Evaluation of five commercial real-time PCR assays for detection of Mycoplasma pneumoniae in respiratory tract specimens.
The performances of five commercial TaqMan real-time PCR assays for the detection of Mycoplasma pneumoniae in respiratory tract specimens were evaluated in comparison with an in-house real-time PCR. All kits allowed prompt and specific results, validated by the use of an internal control. The Nanogen kit showed the best clinical sensitivity.


A radical-anion chain mechanism following dissociative electron transfer reduction of the model prostaglandin endoperoxide, 1,4-diphenyl-2,3-dioxabicyclo[2.2.1]heptane.
The model prostaglandin endoperoxide, 1,4-diphenyl-2,3-dioxabicyclo[2.2.1]heptane (3), was investigated in N,N-dimethylformamide at a glassy carbon electrode using various electrochemical techniques. Reduction of 3 occurs by a concerted dissociative electron transfer (ET) mechanism. Electrolysis at -1.6 V yields 1,3-diphenyl-cyclopentane-cis-1,3-diol in 97% by a two-electron mechanism; however, in competition with the second ET from the electrode, the resulting distonic radical-anion intermediate undergoes a beta-scission fragmentation. The rate constant for the heterogeneous ET to the distonic radical-anion is estimated to occur on the order of 2 x 10(7) s(-1). In contrast, electrolyses conducted at potentials more negative than -2.1 V yield a mixture of primary and secondary electrolysis products including 1,3-diphenyl-cyclopentane-cis-1,3-diol, 1,3-diphenyl-1,3-propanedione, trans-chalcone and 1,3-diphenyl-1,3-hydroxypropane by a mechanism involving less than one electron equivalent. These observations are rationalized by a catalytic radical-anion chain mechanism, which is dependent on the electrode potential and the concentration of weak non-nucleophilic acid. A thermochemical cycle for calculating the driving force for beta-scission fragmentation from oxygen-centred biradicals and analogous distonic radical-anions is presented and the results of the calculations provide insight into the reactivity of prostaglandin endoperoxides.


[Cauda equina syndrome caused by Tarlov's cysts--case report].
Perineural Tarlov cysts located on lumbo-sacral roots can be a cause of cauda equina syndrome. 1) To draw attention to the fact that multiple Tarlov lumbo-sacral perineural cysts can produce serious movement disturbances. 2) To document the usefulness of the magnetic resonance imaging in noninvasive diagnosis of perineural cysts. A male patient, 80 years of age, suffered from progressive weakness of lower limbs, which caused an increasing drop of the feet. The disease began in August 2000, following a long journey by train. The patient additionally complained of urinary incontinence as result of sneezing, coughing or fast walking. The urologist did not find prostatic gland hypertrophy. An examination by the internist revealed atheromatous myocardiopathy in circulation failure stage. Magnetic resonance imaging showed multiple perineural cysts up to 15 mm in diameter on lumbo-sacral roots. This clinical picture, supported by the magnetic resonance imaging allowed to recognize cauda equina syndrome caused by Tarlov lumbo-sacral perineural cysts. This case is a reminder, that part of perineural cysts, particularly multiple, can be a cause of nerve roots injury, and their lumbo-sacral location can produce cauda equina syndrome. As reported by Zarski and Leo, Tarlov cysts were cause of 7.3% of pain syndrome cases 2 patients in the study group showed lower limb claudication. Magnetic resonance imaging of patients with back pain, performed by Paulsen, Call and Murtagh, revealed that Tarlov cysts occurred in 4.6% of patients, but only 1% had the symptoms connected with the presence of those cysts. In available Polish literature no report has been found referring to fixed cauda equina syndrome which was caused by multiple cysts revealed through the magnetic resonance imaging of spinal canal. Only Zarski and Leo, discussing the correlation between the clinical and radicographic picture, described transient cauda equina syndrome in two patients who, beside Tarlov cysts, were also found to have intervertebral lumbosacral disc herniation. Tarlov was the first to describe well documented cauda equina syndromes caused by cysts on the lumbo-sacral roots. It is necessary to emphasize the established role of magnetic resonance of spinal canal in the diagnosis of perineural cysts on the lumbo-sacral roots as well as other anatomical anomalies of cerebrospinal fluid spaces. Despite the fact that cauda equina syndrome in the case reported here was a serious complication of multiple Tarlov cysts in the lumbo-sacral region, a surgical treatment was not undertaken; in such cases this treatment should be the chosen procedure. Multiple perineural Tarlov cysts in lumbo-sacral region, without disc herniation or other cause of vertebral canal stenosis, can produce cauda equina syndrome.


Synthesis and structural and magnetic characterisation of copper(II) complexes of mixed phosphonate-antimonate ligands.
A polynucleating oxygen donor ligand based on condensation of p-chlorophenylstibonic acid (ArSbO(3)H(2)) and t-butylphosphonic acid is reported. [(SbAr)(2)O(HO(3)P(t)Bu)(6)] contains two antimony centres, bridged by an oxide and two hydrogen phosphonates. Reaction with copper acetate under solvothermal conditions produces four new polymetallic copper complexes. With pyridine used as a base the major product is a tetracopper cage, [Cu(4)O(2)(SbAr)(2)(O(3)P(t)Bu)(2)(O(2)CMe)(2)(OMe)(6)], with the four copper centres arranged in a rhombus; a minor product is a tricopper complex, [Cu(3)O(4)(SbAr)(2)(O(3)P(t)Bu)(4)(py)(3)]. With LiOMe as base the major product is again the tetranuclear cage, but the minor product is a heterometallic cage, [Cu(5)Li(4)O(6)(SbAr)(4)(O(3)P(t)Bu)(6)(O(2)CMe)(2)(OMe)(4) (MeOH)(4)]. With 2,6-lutidine as base an octametallic complex is formed, [Cu(8)O(4)(SbAr)(2)(O(3)P(t)Bu)(6)(O(2)CMe)(4)(lutidine)(2)]. Magnetic studies show both anti-ferromagnetic and weak ferromagnetic exchange between the copper centres in these new complexes.


Establishment and characterization of a nontumorigenic cell line derived from a human hepatocellular adenoma expressing hepatocyte-specific markers.
In the present study the establishment and characterization of a nontumorigenic liver epithelial cell line (HACL-1) derived from a human hepatocellular adenoma is described. The HACL-1 cells have a finite life span (i.e., they proliferate for a period of 2 months and then senesce), show cell-cell contact inhibition, do not grow in soft agar, are not tumorigenic when injected in nude mice, and possess a normal diploid karyotype. The cultured cells resemble hepatocytes, but exhibit some features of dedifferentiation. At the ultrastructural level the cells are endowed with round or oval nuclei, abundant cytoplasmic organelles, and varying amounts of glycogen. The rough endoplasmic reticulum is disorganized, while peroxisomes and matrix granules within mitochondria are lacking. HACL-1 cells are cytokeratin 18-positive as well as (transiently) albumin- and alpha-fetoprotein-positive, but do not express cytokeratin 19. Furthermore, no mutations were observed in exons 5-8 of the tumor suppressor gene p53. Taken together these results show that HACL-1 cells are nontumorigenic proliferating liver epithelial cells, which might prove to be of great value in future studies on diverse aspects of human liver cell biology and carcinogenesis.


Ultrafast Excited-State Decays in [Re(CO)3(N,N)(L)]n+: Nonadiabatic Quantum Dynamics.
The ultrafast luminescent decay of [Re(CO)3(phen)(im)]+, representative of Re(I) carbonyl α-diimine photosensitizers, is investigated by means of wavepacket propagations based on the multiconfiguration time-dependent Hartree (MCTDH) method. On the basis of electronic structure data obtained at the time-dependent density functional theory (TD-DFT) level, the luminescence decay is simulated by solving a 14 electronic states multimode problem including both vibronic and spin-orbit coupling (SOC) up to 15 vibrational modes. A careful analysis of the results provides the key features of the mechanism of the intersystem crossing (ISC) in this complex. The intermediate state, detected by means of fs - ps time-resolved spectroscopies, is assigned to the T3 state corresponding to the triplet intraligand (3IL) transition localized on the phen ligand. By switching off/on SOC and vibronic coupling in the model it is shown that efficient population transfer occurs from the optically active metal-to-ligand-charge-transfer1,3MLCT states to T3 and to the lowest long-lived phosphorescent 3MLCT (T1) state. The early ultrafast SOC-driven decay followed by a T3/T1 equilibration controlled by vibronic coupling underlies the photoluminescent properties of [Re(CO)3(phen)(im)]+. The impact of the axial and N,N ligands on the photophysics of this class of Re(I) complexes is further rationalized on the basis of their calculated optical properties. The relative position of the 3IL and upper 3MLCT states with respect to the optically active singlet state is influenced by the N,N ligand and affects the relaxation dynamics.


Parsing the intrinsic networks underlying attention: a resting state study.
The attention system functionally modulates brain activity to exert control over thoughts, feelings and actions. Three distinct but mutually interacting components of attention have been hypothesized: alerting, which mediates the maintenance of a state of vigilance toward an upcoming stimulus; orienting, which supports the selection of sensory information, and executive control that is involved in detecting and resolving cognitive conflicts. The performance of tasks probing these components engages fronto-parietal and thalamic regions. Also, general attention has been associated with the activity of resting-state networks (RSNs), which are sets of brain regions with synchronous temporal fluctuations. Importantly, the association between the intrinsic brain activity of RSNs and the efficiency and integration of the specific attentional components remains largely unexplored. For this aim, we recruited twenty healthy volunteers who performed the Attention Network Test-Revised (ANT-R), assessing the alerting, orienting and executive control components as well as their interactions, and underwent resting-state functional magnetic resonance imaging. For each participant RSNs were estimated using double regression. The RSNs spanning across areas previously implicated in attentional processing were correlated with ANT-R scores using multiple regressions. Significant brain behavior correlations emerged between ANT-R scores and RSNs comprising the regions relevant for attentional processing, i.e., left and right prefronto-parietal (PFC-PC), dorsal attentional (DAN), salience (SN), and default mode (DMN) networks. The activity of PFC-PC networks was correlated with alerting in parietal and frontal regions, and with location conflict in the frontal regions. The DAN connectivity was correlated with flanker, location conflict, and their interaction in parietal regions. SN was associated with flanker by location and flanker by orienting interactions in the inferior frontal regions. Finally, the activity of the DMN was associated with flanker conflict in midline structures such as precuneus and anterior cingulate cortex and also in right angular gyrus. These results suggest that the brain is endowed with an intrinsic functional organization to support attention, not only in its global function, but also in its distinct components.


High expression of CXCR4 and CXCR7 predicts poor survival in gallbladder cancer.
Chemokine receptors play a prominent role in cancer progression and metastasis. This study investigated whether the expression of CXC chemokine receptor types 4 and 7 (CXCR4 and CXCR7, respectively), determined immunohistochemically, was associated with clinicopathological characteristics and postoperative survival in gallbladder cancer specimens from 72 patients. CXCR4 was detected in the cytoplasm and/or nucleus of gallbladder cancer cells, but CXCR7 was detected only in the cytoplasm. Expression of either CXCR7 or CXCR4 in the cytoplasm was associated with tumour stage. Expression of nuclear CXCR4 was associated with lymph node metastases and lymphatic invasion. Cytoplasmic expression of CXCR4 and CXCR7 were each independent risk factors for worse postoperative survival. Further research is required to clarify the mechanisms involved in these associations and to determine their potential prognostic and therapeutic implications.


[Isolated pleurisy revealing ovarian hyperstimulation syndrome].
Ovarian hyperstimulation is a rare but serious iatrogenic complication following induction of ovulation cycles. Release of vasoactive substances by the stimulated ovaries leads to leakage of intravascular fluid into the extracellular and serous spaces due to enhanced capillary permeability. Pleural effusion is a classical finding in the most severe forms, often associated with ascitis and signs of hemoconcentration. We report the case of a women who presented pleural effusion as the sole inaugural sign of ovarian hyperstimulation.


Psychometric validation of the Chinese Health Questionnaire among young people in Hong Kong across 2018 and 2019.
The Chinese Health Questionnaire (CHQ) is a 12-item assessment tool of psychological distress. The present study systematically evaluated the psychometric properties of the CHQ in a large sample of 1968 young people in Hong Kong. The participants completed the CHQ online in 2018 and 869 of them completed a follow-up survey on the CHQ, suicidal ideation, hikikomori, and help-seeking in 2019. Dimensionality of the CHQ was assessed via confirmatory factor analysis using the robust weighted least square estimator in 2018 and 2019. Measurement invariance was investigated across gender, age groups, and time between 2018 and 2019. Convergent validity of the CHQ factors were evaluated with respect to the mental health outcomes in the multiple indicators and multiple causes (MIMIC) approach. Confirmatory factor analyses shortened the CHQ into 10 items and revealed a superior fit for the bifactor model with a general factor and two specific factors on somatic and depressive symptoms in both 2018 and 2019. The general factor demonstrated substantial factor loadings (λ = 0.58-0.91), good reliability (ΩH = 0.85), and temporal stability (r = 0.62), and scalar measurement invariance across gender, age groups, and time. The general factor was significantly and positively associated with suicidal ideation, hikikomori, and help-seeking. The two specific factors displayed lower factor loadings, reliability, temporal stability, and weaker associations with the mental health outcomes. The present findings lend support to a valid and stable bifactor structure with a strong general factor for the CHQ-10 among young people in Hong Kong. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Branhamella catarrhalis as a cause of multiple subpleural abscesses.
A pure growth of Branhamella catarrhalis was obtained from subpleural abscesses in a 65-year-old fisherman with a persistent pneumothorax; underlying disorders included lung fibrosis, rheumatoid arthritis, and diabetes mellitus. A thoracotomy revealed extensive thickening of the visceral pleura covering multiple subpleural abscesses. There was a protracted postoperative course despite surgical debridement and antibiotic treatment with a cephalosporin and erythromycin.


MRI of the female pelvis: a review.
MRI of the female pelvis offers a unique display of pelvic anatomy. On the T2-weighted images, uterine zonal anatomy and temporal changes under hormonal stimuli are well displayed. Benign and malignant uterine neoplasms are accurately demonstrated. However, tumor type cannot be diagnosed. In the staging of endometrial and cervical carcinoma, MRI offers distinct advantages over sonography and/or CT. The main advantages are the abilities to depict tumor and to provide great tissue contrast between the tumor and surrounding normal tissue. In the evaluation of ovarian tumors, experience with MRI is still limited. This is only the beginning of the clinical applications of MRI. Much more work needs to be done to explore fully the value of this versatile and powerful technique.


Efficient organic-inorganic hybrid perovskite solar cells processed in air.
Organic-inorganic hybrid perovskite solar cells with fluorine doped tin oxide/titanium dioxide/CH3NH3PbI3-xClx/poly(3-hexylthiophene)/silver were made in air with more than 50% humidity. The best devices showed an open circuit voltage of 640 mV, a short circuit current density of 18.85 mA cm(-2), a fill factor of 0.407 and a power conversion efficiency of 5.67%. The devices showed external quantum efficiency varying from 60 to 80% over a wavelength region of 350 nm to 750 nm of the solar spectrum. The morphology of the perovskite was investigated using scanning electron microscopy and it was found to be porous in nature. This study provides insights into air-stability of perovskite solar cells.


Application of zeolite-activated carbon macrocomposite for the adsorption of Acid Orange 7: isotherm, kinetic and thermodynamic studies.
In this study, the adsorption behavior of azo dye Acid Orange 7 (AO7) from aqueous solution onto macrocomposite (MC) was investigated under various experimental conditions. The adsorbent, MC, which consists of a mixture of zeolite and activated carbon, was found to be effective in removing AO7. The MC were characterized by scanning electron microscopy (SEM), energy dispersive X-ray, point of zero charge, and Brunauer-Emmett-Teller surface area analysis. A series of experiments were performed via batch adsorption technique to examine the effect of the process variables, namely, contact time, initial dye concentration, and solution pH. The dye equilibrium adsorption was investigated, and the equilibrium data were fitted to Langmuir, Freundlich, and Tempkin isotherm models. The Langmuir isotherm model fits the equilibrium data better than the Freundlich isotherm model. For the kinetic study, pseudo-first-order, pseudo-second-order, and intraparticle diffusion model were used to fit the experimental data. The adsorption kinetic was found to be well described by the pseudo-second-order model. Thermodynamic analysis indicated that the adsorption process is a spontaneous and endothermic process. The SEM, Fourier transform infrared spectroscopy, ultraviolet-visible spectral and high performance liquid chromatography analysis were carried out before and after the adsorption process. For the phytotoxicity test, treated AO7 was found to be less toxic. Thus, the study indicated that MC has good potential use as an adsorbent for the removal of azo dye from aqueous solution.


Long-term Urinary Outcomes After Transvaginal Uterovaginal Prolapse Repair With and Without Concomitant Midurethral Slings.
Many health care providers place concomitant midurethral slings during pelvic organ prolapse repair, yet growing evidence supports staged midurethral sling placement. The aim of this study was to compare urinary function after transvaginal uterovaginal prolapse repair with and without midurethral sling. Secondary analysis of the Study of Uterine Prolapse Procedures Randomized Trial (hysterectomy with uterosacral ligament suspension vs mesh hysteropexy). Our primary outcome was Urinary Distress Inventory score (UDI-6) through 5 years compared between women with and without a concomitant sling within prolapse repair arms. Sling effect was adjusted for select clinical variables and interaction terms (α = .05). The sling group included 90 women (43 hysteropexy, 47 hysterectomy), and the no-sling group included 93 women (48 hysteropexy, 45 hysterectomy). At baseline, the sling group reported more bothersome stress (66% vs 36%, P < 0.001) and urgency incontinence (69% vs 48%, P = 0.007). For hysteropexy, there were no significant long-term differences in UDI-6 scores or bothersome urine leakage between sling groups. For hysterectomy, women with sling had better UDI-6 scores across time points (adjusted mean difference, -5.1; 95% confidence interval [CI], -9.9 to -0.2); bothersome stress and urgency leakage were less common in the sling group (stress adjusted odds ratio, 0.1 [95% CI, 0.0-0.4]; urge adjusted odds ratio, 0.5 [95% CI, 0.2-1.0]). Treatment for stress incontinence over 5 years was similar in the sling (7.9%) versus no-sling (7.6%) groups. Five-year urinary outcomes of concomitant midurethral sling may vary by type of transvaginal prolapse surgery, with possible benefit of midurethral sling at the time of vaginal hysterectomy with apical suspension but not after mesh hysteropexy.


Ca2+ signals and death programmes in neurons.
Cell death programmes are generally defined by biochemical/genetic routines that are linked to their execution and by the appearance of more or less typical morphological features. However, in pathological settings death signals may engage complex and interacting lethal pathways, some of which are common to different cells, whereas others are linked to a specific tissue and differentiation pattern. In neurons, death programmes can be spatially and temporally segregated. Most importantly physiological Ca2+ signals are essential for cell function and survival. On the other hand, Ca2+ overload or perturbations of intracellular Ca2+ compartmentalization can activate or enhance mechanisms leading to cell death. An imbalance between Ca2+ influx and efflux from cells is the initial signal leading to Ca2+ overload and death of ischaemic neurons or cardiomyocytes. Alterations of intracellular Ca2+ storage can integrate with death signals that do not initially require Ca2+, to promote processing of cellular components and death by apoptosis or necrosis. Finally, Ca2+ can directly activate catabolic enzymes such as proteases, phospholipases and nucleases that directly cause cell demise and tissue damage.


Association of Adverse Events in Opioid Addiction Treatment With Quality Measure for Continuity of Pharmacotherapy.
Several quality measures for continuity of substance use care are being used in accountability programs, but it is not known whether they are predictive of better patient outcomes. We analyzed whether opioid use disorder (OUD) patients in the care of clinicians and practices with higher rates on one of these measures-continuity of pharmacotherapy for OUD-have a lower risk of overdose and detox events using Medicare data. For a 10-percentage point increase in an individual clinician's measure rate, the estimated odds ratios of a patient experiencing each of these two events were 0.92 (95% confidence interval [CI] 0.85 to 0.99) for overdose and 0.83 (95% CI 0.75 to 0.92) for detox. The corresponding estimates at the practice level were 0.90 (95% CI 0.85 to 0.95) for overdose and 0.83 (95% CI 0.77 to 0.89) for detox. These results suggest that a clinician's or practice's higher measure rate for continuity of pharmacotherapy for OUD is predictive of their patients' lower likelihood of having an adverse event. The findings contribute to a growing body of evidence on the importance of treatment continuity for OUD and support the validity of measuring continuity in provider-level accountability programs.


Flap complications associated with lamellar refractive surgery.
Corneal lamellar refractive surgery for myopia reduces the risk of corneal haze but adds to the risk of flap complications. We retrospectively determined the incidence of flap complications in the initial series of eyes undergoing lamellar refractive surgery by one surgeon. We assessed the incidence of flap complications overall, the trend in these complications during the surgeon's learning curve, and the impact of the complications on best spectacle-corrected visual acuity. Charts of the first 1,019 eyes that underwent myopic keratomileusis in situ or laser in situ keratomileusis were reviewed for flap complications and visual outcome. Of the 1,019 eyes, 490 eyes underwent myopic keratomileusis in situ, and 529 eyes underwent laser in situ keratomileusis. Eighty-eight (8.6%) of 1,019 eyes had flap-related complications. Six eyes had two complications. Intraoperative complications included irregular keratectomy in nine eyes (0.9%), incomplete keratectomy in three eyes (0.3%), and a free cap in 10 eyes (1.0%). The incidence of intraoperative complications was six (6.0%) in the first 100 consecutive eyes, 14 (2.3%) in the next 600 consecutive eyes (P = .04, chi-square test), and one (0.3%) in the last 300 eyes (P = .03, chi-square test). Postoperative complications included displaced flaps that required repositioning in 20 eyes (2.0%), folds in the flap that required repositioning in 11 eyes (1.1%), diffuse lamellar keratitis in 18 eyes (1.8%), infectious keratitis in one eye (0.1%), and epithelial ingrowth that required removal in 22 eyes (2.2%). The incidence of flap displacement and folds in 200 eyes in which we irrigated under the flap and allowed it to settle without further manipulation averaged 8.5%, whereas the incidence in other groups of 100 consecutive eyes averaged 0.8% (P < .00001, chi-square test). The incidence of diffuse lamellar keratitis was 0.2% in eyes that had undergone myopic keratomileusis in situ and 3.2% in eyes treated by laser in situ keratomileusis (P = .0003, chi-square test). No eye lost 2 or more lines of best spectacle-corrected visual acuity because of flap complications. Flap complications after lamellar refractive surgery are relatively common but rarely lead to a permanent decrease in visual acuity. Physician experience with the microkeratome and with the handling of the corneal flap decreases the incidence of flap complications.


Control of respiration in non-phosphorylating mitochondria is shared between the proton leak and the respiratory chain.
We measured the relationship between rate of respiration and membrane potential in isolated mitochondria titrated with malonate (to inhibit the electron transport chain) or with uncoupler (to increase the proton conductance of the inner membrane). We used the flux control summation and connectivity theorems of metabolic control theory to calculate the control over non-phosphorylating respiration exerted by the respiratory chain (and associated reactions) and by the leak of protons across the inner membrane. At 37 degrees C the flux control coefficient of the leak over respiration was 0.66; the flux control coefficient of the chain over respiration was 0.34. At 25 degrees C the values were 0.75 and 0.25 respectively. We argue that the basis for previous conclusions that all the control is exerted by the proton leak under similar conditions is invalid.


Effect of Electrical Stimulation on Ocular Cells: A Means for Improving Ocular Tissue Engineering and Treatments of Eye Diseases.
Tissue engineering is biomedical engineering that uses suitable biochemical and physicochemical factors to assemble functional constructs that restore or improve damaged tissues. Recently, cell therapies as a subset of tissue engineering have been very promising in the treatment of ocular diseases. One of the most important biophysical factors to make this happen is noninvasive electrical stimulation (ES) to target ocular cells that may preserve vision in multiple retinal and optic nerve diseases. The science of cellular and biophysical interactions is very exciting in regenerative medicine now. Although the exact effect of ES on cells is unknown, multiple mechanisms are considered to underlie the effects of ES, including increased production of neurotrophic agents, improved cell migration, and inhibition of proinflammatory cytokines and cellular apoptosis. In this review, we highlighted the effects of ES on ocular cells, especially on the corneal, retinal, and optic nerve cells. Initially, we summarized the current literature on the in vitro and in vivo effects of ES on ocular cells and then we provided the clinical studies describing the effect of ES on ocular complications. For each area, we used some of the most impactful articles to show the important concepts and results that advanced the state of these interactions. We conclude with reflections on emerging new areas and perspectives for future development in this field.


Identification of Lipid Biomarkers To Discriminate between the Different Production Systems for Asiago PDO Cheese.
The lipid fraction of Asiago Protected Designation of Origin (PDO) cheese was analyzed to identify specific biomarkers of its main production systems through a canonical discriminant analysis. The three main production systems of the cheese were considered. Two were located in the upland (UL): pasture-based (P-UL) vs hay-based total mixed rations (H-UL). The third was located in the lowland (LL) and processed milk from cows fed maize silage-based rations (maize silage lowland: MS-LL). The discriminant analysis selected nine fatty acids and vitamin A as lipid biomarkers useful to separate the three production systems. High contents of conjugated linoleic acids, anteiso-C15:0, and vitamin A were discriminant factors for P-UL cheese. The separation between H-UL and MS-LL cheese was less marked with the former having the higher content of conjugated linoleic acids and some polyunsaturated n-6 fatty acids and with the latter being identified by cyclopropane fatty acid and C9:0.


Purification, kinetic characterization, and molecular cloning of a novel enzyme, ecdysteroid 22-kinase.
This is the first report succeeding in the isolation and characterization of an enzyme and its gene involved in the phosphorylation of a steroid hormone. It has been demonstrated that ecdysteroid 22-phosphates in insect ovaries, which are physiologically inactive, serve as a "reservoir" that supplies active free ecdysteroids during early embryonic development and that their dephosphorylation is catalyzed by a specific enzyme, ecdysteroid-phosphate phosphatase (Yamada, R., and Sonobe, H. (2003), J. Biol. Chem. 278, 26365-26373). In this study, ecdysteroid 22-kinase (EcKinase) was purified from the cytosol of the silkworm Bombyx mori ovaries to about 1,800-fold homogeneity in six steps of column chromatography and biochemically characterized. Results obtained indicated that the reciprocal conversion of free ecdysteroids and ecdysteroid 22-phosphates by two enzymes, EcKinase and ecdysteroid-phosphate phosphatase, plays an important role in ecdysteroid economy of the ovary-egg system of B. mori. On the basis of the partial amino acid sequence obtained from purified EcKinase, the nucleotide sequence of the cDNA encoding EcKinase was determined. The full-length cDNA of EcKinase was composed of 1,850 bp with an open reading frame encoding a protein of 386 amino acid residues. The cloned cDNA was confirmed to encode the functional EcKinase using the transformant harboring the open reading frame of EcKinase. A data base search showed that EcKinase has an amino acid sequence characteristic of phosphotransferases, in that it harbors Brenner's motif and putative ATP binding sites, but there are no functional proteins that share high identity with the amino acid sequence of EcKinase.


The Canadian genetic counseling workforce: Perspectives from employers and recent graduates.
There is a lack of literature devoted to the Canadian genetic counseling workforce. Current and prospective genetic counseling students, graduates, employers, programs, and funding agencies remain largely uninformed of trends in the job market. The purpose of this study was to investigate the employment experiences of recent Canadian genetic counseling graduates and employers of genetic counselors (GCs) in Canada. An online survey was distributed to Canadians who had graduated from North American genetic counseling programs from 2014 to 2018 and to employers with experience hiring patient-facing genetic counselors from 2016 to 2018. Quantitative data were analyzed through descriptive statistics and, where appropriate, logistic regression. Qualitative data were reviewed to illustrate and support the quantitative data. Half of the employer responders (11/22) reported hiring more or many more genetic counselors compared to 3 years ago (2016), and a majority (n = 19, 86%) reported a desire to hire at least one more genetic counselor if funding were available. Most graduates (45/70, 64%) reported securing employment before graduation, 33% (n = 23) within 6 months of graduation, and no one taking longer than 1 year. For recent graduates, location was the most important factor when looking for work, and those who chose to work in Canada experienced significantly more challenges gaining employment as opposed to those who worked internationally (p = 0.03). The specialties in highest demand for genetic counselors and the most common areas of practice for recent graduates included adult general genetics, prenatal genetics, and cancer genetics. Overall, our findings suggest that there is a growth of employment opportunities in Canada and more employer-reported need for clinical genetic counselors; however, there is a lack of funding to support this expansion.


Is handwriting constrained by phonology? Evidence from Stroop tasks with written responses and Chinese characters.
To what extent is handwritten word production based on phonological codes? A few studies conducted in Western languages have recently provided evidence showing that phonology contributes to the retrieval of graphemic properties in written output tasks. Less is known about how orthographic production works in languages with non-alphabetic scripts such as written Chinese. We report a Stroop study in which Chinese participants wrote the color of characters on a digital graphic tablet; characters were either neutral, or homophonic to the target (congruent), or homophonic to an alternative (incongruent). Facilitation was found from congruent homophonic distractors, but only when the homophone shared the same tone with the target. This finding suggests a contribution of phonology to written word production. A second experiment served as a control experiment to exclude the possibility that the effect in Experiment 1 had an exclusively semantic locus. Overall, the findings offer new insight into the relative contribution of phonology to handwriting, particularly in non-Western languages.


Indium-111-labeled polyclonal human immunoglobulin: identifying focal infection in patients positive for human immunodeficiency virus.
Pooled human immunoglobulin labeled with indium-111 (111In-HIgG) was used to identify the presence and extent of infection in patients positive for human immunodeficiency virus (HIV), presenting with either symptoms and/or signs of acute chest infection or with pyrexia without localizing signs or symptoms. Fifty-five studies were performed in 51 patients with suspected chest infection or pyrexia without localizing signs. Of these, 111In-HIgG identified intrapulmonary accumulation in 17 patients with Pneumocystis carinii pneumonia, eight with bacterial pneumonia, five with cytomegalovirus pneumonia, three with pulmonary Mycobacterium avium intracellulare infection and one with a fungal pneumonia. There was no intrapulmonary accumulation of 111In-HIgG in five patients with bronchopulmonary Kaposi's sarcoma and in three patients with intrathoracic lymphoma. Quantification of lung/heart activity was significantly increased (p < 0.05) in patients with active chest infection compared with those with intrapulmonary tumor or no active lung pathology. Indium-111-HIgG scintigraphy also localized at 14 sites of extrapulmonary infection, including six patients with colitis. There were no false-negative studies but false-positive uptake was seen in four studies. These results confirm that 111In-HIgG correctly identifies the presence and extent of infection in patients positive for HIV antibody.


Neutrophil-to-Lymphocyte Ratio Predicts Cerebral Edema and Clinical Worsening Early After Reperfusion Therapy in Stroke.
The mechanisms linking systemic inflammation to poor outcome in ischemic stroke are not fully understood. The authors investigated if peripheral inflammation following reperfusion therapy leads to an increase in cerebral edema (CED), thus hindering the clinical recovery. We designed a single-center study conducted at Centro Hospitalar Universitário São João between 2017 and 2019. Inclusion criteria were being adult, having an anterior circulation acute ischemic stroke, and receiving reperfusion therapy. Neutrophil-to-lymphocyte, platelet-to-lymphocyte ratios, and the systemic inflammatory response syndrome criteria were determined. The presence and grade of CED were evaluated on the computed tomography performed 24 hours following event. The clinical outcomes included early neurological deterioration and functional dependence at 90 days. Adjusted odds ratio and 95% CI were obtained by ordinal and logistic regression models. Optimal cutoff values were defined using receiver operating characteristic analysis in the training cohort and validated in an independent data set. Five hundred fifty-three patients were included. Neutrophil-to-lymphocyte increased with higher degrees of CED at 24 hours (adjusted odds ratio, 1.34 [1.09-1.68], P<0.01) and was associated with early neurological deterioration (adjusted odds ratio, 1.30 [1.04-1.63], P<0.05) and poor functional status at 90 days (adjusted odds ratio, 1.79 [1.28-2.48], P<0.01). Platelet-to-lymphocyte was not associated with the outcomes. Systemic inflammatory response syndrome was related to CED due to altered white blood cell counts. Neutrophil-to-lymphocyte was the best predictor with an area under the curve around 0.7. Neutrophil-to-lymphocyte ≥7 had and accuracy, sensitivity, and specificity around 60%. Increased systemic inflammation is linked to the severity of CED early after reperfusion therapy in stroke. Easily obtained inflammatory markers convey early warning alerts for patients at risk of severe neurological complications with an impact on long-term functional outcome. CED quantification should be included as an end point in proof-of-concept trials in immunomodulation in stroke.


Effect of temperature on respiration of a mesophilic and a thermophilic fungus.
The respiratory rates of mycelia of the mesophilic fungus, Aspergillus niger, and the thermophilic fungus, Thermomyces lanuginosus, were comparable at their respective temperature optima for growth. The respiratory rate of A. niger was independent of changes in temperature between 15 and 40 C. The respiratory rate of T. lanuginosus increased with increase in temperature between 25 and 55 C.


Oxidation of the supplemental methionine source L-2-hydroxy-4-methylthiobutanoic acid by pure L-2-hydroxy acid oxidase from chicken liver.
The peroxisomal enzyme L-2-hydroxy acid oxidase A (EC 220.127.116.11) was isolated from chicken liver to better evaluate its part in the utilization of the L isomer of supplemental DL-hydroxy-4-methylthiobutanoic acid by birds fed diets containing the methionine hydroxy analogue. The 650-fold purified enzyme, a 169 kDa protein composed of four apparently identical subunits, exhibited a specific activity of 1.3 mumol glycolate oxidized.min-1.mg protein-1. Glycolate (Km = 0.10 mmol/L) was actually a better substrate than L-2-hydroxyisocaproate (Km = 0.63 mmol/L), L-2-hydroxy-4-methylthiobutanoate (Km = 1.73 mmol/L) and L-lactate (Km = 10.13 mmol/L). Under all substrate concentrations tested, the enzyme activity toward L-2-hydroxyisocaproate and L-2-hydroxy-4-methylthiobutanoate was 55 and 17%, respectively, of that toward glycolate. Although the highly purified enzyme was unable to oxidize D-lactate, D-methionine, L-methionine, L-mandelate and beta-phenyl-L-lactate, the latter two aromatic substrates were significantly oxidized by the first ammonium sulfate precipitate obtained during the isolation procedure, supposedly because of the presence of L-2-hydroxy acid oxidase isozyme B. Because the hepatic tissue concentration of glycolate, the physiological substrate for the enzyme, was rather low (10 mumol/L) as compared to the concentration of the methionine hydroxy analogue, one can expect that the conversion of L-2-hydroxy-4-methylthiobutanoate to 2-keto-4-methylthiobutanoate prior to L-methionine formation might proceed at a substantial rate in chickens fed the supplemental methionine source.


Interaction of alpha-and beta-oligoarginine-acids and amides with anionic lipid vesicles: a mechanistic and thermodynamic study.
The interaction of alpha- and beta-oligoarginine amides and acids and of alpha-polyarginine with anionic lipid vesicles was studied. The beta-oligoarginines used were beta3-homologues of the alpha-oligoarginines. Lipid bilayers were composed of POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and POPG (1-palmitoyl-2-oleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)]) containing 5 mol % pyrene-PG (1-hexadecanoyl-2-(1-pyrenedecanoyl)-sn-glycero-3-[phospho-rac-1-glycerol]). Kinetic analysis of the binding process onto large unilamellar POPC/POPG (3:7, molar ratio) vesicles (100 nm diameter) shows biphasic time courses for all tested peptides. The first binding step is fast and takes place within approximately 10 s with no disruption of the membrane as indicated by corresponding calcein release measurements. The second binding phase is slow and occurs within the next 30-300 s with substantial membrane disruption. In this context, beta-hexa- and octaarginine amides possess higher second half-times than the beta-hexa- and octaarginine acids of the same chain length. Furthermore beta-octaarginine amide induces a calcein release approximately twice as large as that of the beta-octaarginine acid. Thermodynamic analysis of the binding process, using the complex formation model that assumes that each peptide binds independently to n POPG lipids, reveals apparent binding constants (K(app1)) of approximately 5 x 10(6)-10(8) M(-1) and n-values from 3.7 for beta-hexaarginine acid up to 24.8 for alpha-polyarginine. Although the K(app1)-values are similar, the number of binding sites clearly depends on the chemical nature of the oligoarginine: beta-oligoarginine amides and alpha-oligoarginine acids interact with more lipids than beta-oligoarginine acids of the same length. Calculation of the electrostatic contribution to the total free energy of binding reveals that for all oligoarginines only 25-30% has electrostatic origin. The remaining approximately 70-75% is nonelectrostatic, corresponding to hydrogen bonding and/or hydrophobic interactions. From the obtained data, a mechanism is suggested by which oligoarginines interact with anionic vesicles: (1) initial electrostatic interaction that is fast, nonspecific, and relatively weak; (2) nonelectrostatic interaction that is rate-limiting, stronger, and induces bilayer rigidification as well as release of aqueous contents from the vesicles.


An analog of BIX-01294 selectively inhibits a family of histone H3 lysine 9 Jumonji demethylases.
BIX-01294 and its analogs were originally identified and subsequently designed as potent inhibitors against histone H3 lysine 9 (H3K9) methyltransferases G9a and G9a-like protein. Here, we show that BIX-01294 and its analog E67 can also inhibit H3K9 Jumonji demethylase KIAA1718 with half-maximal inhibitory concentrations in low micromolar range. Crystallographic analysis of KIAA1718 Jumonji domain in complex with E67 indicated that the benzylated six-membered piperidine ring was disordered and exposed to solvent. Removing the moiety (generating compound E67-2) has no effect on the potency against KIAA1718 but, unexpectedly, lost inhibition against G9a-like protein by a factor of 1500. Furthermore, E67 and E67-2 have no effect on the activity against histone H3 lysine 4 (H3K4) demethylase JARID1C. Thus, our study provides a new avenue for designing and improving the potency and selectivity of inhibitors against H3K9 Jumonji demethylases over H3K9 methyltransferases and H3K4 demethylases.


Unilateral acute conjunctivitis due to Oestrus ovis in a veterinary doctor.
Myiasis is the infestation of tissues and organs of animals or man by fly larvae. We report a human case of external ophthalmomyiasis caused by the larvae of a sheep nasal botfly, Oestrus ovis, for the first time in a veterinary doctor. A 25-year-old veterinary doctor presented with severe symptoms of conjunctivitis. The larvae, 3 in number, were observed in the bulbar conjunctiva and the symptoms of the eye improved within a few hours of their removal. It is important for ophthalmologists to be aware of larval conjunctivitis as a significant possibility in the veterinary fraternity especially during the summer season.


MBSJ MCC Young Scientist Award 2010. Recent progress in research on small post-translationally modified peptide signals in plants.
Peptide signaling plays a major role in various aspects of plant growth and development, as has been shown in recent biochemical, genetic and bioinformatic studies. There are over a dozen secreted peptides recognized in plants known to regulate cellular functions. To become functional, these secreted peptide signals often undergo post-translational modifications, such as tyrosine sulfation, proline hydroxylation, and hydroxyproline arabinosylation, and successive proteolytic processing. These types of 'small post-translationally modified peptide signals' are one of the major groups of peptide signals found in plants. In parallel with the discovery of peptide signals, specific receptors for such peptide signals were identified as being membrane-localized leucine-rich repeat receptor kinases. This short review highlights the recent progress in research on small post-translationally modified peptide signals, including our own research.


Health care costs for treatment of disseminated breast cancer.
The rapid development of the care makes it important to have relevant cost information for cost-effectiveness assessments. The aim of this study is to estimate the health care cost of a disseminated breast cancer relapse in Sweden. A retrospective cohort study of women with disseminated breast cancer in Sweden was done. The individual case records were reviewed and all data concerning treatments, hospitalisation, examinations and palliative care were collected. The study included 53 patients with a total mean cost of 93,700 euros (95% Confidence Interval (CI): 78,500 euros - euro109,600 euros ). Drugs and hospitalisations were the largest single cost sources. HER2-positive patients had slightly higher mean costs (euro123,300), while triple negative patients had slightly lower mean costs (70,600 euros). The current costs for patients with disseminated breast cancer are considerably higher than those previously shown, which may have important consequences for economic evaluations of interventions aimed at reducing the risk of disseminated breast cancer.


Amylase activity increases in the yolk of fertilized eggs during incubation in chickens.
Amylase activity was detected in the egg of chickens. In unfertilized eggs, no change of amylase activity was observed during 22 days incubation, however, in fertilized eggs, amylase activity increased markedly during embryonic development. The increase depended upon an increase of amylase in the yolk, not in the albumen. Isoamylases in the yolk were electrophoretically identical to those in the pancreas of the embryo or the hen.


Unraveling the molecular nature of melanin changes in metastatic cancer.
More people die from melanoma after a stage I diagnosis than after a stage IV diagnosis, because the tools available to clinicians do not readily identify which early-stage cancers will be aggressive. Near-infrared pump-probe microscopy detects fundamental differences in melanin structure between benign human moles and melanoma and also correlates with metastatic potential. However, the biological mechanisms of these changes have been difficult to quantify, as many different mechanisms can contribute to the pump-probe signal. We use model systems (sepia, squid, and synthetic eumelanin), cellular uptake studies, and a range of pump and probe wavelengths to demonstrate that the clinically observed effects come from alterations of the aggregated mode from "thick oligomer stacks" to "thin oligomer stacks" (due to changes in monomer composition) and (predominantly) deaggregation of the assembled melanin structure. This provides the opportunity to use pump-probe microscopy for the detection and study of melanin-associated diseases.


Indication for interstitial brachytherapy in carcinoma of the uterine cervix.
More than 40 patients with gynecological, genitourinary, and gastrointestinal malignancies, both primary and recurrent but confined to the pelvis, were treated with interstitial irradiation over a four-year period. Interstitial irradiation was the choice of treatment for early carcinoma of the prostate, carcinoma of the anal canal less than T2, recurrent carcinoma of the uterine cervix, and carcinoma of the cervical stump. The authors' experience in treating recurrent carcinoma of the uterine cervix with interstitial irradiation is the basis for the indications for selecting the technique of interstitial irradiation presented.


Objective quantification of the impact of blepharoplasty on the superior visual field.
Blepharoplasty has both aesthetic and functional benefits in patients with pseudoptosis; however, previous studies could not demonstrate its beneficial effects quantitatively and objectively. The authors objectively analyzed the visual field before and after surgery and investigated whether measurements of the visual field can be applied as a suitable predictor of surgical outcomes. In total, 18 eyelids in nine patients with pseudoptosis who had undergone simple skin excision blepharoplasty were evaluated prospectively from February to May 2016. The visual fields were analyzed preoperatively and 3 months postoperatively using the Goldmann kinetic perimetry test. The visual field test area was assessed using Adobe Photoshop. Blepharoplasty had an average 4.99-fold beneficial effect on the superior visual field. In particular, more improvement was seen in the superior temporal quadrant than in the nasal quadrant. No correlation was found between the preoperative margin-to-reflex distance 1 (MRD1) and the surgical outcome (P=0.119). However, there was a strong correlation between the preoperative superior visual field and the surgical outcome (P=0.001). Using the Goldmann kinetic perimetry test, we objectively and quantitatively proved the beneficial effect of blepharoplasty on patients with pseudoptosis. Furthermore, we demonstrated that the preoperative visual field is a better preoperative surgical outcome predictive factor than the preoperative MRD1.


The effect of treadmill walking on the stride interval dynamics of children.
Treadmills are commonly implemented in rehabilitation and laboratory settings to facilitate gait analysis and training. However, while this locomotor modality is often used with children, its effect on pediatric stride interval dynamics is unknown. This study investigated the stride interval persistence of 30 asymptomatic children after completion of three to six 10-min walking trials comprised of: (i) overground walking (OW), (ii) unsupported treadmill walking (UTW), and (iii) handrail-supported treadmill walking (STW). The primary outcome measure was α, a quantifier of stride interval persistence obtained from detrended fluctuation analysis. Preferred walking speed, number of strides taken, stride interval duration, and stride interval coefficient of variation were also assessed. Stride interval persistence was significantly diminished during both treadmill walking conditions, compared to overground walking, with the largest decrease in α during UTW. Preferred speed, number of strides, and stride interval duration also differed between overground and treadmill walking, and older children demonstrated reduced stride interval variability compared to younger children. The observed treadmill and age effects on stride parameters may be due to a combination of differing locomotor constraints between overground and treadmill walking and developmental differences in sensory processing, cerebellar plasticity, and corticospinal involvement in locomotion.


Anaerobic toluene catabolism of Thauera aromatica: the bbs operon codes for enzymes of beta oxidation of the intermediate benzylsuccinate.
The pathway of anaerobic toluene oxidation to benzoyl coenzyme A (benzoyl-CoA) consists of an initial reaction catalyzed by benzylsuccinate synthase, a glycyl radical enzyme adding the methyl group of toluene to the double bond of a fumarate cosubstrate, and a subsequent beta-oxidation pathway of benzylsuccinate. Benzylsuccinate synthase has been studied in some detail, whereas the enzymes participating in beta oxidation of benzylsuccinate are unknown. We have investigated these enzymes by analyzing substrate-induced proteins in toluene-grown cells. Toluene-induced proteins were identified and N-terminally sequenced. Nine of these proteins are encoded by an 8.5-kb operon consisting of bbs (beta-oxidation of benzylsuccinate) genes whose products are apparently involved in the beta-oxidation pathway of benzylsuccinate. Two of the genes, bbsE and bbsF, code for the subunits of a succinyl-CoA:benzylsuccinate CoA-transferase whose activity was previously detected in toluene-grown Thauera aromatica. The bbsG gene codes for a specific benzylsuccinyl-CoA dehydrogenase, as confirmed by overexpression of the gene in Escherichia coli and detection of enzyme activity. The further enzymes of the pathway are probably encoded by bbsH (enoyl-CoA hydratase), bbsCD (3-hydroxyacyl-CoA dehydrogenase), and bbsB (3-oxoacyl-CoA thiolase). The operon contains two additional genes, bbsA and bbsI, for which no obvious function could be derived. The bbs operon is expressed only in toluene-grown cells and is regulated at the transcriptional level. Promoter mapping revealed a transcription start site upstream of the bbsA gene. This represents the first known promoter site in Thauera spp.


Prevalence of hearing impairment in siblings of deaf children.
To assess the prevalence of hearing impairment in siblings of children with profound to total hearing impairment. Two hundred and twenty siblings of children at a deaf school in Karachi completed the screening program. This consisted of a questionnaire and pure tone audiometry. One out of three (73 siblings) had a threshold of 25 dB or greater in their better ear. In a population, already aware of hearing loss, we note that only fifteen siblings had a previous audiogram. Although a positive family history is associated with hearing impairment in the siblings, no increase due to consanguineous marriages was noted. This assessment has underlined the need to increase public awareness of hearing impairment. It has also exposed the lack of it in families exposed to the condition.


Determination of a locus of instantaneous centers of rotation of the lumbar disc by moiré fringes. A new technique.
The aim of this study was to define the motion of the L4-5 spinal segment moving from full extension to full flexion. A new technique using moiré fringes was applied to measure angles of 3-degree change, a technique proven to be highly accurate for small angular changes. This investigation has identified a locus of centers of rotation (centrode) that is located in the posterior half of the intervertebral disc. The direction of the locus passes from posterior to anterior and back to posterior. The technique can be adapted for evaluation of in vivo radiographs. This technique may prove useful in identifying aberrations in movement associated with spinal segment instability in its earliest stages.


Effects of thiopentone or chlormethiazole on human placental stem villous arteries.
Small placental stem villous arteries were micro dissected from specimens obtained at normal term vaginal delivery (n = 25). Ring preparations of the vessels were mounted in organ baths and isometric tension was measured. Prostaglandin F2 alpha (PGF2 alpha) 10(-7)-10(-4) mol litre-1 produced concentration-dependent contractile responses that were inhibited by thiopentone 10(-4)-10(-3) mol litre-1 and by chlormethiazole 3 x 10(-4)-3 x 10(-3) mol litre-1. Thiopentone 10(-4)-10(-3) mol litre-1 and chlormethiazole 3 x 10(-4)-3 x 10(-3) mol litre-1 decreased the tension in vessels previously treated with PGF2 alpha 10(-5) mol litre-1. Chlormethiazole 3 x 10(-3) mol litre-1 inhibited, and thiopentone 10(-4)-10(-3) mol litre-1 abolished contractile responses to 5-hydroxytryptamine. Contractions induced by angiotensin II were inhibited by thiopentone 10(-3) mol litre-1 and chlormethiazole 3 x 10(-3) mol litre-1. The concentrations of the two drugs needed to affect contractile activation of isolated human stem villous arteries exceeded the free plasma concentrations reached during anaesthesia induced by the agents during Caesarean section, and the present results do not suggest any major effects of thiopentone or chlormethiazole on fetal placental vascular resistance during the clinical use of these drugs.


Comparative effects of two multi-enzyme combinations and a Bacillus probiotic on growth performance, digestibility of energy and nutrients, disappearance of non-starch polysaccharides, and gut microflora in broiler chickens.
The efficacy of two exogenous enzyme combinations and a multi-strain Bacillus probiotic (DFM) on the growth performance, nutrient digestibility, disappearance of non-starch polysaccharides (NSP) and gut microbial composition was investigated in broilers. One-day old Ross 308 chicks were assigned to 36 pens with 22 birds/pen and 6 pens/treatment (Experiment 1) or 36 cages with 8 birds/cage and 6 cages/treatment (Experiment 2). Treatment additives were added to nutritionally complete corn/soy based starter (d 1 to 21) and finisher (d 22 to 42) diets. Treatments included 1) a control diet containing 500 FTU/kg phytase (CTL), 2) CTL + xylanase (2,000 U/kg) and amylase (200 U/kg; XA), 3) CTL+XA + protease (4000 U/g; XAP), 4) CTL+DFM (150,000 cfu/g of 3 strains of Bacillus spp), 5) CTL+DFM+XA, and 6) CTL+DFM+XAP. Supplementation with DFM increased BW, BWG, and FI compared with the CTL (P < 0.05); XAP, but not XA, resulted in increased final BW, BWG and FI compared to the control (P < 0.05). XA and XAP improved apparent ileal digestibility (AID) of starch and fat on d 22 to 42 with XAP improving AMEn (by ∼82 kcal) compared with CTL birds (P < 0.01). DFM+XAP improved apparent ileal digestible energy (AIDE), AID of fat and starch on d 22 to 42, and additionally had a greater than additive effect on AIDE and AMEn. Supplementation with DFM+XAP reduced the ileal and total tract flow of insoluble arabinose and additionally total tract flow of soluble and insoluble xylose and total galactose (P < 0.05); similar effects of XA+DFM were not seen or were lower in magnitude, suggesting that the protease component plays an important role in increasing the availability of NSP for hydrolysis. Supplementation with DFM alone did not affect gut bacterial populations, but XA and XAP reduced numbers of Campylobacter species (by > 2.5 log cfu/g; P < 0.001) and Bacteroides (P < 0.02) in the cecum compared with CTL birds.


[Phacoemulsification of subluxated opacified lens in pseudoexfoliation glaucoma patients, performed with the use of a capsular tension ring and iris retractors].
To evaluate results of phacoemulsification of subluxated lens in patients suffering from pseudoexfoliation-related cataract and glaucoma, performed with the use of a capsular tension ring (CTR) and iris retractors and implantation of artificial intracapsular lens. The retrospective covered 15 patients (15 eyes) at the average age of 75 years, with a subluxated, cloudy lens and pseudoexfoliation glaucoma with IV PEX. Due to poor mydriasis resulting from the course of the pseudoexfoliation syndrome, it was necessary with all the patients to apply iris retractors in order to enlarge the pupil. The opacified lens were removed by means of phacoemulsification. In order to provide additional peripheral support and to maintain the artificial lens in the central position after the surgery, a tension ring was implanted into the lenticular capsule. A foldable intraocular lens was implanted inside the capsule. The observation period was 12 months. The average visual acuity prior the surgery was 0.18+/-0.2, while after a year after the surgery it was 0.56+/-0.32 (p<0.001). Besides, the intraocular pressure was observed to decrease from 18.2+/-5.02 mm Hg before the surgery to 15.8+/-0.84 mmHg (p<0.001) after the surgery. The anti-glaucoma medication ratio was also reduced from 2.1 to 1.3 in the post-surgery period. Inflammatory reaction of the anterior chamber was observed in 7 eyes. Application of a CTR and iris retractors during a surgery of cataract in patients with subluxated opacified lens considerably facilitates the implantation procedure of an artificial lens into the capsule, and it allows to improve the visual acuity and stabilize the intraocular pressure while reducing the quantity of the applied anti-glaucoma drugs.


Relationship between Nitrate Uptake, Flux, and Reduction and the Accumulation of Reduced Nitrogen in Maize (Zea mays L.): II. EFFECT OF NUTRIENT NITRATE CONCENTRATION.
Two maize hybrids were grown under growth chamber conditions on solution or vermiculite medium that contained 2.5, 7.5, or 15 millimolar nitrate. The objectives were to determine: (a) the effect of nitrate supply on N metabolism and growth and (b) the interrelationship between nitrate uptake, flux, and reduction on the accumulation of reduced N and nitrate by the various plant parts and for the whole plant.Increases in nutrient nitrate concentration caused increases in (a) shoot, but not root, dry weight and (b) nitrate uptake, flux, and reduction and accumulation of nitrate and reduced N by the aerial plant parts of both hybrids. Increases in nitrate supply resulted in decreases in nitrate reductase activity and negligible increases in reduced N in the roots of both hybrids. At 2.5 and 15 millimolar, but not at 7.5 millimolar, external nitrate, hybrid B had higher rates of nitrate uptake and flux. Hybrid B also had lower nitrate reductase activity at all levels of external nitrate and accumulated less reduced N than did hybrid C, except when the plants were grown at 2.5 millimolar nitrate. Correlation values between nitrate uptake and flux were significant for each hybrid and for both hybrids, whereas correlations between nitrate reductase activity and flux and nitrate reductase activity and uptake were significant only for a given hybrid. The correlation values (pooling of all data) between (a) nitrate uptake, flux, or reduction and the accumulation of reduced N by the whole plant, and (b) flux x nitrate reductase activity and accumulation of reduced N were all positive and statistically significant. Because nitrate uptake, flux, and reduction (as measured) were all closely associated with the accumulation of reduced N by the plant, all three parameters should be measured in attempts to estimate the genetic potential of a maize genotype to accumulate reduced N.


Clinical Variables Associated With Statural Growth in Pediatric Crohn's Disease Differ by Sex (The Growth Study).
Statural growth impairment is more common in male patients with Crohn's disease (CD). We identified clinical variables associated with height z score differences by sex in children participating in the Growth Study, a prospective multicenter longitudinal study examining sex differences in growth impairment in pediatric CD. Patients with CD (female patients with bone age [BA] ≥4 years 2 months and ≤12 years; male patients with BA ≥5 years and ≤14 years at screening) who had completed study visit 1 qualified. The height z score difference was computed as height z score based on chronological age minus height z score based on BA. One hundred thirteen patients with CD (36% female) qualified. The mean chronological age was 12.0 ± 1.8 (SD) years. The magnitude of the mean height z score difference was significantly greater in female patients (-0.9 ± 0.8) than in male patients (-0.5 ± 0.9; P = 0.021). An initial classification of inflammatory bowel disease as CD (P = 0.038) and perianal disease behavior at diagnosis (P = 0.009) were associated with higher standardized height gain with BA progression, and arthralgia at symptom onset (P = 0.016), azathioprine/6-merpcaptopurine (P = 0.041), and probiotics (P ≤ 0.021) were associated with lower standardized height gain with BA progression in female patients. Patient-reported poor growth at symptom onset (P = 0.001), infliximab (P ≤ 0.025), biologics (P ≤ 0.015), methotrexate (P = 0.042), and vitamin D (P ≤ 0.010) were associated with higher standardized height gain with BA progression, and initial classification as CD (P = 0.025) and anorexia (P = 0.005) or mouth sores (P = 0.004) at symptom onset were associated with lower standardized height gain with BA progression in male patients. Different clinical variables were associated with statural growth in male patients vs female patients, suggesting that sex-specific molecular pathways lead to statural growth impairment in CD.


Evaluation of the contribution to enantioselectivity of quinine and quinidine scaffolds in chemically and physically mixed chiral selectors.
Three "dimeric" C(9)-carbamates of quinine (QN) and quinidine (QD), that is, QN-QN, QD-QD, and QN-QD (chemically prepared mixture of the two cinchona-derived subunits), separated by an ethylene spacer were synthesized and used as chiral selectors for HPLC and capillary electrophoresis (CE) for the resolution of chiral acids. The chiral recognition abilities of these dimers and of several physically prepared mixtures thereof were compared in order to estimate the contribution of every cinchona scaffold to the overall enantioselectivity. The diverse phenomena observed in nonaqueous capillary electrophoresis (NACE), either using the selector added to the background electrolyte (BGE) in the total filling or partial filling mode, led us to rationalize, taking into account the relative mobilities of the chiral selectors in the capillary. The chromatographic and electrophoretic properties were compared with those of the corresponding "monomeric" QN and QD carbamates.


Subwavelength diffractive color beam combiner.
A high-efficiency subwavelength diffractive beam combiner operating in a visible spectral range is designed, fabricated, and demonstrated. Such a device combines red, green, and blue color beams into one output light beam. Diffraction efficiencies of different types of gratings are calculated for various materials, incidence angles, and polarizations of light. It is shown that the plasmon resonance via a grating coupling occurs at the determined conditions. Subwavelength gratings with a period of 400 nm are fabricated and tested using laser and laser diode sources.


The relationship of sanguinaria extract concentration and zinc ion to plaque and gingivitis.
The effects of sanguinaria extract and zinc chloride on plaque growth and gingivitis inhibition were assessed on subjects with initially plaque-free tooth surfaces using a series of oral rinses in a single-blind, crossover, no-oral-hygiene study lasting 2 weeks. A placebo oral rinse containing no sanguinaria or zinc chloride (A), and test rinses containing 150 micrograms/ml sanguinaria and 0.2% zinc chloride (B), 300 micrograms/ml sanguinaria and no zinc chloride (C), and 300 micrograms/ml sanguinaria and 0.2% zinc chloride (D) were evaluated. Subjects using the higher concentration rinses C and D had significantly lower plaque scores than rinse A at 7 and 14 days (p less than 0.05 for C, p less than 0.01 for D). However, groups C and D were not significantly different from each other. Group D had significantly lower plaque (p less than 0.05) and gingivitis (p less than 0.01) scores than group B. Subjects who used rinse B and placebo rinse A had the highest plaque and gingivitis scores and comparison of these two groups revealed no significant difference. At the end of 14 days, the % distribution of 0 plaque and gingivitis scores was greatest among subjects using rinses C and D. Subjects in these 2 groups also had the lowest incidence of plaque and gingivitis scores of 2+. It is concluded that the effects of sanguinaria rinses on developing plaque and gingivitis are influenced more by sanguinaria concentrations than the presence or absence of zinc ion, but that zinc ion may provide a mild enhancement of sanguinaria effectiveness against gingivitis.


The role of 11 beta-hydroxysteroid dehydrogenase in maturation of the intestine.
Glucocorticoids promote the development of many organs including intestine. At the cellular level, the activity of glucocorticoids is regulated by 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) which converts active glucocorticoids to inactive metabolites. As 11 beta HSD is also expressed in the intestine, this enzyme may be an important regulator of intestinal maturation. To investigate this, we have performed the systematic study of the development of intestinal 11 beta HSD activity and its cofactor preference as well as of the effect of 11 beta HSD inhibition by carbenoxolone on postnatal development of sucrase, alkaline phosphatase and Na,K-ATPase in the intestine. The activity of 11 beta HSD was low in ileum of suckling rats and significantly increased during the weaning period. In colon, the activity was already high in suckling rats and gradually rose during the postnatal development. 11 beta HSD activity was undetectable in jejunum both in young and adult rats. At 14.5 nM corticosterone, colonic 11 beta HSD utilized predominantly NAD as a cofactor, but displayed significant sensitivity also to NADP. Ileal 11 beta HSD had similar sensitivity to both cofactors. With NAD as a cofactor, ileal 11 beta HSD had a Km (59 +/- 10 nM) compatible with the colonic enzyme (81 +/- 14 nM). Carbenoxolone administration to suckling and weanling rats in vivo did not result in any changes of sucrase activity in jejunum and ileum, alkaline phosphatase activity in ileum and distal colon or Na,K-ATPase activity in ileum. However, carbenoxolone significantly increased Na,K-ATPase activity in distal colon. Our results indicate that the high-affinity type of 11 beta HSD is expressed not only in colon but also in ileum and that 11 beta HSD is an important factor in the regulation of tissue levels of active glucocorticoids in developing colon but not in the small intestine.


Splenectomy in zebrafish: a new model for immune thrombocytopenia.
In humans, splenectomy is performed to treat many clinical disorders, including immune thrombocytopenia. However, the incidence of splenectomies for immune thrombocytopenia as a therapeutic has significantly declined over the past decade due to the availability of new therapies. Infection and sepsis as a result of splenectomies are well documented, but other long-term effects are not well characterized. Evidence suggests that persons who have had a prior splenectomy may be at an increased risk of vascular conditions. Also, elevated levels of cell-derived microparticles appear to contribute to an increased risk of thrombosis and cardiovascular disease. However, in vivo studies on the increased levels of microparticles following splenectomy are limited. In order to understand the effects of splenectomies, we developed a protocol for splenectomy in adult zebrafish. After anesthesia, the spleen was removed under a stereomicroscope after making an incision on the ventral side of the fish. The spleen was removed by pulling with forceps. The incision was closed by Vetbond tissue glue. Blood collected from both splenectomized zebrafish and those that underwent sham surgeries was immunolabeled with polyclonal antisera against αIIb, followed by flow cytometry. We observed elevated levels of thrombocytes and their microparticles in splenectomized zebrafish. Finally, by injecting αIIb antibody intravenously into zebrafish, we found the thrombocyte counts decreased, suggesting the fish developed immune thrombocytopenia like conditions, which were then reversed by splenectomy. In summary, the model developed here should be useful to study molecular changes due to splenectomy. Also, the zebrafish will be useful in modeling treatment of immune thrombocytopenia like conditions.


The spliced leader-associated RNA is a trypanosome-specific sn(o) RNA that has the potential to guide pseudouridine formation on the SL RNA.
The spliced leader-associated (SLA1) RNA is a trypanosome-specific small RNA with unknown function. SLA1 carries a Sm-like site, and is associated with core Sm proteins. Here we found that SLA1 belongs to a family of hairpin-containing RNAs that are implicated in directing pseudouridylation. A potential for base-pair interaction between SLA1 and spliced leader (SL) RNA agrees with the canonical rules for guiding pseudouridylation on SL RNA. Direct RNA analysis showed that this uridine is indeed pseudouridylated in the SL RNA of Leptomonas collosoma, Leishmania major, and Trypanosoma brucei. This position is conserved in all trypanosomatid SL RNAs. Mutations introduced in the SL RNA to disrupt the interaction domain of SLA1/SL RNA abolished the formation of the pseudouridine. SLA1 is localized both to the nucleolus and nucleoplasm. This study solves a long-standing question regarding the function of this novel RNA and describes the first H/ACA RNA, which, unlike all other pseudouridine guides, is also a bona fide snRNA.


Bio-guided isolation of leishmanicidal and trypanocidal constituents from Pituranthos battandieri aerial parts.
Protozoan pathogens that cause neglected tropical diseases are a major public health concern in tropical and developing countries. In the course of our ongoing search for new lead compounds as potential antiprotozoal agents, this study aims to perform a bio-guided fractionation of Pituranthos battandieri, using an in vitro assay against Leishmania amazonensis and Trypanosoma cruzi. Two known polyacetylenes, (-)-panaxydiol (1) and (-)-falcarindiol (2) were identified from the ethanolic extract of the aerial parts of P. battandieri as the main bioactive constituents. Compounds 1 and 2 showed similar potency (IC50 values of 5.76 and 5.68 μM, respectively) against L. amazonensis to miltefosine (IC50 value of 6.48 μM), the reference drug, and low toxicity on macrophage cell lines J774. Moreover, compound 1 exhibited moderate activity (IC50 23.24 μM) against T. cruzi. In addition, three known furanocoumarins, 8-geranyloxypsoralen (3), 8-geranyloxy-5-methoxypsoralen (4), and phellopterin (5) were isolated. Their structures were elucidated by NMR and MS analysis. Compounds 1 and 2 are described for the first time in the Pituranthos genus, and this is the first report on their antiprotozoal activity. These results highlight this type of polyacetylenes as an interesting scaffold for the development of novel antiparasitic drugs.


Effects of setting events on the problem behavior of students with severe disabilities.
Two studies analyzed the effects of preceding setting events on the problem behavior of students with severe disabilities. Using ABAB withdrawal designs, the occurrence versus nonoccurrence of preceding setting events was analyzed in relation to the frequency of problem behavior. Data were collected throughout a student's school day, with interventions focusing upon the elimination of setting events that occurred before school. The results indicate that (a) the occurrence of preceding setting events was related to higher frequencies of problem behavior and (b) interventions designed to eliminate preceding setting events were consistently associated with low frequencies of problem behavior.


Current prospective of anti-IL-4, -IL-9, and -IL-13 therapies in allergic disease.
While the incidence of allergy and allergic diseases continues to increase, new drugs to treat these disorders have not been forthcoming. The mainstay of therapy continues to be inhaled steroids, leukotriene receptor antagonists, antihistamines and immunotherapy. Even though these drugs work for many patients there remains a group of individuals who fail to improve with these treatments. With the exception of immunotherapy, these drugs improve symptoms, but do not do anything to alter the course of disease. This review will cover recent patents and new drugs that target IL-4, IL-13 and IL-9, molecules involved not only in inflammation associated with disease, but also with the development of the immune repertoire necessary for the perpetuation of disease. Inhibition of these cytokines may lead to true immunomodulation of disease and finally give us drugs that cure the disease rather than just treat symptoms.


RUNX3 is inactivated by promoter hypermethylation in malignant transformation of ovarian endometriosis.
The aim of the present study was to investigate the role of epigenetic inactivation of the runt-related transcription factor 3 gene (RUNX3) in the malignant transformation of ovarian endometriosis. Samples obtained by microdissection and scraping included 30 malignant ovarian endometriotic cyst tissues and 30 corresponding eutopic endometrium tissues from the endometriosis-associated ovarian carcinoma (EAOC) group, 19 benign ovarian endometriotic cyst tissues and 22 corresponding eutopic endometrium tissues from the endometriosis (EM) group and 22 normal eutopic endometrium tissues from the control endometrium (CE) group. RUNX3 methylation status was determined by methylation-specific PCR and bisulfite sequencing, while levels of RUNX3 and ERα protein expression were evaluated using immunohistochemistry. The percentage of RUNX3 methylation and negative RUNX3 protein expression in the malignant ovarian endometriotic cysts from the EAOC group was significantly higher than that in the benign ovarian endometriotic cysts from the EM group. The percentage of RUNX3 methylation and negative RUNX3 protein expression in the eutopic endometrium from the EAOC group was significantly higher than that in the EM and CE groups. An inverse correlation between positive RUNX3 protein expression and methylation was observed and a positive correlation was shown between RUNX3 methylation and ERα protein expression. In the malignant ovarian endometriotic cysts from the EAOC group, there was no significant correlation between methylation frequency of the RUNX3 gene and histological type. However, the percentage of RUNX3 gene methylation was significantly higher in the tissue samples from patients with surgical stage IC EAOC than the percentage in patients with stage IA and IB disease. These results suggest that RUNX3 inactivation by promoter hypermethylation plays a role in the progression of malignant transformation of ovarian EM and is closely related to estrogen metabolism. Negative protein expression and abnormal RUNX3 methylation in the eutopic endometrium could be used as diagnostic markers in patients with ovarian EM who may be at an increased risk of developing EAOC.


Emergency Obstetrics for the Emergency Medicine Provider.
Emergency medicine physicians must have the knowledge and skills to stabilize all life-and-limb-threatening conditions. These skills are especially important considering that the 1989 COBRA act clearly defines active labor as a condition unsuitable to transfer. Given this context, we thought it necessary to create a work that could be used to provide emergency physicians with the necessary skills to assist in deliveries both routine and complex. The total time requirement for the workshop is 4 hours. Before the session begins, learners are asked to fill out a survey. Learners complete two 40-minute small-group sessions on the topics of normal vaginal delivery and shoulder dystocia with hands-on training with birthing manikins. After a short break learners complete a 65-minute small-group session for breech delivery with hands-on training. Each small-group session is preceded by a whole-group demonstration of required skills lasting 15 minutes as well a mini lecture on maternal hemorrhage and estimation of blood loss. Our workshop has been shown to successfully educate emergency physicians with a range of obstetric experience and improve their knowledge base and hands-on skills. One hundred percent of our learners felt this workshop was appropriate for them and met its stated goals. While this is not the first workshop to educate on obstetric deliveries and their possible complications, it is the first to be created with the emergency medicine provider as the intended audience and the first to create a curriculum around uncomplicated delivery, shoulder dystocia, breech delivery, and postpartum hemorrhage.


Role of a Fetal Ultrasound Clinic in Promoting Multidisciplinary and Inter-Facility Perinatal Care.
With the increasing rate of high-risk pregnancies, there is an increased need for early evaluation of at-risk fetuses. Fetal ultrasound imaging has become a pivotal part of this evaluation. To evaluate the role played by a fetal ultrasound clinic in promoting comprehensive perinatal care of patients with high-risk pregnancies, we retrospectively analyzed the indications and findings of fetal scans and the outcomes of the examined fetuses collected over the past 7 years (2014-2020) by our institute, which is reorganized as a perinatal medical center. During the study period, we conducted 345 fetal scans in high-risk pregnancy cases. Of these, 158 cases (46%) were referrals from other institutes. Eighty-nine neonates were admitted to our neonatal intensive care unit (NICU) after being evaluated, of which 10 neonates underwent surgery during their NICU stays. Thirty-nine pregnant women were referred to other tertiary care hospitals mainly due to fetal diagnoses with complex cardiac anomalies. Fourteen cases resulted in intrauterine fetal death or artificial abortion. Fetal ultrasound clinics have established their role in facilitating sophisticated regional perinatal care via multidisciplinary and inter-facility cooperation for high-risk pregnancy cases. In addition, providing psychological support and counseling for pregnant women whose fetuses are diagnosed with severe congenital anomalies should not be neglected.


Vertical-strain-induced spin-splitting in zigzag graphene nanoribbons.
We report a first-principles study of the spintronic properties of zigzag graphene nanoribbons under vertical strain. An apparent spin-splitting of the energy band is obtained when a local deformation is created by the vertically applied strain. In particular, it is found that the spin-splitting is most obvious at the bottom of the conduction band. The value of the spin-splitting is related to the position, depth and size of the deformation. By changing the position of the local deformation from the edge to the center of the ribbon, the optimal position is obtained. Detailed calculations at the optimal position show that, for a given size, the spin-splitting value increases with the depth of the deformation, while for a given depth, the spin-splitting value decreases with the size of the deformation.


The multiple functions of the numerous Chlamydia trachomatis secreted proteins: the tip of the iceberg.
Chlamydia trachomatis serovars are obligate intracellular bacterial pathogens mainly causing ocular and urogenital infections that affect millions of people worldwide and which can lead to blindness or sterility. They reside and multiply intracellularly within a membrane-bound vacuolar compartment, known as inclusion, and are characterized by a developmental cycle involving two morphologically and physiologically distinct chlamydial forms. Completion of the developmental cycle involves the secretion of > 70 C. trachomatis proteins that function in the host cell cytoplasm and nucleus, in the inclusion membrane and lumen, and in the extracellular milieu. These proteins can, for example, interfere with the host cell cytoskeleton, vesicular and non-vesicular transport, metabolism, and immune signalling. Generally, this promotes C. trachomatis invasion into, and escape from, host cells, the acquisition of nutrients by the chlamydiae, and evasion of cell-autonomous, humoral and cellular innate immunity. Here, we present an in-depth review on the current knowledge and outstanding questions about these C. trachomatis secreted proteins.


Pain management: a review of organisation models with integrated processes for the management of pain in adult cancer patients.
This paper reports a review of the literature conducted to identify organisation models in cancer pain management that contain integrated care processes and describe their effectiveness. Pain is experienced by 30-50% of cancer patients receiving treatment and by 70-90% of those with advanced disease. Efforts to improve pain management have been made through the development and dissemination of clinical guidelines. Early improvements in pain management were focussed on just one or two single processes such as pain assessment and patient education. Little is known about organisational models with multiple integrated processes throughout the course of the disease trajectory and concerning all stages of the care process. Systematic review. The review involved a systematic search of the literature, published between 1986-2006. Subject-specific keywords used to describe patients, disease, pain management interventions and integrated care processes, relevant for this review were selected using the thesaurus of the databases. Institutional models, clinical pathways and consultation services are three alternative models for the integration of care processes in cancer pain management. A clinical pathway is a comprehensive institutionalisation model, whereas a pain consultation service is a 'stand-alone' model that can be integrated in a clinical pathway. Positive patient and process outcomes have been described for all three models, although the level of evidence is generally low. Evaluation of the quality of pain management must involve standardised measurements of both patient and process outcomes. We recommend the development of policies for referrals to a pain consultation service. These policies can be integrated within a clinical pathway. To evaluate the effectiveness of pain management models standardised outcome measures are needed.


Slipped upper femoral epiphysis in Hashimoto's thyroiditis in a 29-year-old man.
Slipped upper femoral epiphysis (SUFE) with an open physis is rare in an adult and the condition may present without prior diagnosis of an underlying medical condition. We have treated a 29-year-old man with bilateral SUFE associated with autoimmune hypothyroidism. The management was delayed and complicated by co-existing autoimmune chronic active hepatitis. He underwent thyroxine therapy and bilateral pinning in situ with a single ASNIS screw. Closure of the physis occurred after five months on the right side. The left side required a further corrective intertrochanteric osteotomy, and it was only after 13 months that complete fusion of this physis was seen. The case highlights the need to consider endocrine and metabolic conditions in atypical presentation of SUFE.


An Optimized Isotopic Photocleavable Tagging Strategy for Site-Specific and Quantitative Profiling of Protein O-GlcNAcylation in Colorectal Cancer Metastasis.
O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation is a ubiquitous protein post-translational modification of the emerging importance in metazoans. Of the thousands of O-GlcNAcylated proteins identified, many carry multiple modification sites with varied stoichiometry. To better match the scale of O-GlcNAc sites and their dynamic nature, we herein report an optimized strategy, termed isotopic photocleavable tagging for O-GlcNAc profiling (isoPTOP), which enables quantitative and site-specific profiling of O-GlcNAcylation with excellent specificity and sensitivity. In HeLa cells, ∼1500 O-GlcNAcylation sites were identified with the optimized procedures, which led to quantification of ∼1000 O-GlcNAcylation sites with isoPTOP. Furthermore, we apply isoPTOP to probe the O-GlcNAcylation dynamics in a pair of colorectal cancer (CRC) cell lines, SW480 and SW620 cells, which represent primary carcinoma and metastatic cells, representatively. The stoichiometric differences of 625 O-GlcNAcylation sites are quantified. Of these quantified sites, many occur on important regulators involved in tumor progression and metastasis. Our results provide a valuable database for understanding the functional role of O-GlcNAc in CRC. IsoPTOP should be applicable for investigating O-GlcNAcylation dynamics in various pathophysiological processes.


Risk of anemia in morbidly obese patients after bariatric surgery in Taiwan.
Bariatric surgery is one of most effective long-term treatments for morbid obesity. However, post-bariatric surgery anemia is identified as a common adverse effect and remains a challenge nowadays. To estimate the risk of post-bariatric surgery anemia and to stratify the association between age, gender, and types of surgery. This study is a population-based cohort study. We conducted this nationwide study using claims data from National Health Insurance Research Database in Taiwan. There were 4373 morbidly obese patients in this study cohort. Among patients who were diagnosed with morbid obesity, 2864 received bariatric surgery. All obesity-associated comorbidities decreased in the surgical group. Increasing risk of post-bariatric surgery anemia among obese patients was found by Cox proportional hazards regression [adjusted hazard ratio (HR): 2.36]. Also, we found significantly increasing cumulative incidence rate of anemia among patients receiving bariatric surgery by log-rank test. After adjusting for age and gender, the increasing incidence of post-bariatric surgery anemia was found among women (adjusted HR: 2.48), patients in the 20-29-year-old group (adjusted HR: 3.83), and patients in the 30-64-year-old group (adjusted HR: 2.37). Moreover, malabsorptive and restrictive procedures had significantly higher adjusted HRs, 3.18 and 1.55, respectively. Bariatric surgery give rise to anemia risk among obese patients, specifically in women, young- and middle-aged patients, and patients undergoing malabsorptive procedures in our population-based cohort study in Taiwan.


[Lice (Anoplura) of small mammals in the Volga-Kama Preserve].
18 068 small mammals belonging to 15 species were examined, 25 059 lice of 7 species (Hoplopleura acanthopus, H. edentula, H. affinis, H. longula, Polyplax serrata, P. borealis, Neohaematopinus laeviusculus) were collected from 2355 animals of 14 species. Information is given on the species composition, occurrence and abundance for lice on shrews and rodents. 50 per cent of collected animals belong to Clethrionomys glareolus and about 85 per cent of lice--to Hoplopleura edentula. Frequent cases were recorded of the occurrence of lice on non-typical hosts as a result of interspecific contacts of animals. H. edentula was more often than other species found on non-typical hosts. No specific lice were reported from shrews and some rodents, only vole lice were found. Seasonal and age changes in lice infection rate of mass rodents as well as infection rate in years of greater and lesser abundance of C. glareolus have been studied.


The dual role of domperidone in gastroparesis and lactation.
Domperidone is a prokinetic agent used as a second-line treatment option for gastroparesis in those unable to tolerate metoclopramide. Via inhibition of dopamine-2 receptors within the gastrointestinal tract and various parts of the central and peripheral nervous system, domperidone helps to facilitate peristalsis and gastric emptying. A major side effect of domperidone is prolactinemia, allowing it to be used off-label for the purpose of inducing lactation. In the U.S., domperidone is currently not U.S. Food and Drug Administration approved due to various case reports and literature associating the risks of sudden cardiac death and ventricular arrhythmia with the use of domperidone. Despite the evidence against the use of domperidone, it is still being widely used in Canada and Europe for both gastroparesis and to induce milk let-down. This article is a literature review intending to assess the risks associated with the use of domperidone in gastroparesis and lactation.


[Optimized approach to the surgical treatment of patients with large and giant postoperative ventral hernia].
To optimize surgical approach in patients with large and giant postoperative ventral hernias through an analysis of early and long-term results of modern techniques of hernia repair. There were 680 patients with postoperative ventral hernia over a 15-year period who underwent surgery in the Sklifosovsky Research Institute for Emergency Care and Medical Unit of the Ministry of Internal Affairs (445 (65.4%) women, 235 (34.6%) men). Mean age of patients was 63.2±14.2 years. Middle and elderly (employable) age patients (45-74 years) prevailed in the study (n=510, 75%). Hernia repair using «sublay» technique was performed in 490 (72%) patients without severe comorbidities and relative volume of hernial protrusion up to 18%. Submuscular-inlay technique was used in 95 (14%) patients with significant comorbidities and those over 50 years old or with a relative volume of hernial protrusion over 18%. We have applied a modified repair technique for the last 3 years in 5 (0.75%) patients with a giant postoperative ventral hernia and anterior abdominal tissue deficiency (partial or complete absence of some anatomical structures, for example, rectus muscle). A hybrid technology was applied in 12 patients with severe concomitant diseases, hernias W2 according to European qualifications or recurrent hernias, significant adhesions in the abdominal cavity or hernial sac. Early postoperative wound complications occurred in 27 (5.5%) patients including hematoma (n=12, 2.5%), infiltration (n=7, 1.4%), wound suppuration (n=8, 1.6%). Other complications were observed in 6 (1.2%) patients: pneumonia, pulmonary embolism, intestinal obstruction. Lethal outcomes were absent. Recurrences in long-term period were found in 18 (3.7%) patients. Submuscular-inlay technique of hernia repair was followed by early postoperative wound complications in 5 (5.1%) patients including hematoma (n=3, 3.2%), infiltration (n=1, 1%), wound suppuration (n=1, 1%). There was no mortality. No other early postoperative complications were observed. Recurrences were detected in 5 (5.2%) patients. Preoperative intra-abdominal pressure was 7-10 mm Hg in all patients with tissue deficit. This value did not exceed 12 mm Hg after repair due to creation of a «specified diastasis». Lethal outcomes were absent. There were no early and long-term recurrences or wound complications. Analysis of early and long-term results of the modified hybrid repair of the anterior abdominal wall did not reveal recurrences, local and systemic complications. Persistent minor diastasis between rectus muscles reinforced with a mesh implant was observed in 3 (25%) out of 12 patients. Thus, optimized and personalized approach in patients with large and giant postoperative ventral hernias considers all intra- and postoperative risk factors.


Retinal haemorrhage description tool.
Retinal haemorrhages are an important finding in children with abusive and accidental head trauma. There are no standardised and validated protocols to describe them in a consistent manner. The aim of this web-based study was to establish the reliability and validity of a new retinal haemorrhage description tool. Our tool is a comprehensive questionnaire, which is applied using a retinal schematic that divides the retina into four independent zones. Four independent observers scored retinal haemorrhages from 80 retinal photographs. Inter- and intra-rater agreement (by repeat assessment of 10 photographs for each examiner) were calculated using Fleiss κ statistics. A high inter-rater agreement was noted for haemorrhages in the peripapillary zones, whereas agreement was only fair for all other zones. Intra-rater agreement was high only for the posterior pole. Photographs may be an unreliable way of documenting retinal haemorrhages particularly from the peripheral retina, thus underscoring the importance of a thorough clinical examination. This study shows that the tool achieves some validity for describing haemorrhages in the posterior retina. It performs less well in the peripheral zones.


Aldehyde Dehydrogenase Plays a Pivotal Role in the Maintenance of Stallion Sperm Motility.
Although stallion spermatozoa produce significant quantities of reactive oxygen species, a lag between 4-hydroxynonenal (4HNE) adduction and the loss of motility in stallion spermatozoa suggests the presence of a robust aldehyde detoxification mechanism. Because there is a paucity of studies characterizing the role of aldehyde dehydrogenase (ALDH) in sperm functionality, the aim of this study was to ascertain the relationship between 4HNE production and motility and ALDH expression by stallion spermatozoa. PCR analysis revealed the presence of the ALDH1A3, ALDH1B1, and ALDH2 isoforms in these cells. Strong correlations (P < 0.001) were found between ALDH expression and various motility parameters of stallion spermatozoa including the percentage of progressive (r = 0.79) and rapidly motile (r = 0.79) spermatozoa, whereas repeated measurements over 24 h revealed highly significant correlations among progressive motility loss, 4HNE accumulation, and ALDH expression (P ≤ 0.001). ALDH inhibition resulted in a spontaneous increase in 4HNE levels in viable cells (21.1 ± 5.8% vs. 42.6 ± 5.2%; P ≤ 0.05) and a corresponding decrease in total motility (41.7 ± 6.2% vs. 6.4 ± 2.6%; P ≤ 0.001) and progressive motility (17.0 ± 4.1% vs. 0.7 ± 0.4%; P ≤ 0.001) of stallion spermatozoa over 24 h. Similarly, inhibition of ALDH in 4HNE-challenged spermatozoa significantly reduced total motility over 4 h (35.4 ± 9.7% vs. 15.3 ± 5.1%, respectively; P ≤ 0.05). This study contributes valuable information about the role of the ALDH enzymes in the maintenance of stallion sperm functionality, with potential diagnostic and in vitro applications for assisted reproductive technologies.