ego-supportive psychodynamic approach to supervision in an AIDS psychiatry fellowship.
The challenges of working with medically and mentally ill persons with a paucity of resources, inadequate networks of social support, and multiple stresses and losses maybe daunting to even the most seasoned of caregivers. A psychiatric trainee may be overwhelmed by the despair, sorrow, and desperation en-countered in the day-to-day care of the complex severely ill patient with lethalmedical and lethal psychiatric diagnoses. Individuals who are infected with HIV and hepatitis C, who are polysubstance users, and who are benzodiazepine dependent present with inordinate demands for prescribed substances to use or to sell in the street. The trainee needs to become comfortable with both limit-setting and harm reduction in order to keep the patient engaged in both lifesaving medical and psychiatric care. Nurturing and supportive supervision enables the trainee to integrate skills and work toward an understanding of countertransferences. An ego-supportive psychodynamic approach to supervision in an AIDS psychiatry fellowship facilitates conflict resolution and improves the care of patients with complex and severe medical illness.


Transvenous embolization with Onyx for a cerebral arteriovenous fistula originating from the distal lenticulostriate artery.
We described the first case of transvenous embolization with Onyx for a cerebral arteriovenous fistula (CAVF) originating from the distal lenticulostriate artery (LSA). A 16-year-old patient presented with right intraventricular hemorrhage. Angiography demonstrated that CAVF originating from the right distal LSA directly connected to the contralateral basal vein of Rosenthal. We treated the fistula with Onyx through transvenous approach by the balloon-assisted method. CAVF was completely obliterated and remained closed as ascertained by follow-up angiograms.


Dose-response analyses of osteonecrosis in New Jersey radium workers point to roles for other alpha emitters.
A previous study of 25 radium workers reported radium osteonecrosis to be common down to that study's lower limit of detection of 226Ra. This paper reanalyzes those data using Poisson and linear regression to obtain quantitative dose-response estimates for radium osteonecrosis. A quadratic, supralinear response of the necrosis ratio to skeletal dose and preterminal 226Ra burden was observed at a high level of statistical significance. At low dose the response was linear. Clearly observable necrosis, that appearing in 4% of tissue blocks, was seen in femurs at approximately 0.8 Gy skeletal dose. Comparable effects from plutonium in spongy bone might therefore be expected in the 0.01-0.02 Gy dose range. Prediction equations are presented for preterminal 226Ra burden, for skeletal dose, and, at low doses where the response can be taken as linear, for dose from and uptakes of both 226Ra and 228Ra. Male New Jersey workers in the radium refinery were observed to have necrosis not explained by the 226Ra uptakes, but compatible with skeletal doses from other internal emitters, in the range 0.25-1.2 Gy lifetime dose acquired per year of employment. 210Po, inhaled directly or from inhaled 210Pb, is the most likely source of this dose.


Arginine-metabolizing enzymes in the developing rat small intestine.
Before weaning, arginine biosynthesis from citrulline most likely takes place in the small intestine rather than in the kidney. We studied the expression of ornithine cycle enzymes in the rat small intestine during perinatal development. The spatiotemporal patterns of expression of ornithine aminotransferase, carbamoylphosphate synthetase, ornithine transcarbamoylase, argininosuccinate synthetase, argininosuccinate lyase, and arginase mRNAs were studied by Northern blot analysis and in situ hybridization. In addition, the expression of carbamoylphosphate synthetase and argininosuccinate synthetase protein was studied by immunohistochemistry. Before birth, the developmentally more mature proximal loops of the intestine expressed the mRNAs at higher concentrations than the more distal loops. After birth, this difference was no longer obvious. The mRNAs of argininosuccinate synthetase and argininosuccinate lyase, the enzymes that metabolize citrulline to arginine, were detectable only in the upper part of the villi, whereas the other mRNAs were concentrated in the crypts. The distribution of argininosuccinate synthetase protein corresponded with that of the mRNA, whereas carbamoylphosphate synthetase protein was present in all enterocytes of the crypts and villi. Hepatic arginase mRNA could not be detected in the enterocytes. The spatial distribution of the respective mRNAs and proteins along the villus axis of the suckling small intestine indicates that the basal enterocytes synthesize citrulline, whereas the enterocytes in the upper half of the villus synthesize arginine.


Subacromial osteochondroma: A rare cause of impingement syndrome.
Subacromial impingement syndrome is one of the most common disorders of shoulder. Scapula is a very rare site for osteochondromas, and osteochondromas arising under the acromion cause impingement syndrome. We presented 34-year old female patient with subacromial impingement syndrome secondary to osteochondroma. She had received conservative treatment several times in other clinics. The osteochondroma causing impingement was not diagnosed. Physical examination of the right shoulder revealed 90° flexion, 70° abduction, 20° external rotation and internal rotation to sacrum. X-ray, CT and MRI of the shoulder was obtained. Osteochondroma of the acromion (35×33×25mm) causing impingement was detected. The osteochondroma of acromion compressed, displaced and ruptured the supraspinatus tendon. Also an osseous prominence of glenoid was detected during shoulder arthroscopy, and it was removed arthroscopically. The giant osteochondroma of acromion could not remove arthroscopically due to the size of the lesion, and it was removed totally through a mini open approach. Histopathological examination confirmed the diagnosis of osteochondroma. Scapular, clavicular and humeral osteochondromas cause impingement syndrome. Osteochondroma should be treated with total excision. Recurrences can be seen due to insufficient removal of osteochondromas. We think that, total excision is important to prevent recurrence. Subacromial osteochondroma is a very rare cause of impingement syndrome, and if it isn't diagnosed early it limits shoulder movements, causes severe shoulder impingement and rotator cuff tear. The diagnosis of subacromial osteochondroma should be considered in any patient with shoulder impingement syndrome and good functional results can be expected following total excision.


[Management of hypertension in the hypertension clinic].
A recent Cochrane report concluded that an effective system for hypertension control has yet to be identified. This manuscript presents results from four years' work in a nurse-guided hypertension clinic. The aim of the hypertension clinic was to reduce the number of physician-consultations and to optimize hypertension treatment. All patients were initially examined by physicians. All follow-up visits were performed by the nurses of the hypertension clinic. They initiated and titrated antihypertensive medication according to a treatment algorithm or the physicians' instructions. Blood pressure (BP) measurement and recording of risk profile were performed in accordance with guidelines from the Danish Hypertension Association. During the four years, 186 patients were treated at the Hypertension Clinic. A total of 130 were discharged to general practice. 95% of these reached their target BP. In all, 56 patients continued treatment at cardiological or nephrological out-patient clinics, or preferred to stop their treatment at the hypertension clinic and refused further referral. Most of the patients received combination therapy with 2-7 different antihypertensive drugs. The three primary antihypertensive drugs were the three first drugs to be used and they comprised the majority of the combination therapy. Many patients received betablockers either as an antihypertensive drug or because of ischemic heart disease. Despite many risk factors and severe hypertension, 95% of the patients achieved their target BP. We hope the results will inspire physicians and GP's to adapt the concept.


Art of prevention: Life in the time of coronavirus.
The novel coronavirus disease 2019 (COVID-19) has continued to progress since its discovery in December 2019. A cluster of patients with atypical pneumonia identified in Wuhan, China, served as the epicenter of this recent epidemic. This family of viruses is responsible for the common cold along with the infamous severe acute respiratory syndrome epidemic in 2002 and Middle East respiratory syndrome in 2012. The Southern China Wholesale Market reportedly has connections to the original 27 cases in Wuhan, China. The worldwide confirmed case total has eclipsed 1,450,000, with more than 83,000 deaths. Patient presentation ranges from mild respiratory illness to acute respiratory distress syndrome and subsequent death. Early epidemiologic studies of viral spread support the hypothesis that COVID-19 can remain latent with an extended and infectious incubation period. The U.S. government has issued level 3 precautions for most international travel, along with prohibiting entry to foreign nationals traveling from China, Iran, the United Kingdom, the Republic of Ireland, and the European Schengen area (e.g., France, Italy, Germany). Prevention remains the mainstay in treating and defeating the COVID-19 epidemic. Anyone infected or suspected of being infected should self-quarantine at home or admit themselves to a specified hospital with infrastructure to handle the situation. The combination of prevention and containment provides the best opportunity to stall the spread of COVID-19.


Differentiation status of human renal proximal and distal tubular epithelial cells in vitro: Differential expression of characteristic markers.
The culture of human renal tubular cells of well-defined nephron origin is an important basis in the research of various physiological and pathophysiological mechanisms in the kidney. In vitro differentiation of cultured cells is affected by cell isolation and culture conditions. Our study describes in vitro differentiation of cultured human renal proximal and distal (thick ascending limb and early distal) tubular epithelial cells. Proximal tubular cells (PTC) and early distal tubular cells (DTC) were isolated immunomagnetically and cultured. In vitro differentiation was assessed by Western blot analysis and reverse transcriptase polymerase chain reaction using characteristic markers. Morphologic characterization was shown by fluorescence and scanning electron microscopy. E-cadherin was highly expressed in DTC, whereas expression was low in PTC. In contrast to DTC, in PTC, intercellular adhesion molecule 1 and aquaporin 1 were constitutively expressed at high levels. Both cell types expressed cytokeratin 18 and Na-K-ATPase but not alpha-smooth muscle actin. Morphological analysis showed that PTC develop long microvilli, whereas DTC formed short microvilli in culture, and both express the tight junction protein zona occludens protein 1. We demonstrate differential expression of E-cadherin, intercellular adhesion molecule 1 and aquaporin 1 in cultured PTC and DTC as described for the renal tubule in vivo. We could show the in vitro differentiation of the cells, and thus, their usefulness as an in vitro model of the human proximal and early distal tubule.


Expression and Role of CD166 in the Chronic Kidney Disease.
CD166, an adhesion molecule of the immunoglobulin superfamily, is one of the crucial effectors that traffic lymphocytes into tissues. Till now, the expression and role of CD166 in the chronic kidney disease remains unknown. In the present study, we are to examine the expression of CD166 in the chronic kidney disease, and to explore its function with CD4+ T cells. CD166 expression was tested by Flow Cytometry (FACS) in the primary macrophages stimulated with LPS. In vivo, the expression of CD166 and CD4 were examined in the kidney tissues of adriamycin-induced nephropathy (AN) mice by immnohistochemistry. Macrophages and lymphocytes were co-cultured, the interaction between CD166 and CD4 was tested by immunofluorescent staining. Furthermore, the effects of CD166 on the activation and proliferation of T cells were explored. In this study, CD166 expression was found to be upregulated on activated macrophages and glomerular endothelia in the adriamycin-induced nephropathy (AN) mice and CD4+ T cells were increased with CD166 expression in the AN mice. The interaction between macrophages and CD4+ T cells indicated that CD166 played a key role in the recruitment of lymphocytes in the chronic kidney disease, and neither proliferation nor activation of T cells was affected by CD166. CD166 expressed on macrophages and endothelia in AN kidney, and the function was related to the recruitment of CD4+ T cells into inflamed kidney, indicating that CD166 may be a potential target for reducing the inflammatory infiltrates in the chronic kidney disease.


SLC1 glutamate transporters and diseases: psychiatric diseases and pathological pain.
The solute carrier family 1 (SLC1) consists of two neutral amino acid transporters and five high-affinity excitatory amino acid transporters (EAAT1-5). EAATs are expressed in glial cells (EAAT1/GLAST and EAAT2/GLT-1), neurons (EAAT3/EAAC1 and EAAT4), and the retina (EAAT5), where they precisely regulate extracellular glutamate levels at both synaptic and extrasynaptic sites. EAATs play essential roles in the maintenance of normal excitatory synaptic transmission, protection of neurons from the excitotoxic action of excessive glutamate, and regulation of glutamatemediated neuroplasticity. Therefore, dysfunction of EAATs can cause abnormal excitatory synaptic transmission, neuronal excitotoxicity, and the exaggeration of neuroplasticity-based events. EAAT dysfunction has been implicated in a variety of neurodegenerative and neurological diseases, including amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, ischemia, and epilepsy. Recent evidence suggests that abnormalities of EAATs contribute to the pathogenesis of psychiatric diseases and pathological pain. The present review will briefly discuss novel findings on the roles of EAATs in the pathogenesis of psychiatric diseases such as schizophrenia, mood disorders, and drug dependence/ addiction, and pathological pain, as well as the potential of EAATs as therapeutic targets.


Smoking-Associated Site-Specific Differential Methylation in Buccal Mucosa in the COPDGene Study.
DNA methylation is a complex, tissue-specific phenomenon that can reflect both endogenous factors and exogenous exposures. Buccal brushings represent an easily accessible source of DNA, which may be an appropriate surrogate tissue in the study of environmental exposures and chronic respiratory diseases. Buccal brushings were obtained from a subset of current and former smokers from the COPDGene study. Genome-wide DNA methylation data were obtained in the discovery cohort (n = 82) using the Illumina HumanMethylation450K array. Empirical Bayes methods were used to test for differential methylation by current smoking status at 468,219 autosomal CpG sites using linear models adjusted for age, sex, and race. Pyrosequencing was performed in a nonoverlapping replication cohort (n = 130). Current smokers were significantly younger than former smokers in both the discovery and replication cohorts. Seven CpG sites were associated with current smoking at a false discovery rate less than 0.05 in the discovery cohort. Six of the seven significant sites were pyrosequenced in the replication cohort; five CpG sites, including sites annotated to CYP1B1 and PARVA, were replicated. Correlations between cumulative smoke exposure and time since smoking cessation were observed in a subset of the significantly associated CpG sites. A significant correlation between reduced lung function and increased radiographic emphysema with methylation at cg02162897 (CYP1B1) was observed among female subjects. Site-specific methylation of DNA isolated from buccal mucosa is associated with exposure to cigarette smoke, and may provide insights into the mechanisms underlying differential susceptibility toward the development of smoking-related chronic respiratory diseases.


Comparing treatment response and complications between podophyllin 0.5%/0.25% in ethanol vs podophyllin 25% in tincture benzoin for penile warts.
The aims of this study were to: 1) ascertain if podophyllin resin in 0.5% [PE(0.5%)] and 0.25% [PE(0.25%)] in ethanol (PE) self-applied sequentially for 3 days with 4 days break cycle is as effective as supervised podophyllin 25% in tincture benzoin (PB) applied in the clinic biweekly in treating penile warts and 2) ascertain if PE causes less skin irritation than PB. The clearance rate of penile warts was 36.4% (4/11) in PE (0.5%) treated group, 66.7% (4/6) in the PE (0.25%) treated group and 33.3% (6/18) for PB treated group after 1 week (ns). The wart clearance rate at 6 weeks for PE (0.5%) treated group, PE (0.25%) treated group and PB treated group were 81.8% (9/11), 100% (6/6) and 83.3% (15/17) respectively (ns). There were 47 individual warts on the penis of the 17 patients in the PE treated group and 58 individual warts on the penis of the 18 patients in the PB treated group. Based on the response of individual warts to the 2 treatment regimens, the clearance rate was 42.6% (20/47) for the PE treated group and 25% (15/56) for the PB treated group after 1 week treatment (ns). At 6 weeks follow-up, the clearance rate for the PE treated group and the PB treated group were 85.1% (40/47) and 73.2% (41/56) respectively (ns). Skin irritation including superficial erosions, pain and itch were observed in 47% (8/17) in patients treated with PE compared to 38.9% (7/18) in patients treated with PB (ns) during the 6 weeks follow-up period. The clearance rate of patients treated with PE (0.25%) was compared to those treated with PE (0.5%). Four out of six of PE (0.25%) treated patients had clearance of warts after 1 week and 100% clearance at the end of 6 weeks. None experienced any skin irritation. This study demonstrates that 0.5% podophyllin (and possibly 0.25% podophyllin) in ethanol is effective in eradicating penile warts. It can be used by patients for self-treatment at home with greater convenience and is more cost effective than the conventional podophyllin 25% in tincture benzoin paint.


Role of GABAA/benzodiazepine receptors containing alpha 1 and alpha 5 subunits in the discriminative stimulus effects of triazolam in squirrel monkeys.
Conventional benzodiazepines (BZs), clinically used for treatment of anxiety and insomnia, bind to GABA(A) receptors containing alpha(1), alpha(2), alpha(3), or alpha(5) subunits. The role of these different GABA(A) receptor subtypes in mediating the subjective effects of BZs remains largely unknown. The purpose of the present study was to evaluate the role of GABA(A) receptors containing the alpha(1) or alpha(5) subunits in the discriminative stimulus (DS) effects of the conventional BZ agonist triazolam. Squirrel monkeys were trained to discriminate triazolam (0.03 mg/kg, i.v.) from vehicle under a fixed-ratio 10 schedule of food reinforcement. The GABA(A)/alpha(1)-preferring agonists zolpidem and zaleplon engendered responses predominantly on the triazolam lever (73-80% drug-lever responding), and the GABA(A)/alpha(1) partial agonist CL 218,872 engendered an average maximum of less than 50% triazolam-lever responding. The GABA(A)/alpha(1)-preferring antagonists beta-carboline-3-carboxylate-t-butyl ester (betaCCT) and 3-(propyloxy)-beta-carboline (3-PBC) blocked the DS effects of triazolam and zolpidem in a surmountable manner. Schild analyses for betaCCT and 3-PBC in combination with triazolam and zolpidem suggest that the interactions between these compounds were competitive in nature and mediated by a common population of receptors, presumably GABA(A)/alpha(1) receptors. In contrast, the GABA(A)/alpha(5)-preferring agonist QH-ii-66 did not engender triazolam-lever responding regardless of dose and did not alter the DS effects of triazolam when administered in combination. The results are consistent with GABA(A)/alpha(1) receptor involvement in mediating the DS effects of triazolam. In contrast, binding to GABA(A)/alpha(5) receptors may not play a critical role in mediating triazolam's DS effects.


π-Stacking between Casiopeinas® and DNA bases.
Casiopeínas® are copper complexes with the general formula [Cu(N-N)(N-O)]NO(3) and [Cu(N-N)(O-O)]NO(3) where N-N denotes a substituted bipyridine or phenanthroline, N-O indicates α-aminoacidate or peptide and O-O represents acetylacetonate or salicylaldehyde. This family of compounds has been evaluated in vitro and in vivo showing cytotoxic, genotoxic, and antineoplastic activity. The action mechanism is still not completely elucidated, but the possibility exists that these compounds interact with DNA by intercalation due to the aromatic moiety. In this work we found, using the properties of the electron density of a π-complex model base-Casiopeína®-base, that the stacking mechanism between Casiopeínas® and DNA bases is due to an electron density deficiency of the ligand of the Casiopeína® which is compensated for by an electron transfer from adenines by a π-π interaction.


[Pharmacoepidemiology: lights and shadows].
Adverse drug reactions are a major cause of illness and death. They cause 5-10% of general practice consultations and 5 to 10% of hospital admissions and would be the third or fourth cause of death (after heart attack, stroke and cancer). It is a failure of contemporary medicine. The purpose of pharmacoepidemiology is the study of drug use in populations and its impact on public health. The author describes the four stages of the recent history of pharmacovigilance. The first, spontaneous reporting, has identified many adverse drug reactions but cannot provide with incidence or risk estimates. Observational epidemiological research has shaped second generation pharmacovigilance, providing incidence and relative and absolute risks which are essential for public health decision taking. The meta-analysis of clinical trials would be third-generation pharmacovigilance: it has contributed to the understanding of relatively common adverse drug reactions with great impact on public health. Research on big data will surely be the basis of the fourth generation of pharmacovigilance.


Comprehensive management of subclavian vein effort thrombosis.
Subclavian vein (SCV) effort thrombosis, also known as the Paget-Schroetter syndrome, is a relatively uncommon condition that affects young, active, otherwise healthy individuals. It is considered a form of thoracic outlet syndrome, arising as a consequence of compression and repetitive injury of the SCV between the first rib and the overlying clavicle, as well as the anterior scalene muscle, subclavius muscle, and costoclavicular ligament. Effort thrombosis is distinct from other forms of deep vein thrombosis with respect to pathophysiology, clinical presentation, and functional consequences, and it requires treatment considerations unique to effective management of thoracic outlet compression as well as the obstructed SCV. In this review the comprehensive management of SCV effort thrombosis is addressed, with an emphasis on current interventional radiology techniques used in conjunction with definitive surgical treatment, based on early catheter-based venography, thrombolytic therapy, and prompt paraclavicular thoracic outlet decompression with direct SCV reconstruction.


Systematic approach to design organic magnetic molecules: strongly coupled diradicals with ethylene coupler.
The intramolecular magnetic coupling constant (J) values of diradical systems linked with two monoradicals through a coupler (para-substituted phenyl acetylene (Model I), meta-substituted phenyl acetylene (Model II), ethylene (Model III)) were investigated by unrestricted density functional theory calculations. We divided eight monoradicals into α-group and β-group according to Mulliken spin density values of the connected atoms. The overall trends in the strength of magnetic interactions of diradicals were found to be identical in three different model systems. The diradicals with para-substituted phenyl acetylene coupler resulted in almost twice stronger intramolecular magnetic coupling interactions of the corresponding diradicals as compared to the meta-substituted one with opposite magnetism. NN-Ethylene-PO (nitronyl nitroxide radical coupled to phenoxyl radical via ethylene coupler) was calculated to have the strongest magnetic coupling constant with ferromagnetism, and to be even stronger (more than twice) than NN-ethylene-NN (nitronyl nitroxide diradical with ethylene coupler), which was reported to have strong antiferromagnetic interactions in a previous experiment. It was found that the spin density values of the connected atoms are closely related to the determination of magnetic interactions and J values. The spin states of the ground state in diradical systems were explained by means of the spin alternation rule.