Detection of second malignancies during long-term follow-up of testicular cancer survivors.
Second cancers are an important cause of mortality and morbidity in long-term survivors of testicular germ cell tumors (TGCTs). Studies on the impact of follow-up for the first tumor on the outcome of second malignancies are lacking. The aim of this study was to study the details of diagnosis of second cancers and the role of focused oncology follow-up. Medical records and the electronic database of a tertiary referral center for germ cell neoplasms were searched for second cancers diagnosed in TGCT survivors. In a database of 1057 patients, 63 cases of metachronous second malignancies (26 contralateral testicular cancers and 37 nontesticular cancers) were found in 57 patients. Long-term oncology follow-up consisted of yearly history, physical examination, germ cell tumor markers, and imaging including abdominal computed tomography (CT) scans and chest x-ray. The second malignancies occurred after a medium follow-up of 9.9 years (range, 1.1-33 years) after the diagnosis of the first tumor. Only 17 (27%) of the 63 second tumors were detected by oncology follow-up investigations, and a further 12 (29%) were detected by nononcology physicians during a preplanned clinical visit. In 34 (54%) cases, patients themselves or their relatives initiated a clinical appointment because of symptoms. Follow-up investigations all had low yields for the detection of second malignancies, although CT imaging did detect several cases of cancer at an early stage. In this retrospective study, most second cancers occurring in long-term TGCT survivors were missed by regular oncology follow-up that included yearly physical examination, tumor marker, and imaging.


Specificities of terrorist attacks: organisation of the in-hospital patient-flow and treatment strategies.
Mass-casualty incidents are always a particular challenge not only for healthcare providers and other emergency service responders at the scene but also for receiving hospitals. Terrorism-related mass-casualty incidents can result in a wide variety of different scenarios so that hospitals and their personnel must prepare for far more complex and demanding requirements. In this article, we describe and discuss in-hospital aspects of mass-casualty terrorist incidents and focus on the special medical and in particular surgical care that is required in this setting. The overview presented here is based on the Terror and Disaster Surgical Care (TDSC®) course. The TDSC® course was mainly developed from a comprehensive and structured analysis of the literature, single expert opinions, and expert consensus conferences. The objective of this course is to train clinical decision-makers in how to manage major incidents. The management of a mass-casualty terrorist incident and the care of victims present multiple and unique challenges to hospitals. This applies in particular to the number and distribution of patients arriving at the hospital, injury patterns, infrastructural aspects, and personnel resources. Particular attention must be given to the surgical approach to caring for these patients, e.g., early total care, damage control surgery, or tactical abbreviated surgical care. Mass-casualty terrorist incidents are different from other mass-casualty events in many respects that require special attention. The provision of appropriate public services requires in particular that the preparation and training of personnel as well as the organisation of the in-hospital response be tailored to the incident.


Genetic properties of conjugative R plasmids in Escherichia coli and Salmonella isolated from feral and domestic pigeons, crows and kites.
A total of 62 conjugative R plasmids detected in 48 Escherichia coli and 19 conjugative R plasmids in 16 Salmonella strains from domestic (carrier and emerald) and feral pigeons, crows (Japanese jungle crows and carrion crows) and black kite, were examined for genetic properties. Out of the 62 E. coli R plasmids examined for fertility inhibition (Fi), 29 (46.8%) were Fi+, and the remainder were Fi-. Among the 62 R plasmids, 16 (25.8%) were classified into incompatibility (Inc) group FII, 15 (24.2%) into I alpha, 7 (11.3%) into H1 and 2 (3.2%) into N. The remaining 23 R plasmids could not be classified in this study. Among the 19 Salmonella R plasmids, 4 showed thermosensitive (ts) transfer. Out of the 18 plasmids tested, 13 (72.2%) including 4 ts-R plasmids were Fi-, and the remaining 5 (27.8%) were Fi+. Five R plasmids containing 4 Fi- were IncI alpha, while 4 ts-R plasmids belonged to IncH1 (1 R plasmid) and H2 (3 R plasmids). The remainings were not tested. In E. coli strains, IncFII and I alpha were widely (4 of 6 lots of birds, respectively) distributed, followed by N (2 lots) and H1 (1 lot). IncN R plasmid was detected from domestic pigeons and crows, but not from feral pigeons. In Salmonella strains from 5 lots of birds, IncFII and N plasmids which were detected from E. coli were not found, but IncH2 was detected from domestic pigeons (1 lot) and kite (1 lot). IncI alpha was detected from feral pigeons (1 lot) and kite (1 lot). The potential transfer of R plasmids between Salmonella and E. coli, and of dissemination of the plasmids among the free-flying birds, animals and humans is discussed.


Association between maternal employment and the child´s mental health: a systematic review with meta-analysis.
The recent rise in maternal workforce participation has led to more research regarding the role of maternal employment for (early) childhood mental health. This systematic review with meta-analysis covers new evidence on the association of both variables. A systematic literature search was conducted. Studies had to compare children 0-7 years of age on the basis of their mothers' employment status, working amount, employment duration, i.e., how long the mother had been back at work after birth, or timing of return to work. Child mental health was operationalized as behavior problems and prosocial behavior. Narrative and meta-analytic syntheses of evidence were conducted. Maternal employment was associated with more conduct problems but less internalizing behavior problems and anxious/depressed behavior in children; full-time employment was linked to more externalizing behavior problems and more hyperactivity/inattention. Longer employment duration was related to less (internalizing) behavior problems and more prosocial behavior but also more externalizing behavior problems. Narrative syntheses indicated early maternal return to work to be associated with more child externalizing behavior problems and less prosocial behavior. Whether maternal employment is associated with child mental health strongly depends on both variables' operationalization. Especially part-time employment, longer employment duration, and return to work only after the first year postpartum may be beneficial for child mental health. Practical implications pertain to an expanded offer of family leave and the endorsement of maternal employment after the first year postpartum. Here, factors that may buffer the negative associations with full-time employment warrant consideration.


Inferring patterns of hemispheric specialization for individual subjects from laterality data: a two-task criterion.
Sixty-three subjects (31 dextrals and 32 sinistrals) were given two visual half-field laterality tasks (recognition of words and faces). Subjects were classified as having typical or atypical hemispheric specialization on the basis of the relative magnitude of their asymmetry scores on the two laterality tasks. Those subjects whose word asymmetry scores were larger than their face asymmetry scores (asymmetry scores computed as RVF-LVF for both tasks) were classified into Group Typical and those subjects whose word asymmetry scores were smaller than their face asymmetry scores were classified into Group Atypical. For both dextrals and sinistrals, the proportion of subjects classified into Groups Typical and Atypical was consistent with estimates of the incidence of typical and atypical hemispheric asymmetry patterns based on sodium amytal testing. These results support the hypothesis that the relative magnitude of asymmetry scores on left and right hemisphere specialized tasks index individual differences in patterns of hemispheric specialization.


Possible Engagement of Nicotinic Acetylcholine Receptors in Pathophysiology of Brain Ischemia-Induced Cognitive Impairment.
Post-stroke disabilities like cognitive impairment impose are complex conditions with great economic burdens on health care systems. For these comorbidities, no effective therapies have been identified yet. Nicotinic acetylcholine receptors (nAChRs) are multifunctional receptors participating in various behavioral and neurobiological functions. During brain ischemia, the increased glutamate accumulation leads to neuronal excitotoxicity as well as mitochondrial dysfunction. These abnormalities then cause the increased levels of oxidants, which play key roles in neuronal death and apoptosis in the infarct zone. Additionally, recall of cytokines and inflammatory factors play a prominent role in the exacerbation of ischemic injury. As well, neurotrophic factors' insufficiency results in synaptic dysfunction and cognitive impairments in ischemic brain. Of note, nAChRs through various signaling pathways can participate in therapeutic approaches such as cholinergic system's stimulation, and reduction of excitotoxicity, inflammation, apoptosis, oxidative stress, mitochondrial dysfunction, and autophagy. Moreover, the possible roles of nAChRs in neurogenesis, synaptogenesis, and stimulation of neurotrophic factors expression have been reported previously. On the other hand, the majority of the above-mentioned mechanisms were found to be common in both brain ischemia pathogenesis and cognitive function tuning. Therefore, it seems that nAChRs might be known as key regulators in the control of ischemia pathology, and their modulation could be considered as a new avenue in the multi-target treatment of post-stroke cognitive impairment.


Reduced apoptotic cell death in follicular lymphoma.
It has been hypothesized that inhibition of germinal centre cell apoptosis may underlie the development of follicle centre cell lymphomas. We have performed a comparative, quantitative study of apoptotic cell death in germinal centres and in the neoplastic follicles of centroblastic-centrocytic, follicular, non-Hodgkin's lymphoma (Cb/Cc NHL). Ten cases each of reactive follicular hyperplasia and Cb/Cc NHL were analysed. One-micrometre-thick resin-embedded sections were examined at x 1000 magnification. The total numbers of cells, nuclear containing apoptotic bodies, and mitoses were counted in each follicle and the apoptotic and mitotic indices were derived. Transmission electron microscopy was performed on selected cases to confirm the typical features of apoptosis. The mean apoptotic (4.9 per cent) and mitotic indices (0.9 per cent) for the germinal centres were significantly higher (P much less than 0.001) than those for the neoplastic follicles (0.9 and 0.14 per cent). These results lend support to the recent proposal that reduced apoptotic cell death may be important in the pathogenesis of follicular lymphomas.


Definition of minimal disease activity in psoriasis.
To generate an operational definition to adequately reflect the construct 'Minimal Disease Activity (MDA)' in psoriasis. A systematic review of domains included in clinical trials of psoriasis was presented to a panel of dermatologists and patients. Further domains were elicited by panel discussions. Domains (and instruments measuring these) were items of two consecutive Delphi rounds targeting dermatologists from the Psoriasis Group of the Spanish Academy of Dermatology and Venereology and patients from the Acción Psoriasis association. The instruments selected were used to generate 388 patient vignettes. The expert group then classified these vignettes as 'No MDA/MDA/Unclassifiable'. The items were further reduced by factorial analysis. Using the classification variable as gold standard, several operational constructions were tested in regression models and ROC curves and accuracy was evaluated with area under the curve (AUC). The following domains were included: itching, scaling, erythema and visibility by 0-10 scales, extension by BSA, impact on quality of life by DLQI, special location and presence of arthritis as yes/no. The definition with the highest AUC and best balance between sensitivity and specificity was the one including no presence of arthritis plus at least three others below the upper limit of the 95% confidence interval (AUC, 0.897; sensitivity, 95.2%, specificity, 84.1%). This study provides, for the very first time, the construct of 'Minimal Disease Activity' in psoriasis as agreed by dermatologists and patients. MDA is defined as absence of active arthritis plus 3 out of 6: itching ≤ 1/10; scaling ≤ 2/10; redness ≤ 2/10; visibility ≤ 2/10; BSA ≤ 2; DLQI ≤ 2; and no lesions in special locations. By design, domains are representative of disease impact. This MDA definition may be used as a measure of adequate management and replace other subjective or restrictive tools.


Ascending projections of the brain stem reticular formation in a nonmammalian vertebrate (the lizard Varanus exanthematicus), with notes on the afferent connections of the forebrain.
In the present study an attempt has been made to analyze the ascending reticular projections in the lizard Varanus exanthematicus by means of the horseradish peroxidase (HRP) technique. Reticular projections ascending to the telencephalon were found to arise in the mesencephalon, but not caudal to the mesorhombencephalic border. HRP injections into the dorsal thalamus have demonstrated retrogradely labeled cells in the mesencephalic reticular formation, particularly at the level of the oculomotor nerve and in the medial magnocellular zone of the rhombencephalic reticular formation, predominantly rostrally. HRP infiltrations at the mesodiencephalic border damaged most of the fibers passing beyond this junction, resulting in the uptake of HRP by the damaged axons and subsequent labeling of the cell bodies or origin of ascending reticular projections to the diencephalon and telencephalon. From a comparison of cell-labeling patterns in cases of HRP injections of, respectively, the dorsal thalamus and the mesodiencephalic border, it seems likely that the nucleus reticularis medius and more sparsely the nucleus reticularis inferior project to ventral diencephalic structures (ventral thalamus and hypothalamus), whereas the midbrain reticular formation and the rostral parts of the rhombencephalic reticular formation (nuclei reticulares isthmi and superior) project to both the dorsal thalamus and more ventral diencephalic structures. Projections arising throughout the rhombencephalic reticular formation, but predominantly in the nucleus reticularis inferior, were found to ascend to the midbrain reticular formation. The present experimental data in the lizard Varanus exanthematicus are comparable to the findings in mammals, with the exception of the reticulo-oculomotor pathways which have not been analyzed so far in reptiles. In addition to the aforementioned ascending reticular projections, the present study has demonstrated projections ascending from monoamine cell groups, various diencephalic structures, as well as from neuronal groups involved in somatosensory, auditory, and gustatory systems. Projections were found from the locus coeruleus and the nucleus raphes superior to the telencephalon, as well as from the substantia nigra and the presumable reptilian homologue of the mammalian ventral tegmental area to the basal forebrain and the dorsal thalamus. Bilateral projections were demonstrated from the principal trigeminal nucleus to the telencephalon, reminiscent of the quintofrontal tract of birds. Ascending projections to the diencephalon were found to originate bilaterally in the descending trigeminal nucleus and the dorsal funicular nucleus. Auditory projections to the midbrain arise bilaterally in the superior olivary complex and in the cochlear nuclear complex. Finally, the ascending gustatory pathway arising in the nucleus of the solitary tract was found to project to the "parabrachial region," which in its turn has extensive projections to the forebrain.


[Myocarditis: Uncommon but severe toxicity of immune checkpoint inhibitors].
Traditional cancer therapies, such as treatment with anthracyclines and chest radiation, are known to induce cardiovascular complications. Currently, the increase of cancer therapies will involve new mechanisms such as cancer immunotherapies, also called immune checkpoint inhibitors (PD-1, PD-L1 and CTLA-4 inhibitors). These treatments have shown long-term remissions in subgroup of cancers, including melanomas, non-small-cell lung cancer, urothelial carcinoma, renal cell carcinoma, squamous cell carcinoma of the head and neck and colorectal cancer. Although these treatments will change the natural course of these cancers, they may sometimes induce cardiovascular complications, which has been reported as about 1 % in the literature. Currently, the physicians must keep in mind one uncommon but severe cardiac complication: auto-immune myocarditis. The clinical presentation may include various symptoms like chest pain, heart failure or rhythm disorders. In this situation, a baseline cardiologic check-up before starting cancer immunotherapy may be very helpful. Cardiac biomarkers (troponin and brain natriuretic peptide) and 12-lead resting electrocardiogram must be promptly performed when myocarditis is suspected. A cardiologist's opinion must be requested in emergency to discuss both a transthoracic echocardiography and the appropriate treatment (stopping immunotherapy, adding immunosuppressive treatment such as corticoids) and the monitoring in an intensive care unit. Cardiac MRI and endomyocardial biopsies may help to approach the final diagnosis. In this situation, other cancer therapies may be discussed.


Recent progress and new perspectives in studying T cell responses to allografts.
Studies in the past decade advanced our understanding of the development, execution and regulation of T-cell-mediated allograft rejection. This review outlines recent progress and focuses on three major areas of investigation that are likely to guide the development of graft-prolonging therapies in the future. The discussed topics include the contribution of recently discovered molecules to the activation and functions of alloreactive T cells, the emerging problem of alloreactive memory T cells and recently gained insights into the old question of transplantation tolerance.


Comparison of psychophysical and evoked potential methods in the detection of visual deficits in multiple sclerosis.
We compared the diagnostic sensitivity of traditional visual tests such as the Snellen-test and pattern reversal VEPs with psychophysical and electrophysiological tests involving motion processing and psychophysical tests of contrast processing in detecting visual deficits in a group of MS patients. A total of 30 patients with a definite diagnosis of MS and 22 age-matched controls selected from a pool of healthy volunteers participated in this study. Visual evoked potentials elicited by reversing checkerboards and moving random dot patterns (motion-onset VEPs) were recorded. The recognition of motion-defined forms (motion-defined letter test, MDL-test) and of contrast reduced optotypes was measured psychophysically. Of 30 patients, 29 showed deficits in at least one of the tests applied. The highest detection rate was obtained for a simple psychophysical test, the MDL-test, which revealed abnormalities in 80% of the patients. This is about 12% more than pattern VEPs could detect. Conversely, abnormalities in motion-onset VEPs were found in only 16% of the patients. Our results show that by adding a simple psychophysical test of form-from-motion analysis our capability to demonstrate an involvement of the visual system in MS patients may be promoted considerably.


Prognostic utilization of models based on the APACHE II, APACHE IV, and SAPS II scores for predicting in-hospital mortality in emergency department.
This study was designed to evaluate and compare the prognostic value of the APACHE II, APACHE IV, and SAPSII scores for predicting in-hospital mortality in the ED on a large sample of patients. Earlier studies in the ED setting have either used a small sample or focused on specific diagnoses. A prospective study was conducted to include patients with higher risk of mortality from March 2016 to March 2017 in the ED of Emam Reza Hospital, northeast of Iran. Logistic regression was used to develop three models. Evaluation was performed in terms of the overall performance (Brier Score, BS, and Brier Skill Score, BSS), discrimination (Area Under the Curve, AUC), and calibration (calibration graph). A total of 2205 patients met the study criteria (53% male and median age of 64, IQR: 50-77). In-hospital mortality amounted to 19%. For APACHE II, APACHE IV, and SAPS II the BS was 0.132, 0.125 and 0.133 and the BSS was 0.156, 0.2, and 0.144, respectively. The AUC was 0.755 (0.74 to 0.779) for APACHE II, 0.794 (0.775 to 0.818) for APACHE IV, and 0.751 (0.727 to 0.776) for SAPS II. The APACHE IV showed significantly greater AUC in comparison to the APACHE II and SAPS II. The graphical evaluation revealed good calibration of the APACHE IV model. APACHEIV outperformed APACHEII and SAPSII in terms of discrimination and calibration. More validation is needed for using these models for decision-making about individual patients, although they would perform best at a cohort level.


The detection of antibodies to Mycobacterium tuberculosis by microplate enzyme-linked immunosorbent assay (ELISA).
The detection of antibodies to Mycobacterium tuberculosis by enzyme-linked immunosorbent assay has proved to be a potentially useful technique for the serodiagnosis of tuberculosis. The technique is capable of full automation. The use of a purified antigen should further improve the sensitivity of the method.


Accuracy and cost description of rapid antigen test compared with reverse transcriptase-polymerase chain reaction for SARS-CoV-2 detection.
Fast and accurate detection of SARS-CoV-2 is essential in limiting the COVID-19 pandemic. Rapid antigen (AG) tests provide results within minutes; however, their accuracy has been questioned. The study aims to determine the accuracy and cost of the STANDARD Q COVID-19 AG test compared with RT-PCR. Individuals 18 years or older with an appointment for a RT-PCR test on 26-31 December 2020 at a public test centre in Copenhagen, Denmark were invited to participate. An oropharyngeal swab was collected for RT-PCR analysis, followed by a nasopharyngeal swab examined by the AG test (SD Biosensor). The diagnostic accuracy of the AG test was calculated with RT-PCR as reference. Costs were evaluated for both tests. A total of 4,811 paired conclusive test results were collected (median age: 45 years, female: 53%). The RT-PCR test revealed 221 (4.6%) positive tests. The overall sensitivity and specificity of the AG test were 69.7% and 99.5%, respectively. Viral cycle threshold values were significantly higher in individuals with false negative AG tests than in individuals who were true positives. The RT-PCR test and AG test costs were 67.0 DKK (10.8 USD) and 35.0 DKK (5.7 USD), respectively, per positive case detected at 100,000 daily tests. The AG test enables mass testing and provides immediate results, which is important in SARS-CoV-2 screening. The AG test is a good and relevant supplement to RT-PCR testing in public SARS-CoV-2 screenings. This project received no external funding. Copenhagen Medical A/S delivering the rapid AG tests and provided test personnel but were not otherwise involved. Clinicaltrials.org: NCT04716088.


Predicting radiographic changes at the first visit following operative repair of distal radius fractures.
To test the hypothesis that clinical assessment reliably identifies patients with radiographic changes (including loss of reduction, hardware failure, and hardware migration) at the initial visit following operative repair of distal radius fractures. We identified 102 patients undergoing operative repair of distal radius fractures. Radiographs and clinical notes were reviewed. At the initial postoperative visit, 11 patients had more than normal postoperative pain, 0 had deformity, 0 had crepitus with gentle motion, and 0 had instability at the fracture site on examination. These 11 patients were considered to have positive clinical assessments, but none had radiographic changes on x-rays taken that day. Three patients had negative clinical assessments but had radiographic changes noted at the initial postoperative visit. There were no additional radiographic changes between the series taken at the initial postoperative visit and series taken at later postoperative visits. These data suggest that for purposes of detecting radiographic changes, radiography at the initial visit is helpful, whereas radiography at subsequent visits may not be. Radiography at subsequent visits may be useful to monitor bony healing, which we did not investigate.


Intra-operative conversion is a cause of masked mortality in off-pump coronary artery bypass: a meta-analysis.
Coronary artery bypass surgery can offer excellent results when performed with cardiopulmonary bypass (on pump) or without cardiopulmonary bypass (off pump). The debate as to which technique is superior remains unanswered. Intra-operative conversion from off- to on-pump coronary surgery is a relatively unexplored phenomenon, which cannot be assessed within randomised controlled trial design. We aimed to assess the effect of off-pump conversion on patient mortality. Medline, Embase, Cochrane and Google Scholar databases were systematically reviewed for studies published between 1980 and 2010 that compared the incidence of mortality between converted and non-converted off-pump patients. Publication bias and heterogeneity were assessed and data were extracted independently by multiple observers. We undertook a meta-analysis of these studies using random effects modelling. A total of 17 studies fulfilled our inclusion criteria, containing data for 18,870 off-pump coronary artery bypass operations spanning a decade (1998-2008), involving 920 cases of conversion. Overall, conversion increased mortality by an odds ratio of 6.18 (95% confidence interval 4.65-8.20), whereas emergency conversion further raised the odds ratio of mortality to 6.99 (95% confidence interval 5.18-9.45). The conversion from off- to on-pump cardiac surgery may significantly increase the chance of an adverse outcome, whereas emergency conversion confers a significant rise in mortality. The risk of conversion should be discussed when obtaining the patient's informed consent and its prevention warrants serious consideration by cardiac surgeons and cardiac surgical training programmes.


Ocular findings in Cockayne syndrome.
The ocular findings in eight patients with Cockayne syndrome included enophthalmos, hyperopia, poor pupillary dilation, and retinal dystrophy in all patients. Four patients had strabismus. Two patients had cataracts. Three patients had nystagmus. Visual acuity was relatively well preserved in six patients, including a 25-year-old man with a visual acuity of 20/60 in each eye despite advanced retinal pigmentary changes. Failure of DNA and RNA synthesis to recover after ultraviolet light exposure as well as selective loss of repair of transcriptionally active DNA may account for the ocular abnormality in this progeric syndrome.


Toxicity of formaldehyde vapor in B6C3F1 mice exposed for 13 weeks.
Groups of 10 male and 10 female B6C3F1 mice were exposed to 0, 2, 4, 10, 20, or 40 ppm of formaldehyde vapor 6 h/day, 5 days/week for 13 weeks. Clinical abnormalities (dyspnea, listlessness, and hunched posture), significant mortality, and body weight loss were observed in the 40 ppm groups. Pathologic changes were observed in the nose, larynx, trachea, and bronchi of treated males and females and in the uterus and ovaries of treated females. Squamous metaplasia and inflammation were present in the nasal tissues of male and female mice in the 10, 20, and 40 ppm groups and in the larynx of males and females in the 20 and 40 ppm groups. The trachea had squamous metaplasia and hyperplasia of the epithelium in addition to submucosal fibrosis and inflammation in the 20 and 40 ppm groups. In some mice, epithelial-lined, irregular connective tissue bands spanned the tracheal lumen. Metaplasia of the bronchial epithelium was confined to the 40 ppm exposure groups. These effects on the respiratory system were more prevalent in male than in female mice. Hypoplasia of the uterus and ovaries, probably secondary to body weight loss, was confined to the 40 ppm exposure group. In conclusion, 13-week inhalation exposures of B6C3F1 mice to 10, 20, and 40 ppm of formaldehyde vapor induced histologic lesions in the upper respiratory system and concentrations of 40 ppm were lethal to those mice.


Anti-inflammatory protein TNFα-stimulated gene-6 (TSG-6) reduces inflammatory response after brain injury in mice.
Current research suggests that the glial scar surrounding penetrating brain injuries is instrumental in preserving the surrounding uninjured tissue by limiting the inflammatory response to the injury site. We recently showed that tumor necrosis factor (TNF)-stimulated gene-6 (TSG-6), a well-established anti-inflammatory molecule, is present within the glial scar. In the present study we investigated the role of TSG-6 within the glial scar using TSG-6 null and littermate control mice subjected to penetrating brain injuries. Our findings show that mice lacking TSG-6 present a more severe inflammatory response after injury, which was correlated with an enlarged area of astrogliosis beyond the injury site. Our data provides evidence that TSG-6 has an anti-inflammatory role within the glial scar.


Multiple T state conformations in a fish hemoglobin. Carbon monoxide binding to hemoglobin of Thunnus thynnus.
The blood of the Atlantic bluefin tuna (Thunnus thynnus) contains four hemoglobin components separable by chromatography on diethylaminoethylcellulose. These components are stable and functionally identical in their reactions with carbon monoxide. At low pH they remain in the T state even when liganded, and show two kinetic components in binding and in dissociation, with rates of 1) 1.2 microM-1 s-1 and 0.095 s-1 and 2) 0.013 microM-1 s-1 and 0.195 s-1, respectively, at pH 6, 20 degrees C, 0.1 m KPi. These components have difference spectra separated by more than 2 nm and are present in equal amounts. After CO has bound, there is a conformation change to an altered T state, in terms of the model of Monod et al. (Monod, J., Wyman, J., and Changeux, J. P. (1965) J. Mol. Biol. 12, 88-118), with a half-time of 65 s. At equilibrium, one-third of the slow kinetic component is changed into the new conformer, which binds CO at a rate of 0.14 microM-1 s-1.


Biomechanical signals suppress TAK1 activation to inhibit NF-kappaB transcriptional activation in fibrochondrocytes.
Exercise/joint mobilization is therapeutic for inflammatory joint diseases like rheumatoid and osteoarthritis, but the mechanisms underlying its actions remain poorly understood. We report that biomechanical signals at low/physiological magnitudes are potent inhibitors of inflammation induced by diverse proinflammatory activators like IL-1beta, TNF-alpha, and lipopolysaccharides, in fibrochondrocytes. These signals exert their anti-inflammatory effects by inhibiting phosphorylation of TAK1, a critical point where signals generated by IL-1beta, TNF-alpha, and LPS converge to initiate NF-kappaB signaling cascade and proinflammatory gene induction. Additionally, biomechanical signals inhibit multiple steps in the IL-1beta-induced proinflammatory cascade downstream of IkappaB kinase activation to regulate IkappaBalpha and IkappaBbeta degradation and synthesis, and promote IkappaBalpha shuttling to export nuclear NF-kappaB and terminate its transcriptional activity. The findings demonstrate that biomechanical forces are but another important signal that uses NF-kappaB pathway to regulate inflammation by switching the molecular activation of discrete molecules involved in proinflammatory gene transcription.


Driver seat comfort for level 3-4 autonomous vehicles.
Autonomous vehicles can be classified on a scale of automation from 0 to 5, where level 0 corresponds to vehicles that have no automation to level 5 where the vehicle is fully autonomous and it is not possible for the human occupant to take control. At level 2, the driver needs to retain attention as they are in control of at least some systems. Level 3-4 vehicles are capable of full control but the human occupant might be required to, or desire to, intervene in some circumstances. This means that there could be extended periods of time where the driver is relaxed, but other periods of time when they need to drive. The seat must therefore be designed to be comfortable in at least two different types of use case. This driving simulator study compares the comfort experienced in a seat from a production hybrid vehicle whilst being used in a manual driving mode and in autonomous mode for a range of postures. It highlights how discomfort is worse for cases where the posture is non-optimal for the task. It also investigates the design of head and neckrests to mitigate neck discomfort, and shows that a well-designed neckrest is beneficial for drivers in autonomous mode.


Predictive value of serum uric acid levels for adverse maternal and perinatal outcomes in pregnant women with high blood pressure. A systematic review and meta-analysis.
High serum uric acid seems to be associated with pre-eclampsia. The expected utility of uric acid is related to the probability of occurrence of maternal and neonatal complications. We evaluated the accuracy of uric acid in predicting adverse maternal and perinatal outcomes in pregnant women with high blood pressure. We performed an electronic search for studies evaluating the accuracy of high serum uric acid levels in pregnant women with high blood pressure. The assessment of risk of bias was performed using the QUIPS tool. For each included study, we collected data about study characteristics and diagnostic test accuracy to construct 2 × 2 tables. Pooled sensitivity (Se), specificity (Sp) and diagnostic odds ratio (DOR) were estimated using a bivariate model. Grading the quality of the evidence was assessed using the GRADE approach. Twenty-one studies, testing more than 6,000 women, met the inclusion criteria. The majority of studies were at low risk of bias. Ten studies evaluated the role of serum uric acid to predict pre-eclampsia, the pooled Se was 0.74 (95%CI 0.71-0.77), Sp was 0.66 (95%CI 0.63-0.68), and DOR was 9.67 (95%CI 4.57-20.47). The overall quality of evidence was evaluated as low. The GRADE rating was downgraduate for risk of bias and inconsistency. No robust evidence currently exists to suggest that uric acid measurement is useful in predicting maternal and perinatal adverse outcomes.


High-resolution sonographic guidance for transjugular liver biopsy.
A prospective randomized study was performed to compare conventional right internal jugular vein catheterization technique with high-resolution sonographically guided catheterization for transjugular liver biopsy. Forty-seven patients were assigned to undergo either conventional or high-resolution sonographically guided right internal jugular vein catheterization for transjugular liver biopsy. Sonographic guidance was significantly better than conventional guidance, reducing the number of failed catheterizations, from 22% (5 of 23) to 0% (0 of 24) (p < .05). Sonography also reduced the mean number (+/- SD) of passes required to catheterize the vein from 4.21 +/- 1.53 to 1.54 +/- 0.66 (p < .001) and was successful in 100% (5 of 5) of patients in whom conventional catheterization failed. High-resolution sonographic guidance is strongly recommended for transjugular liver biopsy in patients at high risk for bleeding.


A deep learning approach for the automatic recognition of prosthetic mitral valve in echocardiographic images.
The first step in the automatic evaluation of the cardiac prosthetic valve is the recognition of such valves in echocardiographic images. This research surveyed whether a deep convolutional neural network (DCNN) could improve the recognition of prosthetic mitral valve in conventional 2D echocardiographic images. An efficient intervention to decrease the misreading rate of the prosthetic mitral valve is required for non-expert cardiologists. This intervention could serve as a section of a fully-automated analysis chain, alleviate the cardiologist's workload, and improve precision and time management, especially in an emergent situation. Additionally, it might be suitable for pre-labeling large databases of unclassified images. We, therefore, introduce a large publicly-available annotated dataset for the purpose of prosthetic mitral valve recognition. We utilized 2044 comprehensive non-stress transthoracic echocardiographic studies. Totally, 1597 patients had natural mitral valves and 447 patients had prosthetic valves. Each case contained 1 cycle of echocardiographic images from the apical 4-chamber (A4C) and the parasternal long-axis (PLA) views. Thirteen versions of the state-of-the-art models were independently trained, and the ensemble predictions were performed using those versions. For the recognition of prosthetic mitral valves from natural mitral valves, the area under the receiver-operating characteristic curve (AUC) made by the deep learning algorithm was similar to that made by cardiologists (0.99). In this research, EfficientNetB3 architecture in the A4C view and the EfficientNetB4 architecture in the PLA view were the best models among the other pre-trained DCNN models.


Dyadic effects of distress on sleep duration in advanced cancer patients and spouse caregivers.
Short sleep duration is a common problem for both advanced cancer patients and their spouse caregivers. Sleep and distress have been shown to be interdependent in patient-caregiver and spouse dyads, yet virtually, no work has explored the dyadic effects of psychological distress on sleep in advanced cancer patients and spouse caregivers. The goal of the present study was to examine the dyadic impact of anxiety and depression on sleep duration in a sample of advanced cancer patients and their spouse caregivers. It was hypothesized that, for both patients and caregivers, anxiety and depression in individuals would be associated with sleep duration in both themselves (actor effects) and in their spouses (partner effects). Advanced cancer patients and their spouse caregivers (N = 87 dyads) completed cross-sectional questionnaires assessing demographic variables, subjective health, subjective sleep duration, and anxiety and depression symptoms. Controlling for sex, age, and subjective health, individuals' anxiety was negatively associated with their own and their partner's sleep duration. No significant actor or partner effects were found for depression. Results provided partial support for hypotheses. Although past work has demonstrated links between subjective sleep disturbance and anxiety/psychological distress, this is one of the first studies to examine partner effects of distress on sleep disturbance in advanced cancer patients and spouse caregivers.


Mutagenicity of chalks. A case in which the test results led to the improvement of the quality of commercial goods.
Mutagenicity testing, of methanolic extracts of chalks, by the Salmonella/mammalian-microsome system revealed that the blue and the green chalks contained mutagens. A positive mutagenic response was observed on Salmonella typhimurium strain TA98, both in the presence and absence of the microsome system (S9). The source of the mutagenicity was traced to the blue pigment used for manufacturing these chalks. The pigment, copper phthalocyanine, a product of a Japanese chemical industrial company, was found to contain impurities that were mutagenic. The mutagenic principle giving positive response in the TA98 in the presence of S9 was purified 10(5)-fold from the original pigment. Although its structure is yet to be elucidated, this indirect frame-shift mutagen had a strong activity: 5700 His+ revertants per microgram. This information, delivered in the beginning of 1981, prompted the manufacturer to start supplying a mutagen-free product. As a result, the blue chalks on the market became no longer mutagenic in the summer of 1982.


Purification and characterization of recombinant endoglucanase of Trichoderma reesei expressed in Saccharomyces cerevisiae with higher glycosylation and stability.
Cel5A (endoglucanase II) of Trichoderma reesei was expressed in Saccharomyces cerevisiae then purified. Two components (C1 and C2) of recombinant Cel5A with different glycosylation were obtained. Purified C1 had a larger molecular mass (57 kDa) than that of the native Cel5A produced by T. reesei (48 kDa) due to the different extents of asparagines-linked glycosylation. There was no significant difference in enzymatic activity between the C1 and the native Cel5A from T. reesei. C1 treated with Endoglycosidase H had a molecular mass of 54 kDa and retained about 88% of its original activity. Unpurified C2 was larger form of hyperglycosylation proteins. Its molecular mass was larger than 85 kDa till up to 200 kDa. It still retained activity regardless of its magnitude molecular mass. With increased glycosylation extent of the enzyme components (C2 >C1 >native Cel5A), the pH range of activity become wider, and thermal stability become higher.


Effects of insulin sensitizers on islet transplantation.
To solve the problems of islet engraftment, we investigated the effects of insulin sensitizers, metformin and rosiglitazone, on the in vitro and in vivo function of mouse islets. The in vitro study was done by culturing 30 isolated C57BL/6 mouse islets with glucose (100 or 300 mg/dL) or rosiglitazone (4.5 mumol/L) for 2, 4, 8, or 12 hours. The in vivo study was performed by syngeneically transplanting 150 C57BL/6 mouse islets under the kidney capsule of streptozotocin-diabetic mice. The metformin group was treated with 200 mg/kg/d in water and the control group was pair-fed the same volume of liquid diet. In the in vitro study, insulin release stimulated by 300 mg/dL glucose (n = 6) was the highest at all time points. That stimulated by rosiglitazone (n = 6) was greater than by 100 mg/dL glucose (n = 6) only at 8 hours. In the recipients treated with metformin (n = 17) and controls (n = 13), the blood glucose decreased and body weight increased gradually after transplantation. However, there was no significant difference between the two groups. Their tolerance to intraperitoneal glucose challenge at 2 and 4 weeks was also comparable. At 4 weeks, 12/17 (71%) in the metformin group and 8/13 (62%) in the control group achieved normoglycemia (P = .60). At 4 weeks, the insulin content of the graft was 8.35 +/- 3.42 mg in the metformin group and 5.28 +/- 4.28 mg in the control group (P = .59). Our data indicate that (1) rosiglitazone stimulated isolated islets to release insulin but was less effective than high levels of glucose; and (2) metformin treatment had no beneficial effect on islet recipients.


Ureteral endometriosis in post-menopausal women.
Ureteral obstruction secondary to endometriosis is an infrequently observed phenomenon, particularly in post-menopausal women. Two patients with obstructive uropathy, aged fifty-five and seventy-four, underwent ureteroplasty procedures with pathologic documentation of endometriosis. The possible pathogenetic mechanisms of ureteral endometriosis and previously reported cases are cited.


Fifteen years' experience with the aortic homograft: the conduit of choice for right ventricular outflow tract reconstruction.
Ninety-seven patients with pulmonary atresia underwent right ventricular outflow tract reconstruction using a homograft conduit. There were 46 hospital deaths (47%). Hospital mortality was significantly related to irreversible pulmonary hypertension (p less than 0.001) and thoracotomy for ligation of bronchial collaterals (p less than 0.01). The actuarial survival was 37 +/- 7% at 10 years. Sixteen patients undergoing recatheterization at a mean of 6 years had a mean transconduit gradient of 24 +/- 15 mm Hg. Obstructed conduits (i.e., with a gradient of greater than 50 mm Hg) were replaced in 3 patients, corresponding to 13 +/- 8% at 10 years. In each instance, the obstruction was due to neointimal hyperplasia in the Dacron tube rather than calcification of the homograft valve. The fresh, antibiotic-sterilized aortic homograft is the conduit of choice for right ventricular outflow tract reconstruction. The valve itself appears more resistant to calcification than its xenograft counterpart, and the absence of Dacron removes the problem of fibrinous peel obstructing the conduit. We now construct a tube of autologous pericardium to increase the length of the conduit and avoid complementary thoracotomy for ligation of bronchial collaterals.


Salivary biomarkers associated with myocardial necrosis: results from an alcohol septal ablation model.
To determine if salivary biomarkers demonstrate utility for identifying aspects of myocardial necrosis. Twenty-one patients undergoing alcohol septal ablation (ASA) for treatment of hypertrophic cardiomyopathy provided serum and unstimulated whole saliva at baseline and incremental time points post-ASA. Samples were analyzed for seven biomarkers related to myocardial damage, inflammation, and tissue remodeling using immunosorbent assays. Levels were compared with baseline and levels observed in 97 healthy controls. Biomarkers of myocardial damage and inflammation (ie, troponin I, creatine kinase-MB, myoglobin, C-reactive protein) rose in serum 2- to 812-fold after ASA (P < .01). Significant elevations of 2.0- to 3.5-fold were observed with C-reactive protein and troponin I in saliva (P < .02). Significant correlations between levels in serum and saliva were observed for C-reactive protein, matrix metalloproteinase-9, and myeloperoxidase (P < .001). Select salivary biomarkers reflect changes that occur during, and subsequent to, myocardial necrosis caused by ASA.


Effective modification of cell death-inducing intracellular peptides by means of a photo-cleavable peptide array-based screening system.
Intracellular functional peptides that play a significant role inside cells have been receiving a lot of attention as regulators of cellular activity. Previously, we proposed a novel screening system for intracellular functional peptides; it combined a photo-cleavable peptide array system with cell-penetrating peptides (CPPs). Various peptides can be delivered into cells and intracellular functions of the peptides can be assayed by means of our system. The aim of the present study was to demonstrate that the proposed screening system can be used for assessing the intracellular activity of peptides. The cell death-inducing peptide (LNLISKLF) identified in a mitochondria-targeting domain (MTD) of the Noxa protein served as an original peptide sequence for screening of peptides with higher activity via modification of the peptide sequence. We obtained 4 peptides with higher activity, in which we substituted serine (S) at the fifth position with phenylalanine (F), valine (V), tryptophan (W), or tyrosine (Y). During analysis of the mechanism of action, the modified peptides induced an increase in intracellular calcium concentration, which was caused by the treatment with the original peptide. Higher capacity for cell death induction by the modified peptides may be caused by increased hydrophobicity or an increased number of aromatic residues. Thus, the present work suggests that the intracellular activity of peptides can be assessed using the proposed screening system. It could be used for identifying intracellular functional peptides with higher activity through comprehensive screening.


[Comparative effects of intravitellin injections of p, p'-DDT and of commercial DDT on the germ cells of embryonic gonads of birds].
The p, p'-DDT present in the composition of commercial DDT, is responsible for the germ deficit in the gonads of bird embryos. Administered into the vitellus or on the shell, before incubation, the pesticide exerts the same reduction of the Quail germ population. While, for the Chick, the germ decrease is less significant after injection than after immersion.


Three-dimensional visualization and image processing in the evaluation of patterned injuries. The AFIP/UNC experience in the Rodney King case.
We used image processing to elucidate patterned injuries in a case of assault with a police baton. Three-dimensional visualization techniques were then used to correlate the location of patterned injuries with subjacent fracture and soft tissue damage. The visualization methods are discussed.


Differential diagnosis of peritoneal lesions of müllerian type and similar epithelial tumors of the peritoneum.
The female peritoneum is the site of various tumor-like and tumorous lesions that resemble derivatives of the primary müllerian system. Those lesions can therefore be summarized under the term secondary müllerian system. These lesions can cause problems in macroscopic and microscopic examination if clinicians or pathologists are not acquainted with them. The relationship between the derivatives of the embryonal müllerian duct and the secondary müllerian system is underscored by the expression of many different antigens, as revealed by immunohistology.


Morbidity and mortality in Klinefelter syndrome (47,XXY).
Klinefelter syndrome (KS) (47,XXY) is the most common sex chromosome disorder in man and is a relatively common cause of male infertility and hypogonadism. The syndrome has been known since 1942, and many reports of different diseases associated with KS have been reported since that, but a more systematic knowledge about the long-term outcome was not described until the last decade, where nation-wide epidemiological studies were reported from Britain and Denmark. We here review the epidemiological data from two cohorts of patients with KS in Denmark and Britain, showing a significant increase in both mortality and morbidity from a variety of different causes. Mortality was increased by 50% (SMR 1.5 or HR 1.4) corresponding to a median loss of approximately 2 years. The risk of being admitted to hospital with any diagnosis was increased by 70%. The underlying reason for the poorer health in KS may be caused by interaction of genetic, hormonal and socio-economic factors. Both morbidity and mortality are significantly increased in Klinefelter syndrome with a 50% increase in mortality risk and a 70% increase in risk of being admitted to hospital.


Herpes simplex virus type 1 persistence and latency in cultured rabbit corneal epithelial cells, keratocytes, and endothelial cells.
Cell cultures of rabbit corneal epithelium, keratocytes, and endothelium were used to determine the lytic cycle of herpes simplex virus type 1. Viral growth was fastest in epithelial cells. A novel HSV-1 in-vitro latency system was established in the three distinct cell types. Cell cultures were inoculated at low multiplicities of infection with HSV-1. Temperature manipulation alone was used to induce and reactivate latent HSV-1 infections. The presence of cellular stress proteins was demonstrated at supraoptimal temperatures. All cell types were capable of maintaining latent viral infections under these conditions. Viral persistence was present in 20% of epithelial cell cultures at supraoptimal temperatures, but not in keratocyte cultures or endothelial cell cultures.


Aim to unify the narrow band imaging (NBI) magnifying classification for colorectal tumors: current status in Japan from a summary of the consensus symposium in the 79th Annual Meeting of the Japan Gastroenterological Endoscopy Society.
At present, there are many narrow band imaging (NBI) magnifying observation classifications for colorectal tumor in Japan. To internationally standardize the NBI observation criteria, a simple classification system is required. When a colorectal tumor is closely observed using the recent high-resolution videocolonoscope, a pit-like pattern on the tumor can be observed to a certain degree without magnification. In the symposium we could have a consensus that we will name the pit-like pattern as 'surface pattern.' Using the NBI system, the microvessels on the tumor surface can also be recognized to a certain degree. When the NBI system is used, the structure is emphasized, and consequently, the surface pattern can be recognized easily. Recently, an international cooperative group was formed and consists of members from Japan, the USA and Europe, which is named as the Colon Tumor NBI Interest Group. This group has developed a simple category classification (NBI international colorectal endoscopic [NICE] classification), which classifies colorectal tumors into types 1-3 even by closely observing colorectal tumors using a high-resolution videocolonoscope (Validation study is now ongoing by Colon Tumor NBI Interest Group.). The key advantage of this is simplification of the NBI classification. Although the magnifying observation is the best for getting detailed NBI findings, both close observation and magnifying observation using the NICE classification might give almost similar results. Of course the NICE classification can be used more precisely with magnification. In this report we also refer the issues on NBI magnification, which should be solved as early as possible.


Visual and anatomical outcomes associated with treat-and-extend administration of intravitreal aflibercept for neovascular age-related macular degeneration.
To investigate the visual and anatomical outcomes associated with treat-and-extend (TAE) regimen of intravitreal (IVT) aflibercept in eyes with treatment naïve neovascular age-related macular degeneration (nvAMD). A retrospective chart review of eyes that underwent IVT aflibercept injections for nvAMD between May 2014 and March 2018 was performed. The primary outcome was the change in best corrected visual acuity (BCVA) at 12 months. Secondary outcomes included the change in central retinal thickness (CRT), subretinal fluid (SRF) and intraretinal fluid (IRF). Data from 213 eyes of 213 patients (138 female, 65%) met the inclusion criteria. The mean (SD) age of the patients was 80.4 (± 9.2) years. The mean baseline BCVA (0.92 ± 0.50 logMAR, improved by 0.20 (± 0.40) logMAR units at 12 months (p < 0.001). Seventy-two (34%) eyes gained ≥ 0.3 logMAR and 47 (22%) eyes achieved BCVA ≤ 0.3 logMAR at 12 months. Baseline BCVA, patient age, and the number of aflibercept injections received were predictors of the change in BCVA at 12 months. Mean CRT improved from 347 (± 117) µm at baseline to 246 (± 55) µm at 12 months (p < 0.001). The percentage of eyes with SRF and IRF on SD-OCT declined from 63 to 21% and from 60 to 26% at 12 months, respectively. A TAE regimen of IVT aflibercept in treatment naïve nvAMD is associated with good visual and anatomical outcomes in routine clinical practice. Resolution of exudation occurred in about half of nvAMD cases at 12 months. Individualized administration of IVT aflibercept may reduce injection burden.


Kallmann syndrome in two sisters with other developmental anomalies also affecting their father.
The classical features of Kallmann syndrome with anosmia and hypogonadotropic hypogonadism were observed in two sisters aged 13 and 19. They had additional malformations including anosmia, bilateral vesico-ureteral reflux and unilateral hearing loss. One of the girls had unilateral coloboma of the optic nerve. The father had unilateral hearing loss and duplication of the left ureter; he died of an unrecognized coarctation of the aorta. He had no clinical signs of hypogonadism or anosmia. It is suggested that the malformations observed in these patients may be due to a dominant inherited defect of embryonic cell migration, resulting in different phenotypic expressions within the same family, including the Kallmann syndrome.


Neuropsychiatric manifestations of COVID-19, potential neurotropic mechanisms, and therapeutic interventions.
The coronavirus disease 2019 (COVID-19) pandemic has caused large-scale economic and social losses and worldwide deaths. Although most COVID-19 patients have initially complained of respiratory insufficiency, the presence of neuropsychiatric manifestations is also reported frequently, ranging from headache, hyposmia/anosmia, and neuromuscular dysfunction to stroke, seizure, encephalopathy, altered mental status, and psychiatric disorders, both in the acute phase and in the long term. These neuropsychiatric complications have emerged as a potential indicator of worsened clinical outcomes and poor prognosis, thus contributing to mortality in COVID-19 patients. Their etiology remains largely unclear and probably involves multiple neuroinvasive pathways. Here, we summarize recent animal and human studies for neurotrophic properties of severe acute respiratory syndrome coronavirus (SARS-CoV-2) and elucidate potential neuropathogenic mechanisms involved in the viral invasion of the central nervous system as a cause for brain damage and neurological impairments. We then discuss the potential therapeutic strategy for intervening and preventing neuropsychiatric complications associated with SARS-CoV-2 infection. Time-series monitoring of clinical-neurochemical-radiological progress of neuropsychiatric and neuroimmune complications need implementation in individuals exposed to SARS-CoV-2. The development of a screening, intervention, and therapeutic framework to prevent and reduce neuropsychiatric sequela is urgently needed and crucial for the short- and long-term recovery of COVID-19 patients.


Clinical characteristics at the renal replacement therapy initiation of Japanese pediatric patients: a nationwide cross-sectional study.
Although there is debate regarding the timing of initiation of renal replacement therapy (RRT) in adults with end-stage renal disease, there is a paucity of reliable epidemiological data on pediatric patients. The present study was performed to investigate current practice in Japan with regard to the timing of initiation of RRT in children based on estimated glomerular filtration rate (eGFR). A total of 649 pediatric patients < 20 years old with eGFR at the initiation of RRT between 1 January 2006 and 31 December 2013 were included in the study. Baseline eGFR was calculated for each patient using the Schwartz formula. eGFR at the start of RRT was 12.1 mL/min/1.73 m2 [interquartile range (IQR) 8.4-16.3]. A total of 209 children (32.2%) had high eGFR (eGFR > 15 mL/min/1.73 m2) at the initiation of RRT. Initiation of RRT was more likely in those undergoing preemptive transplantation (PEKT) with high eGFR [odds ratio (OR) 4.16; 95% confidence interval (CI) 1.95-8.90, P < 0.001]. There were 31 deaths of various causes during follow-up, with infections representing the leading causes of death. The median eGFR at the initiation of RRT in children showed a wide range of variation. Further studies are needed to investigate the impact of the decision regarding when to initiate RRT in individual pediatric patients.


Australian beef industry worker's knowledge, attitudes and practices regarding Q fever: A pilot study.
Q fever is a vaccine-preventable zoonotic infection with potentially severe health outcomes and high economic costs that affects agricultural workers, including beef and cattle industry workers, however this population historically have sub-optimal vaccine uptake. To gather quantitative and qualitative pilot data from Australian beef industry workers on their knowledge, attitudes and practices around Q fever and Q fever vaccination. A mixed methods approach was used to ascertain the Q fever disease risk perception and vaccination behavior of a purposive convenience sample of beef industry workers attending an industry expo in Rockhampton, Queensland, Australia between May 7th and 9th, 2018. The quantitative survey response rate was 83% (n = 86). More than 70% of respondents reported exposure to known Q fever risk factors. Eighty six percent were aware of Q fever, the self-reported uptake of Q fever vaccine was 27% and 9% reported undertaking testing which showed evidence of previous infection. Five main themes emerged from the qualitative data: "Finding the time" among other life priorities to attend a doctor for a vaccine; "Employer responsibility" to provide the vaccine; "My doctor knows me" and could suggest Q fever vaccination; "Assigning Risk" across a range of attitudes, including thinking it would not happen to them, 'fatalism', and knowing the danger but taking the risk anyway; and "The Need for Outreach" vaccine delivery services in their communities. These data suggest that a coordinated public health approach to testing and vaccine provision, coupled with an awareness campaign among regional doctors to prompt them to routinely ask patients about their Q fever risk and vaccination history, should form part of a broad approach to Q fever control and prevention.


[Determination of 20 (S)-ginsengnoside Rh2 in the alkali-hydrolysis product of saponins from leaves of Panax qinquefolium by RP-HPLC].
To determine 20(S)-ginsengnoside Rh2 in the hydrolysis product of saponins from leaves of Panax qinquefolium. The separation was performed on ZORBAX EXEND C18 column (4.6 mm x 250 mm, 5 microm), eluted with methanol and water (85:15) as mobile phase with the rate of 1.2 mL x min(-1) at 25 degrees C, the wavelength for measurement was 203 nm. The calibration curve was linear in the range of 0.5-25 microg for 20(S)-ginsengnoside Rh2(r = 0.9999, n = 7). The average recovery was 99.7% (RSD= 1.0%). This method is simple, accurate, reliable and reproducible. The result shows that the transform ratio of 20(S)-ginsengnoside Rh2 is high by this hydrolysis method.


Mechanotransduction: getting morphogenesis down pat.
Embryonic morphogenesis requires the coordination of forces across multiple tissues and their associated extracellular matrices. A new study reports a mechanical feedback loop in the Caenorhabditis elegans embryo between muscle and epidermis that may provide a model for understanding how tissues coordinate morphogenetic events in the embryo.


Electrically evoked auditory brainstem response in peripherally myelin-deficient mice.
The integrity of the myelin sheath is important for normal electrophysiological function and survival of neurons that make up the auditory nerve. It is hypothesized that myelin deficiency of the auditory nerve may change the electrophysiologic characteristics of the auditory system, especially the temporal properties. In this study, the electrically evoked auditory brainstem response (EABR) was systematically evaluated in TrJ and Po-DT-A mice. Both of these mice have a deficit of their peripheral myelin. Correlation between the EABR and degree of myelin deficiency was also evaluated. The EABR in both strains of poorly myelinated mice exhibited prolonged latency, decreased amplitude, elevated threshold of wave I evoked by short-duration stimuli (20 microseconds/phase). A 2-pulse stimulation paradigm was used to evaluate refractory properties. Myelin-deficient mice exhibited slower recovery from the refractory state than controls. Long-duration stimuli (4 ms/phase) were used to assess integration properties. Myelin-deficient mice demonstrated prolonged wave I latency and more gradual latency changes with current level. Myelin thickness showed a strong correlation with EABR threshold for short-duration stimulation (r = -0.784), maximum wave I latency (r = -0.778) and the time constant of the wave I latency-current level function (r = -0.736) for long-duration stimulation and normalized wave I recovery functions (r = -0.718). These findings suggest that EABR measurement may be a promising tool to assess the electrically stimulated properties of auditory neurons, particularly related to the status of myelin sheath.


Results of the percutaneous pinning of proximal humerus fractures with a modified palm tree technique.
Many techniques are available for closed reduction and percutaneous fixation of proximal humeral fractures. The palm tree technique was described by Kapandji in 1989. In that technique three curved wires are inserted through one hole at the V-shaped insertion of the deltoid muscle. It is a good technique but it has some disadvantages. In this study we introduced some modifications for the technique, and we evaluated the clinical results of the modified technique in treatment of 18 cases. Eighteen patients with displaced proximal humeral fractures were treated by closed reduction and percutaneous fixation with the palm tree technique after minor modifications. The age of the patients ranged from 38 to 75 years with an average of 56 years. Eleven were females and seven were males. The fractures were two-part in 13 cases and three-part fractures in five cases. The average time of healing was seven weeks. The follow-up period ranged from 14 months to 39 months with an average of 22 months. The Constant score ranged from 45 to 88 with a mean of 73. The results were satisfactory in 77% and unsatisfactory in 23% of the cases. The complications included pin tract infection in two cases, intraarticular wire migration in one case, skin necrosis around the wires in three cases and malunion with varus deformity in one case. No cases were complicated by neurovascular injury, loss of fixation or avascular necrosis of the humeral head. The palm tree technique is a good method for fixation of proximal humeral fractures. It produces good grip in both of the proximal and distal fragments and allows for early joint movements. Our modifications allow for easy insertion of the wires, increase the stability of fixation and minimize the risk of complications.


Heterologous expression of hAID in E. coli leads to the production of a splice isoform of AID: hAIDδC, a mystery to be explored.
Activation-induced cytidine deaminase (AID) is a key player that initiates antibody diversification in activated B-cell. AID mediates somatic hypermutation (SHM) and class switch recombination (CSR) via the deamination of cytosine to uracil at the Ig locus, resulting in the production of high-affinity antibodies. AID is predominantly restricted to Ig genes, whereas off-targeting of AID leads to lymphocyte-related malignancies. Interestingly, apart from FL-AID other splice isoforms of AID are highly expressed in the lymphocyte malignancies. In our study, we found that the heterologous expression of hAID-FL in E. coli cells produced two induced bands of hAID as demonstrated by SDS-PAGE and western blotting. Remarkably, peptide mapping data predicted that one band is hAID-FL and the other is its splice isoform, hAIDδE4a. To get an insight into why E. coli cells expressed hAID-FL and hAID variant, we mutated the 5' and 3' splice site of a putative intron of hAID, but it failed to produce only hAID-FL. Incidentally, hAID expressed with fusion partners also displayed two bands, and peptide mapping data strongly suggest that besides hAID-FL, the lower band showed a significant number of amino acids missing towards the C-terminal domain (named as hAIDδC). Our results are the first report to show that expression of recombinant hAID alone or irrespective of solubilization tags in E. coli cells produced hAID-FL and hAIDδC. It will be fascinating to explore the potential mechanism underlying the expression of hAIDδC from recombinant hAID plasmid in E. coli cells.


Species-Wide Transposable Element Repertoires Retrace the Evolutionary History of the Saccharomyces cerevisiae Host.
Transposable elements (TE) are an important source of genetic variation with a dynamic and content that greatly differ in a wide range of species. The origin of the intraspecific content variation is not always clear and little is known about the precise nature of it. Here, we surveyed the species-wide content of the Ty LTR-retrotransposons in a broad collection of 1,011 Saccharomyces cerevisiae natural isolates to understand what can stand behind the variation of the repertoire that is the type and number of Ty elements. We have compiled an exhaustive catalog of all the TE sequence variants present in the S. cerevisiae species by identifying a large set of new sequence variants. The characterization of the TE content in each isolate clearly highlighted that each subpopulation exhibits a unique and specific repertoire, retracing the evolutionary history of the species. Most interestingly, we have shown that ancient interspecific hybridization events had a major impact in the birth of new sequence variants and therefore in the shaping of the TE repertoires. We also investigated the transpositional activity of these elements in a large set of natural isolates, and we found a broad variability related to the level of ploidy as well as the genetic background. Overall, our results pointed out that the evolution of the Ty content is deeply impacted by clade-specific events such as introgressions and therefore follows the population structure. In addition, our study lays the foundation for future investigations to better understand the transpositional regulation and more broadly the TE-host interactions.


In situ reductive dehalogenation of groundwater driven by innovative organic carbon source materials: Insights into the organohalide-respiratory electron transport chain.
In situ bioremediation using organohalide-respiring bacteria (OHRB) is a prospective method for the removal of persistent halogenated organic pollutants from groundwater, as OHRB can utilize H2 or organic compounds produced by carbon source materials as electron donors for cell growth through organohalide respiration. However, few previous studies have determined the suitability of different carbon source materials to the metabolic mechanism of reductive dehalogenation from the perspective of electron transfer. The focus of this critical review was to reveal the interactions and relationships between carbon source materials and functional microbes, in terms of the electron transfer mechanism. Furthermore, this review illustrates some innovative strategies that have used the physiological characteristics of OHRB to guide the optimization of carbon source materials, improving the abundance of indigenous dehalogenated bacteria and enhancing electron transfer efficiency. Finally, it is proposed that future research should combine multi-omics analysis with machine learning (ML) to guide the design of effective carbon source materials and optimize current dehalogenation bioremediation strategies to reduce the cost and footprint of practical groundwater bioremediation applications.


Local transcutaneous electrical stimulation (TENS) effects in experimental inflammatory edema and pain.
Few studies in the literature associated transcutaneous electrical stimulation (TENS) use with an antiinflammatory activity. The purpose of this study was to investigate the effects of low (10 Hz)- and high (130 Hz)-frequency TENS on hyperalgesia and edema that occur after injection of carrageenan in rat paw. After induction of inflammation, either low- or high-frequency TENS was applied in the rat paw for 20 min, and the effect of TENS treatment on escape or paw withdrawal and edema was measured. Both low- and high-frequency TENS inhibited by 100% the hyperalgesia but not the edema response. However, low-frequency TENS presented longer lasting effect as compared with high-frequency TENS. Naltrexone-treated animals showed a complete reversion of the analgesic effect induced by low- but not high-frequency TENS. Thus, our data demonstrated absence of an antiinflammatory effect associated to TENS use and confirmed the participation of endogenous opioids on low TENS-induced analgesia.


Density functional theory (DFT) and natural bond orbital (NBO) study of vibrational spectra and intramolecular hydrogen bond interaction of L-ornithine-L-aspartate.
In this study, exhaustive conformations of (S)-4-amino-4-carboxybutan-1-aminium (S)-3-amino-3-carboxypropanoate (LOLA) have been scanned. Experimental and theoretical studies on the structure and vibrations of the title compound are presented. The optimized molecular structure, vibrational wavenumbers, Mulliken atomic charges, natural bond orbital (NBO) and molecular electrostatic potential studies have been performed by density functional theory (DFT) using B3LYP method with the 6-311++G(d,p) basis set. Computed X-ray powder diffraction (XRPD) data has been carried out by DFT calculations and ab initio from measured XRPD finding. The LOLA molecular geometry has been determined which exists in the form of salt by intramolecular H-bonds and ionic bonding. Moreover, calculated vibrational frequencies were applied to simulate IR and Raman spectra of the title compound which showed excellent agreement with observed spectra. Reliable vibrational assignments have been made on the basis of potential energy distribution (PED) and 0.992 has been obtained by least squares method which is the uniform scaled factor for theoretical frequencies at 6-311++G(d,p) basis set. In addition, the hydrogen bonding in LOLA molecule has been explored by calculation of the hyperconjugative charge transfer interaction on [LP X-σ(*)(Y-H)], under NBO analysis, Mulliken atomic charge analysis, molecular electrostatic potential map (MEP) and vibrational spectra. Finally, HOMO-LUMO of the title compound has been plotted for predicting reactive sites.


Effects of 10-min prewarming on core body temperature during gynecologic laparoscopic surgery under general anesthesia: a randomized controlled trial.
Previous research has shown a beneficial effect of prewarming for preventing inadvertent perioperative hypothermia. However, there are few studies of the effects of a short prewarming period, especially in gynecologic laparoscopic surgery. Fifty-four patients were randomly assigned to 2 groups. Patients in the non-prewarming group were only warmed intraoperatively with a forced air warming device, while those in the prewarming group were warmed for 10 min before anesthetic induction and during the surgery. The primary outcome was incidence of intraoperative hypothermia. Intraoperative hypothermia was observed in 73.1% of the patients in the non-prewarming group and 24% of the patients in the prewarming group (P < 0.001). There were significant differences in core temperature changes between the groups (P < 0.001). Postoperative shivering occurred in 8 of the 26 (30.8%) patients in the non-prewarming group and in 1 of the 25 (4.0%) patients in the prewarming group (P = 0.024). Forced air warming for 10 min before induction on the operating table combined with intraoperative warming was an effective method to prevent hypothermia in patients undergoing gynecologic laparoscopic surgery.


Allele frequency of two intragenic microsatellite loci of SEL1L gene in Northern Italian population.
Two cytosine-adenine (CA) repeats CAR/CAL and RepIN20 occur in the human SEL1L gene, which is regarded as a candidate gene for insulin-dependent diabetes mellitus (IDDM) and Grave's disease. We have characterized these repeats to determine if they might serve as effective microsatellite markers for linkage analysis to clarify whether SEL1L gene plays a role in the pathogenesis of these autoimmune diseases. The allele frequencies and average heterozygosity of the microsatellite repeats were analysed in 94 DNA samples from peripheral blood mononuclear (PBMC) cells from adults of Northern Italy. The average heterozygosity was 0.68 for CAR/CAL polymorphism and 0.85 for RepIN20. The size of PCR fragments of CAR/CAL ranged from 207-225 bp and the most frequent allele was 207 bp (40.4%). The size of the fragments of RepIN20 ranged from 237-255 bp and the most frequent allele was 249 bp (30.8%). In the light of the highly polymorphic nature of both microsatellites and their intragenic location in SEL1L gene, we suggest that they could provide a means for linkage analysis to clarify the potential role of SEL1L in conferring susceptibility to IDDM or Grave's disease.


The influence of mean heart rate on measures of heart rate variability as markers of autonomic function: a model study.
Some studies have demonstrated that the assessments of autonomic activities from the alterations of heart rate variations (HRVs) after autonomic blockade and during exercise of high intensity by the spectral analysis of HRV seemed inconsistent with actual situation. The inconsistency is probably caused by the contributions of fluctuating magnitudes and mean levels of autonomic activities on HRV having not been clarified. The alterations of HRV after autonomic blockade and during exercise of high intensity using a mathematical model were simulated. The autonomic activity in normal condition was assumed first according to some experimental evidence. Then autonomic activities after sympathetic blockade, vagal blockade and during exercise of high intensity were appropriately adjusted accordingly. The HRVs in response to these given autonomic activities were simulated. We found that the effect on HRV influenced by the mean level of autonomic activity is helpful to explain alterations of HRV in these conditions. After vagal blockade, a largely reduced low frequency (LF) power could be caused by the reduced mean heartbeat interval induced by a decreased mean level of vagal activity. Increased low and high frequency powers after sympathetic blockade could be caused by the increased mean heartbeat interval induced by a decreased mean level of sympathetic activity. A decreased LF power during exercise of high intensity, in addition to the withdrawal of vagal activity, could also be caused by the decreased mean heartbeat interval induced by an increased mean level of sympathetic activity.


Effects of L-DOPA Pretreatment on the Kinetics, Migration and Carbon Ion Radiation Response of T98G Cells.
Glioblastoma is the most malignant and widespread brain tumor in adults, with a rapid clinical course. Recently, it has been hypothesized that L-DOPA plays a role in the diagnosis and treatment of glioblastoma. The aim of this study was to assess the effects of pretreatment with L-DOPA on the biological behavior of human T98G cells in vitro. T98G cells were treated with 50 μg/ml or 100 μg/ml of L-DOPA for 4 h and their morphology, growth rate, clonogenic survival and migratory capacity in basal conditions and after carbon ion irradiation were evaluated using standard methods. Treated cells showed a lower growth rate and an increased migratory capacity that correlated with the dose of tested L-DOPA. Treatment with L-DOPA increased the growth rate of carbon ion irradiated T98G cells compared to control non-treated cells exposed to the same radiation dose. Our results open further questions about the overall advantage of L-DOPA treatment of glioblastoma.


Regional Oxygenation and Perfusion Monitoring to Optimize Neonatal Packed Red Blood Cell Transfusion Practices: A Systematic Review.
Contemporary packed red blood cell transfusion practices in anaemic preterm infants are primarily based on measurement of hemoglobin or haematocrit. In neonatal intensive care units, most preterm infants receive at least 1 packed red cell transfusion as standard treatment for anaemia of prematurity. Clinicians are faced with a common question "at what threshold should anaemic preterm infants receive packed red blood cell transfusion?". While evidence from interventional trials offers a range of haemoglobin levels to clinicians on thresholds to initiate red cell transfusion, it does not offer identification of exact haemoglobin level at which regional oxygenation and perfusion gets compromised. Assessment of regional oxygenation using near infrared spectroscopy and perfusion using ultrasound could offer a personalized transfusion medicine approach to optimize transfusion practices. We conducted a systematic review of the literature to identify the role of both regional oxygenation and/or ultrasound-based perfusion monitoring as a potential trigger to initiate packed red blood cell transfusion in anaemic preterm infants. MEDLINE, Embase, Maternity and Infant Care database were searched up to March 2021. Publications identified were screened and relevant data was extracted. Changes to regional oxygenation and/or perfusion monitoring before and after packed red blood cell transfusion were the primary outcomes. 44 out of 755 studies met the inclusion criteria and were included in the final analysis. Most were prospective, observational studies in stable preterm infants. Overall, studies reported an improvement in regional oxygenation and/or ultrasound-based perfusion after packed red blood cell transfusion. These changes were more consistently observed when hemoglobin <9.6g/dL or hematocrit was <0.30. Significant variation was found for patient characteristics, postnatal age at the time of monitoring, criteria for diagnosis of anaemia, and period of monitoring as well as regional oxygenation monitoring methodology. Regional oxygenation and/or perfusion monitoring can identify at-risk anaemic preterm infants and are promising tools to individualize packed red blood cell transfusion practices. However, there is lack of evidence for incorporating this monitoring, in their present form, into standard clinical practice. Additionally, consistency in reporting of study methodology should be improved.


[Budget impact analysis of the first-line treatment of relapsing remitting multiple sclerosis in Spain].
To assess the budget impact of the treatment for relapsing remitting multiple sclerosis (RRMS), interferons, and glatiramer acetate, from the National Health System perspective in Spain. A budget impact model was designed to compare the cost of RRMS treatment in different settings, using a five year time-horizon, considering different percentages of administration of each medication. A reference setting o base case using all the available first line treatments (interferons and glatiramer acetate) was compared with five alternatives scenarios excluding each one of these treatments. The cost analysis (euros, year 2010) includes direct medical resources (drugs, administration, visits, disease management, diagnostic tests). Unitary cost data was obtained from the health costs database e-Salud and drugs catalogue. Considering a cohort of 22 255 patients with RRMS, the mean global budget impact per year would be 260 775 470 euros in the base case. The setting that excluded glatiramer acetate increases the budget impact in a 3.23% (372 euros per patient per year). Pharmacological costs were the key drivers of total cost (90%). The use of glatiramer acetate in the first-line-treatment of RRMS patients is a cost-saving strategy, which may decrease the budget impact from the National Health System perspective in Spain.


Impact of Toll-like receptor signalling on urinary tract infection.
Toll-like receptors (TLRs), components of the innate immune system, play a pivotal role in the pathogenesis of urinary tract infection (UTI). TLRs (especially TLR4) expressed both by epithelial and non-epithelial cells, e.g. monocytes, initiate appropriate immune and inflammatory responses to defend and overcome microbial invasion and infection. Virulent uropathogenic strains (Escherichia coli) express P fimbriae, which bind to glycolipid receptors of uroepithelial and kidney tubular cells, triggering TLR4 activation with subsequent recruitment of leukocytes and release of pro-inflammatory cytokines. Tamm-Horsfall glycoprotein (uromucoid), a kidney-specific glycoprotein, not only binds to fimbriated E. coli and activates complement and dendritic cells, but also apparently shows an immunoregulatory function in UTI via a TLR4-dependent mechanism. Dysregulation of TLR and chemokine candidate genes (e.g. CXCR1) might predispose patients to chronic recurrent UTI. TLR antagonists and agonists can influence host defence mechanisms, and some of these immunomodulating agents may help to overcome intrinsic disturbances of the TLR system to offer new therapeutic options in UTI.


Serum testosterone level of patients with gastric carcinoma before and after gastrectomy.
The serum testosterone level (STL) was determined in 84 male and 32 female patients with gastric carcinoma and in 58 male and 20 female patients with benign diseases as a control group. The STL of the male patients with carcinoma was lower (446 +/- 149 ng/dl) than that of the male control group (532 +/- 132 ng/dl) (P less than 0.001). Even 17 male patients of the early carcinoma showed lower STL (440 +/- 117 ng/dl) than the normal group (P less than 0.001). In the female patients, it was also lower (31.6 +/- 16.0 ng/dl) than in the control group (46.3 +/- 15.3 ng/dl) (P less than 0.005). The postoperative STL of the cases surviving the gastrectomy was higher than the preoperative data in 32 male patients (P less than 0.005) as well as in 12 female patients (0.025 greater than P greater than 0.01), whereas it obviously decreased in the patients who died of recurrence. Therefore, it appears that gastric carcinoma decreases the STL by some mechanism.


Corneal astigmatism after phacoemulsification and lens implantation through unsutured scleral and corneal tunnel incisions.
We compared the changes in corneal astigmatism after phacoemulsification and intraocular lens implantation in 93 consecutive eyes with unsutured 4-mm superior scleral tunnel incisions to those through 105 consecutive eyes with unsutured 3.2- to 3.5-mm temporal corneal tunnel incisions. Keratometry measurements were obtained preoperatively and at postoperative day 1, week 1, and week 6. Group differences in scalar and vector astigmatism were compared by using analysis of variance methods. Mean scalar astigmatism in the scleral incision group changed from preoperative astigmatism by 0.65 diopter at postoperative day 1, 0.37 diopter at postoperative week 1, and 0.13 diopter at postoperative week 6. Mean scalar astigmatism in the corneal incision group changed from preoperative astigmatism by 0.39 diopter at postoperative astigmatism by 0.39 diopter at postoperative day 1, 0.21 diopter at postoperative week 1, and 0.13 diopter at postoperative week 6. Mean vector astigmatism in the scleral incision group changed 1.26 diopters at 80 degrees at postoperative day 1, 1.05 diopters at 83 degrees at postoperative week 1, and 0.42 diopter at 103 degrees at postoperative week 6. Mean vector astigmatism in the corneal incision group changed 0.77 diopter at 90 degrees at postoperative week 1, and 0.61 diopter at 89 degrees at postoperative week 6. The differences were statistically significant (P = .003) only by vector analysis at the postoperative day 1 examination. We found significantly greater with-the-rule change in astigmatism in the scleral incision group than in the corneal incision group on the first postoperative day. The effect disappeared by the sixth postoperative week.


Differential modulatory actions of GABAA agonists on susceptibility to GABAA antagonists-induced seizures in morphine dependent rats: possible mechanisms in seizure propensity.
In order to clarify the mechanisms involved in the susceptibility to GABA(A) antagonists-induced seizures in morphine dependent rats, we investigated how GABA(A) agonists modulate this vulnerability. Seizures were induced to animals by infusion of GABA(A) antagonists: pentylenetetrazole (PTZ), picrotoxin (PIC) and bicuculline (BIC). GABA(A) agonists, muscimol (MUS) and 4,5,6,7-tetrahydroisoxazolo [5,4-c]pyridin-3-ol (THIP), were administered intravenous (i.v.) before antagonists. Morphine-dependence significantly decreased the PTZ threshold dose (19.16±1.89 versus 25.74±1.25mg/kg) while, it had no effect on PIC induced seizures. BIC doses for both threshold and tonic-clonic seizures induction were significantly lower in morphine dependent rats (0.10±0.01 and 0.12±0.02 versus 0.25±0.02 and 0.39±0.07mg/kg respectively). In morphine-dependence, although pre-treatment with MUS significantly increased the required dose of PTZ for seizures threshold, THIP significantly decreased the required dose of PTZ for tonic-clonic convulsion. Moreover, MUS pretreatment completely recovered the effect of morphine dependency on BIC seizure activity. The results suggest that the capability of GABA(A) agonists on modulation of propensity to seizures induced by different antagonists in morphine-dependence is dissimilar. Therefore, it seems that long-term morphine alters some properties of GABA system so that the responsive rate of GABA(A) receptors not only to its antagonists, but also to its agonists will change differently.


Effects of Music Therapy on Quality of Life in Adults with Sickle Cell Disease (MUSIQOLS): A Mixed Methods Feasibility Study.
To investigate the feasibility, acceptability, and preliminary efficacy of a 6-session music therapy protocol on self-efficacy, quality of life, and coping skills in adults with sickle cell disease (SCD). Using a mixed-methods intervention design, adults with SCD (ages 21-57; mean age 32.33) were randomized (1:1) to either 1) a 6-session music therapy (MT) intervention (n = 12) or 2) waitlist control (WLC) (n = 12) using stratified randomization where factors were age in years (≤30 vs >30), and sex (male, female). All participants completed two weeks of daily electronic pain diary entries and self-efficacy, quality of life, and coping skills measures before and after their assigned study condition to explore preliminary efficacy. MT participants were taught music exercises accessed via smartphone and subsequently interviewed to determine feasibility and acceptability. The enrollment rate was 89%. All study measures were completed, with high rates of electronic pain diary completion at baseline (70%) and 2-week follow-up (66%). Interviews revealed two overall themes related to MT participants' experience: 1) participants learned new self-management skills and 2) MT improved participants' ability to cope with pain. MT participants demonstrated 100% attendance. In preliminary analyses, MT participants demonstrated significant improvements (means ± SD) in self-efficacy (5.42 ± 5.43, p = 0.008, d = 1.20), PROMIS sleep disturbance (-1.49 ± 6.68, p = 0.023, d = -0.99), PROMIS pain interference (-2.10 ± 4.68, p = 0.016, d = -1.06), and ASCQ-Me social functioning impact scores (2.97 ± 6.91, p = 0.018, d = 1.05) compared to WLC participants. Preliminary findings support the feasibility and acceptability of music therapy for home use in adults with SCD. While music therapy may assist adults with SCD in improving self-efficacy and quality of life, subsequent, fully-powered clinical research is needed to determine its efficacy.


Investigating the prevalence and clinical effects of hepatitis delta viral infection in Taiwan.
To clarify and investigate the prevalence and clinical impact of hepatitis D virus (HDV) infection in Taiwan's communities. HDV infection in patients with chronic hepatitis B viral (HBV) infection was examined using an anti-HDV antibody in Yonghe Cardinal Tien Hospital (YCTH), a district hospital in Taiwan. Clinical characteristics of anti-HDV-positive and anti-HDV-negative patients were collected and compared. These characteristics were also compared with the data collected from a medical center. Continuous variables and confounding factor adjustments were compared using the analysis of covariance method, whereas categorical variables were compared using the logistic regression method. A total of 346 patients with chronic HBV infection were assessed from 2018 to 2019. Among them, 4 (1.15%) were positive for anti-HDV. The clinical, virological, and biochemical characteristics were similar between anti-HDV-positive and anti-HDV-negative groups. None of the four patients was positive for serum HDV RNA. Another 18 anti-HDV-positive patients were identified from National Taiwan University Hospital (NTUH). The clinical, virological, and biochemical characteristics of anti-HDV-positive patients from YCTH and NTUH were also similar. The prevalence of HDV and the serum HDV RNA-positive rate were low in district hospitals in Taiwan. Coexisting HDV infection did not influence the clinical manifestation of patients with chronic HBV infection in Taiwan. However, because the number of HDV RNA cases was very small, our findings may not be conclusive. Besides, since the sensitivity of current anti-HDV kit is not 100%, more sensitive methods are needed to achieve reliable prevalence data.


High molecular weight basic fibroblast growth factor-like protein is localized to a subpopulation of mesencephalic dopaminergic neurons in the rat brain.
A rabbit antiserum (R917) was raised to a purified fraction of bovine brain basic fibroblast growth factor (bFGF). On Western blots of rat midbrain extract, the antiserum did not recognize low molecular weight forms of bFGF. Instead, it recognized a single band of 27-28 kDa. Immunohistochemically, the antiserum preferentially stained a subpopulation of calbindin-negative mesencephalic dopaminergic neurons. The positive somata were mainly packed in a ventral portion of the tegmentum including the A10 region, the ventral tegmental area and the pars compacta of the medial substantia nigra, but were also scattered in both the pars compacta and reticulata portions of the lateral substantia nigra. Processes of dendrites and axons were clearly visible. Terminal fields were located in striosomes, the dorsolateral rim of the neostriatum, the anterodorsal aspect of the nucleus accumbens shell, the infralimbic cortex, and the medial prefrontal cortex. These results suggest that trophic specialization in subpopulations may occur in all three of these dopaminergic projection systems, i.e. the nigrostriatal, mesolimbic and mesocortical pathways.


Simultaneous nitrification and formaldehyde biodegradation in an activated sludge unit.
The simultaneous removal of formaldehyde and ammonium in a lab-scale activated sludge unit was investigated. The unit was operated at a hydraulic retention time of 2.4 days with an ammonium concentration in the influent of 350 mg NH4+-N/L, maintaining the ammonium loading rate at 0.15 g NH4+-N/Ld during the operation time. However, the applied organic loading rate was increased stepwise by increasing the formaldehyde concentration from 26 up to 3168 mg/L, corresponding to 0.01-1.40 g COD/Ld. High formaldehyde removal efficiencies, around 99.5% (+/-0.38), were maintained at all the formaldehyde concentrations. Ammonium removal was also very high during the operation period, around 99.9% (+/-0.01). The ammonium concentration in the effluent was lower than 0.1 mg NH4+-N/L at all applied organic loading rates, indicating that there was no inhibition of nitrification by formaldehyde.


On the contribution of the positively charged headgroup of choline to substrate binding and catalysis in the reaction catalyzed by choline oxidase.
Recent kinetic studies established that the positive charge on the trimethylammonium group of choline plays an important role in substrate binding and specificity in the reaction catalyzed by choline oxidase. In the present study, pH and solvent viscosity effects with the isosteric analogue of choline 3,3-dimethyl-butan-1-ol have been used to further dissect the contribution of the substrate positive charge to substrate binding and catalysis in the reaction catalyzed by choline oxidase. Both the kcat and kcat/Km values with 3,3-dimethyl-butan-1-ol increased to limiting values that were approximately 3- and approximately 400-times lower than those observed with choline, defining pKa values that were similar to the thermodynamic pKa value of approximately 7.5 previously determined. No effects of increased solvent viscosity were observed on the kcat and kcat/Km values with the substrate analogue at pH 8, suggesting that the chemical step of substrate oxidation is fully rate-limiting for the overall turnover and the reductive half-reaction in which the alcohol substrate is oxidized to the aldehyde. The kcat/Km value for oxygen determined with the substrate analogue was pH-independent in the pH range from 6 to 10, with an average value that was approximately 75-times lower than that previously determined with choline as substrate. These data are consistent with the positive charge headgroup of choline playing important roles for substrate binding and flavin oxidation, with minimal contribution to substrate oxidation.


Weight Regain and Breast Cancer-Related Biomarkers Following an Exercise Intervention in Postmenopausal Women.
Epidemiologic studies have reported associations between weight fluctuations and postmenopausal breast cancer risk; however, the biological markers involved in this association are unknown. This study aimed to explore the associations between breast cancer-related biomarkers and weight regain following exercise-induced weight loss. From the 400 participants included in the Breast Cancer and Exercise Trial in Alberta, a total of 214 lost weight during the intervention and had follow-up blood samples, body composition, and covariate measurements. Outcomes were measured at baseline, 12 months (end of the study), and 24 months (follow-up). During follow-up, weight regain was 1.80 kg [95% confidence interval (CI): -0.40-3.90], and was significantly associated with increases in estradiol [treatment effect ratio (TER) = 1.03; 95% CI, 1.01-1.04], estrone (TER = 1.02; 95% CI, 1.01-1.03), free estradiol (TER = 1.04; 95% CI, 1.02-1.05), the homeostatic model assessment for insulin resistance (TER = 1.03; 95% CI, 1.02-1.05), and insulin (TER = 1.03; 95% CI, 1.01-1.04), and decreases in sex hormone-binding globulin (SHBG; TER = 0.98; 95% CI, 0.97-0.99) levels. Nonstatistically significant associations were found for glucose and C-reactive protein. Furthermore, a statistically significant linear trend of increasing levels for all biomarkers, and decreasing SHBG, across weight regain categories was found. These results suggest that weight regain following exercise-induced weight loss is associated with breast cancer-related biomarker changes in postmenopausal women. These findings provide evidence to support the importance of developing effective strategies to prevent weight regain and, consequently, decrease postmenopausal breast cancer risk via changes in adiposity-related biomarkers.