Cardioverter-defibrillator implantation in high-risk patients with hypertrophic cardiomyopathy.
Implantable cardioverter-defibrillators (ICDs) are used with increasing frequency in hypertrophic cardiomyopathy (HCM) patients of all ages for primary and secondary sudden death prevention. Concerns may arise regarding the safety of device implantation because of unique clinical and phenotypic expressions of HCM. The purpose of this study was to assess the efficacy and safety of ICD placement in high-risk patients with HCM. We analyzed the experience with ICDs and transvenous lead systems in 75 consecutive HCM patients at the Minneapolis Heart Institute from 1993 to 2004. The age of the study group patients was 12 to 79 years (mean 36 +/- 16). Patients received ICDs for secondary (n = 4, after cardiac arrest) or primary prevention (n = 71, with > or = 1 risk factor). Thirty-one patients demonstrated disease features that potentially impacted methodology and safety of the implant procedure, most commonly massive left ventricular (LV) hypertrophy and outflow obstruction > or = 50 mmHg. There were no procedure-related deaths; defibrillator implants were successful and uneventful in 71 of 75 patients (95%). In 3 of the 75 patients (4%), defibrillation was unsuccessful because of high thresholds, associated with extreme hypertrophy (wall thickness > 45 mm) and/or ongoing amiodarone therapy. In two of these patients, thoracotomy with epicardial lead placement achieved successful defibrillation; ICD therapy was abandoned in the other patient. ICD placement in children and adults with HCM is generally safe and effective. However, in some patients with massive LV hypertrophy and/or prior administration of amiodarone, transvenous defibrillation proved difficult, and epicardial lead placement was required. High-energy ICD devices and defibrillation threshold testing are recommended for most high-risk HCM patients.


Proton therapy for spinal ependymomas: planning, acute toxicities, and preliminary outcomes.
To report acute toxicities and preliminary outcomes for pediatric patients with ependymomas of the spine treated with proton beam therapy at the MD Anderson Cancer Center. Eight pediatric patients received proton beam irradiation between October 2006 and September 2010 for spinal ependymomas. Toxicity data were collected weekly during radiation therapy and all follow-up visits. Toxicities were graded according to the Common Terminology Criteria for Adverse Events version 3.0. All patients had surgical resection of the tumor before irradiation (7 subtotal resection and 1 gross total resection). Six patients had World Health Organization Grade I ependymomas, and two had World Health Organization Grade II ependymomas. Patients had up to 3 surgical interventions before radiation therapy (range, 1-3; median, 1). Three patients received proton therapy after recurrence and five as part of their primary management. The entire vertebral body was treated in all but 2 patients. The mean radiation dose was 51.1 cobalt gray equivalents (range, 45 to 54 cobalt gray equivalents). With a mean follow-up of 26 months from the radiation therapy start date (range, 7-51 months), local control, event-free survival, and overall survival rates were all 100%. The most common toxicities during treatment were Grade 1 or 2 erythema (75%) and Grade 1 fatigue (38%). No patients had a Grade 3 or higher adverse event. Proton therapy dramatically reduced dose to all normal tissues anterior to the vertebral bodies in comparison to photon therapy. Preliminary outcomes show the expected control rates with favorable acute toxicity profiles. Proton beam therapy offers a powerful treatment option in the pediatric population, where adverse events related to radiation exposure are of concern. Extended follow-up will be required to assess for late recurrences and long-term adverse effects.


Antiaromatic planar cyclooctatetraene: a strategy for developing ambipolar semiconductors for field effect transistors.
Tetra[2,3-thienylene] planarised by sulphur bridges and radially π-extended with (triisopropylsilyl)ethynyl groups had a narrow HOMO-LUMO gap due to the antiaromatic cyclooctatetraene core, and its single crystal FET device exhibited ambipolar characteristics with hole and electron mobilities of up to 0.40 and 0.18 cm(2) V(-1) s(-1), respectively.


Ring-testing and field-validation of a terrestrial model ecosystem (TME)--an instrument for testing potentially harmful substances: effects of carbendazim on nematodes.
The effects of the fungicide carbendazim (applied in the formulation Derosal) on nematodes was determined in Terrestrial Model Ecosystem (TME) tests and field-validation studies. TMEs consisted of intact soil columns (diameter 17.5 cm; length 40 cm) taken from a grassland or, in one case, from an arable site. The TMEs were taken from the same site where the respective field study was performed. The tests were performed in Amsterdam (The Netherlands), Bangor (Wales, England), Coimbra (Portugal) and Flörsheim (Germany). Differences concerning nematode overall abundance, the number of nematode families, the trophical structure of the nematode cenosis and the maturity index (MI) were not found between the controls of TME tests and the respective field-validation studies. Effects caused by the chemical treatment, however, were observed on the number of nematode families, on the trophical structure of the nematode cenosis and on the maturity index (MI). Effects on the relative abundance of the omnivorous nematodes were most pronounced, whereas the overall nematode abundance was not affected. The observed effects appear not to differ between the TME tests and the respective field-validation studies. All measurement endpoints in both TMEs and field, showed rather large variations. Therefore, NOEC-values were often equal or higher than the highest treatment level and EC50-values were calculated only for the omnivorous nematodes. NOEC- and EC50-values derived from the TME ring-test and the field-validation study indicate that the reproducibility (i.e. the variation between the partners) was reasonable, although different soils from different sites were used. The EC50-values determined for the effect of carbendazim on the relative abundance of the omnivorous nematodes ranged between 0.93 and 7.24 kg a.i./ha (1.24-9.63 mg/kg). Due to the higher sensitivity of the relative abundance of the omnivorous nematodes compared to the other measurement endpoints it is recommended to use this parameter as the main endpoint.


Sexuality and ageing in palliative care environments? Breaking the (triple) taboo.
Ageist perceptions continue to constrain the choices available to older adults in terms of their sexual expression. This paper discusses the last stage of life, when older adults may be progressing through a terminal disease, dying and in palliative care environments. Are they (or is anyone, at any age) interested in remaining intimate when they are dying? If yes, how is this interest accepted/facilitated within such environments?. This article does not claim to be definitive, but provides a broad, preliminary sketch of this neglected research area. It suggests that, for many, sexual expression and intimate connection continue to be important until the very end of the lifespan. As such, this important topic deserves recognition as part of an overall response to sexuality and ageing by policy makers and health professionals. Its importance will only become more significant due to greater longevity and population ageing.


A word on the microbiome: considerations about the history, current state, and terminology of an emerging discipline.
Since the beginning of the 21st century, a new discipline, microbiome science, has emerged as a key part of microbiology and related biomedical and ecological sciences. Microbiome science uses highly advanced molecular genetic and bioinformatic methods to study complex microbial communities. Unlike isolated microbes, microbial communities shaped by the environment, referred to as microbial consortia or microbiomes, follow their own laws that allow for significant functional specialization. The synthesis of multimethodology and multidisciplinary data enables microbiome science to move towards a holistic picture of the microbiome in an exceptionally effective way, but on the other hand, it burdens the field with terminological ambiguity of the key terms, which consequently need to be clearly codified in accordance with the international trends in the use of technical nomenclature. To this end, we present in our article the official position of the Czech Microbiome Society of the J. E. Purkyně Czech Medical Society on the use of appropriate Czech terms in both professional and general communication.


Clinical and economic outcomes of involving pharmacists in the direct care of critically ill patients with infections.
To determine whether the absence or presence of clinical pharmacists in intensive care units (ICUs) results in differences in mortality rates, length of ICU stay, and ICU charges for Medicare patients with nosocomial-acquired infections, community-acquired infections, and sepsis. The type and level of pharmacy services provided to ICUs were obtained from a 2004 national survey. Clinical pharmacy services were defined as having at least a partial pharmacist full-time equivalent specifically devoted to the ICU for the purpose of direct involvement in patient care. Infections were defined using International Classification of Diseases, Ninth Revision, Clinical Modification codes. ICU outcome data were drawn from the 2004 modified Medicare provider analysis and review. Depending on the infection studied, the involvement of clinical pharmacists was evaluated in 8,927-54,042 patients from 265 to 276 hospitals. None. Mortality rates, length of ICU stay, Medicare charges, drug charges, and laboratory charges for each of the infections categorized according to the absence or presence of clinical pharmacists. Compared to ICUs with clinical pharmacists, mortality rates in ICUs that did not have clinical pharmacists were higher by 23.6% (p < 0.001, 386 extra deaths), 16.2% (p = 0.008, 74 extra deaths), and 4.8% (p = 0.008, 211 extra deaths) for nosocomial-acquired infections, community-acquired infections, and sepsis, respectively. Similarly, ICU length of stay was longer by 7.9% (p < 0.001, 14,248 extra days), 5.9% (p = 0.03, 2855 extra days), and 8.1% (p < 0.001, 19,215 extra days) for nosocomial-acquired infections, community-acquired infections, and sepsis, respectively. ICUs that did not have clinical pharmacists had greater total Medicare billings of 12% (p < 0.001, $132,978,807 extra billing charges), 11.9% (p < 0.001, $32,240,378 extra billing charges), and 12.9% (p < 0.001, $224,694,784 extra billing charges) for nosocomial-acquired infections, community-acquired infections, and sepsis, respectively. Similar findings were observed for Medicare drug charges and laboratory charges. The involvement of clinical pharmacists in the care of critically ill Medicare patients with infections is associated with improved clinical and economic outcomes. Hospitals should consider employing clinical ICU pharmacists.


Diagnosis of parapneumonic pleural effusion by polymerase chain reaction in children.
Most pleural effusions are associated with bacterial pneumonia, and the identification of the pathogen will assist the therapeutic decision. A specific method that is not affected by previous antibiotic therapy is sought to detect the main causative agents of pneumonia in infants and children (Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus). The aim of the present study was to compare the polymerase chain reaction (PCR) technique with standard culture methods in identifying bacterial infections in infants' and children's pleural effusion. Samples obtained from pediatric patients (n = 37) with a diagnosis of pneumonia associated to pleural effusion, submitted to thoracentesis, were analyzed by PCR with specific primers. The PCR technique identified the presence of bacterial infection in a larger proportion (95.2%) than the standard culture method (33.3%) on complicated pleural effusion samples. The microorganism detection on uncomplicated pleural effusion samples was positive only by the PCR method (31.3%). The frequencies of microorganisms identified on complicated pleural effusion were 57.1% of all patients for methicillin-resistant Staphylococcus; 52.4%, S pneumoniae; 28.6%, S aureus; and 23.8%, H influenzae. The previous use of antibiotics interferes with standard culture method, but it did not interfere with the PCR results. The molecular diagnosis by PCR method could improve the etiologic diagnosis and might help to guide the treatment of parapneumonic effusion in children.


Diagnostic accuracy on fat-saturated T₂ weighted MRI for diagnosis of intra-articular adhesions of the temporomandibular joint.
The purpose of this study is to compare intra-articular adhesions of the temporomandibular joint (TMJ) between fat-saturated T₂ weighted MR images and arthroscopic findings. 50 patients (50 joints) with closed locking of the TMJ who were examined with MRI and then underwent arthroscopic surgery participated in this study. The concordance rate of intra-articular adhesions between fat-saturated T₂ weighted MR images and arthroscopic findings was studied using the kappa coefficient. Intra-articular adhesions were seen on MRI in 21 joints (42%) and in arthroscopic findings in 26 joints (52%). Thus, five joints had false-negative results and mild adhesions were arthroscopically observed in these five joints. There was significant concordance between these two findings (p<0.001). The kappa coefficient was 0.801, which was considered to be complete concordance. On fat-saturated MRI, a low signal intensity area and narrowing image in the joint space of the TMJ may indicate the presence of intra-articular adhesions or fibrosis.


Flapless intrascleral knotting technique for suture fixation of intraocular implants.
We will describe a flapless/grooveless/pocketless and minimally invasive technique for scleral suture fixation of intraocular implants. After introducing the suture into the eye, the two ends of the suture were left exterior to the globe, the free end and the end connected to a curved needle (the needle side). A back-and-forth intrascleral suture passage was performed with the aid of a curved needle. The suture was thus supported by adequate scleral tissue. The suture was fixated to the sclera by knotting it into the sclerotomy. The ends of the suture were finally anchored intrasclerally with the aid of a 30-gauge needle. The technique was employed in 15 eyes of 15 patients. The mean postoperative follow-up period was 9.1 ± 4.6 months. Postoperatively, the intraoperative lenses (IOLs) of all the eyes remained well positioned and stable. The postoperative visual acuities for all of the eyes were also improved. No suture erosion, suture loosening, hypotony, scleral atrophy, chronic inflammation, retinal tears, and/or detachments were observed within the follow-up period. The present technique provides minimal surgical invasion for the scleral suture fixation of intraocular implants.


Severe aseptic inflammation caused by long distance running (246 km) does not increase procalcitonin.
The Spartathlon ultra distance running race (246 kilometres) is an exhausting physical exercise leading to a state of systemic inflammation associated with dramatic elevation of interleukin-6 and acute-phase reactants to levels seen only in critically ill or patients near death. We sought to study the effect of this severe inflammatory response on the levels of serum procalcitonin. Fifteen healthy endurance-trained runners who participated in the 2006 Spartathlon were studied. Blood samples were taken the day before the race, within 15 min after the end of the race and 48 h after the end of the race. Serum interleukin-6, serum amyloid A protein, C-reactive protein, tumour necrosis factor-alpha and procalcitonin concentrations were determined. Serum interleukin-6, serum amyloid A protein and C-reactive protein were dramatically increased after the end of the race (150-, 116- and 10,470- fold increase of the mean values, respectively). Procalcitonin levels remained within normal range (mean +/- standard error of mean, 0.27 +/- 0.02 microg L(-1), 0.26 +/- 0.02 microg L(-1) and 0.27 +/- 0.02 microg L(-1) before, at the end, and 48 h after the race, respectively). Tumour necrosis factor-alpha measurements revealed no significant changes. This study provides strong evidence that Spartathlon, a prolonged endurance exercise resulting in severe stimulation of inflammatory mediators followed by muscle and liver damage, does not induce procalcitonin secretion. The findings cannot directly be applied to other causes of aseptic inflammation.


Predictors of surgical outcomes of uvulopalatopharyngoplasty for obstructive sleep apnea hypopnea syndrome.
To investigate predictors of surgical outcomes of uvulopalatopharyngoplasty (UPPP) for obstructive sleep apnea hypopnea syndrome (OSAHS). Case series with planned data collection. A university medical center. Thirty-nine patients with OSAHS received Z-palatopharyngoplasty (ZPPP) or Han-uvulopalatopharyngoplasty (H-UPPP). All patients were evaluated within 3 months before surgery and at 6 to 12 months after surgery. Statistical analyses were conducted on preoperative parameters that could have affected surgical efficacy and outcome. Success was defined as an apnea-hypopnea index (AHI) fewer than 20 times per hour and a decrease of more than 50%. The success rate was 56.4% (22/39 patients). There were statistically significant differences in AHI, lowest oxygen saturation (L-Sao(2)), time with oxygen saturation less than 90% (CT90), percentage of time with oxygen saturation less than 90% (CT90%), microarousal index (MI), apolipoprotein E (ApoE), high-density lipoprotein (HDL), fasting blood glucose (FBG), and Friedman OSA stage between the treatment success and failure groups. Higher success rate was predicted by lower severity, as indicated by lower AHI, CT90, CT90%, and MI; higher L-Sao(2); and fewer glucose and lipid metabolism abnormalities, shown by lower ApoE and FBG and higher HDL. Disease severity, glucose and lipid metabolism, and Friedman OSA stage may be important predictors of surgical outcome of UPPP for OSAHS.


Position 3 analogues of a crustacean pigment-dispersing hormone: synthesis and biological activity.
In an effort to explain the difference in potencies between the two characterized crustacean pigment-dispersing hormones (alpha-PDH; beta-PDH) and to define a role for residue 3 in these octadecapeptide hormones, we have synthesized and purified seven position 3 alpha-PDH analogues ([Ala3], [Ile3], [Asn3], [Gln3], [Asp3], [Glu3], and [Lys3]alpha-PDH). When tested for melanophore pigment-dispersing activity in destalked Uca, [Glu3]alpha-PDH was found to be 325% more potent than alpha-PDH. Reduced potencies were observed for the [Asp3] (58%), [Asn3] (26%), [Gln3] (11%), and [Ala3] (8%) derivatives. Much lower potencies were displayed by the [Lys3] and [Ile3] analogues (0.73% and 0.66%, respectively). These results suggest that the position 3 side chain carboxylate anion of [Glu3]alpha-PDH stabilizes the active receptor-bound conformer through a charge-charge interaction.


A statistical evaluation of the reproducibility of micronucleus, sister-chromatid exchange, thioguanine-resistance and ouabain-resistance assays in V79 cells exposed to ethyl methanesulfonate and 7,12-dimethylbenz[a]anthracene.
In contrast to the "validation" of short-term in vitro genotoxicity assays by concordance with the rodent cancer bioassay, the present report describes the multiple replication of 4 short-term tests with V79 cells (micronucleus assay, MN; sister-chromatid exchange, SCE; ouabain resistance. OUR; and thioguanine resistance, TGR) within the same assay system following exposure to each of two genotoxins, ethyl methanesulfonate (direct acting) and 7,12-dimethylbenz[a]anthracene (indirect acting). Reproducibility, proportion of genotoxins correctly identified, and proportion of non-genotoxins correctly identified by each test were each determined statistically. Decision rules were formulated to declare a positive response in each assay, and overall accuracy of each was determined. Statistical analysis of the data, obtained under standardized test conditions, showed that for these two chemicals SCE identified 100% of genotoxins and 86% of non-genotoxins, with overall accuracy of prediction of 93%; TGR identified 98% of genotoxins and 74% of non-genotoxins, with overall accuracy of 86%; MN identified 78% of genotoxins and 84% of non-genotoxins, with overall accuracy of 81%; while OUR indicated 100% of genotoxins, but only 50% of non-genotoxins, and only 76% overall accuracy. The results suggested that the best overall accuracy of classification with the V79 assay system could be achieved by measurement of SCE in combination with thioguanine resistance.


Fluorescence derivatizing procedure for 5-hydroxytryptamine and 5-hydroxyindoleacetic acid using 1,2-diphenylethylenediamine reagent and their sensitive liquid chromatographic determination.
A pre-column derivatization method using a fluorogenic reagent, 1,2-diphenylethylenediamine (DPE) was studied for the sensitive HPLC determination of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), which are biosubstances used in the diagnosis of several diseases. For the quantitative determination, the biogenic indole compounds were converted to their corresponding fluorescent derivatives with DPE in the presence of potassium hexacyanoferrate (III) at room temperature, and then the derivatives were separated by reversed-phase liquid chromatography with fluorescence detection. The chromatographic detection limits of the fluorescent peaks at a signal-to-noise ratio of 3 were 0.3 fmol for 5-HT and 0.2 fmol for 5-HIAA. The proposed method permits the simultaneous quantification of 5-HT and 5-HIAA at concentrations higher than 2.4 nM in human urine without a clean-up procedure.


A spatial analysis of the blood-brain barrier damage in experimental allergic encephalomyelitis.
Experimental allergic encephalomyelitis was induced in young male Lewis rats. Following the development of neurological signs, the local distribution of perivascular inflammatory cellular infiltrates and the local blood-to-tissue transfer constants (K1) of alpha-aminoisobutyric acid (AIB) were determined, and these results were compared. Perivascular infiltrative lesions were generally found near areas of the CNS that normally lack an effective blood-brain barrier (BBB) such as the choroid plexus and the entry zones of the cranial and spinal nerve roots. This distribution pattern indicates that the entry of the causative agent into CNS tissue may be by way of the permeable microvessels of these structures. In tissue around inflamed veins, the mean transfer constant was slightly but significantly increased (2.8 +/- 1.5 microliter g-1 min-1) compared with uninvolved regions (0.9 +/- 0.2 microliter g-1 min-1) and similar areas in control animals (0.9 +/- 0.3 microliter g-1 min-1). Analysis of the autoradiographic method of determining transfer constants suggested that the AIB influx rate in the lesion areas may actually be manyfold larger than measured, that BBB permeability may be greatly increased at such sites, and that the areas of lymphocytic infiltration and increased K values may be virtually identical.


Temporal profile of functional visual rehabilitative outcomes modulated by transcranial direct current stimulation.
We have previously reported that transcranial direct current stimulation (tDCS) delivered to the occipital cortex enhances visual functional recovery when combined with three months of computer-based rehabilitative training in patients with hemianopia. The principal objective of this study was to evaluate the temporal sequence of effects of tDCS on visual recovery as they appear over the course of training and across different indicators of visual function. Primary objective outcome measures were 1) shifts in visual field border and 2) stimulus detection accuracy within the affected hemifield. These were compared between patients randomized to either vision restoration therapy (VRT) combined with active tDCS or VRT paired with sham tDCS. Training comprised two half-hour sessions, three times a week for three months. Primary outcome measures were collected at baseline (pretest), monthly interim intervals, and at posttest (three months). As secondary outcome measures, contrast sensitivity and reading performance were collected at pretest and posttest time points only. Active tDCS combined with VRT accelerated the recovery of stimulus detection as between-group differences appeared within the first month of training. In contrast, a shift in the visual field border was only evident at posttest (after three months of training). tDCS did not affect contrast sensitivity or reading performance. These results suggest that tDCS may differentially affect the magnitude and sequence of visual recovery in a manner that is task specific to the type of visual rehabilitative training strategy employed.


Predictors of progression in primary progressive multiple sclerosis in a large Turkish cohort.
Studies on the predictors of progression for primary progressive multiple sclerosis (PPMS) are limited and there is no information in the literature for populations outside Europe and North America. In this study, we aimed to identify predictors of progression in a large Turkish PPMS cohort. We analyzed a cohort of 157 PPMS patients to investigate the effect of age of onset, gender, onset symptoms, presence or absence of relapses, and baseline gadolinium-enhancing lesions on the rate of progression to EDSS6 by using Kaplan-Meier analysis and multivariate Cox regression. Older age of onset and presence of spinal motor symptoms at onset were associated with a shorter time to EDSS6 and presence of supratentorial signs at onset was associated with a longer time to EDSS6 according to Kaplan-Meier analysis. These factors remained significant after multivariate Cox-regression analysis. Clinical relapses were present in 22.3% and gadolinium-enhancing lesions on baseline MRI were present in 28% of patients, but these factors were not predictive of time to EDSS6. We identified age of onset and symptom at onset as predictors of progression in Turkish PPMS patients. Presence of clinical relapses or baseline gadolinium-enhancing lesions did not affect PPMS progression rate.


Motor neuron rigidity. An electrophysiological, pharmacological and pathological study.
A 28-year-old male with generalized muscle stiffness and widespread muscle twitching is described. Continuous electrical activity was present at rest and could be abolished only by succinylcholine, curare, and block of the distal part of the peripheral nerve. Muscle biopsy revealed mild myopathic changes. In addition glycogen depletion was found in muscle fibres which were type IIb in one region of the biopsy and type I in another. With carbamazepine treatment marked improvement occurred both clinically and electromyographically. It is concluded that the abnormal electrical activity originated in the terminal branches of the peripheral motor nerve and that this activity was confined to muscle fibres belonging to single motor unit territories.


Implementing conventional logic unconventionally: photochromic molecular populations as registers and logic gates.
In this paper we detail experimental methods to implement registers, logic gates and logic circuits using populations of photochromic molecules exposed to sequences of light pulses. Photochromic molecules are molecules with two or more stable states that can be switched reversibly between states by illuminating with appropriate wavelengths of radiation. Registers are implemented by using the concentration of molecules in each state in a given sample to represent an integer value. The register's value can then be read using the intensity of a fluorescence signal from the sample. Logic gates have been implemented using a register with inputs in the form of light pulses to implement 1-input/1-output and 2-input/1-output logic gates. A proof of concept logic circuit is also demonstrated; coupled with the software workflow describe the transition from a circuit design to the corresponding sequence of light pulses.


Stress-related dysautonomias and neurocardiology-based treatment approaches.
Cardiovascular and psychiatric disorders are among the most commonly treated conditions worldwide. Research in neurocardiology, psychiatry, and epidemiology have defined bidirectional relationships between psychiatric disorders and heart disease, affirming the role of impaired autonomic nervous system, or dysautonomia in the prognosis and development in these disorders. These studies have fueled rapid clinical translation of experimental findings, with potential to complement existing pharmacological therapies. In this review, we comprehensively discuss the state-of-the-art investigations and novel treatment approaches for stress-related dysautonomias, emphasizing the effects of stress on the cardiac neuronal hierarchy. Increasing evidence suggests that autonomic modulation stands as an attractive therapeutic strategy in the treatment of dysautonomias that could complement existing therapies and possibly reduce the burden of drug-related side effects and treatment-resistant conditions. Further investigations regarding treatment optimization, selectivity, usability, and ethical concerns are required.


Endstopped neurons in the visual cortex as a substrate for calculating curvature.
Neurons in the visual cortex typically respond selectively to the orientation, and velocity and direction of movement, of moving-bar stimuli. These responses are generally thought to provide information about the orientation and position of lines and edges in the visual field. Some cells are also endstopped, that is selective for bars of specific lengths. Hubel and Wiesel first observed that endstopped hypercomplex cells could respond to curved stimuli and suggested they might be involved in detection of curvature, but the exact relationship between endstopping and curvature has never been determined. We present here a mathematical model relating endstopping to curvature in which the difference in response of two simple cells gives rise to endstopping and varies in proportion to curvature. We also provide physiological evidence that endstopped cells in area 17 of the cat visual cortex are selective for curvature, whereas non-endstopped cells are not, and that some are selective for the sign of curvature. The prevailing view of edge and curve determination is that orientations are selected locally by the class of simple cortical cells and then integrated to form global curves. We have developed a computational theory of orientation selection which shows that measurements of orientation obtained by simple cells are not sufficient because there will be strong, incorrect responses from cells whose receptive fields (RFs) span distinct curves (Fig. 1). If estimates of curvature are available, however, these inappropriate responses can be eliminated. Curvature provides the key to structuring the network that underlies our theory and distinguishes it from previous lateral inhibition schemes.


Bidirectional Association Between Sleep Quality and Low Back Pain in Older Adults: A Longitudinal Observational Study.
To investigate the bidirectional relationship by determining whether baseline sleep quality predicts pain intensity and whether baseline pain intensity predicts sleep quality in older individuals with chronic low back pain (LBP). A prospective longitudinal cohort study with a 6-month follow-up period. Community. Older adults with LBP aged 60 years or older (N=215). Not applicable. Data collection occurred at baseline and at 6 months. Pain intensity and sleep quality were measured in both time points of assessment using the numeric pain rating scale (range, 0-10) and the Pittsburg Sleep Quality Index. At baseline, we also collected information on demographic anthropometric variables, cognitive status, depression, and comorbidities. Multivariable linear regression analyses adjusted for potential covariates were performed. A total of 215 individuals with LBP were recruited. Poor sleep quality at baseline predicted high pain intensity at 6 months (β coefficient, 0.18; 95% confidence interval [CI], 0.07-0.30). High pain intensity at baseline predicted poor sleep quality 6 months later (β coefficient, 0.14; 95% CI, 0.01-0.26). Our findings give some support to the bidirectional relationship between pain and sleep quality in older individuals with LBP. This bidirectional relationship may be used as prognostic information by clinicians when managing patients with LBP.


Cardiosome-mediated protection in myocardial ischemia.
Cardiosomes, exosomes released in cardiospheres by cardiomyocytes and progenitor cells, communicate locally and at a distance from different tissues, promoting beneficial cellular changes. For example, miRNAs have emerged as regulators of intercellular communication via transport by extracellular vesicles in general and cardiosomes specifically. Although cardiosomes are considered biomarkers owing to their immense biomedical application in various clinical fields, their role in cardiovascular diseases remains unclear. This mini-review examines the experimental and clinical evidence for cardiosomes as non-invasive diagnostic, treatment and prognostic tools in acute myocardial infarction, the novelty of which is often lost in medical practice. In addition, we discuss the potential role of cardiosomes in physiologic mechanisms and cell signaling in cardiac conditioning strategies against reperfusion injury.


A calcium-redox feedback loop controls human monocyte immune responses: The role of ORAI Ca2+ channels.
In phagocytes, pathogen recognition is followed by Ca(2+) mobilization and NADPH oxidase 2 (NOX2)-mediated "oxidative burst," which involves the rapid production of large amounts of reactive oxygen species (ROS). We showed that ORAI Ca(2+) channels control store-operated Ca(2+) entry, ROS production, and bacterial killing in primary human monocytes. ROS inactivate ORAI channels that lack an ORAI3 subunit. Staphylococcal infection of mice reduced the expression of the gene encoding the redox-sensitive Orai1 and increased the expression of the gene encoding the redox-insensitive Orai3 in the lungs or in bronchoalveolar lavages. A similar switch from ORAI1 to ORAI3 occurred in primary human monocytes exposed to bacterial peptides in culture. These alterations in ORAI1 and ORAI3 abundance shifted the channel assembly toward a more redox-insensitive configuration. Accordingly, silencing ORAI3 increased the redox sensitivity of the channel and enhanced oxidation-induced inhibition of NOX2. We generated a mathematical model that predicted additional features of the Ca(2+)-redox interplay. Our results identified the ORAI-NOX2 feedback loop as a determinant of monocyte immune responses.


Hyaluronic acid hydrogel scaffolds with a triple degradation behavior for bone tissue engineering.
In this study, in order to better mimick the nature of bone extracellular matrix, hyaluronic acid (HA) hydrogels having a triple degradation behavior were synthesized from 3,3'-dithiodipropionate hydrazide-modified HA (DTPH-HA) and polyethylene glycol dilevulinate (LEV-PEG-LEV) via the reaction of the ketone carbonyl groups of LEV-PEG-LEV with the hydrazide groups of DTPH-HA. The HA hydrogels were characterized by solid state (13)C NMR, FT-IR, SEM, and rheological, swelling and degradation tests. The results showed that the HA hydrogels exhibited a highly porous morphology and had pore diameters ranging from 20 to 200 μm. The equilibrium swelling ratio of the HA hydrogels was no less than 37.5. The HA hydrogels could be degraded by hyaluronidase and reducing substances or at acidic pH values. The biocompatibility of the HA hydrogels was evaluated using osteoblast-like MC3T3-E1 cells by live/dead staining and MTT assays. The results revealed that the HA hydrogels had good biocompatibility and could support the attachment and proliferation of MC3T3-E1 cells. All the results indicated that the HA hydrogels synthesized by hydrazone bond crosslinking might have great potential to be used in bone tissue engineering.


Role of xylo-oligosaccharides in protection against salinity-induced adversities in Chinese cabbage.
Soil salinity is a stringent abiotic constraint limiting crop growth and productivity. The present study was carried out to appraise the role of xylo-oligosaccharides (XOSs) in improving the salinity tolerance of Chinese cabbage. Salinity stress (0.5% NaCl solution) and four levels (0, 40, 80, 120 mg L(-1)) of XOSs were imposed on 20-day-old plants cultured under controlled conditions. Salinity stress decreased the aboveground fresh biomass, photosynthesis, transpiration rate, stomatal conductance, internal CO2 concentration, water use efficiency, and chlorophyll contents but increased the stomatal limitation value of Chinese cabbage compared with control. Such physiological interferences, disturbances in plant water relations, and visually noticeable growth reductions in Chinese cabbage were significantly alleviated by the addition of XOSs under salinity stress. Under salinity stress, application of XOSs significantly enhanced the activities of enzymatic (superoxide dismutase, peroxidase, catalase) and non-enzymatic (ascorbate, carotene) antioxidants and reduced the malondialdehyde content in the leaves of Chinese cabbage. The XOS-applied plants under salinity stress also recorded higher soluble sugars, proline, and soluble protein content in their leaves. Exposure of salinity stress increased the ratio of Na(+)/K(+), Na(+)/Ca(2+), and Na(+)/Mg(2+) in shoot as well as root of Chinese cabbage, however, XOS application significantly reduced these ratios particularly in shoot. Lower levels of XOSs (40 or 80 mg L(-1)) were more effective for most of the studied attributes. The greater salinity tolerance and better growth in these treatments were related with enhanced antioxidative defense system, reduced lipid peroxidation, increased osmolyte accumulation, and maintenance of ionic balance.


Stroke induces gene profile changes associated with neurogenesis and angiogenesis in adult subventricular zone progenitor cells.
Neural progenitor cells in the subventricular zone (SVZ) of the lateral ventricular wall give rise to new neurons throughout rodent life. Ischemic stroke induces angiogenesis and neurogenesis. Using laser capture microdissection (LCM) in combination with microarrays containing approximately 400 known genes associated with stem cells and angiogenesis, we investigated gene profiles of SVZ cells in the adult mouse subjected to middle cerebral artery occlusion. Our data revealed that nonstroke SVZ cells expressed sets of genes that are important for neural progenitor cell proliferation, differentiation, and migration. In addition, stroke SVZ cells expressed many genes involved in neurogenesis during embryonic development but were not detected in nonstroke SVZ cells. Stroke upregulated genes were verified by real-time reverse transcriptase-polymerase chain reaction and immunostaining. These data indicate that adult SVZ cells recapture embryonic molecular signals after stroke and provide insight into the molecular mechanisms, which regulate the biological function of neural progenitor cells in the SVZ of adult rodent brain under physiological and stroke conditions.


Diverse, uncultivated bacteria and archaea underlying the cycling of dissolved protein in the ocean.
Dissolved organic nitrogen (DON) supports a significant amount of heterotrophic production in the ocean. Yet, to date, the identity and diversity of microbial groups that transform DON are not well understood. To better understand the organisms responsible for transforming high molecular weight (HMW)-DON in the upper ocean, isotopically labeled protein extract from Micromonas pusilla, a eukaryotic member of the resident phytoplankton community, was added as substrate to euphotic zone water from the central California Current system. Carbon and nitrogen remineralization rates from the added proteins ranged from 0.002 to 0.35 μmol C l(-1) per day and 0.03 to 0.27 nmol N l(-1) per day. DNA stable-isotope probing (DNA-SIP) coupled with high-throughput sequencing of 16S rRNA genes linked the activity of 77 uncultivated free-living and particle-associated bacterial and archaeal taxa to the utilization of Micromonas protein extract. The high-throughput DNA-SIP method was sensitive in detecting isotopic assimilation by individual operational taxonomic units (OTUs), as substrate assimilation was observed after only 24 h. Many uncultivated free-living microbial taxa are newly implicated in the cycling of dissolved proteins affiliated with the Verrucomicrobia, Planctomycetes, Actinobacteria and Marine Group II (MGII) Euryarchaeota. In addition, a particle-associated community actively cycling DON was discovered, dominated by uncultivated organisms affiliated with MGII, Flavobacteria, Planctomycetes, Verrucomicrobia and Bdellovibrionaceae. The number of taxa assimilating protein correlated with genomic representation of TonB-dependent receptor (TBDR)-encoding genes, suggesting a possible role of TBDR in utilization of dissolved proteins by marine microbes. Our results significantly expand the known microbial diversity mediating the cycling of dissolved proteins in the ocean.


Can N-acetylcysteine reverse the antiplatelet effects of clopidogrel? An in vivo and vitro study.
The active metabolite of clopidogrel binds the P2Y12 ADP receptor on the platelet surface via a disulfide bond. N-Acetylcysteine (NAC) is able to reduce disulfide bonds. We postulated that NAC might reverse clopidogrel's effect on platelets. Two groups of patients were investigated. Group 1 included 11 patients with stable coronary disease who, after discontinuation of aspirin, received 14 days of clopidogrel, 75 mg/day. Bleeding time and whole-blood platelet aggregometry (with 5 micromol/L ADP) were compared before and after the 14 days. Patients were then treated with 6 g of NAC orally, followed by repeat measurement of bleeding time and aggregometry. In group 2, 14 patients were treated with clopidogrel (300 mg) and aspirin before a percutaneous coronary intervention. Blood was drawn 22 +/- 3 hours later and divided into 2 samples. One was sent immediately for platelet-rich plasma aggregometry (using 5 and 2 micromol/L ADP, collagen, and arachidonic acid as agonists), thromboelastography, and aggregometry using the Plateletworks assay (Helena Laboratories, Beaumont, Tex). The other sample was treated with NAC (500 mg/L), after which these same platelet function tests were performed. In group 1, NAC therapy did not significantly change the bleeding time or results of aggregometry. In group 2, neither aggregometry nor the Plateletworks assay suggested reversal of inhibition by NAC. These studies reveal that a large dose of NAC does not reduce inhibition of platelet aggregation by clopidogrel in vitro or in vivo.


Phase II trial of carbetimer in metastatic melanoma.
A phase II study of the synthetic polyelectrolyte Carbetimer 6500 mg/m2 i.v. daily for five days every 21-day cycle was conducted in patients with metastatic melanoma. No responses were seen in 18 evaluable patients. Two patients had stable disease for five months. Toxicity was generally manageable and included mild hyperphosphatemia, mild proteinuria, fatigue, pain at the injection site, and nausea. Carbetimer is inactive in metastatic melanoma at this dose and schedule.


Cultural stability of Streptomyces fradiae in the production of xylose isomerase: studies in shake flasks.
Comprehensive studies of pure colonies of Streptomyces fradiae in the production of xylose isomerase by submerged fermentation at shake flask level revealed poor culture stability with respect to enzyme production, biomass formation, degree of pigmentation, quantity of glucose and xylose utilization, level of enzyme in cell-free culture broth and final pH of the fermentation medium. The results serve to stress obligatory evaluation of culture stability of Streptomyces strains in determining their suitability for use in developing fermentation processes for commercial exploitation.


Sympathetic control of antral and pyloric electrical activity in the rabbit.
The effects of section and stimulation of the sympathetic nerve trunk on gastric motility were investigated in conscious and decorticate rabbits. In conscious animals after section of the abdominal splanchnic nerve, rhythm of antral and pyloric bursts was enhanced, becoming more regular, and the period of arrest of the rhythmic bursts, which was usually observed at the end of inflation of the antrum in intact rabbits, was shortened to 33.6 +/- 4.0 s from 112.2 +/- 14.6 s observed before the sympathetic nerve transection. Adrenergic agonists, phenylephrine (100 micrograms/kg), clonidine (5 micrograms/kg) and salbutamol (1 mg/kg) inhibited antral and pyloric activity. In decorticate rabbits the major effect of stimulation of the peripheral or the central end of the thoracic sympathetic trunk was inhibition; this was seen both with the spontaneous and vagally induced e.m.g. activity of the antrum and pylorus. Inhibition induced by stimulation of sympathetic efferents was abolished by beta-blocking agents and that induced by stimulation of the sympathetic afferents disappeared after alpha-adrenergic block. Significance of a dual control of the gastric motility by the sympathetic nerve was discussed.


Resetting the paradigm of reproductive science and conservation.
In the application of reproductive science to conservation breeding, it has long been assumed that artificial insemination using frozen thawed sperm would be the default technology. This has always been problematic considering the wide range of tolerance to freeze thawing among vertebrate sperm. Furthermore, those providing leadership for genome banking should be proactive to preserve maximum genetic diversity, however, for many species there is little or no sperm motility after thawing of cryopreserved sperm. In this review article, there is the contention that a much wider range of tissues should be banked, and the range of evolving advanced reproductive and developmental technologies should be considered for conservation breeding programs, to realize the maximum opportunities of genome banking to contribute to conservation of animal species.


Cutaneous and histopathological features of coronavirus disease 2019 in pediatrics: A review article.
Prevalence of dermatological manifestations of coronavirus disease 2019 (COVID-19) is estimated between 0.25% and 3% in children and adolescents. In this review article, we decided to describe the cutaneous and histopathological manifestations of COVID-19 infection in pediatrics. We searched published articles in PubMed database for key words of "children" or "pediatric" and "cutaneous" or "dermatology" or "skin" and "COVID-19" or "SARS-CoV-2" or "Coronavirus disease 2019" in abstract or title from December of 2019 until September 2020. Finally, 38 articles were selected. The majority of patients were between 11 and 17 years old with predominantly male gender. Most of the patients were either asymptomatic or had a few general symptoms. The latency time from appearance of general symptoms to cutaneous ones was between 1 day and weeks. Skin lesions faded between 3 and 88 days without any sequelae, spontaneously or with either topical or systemic corticosteroids. Skin manifestations were chilblain-like (pseudochilblain), erythema multiforme-like, dactylitis, acral erythema, acute urticaria, livedo reticularis, mottling, acro-ischemia, generalized maculopapular lesions, eyelid dermatitis, miliaria-like, varicelliform lesions, and petechiae and/or purpura. Kawa-COVID-19 patients were presented more frequently with cardiogenic shock, neurological symptoms, lymphocytopenia, and thrombocytopenia as compared to classic Kawasaki's disease. Furthermore, more number of cases were resistant to the first-line treatments.


Dentin bond strength of two mineral trioxide aggregate-based and one epoxy resin-based sealers.
This study aimed at evaluating the bond strength to root dentin of 2 mineral trioxide aggregate (MTA)-based sealers (Endo-CPM sealer and MTA Fillapex) and of 1 epoxy resin-based sealer (AH Plus sealer). Forty-five extracted human teeth with single roots were prepared by using the step-back technique. Irrigation with 2.5% NaOCl and a final rinse with 17% ethylenediaminetetraacetic acid and distilled water were performed. Canals were filled by using Endo-CPM sealer, MTA Fillapex, or AH Plus sealer by means of the gutta-percha lateral condensation technique. After 7 days, the roots were sectioned perpendicularly to its long axis, and the push-out test was carried out. The data were analyzed by using the Kruskal-Wallis and Dunn post hoc tests. Endo-CPM sealer showed the highest values of bond strength to root dentin (8.265 MPa) (P < .05). The values of push-out test were similar for MTA Fillapex (2.041 MPa) and AH Plus (3.034 MPa). On the basis of the findings presented herein and within the limitations of this study, Endo-CPM sealer presented advantages when a post preparation was required. MTA Fillapex presented acceptable resistance to dislodgement, which was similar to that observed in samples filled with AH Plus sealer.


Effect of access to anticoagulation management services on warfarin use in patients with atrial fibrillation.
To determine the effect of access to ambulatory anticoagulation management services (AMS) on the rate of warfarin use in patients with atrial fibrillation. Retrospective medical record review. Two ambulatory care clinics in the same managed care system: one with and one without access to pharmacist-managed AMS. One hundred seventy-eight patients with atrial fibrillation diagnosed between June 2000 and June 2001. Warfarin use was assessed overall and by contraindications and risk factors for stroke. Independent predictors of therapy were identified. The overall rate of warfarin use in atrial fibrillation was higher in the clinic with access to AMS than in the clinic without access (77.9% vs 61.7%, p=0.03). In patients with no known contraindications, warfarin use increased by 20.2% with access to AMS versus no access (80.2% vs 60.0%, p=0.023). Patients aged 65 years or older with one or more risk factors for stroke and no contraindications were more likely to receive warfarin in the clinic with access to AMS than in the clinic without access (85.1% vs 53.8%, p=0.001). Access to AMS was an independent predictor of warfarin use (odds ratio 2.19, 95% confidence interval [CI] 1.05-4.56). Female sex was an independent negative predictor of warfarin use (odds ratio 0.48, 95% CI 0.24-0.96). In the managed care setting, use of warfarin for stroke prophylaxis in patients with atrial fibrillation was higher in the ambulatory care clinic with access to pharmacist-managed AMS than in the clinic without access.


The otolaryngologist's and anesthesiologist's collaborative role in a pandemic: A large quaternary pediatric center's experience with COVID-19 preparation and simulation.
There has been a rapid global spread of a novel coronavirus, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which originated in Wuhan China in late 2019. A serious threat of nosocomial spread exists and as such, there is a critical necessity for well-planned and rehearsed processes during the care of the COVID-19 positive and suspected patient to minimize transmission and risk to healthcare providers and other patients. Because of the aerosolization inherent in airway management, the pediatric otolaryngologist and anesthesiologist should be intimately familiar with strategies to mitigate the high-risk periods of viral contamination that are posed to the environment and healthcare personnel during tracheal intubation and extubation procedures. Since both the pediatric otolaryngologist and anesthesiologist are directly involved in emergency airway interventions, both specialties impact the safety of caring for COVID-19 patients and are a part of overall hospital pandemic preparedness. We describe our institutional approach to COVID-19 perioperative pandemic planning at a large quaternary pediatric hospital including operating room management and remote airway management. We outline our processes for the safe and effective care of these patients with emphasis on simulation and pathways necessary to protect healthcare workers and other personnel from exposure while still providing safe, effective, and rapid care.


Ascaris suum and Onchocerca volvulus: S-adenosylmethionine decarboxylase.
Putrescine-dependent S-adenosylmethionine decarboxylase (EC 126.96.36.199) was demonstrated in Ascaris suum and Onchocerca volvulus; activation was found to be about fourfold by putrescine. Mg2+ did not affect the enzyme activity. A. suum was taken as a model nematode and its S-adenosylmethionine decarboxylase was partially purified and characterized. The molecular weight was estimated to be 220,000. The apparent Km-value for adenosylmethionine was determined to be 17 microM. Methylglyoxal bis(guanylhydrazone) and berenil competitively inhibited the enzyme activity; the apparent Ki-values were found to be 0.24 microM and 0.11 microM, respectively. The dependence of filarial worms on uptake and interconversion of putrescine and polyamines as well as properties of the S-adenosylmethionine decarboxylase, different from the host enzyme, points to the polyamine metabolisms as a useful target for chemotherapy.


EAU guidelines on prostate cancer.
The first summary of the European Association of Urology (EAU) guidelines on prostate cancer was published in 2001. These guidelines have been continuously updated since many important changes affecting the clinical management of patients with prostate cancer have occurred over the past years. The aim of this paper is to present a summary of the 2005 update of the EAU guidelines on prostate cancer. A literature review of the new data has been performed by the working panel. The guidelines have been updated and level of evidence/grade of recommendation added to the text. This enables readers to better understand the quality of the data forming the basis of the recommendations. A full version is available at the EAU Office or at . Systemic prostate biopsies under ultrasound guidance is the preferred diagnostic method and the use of periprostatic injection of a local anaesthetic can significantly reduce pain/discomfort associated with the procedure. Active treatment (surgery or radiation) is mostly recommended for patients with localized disease and a long life expectancy with radical prostatectomy being the only treatment evaluated in a randomized controlled trial. Follow-up is at large based on prostate specific antigen (PSA) and a disease-specific history with imaging only indicated when symptoms occur. Cytotoxic therapy has become an option for selected patients with hormone refractory prostate cancer. The knowledge in the field of prostate cancer is rapidly changing. These EAU guidelines on prostate cancer summarize the most recent findings and put them into clinical practice.


[Current views on the role of disorders of hormonal regulation in the development of altered sensitivity and reactivity of the bronchi].
Altered bronchial sensitivity and reactivity are the basis of different variations of bronchospasm. In addition to exogenous agents, endogenous regulation factors such as adrenal and ovarian hormones are believed to make an important contribution to their development. Asthmatics showed the lowest sensitivity and the highest hyperreactivity to acetylcholine as compared to patients with preasthmatic conditions or chronic bronchitis and healthy consanguins of asthmatic patients. Disturbances of glucocorticoid homeostasis, related to various (adrenal, extra-adrenal (transcortin) and cellular) mechanisms of corticosteroid insufficiency, occurred in the majority of asthmatics and asthmatic bronchitis patients. Identification of various mechanisms of glucocorticoid insufficiency opens up actual approaches to increasing the efficiency of an individual therapy.


Characterization and molecular docking study of cathepsin L inhibitory peptides (SnuCalCpIs) from Calotropis procera R. Br.
Propeptides, released from the autocatalytic activation of its zymogen, are potential inhibitors against proteases involved in cancer cell invasion and migration. Our research team previously obtained novel propeptides (SnuCalCpIs) from transcriptome analysis of the medicinal plant Calotropis procera R. Br. and reported them as promising candidates for cancer therapeutics due to their cathepsin L inhibition activity. In the present study, inhibitory activity among SnuCalCpIs was compared with inhibition efficiency and verified by in silico molecular docking analysis. Only SnuCalCpI03 and SnuCalCpI15, expressed in Escherichia coli, showed inhibitory activity against cathepsin L as competitive inhibitors, and the half-maximal inhibitory concentrations (IC50) values of 2.1 nM and 1.6 nM, respectively. They were stable below 70 °C, maintaining more than 90% inhibitory activity over a wide range of pH (2.0-10.0), except at the isoelectric point (pI). The template-based docking simulation models showed that SnuCalCpI02, SnuCalCpI12, and SnuCalCpI16 could not interact with the substrate-binding cleft of cathepsin L even though they possessed the same conserved domain. In contrast, SnuCalCpI03 and SnuCalCpI15 interacted with cathepsin L along the propeptide binding loop and substrate-binding cleft, resulting in obstruction of substrate access to the active site.


Risk factors for diabetic retinopathy in a South Indian Type 2 diabetic population--the Chennai Urban Rural Epidemiology Study (CURES) Eye Study 4.
To determine risk factors for diabetic retinopathy (DR) in an urban South Indian Type 2 diabetic population. The Chennai Urban Rural Epidemiology Study is a large cross-sectional study conducted in Chennai, South India. A total of 1736 Type 2 diabetic subjects were recruited for this study, which included 1382 known diabetic subjects (90.4% response rate) and 354 randomly selected, newly detected diabetic subjects diagnosed by oral glucose tolerance test. All subjects underwent four-field stereo retinal colour photography, graded by the Early Treatment Diabetic Retinopathy Study protocol. Of the 1736 Type 2 diabetic subjects photographed, photographs could be graded in 1715 subjects. Stepwise ordinal logistic regression analysis revealed that male gender (P = 0.041), duration of diabetes (P < 0.0001), glycated haemoglobin (HbA(1c); P < 0.0001), macroalbuminuria (P = 0.0002) and insulin therapy (P = 0.0001) were significantly associated with severity of DR. The risk for developing DR was 7.7 times (95% confidence interval 4.71-12.48, P < 0.0001) for elevated postprandial plasma glucose levels compared with 4.2 times (95% confidence interval 2.78-6.34, P < 0.0001) for elevated fasting plasma glucose when the fourth quartile values were compared with the first quartile glucose values. In South Indian Type 2 diabetic subjects, duration of diabetes, HbA1c, male gender, macroalbuminuria and insulin therapy were independent risk factors for severity of DR. Postprandial hyperglycaemia indicated a higher risk for DR compared with elevated fasting plasma glucose levels.


Severe bone alterations under beta2 agonist treatments: bone mass, microarchitecture and strength analyses in female rats.
Beta2 adrenergic agonists are widely used in therapeutics and as doping agents by athletes. However, their effects on bone tissue, especially bone microarchitecture, remain poorly understood. Using three-dimensional (3D) microtomography, dual-energy X-ray absorptiometry, biomechanical testing and enzyme-linked immunosorbent assay, we evaluated the effects of two beta2 agonists, clenbuterol and salbutamol, on bone in growing rats. Twelve-week-old Wistar female rats (N = 39), divided in 3 groups, received during 6 weeks either salbutamol (4 mg/kg/day), clenbuterol (2 mg/kg/day) or normal saline (0.5 ml/kg/day) by subcutaneous injections. After 6 weeks, the salbutamol and clenbuterol groups displayed lower bone mineral content (BMC), femoral length and cortical width than controls. Clenbuterol treatment further reduced bone mineral density. Bone microarchitecture was clearly altered by clenbuterol, as evidenced by lower trabecular number (-40.40%; P < 0.001), connectivity and trabecular bone volume (-42.85%; P < 0.001), leading to lower ultimate force. Clenbuterol significantly increased muscle mass (P < 0.01) and reduced fat mass when compared to controls. Salbutamol did not seem to have any effect on bone microarchitecture or body composition. Both beta2 agonists increased the bone resorption marker (C-terminal collagen crosslinks) without any change of a bone formation marker. At the end of the treatment, a drop in leptin was seen in the clenbuterol group only. Leptin levels were correlated with BMC (r = 0.69, P = 0.003). These results confirm the deleterious effect of beta2 agonists on bone mass and show the negative effects of clenbuterol on trabecular bone microarchitecture. Bone loss occurred independently from muscle mass but was related to fat mass. A leptin-mediated effect on bone tissue seems likely. These pathophysiological effects may have important consequences in human therapeutics and doping.


Detection of alcoholism among psychiatric inpatients.
One hundred and eighty four consecutive admissions to male psychiatric open and closed wards were examined for evidence of alcoholism. Michigan Alcoholism Screening Test (MAST) was used for this purpose. The present study shows a prevalence rate of alcohol users to be 41.3 per cent. Nineteen percent could be called alcoholic. MAST correlated well with Spitzer's RDG criteria for alcoholism. The family history of non-users was significantly different from that of the alcohol users. The findings are discussed in the light of existing literature both in India and in the West.


Laparoscopic Radical Hysterectomy After Concomitant Chemoradiation in Locally Advanced Cervical Cancer: A Prospective Phase II Study.
To assess the feasibility of laparoscopic radical surgery in patients with locally advanced cervical cancer (LACC) who receive chemoradiation therapy (CT/RT). Prospective phase II study (Canadian Task Force classification II-1). Patients with LACC (FIGO stage IB2-III) were evaluated for accrual at the Gynecologic Oncology Unit of Catholic University, Rome/Campobasso. Neoadjuvant CT/RT included whole-pelvic irradiation (total dose, 45.0-50.4 Gy) combined with cisplatin and 5-fluorouracil. Objective response to treatment was evaluated according to Response Evaluation Criteria in Solid Tumors criteria. Laparoscopic radical hysterectomy (RH) plus pelvic and/or aortic lymphadenectomy was attempted within 6 to 8 weeks after CT/RT. The feasibility of laparoscopic RH, as well as the rate, pattern, and severity of early and late postoperative complications, were analyzed. Between January 2010 and October 2013, a total of 58 patients were enrolled into the study. After CT/RT, 23 patients (39.6%) underwent type B2 RH, 31 (53.4%) underwent type C1 RH, and 4 (6.9%) underwent type C2 RH. Pelvic lymphadenectomy was performed in all cases. Laparoscopic RH was feasible in 55 of 58 cases (feasibility rate, 94.8%). No intraoperative complications were recorded. During the observation period (median, 22 months; range, 5-50 months), there were 28 complications, of which only 21.4% were grade 2 complications and 14.3% were grade 3 complications. As of January 2015, disease recurrence was documented in 4 cases (6.9%). Total laparoscopic radical surgery is feasible in patients with LACC receiving preoperative CT/RT, providing perioperative outcomes comparable to those registered in early-stage disease.


Genotypic and phenotypic characterization of Brazilian patients with GM1 gangliosidosis.
GM1 gangliosidosis is a lysosomal disorder caused by β-galactosidase deficiency due to mutations in the GLB1 gene. It is a rare neurodegenerative disorder with an incidence of about 1:100,000-1:200,000 live births worldwide. Here we review GLB1 mutations and clinical features from 65 Brazilian GM1 gangliosidosis patients. Molecular analysis showed 17 different mutations and c.1622-1627insG was the most frequent, accounting for 50% of the alleles. Cognitive impairment was the main clinical sign, observed in 82% of patients, followed by hepatosplenomegaly observed in 56% of patients. It was possible to establish a significant correlation between age at onset of symptoms preceding the first year of life and the presence of the mutation c.1622-1627insG (p=0.03). Overall our findings differ from literature and represent the exclusive genotypic profile found in Brazilian GM1 gangliosidosis patients.


Instrumentation Across the Cervicothoracic Junction Does Not Improve Patient-reported Outcomes in Multilevel Posterior Cervical Decompression and Fusion.
This was a retrospective cohort. The objective of this study was to determine if instrumentation across the cervicothoracic junction (CTJ) in elective multilevel posterior cervical decompression and fusion (PCF) is associated with improved patient-reported outcome measures (PROMs). Fusion across the CTJ may result in lower revision rates at the expense of prolonged operative duration. However, it is unclear whether constructs crossing the CTJ affect PROMs. Standard Query Language (SQL) identified patients with PROMs who underwent elective multilevel PCF (≥3 levels) at our institution. Patients were grouped based on anatomic construct: crossing the CTJ (crossed) versus not crossing the CTJ (noncrossed). Subgroup analysis compared constructs stopping at C7 or T1. Independent t tests and χ 2 tests were utilized for continuous and categorical data, respectively. Regression analysis controlled for baseline demographics. The α was set at 0.05. Of the 160 patients included, the crossed group (92, 57.5%) had significantly more levels fused (5.27 vs. 3.71, P <0.001), longer operative duration (196 vs. 161 min, P =0.003), greater estimated blood loss (242 vs. 160 mL, P =0.021), and a decreased revision rate (1.09% vs. 10.3%, P =0.011). Neither crossing the CTJ (vs. noncrossed) nor constructs spanning C3-T1 (vs. C3-C7) were independent predictors of ∆PROMs (change in preoperative minus postoperative patient-reported outcomes) on regression analysis. However, C3-C7 constructs had a greater revision rate than C3-T1 constructs (15.6% vs. 1.96%, P =0.030). Crossing the CTJ in patients undergoing elective multilevel PCF was not an independent predictor of improvement in PROMs at 1 year, but they experienced lower revision rates. Level III.


[Historic account of infirmary at the Instituto Nacional de Cardiología "Ignacio Chávez"].
The historical process of the infirmary has had great evolution in Mexico its beginnings, in the professional order, have taken to a great height to the National Institute of Cardiology; in the year of 1944, the Dr. Ignacio Chávez had great vision and assertivity when considering to religious nurses to direct different services to it; they have been and are at the moment an essential piece to continue the evolution of infirmary in the National Institute of Cardiology. It is possible to mention that the historical way of the infirmary must to the effort of the group of nuns who have known to guide and to lead to the team of nurses of the Institute, promoting at any moment the quality of attention provided to the patients with cardiovascular affections.


Changes in Density of Peripapillary and Intrapapillary Capillaries on OCT Angiography in Acute Retinal Necrosis Treated by Pharmacotherapy Alone without Surgery.
To analyze radial peripapillary capillaris (RPC) and intra-papillary capillaris (IPC) using optical coherence tomography angiography (OCTA) in acute retinal necrosis (ARN) with good outcome. RPC and IPC were analyzed by OCTA in patients diagnosed with ARN and treated with pharmacotherapy alone without surgery at the Tokyo Medical University Hospital. A total of 13 patients were studied. Ophthalmoscopic examination showed no abnormality in the optic disc in 12 of the 13 patients. However, OCTA findings of the affected eye compared with the unaffected fellow eye revealed morphological abnormalities in RPC in nine cases (69%) and decrease in capillary network in RPC or IPC in eight cases (62%). In ARN, RPC and IPC were impaired even in eyes that were healed with medical treatment only without requiring surgical intervention and had no abnormal findings on ophthalmoscopic examination. This result suggests the presence of some degrees of optic neuropathy even in mild cases with good visual prognosis.


Epidemiology of Hepatitis B Virus Infection in China: Current Status and Challenges.
The prevalence of hepatitis B is high in China. Based on the National Disease Supervision Information Management System of China, the mean reported incidence of hepatitis B was 84.3 per 100,000 in China between 2005 and 2010. There are differences in population distribution based on region and ethnic group. Here, risk factors, virological characteristics, and prophylaxis of hepatitis B in China are reviewed. Although the prevalence of HBV infection is gradually declining, there are many challenges in HBV infection control, including higher prevalence in floating population, poor compliance of antiviral therapy, and high disease burden.


Evaluation of Toxoplasma gondii B1 gene in Placental Tissues of Pregnant Women with Acute Toxoplasmosis.
One of the consequences of toxoplasmosis is the risk of passing it from mother to fetus and the onset of congenital toxoplasmosis during pregnancy. The purpose of this study was to evaluate the B1 gene of Toxoplasma gondii in the placental tissues of pregnant women with acute toxoplasmosis. The study was a cross-sectional study. Serum samples of pregnant women who attended to Fatemieh Hospital of Hamadan University of Medical Sciences were tested for immunoglobulin G (IgG) antibodies against T. gondii by enzyme-linked immunosorbent assay. Then, polymerase chain reaction was used to identify the specific B1 gene of T. gondii in IgG seropositive women. The placental tissues of the pregnant women with positive serum B1 gene examined for this gene. Anti-Toxoplasma immunoglobulin M (IgM) was performed on the umbilical cord and neonate blood. Anti-Toxoplasma IgG was detected in 167 out of 653 (25.6%) pregnant women. T. gondii B1 gene was identified in 36 out of 167 (21.6%) of IgG seropositive women. After delivery, the B1 gene was evaluated in 15 out of 36 (41.7%) patients' placental tissues, 13 of which were positive for this gene (86.7%). Anti-Toxoplasma IgM was detected neither in any umbilical cord nor in neonatal blood samples. All newborns, with the exception of one case, were born with normal birth weight and in term birth. The B1 gene was detected in 86.7% of the placental tissue of women who were involved in acute toxoplasmosis during pregnancy.


A study of immunological responses of sheep clinically-affected with paratuberculosis (Johne's disease). The relationship of blood, mesenteric lymph node and intestinal lymphocyte responses to gross and microscopic pathology.
Nineteen adult sheep diagnosed as having clinical paratuberculosis (Johne's disease) and 16 unaffected controls were examined in this study. Animals were tested for the presence of circulating antibodies of Mycobacterium avium ssp. paratuberculosis (M. a. paratuberculosis) and lymphocytes derived from the blood, mesenteric lymph nodes and intestines were examined for cell-mediated immune (CMI) responses to Johnin pure protein derivative (Johnin-PPD: J-PPD). Bacteriological examinations were carried out on faeces and tissues and any mycobacterial isolates identified as M. a. paratuberculosis (IS900+) or M. avium ssp. silvaticum (M. a. silvaticum) (IS901+) by polymerase chain reaction (PCR). Full necropsy and histopathological studies were performed and diseased animals were categorised on the basis of having a lepromatous or tuberculoid form of intestinal pathology. Unaffected control sheep were generally antibody-negative and demonstrated varying CMI responses to J-PPD. Clinically-affected animals were almost always antibody-positive with variable CMI responses. A correlation was observed between the histological lesion type in the intestine and the cellular immune response. Tuberculoid-type lesions were associated with strong CMI responses in lymphocytes derived from the peripheral blood, mesenteric lymph node and intestine, whereas lepromatous-type lesions were associated with weak CMI responses in all tissues examined.


Whole-cell catalyze L-dopa to dopamine via co-expression of transport protein AroP in Escherichia coli.
Dopamine is high-value compound of pharmaceutical interest, but its industrial scale production mostly focuses on chemical synthesis, possessing environment pollution. Bio-manufacturing has caused much attention for its environmental characteristic. Resting cells were employed to as biocatalysts with extraordinary advantages like offering stable surroundings, the inherent presence of expensive cofactors. In this study, whole-cell bioconversion was employed to convert dopa to dopamine. To increase the titer and yield of dopamine production through whole-cell catalysis, three kinds of aromatic amino acid transport protein, AroP, PheP and TyrP, were selected to be co-expressed. The effects of the concentration of L-dopa, pyridoxal-5'- phosphate (PLP), reaction temperature and pH were characterized for improvement of bioconversion. Under optimal conditions, dopamine titer reached 1.44 g/L with molar yield of 46.3%, which is 6.62 times than that of initial conditions. The catalysis productivity of recombinant E. coli co-expressed L-dopa decarboxylase(DDC) and AroP was further enhanced by repeated cell recycling, which maintained over 50% of its initial ability with eight consecutive catalyses. This study was the first to successfully bioconversion of dopamine by whole-cell catalysis. This research provided reference for whole-cell catalysis which is hindered by cell membrane.


True aneurysm originating from the costocervical trunk: surgical excision for recurrence after successful proximal coil embolization.
A rare, true aneurysm of a branch of the right subclavian artery is described. Transcatheter coil embolization of the feeder artery was successful in obliterating blood flow into the aneurysm and the mass reduced in size. However, the aneurysm reenlarged over the next week of follow-up due to development and enlargement of the collateral vascular network. Extirpation of the aneurysm was performed. Histopathological examination revealed a true aneurysm.


Somatic unmyelinated fibre degeneration in rabbits with granulomatous hypersensitivity produced by a non-myelin antigen in sensory peripheral nerve.
Rabbits previously sensitised by injection of human sensory peripheral nerve showed degeneration of somatic unmyelinated fibres at skin test sites when challenged by sensory nerve or certain non-myelin fractions prepared from human sensory nerve. Epithelioid cells were found in the endoneurium and may mediate the nerve damage. The degeneration was consistently found and lasted for at least 58 days. Phagocytosing macrophages were absent. Differences in the pattern of nerve damage to that of EAN and EAE are discussed.


Testing for haplotype concordance with incomplete parental data--modified Q and correction for modified N.
Some errors have been found in the distribution of modified N in a paper by Green & Grennan (1991). These have now been corrected, also a modified form of a new test--criterion Q is presented. Both are applied to data.


Commiphora myrrh: a phytochemical and pharmacological update.
Medicinal plants have a long track record of use in history, and one of them is Commiphora myrrh which is commonly found in the southern part of Arabia, the northeastern part of Africa, in Somalia, and Kenya. Relevant literatures were accessed via Google Scholar, PubMed, Scopus, and Web of Science to give updated information on the phytochemical constituents and pharmacological action of Commiphora myrrh. It has been used traditionally for treating wounds, mouth ulcers, aches, fractures, stomach disorders, microbial infections, and inflammatory diseases. It is used as an antiseptic, astringent, anthelmintic, carminative, emmenagogue, and as an expectorant. Phytochemical studies have shown that it contains terpenoids (monoterpenoids, sesquiterpenoids, and volatile/essential oil), diterpenoids, triterpenoids, and steroids. Its essential oil has applications in cosmetics, aromatherapy, and perfumery. Research has shown that it exerts various biological activities such as anti-inflammatory, antioxidant, anti-microbial, neuroprotective, anti-diabetic, anti-cancer, analgesic, anti-parasitic, and recently, it was found to work against respiratory infections like COVID-19. With the advancement in drug development, hopefully, its rich phytochemical components can be explored for drug development as an insecticide due to its great anti-parasitic activity. Also, its interactions with drugs can be fully elucidated.This review highlights an updated information on the history, distribution, traditional uses, phytochemical components, pharmacology, and various biological activities of Commiphora myrrh. Graphical summary of the phytochemical and pharmacological update of Commiphora myrrh.


Broadening our understanding of clinical quality: from attribution error to situated cognition.
The tendency to overestimate the influence of personal characteristics on outcomes, and to underestimate the influence of situational factors, is known as the fundamental attribution error. We argue that medical-education researchers and policy makers may be guilty of this error in their quest to understand clinical quality. We suggest that to truly understand clinical quality, they must examine situational factors, which often have a strong influence on the quality of clinical encounters.


[Arterial hypertension caused by low renin: comparison of the calcium antagonist nifedipine and the ACE-inhibitor enalapril as to antihypertensive efficacy].
The aim of this study was to compare the clinical effects of calcium-entry blocker Nifedipine and ACE-inhibitor Enalapril in hypertensive patients with glucose intolerance that have lower plasma renin activity. A blood sample for basal PRA was obtained from 21 subjects; then, 11 patients received Nifedipine (20 mg. b.i.d.) and 10 Enalapril (20 mg. q.d.). The extent of blood pressure fall after 12 weeks of treatment was inversely related to basal PRA levels in Nifedipine treated group only; however, the hypotensive effect of both drugs was comparable.


Periosteal chondroma of the cervical spine: one more cause of neural foramen enlargement.
A case of cervical periosteal chondroma presenting with an enlarged neural foramen is described. Review of the literature showed that cervical chondromas are rare but that their characteristic clinical and computed tomographic findings aid in their diagnosis. The computed tomographic findings of two previously reported cases of cervical periosteal chondroma resembled those of the present case. On computed tomographic scanning, an iso-or high-density mass containing stippled calcifications and originating in a posterior cervical neural arch was observed in all three cases. Extensive spinal canal and extradural involvement was observed in five of the seven reported cases, including the one reported here.


A retrospective study on the prognosis of aged patients with epilepsy.
A retrospective follow-up study on the prognosis of 90 patients with epilepsy above 40 years of age has resulted in: 1. In the aged patients, the duration of epilepsy (mean: 23 years) was longer than the period of treatment they underwent (mean: 14 years). The delayed commencement and/or interrupted medication along with the patients' incompliance of taking drugs accounted for the main reasons for at least 70% of the patients. 2. The partial epilepsy (80%) especially with complex symptomatology (55%) were predominating in the aged group. And also, that the tonic-clonic seizures were liable to convert to the complex partial seizures in their thirties and forties, was found in this study. 3. Although almost all the patients (97%) had more or less clinical attacks even at the time of survey, 75% or more decrease in seizure frequency have been exerted for one and a half year, regardless of the seizure types in the majority of the patients (81%). This seems to offer an explanation that an appropriate sociomedical strategy is necessitated for patients with long-standing epilepsies.


Association of body mass index and prognosis in patients with HFpEF: A dose-response meta-analysis.
Although agreements regarding the negative effects of obesity on the development of heart failure with preserved ejection fraction (HFpEF) have been reached, the relationship between body mass index (BMI) and adverse outcomes in HFpEF patients are still debatable. Therefore, we conducted the dose-response meta-analysis to investigate this relationship. We searched the PubMed and Embase databases up to February 2022 for studies that evaluated the association between BMI and prognostic outcomes in patients with HFpEF. A cubic spline random-effects model was used to fit the potential dose-response curve. The effect estimates were expressed as adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 11 studies involving 69,273 patients with HFpEF were included. The summary HR for all-cause mortality was 0.90 (95% CI, 0.84-0.95) per 5 units increase in BMI, but the association was U-shaped (Pnonlinear < 0.01) with the nadir of risk at a BMI of 32-34 kg/m2. The summary HR for HF hospitalization was 1.12 (95% CI, 1.05-1.19) with a significant positive linear association (Pnonlinear = 0.54). For patients with HFpEF, there was a positive linear association of BMI with HF hospitalization, while a U-shaped relationship between BMI and all-cause mortality was observed with the lowest event rate at a BMI of 32-34 kg/m2.


Parental Restriction of Mature-rated Media and Its Association With Substance Use Among Argentinean Adolescents.
To assess the independent relation between parental restrictions on mature-rated media (M-RM) and substance use among South American adolescents. Cross-sectional school-based youth survey of 3,172 students (mean age, 12.8 years; 57.6% boys) in 3 large Argentinean cities. The anonymous survey queried tobacco, alcohol, and drug use using items adapted from global youth surveys. Adolescents reported M-RM restriction for internet and video game use, television programming, and movies rated for adults. Multivariate logistic regression models were used to assess the association between parental M-RM restriction and substance use after adjustment for hourly media use, measures of authoritative parenting style, sociodemographic characteristics, and sensation-seeking. Substance use rates were 10% for current smoking, 32% for current drinking alcohol, 17% for past 30-day binge drinking, and 8% for illicit drug use (marijuana or cocaine). Half of the respondents reported parental M-RM restriction (internet 52%, TV 43%, adult movies 34%, video game 25%). Parental M-RM restriction was only modestly correlated with authoritative parenting measures. In multivariate analyses M-RM restriction on all 4 venues was strongly protective for all substance use outcomes. Compared with no restriction, odds ratios for substance use for full restrictions were 0.32 (0.18-0.59), 0.53 (0.38-0.07), 0.36 (0.22-0.59), and 0.49 (0.26-0.92) for current smoking, drinking, binge drinking, and illicit drug use, respectively. The most important single M-RM venue was movies. Results of this study confirmed the protective association between parental M-RM restriction during adolescence and multiple substance use outcomes, including illicit drugs. M-RM restriction is independent of traditional parenting measures. The preponderance of the evidence supports intervention development.


The rhetoric and realities of integrating air quality into the local transport planning process in English local authorities.
Regardless of its intent and purposes, the first decade of the Local Air Quality Management (LAQM) framework had little or no effect in reducing traffic-related air pollution in the UK. Apart from the impact of increased traffic volumes, the major factor attributed to this failure is that of policy disconnect between the process of diagnosing air pollution and its management, thereby limiting the capability of local authorities to control traffic-related sources of air pollution. Integrating air quality management into the Local Transport Plan (LTP) process therefore presents opportunities for enabling political will, funding and joined-up policy approach to reduce this limitation. However, despite the increased access to resources for air quality measures within the LTP process, there are local institutional, political and funding constraints which reduce the impact of these policy interventions on air quality management. This paper illustrate the policy implementation gaps between central government policy intentions and the local government process by providing evidence of the deprioritisation of air quality management compared to the other shared priorities in the LTP process. We draw conclusions on the policy and practice of integrating air quality management into transport planning. The evidence thereby indicate the need for a policy shift from a solely localised hotspot management approach, in which the LAQM framework operates, to a more holistic management of vehicular emissions within wider spatial administrative areas.


Platelet aggregation occurs in congenital afibrinogenaemia despite the absence of fibrinogen or its fragments in plasma and platelets, as demonstrated by immunoenzymology.
Platelet aggregation of an afibrinogenaemic patient's platelet rich plasma (PRP) was greatly decreased when ADP was used for stimulation. In the presence of collagen or arachidonic acid the changes in light transmission recorded during platelet aggregation of patient's PRP were similar to those observed with normal PRP but the size of aggregates appeared to be smaller in comparison with those observed with normal platelets. In addition, thrombin-induced aggregation of washed platelets was similar to normal platelets. The interpretation was made possible because the fibrinogen level in plasma and in platelets was found to be almost nil as demonstrated by both an Elisa procedure described here and the determination of fibrinopeptide A (fpA). Furthermore, fibrinogen fragments, which could result from abnormal synthesis and therefore replace fibrinogen in platelet aggregation, were undetectable by immunological analysis using specific antibodies against A alpha, B beta and gamma chains and 10 different monoclonal antibodies against fibrin degradation products.


Role of tumor necrosis factor in Listeria resistance of nude mice.
The effects of sheep anti-murine recombinant tumor necrosis factor-alpha (TNF-alpha) on resistance to Listeria monocytogenes infection were studied in T cell-deficient nu/nu mice. The sheep anti-TNF-alpha antibody preparation was specific for TNF since it neutralized 300 U of recombinant murine TNF-alpha in vitro at a dilution of up to 1/1,000 but did not neutralize 32 U of interferon (IFN)-alpha, -beta or 32 U of IFN-gamma in vitro at a 1/20 dilution. When tested in vivo in sublethally Listeria-infected nu/nu or T cell-competent C57BL/6 or ICR mice, a single treatment of 0.2 ml anti-TNF-alpha given intraperitoneally on either day -1,0 or +1 resulted in the death of mice by day 5-7 due to the uncontrolled growth of Listeria; bacterial counts in spleen and liver were increased on days 3-5 by a factor of 10-1,000 in these organs. When examined histologically, organs from mice with the anti-TNF-alpha treatment contained more, and considerably bigger, lesions that exhibited central necrosis. The enhancing effect of anti-TNF-alpha on Listeria infection seemed greater early during Listeria infection on days 1-6 when compared to later phases of the infection around days 6-10. From the data presented we conclude that in addition to other lymphokines, such as IFN-gamma, TNF-alpha is of importance during the entire course of a Listeria infection in nu/nu mice.


Routine screening for placenta accreta spectrum.
Screening for clinically significant placenta accreta spectrum (PAS) is possible with a high degree of accuracy (both sensitivity and specificity >90-95%). The group of women to focus on are those with placenta previa and one or more prior Cesarean deliveries. Screening for PAS not associated with placenta previa is not as productive, and several false negatives have been described. The results of the screening program indicate that women have a low or high probability of PAS. Screen-positive women or those with uncertain ultrasound features should be referred to a center of excellence. Those confirmed to have a high probability of PAS should electively be delivered at such centers.


Oral erythema multiforme: trends and clinical findings of a large retrospective European case series.
Erythema multiforme (EM) continues to be an underestimated disease with a lack of strict classification and diagnostic criteria. We present the analysis of a case series of 60 oral EM patients from 2 centers and illustrate the range of oral clinical presentations. Clinical data from 60 EM patients with oral involvement, diagnosed and treated between 1982 and 2014, were retrospectively collected from the archives of 2 independent hospitals. Statistical analyses of the data were performed using the Pearson χ-squared test and the Mann-Whitney U test. Thirty-one patients (51.7%) were male and 29 (48.3%) were female, with a mean (±SD) age of 37.9 years (±18.1). The frequency of previous occurrences ranged from 0 to 10 (mean ± SD: 1.4 ± 2.0). Twenty-nine patients (48%) had no previous occurrence. Medications (particularly antipyretics, food additives, and antibiotics) were the suspected precipitants in 28 patients (46.7%), whereas herpes simplex virus infection was suspected in 18 (30.0%). All but 1 patient had involvement of multiple oral sites, with the buccal mucosa being the most commonly involved oral site (75%), followed by the vermillion border (71.7%). Patients with EM may present initially to oral health care workers. Medications and herpes simplex virus continue to be the most typically involved precipitating factors. Our data highlight the additional role of food-derived antigens. Although laboratory tests can provide support diagnostically, EM diagnosis continues to be based on clinical features. A medication and food diary should be encouraged particularly in patients with recurrent forms.


Is cardiorespiratory failure induced by bacterial toxins the cause of sudden infant death syndrome? Studies with an animal model (the rabbit).
Recent studies have implicated various toxigenic bacteria and their toxins in the aetiology of sudden infant death syndrome (SIDS). Therefore the effect of six bacterial toxins on the cardiorespiratory system of the rabbit was studied as a model for SIDS. The toxins' effect on the heart rate, arterial blood pressure, and breathing of anaesthetized rabbits was determined and their action compared to that of endotoxin. Intravenous injection of Clostridium perfringens enterotoxin and alpha-toxin, Staphylococcus enterotoxin B, Escherichia coli heat-stable toxin (STa), Clostridium difficile toxin A and B reduced heart rate, blood pressure, respiration and increased, slowed and prolonged thorax expansion, and at higher concentrations caused sudden death without visible stress or trauma. A combination of a low concentration of enterotoxins caused a greater reduction of these activities and sudden death. These effects were generally similar to those produced by endotoxin. In non-anaesthetized rabbits, the toxins slowed metabolism until death occurred without agitation, spasms, visible distress or prolonged illness. Intestinal production of these toxins by toxigenic strains, when conditions are suitable, and their systemic absorption, could therefore cause SIDS by an endotoxin-like shock mechanism.


Meta-Analysis of the Reduction of Norovirus and Male-Specific Coliphage Concentrations in Wastewater Treatment Plants.
Human norovirus (NoV) is the leading cause of foodborne illness in the United States and Canada. Wastewater treatment plant (WWTP) effluents impacting bivalve mollusk-growing areas are potential sources of NoV contamination. We have developed a meta-analysis that evaluates WWTP influent concentrations and log10 reductions of NoV genotype I (NoV GI; in numbers of genome copies per liter [gc/liter]), NoV genotype II (NoV GII; in gc/liter), and male-specific coliphage (MSC; in number of PFU per liter), a proposed viral surrogate for NoV. The meta-analysis included relevant data (2,943 measurements) reported in the scientific literature through September 2013 and previously unpublished surveillance data from the United States and Canada. Model results indicated that the mean WWTP influent concentration of NoV GII (3.9 log10 gc/liter; 95% credible interval [CI], 3.5, 4.3 log10 gc/liter) is larger than the value for NoV GI (1.5 log10 gc/liter; 95% CI, 0.4, 2.4 log10 gc/liter), with large variations occurring from one WWTP to another. For WWTPs with mechanical systems and chlorine disinfection, mean log10 reductions were -2.4 log10 gc/liter (95% CI, -3.9, -1.1 log10 gc/liter) for NoV GI, -2.7 log10 gc/liter (95% CI, -3.6, -1.9 log10 gc/liter) for NoV GII, and -2.9 log10 PFU per liter (95% CI, -3.4, -2.4 log10 PFU per liter) for MSCs. Comparable values for WWTPs with lagoon systems and chlorine disinfection were -1.4 log10 gc/liter (95% CI, -3.3, 0.5 log10 gc/liter) for NoV GI, -1.7 log10 gc/liter (95% CI, -3.1, -0.3 log10 gc/liter) for NoV GII, and -3.6 log10 PFU per liter (95% CI, -4.8, -2.4 PFU per liter) for MSCs. Within WWTPs, correlations exist between mean NoV GI and NoV GII influent concentrations and between the mean log10 reduction in NoV GII and the mean log10 reduction in MSCs.


Diffraction anisotropy and paired refinement: crystal structure of H33, a protein binder to interleukin 10.
Binder H33 is a small protein binder engineered by ribosome display to bind human interleukin 10. Crystals of binder H33 display severe diffraction anisotropy. A set of data files with correction for diffraction anisotropy based on different local signal-to-noise ratios was prepared. Paired refinement was used to find the optimal anisotropic high-resolution diffraction limit of the data: 3.13-2.47 Å. The structure of binder H33 belongs to the 2% of crystal structures with the highest solvent content in the Protein Data Bank.


Growth hormone treatment does not alter lower limb asymmetry in children with Russell-Silver syndrome.
Growth hormone (GH) treatment has been proven to have a beneficial effect on growth in children with Russell-Silver syndrome (RSS). We describe 7 prepubertal children with RSS and lower limb asymmetry treated with GH for 3 years. There was a significant increase in height without any significant change in the asymmetry. We conclude that the rapid growth acceleration to GH treatment does not alter the lower limb asymmetry in children with RSS.


Advanced Imaging of the Equine Eye.
This article reviews the literature for studies describing advanced imaging of the equine eye as a reference for practitioners to help in the selection of image modalities, describe how to use the instruments, and help interpret the image findings. Indications for, technique of, and image interpretation of advanced image modalities such as ultrasound, computed tomography, MRI, optical coherence tomography, confocal microscopy, and angiography are reviewed. The article is organized anatomically, not by instrument, so that the reader will be able to quickly research ways to image specific disease entities or anatomic locations that are affecting their equine patients.


Progress in cerebrovascular disease research in the last year.
Herein, we review the main papers in cerebrovascular diseases published in the Journal of Neurology over the last year.


Removal of cadmium and arsenic from water through biomineralization.
Due to anthropogenic activities, heavy metals such as cadmium (Cd) and arsenic (As) are one of the most toxic xenobiotics contaminating water, thus affecting human health and the environment. The objective of the present investigation was to study the effect of ureolytic bacteria Bacillus paramycoides-MSR1 for the bioremediation of Cd and As from contaminated water. The B. paramycoides showed high resistance to heavy metals, Cd and As, with minimum inhibitory concentration (MIC) of 12.84 μM and 48.54 μM, respectively. The urease activity and calcium carbonate (CaCO3) precipitation were evaluated in artificial wastewater with different concentrations of Cd (0, 10, 20, 30, 40, 50, and 60 μM) and As (0, 20, 40, 60, 80, and 100 μM). The maximum urease activity in Cd-contaminated artificial wastewater was observed after 96 hours, which showed a 76.1% decline in urease activity as the metal concentration increased from 0 to 60 μM. Similarly, 14.1% decline in urease activity was observed as the concentration of As was increased from 0 to 100 μM. The calcium carbonate precipitation at the minimum inhibitory concentration of Cd and As-contaminated artificial wastewater was 189 and 183 mg/100 ml, respectively. The percentage removal of metal from artificially contaminated wastewater with varied concentrations was analyzed using atomic absorption spectroscopy (AAS). After 168 hours of incubation, 93.13% removal of Cd and 94.25% removal of As were observed. Microstructural analysis proved the presence of calcium carbonate in the form of calcite, confirming removal of cadmium and arsenic by microbially induced calcium carbonate precipitation (MICCP) to be promising technique for water decontamination.