RAN proteins in neurodegenerative disease: Repeating themes and unifying therapeutic strategies.
Microsatellite-expansion mutations cause >50 neurological diseases but there are no effective treatments. Mechanistic studies have historically focused on protein loss-of-function and protein or RNA gain-of-function effects. It is now clear that many expansion mutations are bidirectionally transcribed producing two toxic expansion RNAs, which can produce up to six mutant proteins by repeat associated non-AUG (RAN) translation. Multiple types of RAN proteins have been shown to be toxic in cell and animal models, to lead to common types of neuropathological changes, and to dysregulate key pathways. How RAN proteins are produced without the canonical AUG or close-cognate AUG-like initiation codons is not yet completely understood but RNA structure, flanking sequences and stress pathways have been shown to be important. Here, we summarize recent progress in understanding the role of RAN proteins, mechanistic insights into their production, and the identification of novel therapeutic strategies that may be applicable across these neurodegenerative disorders.


Chemical characterization of high-molar-mass fractions in a Norway spruce knotwood ethanol extract.
The low-molar-mass (LMM) fraction, only, i.e., the GC-eluting compounds, which are mainly lignans, has been characterized in Norway spruce knotwood hydrophilic extracts previously. Of this fraction, many lignans and sesquilignans and all GC peaks supposedly representing dilignans remain unidentified. In this work, dilignans and the GC non-eluting compounds (the high-molar mass fractions, HMM) were characterized in a 7-hydroxymatairesinol-reduced knotwood ethanol extract of Norway spruce by using several fractionation and analytical techniques. A methyl tert-butyl ether (MTBE) insoluble fraction of the extract contained mainly HMM material, of which the main part was shown to consist of lignan oligomers. The oligolignans (with a molar mass up to approximately 3700 Da) seemed to be linked by 55' bonds, some of them containing one or two guaiacylglycerol ether units linked to the lignan by βO4 or β5 bonds. Several oligolignans were identified or tentatively identified. The MTBE soluble fraction, which accounted for the major part (81%) of the extract, contained mainly LMM material (lignans, sesqui- and dilignans). The part of the HMM material in the MTBE soluble fraction that was easily isolable (2%) seemed to contain polymers of fatty acids and alcohols, resin acids, and sterols.


Release of [3H]GABA evoked by glutamate agonists from hippocampal slices: effects of dithiothreitol and glutathione.
The effects of dithiothreitol (DTT) and, reduced (GSH) and oxidized (GSSG), glutathione on the release of [3H]GABA evoked by glutamate and its agonists were studied in rat hippocampal slices. DTT had no effect on the basal release of [3H]GABA but it enhanced and prolonged the glutamate agonist-evoked release. This effect was abolished by (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohept-5,10-imine hydrogen maleate (MK-801), a noncompetitive NMDA antagonist, and blocked by Mg2+ ions. It was only slightly attenuated by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA receptor antagonist, and not affected by L-(+)-2-amino-3-phosphonopropionate (L-AP3), a selective antagonist of the metabotropic glutamate receptor. The effect of DTT on the NMDA-evoked release of GABA was only slightly affected by extracellular Ca2+ but completely blocked by verapamil even in the absence of Ca2+. GSH and GSSG attenuated or abolished the effects of DTT on the agonist-induced release of [3H]GABA. The results imply that the enhanced and prolonged release of GABA evoked by the coexistence of DTT and excitatory amino acids and attenuated by endogenous GSH and GSSG is a consequence of sustained activation of the NMDA receptor-governed ionophores, which contain functional thiol groups. DTT, GSH and GSSG may regulate the redox state and accessibility of these groups. In addition to the influx of extracellular Ca2+, DTT mobilizes Ca2+ from intracellular pools distinct from those regulated by metabotropic glutamate receptors.


Improvement in epistaxis management: the experience of a dedicated hereditary haemorrhagic telangiectasia clinic.
Hereditary haemorrhagic telangiectasia (HHT) is a rare genetic vascular disorder which is characterised by the development of arteriovenous malformations and telangiectasias. A key clinical manifestation is recurrent epistaxis. This study examined the impact of a dedicated HHT clinic in a major Australian tertiary hospital on epistaxis symptoms and subjective quality of life. A multidisciplinary HHT clinic was established in 2015. All patients satisfied either genetic diagnosis or fulfilled Curacao criteria. A protocol based clinical assessment was performed and a standardised treatment regimen was implemented. Patients completed quality of life and epistaxis severity score (ESS) questionnaires at each review. Participants of the dedicated clinic included 21 females (58.3%) and 15 males (41.7%), with a mean age of 49.0 ± 24.0 years. The ACVRL1 variant was the most common (n = 20, 55.6%). A statistically significant reduction in epistaxis severity was noted between the baseline and second review (P = 0.02) and was maintained to the third visit (P = 0.015). Patients older than 50 years demonstrate a consistently higher ESS than those less than 50 years old (P = 0.03). This trend is noted throughout the follow up period with the dedicated clinic. The introduction of a multidisciplinary, dedicated HHT clinic to provide enhanced assessment, monitored treatment regimen and greater access to care, resulted in improvement in the management of epistaxis and quality of life in these patients.


TBI 13 years on: factors associated with post-traumatic growth.
To investigate factors associated with post-traumatic growth (PTG) 13 years after severe traumatic brain injury (TBI) and to see if PTG had remained consistent between 11 and 13 years after injury. TBI survivors (n=21), were interviewed and completed face-to face administration of questionnaires measuring PTG and factors potentially associated with PTG. The design was a longitudinal follow-up study. Factors significantly associated with PTG included: having a sense of personal meaning (purpose and coherence), high life satisfaction now, social support, high-activity levels, a high number of life events, having paid work, new stable relationships after injury, milder disability, and having religious faith. Having a high level of "purpose" was the best predictor of PTG. There was no change in PTG between 11 and 13 years after injury suggesting PTG is a relatively stable phenomenon once established after the early years. Clinicians should be aware of PTG and how it is associated with factors such as "meaning" and "purpose" as well as demographic factors such as, social support, activity such as work, new and stable relationships, milder disability and a shift towards spiritual values. Clinicians can focus advice, resource and effort on supporting these developments. [ • People with TBI do perceive benefits or post-traumatic growth (PTG), after time, which once established remains stable.• Factors such as having a sense of "meaning" and "purpose", are predictors of PTG.• Social support, activity such as work, new and stable relationships, a shift toward spiritual values, and milder disability are also associated with PTG.• Clinicians can focus effort into supporting these developments.]


β-cyclodextrin polymer/Soluplus® encapsulated Ebselen ternary complex (EβpolySol) as a potential therapy for vaginal candidiasis and pre-exposure prophylactic for HIV.
Epidemiological findings have discussed recurrent and persistent vulvovaginal candidiasis to be a major manifestation of HIV infected women. Conversely, women with vulvovaginal candidiasis have higher risk of acquiring HIV transmitted during intercourse. Common treatments for such conditions include combined antiretroviral and antifungal therapy. Drug-Drug interaction is a major problem encountered due to common CYP450 metabolic pathway of azoles and antiretroviral drugs. Ebselen (EB), lipophilic, organo-selenium compound has demonstrated promising anti-HIV and anti-fungal activity. The aim of current research was to develop and characterize a rapidly soluble and non-cytotoxic vaginal film of ebselen which could serve dual purpose of treating vulvovaginal candidiasis and pre-exposure prophylactic (PrEP) against HIV. Ebselen/cyclodextrin polymer/Soluplus® (1:10:10) ternary complex (EβpolySol) showed 200 fold enhancement in aqueous solubility and no degradation of EB in thermogravimetry analysis. EβpolySol film with tensile strength of 33.12 ± 1.98 N/cm2 disintegrated within 30 sec, presented instant drug release with no apparent precipitation in simulated vaginal fluid. EβpolySol film showed compatibility with HEC-1A monolayer and HeLa cells compared to VCF®. EβpolySol film showed MIC of 20 μM against Candida species and IC50 of 0.71 μM against HIV.


"I'm not in this alone" the perspective of parents mediating a physical activity intervention for their children with autism spectrum disorder.
Web-based, parent-mediated interventions have shown to be beneficial for children with autism spectrum disorder (ASD) in a variety of domains. We aimed to examine how parents of children with ASD perceive mediating a physical activity intervention delivered via a private Facebook group. Thirteen families participated in a four-week trial of Project CHASE. Inductive thematic analysis of semi-structured interviews and interactions within the Facebook group were conducted to elicit the perspective of the parents. Thematic analysis resulted in three themes emerging: (1) 'Remembering to Act' encompassed the participants' perspectives of Project CHASE as being an intervention that reminded them of the importance of physical activity, and served as a prompt for them to take action; (2) 'A sharing community' included the subthemes of 'sharing success and struggles' and 'sharing ideas'; and, (3) 'Taking control: possibilities and problems' encapsulates the dichotomy between participants who spoke of embracing and rising to the challenge of taking control, with the parents who spoke of the need for more support, direction, and guidance. The current study suggests parent-mediated, web-based interventions may have the potential for improving the effectiveness of physical activity interventions for children with ASD.


Ceramidase and ceramide synthesis in human kidney and cerebellum. Description of a new alkaline ceramidase.
It has been shown that tissues of patients with Farber's disease characteristically lack acid (pH 4.0) ceramidase. In normal cerebellum, however, ceramide cleavage and the reverse reaction, free fatty acid-dependent ceramide synthesis, both occur not only at pH 4.0 but also at pH 9.0, although normal kidney exhibits these activities only at pH 4.0. Both tissues are capable of snythesizing ceramide via an acyl-COA-dependent pathway at neutral pH. The synthetic analog of ceramide, N-oleoyl-ethanolamine, is a potent inhibitor of ceramidase.


Factors influencing early postoperative complications following surgery for symptomatic spinal metastasis: a single-center series and multivariate analysis.
Patients presenting with neurological deficits and/or pain due to spinal metastasis usually require immediate or subacute surgical treatment. Nevertheless, it is unclear whether or not side effects of primary cancer location might influence postoperative complication rate. We therefore analyzed our spinal database to identify factors influencing early postoperative complications after surgery for symptomatic spinal metastases. From 2013 to 2017, 163 consecutive patients suffering from symptomatic spinal metastases were treated at our department. Early postoperative complications were defined as any postoperative event requiring additional medical or surgical treatment within 30 days of spinal surgery. A multivariate regression analysis was performed to identify independent predictors for postoperative complications after surgery for spinal metastasis. Overall, 39 of 163 patients who underwent spinal surgery for spinal metastasis developed early postoperative complications throughout the treatment course (24%). Preoperative ASA score ≥ 3 (p = 0.003), preoperative C-reactive protein level > 10 mg/l (p = 0.008), preoperative Karnofsky Performance Score < 60% (p = 0.03), radiation treatment within 2 months of surgery (p = 0.01), presence of diabetes mellitus (p = 0.008), and preoperative complete neurological impairment (p = 0.04) were significant and independent predictors for early postoperative complications in patients with surgery for spinal metastasis. The ability to preoperatively predict postoperative complication risk is valuable to select critically ill patients at higher risk requiring special attention. Therefore, the present study identified several significant and independent risk factors for the development of early postoperative complication in patients who underwent surgery for spinal metastasis.


Research ethics consultation: an attempt and 5-year experience in a Japanese University Hospital.
Research ethics consultation is an advisory activity that differs from ethics committees, and its role is not yet widely known in Japan. Research ethics consultations were started in 2012 by members of the Clinical Trial Center of Tokushima University Hospital, a support section for clinical trials. We analyzed the research ethics consultation records from Tokushima University Hospital during the 5-year period of 2012-2016 to examine the Japanese context of research ethics consultation. During the study period, 125 research ethics consultations were carried out, 115 (91%) before starting studies. All but one request were from investigators at Tokushima University. The main issue was compatibility with guidance and regulations (n = 74, 67.2%), such as ethical handling of human biological specimens and information utilized in research; only 6 (4.8%) requests involved research ethics issues that investigators face in their research. Therefore, it is necessary to expand the consultation function, with a nationwide system of consultant education and data sharing. Moreover, standardization of consultation should be considered.


Genetics of neuropsychiatric symptoms in patients with Alzheimer's disease: A 1-year follow-up study.
The aim of this study was to investigate the associations between candidate gene variants and domains of neuropsychiatric symptoms (NPS) and the changes in these associations over a 1-year period. Seven hundred and ninety-three Taiwanese participants (47.8% female) with Alzheimer's disease (AD) were enrolled. Genes associated with a risk of developing AD were selected as candidate genes. NPS were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q), and the NPI-Q total score and sub-scores for the Psychosis, Mood, and Frontal Syndrome domains were calculated. Patients with AD and the APOE ε4 allele exhibited more obvious symptoms of psychosis. Mood symptoms were associated with CD33 rs3865444 and EPHA1 rs11767557, and frontal symptoms were associated with SORL1 rs3824968. A 1-year Time × Alleles interaction effect of CD33 rs3865444 on mood symptoms was discerned. Risk genes of AD, which are also associated with NPS, are APOE ε4 for psychosis, CD33 and EPHA1 for mood symptoms, and SORL1 for frontal symptoms. The association between CD33 and mood symptoms is dynamic and could change over 1 year; however, the results should be interpreted with caution because corrections for multiple comparisons were not performed.


[Nurses as a support to improve the quality of life during assisted reproduction].
The aim of this study was to measure how infertility and assisted reproduction treatments (including artificial insemination) could affect the quality of life, and to evaluate how nurses could be helpful in this process, by alleviating anxiety and increasing the quality of life. A cross-sectional observational study was conducted on 48 patients (26 cycles) in an Assisted Reproduction Unit from 2nd December 2013 to 30th April 2014. Socio-demographic data were obtained, with the quality of life being assessed using the FertiQoL questionnaire before and after the treatment, and the consultations with a nurse by telephone or e-mail of these patients were also analyzed. The study results show a decreased quality of life in these patients, which was worse in men and in couples who had no previous children. Patient-centered care improved quality of life and tolerability to the assisted reproduction treatment. Patients frequently telephoned the nurse to solve their doubts and problems. The present study suggests that nurses can play an important role in improving the quality of life of patients undergoing assisted reproduction treatment.


Patient-Doctor Relationship in Dermatology: From Compliance to Concordance.
The concept of what the doctor-patient relationship should be has changed increasingly in recent years. Previously, an asymmetric relationship was assumed. Compliance and adherence are terms used currently. The concordance model goes further and examines the effectiveness of the mutual process between the doctor and the patient. In this model the interaction is two-sided and involves finding a decision as partners. The origins of this approach are to be found in psychoanalytic theory.


Current and future perspectives on the TARGET system: the registration system for Glivec established by the JSH.
Since hematology is a highly specialized field, an individual physician may not have much direct treatment experience with a given disease. Therefore, the Japanese Society of Hematology (JSH) has discussed establishing a registry of hematologic disorders, in order to contribute to improving the quality of treatments and clinical outcomes in this field. As a first step, the Timely and Appropriate Registration System for GLIVEC Therapy (TARGET), a registration system for chronic myeloid leukemia (CML) patients treated with imatinib, was established in October 2003. We present the preliminary results of the first 4 years' experience with this system. CML patients treated with imatinib in Japan were registered through the website and the patient's clinical course, including parameters and events like imatinib dose, blood counts, adverse events, and efficacy were recorded in months 1, 3, 6, 9, and 12 and then every 6 months thereafter. By September 2007, 862 patients from 176 hospitals were registered. Follow-up period was 0-54 months, and 127 patients were followed-up for more than 36 months. Based on these cumulative data, present imatinib treatment trends were analyzed and safety and efficacy were compared with international trial data.


Removal of oxytetracycline from water by S-doped MIL-53(Fe): Synergistic effect of surface adsorption and persulfate activation.
In this study, a novel catalyst based on MIL-53(Fe) was synthesized and modified through sublimed sulfur (S-MIL-53(Fe)) to induce a synergistic effect of surface adsorption and persulfate activation. The S-doped modification not only increased the surface area but also accelerated the electron transfer process of the iron cycle. The performance of the newly synthesized S-MIL-53(Fe) adsorptive catalyst was evaluated by chemical adsorption and peroxydisulfate (PDS) activated removal of an emerging pollutants, oxytetracycline (OTC). The S-MIL-53(Fe) adsorptive catalyst was able to adsorb 61.7% of OTC after 120 min, and the removal efficiency reached 84.8% within 5 min after PDS dosing. The boosting effect of sulfur on the system was confirmed by characterization analysis and experimental testing. Even after 7 cycles, the removal efficiency of S-MIL-53(Fe) (69.0%) for OTC remained superior to that of pure MIL-53(Fe) (25.1%). Additionally, the adsorption kinetics and adsorption isotherm model of the material were investigated. The possible OTC degrading process was proposed based on radical quenching and electron paramagnetic resonance (EPR). This study provides a feasible way to fabricate an S-doped MIL-53(Fe) adsorptive catalyst for the remediation of antibiotics-containing wastewater.


Correction to: Endoscopic Ultrasound-Guided Gastrojejunostomy for Superior Mesenteric Artery Syndrome Secondary to Rapid Weight Loss.
[This corrects the article DOI: 10.14309/crj.0000000000000868.].


Mycotoxins in developing countries: A case study of maize in Nepal.
Maize (Zea mays) is an important food crop in the foothills of the Nepal Himalaya Mountains. Surveys have found that maize in Nepal is contaminated withFusarium species, mainlyF. verticillioides andF. proliferatum, which produce fumonisins, andF. graminearum, which produces trichothecenes, mainly nivalenol and 4-deoxynivalenol. Maize from smallholder farms and markets is often contaminated with fumonisins and trichothecenes above 1000 ng/g, a level of concern for human health. These mycotoxins were not eliminated by traditional fermentation for producing maize beer, but Nepalese women were able to detoxify contaminated maize by hand-sorting visibly disease kernels. An integrated approach to reduce mycotoxins risks in maize in Nepal and other developing countries should include plant breeding to produce ear rot resistant cultivars, along with education in mycotoxins risks and in agricultural and grain storage practices to reduce mycotoxin contamination.


The dinucleotide (CA) repeat polymorphism of estrogen receptor beta but not the dinucleotide (TA) repeat polymorphism of estrogen receptor alpha is associated with venous ulceration.
Venous ulcers are the predominant form of chronic wound in the elderly, accounting for around 70% of all cases. The steroid sex hormone estrogen plays a crucial role in normal human skin maintenance and during cutaneous wound repair following injury. Estrogen can reverse age-related impaired wound healing by dampening the inflammatory response and increasing matrix deposition at the wound site. The molecular actions of estrogen are mediated through two nuclear sex steroid hormone receptors, estrogen receptor alpha (ERalpha) and beta (ERbeta). We have conducted a case-control study to investigate whether dinucleotide repeat polymorphisms in the estrogen receptor genes are associated with venous ulceration in the UK Caucasian population. Genomic fragments containing the ERalpha dinucleotide (TA)(n) repeat polymorphism or the ERbeta dinucleotide (CA)(n) repeat polymorphism were amplified by polymerase chain reaction in subject DNA samples and genotyped according to fragment length by capillary electrophoresis. There was no evidence to suggest that the TA repeat polymorphism of ERalpha was associated with venous ulceration. However, the CA*18 allele of the ERbeta CA repeat polymorphism was significantly associated with venous ulceration (n = 120, OR = 1.8, 95% CI = 1.1-2.8, P = 0.02). When the CA repeats alleles were grouped together into either low (L < or = 18) or high (H > 18) numbers of CA repeats, the low (L) repeat allele was significantly associated with venous ulceration (OR = 1.5, 95% CI = 1.0-2.2, P = 0.03). Our results show that a specific ERbeta variant is associated with impaired healing in the elderly, predisposing individuals to venous ulceration.


Use of a soft sensor for the fast estimation of dried cake resistance during a freeze-drying cycle.
This paper deals with the determination of dried cake resistance in a freeze-drying process using the Smart Soft Sensor, a process analytical technology recently proposed by the authors to monitor the primary drying stage of a freeze-drying process. This sensor uses the measurement of product temperature, a mathematical model of the process, and the Kalman filter algorithm to estimate the residual amount of ice in the vial as a function of time, as well as the coefficient of heat transfer between the shelf and the product and the resistance of the dried cake to vapor flow. It does not require expensive (additional) hardware in a freeze-dryer, provided that thermocouples are available. At first, the effect of the insertion of the thermocouple in a vial on the structure of the product is investigated by means of experimental tests, comparing both sublimation rate and cake structure in vials with and without thermocouple. This is required to assess that the temperature measured by the thermocouple is the same of the product in the non-monitored vials, at least in a non-GMP environment, or when controlled nucleation methods are used. Then, results about cake resistance obtained in an extended experimental campaign with aqueous solutions containing different excipients (sucrose, mannitol and polyvinylpyrrolidone), processed in various operating conditions, are presented, with the goal to point out the accuracy of the proposed methodology.


Hypotensive effect of naloxone on high blood pressure induced by stress in the rat.
A naloxone-reversible enhancement of systolic blood pressure (BP) was induced in rats by application of three different types of stressor, i.e. intense light and sound, cold and foot-shock. In the case of labile high BP provoked by short-term isolation, the opiate antagonist naloxone (1 mg/Kg, i.p.) was also found to reverse hypertension. Naltrexone (2.5 mg/Kg, i.p.) also diminished high BP readings of briefly isolated rats. Conversely, blockade of the opiate receptor with naloxone did not alter elevated BP in cases of established hypertension (spontaneously hypertensive rats, deoxycorticosterone (DOCA)-salt rats and long-term isolated rats). These data can be taken as an evidence of opioid involvement at the onset of high BP readings induced by stress. However, once hypertension becomes established, the opioid system appears to recover its silent features.


Hearing loss in patients with mucopolysaccharidoses-1 and -6 after hematopoietic cell transplantation: A longitudinal analysis.
Hearing loss is frequently seen in mucopolysaccharidoses (MPS) patients. Although hematopoietic cell transplantation (HCT) increases overall survival, disease progression is observed in certain tissues. This study describes the course of hearing loss (HL) over time in transplanted MPS patients. Transplanted MPS patients between 2003 and 2018 were included and received yearly audiological evaluation, including auditory brainstem response (ABR) or pure tone audiometry (PTA). Twenty-eight MPS-1 and four MPS-6 patients were analyzed with a median follow-up of 5 years (range 11 months-16 years). Air conduction threshold improved significantly over time (P < .001) with a PTA 1-year post-HCT of 50 ± 0.7 dB to 23 ± 11 dB 13 years post-HCT. Bone conduction threshold worsened with a PTA 1 year post-HCT of 10 ± 7 dB to 18 ± 9 dB 13 years post-HCT (P = .34). The degree of HL varied from mainly mild-severe early after HCT to normal-mild at longer follow-up. The type of HL consisted of mainly conductive in the first years post-HCT in contrast to mainly sensorineural at longer follow-up. MRIs of the cerebellopontine angle did not show abnormalities. HL is still seen in patients with MPS despite HCT and consists of a conductive type early after HCT in contrast to a sensorineural type at longer follow-up in the majority of cases. Yearly follow-up of HL is necessary to timely intervene, as hearing is important in the speech and language development of children and their academic achievements.


An IUPAC-based approach to estimate the detection limit in co-extraction-based optical sensors for anions with sigmoidal response calibration curves.
An approach based on IUPAC methodology to estimate the limit of detection of bulk optode-based analytical methods for anions has been developed. The traditional IUPAC methodology for calculating the detection limit was modified to be adapted to particular cases where the calibration curves have a sigmoidal profile. Starting from the different full theoretical models for every co-extraction mechanism of the analyte in the membrane in bulk optodes, several particular simplified models at low analyte concentration were obtained and validated. The slope of the calibration curve at low analyte concentration was calculated from the first derivative of the simplified equation and, subsequently, the detection limit was estimated. This fitted-for-purpose estimation strategy was applied to anion quantification for in-house bulk optode-based analytical methods, and the estimated limits of detection were compared with those obtained by applying classical geometrical methodology. This way of establishing the detection limit yields values that maintain their true statistical and probabilistic aspects. It can be easily applied to any analytical system which yields non-linear calibration curves at low analyte concentration.


Structure and regulation of the mouse cardiac troponin I gene.
The gene coding for mouse cardiac troponin I (TnI) has been cloned and sequenced. The cardiac TnI gene contains 8 exons and has an exon-intron organization similar to the quail fast skeletal TnI gene except for the region of exons 1-3, which is highly divergent. Comparative analysis suggests that cardiac TnI exon 1 corresponds to fast TnI exons 1 and 2 and that cardiac exon 3, which codes for most of the cardiac-specific amino-terminal extension and has no counterpart in the fast gene, evolved by exon insertion/deletion. The amino acid sequence of cardiac TnI exon 4 shows limited homology (36% identity) with fast TnI exon 4 but is remarkably similar (79% identity) to the corresponding sequence of slow TnI, possibly reflecting an isoform-specific TnC-binding site. The cardiac TnI gene is one of the very few contractile protein genes expressed exclusively in cardiac muscle. To identify the regulatory sequences responsible for the cardiac-specific expression of this gene we transfected cultured cardiac and skeletal muscle cells with fragments up to 4.0 kilobases of the 5'-flanking region linked to a reporter gene. Deletion analysis reveals four major regions in the 5'-flanking sequence, a minimal promoter region, which directs expression at low level in cardiac and skeletal muscle cells, and two upstream cardiac-specific positive regions separated by a negative region.


Attention and speech-processing related functional brain networks activated in a multi-speaker environment.
Human listeners can focus on one speech stream out of several concurrent ones. The present study aimed to assess the whole-brain functional networks underlying a) the process of focusing attention on a single speech stream vs. dividing attention between two streams and 2) speech processing on different time-scales and depth. Two spoken narratives were presented simultaneously while listeners were instructed to a) track and memorize the contents of a speech stream and b) detect the presence of numerals or syntactic violations in the same ("focused attended condition") or in the parallel stream ("divided attended condition"). Speech content tracking was found to be associated with stronger connectivity in lower frequency bands (delta band- 0,5-4 Hz), whereas the detection tasks were linked with networks operating in the faster alpha (8-10 Hz) and beta (13-30 Hz) bands. These results suggest that the oscillation frequencies of the dominant brain networks during speech processing may be related to the duration of the time window within which information is integrated. We also found that focusing attention on a single speaker compared to dividing attention between two concurrent speakers was predominantly associated with connections involving the frontal cortices in the delta (0.5-4 Hz), alpha (8-10 Hz), and beta bands (13-30 Hz), whereas dividing attention between two parallel speech streams was linked with stronger connectivity involving the parietal cortices in the delta and beta frequency bands. Overall, connections strengthened by focused attention may reflect control over information selection, whereas connections strengthened by divided attention may reflect the need for maintaining two streams in parallel and the related control processes necessary for performing the tasks.


Aging, prospective memory, and health-related quality of life in HIV infection.
HIV infection and older age are each independently associated with lower health-related quality of life (HRQoL) and deficits in prospective memory (PM), which is a distinct aspect of cognition involving the ability to "remember to remember" to do something at a future occasion. The present study investigated associations between PM and HRQoL in 72 older (≥ 50 years) and 41 younger (≤ 40 years) HIV-infected adults. Self-reported PM complaints predicted HRQoL across the entire sample, but there was a significant interaction between performance-based PM and age group on HRQoL, such that lower time-based PM was associated with lower HRQoL only in the younger cohort. Within the younger group, time-based and self-reported PM significantly predicted mental HRQoL independent of other risk factors (e.g. depression). These findings suggest that PM plays a unique role in HRQoL outcomes among younger persons living with HIV infection and support the examination of other age-related factors (e.g. effective use of compensatory strategies) that may regulate the adverse impact of PM on everyday functioning.


Asbestosis diagnosis algorithm combining the lung segmentation method and deep learning model in computed tomography image.
Early detection of asbestosis is important; hence, quick and accurate diagnostic tools are essential. This study aimed to develop an algorithm that combines lung segmentation and deep learning models that can be utilized as a clinical decision support system (CDSS) for diagnosing patients with asbestosis in segmented computed tomography (CT) images. We accurately segmented the lungs in CT images of patients examined at Seoul St. Mary's Hospital using a threshold-based method. Lungs with asbestosis and normal lungs were classified by applying the segmented image to the long-term recurrent convolutional network deep learning model. Performance was evaluated using the area under the receiver operating characteristic curve (AUROC) and F1 score from the test data. The algorithm developed using the DenseNet201pre-trained model showed excellent performance, with a sensitivity of 0.962, specificity of 0.975, accuracy of 0.970, AUROC of 0.968, and F1 score of 0.961. We developed an algorithm with significantly better diagnostic accuracy than a radiologist (0.970 vs. 0.73-0.79). Our developed algorithm is expected to be an excellent support tool if used as a CDSS to diagnose asbestosis using CT images.


Ablative dose proton beam therapy for stage I and recurrent non-small cell lung carcinomas : Ablative dose PBT for NSCLC.
To evaluate the efficacy and safety of ablative dose hypofractionated proton beam therapy (PBT) for patients with stage I and recurrent non-small cell lung carcinoma (NSCLC). A total of 55 patients with stage I (n = 42) and recurrent (n = 13) NSCLC underwent hypofractionated PBT and were retrospectively reviewed. A total dose of 50-72 CGE (cobalt gray equivalent) in 5-12 fractions was delivered. The median follow-up duration was 29 months (range 4-95 months). There were 24 deaths (43.6%) during the follow-up period: 11 died of disease progression and 13 from other causes. Kaplan-Meier overall survival rate (OS) at 3 years was 54.9% and the median OS was 48.6 months (range 4-95 months). Local progression was observed in 7 patients and the median time to local progression was 9.3 months (range 5-14 months). Cumulative actuarial local control rate (LCR), lymph node metastasis-free survival, and distant metastasis-free survival rates at 3 years were 85.4, 78.4, and 76.5%, respectively. Larger tumor diameter was significantly associated with poorer LCR (3-year: 94% for ≤3 cm vs. 65% for >3 cm, p = 0.006) on univariate analysis and also an independent prognostic factor for LCR (HR 6.9, 95% CI = 1.3-37.8, p = 0.026) on multivariate analysis. No grade 3 or 4 treatment-related toxicities developed. One grade 5 treatment-related adverse event occurred in a patient with symptomatic idiopathic pulmonary fibrosis. Ablative dose hypofractionated PBT was safe and promising for stage I and recurrent NSCLC.


[Clinical prospective study on maternal-fetal transmission of human bocavirus].
To investigate maternal-fetal transmission at human bocavirus (HBoV). IgG antibody to HBoV in serum samples of 316 mothers were determined with ELISA and HBoV DNA was determined with real time PCR in the sera of the mothers and their infants. HBoV-IgG was positive in 40.20 percent (127/316) of the mothers, while it was positive in 29.43 percent (93/316) of the cord blood specimens of the infants. The difference between the two groups was significant (X2=8.12, P less than 0.005); 93 samples of both the mothers and the infants were positive for HBoV-IgG. HBoV-IgG can cross the placenta to the fetuses through placenta. Further study is needed to answer the question whether vertical maternal-fetal transmission occurs.


Repeated echocardiographic imaging of aortic stenosis: Real-life lessons.
Timing of aortic valve intervention is dependent on the accuracy and reproducibility of echocardiographic (ECHO) parameters. We aimed to assess haemodynamic subsets of aortic stenosis (AS), their change over time, and variability of ECHO parameters. This retrospective, longitudinal study compared sequential ECHO over 15 months to identify concordant or discordant aortic valve area (AVA) and mean pressure gradient (MPG) in order to determine the real world variability of echocardiographic indices. We included 143 patients with a mean age of 76.0 years. The median length of time between studies was 112 days (IQR 38-208). Initially, participants were classified as 9 (6.4%) mild, 47 (33.6%) moderate, and 84 (60.0%%) severe AS. In 80 (55.9%) AVA and MPG were concordant; stroke volume index (SVi) was < 35 mL/m2 in 53 (74.6%). AS severity was downgraded in 29 (20.7%) patients. MPG was most consistent and AVA was the least consistent between successive investigations (intraclass correlation coefficients R = .86 and R = .76, respectively). Even small variations in left ventricular outflow tract (LVOT) measurement of 1 standard deviation reclassified up to 67% of participants from severe to non-severe. Almost half of patients with AS have valve area/gradient discordance. Variations in LVOT diameter measurement commensurate with clinical practice reclassified AS severity in up to two-third of cases. Change in AS severity should only be accepted following careful scrutiny of all available ECHO data.


Evaluation of restorative care vs usual care for older adults receiving an acute episode of home care.
Illness and hospitalization often trigger functional decline among older persons. Home care services implemented for functional decline provide an opportunity to intervene to improve outcomes. To compare functional status and the likelihood of remaining at home for persons receiving restorative care vs usual home care. Intervention using prospective individual matching conducted between November 1, 1998, and April 30, 2000. Six offices of a home care agency in Connecticut were used. One branch office served as the restorative care unit and the other 5 served as usual care offices. Patients receiving home care through the restorative care office who were 65 years or older; in receipt of Medicare-covered home care lasting at least 7 days; with absence of severe cognitive impairment; and not terminal, bedridden, or requiring total care were matched with patients from 1 of the usual care offices. The matching factors included age, sex, race, baseline self-care function, cognitive status, whether hospitalization preceded the home care episode, and date of the home care episode. Of the 712 eligible restorative care patients, 691 (97%) were matched with a usual care patient. Restorative care, provided by the home care agency nursing, therapy, and home health aide staff, was based on principles from geriatric medicine, nursing, rehabilitation, and goal attainment. Remaining at home, functional status at completion of the home care episode, and duration and intensity of home care episode. Compared with usual care, and after adjusting for baseline characteristics and other factors, restorative care was associated with a greater likelihood of remaining at home (82% vs 71%; odds ratio [OR], 1.99; 95% confidence interval [CI], 1.47-2.69) and a reduced likelihood of visiting an emergency department (10% vs 20%; OR, 0.44; 95% CI, 0.32-0.61). Home care episodes were shorter (mean [SD], 24.8 [26.8] days vs 34.3 [44.2] days; S = -17 821; P<.001). Restorative care patients had better mean (SD) scores than usual care patients in self-care (11.0 [2.1] vs 10.7 [2.5]; P =.07 after adjustment), home management (9.5 [2.9] vs 9.2 [3.0]; P =.05 after adjustment), and mobility (3.3 [0.8] vs 3.2 [0.9]; P =.02 after adjustment). This trial suggests that reorganizing the structure and goals of home care can enhance health outcomes of older patients without increasing health care utilization.


Gene expression signatures after ethanol exposure in differentiating embryoid bodies.
During the differentiation process, various epigenetic factors regulate the precise expression of important genes and control cellular fate. During this stage, the differentiating cells become vulnerable to external stimuli. Here, we used an early neural differentiation model to observe ethanol-mediated transcriptional alterations. Our objective was to identify important molecular regulators of ethanol-related alterations in the genome during differentiation. A transcriptomic analysis was performed to profile the mRNA expression in differentiating embryoid bodies with or without ethanol treatment. In total, 147 differentially expressed genes were identified in response to 50mM ethanol. Of these differentially expressed genes, 78 genes were up-regulated and 69 genes were down-regulated. Our analysis revealed a strong association among the transcript signatures of the important modulators which were involved in protein modification, protein synthesis and gene expression. Additionally, ethanol-mediated activation of DNA transcription was observed. We also profiled ethanol-responsive transcription factors (TFs), upstream transcriptional regulators and TF-binding motifs in the differentiating embryoid bodies. In this study, we established a platform that we hope will help other researchers determine the ethanol-mediated changes that occur during cellular differentiation.


Current and preservice teachers' views and beliefs regarding martial arts and the inclusion of martial arts in Australian school settings: A cross-sectional study.
This study investigates views and beliefs of current and preservice teachers regarding martial arts (MA) and the inclusion of martial arts in schools. Participants completed an anonymous, 28-item questionnaire made available online via Qualtrics (August-November 2020). Data was analysed using SPSS software to compare mean scores by sex, and between qualified teachers and preservice teachers. Qualitative data in the form of quotes was drawn upon and used to complement the quantitative results. Results indicate teachers and preservice teachers view MA as a worthwhile and beneficial activity for school-aged students, and support the inclusion of MA into school settings. These findings may be useful to inform policy and practice in schools, and the development of teacher education programs, professional development courses, and school-based education programs utilizing MA to meet physical education learning outcomes.


A specific microassay for evaluating hepatic LDH activity in co-cultures of hepatocytes with other cells.
This study describes the development of a simple, rapid and reproducible microassay for determining the intracellular LDH activity of rat hepatocytes present in a co-culture system with other cells. The procedure involves treatment of cellular homogenates with an anti-LDH antiserum that specifically inhibits the LDH activity of rat hepatocytes. The assay is performed in 96-well plates and LDH activity can be measured directly in the same wells using a colorimetric method. The difference in LDH activity values measured before and after antiserum incubation reflects the LDH content of the hepatocytes in the sample. The advantages of this method are the small number of cells required, a reduction in sample handling and the possibility of differentiating LDH activity in hepatic and non-hepatic cells. The possible applications of this technique as a parameter for biochemical data and as a test for cytotoxicity studies in co-cultures are also discussed.


Further evidence for the procidin function of C3.
It was found that heat-inactivated serum supported phagocytosis, but did not promote oxygen consumption or killing of Candida, by human polymorphonuclear leucocytes (PMNs). It was also established that C3 is required for activation of the PMN candidacidal related mechanisms of superoxide anion generation and iodination. Addition of purified C3 to C3 deficient serum restored phagocytic killing. Further evidence for C3 involvement in Candida killing was obtained from studies of PMN ingestion and killing in the presence of trypan blue or heparin. Trypan blue, which antagonises C3 receptors, prevented efficient killing, as did heparin, which affects C3 conversion in normal serum. From these results it is evident that phagocytic killing is not an obligatory consequence of ingestion. The findings also indicate that killing by PMNs is dependent upon the interaction of humoral factors, termed procidins, with receptors responsible for initiation of microbicidal mechanisms. Activation products of C3 may stimulate phagocytic killing by engagement of their counterpart receptors on PMNs.


Prostacyclin versus thromboxane metabolite excretion: changes in pregnancy and labor.
Urinary TXB2 and 6-keto-PGF1 alpha were measured by high pressure liquid chromatography combined with radioimmunoassay, in order to determine whether or not urinary excretion of 6-keto-PGF1 alpha and TXB2 followed a same pattern in pregnancy and labor. The excretion of 6-keto-PGF1 alpha was higher than that of TXB2 in both non-pregnant and pregnant women, but the ratio between them increased in pregnancy. The urinary excretion of both 6-keto-PGF1 alpha and TXB2 excretion was significantly increased (p less than 0.001) in pregnancy. Labor was associated with a much wider inter-individual variation in the excretion of 6-keto-PGF1 alpha and TXB2 than observed in pregnancy and in non-pregnant women. Also, the ratio between the two compounds varied more in labor than in pregnancy. The data indicate that the urinary levels of these two compounds do not follow a single well-determined pattern in pregnancy and labor.


Altered FOXO1 activation in the programming of cardiovascular alterations by maternal diabetes.
Maternal diabetes programs cardiovascular alterations in the adult offspring but the mechanisms involved remain unclarified. Here, we addresed whether maternal diabetes programs cardiac alterations related to extracellular matrix remodeling in the adult offspring, as well as the role of forkhead box transcription factor 1 (FOXO1) in the induction of these alterations. The heart from adult offspring from control and streptozotocin-induced diabetic rats was evaluated. Increased glycemia, triglyceridemia and insulinemia and markers of cardiomyopathy were found in the offspring from diabetic rats. In the heart, an increase in active FOXO1 and mRNA levels of its target genes, Mmp-2 and Ctgf, genes related to an altered extracellular matrix remodeling, together with an increase in collagen deposition and a decrease in the connexin43 levels, were found in the offspring from diabetic rats. Altogether, these results suggest an important role of FOXO1 activation in the cardiac alterations induced by intrauterine programming in maternal diabetes.


Home traction in the treatment schedule of overhead traction for developmental dysplasia of the hip.
Our department introduced an overhead traction method (OHT) into the treatment protocol for developmental dysplasia of the hip (DDH) in 1964. With our method, a minimum of 6 weeks of hospitalization was necessary, and the burden for the patients and their families was significant. Since 1998, we have employed home traction into the OHT protocol to shorten the duration of hospitalization. The objective of this study was to investigate the efficacy and safety of home traction in the treatment schedule of OHT for DDH. Home traction was employed for most of the horizontal traction period after initial hospitalization for orientation. We compared 20 patients who underwent home traction in the OHT treatment schedule (Home T group) with 20 patients who underwent hospital traction for the entire period (Hosp. T group). The effect of traction, the complications during traction, the presence or absence of developing avascular necrosis, the total duration of hospitalization, and the total duration of treatment were investigated in the two groups. There were no significant differences in the effect of traction, frequency of complications during traction, or frequency of avascular necrosis after reduction between the Home T and Hosp. T groups. The mean durations of hospitalization were 28.5 and 45.9 days for the Home T and Hosp. T groups, respectively. There was no significant difference in the total duration of treatment between the two groups. Home traction in the OHT schedule is safe and useful because it can shorten the hospitalization period with a traction effect equal to that of hospital traction and without significant differences in complications. A short-term instructive hospitalization period may be useful to reduce the disadvantages of home traction, that is, unreliable performance of traction and increased anxiety of the family.


Risk analysis for plant-made vaccines.
The production of vaccines in transgenic plants was first proposed in 1990 however no product has yet reached commercialization. There are several risks during the production and delivery stages of this technology, with potential impact on the environment and on human health. Risks to the environment include gene transfer and exposure to antigens or selectable marker proteins. Risks to human health include oral tolerance, allergenicity, inconsistent dosage, worker exposure and unintended exposure to antigens or selectable marker proteins in the food chain. These risks are controllable through appropriate regulatory measures at all stages of production and distribution of a potential plant-made vaccine. Successful use of this technology is highly dependant on stewardship and active risk management by the developers of this technology, and through quality standards for production, which will be set by regulatory agencies. Regulatory agencies can also negatively affect the future viability of this technology by requiring that all risks must be controlled, or by applying conventional regulations which are overly cumbersome for a plant production and oral delivery system. The value of new or replacement vaccines produced in plant cells and delivered orally must be considered alongside the probability and severity of potential risks in their production and use, and the cost of not deploying this technology--the risk of continuing with the status quo alternative.


Oxidative stress in chronic vascular disease: From prediction to prevention.
This review article is intended to describe the strong relationship between oxidative stress and vascular disease. Reactive oxygen species (ROS) play an important role in the pathogenesis of vascular disease: oxidative stress is intimately linked to atherosclerosis, through oxidation of LDL and endothelial dysfunction, to diabetes, mainly through advanced glycation end-products (AGEs)/receptor for AGE (RAGE) axis impairment, protein kinase C (PKC), aldose reductase (AR) and NADPH oxidase (NOX) dysfunction, and to hypertension, through renin–angiotensin system(RAS) dysfunction. Several oxidative stress biomarkers have been proposed to detect oxidative stress levels and to improve our current understanding of the mechanisms underlying vascular disease. These biomarkers include ROS-generating and quenching molecules, and ROS-modified compounds, such as F2-isoprostanes. An efficient therapeutic approach to vascular diseases cannot exclude evaluation and treatment of oxidative stress. In fact, oxidative stress represents an important target of several drugs and nutraceuticals, including antidiabetic agents, statins, renin-angiotensin system blockers, polyphenols and other antioxidants. A better understanding of the relations between atherosclerosis, diabetes, hypertension and ROS and the discovery of new oxidative stress targets will translate into consistent benefits for effective vascular disease treatment and prevention.


Asymptomatic simian immunodeficiency virus infection decreases blood CD4(+) T cells by accumulating recirculating lymphocytes in the lymphoid tissues.
Declining blood CD4(+) T-cell counts mark the progress of simian immunodeficiency virus (SIV) disease in macaques and model the consequences of untreated human immunodeficiency virus infection in humans. However, blood lymphocytes are only a fraction of the recirculating lymphocyte pool, and their numbers are affected by cell synthesis, cell depletion, and distribution among blood and lymphoid tissue compartments. Asymptomatic, SIV-infected macaques maintained constant and nearly normal numbers of recirculating lymphocytes despite the decline in CD4(+) T-cell counts. Substantial depletion was detected only when blood CD4(+) T-cell counts fell below 300/microliter. In asymptomatic animals, changes in CD4(+) T-cell distribution were more important than lymphocyte depletion for controlling the blood cell levels.


Do different metabolic syndrome definitions predict cerebrovascular events and coronary heart disease independent of their components?: 9 years follow-up of the tehran lipid and glucose study.
The purpose of this study was to examine whether metabolic syndrome (MetS), applying different definitions, predicts incident coronary heart disease (CHD) and cerebrovascular events (CVAs) independent of its components. Among 2548, aged ≥ 50 years, World Health Organization, International Diabetes Federation, and Joint Interim Statement criteria were used to define MetS. Cox proportional hazards regression was implemented to estimate hazard ratios of incident CVA and CHD. During 9.3 years of follow-up, 72 and 343 cases of CVA and CHD events occurred. The multivariate hazard ratios (95% CI) of incident CVA and CHD were 2.71 (1.57-4.68) and 2.07 (1.63-2.64) for MetS as defined by the Joint Interim Statement, respectively. There was no difference among the 3 definitions of MetS regarding the prediction of the CVA incidence. However, MetS as defined by the Joint Interim Statement predicted CHD better than the International Diabetes Federation definition. After adjustment for components, MetS lost its association with CHD and CVA; in this model, the elevated blood pressure and high fasting plasma glucose (International Diabetes Federation definition) showed significant risk for CVA events; regarding CHD events, the elevated blood pressure, high fasting plasma glucose, and, for World Health Organization definition, obesity and dyslipidemia remained as predictors. All definitions of MetS were associated with CVA and CHD events. After adjusting its components, MetS lost its association with incident CVA and CHD; however, elevated blood pressure for both CVA and CHD events and high fasting plasma glucose for CHD events remained as independent predictors in all definitions.


Fluorescence decay and quantum yield characteristics of acridine orange and proflavine bound to DNA.
Fluorescence properties (quantum yield, decay curve, lifetime and polarization) of acridine orange and proflavine bound to DNA were examined as a function of nucleotide to dye (P/D) ratio. First, mean fluorescence lifetimes were determined by the phase-shift measurements. The lifetime and quantum yield of acridine orange increased in a parallel fashion with increasing P/D ratio. There was no parallel relation between the lifetime and quantum yield for proflavine; the lifetime showed a minimum around P/D equals 10...


[Selection of patients for transcatheter aortic valve implantation].
A good selection of patients is a crucial step before transcatheter aortic valve implantation (TAVI) in order to select the good indications and choose the access route. TAVI should be considered only in patients with symptomatic severe aortic stenosis and either contraindication or high surgical risk. Indication for TAVI should be discussed in a multidisciplinary team meeting. Echocardiography and/or CT scan are mandatory to evaluate the aortic annulus size and select the good prosthesis size. The possibility of transfemoral implantation is evaluated by angiography and CT scan, and based on the arterial diameters, but also on the presence of tortuosities and arterial calcifications.


Transgenic overexpression of heat shock protein 72 in mouse muscle protects against exhaustive exercise-induced skeletal muscle damage.
Lifelong overexpression of heat shock protein (HSP) 72 in skeletal muscle is known to protect against age-related oxidative stress and muscle damage. This study aimed to ascertain whether exhaustive exercise (EE)-induced muscle fatigue and damage can be prevented by lifelong overexpression of HSP72 in skeletal muscle. Transgenic mice heterozygous for the porcine HSP70.2 gene ([+]HSP72) and transgene-negative littermate controls ([-]HSP72) were subjected to an EE protocol. Mice were randomly divided into four groups: sedentary [-]HSP72, sedentary [+]HSP72, EE [-]HSP72, and EE [+]HSP72. Animals were killed 82 minutes after the start of EE to determine muscular levels of HSP72, serum levels of superoxide dismutase (SOD, an antioxidant enzyme) and lactate (an indicator of muscle fatigue), muscular levels of matrix metalloproteinase (an indicator of inflammatory myopathies), and muscular damage. During the test, the latency value for the occurrence of EE was 79-85 minutes and 100-110 minutes for [-]HSP72 and [+]HSP72 mice, respectively. After EE, [+]HSP72 mice had significantly higher serum SOD and significantly lower serum lactate, muscular matrix metalloproteinase or myeloperoxidase activity, and muscle damage compared to [-]HSP72 mice. The results suggest that HSP72 overexpression in skeletal muscle may improve muscle fatigue and damage in EE by reducing oxidative damage and phagocytic infiltration, at least in mice.


Biological variation in clozapine and metabolite reporting during therapeutic drug monitoring.
Clozapine (CLO) is an atypical antipsychotic used in management of treatment-resistant schizophrenia. Adverse drug reactions are caused by both CLO and its primary metabolite, norclozapine (NCLO). We defined the biological variability of CLO, NCLO, and the CLO to NCLO ratio (CNR) as well as assess the impact of reporting CLO and NCLO routinely. The CVi and CVg were calculated from 1904 results from 247 patients by CV-ANOVA, and ANOVA, respectively, for CLO, NCLO, and the CNR. Association between each were also analyzed against a number of parameters including age and gender, complete blood count (CBC), kidney and liver function tests, lipids, and glucose within 24 h of CLO measurement. For CLO, NCLO and CNR, the CVi was calculated as 19.3%, 19.2%, and 14.7%, and the CVg was 46.9%, 51.4%, and 36.3%, respectively. A total of 87 patients (19.7%) demonstrated higher NCLO results than CLO, with a ratio as low as 0.47. Kidney function was also found to have a statistically significant relationship to CLO and NCLO levels. We provide data for biological variability of CLO metabolism as well as while providing some evidence for reporting NCLO values clinically.


The use of the psychiatric consultation record for residency training.
The Psychiatric Consultation Record (PCR) is an instrument developed to aid in the teaching of consultation psychiatry, to evaluate the impact of this teaching, and to provide an overall assessment of the consultation training program at St. Luke's Hospital. The PCR both structures the resident's training experience and provides a tool with which he or she can integrate theoretical and practical knowledge pertaining to consultation work. Its use has enabled supervisors to detect the degree to which didactic material has become integrated into residents' thinking and has provided data through which the scope and quality of each resident's work can be rapidly assessed. Finally, its use has brought to light deficiencies in service delivery which, before the use of this instrument, had not been apparent.


[Vegetations of the mitral valve and the mitral prosthesis in patients with subacute bacterial endocarditis. Echocardiographic diagnosis].
In a patient with SBE in three differents ocassions in a period approximately of 9 months, the mitral valve was replaced on two occasions. The echocardiogram detected vegetations on two ocassions. The diagnosis of vegetation at the level of the mitral valve, was done for the first time in our hospital by this method. During the last admission, the echocardiogram suggested a vegetation at the level of the artificial mitral valve, projecting into the left atrium with the systole. This was confirmed by surgery.


Localization of pancreatic polypeptide cells in a limited lobe of the human neonate pancreas: remnant of the ventral primordium?
The localization of pancreatic polypeptide (PP) cells was studied in the pancreas of four human neonates by specific immunocytochemical techniques. PP cells were detected in all parts of the pancreas. However, examination at low magnification showed that they were considerably more numerous in a small lobe, located at the posterior-inferior part of the head region. It is suggested that this lobe corresponds to the part of the pancreas that is derived from the ventral primordium. Both in the lobe rich in PP cells and in the remainder of the pancreas, approximately 75% of PP cells were present in the islets and 25% distributed among acini and ducts.


["Forced normalization" EEG phenomenon and several mechanisms of psychopathologic symptoms in epileptic patients].
Some electrophysiological correlations of periodically exacerbating psychopathological manifestations in epilepsy are discussed. It was established that in phenomenon of a "forced normalization" of the EEG deep structures of the lymbic system may show active foci of epileptical bioelectrical activity. It is suggested that such pictures of bioelectrical activity in the different brain structures are formed as a result of dissociated inhibitory influences of the brain stem. The necessity of a stereoelectroencephalographic study in this group of patients is emphasized in order to assess the possibilities of a successful surgical operation.


Paintable Physical Unclonable Functions using DNA.
Controversy over artwork's authenticity is ongoing despite numerous technologies for copyright protection. Artists should build their own ways to protect the authority, but these are still open to piracy. Here, a platform is proposed for developing anticounterfeiting labels based on physical unclonable functions (PUFs), in an artist-friendly manner, brushstrokes. Deoxyribonucleic acid (DNA), which is natural, biocompatible, and eco-friendly, can be applied as a paint that shows entropy-driven buckling instability of the liquid crystal phase. Brushed and wholly dried DNA exhibits line-shaped zig-zag textures with inherent randomness as a source of the PUF, and its primary performance and reliability are systematically examined. This breakthrough enables the utilization of these drawings in a wider range of applications.


Urokinase-type plasminogen activator (uPA) and its inhibitor PAI-I: novel tumor-derived factors with a high prognostic and predictive impact in breast cancer.
Urokinase-type plasminogen activator (uPA) and its inhibitor, PAI-I, play a key role in tumor invasion and metastasis. They were the first novel tumor biological factors to be validated at the highest level of evidence (LOE I) regarding their clinical utility in breast cancer. Their antigen levels are determined in tumor tissue extracts by standardized, quality-assured immunometric assays (ELISA). Since the late 1980s, numerous independent studies have demonstrated that patients with low levels of uPA and PAI-I in their primary tumor tissue have a significantly better survival than patients with high levels of either factor. These prognostic data have recently been validated by an EORTC (European Organization for Research and Treatment of Cancer) pooled analysis comprising more than 8,000 breast cancer patients. In addition, results from a multicenter prospective randomized therapy trial in node-negative breast cancer ("Chemo N(0)") showed that node-negative breast cancer patients with low levels of uPA and PAI-I in their primary tumor have a very good prognosis, and may thus be candidates for being spared the burden of adjuvant chemotherapy. In contrast, node-negative patients with high uPA/PAI-I are at substantially increased risk of disease recurrence, comparable to that of patients with three or more tumor cell positive axillary lymph nodes. The "Chemo N(0)" trial as well as retrospective data also indicate that these high-risk patients benefit from adjuvant chemotherapy. In conclusion, over a period of about 15 years sufficient evidence has been put forward to demonstrate that determination of uPA and PAI-I in primary breast cancer patients supports risk-adapted individualized therapy decisions, particularily in patients with node-negative disease.


The treatment of lumbosacral instability by the Diapason system.
To introduce a new internal fixation system of spine and its characteristics. To review 16 patients with lumbosacral instability who were their clinical outcomes and radiographic evaluation. Fifteen patients gained complete recovery from their preoperative symptoms. One patient who had experienced two operations before and with problems of urinary and fecal incontinence and walking difficulty still had lower limb pain, muscle weakness and urinary incontinence after operation. There is no evidence of spine glide on X-ray, implant failure, neural complication or infection during follow up. Diapason system can achieve good early postoperative results with few complications and ease to use for lumbosacral instability.


The relationship between pelvic tilt, frontal, and axial leg alignment in healthy subjects.
The relationship between anterior pelvic tilt and overall sagittal alignment has been well-described previously. However, the relationship between pelvic tilt, frontal, and axial leg alignment remains unclear. The aim of the study was to analyze the relationship between pelvic tilt and frontal and axial leg alignment in healthy subjects. Thirty healthy subjects (60 legs) without prior surgery underwent standing biplanar long leg radiograph. Pelvic parameters (pelvic tilt, pelvic incidence, sacral slope), hip-knee-ankle angle (HKA), femoral antetorsion and tibial torsion were measured using SterEOS (EOS Imaging) software. EOS was acquired with the feet directing straight anteriorly, which corresponds to a neutral foot progression angle (FPA). The influence of HKA, femoral antetorsion, tibial torsion and gender on pelvic tilt was analyzed in a univariate correlation and multiple regression model. Sixteen female subjects and 14 male subjects with a mean age of 27.1 years ± 10 (range 20-67) were included. HKA, femoral antetorsion, and tibial torsion correlated with anterior pelvic tilt in univariate analysis (all p < 0.05). Anterior pelvic tilt increased 1.1° (95% CI: 0.7 to 1.5) per 1° of knee valgus (p < 0.001) and 0.5° (95% CI: 0.3 to 0.7) per 1° of external tibial torsion (p < 0.001). Overall, linear regression model fit explained 39% of variance in pelvic tilt by the HKA, femoral antetorsion and tibial torsion (R2 = 0.385; p < 0.001). Valgus alignment and increasing tibial torsion demonstrated a weak correlation with an increase in anterior pelvic tilt in healthy subjects when placing their feet anteriorly. The relationship between frontal, axial leg alignment and pelvic tilt needs to be considered in patients with multiple joint disorders at the hip, knee and spine. Alteration of the frontal, or rotational profile after realignment surgery or by implant positioning might influence the pelvic tilt when the FPA is kept constant.


The evolving role of helicopter emergency medical services in the transfer of stroke patients to specialized centers.
In 1996, when the Food and Drug Administration (FDA) approved use of thrombolytic therapy for ischemic stroke, interfacility transport of stroke patients assumed increasing urgency. To describe one helicopter emergency medical services (HEMS) program's 15-year experience with interfacility transport of patients with suspected stroke, with emphasis on reporting changing patterns seen after the advent of thrombolytic therapy for stroke. This was a retrospective study of patients undergoing HEMS transport, during 1985-1999, with a pre-transport diagnosis of suspected ischemic stroke. Data collected included patient demographics and times of symptom onset, community hospital arrival, community hospital request for HEMS, and receiving hospital arrival. Patients were divided into pre-thrombolysis era (1985-1995) and thrombolysis era (1996-1999). Group characteristics were compared using Pearson chi-square, Fisher's exact, rank-sum, and logistic regression analysis. There were 192 total transports, 76 (40%) pre-thrombolysis era and 116 (60%) thrombolysis era. Thrombolysis era patients were more likely (p < 0.0001) to have time of symptom onset documented, and also had significantly (p = 0.0003) shorter time intervals between referring and receiving hospital arrival. The shorter time intervals were due in part to decreased time lapse between referring hospital arrival and that hospital's request for helicopter transport; thrombolysis era patients were 2.5 times more likely than pre-thrombolysis era patients to have HEMS activation within three hours of community hospital arrival. Helicopter EMS transport is playing an increasing role in interfacility transfer of patients with ischemic stroke. Earlier HEMS activation is associated with decreased time lapse between referral and receiving hospital arrival.


Comparison of several immunoassays used in drugs of abuse screening: Assessment against gold standard methods and calculation of measurement uncertainty.
Immunoassays provide simple, powerful and inexpensive screening methods for urine drug screening. Other substances and/or factors may interfere with the test and cause false or positive results. It is essential to understand the differences between methods to be able to evaluate their impact on the results. All evaluated immunoassays were assessed in comparison with GC-MS or LC-MS/MS, which are generally accepted as vigorous confirmation gold standard techniques. CEDIA, DRI, EIA and EMIT II Plus screening immunoassays were evaluated on Beckman-Coulter AU5810 analyser. All results were confirmed using GC-MS or LC-MS/MS methods. Measurement Uncertainty for immunoassays was calculated by using standard deviation multiplied by 1.96 to cover 95% confidence interval of tested samples. No discrepancy was found between CEDIA and EMIT II Plus for cocaine, methadone, heroin, and benzodiazepines assays. No discrepancy was found between oxycodone DRI assay and Immunalysis enzyme immunoassay (EIA). Cannabinoids EMIT II Plus assay performed better than DRI assay. EMIT II Plus assays for amphetamine and ecstasy performed better than CEDIA amphetamine/ecstasy combined assay. Opiates EMIT II Plus assay performed better than CEDIA assay. Fentanyl Ark EIA method performed slightly better than the DRI method. Buprenorphine CEDIA second-generation assay performed better than CEDIA first-generation assay, EMIT II Plus assay and EMIT II Plus with added Beta-Glucuronidase assay. Measurement Uncertainty for immunoassays was calculated and tabulated. This study covered a fundamental gap in available knowledge by evaluating the performance of screening the current new generation of immunoassays methods for drugs of abuse in urine against gold standard methods.


Automated image analysis of cardiac myocyte Ca2+ dynamics.
Intracellular Ca(2+) dynamics act as a key link between the electrical and mechanical activity of the heart. Here we present a method for high-throughput measurement, automated cell segmentation and signal analysis of Ca(2+) transients in isolated adult ventricular myocytes. In addition to increasing experimental throughput ~10-fold compared to conventional approaches, this approach allows the study of individual cell-cell variability and relationships between Ca(2+) signaling and cell morphology.


Real-World Data Analysis of Second-Line Antiangiogenic Targeted Treatments Following Anti-Epidermal Growth Factor Receptor Monoclonal Antibodies and First-Line FOLFOX for Patients with Metastatic Colorectal Cancer.
Evidence is lacking on second-line and later treatments for patients with RAS wild-type colorectal cancer (CRC) who receive first-line anti-epidermal growth factor receptor (EGFR) antibody therapy. In this study, we explored the real-world treatment sequences, treatment duration, and factors associated with treatment sequences and durations in Japanese patients with CRC. This retrospective observational cohort study used a Japanese administrative claims database (April 2008 to July 2021). Patients with confirmed CRC (presumed RAS wild-type) who received first-line FOLFOX (leucovorin + 5-fluorouracil + oxaliplatin) plus anti-EGFR therapy in or after May 2016, followed by second-line irinotecan-based chemotherapy plus an antiangiogenic drug, were included. Treatment durations were estimated by the Kaplan-Meier method. Cox regression analysis was used to identify factors associated with treatment duration. Analysis populations consisted of 1163 (first-line and second-line) and 645 (third-line) patients. At the start of first-line therapy, 67.8% of patients were male, the mean age was 64 years, 83.4% had left-sided CRC, and 84.3% were prescribed FOLFOX plus panitumumab. For second-line therapy, patients were prescribed bevacizumab (63%), ramucirumab (27%), or aflibercept beta (10%). Median (95% CI) treatment durations from the start of second-line therapy to the end of antitumor drug therapies were similar for bevacizumab (12.5 months [11.2, 14.0]), ramucirumab (12.5 months [11.2, 14.8]), and aflibercept beta (14.0 months [10.4, 17.0]). Treatment duration from second-line was positively associated with first-line treatment duration of 6 months or more, CRC surgery before starting first-line therapy, and liver surgery during first-line therapy, and was negatively associated with use of nonsteroidal anti-inflammatory drugs before second-line therapy. Real-world data revealed that all three antiangiogenic drugs were used as second-line therapy after first-line anti-EGFR antibodies and showed similar treatment durations.


Allergies and Eosinophilic Esophagitis-Current Updates for the Pediatric Gastroenterologist.
The purpose of this article is to review recent developments demonstrating the role of allergies, the utility of allergy testing, and the role of the allergist in eosinophilic esophagitis (EoE) management. The majority of patients with EoE have concurrent atopic disorders including food anaphylaxis, asthma, allergic rhinitis, and eczema. An atopic population likely is at greater risk for EoE. Delayed type hypersensitivity to food antigens is the most common pathogenic mechanism. Aeroallergens and pollen-food cross-reactivity also can trigger EoE. Th2 cell-mediated adaptive and innate immunity in response to epithelial damage occurs via IL-13- and IL-4-producing T cells and innate lymphoid cells. While IgE testing for foods is insufficient to build an elimination diet, IgE-mediated allergy may play a role in EoE severity and clinical course. There is strong evidence that Th2 immunity drives EoE. Optimal EoE management should include elucidating and managing EoE triggers and concurrent atopic diatheses.


Altered response control and anterior cingulate function in attention-deficit/hyperactivity disorder boys.
To investigate mechanisms and structures underlying prefrontal response control and inhibition in boys suffering from attention-deficit/hyperactivity disorder (ADHD). Sixteen boys with ADHD and 19 healthy controls were investigated electrophysiologically during performance of a visual Go-Nogo task (Continuous Performance Test, CPT). An electrophysiological source localization method was employed to further analyze the data. The ADHD boys showed a significantly diminished central Nogo-P3, due to a lack of Nogo-related frontalization of the positive brain electrical field in this group. This two-dimensional effect was associated with a significantly reduced activation of the anterior cingulate cortex (ACC) in the ADHD boys in the Nogo condition of the CPT. Both groups did not significantly differ regarding the amplitude of the Nogo-N2. The results indicate deficits in prefrontal response control in unmedicated ADHD boys that do not seem to be specifically inhibitory in nature. A supposed dysfunction of the ACC in ADHD was confirmed.


The biochemical basis of neurodegenerative disease: The role of immunoexcitoxicity and ways to possibly attenuate it.
There is growing evidence that inflammation secondary to immune activation is intimately connected to excitotoxicity. We now know that most peripheral tissues contain fully operational glutamate receptors. While most of the available research deals with excitotoxicity in central nervous system (CNS) tissues, this is no longer true. Even plant has been found to contain glutamate receptors. Most of the immune cells, including mask cells, contain glutamate receptors. The receptors are altered by inflammation, both chemokine and cytokines. A host of new diseases have been found that are caused by immunity to certain glutamate receptors, as we see with Rasmussen's encephalitis. In this paper, I try to explain this connection and possible ways to reduce or even stop the reaction.


En bloc resection for nonmuscle-invasive bladder cancer: selecting a proper laser.
To discuss the most recent surgical lasers that have been made available to us and to evaluate their potential in performing en bloc resection of nonmuscle invasive bladder cancer. Laser en bloc resection of bladder tumors (ERBT) can be performed with a number of laser systems including Ho:YAG, GreenLight, diode, Tm:YAG and thulium fiber lasers (TFL). The data that is currently available suggests that the water-targeting devices (utilizing water as a primary chromophore - Ho:YAG, Tm:YAG, TFL) may have a number of advantages over hemoglobin-targeting systems (potassium titanyl phosphate:YAG, lithium triborate:YAG). One recent addition to the surgical armamentarium Moses effect enhanced Ho:YAG and the TFL (being able to work both in quasi-continuous and SuperPulsed modes) necessitates careful discussion and comparison with the other available devices. The majority of available lasers have proven to be safe to use and compared to electrocautery allow for lower rates of obturator nerve reflex and result in fewer bleeding complications. The minimal penetration depth and decreased peak power of Tm:YAG and TFLs render them the devices of choice when it comes to ERBT. Unfortunately, more studies on ERBT with TFL are needed in order for us to make a sound assessment of the respective pros and cons.


Rebamipide decreases the susceptibility of gastric mucosa to acid-induced injury in rats by inhibiting neutrophil activation.
We previously demonstrated that activated neutrophils increased the susceptibility of gastric mucosa to acid-induced injury in rats. As rebamipide, an anti-ulcer agent, inhibits neutrophil activation, we examined whether the rebamipide reduces stress-induced gastric mucosal injury by decreasing susceptibility to acid-induced gastric mucosal injury in rats. Increase in both gastric mucosal permeability and gastric microvascular permeability evaluated by (51)Cr-EDTA clearance and Evans blue leakage, respectively, at 6 hr after Water-Immersion Restraint Stress (WIR) were significantly lower in animals with leukocytopenia than those in controls. Pretreatment with neutrophil elastase (NE) inhibitors, an anti-P-selectin monoclonal antibody (MAb), and rebamipide significantly inhibited these increases at 6 hr after WIR. These treatments also inhibited decrease in gastric mucosal blood flow observed at 6 hr after WIR. Acid-induced exacerbation of gastric mucosal injury in rats at 6 hr after WIR was inhibited by NE inhibitors, anti-P-selectin MAb, and rebamipide. Rebamipide significantly inhibited WIR-induced increase in gastric MPO activity at 8 hr after WIR. Observations in the present study raised a possibility that rebamipide decreases the susceptibility of gastric mucosa to acid-induced injury by inhibiting neutrophil activation.


Posterior hyaloid peeling in advanced stages of aggressive posterior ROP.
To evaluate the indications and timing of surgical intervention on eyes with aggressive posterior retinopathy of prematurity (ROP). Retrospective review of a consecutive case series of 9 eyes of 7 children, with aggressive posterior ROP, who underwent early lens-sparing vitrectomy. Preoperative retinal and vitreal features, intraoperative and postoperative complications, postoperative anatomic status, and fixation behavior 1 year after surgery were investigated. Vitreous hemorrhage and recurrence of plus disease with retinal detachment were the main indications for surgery. Vitrectomy was performed from the 37th to the 44th postmenstrual week (mean 40th week). In 7 eyes, vitrectomy could stop the disease progression. In all of these cases, posterior hyaloid could be peeled together with the proliferative tissue. Lens-sparing vitrectomy with posterior hyaloid peeling at early postmenstrual ages (37-40 postmenstrual weeks) seems to be advantageous in infants with aggressive posterior ROP. The formation of a gliotic membrane growing ahead to the posterior surface of the lens resulted in unfavorable outcomes in our cases.


Draft Genome Sequence of Phenol-Degrading Variovorax boronicumulans Strain c24.
We report the draft genome sequence of Variovorax boronicumulans strain c24, which was isolated from a soil-inoculated chemostat culture amended with phenol as a sole carbon and energy source. The genome data will provide insights into phenol and other xenobiotic compound degradation mechanisms for bioremediation applications.


Comparison of Dynamic Knee Contact Mechanics with T2 Imaging in Different Ages of Healthy Participants.
Aging is a known risk factor for Osteoarthritis (OA), however, relations between cartilage composition and aging remain largely unknown in understanding human OA. T2 imaging provides an approach to assess cartilage composition. Whether these T2 relaxation times in the joint contact region change with time during gait remain unexplored. The study purpose was to demonstrate a methodology for linking dynamic joint contact mechanics to cartilage composition as measured by T2 relaxometry. T2 relaxation times for unloaded cartilage were measured in a 3T General Electric magnetic resonance (MR) scanner in this preliminary study. High-speed biplanar video-radiography (HSBV) was captured for five 20-30-year-old and five 50-60-year-old participants with asymptomatic knees. By mapping the T2 cartilages to the dynamic contact regions, T2 values were averaged over the contact area at each measurement within the gait cycle. T2 values demonstrated a functional relationship across the gait cycle. There were no statistically significant differences between 20- and 30-year-old and 50-60-year-old participant T2 values at first force peak of the gait cycle in the medial femur (p = 1.00, U = 12) or in the medial tibia (p = 0.31, U = 7). In the medial and lateral femur in swing phase, the joint moved from a region of high T2 values at 75% of gait to a minimum at 85-95% of swing. The lateral femur and tibia demonstrated similar patterns to the medial compartments but were less pronounced. This research advances understanding of the linkage between cartilage contact and cartilage composition. The change from a high T2 value at ~ 75% of gait to a lower value near the initiation of terminal swing (90% gait) indicates that there are changes to T2 averages corresponding to changes in the contact region across the gait cycle. No differences were found between age groups for healthy participants. These preliminary findings provide interesting insights into the cartilage composition corresponding to dynamic cyclic motion and inform mechanisms of osteoarthritis.


Clinical features and prognosis of patients with benign thyroid disease accompanied by an incidental papillary carcinoma.
To investigate the clinical features and prognosis of papillary thyroid carcinoma (PTC) with a background of benign disease. A total of 709 patients with papillary thyroid carcinoma undergoing surgical resection were analyzed retrospectively. In 147 patients who underwent surgery for benign thyroid disease, incidental PTC (IPC group) were identified by intraoperative or postoperative pathological examination of surgical specimens but were not detected by preoperative imaging studies. In the other group, according to the pathological examination with or without co-existing benign thyroid disease, 253 cases were clarified as concomitant PTC and 309 cases were clarified as dominant PTC. Incidental PTC was more common in women, about 85.7%, the mean age was 47.6±11.3 years old. Average tumor diameter was 4.4±2.2 mm, multiple lesions accounted for 12.9% (19/147), and the cervical lymph node metastasis rate was 6.1% (9/147). After radical resection 8 cases recurred, the median time of recurrence was about 12 months (0.5 to 162), there was no tumor-related death. The tumor-free survival rates were 97.3%, 95.9%, 91.5%, and 79.3% in 1, 5, 10 and 14 year respectively. Incidental PTC with a background of benign lesions is common, and the generally good prognosis can be attributed to tumor early detection and early treatment. On the intraoperative finding of incidental PTC, lobectomy (unilateral) or total thyroidectomy (bilateral) should be the first choice, but with a postoperative pathologic finding of incidental PTC, further treatment, such as completion thyroidectomy or immediate lymph dissection is not necessary. Central lymph node dissection is also not needed unless lymphadenectasis is present.


The effect of migration on local adaptation in a coevolving host-parasite system.
Antagonistic coevolution between hosts and parasites in spatially structured populations can result in local adaptation of parasites; that is, the greater infectivity of local parasites than foreign parasites on local hosts. Such parasite specialization on local hosts has implications for human health and agriculture. By contrast with classic single-species population-genetic models, theory indicates that parasite migration between subpopulations might increase parasite local adaptation, as long as migration does not completely homogenize populations. To test this hypothesis we developed a system-specific mathematical model and then coevolved replicate populations of the bacterium Pseudomonas fluorescens and a parasitic bacteriophage with parasite only, with host only or with no migration. Here we show that patterns of local adaptation have considerable temporal and spatial variation and that, in the absence of migration, parasites tend to be locally maladapted. However, in accord with our model, parasite migration results in parasite local adaptation, but host migration alone has no significant effect.


Quantitative angiography prognosis of intracranial aneurysm treatment failure using parametric imaging and distal vessel analysis.
Data-driven methods based on x-ray angiographic parametric imaging (API) have been successfully used to provide prognosis for intracranial aneurysm (IA) treatment outcome. Previous studies have mainly focused on embolization devices where the flow pattern visualization is in the aneurysm dome; however, this is not possible in IAs treated with endovascular coils due to high x-ray attenuation of the devices. To circumvent this challenge, we propose to investigate whether flow changes in the parent artery distal to the coil-embolized IAs could be used to achieve the same accuracy of surgical outcome prognosis. Eighty digital subtraction angiography sequences were acquired from patients with IA embolized with coils. Five API parameters were recorded from a region of interest (ROI) placed distal to the IA neck in the main artery. Average API values were recorded and pre-treatment values. A supervised machine learning algorithm was trained to provide a six-month post procedure binary outcome (occluded/not occluded). Receiver operating characteristic (ROC) analysis was used to assess the accuracy of the method. Use of API parameters with data driven methods yielded an area under the ROC curve of 0.77 ±0.11 and accuracy of 78.6%. Single parameter-based analysis yielded accuracies which were suboptimal for clinical acceptance. We determined that data-driven method based on API analysis of flow in the parent artery of IA treated with coils provide clinically acceptable accuracy for the prognosis of six months occlusion outcome.


The Prevalence of Exfoliation Syndrome in an Iranian Population Aged 45-69 Years.
To determine the prevalence of exfoliation syndrome (XFS) and some of its related factors in an Iranian population aged 45-69 years. In the first phase of the Shahroud Eye Cohort Study, 5190 people in 300 clusters from Shahroud city in the northeast of Iran participated in the study. The second phase of the study was conducted 5 years later in 2014. Vision testing, refraction, slit lamp examination, and fundus examination were performed for all participants. In this study, XFS was determined by an ophthalmologist using slit lamp biomicroscopy. Of the 5190 first phase study participants, 4737 participated in the second phase (response rate 91.3%). In this study, the prevalence of XFS was 0.46% (95% confidence interval, CI, 0.24-0.68%) and the prevalence of bilateral XFS was 0.20% (95% CI 0.07-0.33%). XFS prevalence in men was 0.74% (95% CI 0.28-1.20%) and in women 0.26% (95% CI 0.07-0.45%). In a multivariable-adjusted logistic regression model, age, sex, diabetes, smoking status, dyslipidemia, and hypertension were entered into the model as covariables, where older age (odds ratio, OR, 1.18, 95% CI 1.08-1.28) was the only variable that remained significantly associated with XFS prevalence. The prevalence of XFS in this study was very low. Similar to other studies, age was a factor associated with this syndrome.


Idiopathic Facial Aseptic Granuloma: Updated Review of Diagnostic and Therapeutic Difficulties.
Idiopathic facial aseptic granuloma is a pediatric skin condition involving asymptomatic reddish nodules. The etiology and pathogenesis is still under discussion, although the literature tends to place this condition within the spectrum of childhood rosaceas. The clinical course is chronic but benign, and cases have been reported to resolve spontaneously in less than a year. Even though no well-defined treatment has emerged, a conservative approach that avoids aggressive therapies is preferred.


Impact of UV-B radiation on thylakoid membrane and fatty acid profile of Spirulina platensis.
Ultraviolet-B (UV-B) radiation to thylakoid membrane and fatty acid profile has been investigated in cyanobacterium, Spirulina platensis. The thylakoid membrane was isolated by mechanical disruption of the freeze-dried and lysozyme-treated cells followed by differential density gradient centrifugation and morphological variations were examined. UV radiation distorted the membrane on the outer side with reduced chlorophyll a (chl a) content compared to its untreated counterpart. Liquid chromatography-mass spectrometry (LC-MS) was used for characterization of chl a of the thylakoid membrane. UV-B exposure resulted in alterations in the pigment-protein complexes 47 kDa and 43 kDa. Furthermore, 94 kDa and 20 kDa protein appeared in UV-B-exposed thylakoid membrane of S. platensis. The composition of fatty acid in response to UV-B radiation was detected by gas chromatography-mass spectrometry having 23.5% saturated fatty acid (SFA), 76.4% monounsaturated fatty acid (MUFA), and polyunsaturated fatty acid (PUFA). In contrast to its UV-B-untreated counterpart, SFA was 46.6%, and MUFA and PUFA were 53.3%. Our findings suggest that UV-B radiation not only affects membrane morphology and its protein profile but also reduces saturated fatty acid and increases unsaturated fatty acids in S. platensis.


Determination of herbicides, including thermally labile phenylureas, by solid-phase microextraction and gas chromatography-mass spectrometry.
A method for the determination of 10 herbicides, including thermally unstable compounds, has been developed. The method uses solid-phase microextraction (SPME) with a polyacrylate fibre. Separation, identification and quantification were accomplished with gas chromatography-mass spectrometry. The herbicides chosen belong to different chemical groups and were alachlor, atrazine, chlorotoluron, diclofop, diflufenicam, ethofumesate, isoproturon, linuron, terbutryn and trifluralin. In the present work we studied the chromatographic behaviour of three phenylureas as a function of the medium and injection mode employed. The compounds generated as a function of the solvent used in direct injection of the phenylureas (ethyl acetate, methanol and methanol-water) and those obtained when injection was accomplished using the polyacrylate fibre were determined. The results allow us to propose a method for the determination of stable and thermally unstable herbicides as long as a preconcentration step involving SPME is carried out. In the proposed method, the limits of detection varied between 0.02 microg/l for ethofumesate and 0.11 microg/l for chlorotoluron. The method was applied to the determination of these herbicides in surface and ground water samples, performing quantification by standard addition calibration. The contents of chlorotoluron and atrazine found were significantly equal to those obtained using HPLC after a preconcentration stepwith styrene-divinylbenzene sorbents.


Biochemical and immunohistochemical determination of 5-hydroxytryptamine located in mast cells in the trigeminal ganglion of the rat and guinea pig.
The presence of 5-hydroxytryptamine (5-HT), as well as its precursor (5-HTP) and metabolite (5-HIAA), were biochemically determinated in the trigeminal ganglion of the guinea pig and rat. The distribution of 5-HT in the ganglion and in its posterior root was studied using both indirect immunofluorescence and the peroxidase-antiperoxidase method. In order to increase the possible 5-HT content of primary sensory neurons for subsequent immunohistochemical visualization, animals were first treated with nialamide, an inhibitor of monoamine oxidase, and then loaded with L-tryptophan. Another group of animals received colchicine to inhibit intra-axonal transport of transmitter substances. However, even combined use of loading and colchicine treatment did not reveal 5-HT immunoreactivity in ganglion cells. The only source of 5-HT immunoreactivity in the trigeminal ganglion and its posterior root was mast cells. These cells were located around the ganglion in adjacent leptomeningeal and connective tissues, as well as between the ganglion cells and nerve fibers. Only occasionally were mast cells found in the posterior root of the ganglion.


Erratum: A network of networks: 40 years of uniting global agendas toward universal health and equitable care.
[This corrects the article DOI: 10.4103/efh.EfH_203_19].


Confessions of a converted anatomist: teaching without anatomical donors.
In the field of anatomy education, the debate over the superiority of learning with or without human donors is decades long and ongoing. Arguments for or against the use of human donors in anatomy education vary, depending on the healthcare discipline. Physical therapy programs have been particularly resistant to the trend away from the use of human donors. In this personal view, I present my history of anatomy education and how my perspectives on teaching and learning anatomy have changed dramatically throughout my teaching experiences. The purpose of this article is to support instructors who are creating anatomy courses for all healthcare trainees without donors, inspire those teaching with donors to incorporate other methods of instruction and evaluation, challenge educators to examine their own biases surrounding anatomy education, and provide recommendations for developing an anatomy course without human donors. Included in this article is the perspective of a practicing physical therapist who learned through human dissection and has assisted me in the development and management of the human anatomy course in our physical therapy curriculum.NEW & NOTEWORTHY This article provides an overview of how to design an anatomy course without anatomical donors for doctor of physical therapy students and includes recommendations for instructors who need to reduce or eliminate anatomical donors from their anatomy curriculum.