Clinical and laboratory features of pertussis in hospitalized infants with confirmed versus probable pertussis cases.
The clinical presentations of pertussis infection have considerable variation. Many infections and illnesses can cause prolonged repetitive paroxysmal cough that could be confused with Bordetella pertussis infection. This retrospective study was designed to compare the clinico-laboratory findings between two groups of hospitalized infants with confirmed, and those who have clinical pertussis disease; to identify the possible additional diagnostic clues "for the diagnosis of confirmed pertussis disease". The study population consisted of infants ≤12 months of age with clinical diagnosis of pertussis that fulfilled the World Health Organization definition for pertussis or those diagnosed by physicians. Clinico-laboratory findings were compared between two groups of patients (confirmed vs. clinical cases). From a total of 118 infants admitted with a clinical diagnosis of pertussis, 16% (19/118) were confirmed by laboratory to have confirmed pertussis. Twelve of 19 (63%) and 71.99% of confirmed and clinical cases were younger than 6 months of age, respectively. For most patients, the duration of symptoms before hospitalization was <14 days. There were no significant differences between two groups of patients for paroxysmal cough and facial discoloration. However, whoop and apnea were more common among confirmed pertussis cases: P = 0.01, and P = 0.02, respectively. Leukocytosis (≥16,000/ml) (P = 0.01) and lymphocytosis (≥11,000) (P = 0.02) were reported significantly more frequently in confirmed pertussis cases. Given the unavailability of a highly sensitive diagnostic test, in every afebrile patient with paroxysmal cough lasting for ≥7 days associated with whoop and/or apnea, particularly if accompanied by leukocytosis/lymphocytosis, pertussis disease should be considered. In this situation, prompt administration of empiric treatment for cases, and providing control measures to prevent infection transmission to contacts are recommended.


[The significance of serum gamma-glutamyl transpeptidase (gamma-GTP) elevation caused by antiepileptic drug(s). Using the antipyrine metabolic capacity as a parameter of microsomal enzyme activity].
Of 242 patients who were given antiepileptic drugs (AEDs), 40 exhibited a high level of serum gamma-glutamyl transpeptidase (gamma-GPT). The significance of the high level was examined. "Antipyrine test" was also performed on 9 healthy controls and 39 patients with AEDs administration, and the antipyrine half-life (APt 1/2), a reliable index for hepatic microsomal enzyme activity (MEA), was calculated for each subject. A high level of serum gamma-GTP occurred more frequently in phenytoin (PHT) administered group than in PHT non-administered group. Furthermore, the maximum level was significantly higher in the former than in the latter. In 17 out of the 40 cases, the serum gamma-GTP level was decreased to a normal level without reducing AED doses or stopping the AED administration, or changing to different AEDs. On the other hand, in almost all cases with AED administration, APt 1/2 was shortened (i.e., induction of the microsomal enzyme). Furthermore, there was no correlation between serum gamma-GTP level and APt 1/2 in the cases with AED administration, indicating that the serum gamma-GTP level was not a proper index for MEA. It was also shown that phenobarbital, PHT and carbamazepine, each being used alone within the therapeutic dose, could cause almost the maximal degree of hepatic microsomal enzyme induction. Thus it is suggested that the elevation of serum gamma-GTP level due to AED does not necessarily indicate hepatocellular damages. If this is accepted, it follows that even if patients with AED administration have a high level of serum gamma-GTP, it is not necessary to reduce the AED doses, or discontinue them, or change to different AEDs.


[Acute myocardial infarct in the aged. Omissions in treatment].
The pre-hospital phase of acute myocardial infarction may be of crucial importance for the further fate of the subject. Mortality of old people seems to be twice that of middle aged persons during the pre-hospital phase of acute infarction. This may be due partially to the longer duration of latency between onset of symptoms and arrival at the hospital of older patients causing waste of time especially for resuscitation from lethal arrhythmias. The delay of therapy is promoted by difficulties in diagnosis due to lack of typical pain often veiled by other symptoms and failure of the electrocardiogram in old patients. Need of urgent hospitalization for reduction of pre-hospital mortality seems not to have been generally accepted among general practitioners. Standard management of emergency care of patients with suspected myocardial infarction is reviewed.


Biphasic pleural mesothelioma in a goat.
An 8-year-old Saanen goat doe was seen for inappetence, tachycardia, and intermittent bluish-grey discoloration of the oral mucous membranes. On physical examination, the goat was mildly tachypneic and tachycardic, with reduced sounds auscultated on the left side of the thorax. Euthanasia was elected. Necropsy revealed an infiltrative, multinodular mass within the left thoracic cavity and innumerable small, tan nodules disseminated across the pleura of the lungs, thoracic walls, and diaphragm. Upon histologic examination, the mass was composed of highly pleomorphic, fusiform to polygonal cells. Neoplastic cells exhibited positive immunoreactivity for both cytokeratin and vimentin, consistent with a diagnosis of biphasic pleural mesothelioma. Key clinical message: Mesothelioma has rarely been described in the goat but should be considered as a differential diagnosis for thoracic masses in small ruminants, along with thymoma; metastatic neoplasia; carcinomatosis; and granulomatous lesions caused by parasites, bacteria, and fungi.


A pilot project for the Japan arthroplasty register.
National arthroplasty registers are valuable tools for reporting on an updated epidemiologic survey of arthroplasties and for evaluating the performance of implants and operative procedures through the early identification of failure risk factors. More than ten registers have been launched globally, but no national register has been reported in Asia. In February 2006, a pilot project of the Japan Arthroplasty Register (JAR) for total hip arthroplasty (THA) and total knee arthroplasty/unicompartmental knee arthroplasty (TKA/UKA) was launched by the Japanese Orthopaedic Association (JOA). Data obtained include information about patients, primary and revision arthroplasty operative procedures, and implants and materials used. The JAR office accumulated and processed all data and reports annually. Up to May 2011, 83 of 130 hospitals nominated by the JOA (64 %) participated in the JAR pilot project. From 2006 to 2011, 33,080 data collection forms were submitted; 17,534 for THA and 17,269 for TKA/UKA. A brief summary of the annual report of the JAR is available from The Japanese Society for Replacement Arthroplasty web site at http://jsra.info/ . A national arthroplasty register is a useful tool for evaluating the outcomes of interventions and the materials used in arthroplasties and for providing rapid feedback to practitioners and patients about any failure of THA and TKA/UKA. As the first national arthroplasty register in Asia, the JAR will help guide the development of registers of arthroplasty characteristics specific to Asian populations.


[Immunogenetic factors in the onset of experimental tumors].
The influence of immunological and genetic factors on the appearance of experimental tumors has been studied in mice by means of bidirectional selection. We found that the incidence of lymphomas, solid tumors and chronic nephritis is greater in mice selected for low antibody response than in mice selected for high antibody response. These findings suggest that the genes that control the antibody response also regulate life-span and resistance to neoplastic and inflammatory diseases. Similarly, we are carrying out bidirectional selective breeding to obtain two lines of mice, one sensitive and one resistant to the induction of cutaneous papillomas by chemical carcinogens. The two lines differ notably in terms of both percent of incidence and tumor multiplicity. The results of this study demonstrate clearly that resistance and susceptibility to carcinogenesis are subject to polygenic control.


Results of surgery and irradiation or irradiation alone for pituitary adenomas.
A retrospective analysis was performed on the clinical course of all patients with pituitary adenomas treated at the Radiation Oncology Center, Mallinckrodt Institute of Radiology, Washington University Medical Center, St. Louis, Missouri. Of 212 patients treated from April 1954 through December 1982, 70 were treated with radiotherapy alone (XRT), 121 began immediate post-operative XRT (2-6 weeks) and 20 received XRT following surgical failure. Several sub-groups of adenomas were identified and analyzed, including secreting versus non-secreting adenomas (33.0% secreting) and by clinical syndrome; 27% with amenorrhea/galactorrhea, 18.4% acromegalic, Cushing's disease in 6.1% and 3.3% with Nelson's syndrome. The median follow-up time from the data of diagnosis for those patients alive at the time of last follow-up was 11.9 years (range 3.0 to 30.0 years). Actuarial overall and disease-free survival was analyzed up to 25 years. The 10-year overall and disease-free survival was 77.8 and 75.3% for those patients treated with XRT alone, 86.4 and 87.2% for those treated with immediate post-operative XRT and 100.0 and 87.5% for those who were irradiated after surgical failure. Complications related directly to XRT occurred in only five patients. One patient had documented central nervous system radionecrosis, two had visual complications, and tumor necrosis with hemorrhage occurred in the other two patients. In conclusion, overall survival for all patients did not significantly differ from an age, sex and race matched population. Control of local disease was greater for those patients receiving surgery and post-operative XRT than for those receiving XRT only. XRT salvage of surgical failures was possible. Treatment with XRT results in a low complication rate.


New approach in paediatric dentistry: ultrasonic nondestructive evaluation of restorative dental materials. Experimental study.
The ultrasonic inspection is a non invasive method which is very developed in the industrial field, for the non-destructive evaluation of materials, and in the medical field, for the ultrasound diagnostic analysis. In paediatric dentistry the most widely used non- destructive evaluation is the X-ray technique. Radiographs are valuable aids in the oral health care of infants, children, adolescents, allowing dentists to diagnose and treat oral diseases that cannot be detected during a visual clinical examination. The aim of this in vitro study was to analyse the ultrasonic non-destructive evaluation (UT-NDE) technique to inspect both dental materials internal structure and the form and position of internal defects in order to obtain a diagnostic method, free of ionising radiations, in paediatric dentistry. Moreover the ultrasonic inspection (UT) could be a rapid method of diagnosis in uncooperative paediatric patients. Study Design: Experimental samples were manufactured with the characteristics of a large composite or glass ionomer cement paediatric dental restoration, in terms of either size or operative technique used. Characteristics of the common restorations were analysed and reproduced in vitro, using the same operative conditions, also adding operative defects into some samples. All the samples were subjected to an innovative UT test using the pulse echo immersion scanning technique. Both C-scans and full volume scans were carried out during the experimental programme. To enhance the data obtained from the UT scan, a digital system (Ecus Inspection software) for signal detection, archiving, processing and displaying was used. UT images showed the presence of internal defects in the dental materials. It was also possible to inspect very thin discontinuity such as the one represented by the fluid resin. In order to execute the statistical analysis, the values of electric voltage measured in five higher white points and in five higher grey points of the pictures pixels, were measured for each sample. Then, the average values and the standardised data were calculated. n In conclusion, the ultrasonic test could be a diagnostic non-invasive method in paediatric patients, capable to evaluate the quality of the restorative teeth filling, showing internal little defects. In vivo application of this diagnostic method should be developed.


Open Technique for In Situ Subtalar Fusion.
The subtalar joint plays an important role for the hindfoot when accommodating during gait. Joint degeneration may be caused by posttraumatic, inflammatory, and pathologic biomechanical changes. Once conservative treatment has failed, subtalar fusion should be considered. The indication for surgery is based on thorough clinical and radiographic evaluation. Several techniques for subtalar fusion are published in literature. This article aims to describe a technique for in situ arthrodesis of the subtalar joint, paying special attention to biomechanical aspects as well as preoperative clinical and radiological work-up.


A Bayesian Filtering Approach for Tracking Arousal From Binary and Continuous Skin Conductance Features.
Neuroanatomical structures within the cortical and sub-cortical brain regions process emotion and cause subsequent variations in signals such as skin conductance and electrocardiography. The signals often encode information in their continuous-valued amplitudes or waves as well as in their underlying impulsive events. We propose to track psychological arousal from this hybrid source of skin conductance information. We present a point process state-space method in tandem with Bayesian filtering for determining a continuous-valued arousal state from skin conductance measurements. To perform state estimation, we relate arousal to binary- and continuous-valued observations derived from the phasic and tonic parts of a skin conductance signal, and recover model parameters using expectation-maximization. We evaluate our model on both synthetic and two different experimental data sets. Stress was artificially induced in the first experimental data set and the second comprised of a fear conditioning experiment. Results on the first data set indicate high levels of arousal during exposure to cognitive stress and low arousal during relaxation. Plausible results are also obtained in the fear conditioning data set consistent with previous skin conductance studies in similar experimental contexts. The state-space approach-which does not rely on external classification labels-is able to continuously track an arousal level from skin conductance features. The method is a promising arousal estimation scheme utilizing only skin conductance. The approach could find applications in wearable monitoring and the study of neuropsychiatric conditions such as post-traumatic stress disorder.


Lightweight Seizure Detection Based on Multi-Scale Channel Attention.
Epilepsy is one kind of neurological disease characterized by recurring seizures. Recurrent seizures can cause ongoing negative mental and cognitive damage to the patient. Therefore, timely diagnosis and treatment of epilepsy are crucial for patients. Manual electroencephalography (EEG) signals analysis is time and energy consuming, making automatic detection using EEG signals particularly important. Many deep learning algorithms have thus been proposed to detect seizures. These methods rely on expensive and bulky hardware, which makes them unsuitable for deployment on devices with limited resources due to their high demands on computer resources. In this paper, we propose a novel lightweight neural network for seizure detection using pure convolutions, which is composed of inverted residual structure and multi-scale channel attention mechanism. Compared with other methods, our approach significantly reduces the computational complexity, making it possible to deploy on low-cost portable devices for seizures detection. We conduct experiments on the CHB-MIT dataset and achieves 98.7% accuracy, 98.3% sensitivity and 99.1% specificity with 2.68[Formula: see text]M multiply-accumulate operations (MACs) and only 88[Formula: see text]K parameters.


Delta radiomics model for the prediction of progression-free survival time in advanced non-small-cell lung cancer patients after immunotherapy.
To assess the validity of pre- and posttreatment computed tomography (CT)-based radiomics signatures and delta radiomics signatures for predicting progression-free survival (PFS) in stage III-IV non-small-cell lung cancer (NSCLC) patients after immune checkpoint inhibitor (ICI) therapy. Quantitative image features of the largest primary lung tumours were extracted on CT-enhanced imaging at baseline (time point 0, TP0) and after the 2nd-3rd immunotherapy cycles (time point 1, TP1). The critical features were selected to construct TP0, TP1 and delta radiomics signatures for the risk stratification of patient survival after ICI treatment. In addition, a prediction model integrating the clinicopathologic risk characteristics and phenotypic signature was developed for the prediction of PFS. The C-index of TP0, TP1 and delta radiomics models in the training and validation cohort were 0.64, 0.75, 0.80, and 0.61, 0.68, 0.78, respectively. The delta radiomics score exhibited good accuracy for distinguishing patients with slow and rapid progression to ICI treatment. The predictive accuracy of the combined prediction model was higher than that of the clinical prediction model in both training and validation sets (P<0.05), with a C-index of 0.83 and 0.70, respectively. Additionally, the delta radiomics model (C-index of 0.86) had a higher predictive accuracy compared to PD-L1 expression (C-index of 0.50) (P<0.0001). The combined prediction model including clinicopathologic characteristics (tumour anatomical classification and brain metastasis) and the delta radiomics signature could achieve the individualized prediction of PFS in ICIs-treated NSCLC patients.


Diagnosis and treatment of bladder cancer: how can we improve?
The majority of patients with bladder cancer will be diagnosed following an episode of hematuria. With few exceptions, these patients should be referred for a complete urologic evaluation, including a history and physical examination, flexible cystoscopy, imaging of the upper urinary tract, and optional urine cytology. Those found to have a bladder tumor should undergo transurethral resection for the combined purposes of initial staging and treatment. Delays in diagnosing invasive bladder cancer are associated with adverse outcomes. In this review, we cover the diagnosis and management of bladder cancer. In addition, we discuss ways to improve outcomes through increased public awareness, improvements in tumor detection, accurate staging, and regimented patient surveillance.


Long-term evolution of the Luteoviridae: time scale and mode of virus speciation.
Despite their importance as agents of emerging disease, the time scale and evolutionary processes that shape the appearance of new viral species are largely unknown. To address these issues, we analyzed intra- and interspecific evolutionary processes in the Luteoviridae family of plant RNA viruses. Using the coat protein gene of 12 members of the family, we determined their phylogenetic relationships, rates of nucleotide substitution, times to common ancestry, and patterns of speciation. An associated multigene analysis enabled us to infer the nature of selection pressures and the genomic distribution of recombination events. Although rates of evolutionary change and selection pressures varied among genes and species and were lower in some overlapping gene regions, all fell within the range of those seen in animal RNA viruses. Recombination breakpoints were commonly observed at gene boundaries but less so within genes. Our molecular clock analysis suggested that the origin of the currently circulating Luteoviridae species occurred within the last 4 millennia, with intraspecific genetic diversity arising within the last few hundred years. Speciation within the Luteoviridae may therefore be associated with the expansion of agricultural systems. Finally, our phylogenetic analysis suggested that viral speciation events tended to occur within the same plant host species and country of origin, as expected if speciation is largely sympatric, rather than allopatric, in nature.


Foxa2 controls vesicle docking and insulin secretion in mature Beta cells.
The winged-helix transcription factor Foxa2 regulates Pdx1 gene expression and fetal endocrine pancreas development. We show here by inducible gene ablation that Foxa2 inactivation in mature beta cells induces hyperinsulinemic hypoglycemia in Foxa2(loxP/loxP),Pdx1-CreERT2 adult mice. Mutant beta cells exhibited a markedly increased pool of docked insulin granules, some of which were engaged in sequential or compound exocytosis, consistent with increased first-phase glucose-stimulated insulin secretion. Expression of multiple genes involved in vesicular trafficking, membrane targeting, and fuel-secretion pathways is dependent on Foxa2. In addition, impaired cytosolic Ca(2+) oscillations and elevated intracellular cyclic AMP production accompanied this secretory defect and were likely contributors to the sensitization of the exocytotic machinery. Thus, in the absence of Foxa2, alterations in intracellular second-messenger signaling redistribute the insulin granules into the readily releasable pool. We conclude that Foxa2 is required for both fetal pancreas development and the function of mature beta cells.


A DESD-box helicase functions in salinity stress tolerance by improving photosynthesis and antioxidant machinery in rice (Oryza sativa L. cv. PB1).
The exact mechanism of helicase-mediated salinity tolerance is not yet understood. We have isolated a DESD-box containing cDNA from Pisum sativum (Pea) and named it as PDH45. It is a unique member of DEAD-box helicase family; containing DESD instead of DEAD/H. PDH45 overexpression driven by constitutive cauliflower mosaic virus-35S promoter in rice transgenic [Oryza sativa L. cv. Pusa Basmati 1 (PB1)] plants confers salinity tolerance by improving the photosynthesis and antioxidant machinery. The Na(+) ion concentration and oxidative stress parameters in leaves of the NaCl (0, 100 or 200 mM) treated PDH45 overexpressing T1 transgenic lines were lower as compared to wild type (WT) rice plants under similar conditions. The 200 mM NaCl significantly reduced the leaf area, plant dry mass, net photosynthetic rate (PN), stomatal conductance (gs), intercellular CO2 (Ci), chlorophyll (Chl) content in WT plants as compared to the transgenics. The T1 transgenics exhibited higher glutathione (GSH) and ascorbate (AsA) contents under salinity stress. The activities of antioxidant enzymes viz. superoxide dismutase (SOD), ascorbate peroxidase (APX), guaiacol peroxidase (GPX) and glutathione reductase (GR) were significantly higher in transgenics; suggesting the existence of an efficient antioxidant defence system to cope with salinity induced-oxidative damage. Yeast two-hybrid assay indicated that the PDH45 protein interacts with Cu/Zn SOD, adenosine-5'-phosphosulfate-kinase, cysteine proteinase and eIF(4G), thus confirming the involvement of ROS scavenging machinery in the transgenic plants to provide salt tolerance. Furthermore, the T2 transgenics were also able to grow, flower, and set viable seeds under continuous salinity stress of 200 mM NaCl. This study provides insights into the mechanism of PDH45 mediated salinity stress tolerance by controlling the generation of stress induced reactive oxygen species (ROS) and also by protecting the photosynthetic machinery through a strengthened antioxidant system.


The validity of functional assessments of communication and the Activity/Participation components of the ICIDH-2: do they reflect what really happens in real-life?
This paper aims to provide a better understanding of the nature of functional communication activities so that assessment and treatment efforts are based on a theoretical framework and empirical data. Three sources of information are discussed. The first is the Activity/Participation dimensions of the World Health Organization's International Classification of Functioning, Disability, and Health. The second source is existing assessments of functional communication. The final source is data obtained from observational studies conducted in our research unit. The studies have observed the everyday communication of people with aphasia, people with Traumatic Brain Injury (TBI), and patients in hospital. The simplification of real-life communication in the WHO classification scheme, the variability of item sampling in existing assessments, and the complexity of communication observed in real-life settings has led to the conclusion that there are three levels of functional communication assessment: generic, population-specific, and individualized. Clinicians may choose which level suits their purpose. When clinicians routinely choose from a range of sophisticated functional assessments to inform their therapy, the seed that Martha Taylor Sarno planted and nourished for the past 30 years or more will truly flourish throughout the world of speech-language pathology. As a result of this activity, participants will (1) understand the theoretical framework and data base that motivates assessment and treatment of functional communication activities, (2) be able to discuss the World Health Organization's Classification of Functioning, Disability and Health and (3) gain information about functional assessment and observational sampling of real world communication activities across three levels.


Comprehensive cognitive neurological assessment in stroke.
Cognitive syndromes (CS) after stroke may be important to measure and monitor for management and emerging therapies. To incorporate known behavioral neurological and neuropsychiatric syndromes into a bedside cognitive assessment in patients with stroke. A validated cognitive examination (comprehensive cognitive neurological test in stroke, Coconuts) was administered during the first month of stroke presentation and analyzed according to five large-scale networks for cognition and correlated with neuropsychological tests. Validity testing of the test was performed for overall sensitivity, specificity, positive predictive value and negative predictive value to stroke in comparison with MRI diagnosis of stroke as well as discriminant validity, construct validity and inter-rater reliability. Overall the sensitivity of the Coconuts scale was 91% and specificity 35%, PPV 88% and NPV 41% vs stroke lesions using MRI. Cognitive syndrome frequencies: frontal network syndrome frequency was 908/1796 (51%), left hemisphere network syndrome frequency was 646/1796 (36%), right hemisphere network included 275/1796 (15.3%), occipitotemporal network for complex visual processing 107/1796 (6%), the hippocampal limbic network for amnesias and emotional disorders 397/1796 (22%) and miscellaneous network syndromes 481/1796 (27%). The Coconuts is a valid and practical test of a comprehensive array of known behavioral neurological and neuropsychiatric syndromes in patients with stroke.


Counterregulatory hormones in insulin-treated diabetic patients admitted to an accident and emergency department with hypoglycaemia.
The aim of the study was (1) to describe hormone responses in insulin-induced hypoglycaemia and (2) to investigate if a combined treatment with intravenous glucose and intramuscular glucagon (group A) would improve glucose recovery as compared to treatment with intravenous glucose alone (group B). Eighteen adult patients with insulin-treated diabetes mellitus admitted to the Accident and Emergency Department with hypoglycaemia (plasma glucose 1.23 +/- 0.15 mmol l(-1) on admission) were randomized to one of the above treatments and plasma glucose and counterregulatory hormones were measured before and 30-120 min after treatment. Pre-treatment counterregulatory hormone concentrations were significantly lower than hormone concentrations during induced hypoglycaemia in healthy control subjects but significantly higher than healthy fasting concentrations for plasma adrenaline (p = 0.020), glucagon (p = 0.008), growth hormone (p = 0.011), and cortisol (p<0.00001). Thus, although glucagon and adrenaline responses may be absent when studying Type 1 diabetic patients in the experimental setting, both hormones increase to a significant extent in 'real-life' hypoglycaemia in this patient group, although to a lesser degree than might be expected. Plasma glucose did not differ significantly between the two treatments at any time point. Despite access to food, one of four patients in group B and one of five patients in group A had plasma glucose below 4.0 mmol l(-1) after 120 min. In conclusion, low yet significantly elevated concentrations of adrenaline and glucagon were found in diabetic patients admitted with severe hypoglycaemia to an Accident and Emergency Department.


Angiotensin converting enzyme inhibition: discrepancy between antihypertensive effect and suppression of enzyme activity.
With chronic angiotensin converting enzyme (ACE) inhibition, blood pressure remains controlled throughout the day despite intermittent recovery of normal function of the renin-angiotensin system. This has been taken as evidence to suggest that the disappearance of angiotensin II (Ang II) from the circulation is not the main mechanism involved in the blood pressure-lowering action of ACE inhibitors. However, the degree of ACE inhibition is often not reliably estimated by the commonly used measurements of plasma ACE activity in vitro or plasma immunoreactive Ang II levels. The most appropriate method to assess ACE activity seems to be the measurement of the ratio between circulating angiotensin-(1-8)octapeptide and angiotensin I (Ang I) concentrations. The octapeptide and angiotensin I (Ang I) concentrations. The octapeptide Ang II can be measured precisely using high pressure liquid chromatography followed by a radioimmunoassay. Even using such improved methods, with long-term ACE inhibition, there exists a clear dissociation between the time course of ACE inhibition and that of the antihypertensive effect. Although it is attractive to speculate on this basis that other pathways such as blockade of tissue renin or enhanced vasodilator activity are responsible for the antihypertensive effect of ACE inhibitors, it is important to remember that the dissociation between the pharmacokinetic profile and the time course of the antihypertensive effect is not specific for ACE inhibitors and is well known with other agents. Since intermittent reduction of circulating Ang II is still an omnipresent feature of ACE inhibition, it seems at present that ACE inhibitors reduce blood pressure predominantly by this mechanism.


Role of Lactobacillus plantarum MTCC1325 in membrane-bound transport ATPases system in Alzheimer's disease-induced rat brain.
Introduction: Alzheimer's disease (AD) is a neurodegenerative disorder, clinically characterized by memory dysfunction and progressive loss of cognition. No curative therapeutic or drug is available for the complete cure of this disease. The present study was aimed to evaluate the efficacy of Lactobacillus plantarum MTCC1325 in ATPases activity in the selected brain regions of rats induced with Alzheimer's. Methods: For the study, 48 healthy Wistar rats were divided into four groups: group I as control group, group II as AD model (AD induced by intraperitoneal injection of D-Galactose, 120 mg/kg body weight for 6 weeks), group III as normal control rats which were orally administered only with L. plantarum MTCC1325 for 60 days, and group IV where the AD-induced rats simultaneously received oral treatment of L. plantarum MTCC1325 (10ml/kg body weight, 12×108 CFU/mL) for 60 days. The well known membrane bound transport enzymes including Na+, K+-ATPases, Ca2+-ATPases, and Mg2+-ATPases were assayed in the selected brain regions of hippocampus and cerebral cortex in all four groups of rats at selected time intervals. Results: Chronic injection of D-Galactose caused lipid peroxidation, oxidative stress, and mitochondrial dysfunction leading to the damage of neurons in the brain, finally bringing a significant decrease (-20%) in the brain total membrane bound ATPases over the controls. Contrary to this, treatment of AD-induced rats with L. plantarum MTCC1325 reverted all the constituents of ATPase enzymes to near normal levels within 30 days. Conclusion:Lactobacillus plantarum MTCC1325 exerted a beneficial action on the entire ATPases system in AD-induced rat brain by delaying neurodegeneration.


[Arthroscopic menisectomy in older patients: assessing health-related quality of life].
Little information is available on partial arthroscopic menisectomy in patients 60 years of age or older. Due to the co-morbidity of meniscal tears and osteoarthritis in this age group, the effectiveness of this procedure is controversial. The purpose of this study was to evaluate the outcome of this procedure in terms of function and mobility in patients 60 years of age or older. Between 1990 and 1999, 1920 arthroscopies of the knee were performed in a single primary care institution, and 51 patients, 60 years of age or older, had a partial arthroscopic menisectomy done. Outcomes were rated using the SF-36 Health Survey and a specially designed questionnaire including items of published scores. The mean age at surgery was 67 years (range: 60.3 - 78.9) and the mean follow-up was 5 years (range: 2 - 12). Due to persistent pain, 4 patients underwent a second operation including knee replacement in 3 cases and a high tibial osteotomy in 1 case. 41 patients (87.1 %) stated the arthroscopy had improved their quality of life. In terms of pain and daily life activities, the majority of the subjects showed an improvement after surgery. The SF-36 showed no clinically relevant difference compared to the control in all but one subscale. Despite of the presence of osteoarthritis in this age group, arthroscopic partial menisectomy can improve pain, function and mobility in the mid-term course.


Neural connectivity abnormalities in autism: insights from the Tuberous Sclerosis model.
Autism Spectrum Disorder (ASD) is a behavioral syndrome caused by complex genetic and non-genetic risk factors. It has been proposed that these risk factors lead to alterations in the development and 'wiring' of brain circuits and hence, the emergence of ASD. Although several lines of research lend support to this theory, etiological and clinical heterogeneity, methodological issues and inconsistent findings have led to significant doubts. One of the best established, albeit rare, causes of ASD is the genetic condition Tuberous Sclerosis Complex (TSC), where 40% of individuals develop ASD. A recent study by Peters and Taquet et al. analyzed electroencephalography (EEG) data using graph theory to model neural 'connectivity' in individuals with TSC with and without ASD and cases with 'idiopathic' ASD. TSC cases exhibited global under-connectivity and abnormal network topology, whereas individuals with TSC + ASD demonstrated similar connectivity patterns to those seen in individuals with idiopathic ASD: decreased long- over short-range connectivity. The similarity in connectivity abnormalities in TSC + ASD and ASD suggest a common final pathway and provide further support for 'mis-wired' neural circuitry in ASD. The origins of the connectivity changes, and their role in mediating between the neural and the cognitive/behavioral manifestations, will require further study.Please see related research article here http://www.biomedcentral.com/1741-7015/11/54.


An unusual patient with hypothyroidism, tophaceous gout, and marked joint destruction.
This report describes a 75-year-old Caucasian man with extensive urate deposits and severe gouty arthropathy that confined him to a wheelchair. Since age 50, he suffered multiple acute gout flares and progressive deformities in his hands, feet, knees, and elbows (tophi). Serum creatinine was 1.4 mg/dL and serum urate 9.4 mg/dL. Conditions known to increase uric acid production (psoriasis, chronic bronchitis) and to decrease uric acid excretion (hypothyroidism, metabolic syndrome, and nephroangiosclerosis) may operate in a single patient, illustrating the dramatic clinical course of untreated gout.


Secretion of lipids, apolipoproteins, and lipoproteins by human hepatoma cell line, HepG2: effects of oleic acid and insulin.
The aim of this study was to determine the effect of oleic acid and insulin on the secretion of lipoproteins by HepG2 cells grown in minimum essential medium. Triglycerides were the major neutral lipid (57% of total) and apoB was the predominant apolipoprotein (56% of total) secreted by these cells. The addition of oleate resulted in a two-fold increase in the concentration of neutral lipids but only a slight to moderate increase in the apolipoprotein (A-I, A-II, B, and E) levels. The secretion of very low density lipoproteins (VLDL) was stimulated by 425%, low density lipoproteins (LDL) by 77%, and high density lipoproteins (HDL) by 68%. Whereas neutral lipid composition of LDL was unchanged, the VLDL particles contained a significantly higher percentage of triglyceride and lower percentages of cholesterol and cholesteryl esters compared with VLDL secreted in the absence of oleate. Oleate had no significant effect on the composition of apolipoproteins in VLDL, LDL and HDL. In basal medium, insulin caused a significant decrease in the secretion of neutral lipids and apolipoproteins, particularly triglycerides and apoB. In addition to a 60-68% reduction in the total concentration of VLDL and LDL, insulin altered their composition by producing particles that had a significantly lower content of triglycerides, contained less apoB, and were deficient in apoE. There were no major changes in the concentration or composition of HDL particles. Insulin had a similar but less pronounced effect on the concentration and composition of lipoproteins secreted in the presence of oleate. The increased accumulation of triglycerides in the HepG2 cells concomitant with their reduced levels in the medium suggests that insulin may affect the secretion rather than synthesis of triglyceride-rich lipoproteins.


Brain abscess after stent-assisted coiling for ruptured middle cerebral artery aneurysm.
A 24-year-old man was admitted with sudden severe headache. Brain computed tomography (CT) revealed a subarachnoid hemorrhage in the basal cistern and both Sylvian cisterns and a left internal carotid artery angiogram showed a small aneurysm on the bifurcation of the left middle cerebral artery. We performed Y-configured stent-assisted coil embolization. On the fifth post-embolization day, the patient had chills, and his body temperature was over 38℃. Staphylococcus aureus was cultured from the venous blood sample. Central venous catheter-induced bacteremia was suspected. The central venous catheter was immediately removed, and an antibiotic to which the organism was susceptible (nafcillin) was injected for 15 days according to the result of the antibiotics sensitivity test. He was discharged without any clinical or neurological symptoms on the 32nd hospital day. Three months after treatment, the patient complained in the outpatient department of headache, nausea and vomiting. Brain magnetic resonance imaging showed several well-rimmed enhancing lesions in the left temporoparietal lobe. The headache, nausea and vomiting was aggravated, and brain CT showed more enlarging cysts and aggravation of the midline shift. Stereotactic aspiration was performed for the three biggest cysts, and greenish-white colored pus was aspirated. The identified pathogen was methicillin-sensitive Staphylococcus aureus in the culture study. Vancomycin and ceftriaxone were administered intravenously for three weeks, followed by intravenous injection of nafcillin for five weeks. The patient's postoperative course was clinically uneventful, and brain CT on postoperative day 57 showed total disappearance of the rim-enhanced abscess.


In-band pumped Ho3+:KY3F10 2 μm laser.
We report the first observation to our knowledge of room-temperature continuous-wave laser operation on the (5)I(7)→(5)I(8) transition of Ho(3+) ions in a KY(3)F(10) single crystal. Using a Tm-doped silica fiber laser operating at 1938 nm as a pump source, a maximum laser power of 1.8 W was obtained at a wavelength of ~2040 nm for 27 W of absorbed pump power with a slope efficiency of 19.1% with respect to absorbed power. At low cavity output coupling, the lasing wavelength shifted to 2060.5 nm. The beam propagation factor (M(2)) was measured to be <1.06 at the maximum output power, confirming fundamental transverse-mode (TEM(00)) operation. Performing a Caird analysis, we determined resonator round-trip losses and intrinsic slope efficiency of 30% and 43.8%, respectively.


MCM4 and MCM7, potential novel proliferation markers, significantly correlated with Ki-67, Bmi1, and cyclin E expression in esophageal adenocarcinoma, squamous cell carcinoma, and precancerous lesions.
Minichromosomal maintenance (MCM) proteins are participants of DNA replication and may represent more accurate markers in determining the proliferative fraction within a tumor than proliferative marker Ki-67. Our study investigated the correlation between MCM4 and MCM7 expression and Ki-67, Bmi1, and cyclin E expression in esophageal adenocarcinoma, squamous cell carcinoma, and precancerous lesions. MCM4 and MCM7 expression had similar distribution as Ki-67 and Bmi1 expression in esophageal carcinoma and precancerous lesions. The mean percentage of MCM4, MCM7, and Ki-67 expression increased from squamous epithelium (5.5%, 7.3%, and 5.9%, respectively), to columnar cell metaplasia (11.2, 13.5%, and 3.4%), Barrett's esophagus (27.7%, 35.3%, and 8.3%), low-grade dysplasia (42.6%, 52.2%, and 12.9%), high-grade dysplasia (63.2%, 77.7%, and 29.6%), adenocarcinoma (61.3%, 75.5%, and 24.5%), and squamous cell carcinoma (74.1, 85.4%, and 36.3%). The percentages of MCM4 and MCM7 expression were significantly higher than Ki-67 expression. Using univariate analysis we found a high percentage of MCM4 expression (>70%) to be significantly associated with lymph node metastasis and shorter survival in the adenocarcinoma group. We also demonstrated the percentage of MCM4 and MCM7 expression to be significantly correlated with Ki-67, Bmi1, and cyclin E expression in esophageal carcinoma and precancerous lesions. MCM4 and MCM7 may serve as more sensitive proliferative markers for the evaluation of esophageal lesions.


[Population mobility and HIV/AIDS in Central America and Mexico].
Estimate the magnitude of the association between population mobility, measured by net migration rate (NMR), and HIV prevalence in Central America and Mexico. Using time series models, based on public information from UNAIDS, UNDP, ECLAC, and the World Bank for the period 1990-2009, this association was studied in individuals aged 15-49 years, and adjusted for socioeconomic factors (education, unemployment, life expectancy, and income). NMR was negative in all countries except Costa Rica and Panama. Unadjusted results of the model show a positive association and that NMR can explain 6% of recorded HIV prevalence. When socioeconomic cofactors are included by country (education, health, and income), the magnitude increases to 9% (P<0.05). NMR, even when adjusted for socioeconomic factors, explains some of recorded HIV prevalence. All socioeconomic indicators show improvements in Central America and Mexico, although large gaps persist among countries. The modest association observed between population mobility and HIV prevalence is conditioned by the socioeconomic status of the countries studied. Information availability limited the study's ability to establish the existence of this association with greater certainty. Accordingly, based on available information, it is not possible to affirm that migration plays a key role in the spread of HIV.


Categorical versus dimensional approaches to autism-associated intermediate phenotypes in 22q11.2 microdeletion syndrome.
22q11.2 Microdeletion syndrome (22q11DS) is associated with elevated rates of autism spectrum disorders (ASDs), although the diagnosis is controversial. In order to determine whether there is a biological substrate of ASD in 22q11DS, we examined neurocognitive and structural neuroanatomic differences between those with 22q11DS and an ASD diagnosis (22q11DS-ASD+) and those with 22q11DS without ASD (22q11DS-ASD-); we then determined whether these differences were better characterized within a categorical or dimensional framework. We collected multiple neurocognitive measures and high-resolution T1-weighted scans on 116 individuals (29 22q11DS-ASD+, 32 22q11DS-ASD-, 55 typically developing controls) between 6 and 26 years of age. Measures of subcortical volume, cortical thickness (CT), and surface area were extracted using the FreeSurfer image analysis suite. Group differences in neurocognitive and neuroanatomic measures were assessed; regression analyses were then performed to determine whether a categorical or dimensional measure of ASD was a better predictor of neurocognitive impairment and/or neuroanatomic abnormalities observed in 22q11DS-ASD+. In comparison to 22q11DS-ASD-, 22q11DS-ASD+ participants exhibited decreased bilateral hippocampal CT and decreased right amygdala volumes. Those with 22q11DS-ASD+ also showed slowed processing speed and impairments in visuospatial and facial memory. Neurocognitive impairments fit a dimensional model of ASD, whereas reductions in parahippocampal CT were best explained by a categorical measure of ASD. A combination of categorical and dimensional measures of ASD may provide the most comprehensive understanding of ASDs in 22q11DS.


Characteristic fragmentation behavior of phosphoamino acid conjugates with 3'-azido-3'-deoxythymidine by electrospray ionization tandem mass spectrometry.
The conjugates of phosphoamino acids with 3'-azido-3'-deoxythymidine were synthesized and their structures were determined by various spectral methods. In positive and negative ion electrospray mass spectrometry (ESI-MS), the fragmentation pathways were investigated in conjunction with tandem mass spectrometry (MS/MS). The results showed that there were very different characteristic fragment ions in the positive ion MS/MS spectra and the negative ion MS/MS spectra.


Vitamin E and risk of cardiovascular diseases: a review of epidemiologic and clinical trial studies.
Cardiovascular diseases are the leading cause of worldwide mortality. There is strong epidemiologic evidence for a beneficial effect of vitamin E on cardiovascular disease risk. However, conflicting results have been reported by intervention studies. To assess the potential benefit of vitamin E intake on the risk of cardiovascular diseases, fifty-nine published reports from observational studies, retrospective and prospective, randomised clinical trials, meta-analyses as well as pooling analyses were reviewed. The paper provides a detailed discussion about design, quality and limitations of these studies with regard to the evidence of the hypothesized relationship between vitamin E and cardiovascular diseases.


A comparative study of five physiological key parameters between four different human trophoblast-derived cell lines.
The human placenta plays a crucial role as the interface between mother and fetus. It represents a unique tissue that undergoes morphological as well as functional changes on the cellular and tissue level throughout pregnancy. To better understand how the placenta works, a variety of techniques has been developed to re-create this complex physiological barrier in vitro. However, due to the low availability of freshly isolated primary cells, choriocarcinoma cell lines remain the usual suspects as in vitro models for placental research. Here, we present a comparative study on the functional aspects of the choriocarcinoma cell lines BeWo, JAR and Jeg-3, as well as the first trimester trophoblast cell line ACH-3P as placental in vitro barrier models for endocrine and transport studies. Functional assays including tight junction immunostaining, sodium fluorescein retardation, trans epithelial resistance, glucose transport, hormone secretion as well as size-dependent polystyrene nanoparticle transport were performed using the four cell types to evaluate key functional parameters of each cell line to act a relevant in vitro placental barrier model.


Optimization of an Industrial Medium and Culture Conditions for Probiotic Weissella cibaria JW15 Biomass Using the Plackett-Burman Design and Response Surface Methodology.
The objective of this study was to optimize industrial-grade media for improving the biomass production of Weissella cibaria JW15 (JW15) using a statistical approach. Eleven variables comprising three carbon sources (glucose, fructose, and sucrose), three nitrogen sources (protease peptone, yeast extract, and soy peptone), and five mineral sources (K2HPO4, potassium citrate, L-cysteine phosphate, MgSO4, and MnSO4) were screened by using the Plackett-Burman design. Consequently, glucose, sucrose, and soy peptone were used as significant variables in response surface methodology (RSM). The composition of the optimal medium (OM) was 22.35 g/l glucose, 15.57 g/l sucrose, and 10.05 g/l soy peptone, 2.0 g/l K2HPO4, 5.0 g/l sodium acetate, 0.1 g/l MgSO4·7H2O, 0.05 g/l MnSO4·H2O, and 1.0 g/l Tween 80. The OM significantly improved the biomass production of JW15 over an established commercial medium (MRS). After fermenting OM, the dry cell weight of JW15 was 4.89 g/l, which was comparable to the predicted value (4.77 g/l), and 1.67 times higher than that of the MRS medium (3.02 g/l). Correspondingly, JW15 showed a rapid and increased production of lactic and acetic acid in the OM. To perform a scale-up validation, batch fermentation was executed in a 5-l bioreactor at 37°C with or without a pH control at 6.0 ± 0.1. The biomass production of JW15 significantly improved (1.98 times higher) under the pH control, and the cost of OM was reduced by two-thirds compared to that in the MRS medium. In conclusion, OM may be utilized for mass producing JW15 for industrial use.


Engineered neurogenesis in naïve adult rat cortex by Ngn2-mediated neuronal reprogramming of resident oligodendrocyte progenitor cells.
Adult tissue stem cells contribute to tissue homeostasis and repair but the long-lived neurons in the human adult cerebral cortex are not replaced, despite evidence for a limited regenerative response. However, the adult cortex contains a population of proliferating oligodendrocyte progenitor cells (OPCs). We examined the capacity of rat cortical OPCs to be re-specified to a neuronal lineage both in vitro and in vivo. Expressing the developmental transcription factor Neurogenin2 (Ngn2) in OPCs isolated from adult rat cortex resulted in their expression of early neuronal lineage markers and genes while downregulating expression of OPC markers and genes. Ngn2 induced progression through a neuronal lineage to express mature neuronal markers and functional activity as glutamatergic neurons. In vivo retroviral gene delivery of Ngn2 to naive adult rat cortex ensured restricted targeting to proliferating OPCs. Ngn2 expression in OPCs resulted in their lineage re-specification and transition through an immature neuronal morphology into mature pyramidal cortical neurons with spiny dendrites, axons, synaptic contacts, and subtype specification matching local cytoarchitecture. Lineage re-specification of rat cortical OPCs occurred without prior injury, demonstrating these glial progenitor cells need not be put into a reactive state to achieve lineage reprogramming. These results show it may be feasible to precisely engineer additional neurons directly in adult cerebral cortex for experimental study or potentially for therapeutic use to modify dysfunctional or damaged circuitry.


Keyhole surgery of the kidney at sultan qaboos university hospital, oman.
Percutaneous access surgery of the kidneys was introduced in Sultan Qaboos University Hospital (SQUH) in 1998. We are presenting our early experience in the first 31 patients operated on over an eight year period using the percutaneous approach. A retrospective review of 25 patients, who underwent percutaneous nephrolithotomy (PCNL) for the treatment of large renal stones and 6 patients who underwent endopyelotomy for the treatment of pelviureteric junction (PUJ) obstruction. In the PCNL group complete stone clearance was achieved in 68% (17/25) patients and the complication rate was 28% (7/25). In the endopyelotomy group the success rate of relief of obstruction of PUJ measured by renogram and relief of symptoms was 83% (5/6 patients). Our early results of PCNL are promising and comparable to international results.


[Mutation process in the protein-coding genes of human mitochondrial genome in context of evolution of the genus].
The human mitochondrial genome, although it has a small size, is characterized by high level of variation, non-uniformly distributed in groups of nucleotide positions that differ in the degree of variability. Considering the mutation process in human mtDNA relative to the mitochondrial genomes of the genus Homo-neandertals, denisova hominin and other primate species, it appears that more than half (56.5%) variable positions in the human mtDNA protein-coding genes are characterized by back (reverse) mutations to the pre-H. sapiens state of mitochondrial genome. It has been found that hypervariable nucleotide positions show a minimal proportion of specific to H. sapiens mutations, and, conversely, a high proportion of mutations (both nucleotide and amino acid substitutions), leading to the loss of Homo-specific variants of polymorphisms. Most often, polymorphisms specific to H. sapiens arise in result of single forward mutations and disappear mainly due to multiple back mutations, including those in the mutational "hotspots".


cDNA cloning of a cadmium-inducible mRNA encoding a novel cysteine-rich, non-metallothionein 25-kDa protein in an enchytraeid earthworm.
Cadmium accumulation and its effect on gene expression have been investigated at sublethal cadmium concentrations in the soil oligochaete Enchytraeus buchholzi. This worm is capable of accumulating cadmium to large amounts, which coincides with the induction of a mRNA isolated as a cDNA clone by differential screening of a cDNA library constructed from cadmium-treated enchytraeids. The cDNA clone designated CRP1 is 1474 base pairs in length and contains a 753-base pair open reading frame, encoding a novel Cys-rich non-metallothionein protein. In vitro translation of the in vitro transcribed CRP1 results in a protein with a molecular mass of 25 kDa and an pI of approximately 7.5. These values are consistent with those predicted from the deduced amino acid sequence. The CRP protein contains 27% Cys, most of them arranged in Cys-X-Cys and Cys-Cys segments. The sequence is also characterized by a 31-amino-acid motif, which is tandemly repeated along the sequence. Northern blot analysis reveals that the CRP gene is not constitutively expressed in untreated worms, but rather it is rapidly induced by cadmium. The CRP gene may be a promising candidate gene for monitoring bioavailable cadmium at subtoxic levels in terrestric environments.


Acceptance and Commitment Coaching for Music Performance Anxiety: Piloting a 6-Week Group Course With Undergraduate Dance and Musical Theatre Students.
Treatments for students with problematic levels of music performance anxiety (MPA) commonly rely on approaches in which students are referred to psychotherapists or other clinical professionals for individual care that falls outside of their music training experience. However, a more transdisciplinary approach in which MPA treatment is effectively integrated into students' training in music/performing arts colleges by teachers who work in consultation with clinical psychologists may prove more beneficial, given the resistance students often experience toward psychotherapy. Training singing teachers, and perhaps music teachers at large, to use an evidence-based coaching strategy like Acceptance and Commitment Coaching (ACC) to directly manage students' MPA is one such approach. Building on the work of a previous study in which ACC was administered by a singing teacher to a musical theatre student with problematic MPA, we piloted the effectiveness of a six-session, group ACC course for a sample of performing arts students (N = 6) with MPA related to vocal performances, using a mixed-methods design. The coach here was also a singing teacher without a clinical background, and her training in ACC by a clinical psychologist was of a similar duration (8 h) as the previous teacher's (7 h). Similar to the musical theatre student, the students reported being significantly less fused with their MPA-related cognitions, more accepting of their MPA-related physiological symptoms, and more psychologically flexible while performing in general, and these improvements were maintained after 3 months. Furthermore, they appeared to lower their shame over having MPA and change how they thought in relation to one another. Of note, these improvements were similar to those shown by seven vocal students with MPA after they received Acceptance and Commitment Therapy from a clinical psychologist, but with larger reductions in shame and better acceptance of MPA, which suggests a non-clinical, group ACC intervention that includes supportive discussions to normalize MPA and challenges attempts to control it may be more helpful than individual psychotherapy. These results are promising and indicate a brief training in ACC (<10 h) may be sufficient for singing teachers to provide significant benefit for students with problematic MPA.


Morphological characterizations of parsnip (Pastinaca sativa L.) to select superior genotypes.
Parsnip (Pastinaca sativa L.) is an edible root that has long been used in cooking and preparing baby food and livestock. The present study was performed to evaluate the phenotypic diversity of 69 accessions of this species to select superiors in terms of root quality in Paykan village, Isfahan province, Iran, in the year 2022. There were significant differences among the accessions investigated (ANOVA, p < .01). Coefficient of variation (CV) was more than 20.00% in the majority of measured characters (64 out of 66 characters), indicating high diversity among the accessions. Foliage width (crown) ranged from 10 to 55 cm with an average of 32.32 cm. Root shape was tapering (33), obtriangular (10), narrow oblong (5), wide oblong (5), obovate (13), and fusiform (3). Root length ranged from 81.2 to 294 mm with an average of 166.44 mm. Root diameter at its middle point ranged from 15.58 to 125.12 mm with an average of 51.83 mm. Root weight ranged from 15 to 1200 g with an average of 315.36 g. Inner core (xylem) pigmentation/color was cream yellow (11 accessions), light yellow (12), yellow (42), dark yellow (2), and yellow-light orange (2). In the cluster analysis based on Ward's method, the accessions were divided into two main clusters according to morphological traits. This is despite the fact that parsnip is part of the medicinal plant native and valuable in most farms in tropical cities. Compared with carrots, parsnip plants are more adaptable to different environmental conditions. The accessions studied here showed high phenotypic diversity. Based on ideal values of the important and commercial characters of parsnip, such as root length, root weight, inner core (xylem) pigmentation/color, root shape, flesh color intensity, flesh palatability, and total soluble solids, 14 genotypes, including Parsnip-3, Parsnip-9, Parsnip-24, Parsnip-32, Parsnip-32, Parsnip-48, Parsnip-51, Parsnip-52, Parsnip-58, Parsnip-60, Parsnip-62, Parsnip-65, Parsnip-67, and Parsnip-69, were promising and are recommended for cultivation.


Characteristics and therapeutic strategies of brain and cranial radiation-induced sarcoma: analysis of 165 cases from our case experience and comprehensive review.
Radiation-induced sarcoma (RIS) is among the neoplasms potentially caused by radiation therapy (RT) for brain tumors. However, the clinical characteristics of and ideal treatment for RIS are unclear. We analysed our case experience and conducted a comprehensive literature review to reveal the characteristics of brain and cranial RIS. We analysed 165 cases of RIS from the literature together with the RIS case treated at our institution. In each case, the latency period from irradiation to the development of each RIS and the median overall survival (OS) of the patients was analysed by Kaplan-Meier analysis. Spearman's correlation test was used to determine the relationship between the latency period and radiation dose or age at irradiation. The mean age at the development of RIS was 39.63 ± 17.84 years. The mean latency period was 11.79 ± 8.09 years. No factors associated with early development of RIS were detected. The median OS was 11 months, with fibrosarcoma showing significantly shorter OS compared with osteosarcoma and other sarcomas (p = 0.0021), and intracranial RIS showing a worse prognosis than extracranial RIS (p < 0.0001). Patients treated with surgery (p < 0.0001) and postoperative chemotherapy (p = 0.0157) for RIS presented significantly longer OS, whereas RT for RIS was not associated with a survival benefit. Although prognosis for RIS is universally poor, pathological characteristics and locations are associated with worse prognosis. Surgery and chemotherapy may be the ideal treatment strategies for RIS.


Pyramid environment reduces the wound healing suppressant properties of dexamethasone in albino rats.
With a view to investigate the contribution and role of environment within a wooden pyramid model on the wound healing suppressant effect of dexamethasone in rats, wound breaking strength, dry weight, hydroxyproline content and histology of granulation tissue of the dead space wound were studied in rats. The results indicate that the environment within the wooden pyramid not only promotes significant wound healing but also reduces the wound healing suppressant effect of dexamethasone. Histological studies also confirmed the results.


[The fight against tuberculosis and developments in public health from 1890 to 1930 in Italy].
The author presents the developments in society and public health that paved the way, thanks to the birth of social and scientific associations and later to state intervention, for the establishment of hospitals for tuberculosis in Italy at the beginning of the 20th century. From 1890 onwards many fruitful meetings, conferences and debates ultimately led to the passing of a specific law on public health care; in 1927 this law covered about half the population. The First World War was undoubtedly the prime cause that stopped the downward trend in mortality and morbidity from the tuberculosis epidemic in the early 20th century. Early on, Bologna, together with other cities in Tuscany and Lombardy, developed plans for therapy (i.e. hospitals for tuberculosis) and prevention (i.e. holiday camps). However, in Italy in the 1930s tuberculosis continued to be a major problem despite such improvements in public health. In Europe, Germany was the nation that pioneered the fight against tuberculosis by social, scientific and legislative means. Since 1883 there had been a specific law for insurance against illnesses and a network of sanatoria had been established.


The Metabotropic Glutamate 5 Receptor in Sleep and Wakefulness: Focus on the Cortico-Thalamo-Cortical Oscillations.
Sleep is an essential innate but complex behaviour which is ubiquitous in the animal kingdom. Our knowledge of the distinct neural circuit mechanisms that regulate sleep and wake states in the brain are, however, still limited. It is therefore important to understand how these circuits operate during health and disease. This review will highlight the function of mGlu5 receptors within the thalamocortical circuitry in physiological and pathological sleep states. We will also evaluate the potential of targeting mGlu5 receptors as a therapeutic strategy for sleep disorders that often co-occur with epileptic seizures.


A three-dimensional adaptive rational interpolation algorithm for removing TMS-EEG pulse artifacts.
Objective.Transcranial magnetic stimulation in combination with electroencephalography (TMS-EEG) has been widely used to study the reactivity and connectivity of brain regions. In order to efficiently and fast solve the pulse artifacts problem caused by TMS electromagnetic pulses, a three-dimensional adaptive rational quadratic Hermite interpolation algorithm is proposed.Approach.Firstly, a three-dimensional signal matrix is obtained by a signal recombination algorithm, where the removed window is automatically obtained by a derivative threshold. Secondly, the adaptive rational quartic Hermite interpolation algorithm is used to interpolate the removed window. Finally, the performance of the algorithm is verified using simulated and public database data.Main results.The simulation results show that the proposed algorithm improves the SNR by 23.88%-47.60%, reduces the RMSE by 46.52%-81.11%, reduces the average MAE by 47.83%-58.33%, and reduces the time consumption of the proposed algorithm by 45.90% compared with the piecewise cubic Hermite interpolation algorithm.Significance.Therefore, TMS-EEG pulse artifacts can be removed effectively and quickly with the proposed algorithm.


Somatic cell nuclear transfer and derivation of embryonic stem cells in the mouse.
Addressing the fundamental questions of nuclear equivalence in somatic cells has fascinated scientists for decades and has resulted in the development of somatic cell nuclear transfer (SCNT) or animal cloning. SCNT involves the transfer of the nucleus of a somatic cell into the cytoplasm of an egg whose own chromosomes have been removed. In the mouse, SCNT has not only been successfully used to address the issue of nuclear equivalence, but has been used as a model system to test the hypothesis that embryonic stem cells (ESCs) derived from NT blastocysts have the potential to correct--through genetic manipulations--degenerative diseases. This paper aims to provide a comprehensive description of SCNT in the mouse and the derivation of ESCs from blastocysts generated by this technique. SCNT is a very challenging and inefficient procedure because it is technically complex, it bypasses the normal events of gamete interactions and egg activation, and it depends on adequate reprogramming of the somatic cell nucleus in vivo. Improvements in any or all those aspects may enhance the efficiency and applicability of SCNT. ESC derivation from SCNT blastocysts, on the other hand, requires the survival of only a few successfully reprogrammed cells, which have the capacity to proliferate indefinitely in vitro, maintain correct genetic and epigenetic status, and differentiate into any cell type in the body--characteristics that are essential for transplantation therapy or any other in vivo application.


miR-223 Inhibits Lipid Deposition and Inflammation by Suppressing Toll-Like Receptor 4 Signaling in Macrophages.
Atherosclerosis and its complications rank as the leading cause of death with the hallmarks of lipid deposition and inflammatory response. MicroRNAs (miRNAs) have recently garnered increasing interests in cardiovascular disease. In this study, we investigated the function of miR-223 and the underlying mechanism in atherosclerosis. In the atherosclerotic ApoE-/- mice models, an obvious increase of miR-223 was observed in aortic atherosclerotic lesions. In lipopolysaccharide (LPS) activated macrophages, its expression was decreased. The miR-223 overexpression significantly attenuated macrophage foam cell formation, lipid accumulation and pro-inflammatory cytokine production, which were reversed by anti-miR-223 inhibitor transfection. Mechanism assay corroborated that miR-223 negatively regulated the activation of the toll-like receptor 4 (TLR4)-nuclear factor-κB (NF-κB) pathway. Pretreatment with a specific inhibitor of NF-κB (pyrrolidinedithiocarbamate, PDTC) strikingly abrogated miR-223 silence-induced lipid deposition and inflammatory cytokine production. Furthermore, PI3K/AKT was activated by miR-223 up-regulation. Pretreatment with PI3K/AKT inhibitor LY294002 strikingly ameliorated the inhibitory effects of miR-223 on the activation of TLR4 and p65, concomitant with the increase in lipid deposition and inflammatory cytokine production. Together, these data indicate that miR-223 up-regulation might abrogate the development of atherosclerosis by blocking TLR4 signaling through activation of the PI3K/AKT pathway, and provides a promising therapeutic avenue for the treatment of atherosclerosis.


The inactivation of JAK2/STAT3 signaling and desensitization of M1 mAChR in minimal hepatic encephalopathy (MHE) and the protection of naringin against MHE.
We previously reported that elevation of intracranial dopamine (DA) levels from cirrhotic livers is implicated in the pathogenesis of minimal hepatic encephalopathy (MHE). Intracellular events in neurons, which lead to memory loss in MHE by elevated DA, however, remain elusive. In our present study, an MHE rat model, a DA - intracerebroventricularly (i.c.v.) injected rat model and DA-treated primary cortical neurons (PCNs) were used to study this issue using behavioral tests, double-labeled fluorescent staining, immunoblotting, and semi-quantitative RT-PCR. Cognitive impairment was observed in MHE rats and DA (10 µg, i.c.v.)-treated rats. The levels of DA in the cerebral cortex of both MHE and DA (10 µg)-treated rats were increased. DA conversely modulated the p-JAK2/p-STAT3 levels in PCNs. In accordance, DA downregulated an anacetylcholine-producing enzyme, choline acetyltransferase (ChAT), and desensitized the M1-type muscarinic acetylcholine receptor (M1 mAChR). Furthermore, naringin completely restored cognitive function in MHE/DA (10 µg)-treated models by activating the JAK2/STAT3 axis, paralleling the upregulation of ChAT and sensitization of M1 mAChR. We propose a hypothesis accounting for memory impairment related to MHE: DA-dependent inactivation of the JAK2/STAT3 axis causes memory loss through cholinergic dysfunction. Our findings provide not only a novel pathological hallmark in MHE but also a novel target in MHE therapy.


Age of Postmenopause Women: Effect of Soy Isoflavone in Lipoprotein and Inflammation Markers.
Menopause is associated with adverse metabolic changes in plasma lipoprotein and inflammation markers. Estrogens have beneficial effects on lipid metabolism and inflammation. Isoflavones (ISO) have structurally similar to estradiol. Our objective was analize the effect of soy-ISO on serum lipid and inflammatory markers (sP-selectin and sCD40L) in postmenopausal women. A 12-week randomized, double-blind, placebo-controlled intervention with soy-ISO (50 mg, twice daily) was conducted in 35 healthy postmenopausal women (55-72 years old). The women were divided in 2 groups: 20 were allocated to soy-ISO, and 15 to a placebo group. The changes of total cholesterol (TC), triglycerides, low-density lipoproteins-cholesterol (LDL-C), high-density lipoprotein-cholesterol, Apo-A1, sP-selectin and sCD40L in 2 groups before and after 12-week treatment showed no statistical significance. In subgroup analysis, soy-ISO supplementation significantly decreased the levels of TC, LDL-C and sCD40L in women under 65 years old, and with null effects on serum lipid and inflammation markers in women over 65 years old. Soy-ISO did not significantly favorable effects on the lipid profile and inflammatory markers in postmenopausal women. However, in women under 65 years of age, soy-ISO significantly decreased the TC, LDL-C and sCD40L, whereas, no effects on lipid profile and inflammation markers in women over 65 years old were observed.


Obstructive jaundice secondary to chronic pancreatitis in children: report of two cases and review of the literature.
Chronic pancreatitis is a rare childhood illness, most often presenting with nausea, vomiting, and recurrent abdominal pain. Obstructive jaundice secondary to biliary stricture is an uncommon manifestation of childhood pancreatitis, with only 11 patients previously described in the surgical literature. We report our experience with two additional children with jaundice secondary to pancreatitis and review the literature on this problem. Laboratory tests are often of little diagnostic value, and a high index of suspicion is essential for correct diagnosis. Endoscopic retrograde cholangiopancreatography is emerging as an extremely useful diagnostic study in these patients. The surgical management of this uncommon pediatric illness remains controversial.


Eosinophilic folliculitis: before and after the introduction of antiretroviral therapy.
To characterize the relationship of new eosinophilic folliculitis (EF) cases between June 30, 1994, and January 5, 2000, and antiretroviral therapy (ART) status and immune reconstitution. Retrospective cohort analysis. Dermatology clinics at a county hospital. Fifty-seven consecutive subjects with biopsy-proved EF from the pathology database. Subject groups were as follows: naïve to ART, receiving ART without protease inhibitors/nonnucleoside reverse transcriptase inhibitors, and receiving ART containing protease inhibitors/nonnucleoside reverse transcriptase inhibitors. Onset of EF, CD4 cell count and nadir at EF onset, and time of ART initiation. Among the 3 groups previously described, mean CD4 cell counts (86.26/microL vs 113.82/microL vs 145.65/microL, respectively [Kruskal-Wallis rank sum test, P = .15]) and nadir (68.43/microL vs 66.18/microL vs 64.17/microL, respectively [Kruskal-Wallis rank sum test, P = .41]) at EF diagnosis were not statistically different. Fifty-two subjects (91%), regardless of treatment group, had a nadir below 200/microL. Of the subjects undergoing ART, 28 (82%) developed EF within 6 months of initiating ART; their average CD4 cell count increase was 108/microL. Of the 23 subjects receiving protease inhibitor/nonnucleoside reverse transcriptase inhibitor-containing ART regimens, 17 (74%) were diagnosed as having EF within 3 months, with 4 additional subjects diagnosed as having EF within 6 months (a total of 21 [91%] of the 23 subjects). This is not significantly different from the 7 (64%) of 11 subjects diagnosed as having EF at 3 and 6 months of starting ART without protease inhibitors/nonnucleoside reverse transcriptase inhibitors (P = .07) (odds ratio, 0.18; 95% confidence interval, 0.01-1.54). Our study shows an association between low nadir (66.28/microL) and low CD4 cell count (115.54/microL) and the development of EF, regardless of subjects' ART status. However, most subjects receiving ART were diagnosed as having EF within 3 to 6 months of ART initiation, regardless of the regimen.


Thermal tolerance in a south-east African population of the tsetse fly Glossina pallidipes (Diptera, Glossinidae): implications for forecasting climate change impacts.
For tsetse (Glossina spp.), the vectors of human and animal trypanosomiases, the physiological mechanisms linking variation in population dynamics with changing weather conditions have not been well established. Here, we investigate high- and low-temperature tolerance in terms of activity limits and survival in a natural population of adult Glossina pallidipes from eastern Zambia. Due to increased interest in chilling flies for handling and aerial dispersal in sterile insect technique control and eradication programmes, we also provide further detailed investigation of low-temperature responses. In wild-caught G. pallidipes, the probability of survival for 50% of the population at low-temperatures was at 3.7, 8.9 and 9.6 degrees C (95% CIs: +/-1.5 degrees C) for 1, 2 and 3 h treatments, respectively. At high temperatures, it was estimated that treatments at 37.9, 36.2 and 35.6 degrees C (95% CIs: +/-0.5 degrees C) would yield 50% population survival for 1, 2 and 3 h, respectively. Significant effects of time and temperature were detected at both temperature extremes (GLZ, p<0.05 in all cases) although a time-temperature interaction was only detected at high temperatures (p<0.0001). We synthesized data from four other Kenyan populations and found that upper critical thermal limits showed little variation among populations and laboratory treatments (range: 43.9-45.0 degrees C; 0.25 degrees C/min heating rate), although reduction to more ecologically relevant heating rates (0.06 degrees C/min) reduce these values significantly from approximately 44.4 to 40.6 degrees C, thereby providing a causal explanation for why tsetse distribution may be high-temperature limited. By contrast, low-temperature limits showed substantial variation among populations and acclimation treatments (range: 4.5-13.8 degrees C; 0.25 degrees C/min), indicating high levels of inter-population variability. Ecologically relevant cooling rates (0.06 degrees C/min) suggest tsetses are likely to experience chill coma temperatures under natural conditions (approximately 20-21 degrees C). The results from acute hardening experiments in the Zambian population demonstrate limited ability to improve low-temperature tolerance over short (hourly) timescales after non-lethal pre-treatments. In flies which survived chilling, recovery times were non-linear with plateaus between 2-6 and 8-12 degrees C. Survival times ranged between 4 and 36 h and did not vary between flies which had undergone chill coma by comparison with flies which had not, even after factoring body condition into the analyses (p>0.5 in all cases). However, flies with low chill coma values had the highest body water and fat content, indicating that when energy reserves are depleted, low-temperature tolerance may be compromised. Overall, these results suggest that physiological mechanisms may provide insight into tsetse population dynamics, hence distribution and abundance, and support a general prediction for reduced geographic distribution under future climate warming scenarios.


Genomic signatures and prognosis of advanced stage Chinese pediatric T cell lymphoblastic lymphoma by whole exome sequencing.
To investigate the genomic signatures and prognosis of advanced-stage T cell lymphoblastic lymphoma (T-LBL) and to examine the relationship between T-LBL and T cell acute lymphoblastic leukemia (T-ALL). 35 Chinese T-LBL children with stage III or IV disease were recruited for this study. They were treated with combination chemotherapy and whole exome sequencing. The relationship of the clinical features, prognosis and specific gene mutations was researched. Gene chips of T-LBL and T-ALL were downloaded from a database, and differential gene expression was analyzed. Germline causal gene mutations (CARS or MAP2K2) were detected in 2 patients; 3.06 ± 2.21 somatic causal gene mutations were identified in the 35 patients, and somatic mutations were observed in the NOTCH1, FBXW7, PHF6 and JAK3 genes. NOTCH1 mutations were significantly associated with FBXW7 mutations, and the age at diagnosis of patients with NOTCH1-FBXW7 mutations was less than that of patients without such mutations (P < 0.05). 32 patients achieved complete remission (CR), and 14 and 18 patients were classified into the intermediate risk (IR) group and high risk (HR) group. During a median follow-up of 44 months, 3 patients relapsed. Three-year prospective event free survival (pEFS) was 82.286%, and no significant differences of pEFS were found for different sexes, ages, or statuses of NOTCH1-FBXW7 mutations, (P > 0.05); however, the mean survival time of the IR group was longer than that of the HR group (P < 0.05). Differential expression of genes in the T-LBL and/or T-ALL datasets was analyzed using the R package limma, and 1/3 of the differentially expressed genes were found in both the T-ALL and T-LBL datasets. High expression of PI3K-Akt signal pathway genes and the USP34 gene was found in the T-LBL dataset. Although T-ALL and T-LBL both originate from precursor T-cells and are considered different manifestations of the same disease and the outcome of T-LBL is favorable when using T-ALL-based chemotherapy, there are differences in the gene distribution between T-LBL and T-ALL. It seems that the PI3K-Akt signaling pathway and the USP34 gene play important roles in T-LBL, but medicines targeting the USP34 gene or the PI3K-Akt pathway may be invalid.


Design, Synthesis, and Biological Evaluation of 5-Formyl-pyrrolo[3,2-b]pyridine-3-carboxamides as New Selective, Potent, and Reversible-Covalent FGFR4 Inhibitors.
The FGF19-FGFR4 signaling pathway has been extensively studied as a promising target for the treatment of hepatocellular carcinoma (HCC). Several FGFR4-selective inhibitors have been developed, but none of them receives approval. Additionally, acquired resistance caused by FGFR4 gatekeeper mutations is emerging as a serious limitation for these targeted therapies. Herein, we report a novel series of 5-formyl-pyrrolo[3,2-b]pyridine derivatives as new reversible-covalent inhibitors targeting wild-type and gatekeeper mutant variants of FGFR4 kinase. The representative compound 10z exhibited single-digit nanomolar activity against wild-type FGFR4 and the FGFR4V550L/M mutant variants in biochemical and Ba/F3 cellular assays, while sparing FGFR1/2/3. Furthermore, 10z showed significant antiproliferative activity against Hep3B, JHH-7, and HuH-7 HCC cells with IC50 values of 37, 32, and 94 nM, respectively. MALDI-TOF-MS and X-ray protein crystallography studies were consistent with 10z acting as a reversible-covalent inhibitor of FGFR4, serving as a promising lead compound for further anticancer drug development.


The current regenerative medicine approaches of craniofacial diseases: A narrative review.
Craniofacial deformities (CFDs) develop following oncological resection, trauma, or congenital disorders. Trauma is one of the top five causes of death globally, with rates varying from country to country. They result in a non-healing composite tissue wound as they degenerate in soft or hard tissues. Approximately one-third of oral diseases are caused by gum disease. Due to the complexity of anatomical structures in the region and the variety of tissue-specific requirements, CFD treatments present many challenges. Many treatment methods for CFDs are available today, such as drugs, regenerative medicine (RM), surgery, and tissue engineering. Functional restoration of a tissue or an organ after trauma or other chronic diseases is the focus of this emerging field of science. The materials and methodologies used in craniofacial reconstruction have significantly improved in the last few years. A facial fracture requires bone preservation as much as possible, so tiny fragments are removed initially. It is possible to replace bone marrow stem cells with oral stem cells for CFDs due to their excellent potential for bone formation. This review article discusses regenerative approaches for different types of craniofacial diseases.


Limit to cardiac compensation during acute isovolemic hemodilution: influence of coronary stenosis.
We assessed limit to cardiac compensation during isovolemic hemodilution (HD) in 14 anesthetized dogs. Radioactive microspheres were used to evaluate myocardial blood flow (MBF) and its transmural distribution (endo/epi). Myocardial O2 consumption (MVO2) and percent lactate extraction were determined. Coronary vasodilator reserve was assessed from reactive hyperemic responses. Dogs were divided into group 1, with intact left anterior descending coronary artery (LAD), and group 2, with critical stenosis of LAD. Measurements were obtained at baseline and during graded HD (Hespan) until cardiac failure (CF). CF occurred at lower hematocrit in group 1 compared with group 2 (9 +/- 1 vs. 17 +/- 1%). In group 1, MBF increased during HD to maintain MVO2 constant; increases in MBF were transmurally uniform until CF, when decreased endo/epi and lactate production suggested subendocardial ischemia. Coronary vasodilator reserve decreased progressively during HD and was absent at CF. In group 2, stenotic LAD demonstrated constant MBF (resulting in decreased MVO2) during HD. At CF, these responses along with reduced endo/epi and lactate production indicated local myocardial ischemia. We conclude that 1) with normal coronary circulation, cardiac function was well maintained over a wide range of hematocrits because increases in MBF were transmurally uniform and sufficient to maintain myocardial oxygenation: CF occurred during extreme HD when MBF became maldistributed, resulting in subendocardial ischemia; 2) critical coronary stenosis impaired coronary vascular adjustment to HD and reduced significantly tolerance of left ventricle to HD; and 3) present findings underscore the importance of recruitment of coronary vasodilator reserve in preserving total and regional myocardial oxygenation during HD.


Optically Patternable Metamaterial Below Diffraction Limit.
We report an optically patternable metamaterial (OPM) for ultraviolet nanolithography below the diffraction limit. The OPM features monolayered silver nanoislands embedded within a photosensitive polymer by using spin-coating of an ultrathin polymer, oblique angle deposition, and solid-state embedment of silver nanoislands. This unique configuration simultaneously exhibits both negative effective permittivity and high image contrast in the ultraviolet range, which enables the surface plasmon excitation for the clear photolithographic definition of minimum feature size of 70 nm (≲ λ/5) beyond the near-field zone. This new metamaterial provides a new class of photoresist for ultraviolet nanolithography below the diffraction limit.


Incidence of surgery in conservatively treated patients with scoliosis.
The effectiveness of bracing and the effectiveness of conservative treatment of scoliosis as a whole is widely denied and rejected. We therefore carried out the present study in order to establish whether the work involved in the conservative treatment of scoliosis is reasonable and worthwhile, including as it does the education of patients, techniques of brace moulding, time-consuming follow-ups and the strain put on patients by the treatment itself. A retrospective analysis of the incidence of surgery in patients with scoliosis presenting every kind of aetiology. To improve comparison with data already published by other centres, this group of patients was matched with the study design of the control group. Since 1992, in addition to the intensive inpatient rehabilitation programme developed at our centre, we have also been practising moulding techniques according to Chêneau in order to construct scoliosis orthoses of high correction. For the purposes of this study we chose a number of scoliosis patients from our data bank who had had conservative treatment at our centre between 1993 and 1996. All the patients, like those of the untreated control group, were at least 15 years of age at the time they were last investigated or questioned. The incidence of surgery in our group was compared statistically with data published by other centres. Three hundred and forty-three patients (females only) with a curvature of 33.4 degrees (SD = 18.9) were included in our study and could be followed up under the described pre-conditions. Forty-one patients (11.95%) had had surgery. In patients with adolescent idiopathic scoliosis, we found an incidence of surgery of only 7.3% compared with 28% in the control group with the same diagnosis. Statistically, therefore, the incidence of surgery in our group was highly significantly lower than the incidence of surgery in the control group from Ireland and other centres described in literature. The conservative treatment of scoliosis (which includes outpatient physiotherapy, inpatient intensive scoliosis rehabilitation (SIR) and high-correction-effect bracing based on plastercasting) shows an obvious reduction in the rate of surgery in patients with idiopathic scoliosis compared with untreated scoliosis patients. Thus it can be seen that the conservative treatment of scoliosis may reduce the incidence of surgery, which not only causes considerable medical expenses but also carries with it the risk of repeated operations and further complications. In our study, we also found highly significant differences by comparison with the work of a bracing centre in the USA. Therefore, the quality of the bracing itself and the effects of primary correction must receive greater consideration in future scientific studies on the subject of "conservative" treatment of scoliosis.


Antibacterial photosensitization through activation of coproporphyrinogen oxidase.
Gram-positive bacteria cause the majority of skin and soft tissue infections (SSTIs), resulting in the most common reason for clinic visits in the United States. Recently, it was discovered that Gram-positive pathogens use a unique heme biosynthesis pathway, which implicates this pathway as a target for development of antibacterial therapies. We report here the identification of a small-molecule activator of coproporphyrinogen oxidase (CgoX) from Gram-positive bacteria, an enzyme essential for heme biosynthesis. Activation of CgoX induces accumulation of coproporphyrin III and leads to photosensitization of Gram-positive pathogens. In combination with light, CgoX activation reduces bacterial burden in murine models of SSTI. Thus, small-molecule activation of CgoX represents an effective strategy for the development of light-based antimicrobial therapies.


The neurotoxicity of amyloid beta protein in aged primates.
Amyloid beta protein deposition is a universal feature of Alzheimer's disease brain. To investigate the effects of amyloid beta protein in aged primates, intracerebral microinjections of solubilized amyloid beta (A beta (1-40)) and control peptides were made into the frontal cortex of 7 primates under stereotactic guidance. Control injections consisted of vehicle alone, a 37 amino acid non toxic peptide (A37), scrambled peptide (CA4), and reverse peptide (A beta (40-1)). Amyloid beta peptide produced dose-dependent cortical lesions that were significantly larger than those produced by vehicle or by isomolar control peptides (3.28 and 2.20 fold larger respectively) (p = < 0.005). In 5 aged primates, the cortex surrounding the amyloid beta lesions contained argyrophilic, thioflavine S fluorescent, Alz 50 and ubiquitin immunoreactive neurons and perikarya. The number of Alz 50 immunoreactive neurons surrounding the amyloid beta injections was significantly greater (mean 127 +/- 39) than the number found surrounding reverse peptide injections (mean 20 +/- 13) and other control peptides (mean 0.8 +/- 0.3) (p < 0.05). Neuronal and neuritic alterations were not found adjacent to the amyloid beta peptide lesions in young monkeys and control injections produced insignificant Alz 50 neuronal positivity. These findings suggest that amyloid beta peptide is neurotoxic in primate brain and that the cytoskeletal response to amyloid beta protein is specific and age-related.


Clinical significance of antibodies to histones in systemic lupus erythematosus.
IgG antibodies to whole histones and to individual histones H1, H2A+H4, H2B and H3 were measured by enzyme linked immunosorbent assay in serum samples from 46 untreated patients with systemic lupus erythematosus (SLE) who had undergone renal biopsy. Patients with the WHO Class IV lupus nephritis had significantly higher levels of antibodies to histones (except H1) than those with milder forms of nephritis. Among antibodies to individual histones, the levels of antibodies to H2B histones best correlated with the renal histologic and the clinical activity of disease (rs = 0.759, rs = 0.577, p less than 0.001, respectively).


Human Leukocyte Antigen (HLA) Class II -DRB1 and -DQB1 Alleles and the Association with Cervical Cancer in HIV/HPV Co-Infected Women in South Africa.
A subset of women who are co-infected with Human Immunodeficiency Virus type 1 (HIV) and Human papillomavirus (HPV), progress rapidly to invasive cervical cancer regardless of antiretroviral therapy (ART) or immune status. We posit that HIV/HPV co-infection along with specific host HLA II -DRB1 and -DQB1 alleles play a major role in cervical cancer development. We conducted a hospital-based genetic susceptibility case-control study in Cape Town, South Africa. We recruited 256 women of the same race, from which a total of 624 HLA-DRB1 and -DQB1 class II genotypes were studied. We characterized HLA II candidate genes using PCR based, Luminex intermediate resolution genotyping and confirmed significant associated genotypes at four-digit resolution by high resolution gel typing. We analyzed 160 alleles from cancer, 64 alleles from pre-cancer and 400 alleles from healthy control women. Whole blood was used for HIV antibody test and HLA II typing. Cervical tumor tissue biopsies were used for HPV genotyping. Tests were statistically significant if p<0.05. Women who were co-infected with HIV/HPV had advanced cervical disease compared to women who were HIV negative. HLA class II -DQB1*03:01 and -DQB1*06:02 alleles were associated with cervical cancer in HIV/HPV co-infected women (p=0.001 and p<0.0001, respectively) while HLA class II -DRB1*13:01 and -DQB1*03:19 were rare or absent in women with cervical disease when compared to the control population (p=0.012 and 0.011, respectively). We describe associations between HLA class II genotypes with cervical cancer, or likely protection from cervical cancer disease in HIV/HPV co-infected South African women. Identifying mechanisms that give rise to this likely protective HLA association will provide insight into development of immune-based prevention measures.


Evaluating from the outside: conducting cross-cultural evaluation research on an American Indian reservation.
There is limited guidance for conducting competent and responsive cross-cultural evaluation research with American Indian communities. The authors draw on Fisher and Ball's Tribal Participatory Research Model to highlight ways in which this project is attempting to be culturally appropriate and sensitive as they partner with an American Indian community to implement and evaluate a youth-based initiative. Challenges encountered during the evaluation are shared, as well as the authors' collective responses to such challenges. Implications for future cross-cultural evaluation researchers are also discussed in light of these experiences.


Association of Perforator Stroke After Basilar Artery Stenting With Negative Remodeling.
Background and Purpose- We try to evaluate whether plaque features and perforator stroke after intracranial stenting is associated with the arterial remodeling patterns in patients with severe basilar artery stenosis. Methods- We studied patients with symptomatic intracranial arterial stenosis who underwent high-resolution magnetic resonance imaging from September 2014 to January 2017. Among them, patients with basilar artery stenosis underwent angioplasty and stenting were recruited. Arterial remodeling patterns were divided into negative or nonnegative remodeling. Plaque features were investigated by high-resolution magnetic resonance imaging, which includes plaque distribution, intraplaque hemorrhage, calcification, as well as enhancement patterns. Incidence of perforator strokes after intracranial stenting was recorded. Plaque features and incidence of poststenting perforator stroke were compared between negative and nonnegative remodeling. Results- Two hundred ninety-eight consecutive patients were enrolled. Among them, 30 patients fulfilled the inclusion criteria. There were 11 patients (36.7%) with negative remodeling and 19 (63.3%) with nonnegative remodeling. Twenty-six patients (86.7%) had diffuse distribution, 5 patients (16.7%) had intraplaque hemorrhage, 2 patients (6.7%) had calcification, and 17 patients (65.4%) had enhancement. Three patients had perforator stroke after stenting. Plaque features were similar between negative and nonnegative remodeling groups. Patients with negative remodeling were more likely to have perforator stroke after stenting comparing with patients with nonnegative remodeling (27.3% versus 0%, P=0.041). Conclusions- Perforator stroke after basilar artery stenting may be related to negative remodeling on high-resolution magnetic resonance imaging. The finding needs to be confirmed in future studies. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02705599.


Primary Signet Ring Cell Carcinoma of Rectum Diagnosed by Boring Biopsy in Combination with Endoscopic Mucosal Resection.
A 46-year-old man with severe back pain visited our hospital. Magnetic resonance imaging revealed extensive bone metastasis and rectal wall thickness. Colonoscopy revealed circumferential stenosis with edematous mucosa, suggesting colon cancer. However, histological findings of biopsy specimens revealed inflammatory cells but no malignant cells. The patient underwent endoscopic ultrasound, which demonstrated edematous wall thickness without destruction of the normal layer structure. After unsuccessful detection of neoplastic cells by boring biopsies, we performed endoscopic mucosal resection followed by boring biopsies that finally revealed signet ring cell carcinoma. Herein, we present a case and provide a review of the literature.