A systematic review of the relationships among psychosocial factors and coping in adults with type 2 diabetes mellitus.
Type 2 diabetes mellitus contributes to poor health outcomes including mortality, yet there is a gap in the literature when seeking to understand the influence of psychosocial factors on coping in this population. The paper presents a systematic review of quantitative studies that examined relationships among psychosocial determinants and coping in adults with type 2 diabetes. This review is the second layer of knowledge discovery for the concept, "Taking on a life-altering change is a rhythmical journey of experiencing ups and downs on the way to acceptance." The life-altering change was determined to be a diagnosis of type 2 diabetes, the journey is the ups and downs of coping with the diagnosis as people work toward acceptance of type 2 diabetes. The review includes a synthesis of findings from 22 quantitative studies of psychosocial factors and coping in adults with type 2 diabetes. Anxiety, depression, stress, and diabetes distress were identified as key influential psychosocial factors. Increased social support was inversely related to emotional distress and coping styles were related to social well-being, psychological health, and physical health outcomes. The positive coping style of problem-focused coping was linked to improved psychological and physical health. Emotional responses to diagnosis were related to depression and anxiety. Negative coping styles of resignation, protest, or isolation were higher in women and linked to poorer quality of life, while avoidance was linked to increased diabetes-related distress and depressive symptoms.


Phenotype variability in the Miller acrofacial dysostosis syndrome. Report of two further patients.
In this report we present two unrelated patients with the postaxial dysostosis syndrome (Miller syndrome) and document further the phenotypic variability of the craniofacial stigmata and of the postaxial (and preaxial) upper and lower limb reduction anomalies.


A behavioural polymorphism in the marine snail Nassarius pauperatus: Geographic variation correlated with food availability, and differences in competitive ability between morphs.
The snail Nassarius pauperatus (Lamarck) is common on intertidal sandflats in southern Australia. A behaviour described and defined as being a "Twister" was observed in some individuals. Upon contacting a member of their own species, Twisters gave a very specific response, rotating their shell from side to side in a way similar to the escape responses displayed by many gastropods to predators. However, some individuals, defined as "Non Twisters", never gave this response after contacting another N. pauperatus. Breeding experiments suggested that being a Twister was heritable. The frequency of Twisters varied between populations of N. pauperatus, and was negatively correlated with food availability (as estimated by measuring hunger) and positively correlated with the population density of juvenile N. pauperatus.It was found in the laboratory that Twisters were better than Non Twisters at competing for space to feed, when food was in short supply and distributed as discrete patches. There was also evidence that competition for space to feed occurred when food was in short supply in the field and it was postulated that Twisters thus had a selective advantage compared to Non Twisters in such situations.These results are discussed in terms of whether the behavioural differences between populations can be attributed to either selection or stochastic factors.


Healing process of acetic acid-induced gastric ulcer and gastric mucosal prostaglandin E generation level in rats.
The prostaglandin E (PGE) generation level (PGE level) in the gastric mucosa was investigated in relation to the healing and relapse of acetic acid-induced gastric ulcers in the rat. The PGE level around ulcers showed higher levels after ulcer induction and decreased during the ulcer diminishing period. Thereafter, the PGE levels showed an inclination to increase during the ulcer exacerbation period. In reulcerated rats, PGE levels were significantly higher. In conclusion, a high level of PGE may indicate an ulcer exacerbation state.


Serum copper elevation from estrogen effect, masquerading as fungicide toxicity.
Copper toxicity has previously been reported from the wood preservative, copper naphthenate. Serum copper levels may be elevated by estrogen. Reported here is a case of a woman who was initially diagnosed with elevated serum copper levels from copper naphthenate exposure. She was later found to have a normal RBC copper level with resolution of her elevated serum copper level following discontinuation of estrogen. A previously healthy 44-year-old Caucasian female was referred for toxicology consultation due to persistently elevated serum copper levels following copper naphthenate applied in her home. She had initial nausea, nasal congestion and headache from the fumes but then remained asymptomatic. No evidence of underlying systemic disease or organ injury was found. Despite this and no further exposure, her serum copper remained elevated by 30% above normal over 9 months, peaking at 2301 microg/L (36 micromol/L). Review of the literature confirmed that oral contraceptive use will routinely elevate serum copper levels to the extent noted in this case. Her RBC copper level was normal. Cessation of the oral contraceptive for 2 months returned the serum copper levels to normal. This patient's elevations in serum copper were probably unrelated to her chemical exposure to copper naphthenate. Serum levels of copper were falsely elevated as a result of concomitant estrogen use, and were returned to normal when estrogen was discontinued.


High-performance liquid chromatographic method for measuring total plasma homocysteine levels.
We have modified a high-performance liquid chromatographic (HPLC) procedure based on SBD-F (ammonium-7-fluorobenzo-2-oxa-1,3-diazole-4-sulphonate) pre-column derivatization to obtain an assay that is useful for routine clinical total plasma homocysteine (tHcy) analysis. The introduction of easily handled sodium borohydride instead of the traditional tri-n-butylphosphine in dimethylformamide as a reductant and a 14-min run-time using basic isocratic HPLC equipment are the more notable advantages. The addition of mercaptopropionylglycine as an internal standard contributed to improvements in the reproducibility of the assay, yielding within- and between-run precisions of 1.9 and 4% (C.V.), respectively. Reference values for fasting tHcy were 7.65+/-2.3 and 8.9+/-2.4 micromol/l, while post-methionine load gave tHcy levels of 19.9+/-5.5 and 26.8+/-5.5 micromol/l, for women and men, respectively (n=40).


Development and reliability of a self-report questionnaire to examine children's perceptions of the physical activity environment at home and in the neighbourhood.
Environmental factors are increasingly being implicated as key influences on children's physical activity. Few studies have comprehensively examined children's perceptions of their environment, and there is a paucity of literature on acceptable and reliable scales for measuring these. This study aimed to develop and test the acceptability and reliability of a scale which examined a broad range of environmental perceptions among children. Based on constructs from ecological models, a survey incorporating items on children's perceptions of the physical and social environment at home and in the neighbourhood was developed. This was administered on two occasions, nine days apart, to a sample of 39 children aged 11 years (54% boys), attending a metropolitan Australian elementary school. The acceptability of the survey was determined by the proportion of missing responses to each item. The test-retest reliability of individual items, scores and scales were determined using Kappa statistics and percent agreement for categorical variables, and intraclass correlation coefficients (ICC) for continuous variables. There were few missing responses to each question, with only 4% of all responses missing. Although some Kappa values were low, all categorical variables showed acceptable reliability when examined for percent agreement between test and retest (range 68%-100% agreement). Continuous variables all showed moderate to good ICC values (range 0.72-0.92). Findings suggest this questionnaire is reliable and acceptable to children for assessing environmental perceptions relevant to physical activity among 11-year-old children.


Fatty acid profile of major lipid classes in plasma lipoproteins of patients with Friedreich's ataxia-demonstration of a low linoleic acid content most evident in the cholesterol-ester fraction.
Studies were undertaken to further characterize plasma lipids and lipoprotein abnormalities in Friedreich's ataxia. The high density lipoprotein (HDL) apo AI/AII ratio was quantitated by densitometry and found to be normal. The free to esterified cholesterol ratio in HDL was lower in Friedreich's ataxia because of a reduction in the amount of free cholesterol in this lipoprotein class. The fatty acid profile of the cholesteryl-ester (CE) fraction was markedly deficient in linoleic acid (18:2) in both total plasma and HDL. There was a compensatory increase in saturated acids. The HDL phospholipid (PL) fraction also showed a reduction in the proportion of 18:2 with a concomitant increase in stearic (18:0) and oleic acid (18:1) while the HDL triglyceride (TG) fraction showed only an increase in palmitoleic (16:1) and oleic acids. Feeding of soya lecithin rich in 18:2 failed to increase significantly the 18:2 content of HDL-CE and HDL-PL but lowered the percentage of 16:1 and 18:1 in all 3 lipid classes of HDL. Although the total plasma CE fatty acid profile was perturbed in Friedreich's Ataxia, total plasma PL and TG fatty acid patterns were unaffected. Among the plasma lipoprotein fatty acid profiles, that of the low density lipoprotein (LDL) was most affected, then that of the HDL. The very low density lipoprotein (VLDL) fatty acid composition showed an increase in 16:1 and a decrease in 18:2 which were entirely corrected by lecithin feeding. These results suggest the existence of a metabolic defect in the incorporation of 18:2 into chylomicron phospholipids within the intestinal mucosa.


Epigenetics of Neurodevelopmental Disorders Comes of Age with Roles in Clinical and Educational Applications.
Epigenetics is a gene regulation mechanism that does not depend on genomic DNA sequences, but depends instead on chemical modifications of DNA and histone proteins. [...].


[Electrophysiology and analysis of the image of the development of Purkinje cells in culture and in the intact animal].
The electrophysiological and morphological properties of the Purkinje cells (P cells) grown in organotypic cultures were studied in HRP intracellulary labelled neurons and compared to Golgi stained P cells from kitten of different ages. The effects of afferent fiber depletions on the final dendritic topological parameters were investigated by 3-dimensional reconstructions and computerized methods. In culture, the P cell dendritic trees always appeared reduced in size when compared to their in vivo counterparts. A discriminant analysis permitted the recognition of 3 populations of cultured P cells according to the type of deafferentation. In intact animals, the dendritic organization appeared biplanar around day 13. These results demonstrate that the presence of all normal inputs is required to achieve the full elaboration and the monoplanar disposition of the P cell dendrites.


Abnormal ion content, hydration and granule expansion of the secretory granules from cystic fibrosis airway glandular cells.
The absence or decreased expression of cystic fibrosis transmembrane conductance regulator (CFTR) induces increased Na(+) absorption and hyperabsorption of the airway surface liquid (ASL) resulting in a dehydrated and hyperviscous ASL. Although the implication of abnormal airway submucosal gland function has been suggested, the ion and water content in the Cystic Fibrosis (CF) glandular secretory granules, before exocytosis, is unknown. We analyzed, in non-CF and CF human airway glandular cell lines (MM-39 and KM4, respectively), the ion content in the secretory granules by electron probe X-ray microanalysis and the water content by quantitative dark field imaging on freeze-dried cryosections. We demonstrated that the ion content (Na(+), Mg(2+), P, S and Cl(-)) is significantly higher and the water content significantly lower in secretory granules from the CF cell line compared to the non-CF cell line. Using videomicroscopy, we observed that the secretory granule expansion was deficient in CF glandular cells. Transfection of CF cells with CFTR cDNA or inhibition of non-CF cells with CFTR(inh)-172, respectively restored or decreased the water content and granule expansion, in parallel with changes in ion content. We hypothesize that the decreased water and increased ion content in glandular secretory granules may contribute to the dehydration and increased viscosity of the ASL in CF.


Unweaving the autism spectrum.
Although genes associated with human autism spectrum disorders have been identified, bridging the gap between genetics and the patchwork of behavioral deficits associated with the disease remains an enormous challenge. Peñagarikano et al. (2011) now show that mice lacking CNTNAP2, a gene that causes a rare form of epilepsy associated with autistic features and language impairment, display similar phenotypes to their human counterparts, raising hopes that such models may speed the identification of neuronal circuitries underlying the core features of autism.


Cholesterol Assay Based on Recombinant Cholesterol Oxidase, ABTS, and Horseradish Peroxidase.
Cholesterol determination by cholesterol oxidase reaction is a fast, convenient, and highly specific approach with widespread use in clinical diagnostics. Routinely, endpoint measurements with 4-aminophenazone or 4-aminoantipyrine as chromogens and sodium cholate, surfactants, or alcohols as solubilizing agents are used. Here we describe a novel kinetic method to determine cholesterol in 0.05-0.75 mM range in neutral or acidic buffers by use of recombinant cholesterol oxidase from Nocardioides simplex in a coupled reaction with horseradish peroxidase, ABTS as a chromogen, and methyl-β-cyclodextrin as a solubilizing agent.


Effects of spinally and supraspinally injected 3-isobutyl-1-methylxanthine, cholera toxin, and pertussis toxin on immobilization stress-induced antinociception in the mouse.
The effects of intracerebroventricular (i.c.v.) and intrathecal (i.t.) 3-isobutyl-1-methylxanthine (IBMX), cholera toxin (CTX) and pertussis toxin (PTX) administration on immobilization-induced antinociception were studied in ICR mice. Antinociception was assessed by the tail-flick assay. Immobilization of the mouse increased inhibition of the tail-flick response for at least 1 h. The pretreatment with i.t. IBMX (0.01-1 ng), but not i.c.v. IBMX, significantly attenuated immobilization-induced inhibition of the tail-flick response. The pretreatments with i.c.v. PTX (0.05-0.5 microg) as well as i.t. CTX, but neither i.c.v. CTX (0.05-0.5 microg) nor i.t. PTX, potentiated the inhibition of the tail-flick response induced by immobilization stress. Our results suggest that spinally located phosphodiesterase appears to be involved in the production of immobilization stress-induced antinociception. In addition, inactivation of supraspinally located PTX-sensitive G-proteins and spinally located CTX-sensitive G-proteins may modulate immobilization stress-induced antinociception.


Consistency of voice frequency and perturbation measures in children using cepstral analyses: a movement toward increased recording stability.
Few studies have evaluated the pediatric voice objectively using acoustic measurements. Furthermore, consistency of these measurements across time, particularly for continuous speech, has not been evaluated. (1) To evaluate normal pediatric voice frequency and perturbation using both time-based and frequency-based acoustic measurements, and (2) to determine if continuous speech samples facilitate increased recording stability. DESIGN Prospective, longitudinal study. Pediatric otolaryngology practice within a tertiary hospital. Forty-three children, ages 4 to 17 years. INTERVENTION OR EXPOSURE: Sustained vowel utterances and continuous speech samples, which included 4 Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) sentences and the first sentence of the "rainbow passage" ("A rainbow is a division of white light into many beautiful colors that takes the shape of a long round arch, with its path high above and its 2 ends apparently beyond the horizon") were obtained at 2 time points. Intraclass correlation coefficients (ICCs) were calculated to assess reliability between speech samples. Fundamental frequency of sustained vowel utterances had excellent reliability (ICC ≥ 0.94). Time-based analyses of perturbation in sustained vowel utterances demonstrated poor reliability (ICC < 0.40), while frequency-based analyses of perturbation for these utterances demonstrated good to excellent reliability (ICC > 0.40). Fundamental frequency of continuous speech sample had excellent reliability (ICC > 0.94). Frequency-based analyses of continuous speech samples demonstrated excellent reliability (ICC > 0.75) for all but 1 variable, which demonstrated good reliability (cepstral-spectral index of dysphonia of the all voiced sample; ICC =0.72). Sustained vowel utterance and continuous speech samples provide consistent measures of fundamental frequency. Frequency-based analysis of sustained vowel recordings improves the reliability of perturbation measures. Continuous speech recordings can be obtained in children and demonstrate good to excellent reliability across recordings. This suggests that frequency-based analysis of continuous speech may be more representative of a child's voice and therefore may be of use in the study both of the developmental changes of the pediatric voice as well as the study of vocal changes pretreatment and posttreatment in children with voice disorders.


Major improvement of the reference method of the French drug resistance network for P-glycoprotein detection in human haematological malignancies.
The aim of this study was to improve significantly the sensitivity and specificity of the flow cytometric assay of P-glycoprotein (Pgp) implemented and validated by the laboratories of the French Drug Resistance Network [Huet S, Marie JP, Gualde N, Robert J. Reference method for detection of Pgp mediated multidrug resistance in human hematological malignancies: a method validated by the laboratories of the French Drug Resistance Network. Cytometry 1998;34:248-56] in cells displaying low level of resistance. Fluoresceine-conjugated monoclonal antibodies (Mabs) and propidium iodide were respectively replaced by phycoerythrin-conjugated Mabs and Sytox green. The removal of erythrocytes and granulocytes by density gradient was replaced by the lysis of erythrocytes after Mab incubation. Using these conditions, Pgp could be detected in the K-H30 line, which was negative in former studies, with Mab/Control ratios increasing by 3.7- to 5.9-fold, and Mab/Control ratios in the parental sensitive K562 line still ranging between 0.8 and 1.2. When tested on 16 blood samples from patients presenting haematological malignancies, six samples presented low positivity, which was not detected with the former method, while 10 samples remained negative with the two methods. Pgp was specifically detected in pathological blood cells in the six positive samples.


Hemorrhagic infarct of basal ganglia in cardiac arrest. CT and MRI findings. 2 cases.
We report the CT and MRI findings in two cases of hemorrhagic infarct of the basal ganglia (BG), following out-of-hospital cardiac arrest (CA). In case 1, Brain-CT realized at day 2 showed bilateral and almost symmetric hemorrhagic infarct of the BG and infarct of the tectum of the mesencephalon. In case 2, MRI realized at day 6 showed hemorrhagic infarct of both lenticular nuclei on T2 GE images. In both cases there was no medical history and the cardiovascular and the coagulation profile were normal. In these cases, the lesions are observed earlier than reported in a few previous radiological cases. Similar lesions have been reported in pathological studies. These lesions seem occur early after CA. Reperfusion is probably responsible for the hemorrhagic transformation. The reason why some patients present either BG or brainstem infarct or both remains unclear. Bilateral and symmetric hemorrhagic infarct of the BG, especially of the Lenticular nuclei, and infarct of the dorsal pons and mesencephalic tegmentum seem to be a characteristic feature of profound and prolonged hypotension or of CA.


Determinants of Use of Biotherapeutics in sub-Saharan Africa.
Biologic drugs are reshaping clinical practice in various disciplines, even while access to them is imbalanced across global settings. In sub-Saharan Africa, biotherapeutics have potential roles to play in the treatment of a range of conditions that include infectious and noncommunicable diseases (NCDs). However, the literature is scarce on guidance for addressing local access challenges, including technical, regulatory, affordability, and other healthcare delivery aspects. This article aims to assess fundamental determinants of use of biologic medicines in sub-Saharan Africa. The purpose is to inform strategic actions of scientists, physicians, policymakers, and other stakeholders that are working to improve access to innovative therapies in low resource parts of the world.


Bubble cell for magnetic bead trapping in capillary electrophoresis.
A bubble cell capillary classically used to extend the optical path length for UV-vis detection is employed here to trap magnetic beads. With this system, a large amount of beads can be captured without inducing a strong pressure drop, as it is the case with magnetic beads trapped in a standard capillary, thereby having less effect on the experimental conditions. Using numerical simulations and microscopic visualizations, the capture of beads inside a bubble cell was investigated with two magnet configurations. Pressure-driven and electro-osmotic flow velocities were measured for different amounts of protein-A-coated beads or C18-functionalized beads (RPC-18). Solid-phase extraction of a model antibody on protein-A beads and preconcentration of fluorescein on RPC-18 beads were performed as proof of concept experiments.


[Survey of caries in 1052 non native children located in Putuo District of Shanghai City].
To investigate the prevalence of caries in non-native children located in Putuo District of Shanghai. A survey of caries was performed in 1052 non-native children according to the Criteria for National Oral Epidemiologic Survey. Caries prevalence rate in deciduous teeth was 85.8%, DFT was 4.61. Caries prevalence rate in permanent teeth was 6.45%, DFT was 1.4. The prevalence rate of caries in non-native children located in Putuo District of Shanghai was still higher. More attention should be addressed in prevention and treatment.


Victims of Alzheimer's disease and the environment.
The environment plays an essential role in the functioning and care of older persons, particularly those with Alzheimer's disease. This article describes the characteristics of the environment that affect the functioning of persons with Alzheimer's disease and the interaction between the person and environment. Assessment and interventions based on environmental characteristics and person-environment interaction are identified.


Exorcism as psychiatric treatment: a homosexual case study.
A case of exorcism as apparently successful treatment of transsexualism has previously been reported. The actual procedure in a similar case of exorcism by a psychiatrist is reported, together with details of the outcome and a discussion of theoretical, applied, and ethical aspects of the case.


Gene editing in human stem cells using zinc finger nucleases and integrase-defective lentiviral vector delivery.
Achieving the full potential of zinc-finger nucleases (ZFNs) for genome engineering in human cells requires their efficient delivery to the relevant cell types. Here we exploited the infectivity of integrase-defective lentiviral vectors (IDLV) to express ZFNs and provide the template DNA for gene correction in different cell types. IDLV-mediated delivery supported high rates (13-39%) of editing at the IL-2 receptor common gamma-chain gene (IL2RG) across different cell types. IDLVs also mediated site-specific gene addition by a process that required ZFN cleavage and homologous template DNA, thus establishing a platform that can target the insertion of transgenes into a predetermined genomic site. Using IDLV delivery and ZFNs targeting distinct loci, we observed high levels of gene addition (up to 50%) in a panel of human cell lines, as well as human embryonic stem cells (5%), allowing rapid, selection-free isolation of clonogenic cells with the desired genetic modification.


Assessment of diabetes screening by general practitioners in France: the EPIDIA Study.
To audit Type 2 diabetes screening in general practice in France and to determine the frequency of undiagnosed diabetes in patients at high risk, after systematic screening and diagnosis. For this study, 288 general practitioners volunteered to include all consecutive non-diabetic patients aged < 65 years who had at least two risk factors for diabetes, whatever the reason for consultation. If a plasma glucose had not been recorded in the previous 12 months, a fasting plasma glucose (FPG) was performed, with a second test if FPG >or= 7.0 mmol/l. There were 5950 patients included. The most frequent diabetes risk factors were: age >or= 40 years, 92%; overweight [body mass index (BMI) >or= 27 kg/m2], 59%; treated hypertension, 48%; treated dyslipidaemia, 37%; family history of diabetes, 24%. Of these subjects at high risk for diabetes, 88% had a FPG measurement in their medical record (75% measured during the preceding 12 months). In the 1499 patients in whom FPG was measured, diabetes was diagnosed in 40 patients (2.7% 95% CI 1.9-3.5) and 22% had impaired fasting glucose (IFG). Thus, the frequency of undiagnosed diabetes in the 5950 high-risk patients was 0.67% (0.46-0.88). Screening for diabetes by general practitioners in France appears to be adequate and undiagnosed diabetes is rare in patients with risk factors for diabetes, at least in those consulting the general practitioners studied.


Purification, preparation, and use of chaperone-peptide complexes for tumor immunotherapy.
The molecular chaperone heat-shock protein 70 (Hsp70) possesses immune stimulatory properties that have been employed in the preparation of anticancer vaccines. Hsp70 binds antigenic peptides in the cytoplasm of cancer cells. Hsp70 thus serves as a convenient, non-discriminating transporter of antigens and can protect the peptides during internalization by APC and cross presentation to T lymphocytes. We describe a method for purifying Hsp70-peptide complexes that can be used to prepare molecular chaperone-based vaccines, involving sequential gel filtration, ion exchange, and affinity chromatography.


Associations of brachial-ankle pulse wave velocity with left atrial stiffness and left atrial phasic function in inpatients with hypertension.
Hypertension induces left atrial (LA) and left ventricular (LV) dysfunction, and an increase in arterial stiffness. This study aimed to investigate the associations of brachial-ankle pulse wave velocity (baPWV) with LA stiffness and LA phasic function in hypertension. A total of 305 hypertensive inpatients enrolled and were divided into two groups based on baPWV [Group I, baPWV ≤ 1515 (cm/s), n = 153; Group II, baPWV > 1515 (cm/s), n = 152]. Two-dimensional speckle tracking echocardiography (2D-STE) based LA phasic strains (LAS-S, LAS-E, LAS-A) and LV global longitudinal strain (LVGLS) were evaluated. LA stiffness index (LASI) was defined as the ratio of E/e' to LAS-S. Multivariate linear regression modeling was used to analyze the associations of baPWV with LASI and LA phasic function in all patients as well as age-specific and sex-specific subgroups. LASI was significantly higher in Group II [0.35(0.26, 0.52)] compared with Group I [0.26(0.20, 0.36)] (P < 0.001). After adjusting cardiovascular risk factors, medication, and LV structural and functional parameters (LVEF, LVMI, E/A ratio, and LVGLS), baPWV remained significantly correlated with LASI (P < 0.05). We also evaluated the predictive value of baPWV for LASI, the area under the curve (AUC) was 0.663 (95% CI: 0.607-0.716, P < 0.001). In conclusion, BaPWV was independently associated with LA stiffness in hypertensive inpatients. BaPWV also exhibited a certain predictive value for LA stiffness in these inpatients. Measuring arterial stiffness can provide clinicians clues for early cardiac target organ damage (TOD) in addition to vascular TOD.


Diagnostic accuracy of pleural fluid polymorphonuclear elastase in the differentiation between pyogenic bacterial infectious and non-infectious pleural effusions.
To establish the diagnostic accuracy of the markers of neutrophil activity (elastase and lysozyme) determined in pleural fluid, for differentiating between pyogenic bacterial infectious and non-infectious pleural effusions. At our tertiary referral teaching hospital, 160 patients over 14 years with pleural effusion (PE), classified as pyogenic bacterial infectious (41 parapneumonic complicated, 32 parapneumonic non-complicated) and non-infectious (32 neoplasm and 55 undiagnosed pleural exudates) were examined in a prospective study. Polymorphonuclear elastase (PMN-E) was determined by an immunoactivation method and lysozyme by a turbidimetric method. Receiver operating characteristic (ROC) curves were used to evaluate diagnostic accuracy. Pleural fluid PMN-E was the biochemical marker that best differentiated between pyogenic bacterial infectious and non-infectious PE. The ROC area under the curve (AUC) for PMN-E was 0.8276. A PMN-E value over 230 microg/l diagnosed infectious PE with a specificity of 0.81 and a sensitivity of 0.74. The ROC AUC for proteins plus lactate dehydrogenase was 0. 7430. Differences between the two ROC curves were significant (p = 0. 032). After excluding purulent parapneumonic complicated PE, the sensitivity of a pleural fluid PMN-E value equal to or greater than 230 microg/l was 0.64 and the specificity 0.81. Pleural fluid PMN-E was the marker that best differentiated infectious from non-infectious PE, and PMN-E values lower than 230 microg/l suggest non-infectious PE.


Hearing in slow-motion: Humans underestimate the speed of moving sounds.
Perception can often be described as a statistically optimal inference process whereby noisy and incomplete sensory evidence is combined with prior knowledge about natural scene statistics. Previous evidence has shown that humans tend to underestimate the speed of unreliable moving visual stimuli. This finding has been interpreted in terms of a Bayesian prior favoring low speed, given that in natural visual scenes objects are mostly stationary or slowly-moving. Here we investigated whether an analogous tendency to underestimate speed also occurs in audition: even if the statistics of the visual environment seem to favor low speed, the statistics of the stimuli reaching the individual senses may differ across modalities, hence potentially leading to different priors. Here we observed a systematic bias for underestimating the speed of unreliable moving sounds. This finding suggests the existence of a slow-motion prior in audition, analogous to the one previously found in vision. The nervous system might encode the overall statistics of the world, rather than the specific properties of the signals reaching the individual senses.


Silent cerebral infarction in heart failure: vascular or thromboembolic?
Silent cerebral infarction in heart failure as reported by Siachos et al is significantly higher than reports of symptomatic cerebral infarction. Are we underestimating the occurrence of silent cerebral infarction, or can this finding be accounted for by concomitant conditions?


Cryoablation for Secondary Renal Cell Carcinoma After Surgical Nephrectomy.
To retrospectively evaluate the clinical outcomes of cryoablation for secondary renal cell carcinoma for patients with a history of nephrectomy for initial renal cell carcinoma. Thirty patients with 40 renal tumors who had undergone a nephrectomy for initial renal cell carcinoma and cryoablation for renal cell carcinoma as a secondary treatment during the period from April 2014 to December 2018 at a single center institution were enrolled. The patients' overall survival, local control, relapse-free survival, change of renal function, and complications were evaluated. The clinical factors of relapse-free survival were also evaluated. The 5 year overall survival rate was 94.5%, the 5 year local control rate was 89.3%, and the 5 year relapse-free survival rate (RFSR) was 56.3%. There was an average reduction in renal function of 8.5% after 1 year, and > grade 3 complications occurred in only one case. The RFSR in the patients whose initial stage was T3 was 0%, significantly lower than the 70.4% RFSR in the patients whose initial stage was T1 or T2. Cryoablation for secondary renal cell carcinoma after nephrectomy was safe and provided good local control with preserved renal function. However, the indications for cryoablation should be carefully considered for patients with T3-stage initial renal cell carcinoma, because of the high risk of relapse. III.


Neuronal profilins in health and disease: Relevance for spine plasticity and Fragile X syndrome.
Learning and memory, to a large extent, depend on functional changes at synapses. Actin dynamics orchestrate the formation of synapses, as well as their stabilization, and the ability to undergo plastic changes. Hence, profilins are of key interest as they bind to G-actin and enhance actin polymerization. However, profilins also compete with actin nucleators, thereby restricting filament formation. Here, we provide evidence that the two brain isoforms, profilin1 (PFN1) and PFN2a, regulate spine actin dynamics in an opposing fashion, and that whereas both profilins are needed during synaptogenesis, only PFN2a is crucial for adult spine plasticity. This finding suggests that PFN1 is the juvenile isoform important during development, whereas PFN2a is mandatory for spine stability and plasticity in mature neurons. In line with this finding, only PFN1 levels are altered in the mouse model of the developmental neurological disorder Fragile X syndrome. This finding is of high relevance because Fragile X syndrome is the most common monogenetic cause for autism spectrum disorder. Indeed, the expression of recombinant profilins rescued the impairment in spinogenesis, a hallmark in Fragile X syndrome, thereby linking the regulation of actin dynamics to synapse development and possible dysfunction.


Astrocyte metabolism and signaling during brain ischemia.
Brain ischemia results from cardiac arrest, stroke or head trauma. These conditions can cause severe brain damage and are a leading cause of death and long-term disability. Neurons are far more susceptible to ischemic damage than neighboring astrocytes, but astrocytes have diverse and important functions in many aspects of ischemic brain damage. Here we review three main roles of astrocytes in ischemic brain damage. First, we consider astrocyte glycogen stores, which can defend the brain against hypoglycemic brain damage but may aggravate brain damage during ischemia due to enhanced lactic acidosis. Second, we review recent breakthroughs in understanding astrocytic mechanisms of transmitter release, particularly for those transmitters with known roles in ischemic brain damage: glutamate, D-serine, ATP and adenosine. Third, we discuss the role of gap-junctionally connected networks of astrocytes in mediating the spread of damaging molecules to healthy 'bystanders' during infarct expansion in stroke.


Urethral duplication in girls: Three cases associating an accessory epispadiac urethra and a main hypospadiac urethra.
Urethral duplication is extremely rare in girls, with less than 40 cases reported so far. Most of them present as a prepubic sinus. Literature is scare regarding aetiology, classification and management in other forms. This study presents three cases of sagittal urethral duplication in girls presenting a main hypospadiac urethra and an accessory epispadiac urethra. Medical records were retrospectively reviewed of three girls with urethral duplication managed over a 30-year period at a single institution. Circumstances of diagnosis, management and outcomes were analysed. The oldest case presented as a neonatal retrovesical mass with an accessory clitoral stream, whereas the two more recent cases presented with antenatal hydrocolpos and bilateral ureterohydronephrosis. Cases 1 and 3 had an incomplete duplication, while Case 2 had a complete form. In Case 3, the duplication was associated with a urogenital sinus and an anteriorly placed anus. Management involved resection of the epispadiac accessory urethra to achieve continence, with dilatation and/or mobilisation of the hypospadiac one. All girls are now aged >5 years old and are continent, and one is old enough to have normal menstruation. Renal function is normal in all. The summary table presents the schematic anatomical description as shown on micturating cystourethrogram and endoscopy, as well as the management for each patient. Step-by-step management is necessary in urethral duplication. The neonatal emergency is to release the urinary tract compression by evacuating urinary retention or hydrocolpos. Later in infancy, decision has to be taken regarding the urethras. If the resection of the epispadiac accessory urethra seems acceptable to achieve continence, the attitude towards the hypospadiac channel is more controversial and should be individualised. Embryologic and aetiopathogenic pathways are still missing to uniformly characterise the malformation. Paediatric urologists should remember that there is a wide spectrum of urethral duplication in girls, and that various presentations exist beside the more classic prepubic sinus.


Seed predation by mammals and forest dominance by Quercus oleoides, a tropical lowland oak.
Quercus oleoides Cham. and Schlecht is an unusual tree in several respects: it is an oak found in neotropical lowland forests, its distribution is not continuous but ratherdivided into many patches of various sizes, and it is a dominant in all the forests in which it occurs, attaining densities far higher than most species of tropical trees. This density pattern is related to the vulnerability of Q. oleoides acorns to predation by mammals. Observations of agoutis, deer, peccaries, squirrels, pocket mice and other seed consumers in Santa Rosa National Park, Costa Rica, showed that these mammals act only as predators, not dispersers, of Q. oleoides acorns. Experiments which involved placing acorns in deciduous forest where Q. oleoides does not occur, demonstrated that, due to high predation rates, the number of acorns produced by an isolated tree is far too low for adults to replace themselves.In oak forest, on the other hand, where the combined acorn crops of many oaks satiate the seed predators, acorn survivorship until germination is high enough to maintain the population. Furthermore, acorn survivorship in oak forest areas is inversely proportional to the apparent mammal density in those areas. Thus the pattern of forest dominance and patchy distribution is related to positively density-dependent acorn survivorship: where Q. oleoides is the forest dominant, it will survive, but if its density falls to the level typical of tropical trees, it will go locally extinct.


Effect of embolic particles during coronary interventional procedures on regional wall motion in patients with stable angina pectoris.
Microembolization during percutaneous coronary intervention (PCI) causes minor myocardial injury, and a Doppler guidewire can detect embolic particles as high-intensity transient signals (HITS). The present study investigated the effect of microembolization during PCI on regional wall motion using a Doppler guidewire and myocardial strain analysis. We performed PCI to the left anterior descending coronary artery in 25 patients (18 men and 7 women, 68 ± 8 years old) with stable angina pectoris. Coronary flow spectrums were obtained with a Doppler guidewire to count the total number of HITS throughout the PCI procedures. On the days before and after PCI, we recorded echocardiography and measured the longitudinal peak systolic strain, peak strain rate, and early diastolic strain rate in the left anterior descending territory using a 2-dimensional speckle tracking method. PCI was successfully performed, and 10 ± 6 HITS (range 0 to 22, median 9) were recognized during PCI. The echocardiographic study showed no visible wall motion abnormalities in the left anterior descending territory either after or before PCI. In cases in which the total number of HITS was ≥10, the peak systolic strain, peak strain rate, and early diastolic strain rate worsened on the day after PCI compared with those on the day before PCI (p <0.01). The rates of change in peak systolic strain and early diastolic strain rate, defined as the ratios of those parameters after PCI to those before PCI, had modest to strong inverse correlations with the total number of HITS (R(2) = 0.35 and R(2) = 0.46, respectively). In conclusion, periprocedural microembolization during PCI reduces subclinical cardiac function in patients with stable angina pectoris.


Tamsulosin: a review of its pharmacology and therapeutic efficacy in the management of lower urinary tract symptoms.
Tamsulosin is a subtype-selective alpha(1A)- and alpha(1D )-adrenoceptor antagonist. alpha(1)-Receptors predominate in the prostate gland, prostatic capsule, prostatic urethra and bladder, and the relaxation of prostate and bladder smooth muscles is associated with improved maximal urine flow (Q(max)) and alleviation of lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH). Tamsulosin 0.4 mg once daily in a modified-release formulation increased Q(max) and improved symptom scores relative to baseline to a greater extent than placebo in 12- and 13-week double-blind, randomised, multicentre, clinical trials in patients with LUTS, with statistical significance between treatments for Q(max) values in two of three published US and European studies. Tamsulosin is effective in patients with mild to severe LUTS associated with BPH, in patients with diabetes mellitus and in the elderly, and does not interfere with concomitant antihypertensive therapy. Pooled data based on patients receiving tamsulosin 0.4 or 0. 8mg once daily indicate maintenance of efficacy for up to 6 years. Tamsulosin 0.4 mg once daily was of similar efficacy to alfuzosin 2.5 mg three times daily, with less tendency to cause hypotensive effects, in a double-blind, randomised 12-week trial. Benefit of the drug has also been shown in patients with acute urinary retention or chronic abacterial prostatitis, those receiving high energy transurethral microwave thermotherapy, and in patients with prostate cancer with radiation-induced urethritis. Dizziness and abnormal ejaculation are stated to be the most common adverse events, with asthenia, postural hypotension and palpitations being seen less frequently (1 to 2% incidence), in patients receiving tamsulosin 0.4 mg once daily. Tamsulosin has not been associated with clinically significant changes in blood pressure in clinical trials. The alpha(1A)- and alpha(1D)-adrenoceptor antagonist tamsulosin, given at a dosage of 0.4 mg once daily in a modified-release formulation, is effective and well tolerated in the treatment of LUTS associated with BPH. Although the drug has been directly compared to date with one other agent only, data show overall that tamsulosin clearly offers advantages over other alpha(1)-adrenoceptor antagonists in terms of the need for a single daily dose only, and its low potential for hypotensive effects or interference with concomitant antihypertensive therapy. Dosage titration at the start of treatment is not necessary. Tamsulosin has a rapid onset of action and is effective in patients with moderate or severe symptoms. The drug is therefore a valuable therapeutic option, with both demonstrated and potential advantages over older nonselective agents, in the management of patients with LUTS associated with BPH.


Questionnaires that assess disability in children and adolescents with low back pain adhere to the concepts of the International classification of functioning, disability and health (ICF), but lack validity for this population: a systematic review.
We aimed to identify Patient-Reported Outcome Measures (PROMs) that assess disability in children and adolescents with low back pain (LBP), analyzing their adherence to the International Classification of Functioning, Disability and Health (ICF) biopsychosocial model; and to describe the measurement properties of these PROMs. We searched Pubmed, Embase and CINAHL databases. The review included searches up to March 2022. Meaningful concepts of the PROMs were linked to ICF domains, and we manually searched for the measurement properties of each included PROM. We included 23 studies, of which eight PROMs were analyzed. We retrieved 182 concepts in total. Activities was the domain with the highest number of linked concepts, whereas personal factors had no linked concepts. The modified Hannover Functional Ability Questionnaire (mHFAQ) and the Micheli Functional Scale (MFS) had measurement properties tested in children and adolescents, but had no information about construct validity. Although most of the identified PROMs had broad coverage of their concepts in the ICF, only two PROMs had measurement properties tested in the population of interest in this review, in which the mHFAQ presented wide coverage in relation to the ICF. Further studies are needed to investigate content validity of these PROMs.


Urotensin II in chronic liver disease: in vivo effect on vascular tone.
Urotensin II (UII) is now recognized as the most potent human vasoconstrictor. Although its role in human pathophysiology is unknown, vasoactive mediators are known to be important in the pathogenesis of portal hypertension complicating chronic liver disease. The objective of this study was to investigate the role of UII in liver cirrhosis via examination of the in vivo effect of UII in this patient group. The vasoactive effects of UII were measured using Laser Doppler velocimetry on cirrhotic patients (n = 14) and age-matched healthy controls (n = 14) after UII administration by iontophoresis to the cutaneous microcirculation of the forearm. In vivo administration of UII produced vasoconstriction of the cutaneous microcirculation in the cirrhotic group and vasodilatation in the controls, with values differing significantly at the two highest doses of UII: 10(-9) mol (p = 0.01) and 10(-7) mol (p = 0.004). UII mediates vasoconstriction of the microcirculation of cirrhotics but not of controls. This suggests that UII has pathophysiological relevance in the portal hypertensive population through its vasoactive properties. Further studies of UII and UII-antagonists are warranted in this patient population.


Enhanced antibody responses in mice by combined administration of interferon with rabies vaccine.
Exogenous interferon administered to mice at the time of, and 6 hours after the first dose of 3 daily vaccinations accelerated and enhanced the IgM and IgG antibody responses to rabies virus. The effect of interferon was not evident when the interferon was administered later in the vaccination schedules and was abrogated by prior administration of anti-interferon antibody to the mice. The number of IgM antibody secreting cells in the spleen was significantly greater in mice treated with interferon than in controls.


Baboon lipoprotein lipase: cDNA sequence and variable tissue-specific expression of two transcripts.
We have isolated two lipoprotein lipase (LPL)-encoding cDNA (LPL) clones from a baboon cardiac cDNA library, one of which spans a region from nucleotide (nt) 705 of the coding sequence to the poly(A) tail (2.8 kb). We used reverse transcription followed by PCR (RT-PCR), and anchor-ligated rapid amplification of cDNA ends (RACE) to amplify the remaining 5' region of the LPL transcript. Sequence comparisons reveal that the baboon nt sequence is 95% identical to the human cDNA sequence (ranging from 97.5 to 92.7% in the coding and noncoding regions, respectively). Less than 2% of nt substitutions cause changes between baboon and human amino acid (aa) sequences. The aa in the catalytic triad residues, the heparin-binding site in exon 6, as well as aa in positions where missense mutations cause LPL deficiency, are identical in baboons and humans. Characterization of the tissue-specific expression of LPL using Northern blots of total RNA showed that spinal cord expressed the most LPL transcripts of all baboon tissues examined. Like humans, baboons have two transcript sizes of approx. 3.6 and 3.4 kb in most tissues that express LPL, and sequencing of the 3' untranslated region (UTR) shows this is due to two polyadenylation sites. In contrast, only the larger 3.6-kb transcript is detected in RNA isolated from central nervous system (CNS) tissues. We used RT-PCR to show that the polyadenylation signal that produces the 3.4-kb message is present in CNS LPL transcripts, but is not utilized.


Androgen receptor in electroresected and cold punch-resected specimens. Usefulness of Kaplan cold punch resectoscope.
The measurement of androgen receptor and 5 alpha-dihydrotestosterone (DHT) levels in prostatic carcinoma may be of value in predicting responsiveness to anti-androgenic therapy. A sufficient amount of prostatic carcinoma tissue must be removed for measuring androgen receptor and DHT levels. We have studied the usefulness of Kaplan cold punch-resection compared with electroresection for obtaining tissue in 29 cases of enucleated benign prostatic hyperplasia. DHT level in electroresected specimens was similar to controls. However, following low, moderate, and high-power electroresection an average of total R1881 binding sites (Bmax) of electroresected specimens was reduced to 82.2, 71.9, and 52.1 per cent of corresponding controls, respectively. In contrast, the per cent decrease of Bmax of Kaplan cold punch-resected specimens was only 10 per cent of the control. From our data, Kaplan cold punch-resection of the prostate appears to be a useful tool for obtaining tissue suitable for measuring androgen receptor levels.


Acquired hydrocephalus. V. Determination of the formation rate of albumin in the ventricular system.
By quantitative isotope ventriculography (QIV), the formation rate of albumin in the ventricular system (FRalb) was determined in 14 hydrocephalic and 14 nonhydrocephalic patients. The FRalb was significantly reduced in the patients with acquired hydrocephalus. By a comparison of the mean formation rate of albumin (MFRalb) and the mean absorption rate of albumin (MARalb), a significant biological difference in the two groups of patients was demonstrated.


Stereoselective hydroxylation of mexiletine in human liver microsomes: implication of P450IID6--a preliminary report.
Mexiletine, a class Ib antiarrhythmic drug, is used clinically as a racemic mixture of two enantiomers. Aromatic and aliphatic hydroxylation are the two major metabolic steps. In the liver, this metabolism is catalyzed by the cytochrome P450IID6, an isoenzyme of cytochrome P450 due to genetic polymorphism in humans. In the present study, the metabolism of the two stereoisomers was compared in vitro in human liver microsomes. Parahydroxylation (aromatic hydroxylation) is favored for S(+)-mexiletine with a mean intrinsic clearance higher than for R(-)-mexiletine. The R(-) enantiomer exhibits a threefold higher mean Vmax value for aliphatic hydroxylation than S(+)-mexiletine. We showed that (i) the high-affinity component of dextrometorphan O-demethylation was competitively inhibited by R(-)- and S(+)-mexiletine and that (ii) hydroxylations of the two enantiomers were very strongly competitively inhibited by quinidine. Hydroxylation reactions of mexiletine exhibit stereoselectivity in vitro in human liver microsomes and are catalyzed by P450IID6.


Perspectives from the other side: a physician and cancer survivor.
ASCO has made great strides to integrate palliative care into the comprehensive care model. However, much work remains to ensure that all patients, whether receiving curative or palliative therapy, have a good quality of life.


SLC10A3 Is a Prognostic Biomarker and Involved in Immune Infiltration and Programmed Cell Death in Lower Grade Glioma.
The association between SLC10A3 (solute carrier family 10 member 3) and lower grade glioma (LGG) remains unclear. We used public databases and bioinformatics analysis to analyze SLC10A3. These included The Cancer Genome Atlas, Genotype-Tissue Expansion, Chinese Glioma Genome Atlas, Human Protein Atlas, GeneCards, cBioPortal, Search Tool for the Retrieval of Interacting Genes/Proteins, Gene Expression Profiling Interactive Analysis, Tumor Immune Estimation Resource, Tumor-Immune System Interaction Database, receiver operating characteristic curve analysis, Kaplan-Meier analysis, Cox analysis, nomograms, calibration plots, gene ontology/Kyoto Encyclopedia of Genes and Genomes enrichment analysis, gene set enrichment analysis, single-sample gene set enrichment analysis, and Spearman's correlation analysis. SLC10A3 was upregulated in adrenocortical carcinoma, glioblastoma, and LGG and was associated with good overall survival (OS) in adrenocortical carcinoma and poor OS in LGG and glioblastoma. SLC10A3 was increased with increased World Health Organization grade, upregulated in isocitrate dehydrogenase-wild type, 1p/19q (chromosome arms 1p and 19q) non-co-deleted, and higher in astrocytoma. Patients with LGG were grouped by the occurrence of the clinical outcome endpoints (i.e., OS, disease-specific survival [DSS], and progression-free interval events). Genetic alterations in SLC10A3 were associated with poor progression-free survival in LGG. Most of clinical characteristics were associated with the SLC10A3 expression level. SLC10A3 with diagnostic and prognostic value (OS, DSS, and progression-free interval) was an independent prognostic factor in LGG. Moreover, Nomograms (WHO grade, 1p/19q codeletion, age and SLC10A3) had moderately accurate predictive for OS and DSS. Functional analysis showed that SLC10A3 might participate in the transport of multiple substances, neurogenic signaling, immune response, and programmed cell death in LGG. SLC10A3 correlated with immune infiltration in LGG and moderately correlated with the gene signature of pyroptosis, lysosome-dependent cell death, necroptosis, apoptosis, ferroptosis, alkaliptosis, and autophagy-dependent cell death. SLC10A3 is a potential diagnostic and prognostic biomarker for LGG and might be associated with substance transport, neurogenic signaling, immune infiltration, and programmed cell death in LGG.


Aspirin Resistance in Single-Ventricle Physiology: Aspirin Prophylaxis Is Not Adequate to Inhibit Platelets in the Immediate Postoperative Period.
Incidence of thrombosis after initial stage 1 single-ventricle palliation is high. Most centers use aspirin as an antiplatelet agent to prevent thrombosis in surgically placed shunts. We hypothesize there is a significant incidence of aspirin resistance in infants after stage 1 palliation and this resistance can be overcome by an increased aspirin dose. This is a prospective observational study of 20 patients with single-ventricle physiology who required single-ventricle palliation with a controlled source of pulmonary blood flow (Norwood/Sano, Norwood/Blalock-Taussig [BT] shunt or BT shunt alone). Aspirin resistance was determined using thromboelastography with platelet mapping (TEG) and urine thromboxane (UTX). The UTX level of less than 1,500 pg/mL and TEG value of more than 50% were used to define as adequate platelet inhibition. The UTX was measured prior to starting aspirin (20 mg/day) and TEG and UTX were obtained after 5 days of aspirin therapy A repeat UTX was measured for patients who were determined to be aspirin resistant by TEG (<50% arachidonic acid inhibition) after doubling the dose (40 mg/day). Clinical variables including patient diagnosis, age of surgery, and cardiopulmonary bypass requirement, weight, hemoglobin, and platelet count were assessed to determine their association with aspirin resistance. Eighty percent of patients were aspirin resistant using TEG (95% CI, 56% to 94%) and none of the patients achieved a UTX level of less than 1,500 pg/mL. Aspirin resistant patients did not respond to an increased dose of aspirin between the fifth and tenth days of therapy (p = 0.820). Patients did, however, respond to aspirin treatment when comparing the baseline UTX measurement with those recorded on the fifth day (p = 0.008) and the tenth day (p = 0.0361) of aspirin therapy. The UTX levels did not differ between those who were and those who were not aspirin resistant by TEG at any of the measurement times. The clinical variables were not associated with aspirin resistance status. There is a high incidence of aspirin resistance in the immediate postoperative period after single-ventricle shunt palliation. Aspirin might not be an adequate agent for shunt prophylaxis in this patient population. Further studies are needed to identify at-risk patients who might benefit from additional testing and specific anticoagulation.


Ensemble of nucleic acid absolute quantitation modules for copy number variation detection and RNA profiling.
Current gold standard for absolute quantitation of a specific DNA sequence is droplet digital PCR (ddPCR), which has been applied to copy number variation (CNV) detection. However, the number of quantitation modules in ddPCR is limited by fluorescence channels, which thus limits the CNV sensitivity due to sampling error following Poisson distribution. Here we develop a PCR-based molecular barcoding NGS approach, quantitative amplicon sequencing (QASeq), for accurate absolute quantitation scalable to over 200 quantitation modules. By attaching barcodes to individual target molecules with high efficiency, 2-plex QASeq exhibits higher and more consistent conversion yield than ddPCR in absolute molecule count quantitation. Multiplexed QASeq improves CNV sensitivity allowing confident distinguishment of 2.05 ploidy from normal 2.00 ploidy. We apply multiplexed QASeq to serial longitudinal plasma cfDNA samples from patients with metastatic ERBB2+ (HER2+ ) breast cancer seeking association with tumor progression. We further show an RNA QASeq panel for targeted expression profiling.


Phytochemical Characterization and Evaluation of the Antioxidant and Anti-Enzymatic Activity of Five Common Spices: Focus on Their Essential Oils and Spent Material Extractives.
The essential oil industry of aromatic herbs and spices is currently producing a significant amount of by-products, such as the spent plant materials remaining after steam or hydrodistillation, that are simply discarded. The aim of this study was to comparatively investigate the phytochemical composition, antioxidant and multi-enzymatic inhibitory potential of the essential oils and spent plant material extractives obtained from cinnamon, cumin, clove, laurel, and black pepper. The essential oils were characterized by the presence of several phytochemical markers (cinnamaldehyde, cuminaldehyde, eugenol, eucalyptol, α-terpinene, limonene, β-caryophyllene or β-pinene). On the other hand, the LC-HRMS/MS profiling of the spent material extracts allowed the annotation of species specific and non-specific metabolites, such as organic acids, phenolic acids, flavonoids, proanthocyanidins, hydrolysable tannins, fatty acids, or piperamides. All samples exhibited very strong antioxidant effects, with the clove essential oil displaying the strongest radical scavenging (525.78 and 936.44 mg TE/g in DPPH and ABTS assays), reducing (2848.28 and 1927.98 mg TE/g in CUPRAC and FRAP), and total antioxidant capacity (68.19 mmol TE/g). With respect to the anti-acetylcholinesterase (0.73-2.95 mg GALAE/g), anti-butyrylcholinesterase (0-3.41 mg GALAE/g), anti-tyrosinase (0-76.86 mg KAE/g), anti-amylase and anti-glucosidase (both 0-1.00 mmol ACAE/g) assays, the spice samples showed a modest activity. Overall, our study reports that, not only the volatile fractions of common spices, but also their spent plant materials remaining after hydrodistillation can be regarded as rich sources of bioactive molecules with antioxidant and multi-enzymatic inhibitory effects.


Auxin-mediated regulation of arbuscular mycorrhizal symbiosis: A role of SlGH3.4 in tomato.
Most land plants can establish symbiosis with arbuscular mycorrhizal (AM) fungi to increase fitness to environmental challenges. The development of AM symbiosis is controlled by intricate procedures involving all phytohormones. However, the mechanisms underlying the auxin-mediated regulation of AM symbiosis remains largely unknown. Here, we report that AM colonisation promotes auxin response and indole-3-acetic acid (IAA) accumulation, but downregulates IAA biosynthesis genes in tomato (Solanum lycopersicum). External IAA application modulates the AM symbiosis by promoting arbuscule formation at low concentrations but repressing it at high concentrations. An AM-induced GH3 gene, SlGH3.4, encoding a putative IAA-amido synthetase, negatively regulates mycorrhization via maintaining cellular auxin homoeostasis. Loss of SlGH3.4 function increased free IAA content and arbuscule incidence, while constitutively overexpressing SlGH3.4 in either tomato or rice resulted in decreased IAA content, total colonisation level and arbuscule abundance in mycorrhizal roots. Several auxin-inducible expansin genes involved in AM formation or resistance to pathogen infection were upregulated in slgh3.4 mycorrhizal roots but downregulated in the SlGH3.4-overexpressing plants. Taken together, our results highlight a positive correlation between the endogenous IAA content and mycorrhization level, particularly arbuscule incidence, and suggest that the SlGH3.4-mediated auxin homoeostasis and regulation of expansin genes is involved in finely tuning the AM development.


The demonstration of sIg, MHC and T cell antigens and Fc receptors on the lymphocyte surface by anti-globulin rosetting reactions: some technical considerations.
The previously shown marked difference in sensitivity of antiglobulin rosette formation and immunofluorescence was confirmed in detection of varying amounts of anti-Ig bound to B cells. The direct and indirect rosette method revealed twice the number of sIg+ cells shown by direct immunofluorescence (DIF), and at least an order of magnitude more antibody on the cell surface is necessary to detect the conventional B cells (shown by DIF) by indirect immunofluorescence compared with indirect antiglobulin (IARR) rosette formation. Variants of the sensitive IARR test were developed to reveal general lymphocyte, MHC class I and class II and T cell-specific antigens and Fc receptors using xenogeneic or allogeneic reagents. Sensitive indicator cells were used which form almost no rosettes with unsensitized lymphocytes although coated with IgG which would otherwise bind to the Fc receptor. The suggestion that chromic chloride treatment inactivates the relevant Fc determinants was supported by experiments showing the failure of IgG antibody-sensitized bovine RBC (standard Fc indicator cells) to form rosettes after treatment with chromic chloride.


Tocilizumab administration is associated with the reduction in biomarkers of coronavirus disease 2019 infection.
Coronavirus disease 2019 (COVID-19) has caused a significant impact on all aspects of life, with the number of death cases still increasing. Therefore, identification of potential treatment for reducing the severity of the disease is important. Currently, the data regarding the effectiveness of tocilizumab as treatment agents for COVID-19 infection is still conflicting. This study aims to give clear evidence regarding the potential benefit of tocilizumab in reducing the biomarkers of COVID-19 infection. We systematically searched the PubMed Central database using specific keywords related to our aims until July 24th, 2020. All articles published on COVID-19 and tocilizumab were retrieved. A total of 9 studies with a total of 577 patients were included in our analysis. Our meta-analysis showed that tocilizumab treatment is associated with reduction of C-reactive protein (mean difference [MD]: -106.69 mg/L [95% confidence interval [CI]: -146.90, -66.49 mg/L], p < .00001; I2 = 98%, random-effect modeling), d-dimer (MD: -3.06 mg/L [95% CI: -5.81, -0.31 mg/L], p = .03; I2 = 98%, random-effect modeling), Ferritin (MD: -532.80 ng/ml [95% CI: -810.93, -254.67 ng/ml], p = .0002; I2 = 25%, random-effect modeling), procalcitonin (MD: -0.67 ng/ml [95% CI: -1.13, -0.22 ng/ml], p = .004; I2 = 92%, random-effect modeling], and increment in the levels of lymphocyte count (MD: 0.36 × 103 /μl [95% CI: 0.18, 0.54 × 103 /μl], p < .0001; I2 = 88%, random-effect modeling). Administration of tocilizumab is effective in reducing the biomarkers of the COVID-19 infection.


Introduction of Voice Type Component (VTC) as an Effective Acoustic Voice Analysis Method in Tele-evaluation.
Telepractice in voice health care and evaluation services has attracted much attention in recent years. Multiple studies have proven the effectiveness of voice therapy with telepractice. However, voice evaluations are still mostly conducted in person due to the lack of sensitive acoustic analysis methods. This study examined various acoustic analysis methods for voice evaluation in telepractice. Eighteen female elementary school teachers with self-reported voice disorders volunteered to participate in the study. Speech samples were collected before and after the interventions using two voice sampling methods concurrently. One set of data was collected using the traditional voice sample collection method by the therapist in person. The second set of data was collected on the same speech samples using the clients' own smartphones, and the collected voice samples were later sent to the researcher for further acoustic analysis. The voice type component (VTC) measurement represented the proportion of different VTCs in a voice by measuring the chaos and intrinsic dimension. Voice analyses were conducted on both sets of data, and the correlation between the two sampling procedures was analyzed. It appears that the VTC could be a more reliable method for producing acoustic analysis results with voice samples collected from smartphones compared to other objective voice assessment procedures. This reliability has been demonstrated via statistical analysis, including correlation coefficient, pairwise t test, d-prime, and area under the curve. The results of this study highlighted the VTC as an effective and accurate acoustic analysis method in tele-evaluation. This feasible voice sampling method, which utilizes participants' own smartphones, will reduce barriers to accessing limited voice specialists due to distance and will decrease the cost of care by minimizing expenses associated with travel and additional equipment for voice sampling. Ultimately, this approach will enhance the effectiveness of voice care delivered through telepractice to patients in remote and underserved areas.


Intensive care unit capacity strain and adherence to prophylaxis guidelines.
The purpose of the study is to examine the relationship between different measures of capacity strain and adherence to prophylaxis guidelines in the intensive care unit (ICU). We conducted a retrospective cohort study within the Project IMPACT database. We used multivariable logistic regression to examine relationships between ICU capacity strain and appropriate usage of venous thromboembolism prophylaxis (VTEP) and stress ulcer prophylaxis (SUP). Of 776,905 patient-days eligible for VTEP, appropriate therapy was provided on 68%. Strain as measured by proportion of new admissions (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.90-0.91) and census (OR, 0.97; 95% CI, 0.97-0.98) was associated with decreased odds of receiving VTEP. With increasing strain as measured by new admissions, the degradation of VTEP utilization was more severe in ICUs with closed (OR, 0.85; 95% CI, 0.83-0.88) than open (OR, 0.91; 95% CI, 0.91-0.92) staffing models (interaction P<.001). Of 185425 patient-days eligible for SUP, 48% received appropriate therapy. Administration of SUP was not significantly influenced by any measure of strain. Rising capacity strain in the ICU reduces the odds that patients will receive appropriate VTEP but not SUP. The variability among different types of ICUs in the extent to which strain degraded VTEP use suggests opportunities for systems improvement.


Advancing Cancer Treatment by Targeting Glutamine Metabolism-A Roadmap.
Tumor growth and metastasis strongly depend on adapted cell metabolism. Cancer cells adjust their metabolic program to their specific energy needs and in response to an often challenging tumor microenvironment. Glutamine metabolism is one of the metabolic pathways that can be successfully targeted in cancer treatment. The dependence of many hematological and solid tumors on glutamine is associated with mitochondrial glutaminase (GLS) activity that enables channeling of glutamine into the tricarboxylic acid (TCA) cycle, generation of ATP and NADPH, and regulation of glutathione homeostasis and reactive oxygen species (ROS). Small molecules that target glutamine metabolism through inhibition of GLS therefore simultaneously limit energy availability and increase oxidative stress. However, some cancers can reprogram their metabolism to evade this metabolic trap. Therefore, the effectiveness of treatment strategies that rely solely on glutamine inhibition is limited. In this review, we discuss the metabolic and molecular pathways that are linked to dysregulated glutamine metabolism in multiple cancer types. We further summarize and review current clinical trials of glutaminolysis inhibition in cancer patients. Finally, we put into perspective strategies that deploy a combined treatment targeting glutamine metabolism along with other molecular or metabolic pathways and discuss their potential for clinical applications.


Ocular histoplasmosis: clinicopathologic correlation of 3 cases.
The eyes of three patients followed clinically for many years with a diagnosis of macular disciform scarring, secondary to ocular histoplasmosis, were studied histopathologically. A fibrovascular scar interposed between the choroid and retina was observed in all cases. Vessels passing from the choroid through defects in Bruch's membrane into the nodule were demonstrated. Theories of the pathogenesis of the lesion are discussed.


Thiol peroxidase is critical for virulence and resistance to nitric oxide and peroxide in the fungal pathogen, Cryptococcus neoformans.
Cryptococcus neoformans is a fungal pathogen most commonly causing meningitis in immunocompromised patients. Current therapies are inadequate, and novel antifungal targets are needed. We have identified by proteomics two thiol peroxidases that are differentially expressed at 37 degrees C, the temperature of the mammalian host. Consistent with their antioxidant role, we show that the genes encoding these thiol-specific antioxidants, TSA1 and TSA3, are transcriptionally induced when C. neoformans is exposed to hydrogen peroxide. Genome sequence analysis of C. neoformans revealed a third thiol peroxidase, TSA4. We constructed single, double and triple mutants of the thiol peroxidase genes through homologous recombination and analysed their function by comparing the growth of these mutants with that of the wild-type strain. The tsa1 Delta mutant shows sensitivity to hydrogen peroxide and t-butylhydroperoxide, as well as significant growth retardation at 25 degrees C and 38.5 degrees C. The tsa1 Delta mutant is also sensitive to NO, demonstrating a link between oxidative and nitrosative stress pathways. In two mouse models of cryptococcosis, the tsa1 Delta mutant is significantly less virulent.


Evidence for clinical and genetic heterogeneity of syndactyly type I: the phenotype of second and third toe syndactyly maps to chromosome 3p21.31.
There is good evidence from the medical literature that type I syndactyly, the most common form of the nonsyndromic syndactylies, is clinically heterogeneous. We therefore propose to group the condition into four subtypes, which are all autosomal dominantly inherited. Subtype 1, zygodactyly (cutaneous webbing of second and third toe without hand involvement) is the mildest and most common form. The phenotype varies from unilateral minor impression of webbing to bilateral complete webbing of second and third toe including a fusion of nails. Bony involvement is never observed. Subtype 2 is characterized by bilateral cutaneous and/or bony webbing of third and fourth finger, and second and third toe. The phenotype maps on chromosome 2q34-q36 and was designated as SD1 (ie syndactyly 1). The hallmark of subtype 3 is bilateral cutaneous or bony webbing of third and fourth finger, while subtype 4 shows bilateral cutaneous webbing of fourth and fifth toe. Both, subtype 3 and 4, are rare entities. Here, we present clinical and molecular data of a large Pakistani family with zygodactyly that was mapped to a new locus on chromosome 3p21.31 by genome-wide linkage analysis. The highest LOD score (Zmax=3.38) was obtained with microsatellite marker D3S2409. The disease interval is flanked by markers Chr3_4919 and Chr3_4940 encompassing about 0.20 Mb. Since the same phenotype appears not to be linked to this locus in a German family, we predict genetic heterogeneity in zygodactyly and propose to designate the 3p21.31 locus as ZD1 (i.e., zygodactyly 1).


Inhibitors of the bacterial cell wall biosynthesis enzyme MurD.
A series of transition-state analog inhibitors of the D-glutamic acid-adding enzyme (MurD) of bacterial peptidoglycan biosynthesis has been synthesized and evaluated for inhibition of the E. coli enzyme.


Surface chemistry mediates thermal transport in three-dimensional nanocrystal arrays.
Arrays of ligand-stabilized colloidal nanocrystals with size-tunable electronic structure are promising alternatives to single-crystal semiconductors in electronic, optoelectronic and energy-related applications. Hard/soft interfaces in these nanocrystal arrays (NCAs) create a complex and uncharted vibrational landscape for thermal energy transport that will influence their technological feasibility. Here, we present thermal conductivity measurements of NCAs (CdSe, PbS, PbSe, PbTe, Fe3O4 and Au) and reveal that energy transport is mediated by the density and chemistry of the organic/inorganic interfaces, and the volume fractions of nanocrystal cores and surface ligands. NCA thermal conductivities are controllable within the range 0.1-0.3 W m(-1) K(-1), and only weakly depend on the thermal conductivity of the inorganic core material. This range is 1,000 times lower than the thermal conductivity of silicon, presenting challenges for heat dissipation in NCA-based electronics and photonics. It is, however, 10 times smaller than that of Bi2Te3, which is advantageous for NCA-based thermoelectric materials.


Effects of rapid maxillary expansion on facial soft tissues : Deviation analysis on three-dimensional images.
Changes in soft tissue in various morphological regions of the face immediately after rapid maxillary expansion (RME) were examined using three-dimensional (3D) deviation analyses. A total of 50 patients were included in the study; 25 patients (11 female and 14 male) presented with a unilateral or bilateral posterior crossbite malocclusion requiring RME. In addition, 25 patients (13 female and 12 male) were included as a control group. The mean ages of the study group and control group were 9.8 years (range 8.1-12.6 years) and 9.6 years (range 8.3-12.2 years), respectively. The 3D stereophotogrammetric images acquired immediately before the appliance was cemented and after expansion had been completed in the treatment group were compared using Rapidform software. The 3D deviation analyses were made for the complete face and in the upper and lower face, upper and lower lips and nose regions. The amount of negative and positive deviations and the mean deviations were examined on the facial meshes for the 95th percentiles. Immediately after RME, the mean absolute deviation over the complete face was 0.54 ± 0.16 mm. The mean change for the upper face was 0.42 ± 0.17 mm (mean positive deviation: 0.37 ± 0.17 mm; mean negative deviation: -0.48 ± 0.18 mm). The mean absolute deviation was 0.62 ± 0.28 mm in the upper lip and 0.60 ± 0.34 mm in the lower lip. In the nose area, the absolute deviation was 0.41 ± 0.21 mm (mean positive deviation: 0.39 ± 0.16 mm; mean negative deviation: -0.43 ± 0.26 mm). Changes in facial soft tissues in the upper face, lower face, nasal soft tissues, and lower and upper lip regions were observed after RME.


Photodynamic Therapy With Topical 5% 5-Aminolevulinic Acid for the Treatment of Truncal Acne in Asian Patients.
Photodynamic therapy (PDT) using topical application of aminolevulinic acid (ALA) is an effective treatment for acne vulgaris. However, there is no clear consensus on the treatment regime in Asians.
 To determine the efficacy, safety and tolerability of 5% ALA PDT in the treatment of truncal acne in Asians.
 Patients with truncal acne were treated with 5%-ALA under occlusion for 3 hours. All were subsequently treated with a red light source at wavelength 630 nm and an irradiance of 38mW/cm2 giving a total dose of 37 J/cm2. The numbers of acne lesions were recorded at baseline and regular intervals after treatment together with any adverse effects.
 Fifteen patients were recruited. Overall, there was a 64.2% reduction in the inflammatory lesions count and a 24.3% reduction in the non-inflammatory lesions count at the end of the 12 weeks follow-up. Both mean lesions counts were significantly lower than baseline at all follow-up time points with paired t tests (all P values <0.05). Pain was well tolerated among our patients.
 A single treatment session of 5%-ALA PDT was effective for the treatment of truncal acne with little side effects and acceptable in our Asian patients.

 J Drugs Dermatol. 2016;15(6):727-732.


Enhanced humoral response in pregnant mice immunized with liposome encapsulated recombinant neutralizing epitope protein of Hepatitis- E virus.
Pregnant women from developing countries are at high-risk of hepatitis E-associated high mortality and constitute priority population for vaccination. So far, candidate vaccines have not been evaluated during pregnancy. We evaluated our vaccine candidate, recombinant Neutralizing Epitope protein (rNEp) encapsulated in liposomes, in pregnant mice. A single dose (10 μg) of the formulation was administered intramuscularly on day 7 of pregnancy. Titres of serum IgG antibodies to hepatitis E virus (IgG-anti-HEV), levels of cytokines and biochemical parameters were determined. Spleens were harvested from pregnant and non-pregnant mice for immunophenotyping (flow cytometry), cytokines (cytometric bead array, CBA) and gene expression of immune response genes (Taqman low density array, TLDA). Histopathology studies of spleen, liver, kidneys, brain and muscle was carried out. The vaccine was well-tolerated during pregnancy as evidenced by histopathology and serum biochemical parameters. Anti-HEV titres were significantly higher in the pregnant balb/c and C57BL/6 mice (3592 ± 802 and 1016 ± 138 respectively, than in non-pregnant groups (634 ± 191 and 320 ± 55 respectively, p < 0.001 for both) suggesting that the higher antibody response in pregnant mice was independent of the genetic makeup of the host but immunogen-driven. Pups receiving vertically transferred antibodies developed lower anti-HEV antibodies (p < 0.05) when immunized with the formulation after seronegativity than in the age-matched mice without such antibodies. In non-pregnant mice, a Th1 response and discordance between splenic and serum cytokines was evident while in pregnancy, a Th2 bias was observed irrespective of immunization. Increased CD19 levels correlated with higher anti-HEV titres in pregnant mice. The single dose of the vaccine was safe and highly immunogenic in pregnant mice. Degree and type of immune response to vaccination during pregnancy is immunogen-driven. In-depth studies are needed to understand the underlying immunologic mechanism(s). These encouraging results for a vaccine intended for use in pregnant women should be confirmed in higher animals.


Metabolic plasticity and hematopoietic stem cell biology.
Hematopoietic stem cells (HSCs) residing in the hypoxic niches can both self-renew and give rise to progeny. Multiple regulatory mechanisms for these cellular processes have been identified. Emerging evidence has revealed that metabolism and bioenergetics play important roles in determining stem cell fate in concert with other regulatory networks. In this review, we will discuss recent advances in this field. Recent studies have helped define and redefine metabolic regulation of HSCs. Resting quiescent stem cells use primarily anaerobic glycolysis for energy production and this metabolic program is required to maintain a functional quiescent state. However, when they exit this state and rapidly proliferate and differentiate into different blood cell types, a robust up-regulation of energy metabolism is expected to meet the quickly rising energy demand. Dysregulation of metabolism in HSCs results in various blood disorders, including leukemia. Energy metabolism and HSC activity influence and interlink each other in a highly sophisticated and orchestrated manner. Understanding metabolic regulation of HSC function has significant implications for HSC-based therapies and leukemogenesis research.


Assessment of microcrystal quality by transmission electron microscopy for efficient serial femtosecond crystallography.
Serial femtosecond crystallography (SFX) employing high-intensity X-ray free-electron laser (XFEL) sources has enabled structural studies on microcrystalline protein samples at non-cryogenic temperatures. However, the identification and optimization of conditions that produce well diffracting microcrystals remains an experimental challenge. Here, we report parallel SFX and transmission electron microscopy (TEM) experiments using fragmented microcrystals of wild type (WT) homoprotocatechuate 2,3-dioxygenase (HPCD) and an active site variant (H200Q). Despite identical crystallization conditions and morphology, as well as similar crystal size and density, the indexing efficiency of the diffraction data collected using the H200Q variant sample was over 7-fold higher compared to the diffraction results obtained using the WT sample. TEM analysis revealed an abundance of protein aggregates, crystal conglomerates and a smaller population of highly ordered lattices in the WT sample as compared to the H200Q variant sample. While not reported herein, the 1.75 Å resolution structure of the H200Q variant was determined from ∼16 min of beam time, demonstrating the utility of TEM analysis in evaluating sample monodispersity and lattice quality, parameters critical to the efficiency of SFX experiments.


Examining the impact of physical and sexual abuse on the employment of women with disabilities in the United States: an exploratory analysis.
The relationship between the employment status of women with disabilities and the incidence of physical and sexual abuse in the United States was examined. Data from the 2005 Behavioural Risk Factor Surveillance System (BRFSS) were analyzed using descriptive analysis and proportional analysis to determine the significance of the relationship between the experience of abuse and employment status for women with disabilities. Due to the large sample size, effect size was examined through Cohen's h. Logistic regression analysis was also used to examine the risk of unemployment for women with disabilities who are abused. Women with disabilities who have been abused have higher levels of unemployment than women without disabilities who have not been abused. In addition, women with disabilities who have been abused have higher levels of unemployment than women without disabilities who have not been abused. Finally, experiencing physical and sexual abuse increases the risk of unemployment for women with disabilities. Unemployment increases the disadvantage for an already vulnerable population and potentially prevents women with disabilities from being able to break the cycle of violence they are experiencing. Recommendations are discussed with regard to intervention by rehabilitation professionals to assist women with disabilities who experience abuse.


The factor structure of the GHQ: a scaled version for a hospital's general practice service in Mexico.
This paper reports the factor structure of the symptoms comprising the GHQ when it is administered in the general practice service of a hospital. Two shorter versions are proposed: one with 6 scales and 30 items, and the other with 4 scales and 28 items. The latter is compared with the 28-item English version. Preliminary data concerning the validity of the scales are presented. In a comparison of the screening potentiality of the 60- and 28-item versions, no significant differences were found.


Resistance Exercise Counteracts the Impact of Androgen Deprivation Therapy on Muscle Characteristics in Cancer Patients.
Androgen deprivation therapy (ADT) forms the cornerstone in prostate cancer (PCa) treatment. However, ADT also lowers skeletal muscle mass. To identify the impact of ADT with and without resistance exercise training on muscle fiber characteristics in PCa patients. Twenty-one PCa patients (72 ± 6 years) starting ADT were included. Tissue samples from the vastus lateralis muscle were assessed at baseline and after 20 weeks of usual care (n = 11) or resistance exercise training (n = 10). Type I and II muscle fiber distribution, fiber size, and myonuclear and capillary contents were determined by immunohistochemistry. Significant decreases in type I (from 7401 ± 1183 to 6489 ± 1293 μm2, P < .05) and type II (from 6225 ± 1503 to 5014 ± 714 μm2, P < .05) muscle fiber size were observed in the usual care group. In addition, type I and type II individual capillary-to-fiber ratio (C/Fi) declined (-12% ± 12% and -20% ± 21%, respectively, P < .05). In contrast, significant increases in type I (from 6700 ± 1464 to 7772 ± 1319 μm2, P < .05) and type II (from 5248 ± 892 to 6302 ± 1385 μm2, P < .05) muscle fiber size were observed in the training group, accompanied by an increase in type I and type II muscle fiber myonuclear contents (+24% ± 33% and +21% ± 23%, respectively, P < .05) and type I C/Fi (+18% ± 14%, P < .05). The onset of ADT is followed by a decline in both type I and type II muscle fiber size and capillarization in PCa patients. Resistance exercise training offsets the negative impact of ADT and increases type I and II muscle fiber size and type I muscle fiber capillarization in these patients.


Ex-PRESS R-50 miniature glaucoma implant insertion under the conjunctiva combined with cataract extraction.
To evaluate the efficacy and safety of the Ex-PRESS R-50 implant (Optonol Ltd.) in eyes operated on for open-angle glaucoma combined with phacoemulsification. Glaucoma Unit, Ophthalmology Department, University of Lausanne, Lausanne, Switzerland. Between November 2000 and June 2002, the Ex-PRESS R-50 shunt was implanted in 35 eyes of 35 patients. The best corrected visual acuity (BCVA), intraocular pressure (IOP), number of medications, and complications were recorded preoperatively as well as postoperatively at 1 and 7 days and 1, 2, 3, 6, 9, 12, 24, 36, and 48 months. Temporal clear corneal phacoemulsification with intraocular lens implantation was performed first. The ophthalmic viscosurgical device was not removed, and the Ex-PRESS R-50 was implanted under the conjunctiva into the anterior chamber. The mean follow-up was 36.9 months +/- 18.2 (SD) and the mean age of the patients, 74.6 +/- 10.9 years. The mean preoperative IOP of 19.3 +/- 6.3 mm Hg decreased postoperatively to 15.3 +/- 6.2 mm Hg, 15.1 +/- 4.6 mm Hg, 13.8 +/- 2.8 mm Hg, 14.6 +/- 2.9 mm Hg, and 13.3 +/- 2.0 mm Hg at 6 months, 12 months, 24 months, 36 months, and 48 months, respectively (P<.005). At 48 months, the mean BCVA was 0.74 +/- 0.34 and the number of medications was reduced by 57% (P<.005). The microtube was removed in 10 patients, and bleb management was performed in 10 eyes. Ten patients (32%) had satisfactory IOP control (mean 13.2 +/- 2.2 mm Hg) without medication; minor transient complications were observed in 10 patients. Based on the cumulative survival curve after 48 months, the complete success rate was 32.7% and the qualified success rate, 53.7% (P<.05). Ex-PRESS R-50 implantation under the conjunctiva was associated with a relatively high number of complications, despite good IOP control in the uncomplicated cases. Refinement in the tube design and implantation technique would increase the success rate.


Electrosurgical epilation.
This article discusses alternative methods for the removal of unwanted hair, the mechanisms of action of each, and their advantages and disadvantages. Epilating needle design is discussed and epilating technique is described. Physician-patient interaction and the role of the dermatologist in electrosurgical epilation are explored.


Effect of cadmium on oxidative stress and immune function of common carp (Cyprinus carpio L.) by transcriptome analysis.
Cadmium (Cd) is an increasingly important environmental pollutant which causes irreversible toxicity to fish. To understand how Cd impacts the immune response and oxidative stress in common carp, we performed transcriptomic profiles for head kidney, the immune organ of common carp which were underwent Cd exposure. Totally there are 42,489,124 and 48,562,526 high quality clean reads obtained from the Cd exposure groups, and 44,677,578 and 44,106,696 clean reads from the control groups. Among them, 308 genes were differently expressed, including 101 upregulated and 207 down-regulated genes. The identified genes were enriched using databases of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Antioxidant systems and immune function genes and pathways were identified and validated by quantitative real-time RT-PCR. Our results showed that Cd exposure leads to oxidative stress and immunosuppression in head kidney of common carp. These results provide new insights for unveiling the biological effects of Cd in common carp.


Dominant and recessive forms of fibrochondrogenesis resulting from mutations at a second locus, COL11A2.
Fibrochondrogenesis is a severe, recessively inherited skeletal dysplasia shown to result from mutations in the gene encoding the proα1(XI) chain of type XI collagen, COL11A1. The first of two cases reported here was the affected offspring of first cousins and sequence analysis excluded mutations in COL11A1. Consequently, whole-genome SNP genotyping was performed to identify blocks of homozygosity, identical-by-descent, wherein the disease locus would reside. COL11A1 was not within a region of homozygosity, further excluding it as the disease locus, but the gene encoding the proα2(XI) chain of type XI collagen, COL11A2, was located within a large region of homozygosity. Sequence analysis identified homozygosity for a splice donor mutation in intron 18. Exon trapping demonstrated that the mutation resulted in skipping of exon 18 and predicted deletion of 18 amino acids from the triple helical domain of the protein. In the second case, heterozygosity for a de novo 9 bp deletion in exon 40 of COL11A2 was identified, indicating that there are autosomal dominant forms of fibrochondrogenesis. These findings thus demonstrate that fibrochondrogenesis can result from either recessively or dominantly inherited mutations in COL11A2.


Two-Lines-Four-Regions: A New Concept in Endoscopic-Assisted Surgery of Parotid Gland Tumors.
Endoscopic-assisted surgery of parotid gland tumor is challenging due to the complex anatomic structures. This study compared an innovative endoscopic-assisted operation called the two-lines-four-regions method to a traditional endoscopic-assisted surgery in the treatment of parotid gland tumors. In this retrospective cohort study, patients were assigned to the traditional endoscopic group (Trad-En group) and the two-lines-four-regions endoscopic group (Tlfr-En group) according to whether two-lines-four-regions concept was used before the surgery. The primary outcomes are operation time (minutes) and postoperative complications present or absent. Other outcomes including intraoperative blood loss (milliliter), whether to increase auxiliary incision (yes/no), postoperative drainage (milliliter), and retention time (day) are the secondary outcomes. χ2 analysis or Fisher exact test was used to compare the statistical differences of those variables in 2 groups, and a P value of less than .05 was considered to indicate statistical significance. A total of 121 patients with parotid gland tumors underwent endoscopic-assisted surgery; 59 patients were assigned to the Trad-En group, and 62 patients were assigned to the Tlfr-En group. The mean operation times (65.24 ± 14.82 min), blood loss (9.85 ± 3.38 mL), and the amount of drainage (10.52 ± 3.17 mL) in the Tlfr-En group were shorter than the values in the Trad-En group (75.75 ± 14.16 min, 10.52 ± 3.17 mL, and 16.54 ± 3.21 mL, respectively; P < .05). The median follow-up time was 34 months (range 4 to 70 months). No tumor recurrence was found in all patients. This study demonstrated that the new concept of two-lines-four-regions of parotid gland makes the endoscopic-assisted surgery of parotid gland tumors more simplified, efficient, and minimally invasive.


Lamina Cribrosa Thickening in Early Glaucoma Predicted by a Microstructure Motivated Growth and Remodeling Approach.
Glaucoma is among the leading causes of blindness worldwide. The ocular disease is characterized by irreversible damage of the retinal ganglion cell axons at the level of the lamina cribrosa (LC). The LC is a porous, connective tissue structure whose function is believed to provide mechanical support to the axons as they exit the eye on their path from the retina to the brain. Early experimental glaucoma studies have shown that the LC remodels into a thicker, more posterior structure which incorporates more connective tissue after intraocular pressure (IOP) elevation. The process by which this occurs is unknown. Here we present a microstructure motivated growth and remodeling (G&R) formulation to explore a potential mechanism of these structural changes. We hypothesize that the mechanical strain experienced by the collagen fibrils in the LC stimulates the G&R response at the micro-scale. The proposed G&R algorithm controls collagen fibril synthesis/degradation and adapts the residual strains between collagen fibrils and the surrounding tissue to achieve biomechanical homeostasis. The G&R algorithm was applied to a generic finite element model of the human eye subjected to normal and elevated IOP. The G&R simulation underscores the biomechanical need for a LC at normal IOP. The numerical results suggest that IOP elevation leads to LC thickening due to an increase in collagen fibril mass, which is in good agreement with experimental observations in early glaucoma monkey eyes. This is the first study to demonstrate that a biomechanically-driven G&R mechanism can lead to the LC thickening observed in early experimental glaucoma.


Effect of CYP2C19 genetic variants on bleeding and major adverse cardiovascular events in a cohort of Arab patients undergoing percutaneous coronary intervention and stent implantation.
One-third of patients have clopidogrel resistance that may lead to major adverse cardiac events (MACEs). By contrast, it was found that some clopidogrel-treated patients have hyperresponsive platelets that are associated with higher bleeding risk. Several studies have shown that polymorphisms in the gene encoding the CYP2C19 contribute to the variability in response to clopidogrel. Data on genetic and nongenetic factors affecting clopidogrel response in the Arab population are scarce. In this prospective cohort study, we sought to assess the association between the increased function allele (CYP2C19*17) and bleeding events, and validate the effect of the CYP2C19 genetic variants and nongenetic factors on the incidence of MACEs. Blood samples were collected from patients that were undergoing percutaneous coronary intervention and receiving clopidogrel at the Heart Hospital, a specialist tertiary hospital in Doha, Qatar. Patients were followed for 12 months. Genotyping was performed for CYP2C19*2, *3, and *17 using TaqMan assays. In 254 patients, the minor allele frequencies were 0.13, 0.004, and 0.21 for *2, *3, and *17, respectively. Over a 12-month follow-up period, there were 21 bleeding events (8.5 events/100 patient-year). CYP2C19*17 carriers were found to be associated with increased risk of bleeding (OR, 21.6; 95% CI, 4.8-96.8; P < 0.0001). CYP2C19*2 or *3 carriers were found to be associated with increased risk of baseline and incident MACE combined (OR, 8.4; 95% CI, 3.2-23.9; P < 0.0001). This study showed a significant association between CYP2C19*17 allele and the increased risk of bleeding, and CYP2C19*2 or *3 with MACE outcomes.