Isolated bilateral orbital and paranasal Rosai-Dorfman disease affecting two brothers: a case report and a systematic literature review.
A systematic literature review revealed 88 Rosai-Dorfman Disease (RDD) cases affecting the orbit. We present a review of the literature on orbital RDD in addition to two brothers with isolated bilateral extra-nodal orbital RDD cases associated with G-6PD deficiency. The disease manifested as asymmetric extensive orbital and paranasal sinus infiltration, with orbital bone destruction. Orbital mass debulking and steroids improved the condition in both patients. This is the most extensive case series of orbital RDD reported, including clinical manifestation, imaging, pathologic results, management, and outcome. Vigilant follow-up is essential to monitor for potential malignant transformation, systemic manifestations, potential vision loss, or life-threatening recurrences.


2-Deoxyglucose transport by intestinal epithelial cells isolated from the chick.
Characteristics of 2-deoxyglucose uptake (2DG) by intestinal epithelial cells isolated from chickens were evaluated as a means of discriminating between the concentrative transport system for monosaccharides, associated with the mucosal brush border, and other possible routes of monosaccharide entry. 2DG was chosen as it is not a substrate for the mucosal transport system. The deoxysugar enters via a saturable pathway which is not Na+-dependent, is not inhibited by K+, does not accumulate solute against a concentration gradient; exhibits a high sensitivity to inhibition by phloretin; is relatively insensitive to phlorizin inhibition; and has low affinity [but high capacity relative to Na+-dependent mucosal transport of 3-O-methylglucose (3-OMG) and other monosaccharides]. These characteristics confirm those established in an earlier report for Na+-independent uptake of 3-OMG. Complications encountered in the use of 2DG as a test sugar include significant rates of metabolic conversion to an anionic form which presumably is a phosphorylated species. Methods for distinguishing between transport and subsequent metabolism are described. Inhibition of 2DG entry by several other sugars is described and inhibitory constants (K's) given for each.


Transcriptome analysis reveals the promotive effect of potassium by hormones and sugar signaling pathways during adventitious roots formation in the apple rootstock.
Apples are economically valuable and widely consumed fruits. The adventitious roots (ARs) formation is gridlock for apple trees mass propagation. The possible function of multiple hormones and sugar signaling pathways regulating ARs formation has not been completely understood in apple. In this study, B9 stem cuttings were treated with KCl treatment, where the highest root numbers (220) and maximum root length of 731.2 cm were noticed in KCl-treated cuttings, which were 98.2% and 215% higher than control cuttings. The content of endogenous hormones: IAA, ZR, JA, GA, and ABA were detected higher in response to KCl at most time-points. To figure out the molecular mechanisms underlying this effect, we investigated transcriptome analysis. In total, 4631 DEGs were determined, from which about 202 DEGs were considerably enriched in pathways associated with hormone signaling, sugar metabolism, root development, and cell cycle-related and were thereupon picked out on their potential involvements in ARs formation. Though, IAA accumulation and up-regulation of various genes contribute to induce AR formation. These results suggest that AR formation is a complex biological process in apple rootstocks, influenced mainly by the auxin signaling pathway and sugar metabolism.


Selective bilateral hippocampal lesions after theophylline-induced status epilepticus causes a permanent amnesic syndrome.
Theophylline is known to increase the risk of epileptic seizures and might have a role in seizure-induced brain damage. We present a 55-year-old man who developed an amnesic syndrome after status epilepticus, caused by accidental theophylline intoxication. Imaging studies revealed acute, selective bilateral hippocampal damage, which corresponded to severe disturbances in bilateral temporal functions on neuropsychological testing. Three months later, the memory deficits persisted, while imaging exhibited bilateral atrophy of the hippocampus. Upon his long-term, 18-month follow-up, the patient demonstrated improvements in his daily living abilities, despite the persistence of bilateral temporal deficits. This report provides evidence that theophylline has the potential to provoke permanent seizure-induced neural damage, presumably via inhibition of adenosine receptors, and especially in vulnerable regions of the brain, such as the hippocampus.


A digital health solution for using and managing medications: wirelessly observed therapy.
Taking oral medication on a prescribed schedule can be a nuisance, especially for elderly individuals and busy people with lots of things on their minds. Nonetheless, taking medication as prescribed is important for maintaining health and well-being. In cases where medication use is part of a clinical trial, taking prescribed medication is important to the entire investigation and outcome of the study, including the determination of whether a drug is effective and safe.


The sleep of dysthymic patients: a comparison with normal controls.
All-night electroencephalographic (EEG) sleep recordings were compared in dysthymic patients and normal controls. Patients were selected according to DSM-III and underwent 2 weeks of treatment with placebo before the sleep evaluation, which also included self-assessments of sleep quality. As compared with normals, dysthymic patients demonstrated fragmented and superficial sleep with no changes in rapid eye movement (REM) sleep. In addition to sleep continuity disturbances, dysthymics had a higher percentage of stage 1 and a reduction of slow wave sleep (SWS), mainly due to a diminished percentage of stage 4. Other differences were related to a higher incidence of some EEG events, and it is suggested that the analysis of sleep microstructure is a useful approach to study sleep physiology in psychiatric patients. The classification of minor forms of depression is a controversial issue and therefore the nosological implications of our findings are discussed.


Does green finance improve the industrial eco-efficiency in China?
Improving industrial eco-efficiency is of great significance for building a beautiful China and achieving its carbon peak and neutrality targets. Based on the panel data of 30 provinces in China from 2007 to 2018, this paper uses the super-efficiency SBM model to measure industrial eco-efficiency and empirically tests the influence of green finance on Chinese industrial eco-efficiency from the national and regional levels. The results show that the average level of industrial eco-efficiency in China is relatively stable during the study period with a large space for advancement. Second, there is spatial heterogeneity in Chinese industrial eco-efficiency, showing a gradually decreasing "southeast-northwest" ladder-like distribution. Third, the national-level regression results show that there is a significant "U-shaped" relationship between green financing and industrial eco-efficiency. In addition, the regression results at the regional level indicate that there is regional heterogeneity in the impact of green finance on industrial eco-efficiency. Finally, based on the research conclusions, specific suggestions on how green finance can improve industrial eco-efficiency in China are put forward, including vigorously developing green finance at the macro and micro levels, and exerting the positive effects of green finance in improving industrial eco-efficiency according to the area and the development level of green finance.


Nanopore long-read RNA-seq and absolute quantification delineate transcription dynamics in early embryo development of an insect pest.
The olive fruit fly, Bactrocera oleae, is the most important pest for the olive fruit but lacks adequate transcriptomic characterization that could aid in molecular control approaches. We apply nanopore long-read RNA-seq with internal RNA standards allowing absolute transcript quantification to analyze transcription dynamics during early embryo development for the first time in this organism. Sequencing on the MinION platform generated over 31 million reads. Over 50% of the expressed genes had at least one read covering its entire length validating our full-length approach. We generated a de novo transcriptome assembly and identified 1768 new genes and a total of 79,810 isoforms; a fourfold increase in transcriptome diversity compared to the current NCBI predicted transcriptome. Absolute transcript quantification per embryo allowed an insight into the dramatic re-organization of maternal transcripts. We further identified Zelda as a possible regulator of early zygotic genome activation in B. oleae and provide further insights into the maternal-to-zygotic transition. These data show the utility of long-read RNA in improving characterization of non-model organisms that lack a fully annotated genome, provide potential targets for sterile insect technic approaches, and provide the first insight into the transcriptome landscape of the developing olive fruit fly embryo.


Spontaneous morphine withdrawal from the rat spinal cord.
A characteristic and reproducible sign of narcotic withdrawal is the naloxone induced increase in arterial pressure. In morphine-dependent rats allowed to undergo spontaneous withdrawal (6-24 h) and then transected at the spinal C-1 level, arterial pressure was maintained at a significantly higher level than either spinal-transected nondependent controls or morphine-dependent, spinal-transected rats pithed from C-1 to L-4. These findings indicate that the morphine-dependent spinal cord, independent of supraspinal influences, is able to exhibit an autonomic component of spontaneous withdrawal.


Residues 287-301 of human ribonuclease inhibitor do not affect ribonuclease activity and inhibitor binding; a reply.
Residues 287-301 of human placental ribonuclease inhibitor have been reported to inhibit pancreatic ribonuclease A in a similar way as the entire inhibitor (Crevel-Thieffry, I., Cotterill, S. and Schuller, E. (1992) Biochim. Biophys. Acta 1122, 107-112). Using three different assays, we were unable to observe inhibition by the synthetic peptide. Moreover, the peptide did not compete with the entire inhibitor for binding to RNAase A.


Comparison of porcine ALG and rabbit ATG on outcomes of HLA-haploidentical hematopoietic stem cell transplantation for patients with acquired aplastic anemia.
To evaluate the efficacy and safety of P-ALG (porcine anti-lymphocyte globulin) and R-ATG (rabbit anti-thymocyte globulin) in the conditioning regime for patients with acquired aplastic anemia who underwent HLA-haploidentical hematopoietic stem cell transplantation (halpo-HSCT). A total of 91 patients with acquired aplastic anemia who received haplo-HSCT at our center between January 2014 and December 2020 were retrospectively reviewed. Twenty-eight patients were in the P-ALG group while sixty-three patients were in the R-ATG group. The median time was 11 versus 13 days (P = 0.294) for myeloid engraftment and 12.5 versus 15 days (P = 0.465) for platelet engraftment in the P-ALG and R-ATG groups, respectively. There were no significant difference in 5-year overall survival (74.83% ± 8.24% vs 72.29% ± 6.26%, P = 0.830), GVHD-free, failure-free survival (71.05% ± 8.65% vs 62.71% ± 6.22%, P = 0.662), failure-free survival (74.83% ± 8.24% vs 66.09% ± 5.84%, P = 0.647) and transplantation-related mortality (25.17% ± 8.24% vs 26.29% ± 6.22%, P = 0.708) between the two groups. The incidence of aGVHD (acute graft versus host disease) (65.39% ± 9.33% vs 62.71% ± 6.30%, P = 0.653), II-IV aGVHD (38.46% ± 9.54% vs 35.64% ± 6.24%, P = 0.695), III-IV aGVHD (19.23% ± 7.73% vs 10.53% ± 4.07%, P = 0.291), cGVHD (chronic graft versus host disease) (22.22% ± 12.25% vs 22.31% ± 6.30%, P = 0.915), and moderate to severe cGVHD (5.56% ± 5.40% vs 9.28% ± 4.46%, P = 0.993) were not significantly different. Similar outcomes were observed between the P-ALG and R-ATG groups for severe bacterial infection (17.9% vs 25.4%, P = 0.431), invasive fungal diseases (3.6% vs 9.5%, P = 0.577) and graft rejection (0% vs 9.5%, P = 0.218). However, the incidence of cytomegalovirus infection and Epstein-Barr virus infection was significantly lower in the P-ALG group (46.4% vs 71.4%, P = 0.022; 3.6% vs 25.4%, P = 0.014). The efficacy and safety of P-ALG were similar with R-ATG in the setting of haplo-HSCT for patients with acquired aplastic anemia patients. P-ALG could be an alternative for R-ATG.


Age-correlated changes of the erythrocyte catalase activity in the Spanish population.
Oxygen free radical and reactive oxygen species are involved in many diseases and ageing. Scavening enzymes represent one of the several natural defence mechanisms against free radical induced damage. Catalase (CAT) is an enzyme that is involved in antioxidant defence. In order to establish a comprehensive profile of the erythrocyte CAT activity during ageing, we investigated this activity in human erythrocytes from 2,827 apparently healthy Spanish subjects (1,388 males and 1,439 females). We divided the subjects into twelve age groups (newborns and 1-3, 4-9, 10-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, 80-89, and >90 years of age) to evaluate ageing changes. The CAT activity was measured in haemolysates by the method of Aebi (see text). No significant variations with respect to sex were detected, except for the 70- to 93-year age groups. In these elderly subjects, the CAT activity in males remained constant with no significant variations between age groups, whereas the CAT activity showed a significant increase in females. This fact is considered to be one of the outcomes of the greater longevity in females. Significant age-related modifications in erythrocyte CAT activity appeared in the group of newborns (p < 0.001), in the group 1-3 years of age (p < 0.025), and in the elderly groups: 70-79 years (p < 0.025) and 80-89 years (p < 0.05) of age. Our results confirm that the CAT activity in the Spanish population shows an interindividual variability and suggest that this variability may be due, at least in part, to the age of the individuals.


Migratory Response of Cells in Neurogenic Niches to Neuronal Death: The Onset of Harmonic Repair?
Harmonic mechanisms orchestrate neurogenesis in the healthy brain within specific neurogenic niches, which generate neurons from neural stem cells as a homeostatic mechanism. These newly generated neurons integrate into existing neuronal circuits to participate in different brain tasks. Despite the mechanisms that protect the mammalian brain, this organ is susceptible to many different types of damage that result in the loss of neuronal tissue and therefore in alterations in the functionality of the affected regions. Nevertheless, the mammalian brain has developed mechanisms to respond to these injuries, potentiating its capacity to generate new neurons from neural stem cells and altering the homeostatic processes that occur in neurogenic niches. These alterations may lead to the generation of new neurons within the damaged brain regions. Notwithstanding, the activation of these repair mechanisms, regeneration of neuronal tissue within brain injuries does not naturally occur. In this review, we discuss how the different neurogenic niches respond to different types of brain injuries, focusing on the capacity of the progenitors generated in these niches to migrate to the injured regions and activate repair mechanisms. We conclude that the search for pharmacological drugs that stimulate the migration of newly generated neurons to brain injuries may result in the development of therapies to repair the damaged brain tissue.


Phase II trial of danazol in advanced, recurrent, or persistent endometrial cancer: a Gynecologic Oncology Group study.
To evaluate the activity and toxicity of danazol in advanced, recurrent, or persistent endometrial carcinoma. Eligible patients with advanced, recurrent, or persistent endometrial carcinoma not amenable to curative therapy were treated with danazol at a dose of 100 mg four times per day until disease progression or toxicity necessitated discontinuation. Eligibility criteria included the presence of measurable disease and no prior chemotherapy. Immunohistochemical analysis of metastatic tumor tissue for estrogen and progesterone receptors was required. Twenty-five patients were enrolled and 3 were excluded. Six patients had tumors staining positive for both estrogen and progesterone receptors. There were no responders among 22 eligible patients. Six patients (27%) demonstrated stable disease as their best response. The median progression-free survival and overall survival were 1.9 and 14.4 months, respectively. A median total dose of 21.7 (range: 1.4 to 67.2) of danazol was administered. Therapy was discontinued in 5 eligible patients due to toxicity. Four of these patients experienced hepatic toxicity. Danazol has minimal activity in advanced, recurrent, or persistent endometrial carcinoma.


Aberrant dynamic functional connectivity in corticostriatal circuitry in depressed bipolar II disorder with recent suicide attempt.
The underlying neurobiological mechanisms on suicidal behavior in bipolar disorder remain unclear. We aim to explore the mechanisms of suicide by detecting dynamic functional connectivity (dFC) of corticostriatal circuitry and cognition in depressed bipolar II disorder (BD II) with recent suicide attempt (SA). We analyzed resting-state functional magnetic resonance imaging (fMRI) data from 68 depressed patients with BD-II (30 with SA and 38 without SA) and 35 healthy controls (HCs). The whole-brain dFC variability of corticostriatal circuitry was calculated using a sliding-window analysis. Their correlations with cognitive dysfunction were further detected. Support vector machine (SVM) classification tested the potential of dFC to differentiate BD-II with SA from HCs. Increased dFC variability between the right vCa and the right insula was found in SA compared to non-SA and HCs, and negatively correlated with speed of processing. Decreased dFC variability between the left dlPu and the right postcentral gyrus was found in non-SA compared to SA and HCs, and positively correlated with reasoning problem-solving. Both SA and non-SA exhibited decreased dFC variability between the right dCa and the left MTG, and between the right dlPu and the right calcarine when compared to HCs. SVM classification achieved an accuracy of 75.24 % and AUC of 0.835 to differentiate SA from non-SA, while combining the abnormal dFC features between SA and non-SA. Aberrant dFC variability of corticostriatal circuitry may serve as potential neuromarker for SA in BD-II, which might help to discriminate suicidal BD-II patients from non-suicidal patients and HCs.


Kentucky pharmacists' perceptions regarding provision of hormonal contraception.
Although Kentucky pharmacists recently gained authority to provide protocol-driven care for 13 conditions, provision of prescription hormonal contraception (HC) services is not currently authorized. A board-approved protocol allowing for provision of nonprescription over-the-counter (OTC) emergency contraception (EC) was recently approved by the Kentucky Board of Pharmacy but has yet to be implemented. The objectives of this study were (1) to assess Kentucky pharmacists' interest in providing prescription HC and OTC EC services via protocol and (2) to identify perceived benefits/barriers regarding provision of prescription HC. An online questionnaire was disseminated electronically to a convenience sample of Kentucky pharmacists. The questionnaire collected (1) demographic information, (2) opinions regarding provision of prescription HC and OTC EC, and (3) perceived benefits and barriers regarding provision of prescription HC. For analysis, responses were limited to pharmacists in community-based practice. McNemar's test was used to identify statistically significant differences in support by dosage form. In addition, a multivariable logistic regression model was used to examine associations between demographic factors and support for pharmacist provision of prescription HC. We received 151 responses from community-based pharmacists. Support for provision of prescription HC was highest for oral (61%) and transdermal (54%) forms. We found no statistically significant differences in support among demographic factors other than number of years in practice, with more recent graduates being at higher odds of support. In addition, time, reimbursement, training, and belief in the need for pelvic exams were the most commonly cited barriers to implementation. With regard to OTC EC provision, pharmacists were largely supportive (62%) and confident in their abilities. Community-based pharmacists in Kentucky are supportive of provision of oral, vaginal, and transdermal prescription HC as well as OTC EC via protocol. Barriers, including time, reimbursement, training, and belief in the need for pelvic exams, should be addressed to increase support for prescription HC provision.


Targeting breast cancer through its microenvironment: current status of preclinical and clinical research in finding relevant targets.
It is increasingly evident that not only breast cancer cells, but also the tissue embedding these cells: the tumor microenvironment, plays an important role in tumor progression, metastasis formation and treatment sensitivity. This review focuses on the current knowledge of processes by which the microenvironment affects breast cancer, including formation of the metastatic niche, metabolic stimulation, stimulation of tumor cell migration, immune modulation, angiogenesis and matrix remodeling. The number of drugs targeting key factors in these processes is expanding, and the available clinical data is increasing. Therefore current strategies for intervention and prediction of treatment response are outlined. At present, targeting the formation of the metastatic niche and metabolic stimulation by the breast cancer microenvironment, are already showing clinical efficacy. Intervening in the stimulation of tumor cell migration and immune modulation by the microenvironment upcoming fields of great research interest. In contrast, targeting microenvironmental angiogenesis or matrix remodeling appears to be of limited clinical relevance in breast cancer treatment so far. Further research is warranted to optimize intervention strategies and develop predictive tests for the relevance of targeting involved factors within the microenvironment in order to optimally personalize breast cancer treatment.


Myocardial T1 and ECV Measurement: Underlying Concepts and Technical Considerations.
Myocardial native T1 and extracellular volume fraction (ECV) mapping have emerged as cardiac magnetic resonance biomarkers providing unique insight into cardiac pathophysiology. Single breath-hold acquisition techniques, available on clinical scanners across multiple vendor platforms, have made clinical T1 and ECV mapping a reality. Although the relationship between changes in native T1 and alterations in cardiac microstructure is complex, an understanding of how edema, blood volume, myocyte and interstitial expansion, lipids, and paramagnetic substances affect T1 and ECV can provide insight into how and why these parameters change in various cardiac pathologies. The goals of this state-of-the-art review will be to review factors influencing native T1 and ECV, to describe how native T1 and ECV are measured, to discuss potential challenges and pitfalls in clinical practice, and to describe new T1 mapping techniques on the horizon.


Establishing the diagnosis of peanut allergy in children never exposed to peanut or with an uncertain history: a cross-Canada study.
The diagnosis of peanut allergy (PA) can be complex especially in children never exposed to peanut or with an uncertain history. The aim of the study is to determine which diagnostic algorithms are used by Canadian allergists in such children. Children 1-17 yrs old never exposed to peanut or with an uncertain history having an allergist-confirmed diagnosis of PA were recruited from the Montreal Children's Hospital (MCH) and allergy advocacy organizations. Data on their clinical history and confirmatory testing were compared to six diagnostic algorithms: I. Skin prick test (SPT) >or=8 mm or specific IgE >or=5 kU/l or positive food challenge (+FC); II. SPT >or=8 or IgE >or=15 or +FC; III. SPT >or=13 or IgE >or=5 or +FC; IV. SPT >or=13 or IgE >or=15 or +FC; V. SPT >or=3 and IgE >or=5 or IgE >or=5 or +FC; VI. SPT >or=3 and IgE >or=15 or IgE >or=15 or +FC. Multivariate logistic regression analysis was used to identify factors associated with the use of each algorithm. Of 497 children recruited, 70% provided full data. The least stringent algorithm, algorithm I, was applied in 81.6% (95% CI, 77-85.6%) of children and the most stringent, algorithm VI, in 42.6% (95% CI, 37.2-48.1%).The factor most associated with the use of all algorithms was diagnosis made at the MCH in those never exposed to peanut. Other factors associated with the use of specific diagnostic algorithms were higher paternal education, longer disease duration, and the presence of hives, asthma, eczema, or other food allergies. Over 18% (95% CI, 14.4-23.0%) of children were diagnosed with PA without fulfilling even the least stringent diagnostic criteria.


Institutional review boards, professionalism, and the internet.
Even as the Internet generates pressures that erode professional authorities of all kinds, it also provides opportunities for researchers and their institutional review boards to bolster their status as trusted sources. To this end, we must work to improve clinical protocol design and approval procedures and maintain the integrity of the study participant recruitment process in clinical trials.


The Incidence and Temporal Trends of Dislocation After the Use of Constrained Acetabular Components and Dual Mobility Implants in Primary Total Hip Replacements: A Systematic Review and Meta-Analysis of Longitudinal Observational Studies.
Dislocation after a primary total hip replacement (pTHR) remains a common cause of treatment failure. Constrained acetabular components (CACs) and dual mobility implants (DMIs) may mitigate this in patients at high risk of dislocation or with significant intraoperative instability. This meta-analysis evaluated the incidence and temporal trends of dislocation after implantation with CACs and DMIs in pTHR. Longitudinal studies reporting dislocation after the use of CACs or DMIs in pTHR were sought from Medline and Embase to September 2020. Secondary outcomes included revision surgery for dislocation and for all causes. A total of 46 studies (3 CAC and 43 DMI) comprising 582 CACs and 18,748 DMIs were included. The pooled incidence of dislocation was 1.08% (95% confidence interval [CI]: 0.00-3.72; range 0.27%-2.60%) over a weighted mean follow-up of 4.1 years for CACs, compared with 0.25% (95% CI: 0.08-0.46; range 0.00%-4.72%) over 6.2 years for DMIs. For DMIs, there was a temporal decline in dislocations from the 1980s onward, and dislocation rates remained low (<1%) until 15 years postoperatively. There were insufficient data for similar analysis of CACs. All studies were at high risk of bias. The incidence of revision for dislocation after CACs was 0.3% vs 0.1% for DMIs, and the incidence of revision for all causes after CACs was 4.8% vs 2.7% for DMIs. DMIs demonstrated a lower incidence of dislocation compared with CACs; however, there was a relative absence of CACs used in the context of pTHR in the literature. Temporal trends in dislocation have improved over time for DMIs.


Antioxidant status and growth performance of broiler chickens fed diets containing graded levels of supplementary dihydroquercetin.
Dihydroquercetin (DHQ), also known as taxifolin, is a natural antioxidant that can be commercially obtained by extraction from Siberian Larch (Larix sibirica). Four wheat-soy based diets, formulated to contain 0, 0.5, 1.5 and 4.5 g/kg of supplementary DHQ were prepared. Each diet was fed ad libitum to birds in seven pens (three birds in each pen) in a randomised block design from 7 to 21 days of age. The effect of DHQ on weight gain was not significant overall (P > 0.05), although there was an indication of a linear increase (L < 0.05). The blood glutathione peroxidase responded (P < 0.001) in a curvilinear manner (L < 0.001 and Q < 0.05) to increased dietary DHQ. The results from this study indicate that dietary DHQ supplementation may be beneficial at levels greater than 1.5 g/kg feed, due to improved bird antioxidant status. Further research to define an upper inclusion level and optimal timing for phase feeding programmes is warranted.


Annual trends in adverse events following mumps vaccination in Japan: A retrospective study.
In Japan, a monovalent mumps vaccine is provided on a voluntary basis. Due to public concerns over post-vaccination aseptic meningitis, the vaccination coverage is not high enough. The present study investigated the incidence of adverse events, including aseptic meningitis, after Torii strain-derived mumps vaccination. This retrospective, observational study used data collected by a vaccine manufacturer regarding adverse events following mumps vaccinations at medical institutions between 1992 and 2018. In addition, the number of Torii strain-derived mumps vaccines shipped each year was obtained. The incidence (per 100,000 doses) and 95% confidence intervals (CIs) were calculated for all adverse events and each adverse event, categorized as aseptic meningitis, encephalitis, mumps, mumps complications, and others. During the study period, 8,262,121 mumps vaccine doses were shipped, and 688 subjects reported adverse events. The incidence for all adverse events (per 100,000 doses) was 8.33, and the incidence was 4.19 for aseptic meningitis, 0.33 for encephalitis, 0.80 for mumps, 0.25 for mumps complications, and 3.78 for others. The incidence of aseptic meningitis (per 100,000 doses) was 7.90 (95% CI: 5.61-10.18) between 1998 and 2000 but declined by half, to 3.91 (2.46-5.36), between 2001 and 2003. The most recent incidence (per 100,000 doses) of aseptic meningitis, for the period 2016 to 2018, was 2.78 (1.94-3.62). The incidence of post-vaccination aseptic meningitis has declined significantly since 2001, and the incidence has remained stable at fewer than 3 cases per 100,000 doses since 2010. Multiple factors might have contributed to the decline in aseptic meningitis incidence, including (i) lowered misclassification of aseptic meningitis resulting from echovirus infection; (ii) changes in the vaccine manufacturing process in 2000; and (iii) publication in 2008 of the recommendation for vaccination of children at 1 year of age.


Extracellular vesicles as regulators of kidney function and disease.
Extracellular vesicles (EVs) are small, lipid bilayer-delimited particles of cellular origin that recently gained increasing attention for their potential use as diagnostic biomarkers, and beyond that for their role in intercellular communication and as regulators of homeostatic and disease processes. In acute kidney injury (AKI) and chronic kidney disease (CKD), the potential use of EVs as diagnostic and prognostic markers has been evaluated in a series of clinical studies and contributions to pathophysiologic pathways have been investigated in experimental models. While EV concentrations in biofluids could not distinguish renal patients from healthy subjects or determine disease progression, specific EV subpopulations have been identified that may provide useful diagnostic and prognostic tools in AKI. Specific EV subpopulations are also associated with clinical complications in sepsis-induced AKI and in CKD. Beyond their role as biomarkers, pathophysiologic involvement of EVs has been shown in hemolytic uremic syndrome- and sepsis-induced AKI as well as in cardiovascular complications of CKD. On the other hand, some endogenously formed or therapeutically applied EVs demonstrate protective effects pointing toward their usefulness as emerging treatment strategy in kidney disease.


Low growth ability of recent influenza clinical isolates in MDCK cells is due to their low receptor binding affinities.
Madin Darby canine kidney (MDCK) cells have generally been used to isolate influenza viruses from patients. However, in recent years, most fresh isolates of the H3N2 subtype have shown poor growth in MDCK cell cultures. Such low-growth viruses were often converted to high-growth viruses after several passages through MDCK cell cultures. In the present study, viruses were found to lose a potential glycosylation site near the receptor-binding pocket of hemagglutinin (HA), at the same time as they acquired the high-growth property. The growth curves of viruses in MDCK cell cultures revealed that multi-cycle replication did not function well in the low-growth viruses. However, the production of progeny viruses within a single cycle of growth did not differ much between the low- and high-growth viruses. The high-growth viruses showed higher infection efficiency in MDCK cell cultures than the low-growth viruses. The HA genes of both low- and high-growth viruses were separately cloned into the SV40 vector to compare their receptor binding affinities. The HA of high-growth viruses showed a much higher receptor binding affinity than that of low-growth viruses, when assayed by hemadsorption and the release kinetics of erythrocytes with bacterial neuraminidase. Reverse genetics studies demonstrated that HA was a crucial determinant for multi-cycle replication in MDCK cell cultures. Taken together, these results demonstrate that inefficient multi-cycle growth of fresh isolates is due to their low receptor binding affinities.


Lavender improves fatigue symptoms in multiple sclerosis patients: A double-blind, randomized controlled trial.
Fatigue is one of the most common complications of Multiple Sclerosis (MS) patients. Several pharmacological and non-pharmacological interventions have been recommended to control this complication. Lavender is one of the plants considered by Persian Medicine (PM) and recommended by scholars of past centuries in the treatment of neurological diseases. This study aimed to investigate the efficacy of lavender capsule on improving fatigue symptoms in MS patients. In a double-blind, controlled trial, using a computer block randomization approach, 48 confirmed MS patients with eligibility criteria of being 18 years or older, Modified Fatigue Impact Scale (MFIS) ≥25, relapsing-remitting MS patients, EDSS ≤6, not pregnant, not breastfeeding, and not suffering from other diseases that cause fatigue, were randomized to receive capsules containing 600mg of lavender flowers as the intervention group or capsules containing 600mg cornstarch as the control group. Patients were randomized after completing the MFIS and were asked to take one capsule three times daily for 60 days. The MFIS again checked to assess the impact of two interventions. Analysis of Covariance (ANCOVA) was used to assess the impact of two interventions. 24 patients included in each group. The mean (standard deviation) of MFIS was 40.56 (7.63) in the intervention and 41.43 (7.89) in the control groups (p=0.706) before the intervention. However, there was a significant reduction (p0.001˂) in the intervention group, 7.04 (4.91) compared to the control group, 38.17 (9.78) after the intervention. In comparison to cornstarch capsules, consuming the capsules of lavender flowers decreased the MFIS in MS patients.


[System of innate immunity in plants].
The review deals with the mechanisms of innate immunity in plants with a focus on families of pattern-recognition receptors and regard for recent data on complete sequencing of the genomes of several plant species. Plants utilize several families of such receptors, both membrane-bound and cytoplasmic ones, which contain conservative leucine-rich repeats. The lack of adaptive immunity and there to related rearrangements in genes encoding immune receptors in plants are partly compensated by mechanisms of "specific" immunity to counter particular pathogens; such mechanisms being fully encoded within a plant genome. At the level of intracellular signal transduction, as well as in respect of effector mechanisms, similarities between plant and animal innate immune systems can be found, although the latter has many additional aspects.


Usefulness of bone scintigraphy for the diagnosis of Complex Regional Pain Syndrome 1: A systematic review and Bayesian meta-analysis.
Since 2007, the Budapest criteria are recommended for the diagnosis of Complex Regional Pain Syndrome (CRPS) 1. The usefulness of bone scintigraphy (BS, index test) for the diagnosis of CRPS 1 remains controversial. Imperfect reference tests (RT) result in underestimation of the diagnostic accuracy of BS. Further, biased results can occur when a dependency between the RT and BS exists. The objective was to assess the impact of different RTs, specifically the Budapest criteria, and the assumed imperfect nature of the RT on the diagnostic accuracy of BS. Further, we analyzed the association between baseline characteristics and positive BS in patients with CRPS 1. Systematic literature review and Bayesian meta-analysis to assess the test accuracy of BS with and without accounting for the imperfect nature of the RT. We examined correlations (Spearman correlation coefficients / Wilcoxon tests) between baseline characteristics and the proportion of positive BS in patients with CRPS 1. The pooled sensitivity was 0.804 (95% credible interval (CI) 0.225-1.0, 21 studies) and specificity 0.853 (95%CI 0.278-1.00). Sensitivity and specificity of BS increased when accounting for the imperfect nature of the RT. However, in studies using Budapest criteria as reference, the sensitivity decreased (0.551; 95% CI 0.046-1) and the specificity increased (0.935; 95% CI 0.306-1). Shorter disease duration and a higher proportion of males were associated with a higher proportion of positive BS (27 studies, disease duration <52 weeks Wilcoxon test p = 0.047, female proportion Spearman correlation -0.63, p = 0.009). Compared to the accepted Budapest diagnostic criteria BS cannot be used to rule-in the diagnosis of CRPS 1. In patients with negative BS CRPS 1 is less likely the underlying illness. Studies using older or no diagnostic criteria should not be used to evaluate the diagnostic accuracy of BS in CRPS 1.


No Solid Colloidal Carriers: Aspects Thermodynamic the Immobilization Chitinase and Laminarinase in Liposome.
The present review describes the basic properties of colloidal and vesicular vehicles that can be used for immobilization of enzymes. The thermodynamic aspects of the immobilization of enzymes (laminarinase and chitinase) in liposomes are discussed. These systems protect enzymes against environmental stress and allow for a controlled and targeted release. The diversity of colloidal and vesicular carriers allows the use of enzymes for different purposes, such as mycolytic enzymes used to control phytopathogenic fungi.


Functional results 5 years after successful percutaneous mitral commissurotomy in a series of 528 patients and analysis of predictive factors.
This study sought to assess late functional results after successful percutaneous mitral commissurotomy and to determine their predictors. Few studies have reported late results of percutaneous mitral commissurotomy or have analyzed their late results regardless of immediate results, despite the fact that late deterioration may well be related either to a decrease in valve area or to poor initial results. Between 1986 and 1992, 528 patients underwent successful percutaneous mitral commissurotomy (mean [+/- SD] age 46 +/- 18 years; mean follow-up 32 +/- 18 months). A successful procedure was defined by a mitral valve area > or = 1.5 cm2 and no regurgitation > 2/4. Dilation was performed using a single balloon in 13 patients, a double balloon in 349 and the Inoue balloon in 166. Multivariate analysis was performed with a Cox model. The survival rate for patients in New York Heart Association functional class I or II, with no cardiac-related deaths or need for mitral surgery or repeat dilation, was 76 +/- 6% at 5 years. By multivariate analysis, the independent predictors of good functional results were echocardiographic group (p = 0.01), functional class (p = 0.02) and cardiothoracic index (p = 0.005) before the procedure and valve area after the procedure (p = 0.007). The predictive model derived allowed estimation of the probability of good functional results according to the value of these four predictors for any given patient. Good functional results were observed 5 years after successful percutaneous mitral commissurotomy in a large series of varied patients. The analysis of predictive factors may provide useful indications for follow-up results in patients undergoing this technique.


Pseudoxanthomonas beigongshangi sp. nov., a novel bacteria with predicted nitrite and nitrate reduce ability isolated from pit mud of Baijiu.
A Gram-negative and rod-shape bacterium designated REN9T, was isolated from pit mud of Baijiu in Sichuan, China. The 16S rRNA sequence of strain REN9T had a high similarity to Pseudoxanthomonas indica P15T (99.21%), P. mexicana AMX 26BT (97.74%) and P. japonensis 12-3T (97.43%). Phylogenetic analysis showed that REN9T belongs to the genus Pseudoxanthomonas and formed distinct cluster. The ANI and DDH values between strains REN9T and P15T were 80.94% and 24%, respectively. Strain REN9T grew optimally at 37 °C, pH 7.0 and 2% NaCl. PE (phosphatidylethanolamine), PG (phosphatidylglycerol) and DPG (diphosphatidylglycerol) were the major polar lipids of REN9T. Ubiquinone 8 (Q-8) was the predominant quinone, and Iso-C15:0 (64.32%), anteiso-C15:0 (12.04%) and Iso-C14:0 (4.56%) were the majority fatty acids. The DNA G + C content of strain REN9T was 67.3 mol%. Genomic analysis showed that strain REN9T had two secondary metabolite biosynthesis gene clusters. Moreover, strain REN9T had 43 glycoside hydrolases, 41 glycosyl transferases and 41 carbohydrate esterases. Based on the polyphasic taxonomic analysis, strain REN9T is recommended as a novel species within the genus Pseudoxanthomonas, for which the name Pseudoxanthomonas beigongshangi is proposed. The type stain is REN9T (= JCM 33961T = GDMCC 1.2210T).


Trace Element Levels in Scalp Hair of School Children in Shigatse, Tibet, an Endemic Area for Kaschin-Beck Disease (KBD).
Kaschin-Beck disease (KBD) is an endemic osteoarthritis, and the etiology is closely related with levels of trace elements in the human body. Currently, it is clear that the selenium (Se) status of children in KBD areas is lower than that in non-KBD areas in the Tibetan Plateau, whereas role of other elements are yet unknown. This study aimed to assess some essential trace elements (Se, Mo, Mn, Zn, Fe, Cu, Co, and Sr) in children using scalp hair as a biomarker, and 157 samples from school children aged 8-14 years old were collected from both KBD and non-KBD areas in Shigatse, Tibet. Se and Mo were measured by inductive coupled plasma mass spectrometry, and the other elements were determined by inductive coupled plasma optical emission spectrometry. Compared with the non-KBD areas, Se, Mo, Mn, Fe, Zn, Co, and Sr levels of children in KBD areas were found to be significantly different (P < 0.05); while in linear discriminant analysis, only Se and Zn were found to contribute to the KBD prevalence in the study area. The hair Se level of children in KBD areas ranged from 0.115 to 0.299 mg/kg, while in non-KBD areas it ranged from 0.135 to 0.519 mg/kg. The Zn content of children's hair was between 83 and 207 mg/kg in KBD areas, while it was 37 and 219 mg/kg in non-KBD areas. Lower Se and higher Zn levels in children in KBD areas was found when compared with non-KBD groups. In addition, Mo levels were found to be different between KBD areas and non-KBD areas on the opposite side of the Yarlung Zangbo River, but no close relationship was shown because there was no difference compared with the non-KBD area on the same side of the river. Our observations suggest that Se deficiency is still an important factor for the occurrence and prevalence of KBD, while the relationship between Zn and KBD needs to be further explored in the Tibetan Plateau.


Electrochemical Production of Formic Acid from CO2 with Cetyltrimethylammonium Bromide-Assisted Copper-Based Catalysts.
The electrochemical reduction of CO2 (ERC) to valuable chemicals has attracted extensive attention. However, the relatively low selectivity and efficiency of the reaction remain challenges. In this study, Cu electrodes derived from Cu2 O with predominant (111) facets are synthesized by cetyltrimethylammonium bromide-assisted preparation. The optimized electrode shows a high faradaic efficiency of 90 % for HCOOH obtained by ERC at -2.0 V (vs.SCE), which surpasses most reported Cu electrodes. Based on a comprehensive analysis of the relationship between the catalytic activity and the thickness of the Cu2 O layer, the catalytic activity of the unit active site on the Cu2 O-derived Cu electrodes is found to be higher than that on the blank Cu electrode. DFT calculations indicate that OCHO* would be produced preferentially over *COOH in the presence of cetyltrimethylammonium bromide (CTAB). This deduction is verified by testing of the effects of CTAB and KBr addition on HCOO- selectivity.


Insertion and fixation of fiducial markers for setup and tracking of lung tumors in radiotherapy.
Internal 1.5-mm fiducial markers were used in real-time tumor-tracking radiotherapy (RT) for lung cancer. The fixation rate of the markers using the bronchial insertion technique, reliability of the setup using markers around the target volume, dislocation of the markers after real-time tumor-tracking RT, and long-term toxicity of marker insertion were investigated. Between July 2000 and April 2004, 154 gold markers were inserted into 57 patients with peripheral lung cancer. The distances between the implanted markers in 198 measurements in 71 set-ups in 11 patients were measured using two sets of orthogonal diagnostic X-ray images of the real-time tumor-tracking RT system. The distance between the markers and the chest wall was also measured in a transaxial CT image on 186 occasions in 48 patients during treatment planning and during follow-up. The median treatment time was 6 days (range, 4-14 days). In 115 (75%) of the 154 inserted markers, the gold marker was detected throughout the treatment period. In 122 markers detected at CT planning, 115 (94%) were detected until the end of treatment. The variation in the distances between the implanted markers was within +/-2 mm in 95% and +/-1 mm in 80% during treatment. The variation in the distances between the implanted markers was >2 mm in at least one direction in 9% of the setups for which reexamination with a CT scan was indicated. The fixation rate in the left upper lobe was lower than in the other lobes. A statistically significant relationship was found between a shorter distance between the markers and the chest wall and the fixation rate, suggesting that the markers in the smaller bronchial lumens fixed better than those in the larger lumens. A learning curve among the endoscopists was suggested in the fixation rate. The distance between the markers and the chest wall changed significantly within a median of 44 days (range, 16-181 days) after treatment. The fixation of markers into the bronchial tree was useful for the setup for peripheral lung cancer and had an accuracy of +/-2 mm during the 1-2-week treatment period. The relationship between the markers and tumor can change significantly after 2 weeks, suggesting that adaptive four-dimensional RT is required.


LncRNA RGMB-AS1 up-regulates ANKRD1 Through Competitively Sponging miR-3614-5p to Promote OSA Cell Proliferation and Invasion.
Osteosarcoma (OSA) is associated with unfavorable prognosis. The overall survival rate for patients with OSA recurrence or metastasis is only about 20%. Long non-coding RNAs (lncRNAs) significantly function in gene expression and the progression of various cancers including OSA. The expression of repulsive guidance molecule BMP co-receptor b antisense RNA 1 (RGMB-AS1) was detected in OSA cells via qRT-PCR. Western blot assay exposed the protein level of ankyrin repeat domain 1 (ANKRD1). The function assays showed the role of RGMB-AS1, miR-3614-5p, ANKRD1 on OSA cell proliferation and invasion. Subcellular Fraction assay was conducted to detect RGMB-AS1 localization. Rescue assays manifested the mechanism of RGMB-AS1/miR-3614-5p/ANKRD1 axis in OSA cells. FOXA1-activated RGMB-AS1 positively regulated OSA cell progression including proliferation and invasion but negatively modulated apoptosis. miR-3614-5p interacted with RGMB-AS1 and functioned as the tumor suppressor in OSA cells. ANKRD1 was targeted by miR-3614-5p and was negatively interacted by miR-3614-5p. RGMB-AS1 and ANKRD1 competitively bound with miR-3614-5p. The suppression of silencing RGMB-AS1 on OSA cell progression was rescued by ANKRD1 overexpression or miR-3614-5p down-regulation. FOXA1-activated RGMB-AS1 promoted cell proliferation and invasion in OSA via miR-3614-5p/ANKRD1 pathway.


Displaywide visual features associated with a search display's appearance can mediate attentional capture.
Whether or not the capture of visual attention is driven solely by the salience of an attention-capturing stimulus or mediated by top-down control has been a point of contention since Folk, Remington, and Johnston (1992) introduced their contingent involuntary orienting hypothesis, which states that the capture of attention by a salient stimulus depends on its relevance to a feature distinguishing the target from nontargets. Gibson and Kelsey (1998) extended Folk et al.'s (1992) hypothesis by demonstrating that features associated with the appearance of the target display also mediate capture. Although similar to Folk et al. (1992), Gibson and Kelsey's displaywide contingent orienting hypothesis makes it difficult to demonstrate stimulus-driven capture, because an observer must always use some perceptible feature as a signal of the target display's appearance; hence, such features could always be mediating capture. The present article reviews and applies the logic of Gibson and Kelsey's and Folk et al.'s (1992) hypotheses to experiments from the attentional capture literature, and assesses whether previously reported capture effects were mediated by top-down attentional control. It concludes that these capture effects were not stimulus-driven.


Synthesis, Isolation and Crystal Structures of the Metalated Ylides [Cy3P-C-SO2Tol]M (M = Li, Na, K).
The preparation and isolation of the metalated ylides [Cy3PCSO2Tol]M ( Cy1-M) (with M = Li, Na, K) are reported. In contrast to its triphenylphosphonium analogue the synthesis of Cy1-M revealed to be less straight forward. Synthetic routes to the phosphonium salt precursor Cy1-H2 via different methods revealed to be unsuccessful or low-yielding. However, nucleophilic attack of the ylide Cy3P = CH2 at toluenesulfonyl fluoride under basic conditions proved to be a high-yielding method directly leading to the ylide Cy1-H. Metalation to the yldiides was finally achieved with strong bases such as nBuLi, NaNH2, or BnK. In the solid state, the lithium compound forms a tetrameric structure consisting of a (C-S-O-Li)4 macrocycle, which incorporates an additional molecule of lithium iodide. The potassium compound forms a C 4-symmetric structure with a (K4O4)2 octahedral prism as central structural motif. Upon deprotonation the P-C-S linkage undergoes a remarkable contraction typical for metalated ylides.


Sylvian triangle. Angiographic evaluation of its appearance in normal and pathologic conditions.
Description of a method for determining the size of the Sylvian triangle on lateral films. A cranio-insular index is constructed which allows differentiation between normal cases, paracapsular and subdural hematomas.


Wastewater treatment by microalgae.
The growth of the world's population increases the demand for fresh water, food, energy, and technology, which in turn leads to increasing amount of wastewater, produced both by domestic and industrial sources. These different wastewaters contain a wide variety of organic and inorganic compounds which can cause tremendous environmental problems if released untreated. Traditional treatment systems are usually expensive, energy demanding and are often still incapable of solving all challenges presented by the produced wastewaters. Microalgae are promising candidates for wastewater reclamation as they are capable of reducing the amount of nitrogen and phosphate as well as other toxic compounds including heavy metals or pharmaceuticals. Compared to the traditional systems, photosynthetic microalgae require less energy input since they use sunlight as their energy source, and at the same time lower the carbon footprint of the overall reclamation process. This mini-review focuses on recent advances in wastewater reclamation using microalgae. The most common microalgal strains used for this purpose are described as well as the challenges of using wastewater from different origins. We also describe the impact of climate with a particular focus on a Nordic climate.


Revision of the leafhopper genus Soractellus Evans (Cicadellidae: Deltocephalinae) with description of a new species from Pakistan.
The leafhopper genus Soractellus Evans, 1966 is reviewed and a new short-winged species, Soractellus lalianensis sp. nov. from Pakistan, is described and illustrated. A key to distinguish all species in this genus is given.


Developing clinical knowledge through a narrative-based method of interpretation.
The results of research using a narrative analysis provide new clinical knowledge, but the methods used are unknown to many readers. In this paper we present an example of how an analysis may be performed in practice. The purpose of the interpretation of this specific story was to develop clinical knowledge of how it is to live with chronic heart failure from a daily life perspective. The steps in the interpretation process, within the framework of Paul Ricoeur's Interpretation theory, were: (1) general or naïve reading, (2) distancing, (3) examination of discourse, (4) conjectures and questions, and (5) reflection over the whole. The demonstrated interpretation of the interview resulted in a theme called: "Struggling to comprehend medical information". This systematic way of working with narratives makes implicit assumptions about the relationship between meaning and language explicit. These themes can be used in everyday practice as clinical tools. Because of the interpretative nature of human understanding the experienced health professional will be capable of integrating evidence-based research findings and individual illness experience.


Desire for biological parenthood and patient counseling on the risk of infertility among adolescents and adults with hemoglobinopathies.
Both diagnosis and treatment of hemoglobinopathies have been associated with an increased risk of fertility impairment. German guidelines recommend annual monitoring of fertility parameters to enable early detection of fertility impairment and/or to offer fertility preservation (FP) when indicated. We explored the general desire for parenthood, the frequency of recalling fertility counseling and testing, and the utilization of FP in adolescents and adults with hemoglobinopathies. In a cross-sectional study, patients aged 12-50 years, treated in Germany, Austria, or Switzerland, were surveyed on fertility-related aspects. Medical data, including fertility testing results, were collected from patient records. Overall, 116/121 eligible patients, diagnosed with sickle cell disease (70.7%), thalassemia (27.6%), or other hemoglobinopathy (1.7%), participated in our study (57.8% female, median age 17.0 years, range 12-50 years). All participants required treatment of the underlying hemoglobinopathy: 68.1% received hydroxyurea, 25.9% required regular blood transfusions, and 6.0% underwent hematopoietic stem cell transplantation (HSCT). Most patients (82/108, 75.9%) stated a considerable to strong desire for (future) parenthood, independent of sex, education, diagnosis, or subjective health status. Fertility counseling was only recalled by 32/111 patients (28.8%) and least frequently by younger patients (12-16 years) or those treated with regular blood transfusions or hydroxyurea. While fertility testing was documented for 59.5% (69/116) in medical records, only 11.6% (13/112) recalled previous assessments. FP was only used by 5.4% (6/111) of patients. Most patients with hemoglobinopathies wish to have biological children, yet only few recalled fertility counseling and testing. Adequate patient counseling should be offered to all patients at risk for infertility.


Criminal Justice Involvement among Young People Exchanging Sex in Detroit.
For young adult sex workers, the risk of arrest and incarceration are dramatically influenced by the venue of sex exchange and individual and neighborhood characteristics. Using a unique venue-based survey sample of young adults in Detroit who are exchanging sex, multivariable logistic regression models were used to identify associations with arrest and incarceration. Criminal justice involvement was normative, and risk was increased by working on the street venue, using drugs, lacking stable housing, juvenile arrest or incarceration, dropping out of school before age 18, and neighborhood characteristics. Several promising points of intervention could reduce criminal justice involvement for young adults exchanging sex.


A pilot study to gauge nutritional behavior regarding eye health in an urban community health center population.
The purpose of this pilot study was to assess the knowledge base of an urban community health center population on the link between nutrition and eye health to determine current habits and then utilize this information for an educational intervention. A survey was given to 150 patients of an ethnically mixed, lower socioeconomic cohort. The data served as a guide for a focus group. An exit survey and a 1-month follow-up call were used to assess the success of the group. Approximately 83% of respondents were aware of a link between healthy food and healthy eyes. Fewer knew of the ocular benefits of specific nutrients such as omega-3 (42.7%) or vitamin C, vitamin E, lutein, and zeaxanthin (32.7%). Only 60% knew smoking could negatively affect eyesight. The largest age group was older than 55 years (26%), and the largest racial group was black (31.3%). The majority (64.7%) ate fish 1 to 2 days a week, and 40% ate green leafy vegetables 3 to 4 days a week. In the cohort, 73.3% reported they would take supplements or change eating habits to improve ocular health. Only 8% who participated in the survey attended the focus group. At the 1-month follow-up, 75% said they had changed their eating habits based on the information presented. Although educating a community health center population about nutrition and ocular health can have a positive effect on patient behaviors, it is difficult, even with incentives, to engage this cohort in participating in focus groups aimed at changing behavior.


Nickel decorated manganese oxynitride over graphene nanosheets as highly efficient visible light driven photocatalysts for acetylsalicylic acid degradation.
In this work, we prepared nanocomposites of nickel-decorated manganese oxynitride on graphene nanosheets and demonstrated them as photocatalysts for degradation of acetylsalicylic acid (ASA). The catalyst exhibited a high degradation efficiency over ASA under visible light irradiation and an excellent structural stability after multiple uses. Compared to manganese oxide (MnO) and manganese oxynitride (MnON) nanoparticles, larger specific surface area and smaller band gap were observed for the nanocomposite accounting for the enhanced photocatalytic efficiency. Besides the compositional effect of the catalyst, we also examined the influence of various experimental parameters on the degradation of ASA such as initial concentration, catalyst dose, initial pH and additives. The best performance was obtained for the nanocomposite when the catalyst dose was 10 mg/mL and the initial pH 3. Detection of intermediates during photocatalysis showed that ASA undergoes hydroxylation, demethylation, aromatization, ring opening, and finally complete mineralization into CO2 and H2O by reactive species. For practical applications as a photocatalyst, cytotoxicity of the nanocomposite was also evaluated, which revealed its insignificant impact on the cell viability. These results suggest the nanocomposite of nickel-decorated manganese oxynitride on graphene nanosheets as a promising photocatalyst for the remediation of ASA-contaminated water.


Biomechanical assessment of the sitting posture maintenance in patients with stroke.
Regaining control of sitting posture is one of the first goals in the rehabilitation of patients with stroke. So, it requires a precise quantification of this postural behaviour. The purpose of the present investigation was thus to assess postural control during sitting in people with hemiparesis through a biomechanical analysis. Centre-of-pressure displacements were recorded by means of a force platform on which 10 patients with stroke and 10 age-matched healthy subjects were sitting. Centre-of-pressure trajectories were processed through space-time and frequency analyses. These centre-of-pressure displacements of the patients with stroke were characterised by an increased control for maintaining sit position and by reduced postural performance, as enlightened by the larger surfaces covered by the centre-of-pressure displacements (P<.05) and increased velocities (P<.001), respectively. As shown from the frequency analysis, the impairment have affected predominantly the displacements occurring along the antero-posterior axis (P<.05). The analysis of centre-of-pressure displacements during sitting posture indicates an increased postural disturbance in patients with stroke. A platform device, because of the non-invasive, easy and fast measures carried out, should thus be viewed as an attractive tool for assessing the postural dysfunctioning encountered in sat patients with stroke. This tool could also be used for evaluating, the rehabilitation process following stroke.


Tobacco withdrawal components and their relations with cessation success.
Tobacco withdrawal is a key factor in smoking relapse, but important questions about the withdrawal phenomenon remain. This research was intended to provide information about two core components of withdrawal (negative affect and craving): (1) how various withdrawal symptom profile dimensions (e.g., mean level, volatility, extreme values) differ between negative affect and craving; and (2) how these dimensions relate to cessation outcome. Adult smokers (N = 1,504) in a double-blind randomized placebo-controlled smoking cessation trial provided real-time withdrawal symptom data four times per day for 4 weeks (2 weeks pre-quit and 2 weeks post-quit) via palmtop computers. Cessation outcome was biochemically confirmed 8-week point-prevalence abstinence. Examination of craving and negative affect dimensions following a cessation attempt revealed that craving symptoms differed from negative affect symptoms, with higher means, greater variability, and a greater incidence of extreme peaks. Regression analyses revealed that abstinence was associated with lower mean levels of both craving and negative affect and fewer incidences of extreme craving peaks. In a multivariate model, the increase in mean craving and negative affect scores each uniquely predicted relapse. Real-time reports revealed different patterns of abstinence-related negative affect and craving and that dimensions of both predict cessation outcome, suggesting that negative affect and craving dimensions each has motivational significance. This underscores the complexity of withdrawal as a determinant of relapse and the need to measure its distinct components and dimensions.


Protective effect of Y-20811, a long-lasting thromboxane synthetase inhibitor, on endotoxin shock in rabbits.
The effect of sodium 4-[alpha-hydroxy-5-(imidazolyl)-2-methylbenzyl]-3,5-dimethyl benzoate dihydrate (Y-20811), a selective thromboxane (TX) synthetase inhibitor, on endotoxin shock was investigated in comparison with aspirin. The drugs were orally administered to rabbits at 24 and 1 hour before injection of endotoxin (5 mg/kg, i.v.). Y-20811 (1 mg/kg) promoted the recovery of decreased platelet counts, and inhibited hypotension induced by endotoxin. It also inhibited the increase in plasma TXB2 and 6-keto PGF1 alpha. Aspirin at 30 mg/kg, inhibited hypotension and the increase in both plasma TXB2 and 6-keto PGF1 alpha levels, but it failed to inhibit the decrease in platelet counts. In the control group, all rabbits died within 180 min after endotoxin injection, while Y-20811 completely protected animals against death at a dose of 0.3 mg/kg. Aspirin also protected animals against death at a dose of 30 mg/kg, which was, however, about one hundredth potent of Y-20811. These results indicate that Y-20811 is useful in treating endotoxin shock.


Familial polyposis coli associated with bile duct cancer.
The clinical features and surgical management of two patients with primary adenocarcinoma of the bile duct in association with familial polyposis coli are described. The first patient had had subtotal colectomy for familial polyposis coli, and several resections of duodenal tumors. Carcinoma developed in the common bile duct and was treated with intubation and radiation therapy; he is still alive 2 years later. A second patient with cancer at the bifurcation of the bile ducts was treated with intubation and radiotherapy; 1 year later she had intestinal hemorrhage from a sigmoid colon cancer, and multiple colonic polyps were noted. We believe that this is the first report in the English literature of biliary cancer in association with familial polyposis coli or Gardner's syndrome.


Sexual myths and attitudes regarding sexuality of nursing students: A mixed method study.
To determine the nursing students' sexual myths and attitudes regarding sexuality, and to explore their views towards sexual care in practice. A mixed-method sequential explanatory design was used. Data were collected using Questionnaire Form, Sexual Myths Scale (SMS), Sexual Attitude and Beliefs Scale (SABS), and Focus-Group Interview Form. The average scores on the SMS and the SABS were 58.66 ± 18.74 and 37.50 ± 6.97, respectively, indicating students' sexual myths and their attitudes regarding sexuality were moderate. A positive, significant correlation was found between SMS and SABS scores (p < 0.001). In the interviews, the views on the barriers and facilitators in sexual care and the negative effect of sexual myths on sexual care were revealed. Courses regarding sexuality should include into nursing curriculum from the first years of undergraduate education.


A coarse-to-fine deep learning framework for optic disc segmentation in fundus images.
Accurate segmentation of the optic disc (OD) depicted on color fundus images may aid in the early detection and quantitative diagnosis of retinal diseases, such as glaucoma and optic atrophy. In this study, we proposed a coarse-to-fine deep learning framework on the basis of a classical convolutional neural network (CNN), known as the U-net model, to accurately identify the optic disc. This network was trained separately on color fundus images and their grayscale vessel density maps, leading to two different segmentation results from the entire image. We combined the results using an overlap strategy to identify a local image patch (disc candidate region), which was then fed into the U-net model for further segmentation. Our experiments demonstrated that the developed framework achieved an average intersection over union (IoU) and a dice similarity coefficient (DSC) of 89.1% and 93.9%, respectively, based on 2,978 test images from our collected dataset and six public datasets, as compared to 87.4% and 92.5% obtained by only using the sole U-net model. The comparison with available approaches demonstrated a reliable and relatively high performance of the proposed deep learning framework in automated OD segmentation.


Development of a polymeric biomedical device platform with controlled disassembly and in vivo testing in a swine intestinal model.
The aim of this study was to create a surgical guide platform that maintains its integrity while the surgeon performs an intestinal anastomosis or another similar procedure, which then breaks apart and is eliminated from the body in a controlled manner. The device contains mixed polymeric structures that give it a controlled rate of disassembly that could meet the requirements of a specific surgical purpose. The intraluminal anastomotic guide was manufactured as a hollow cylinder composed of layers of porous polyurethane/PCL with polyvinylpyrrolidone as the binding agent similar to a "brick-mortar" architecture. This combination of polymeric structures is a promising manufacturing method from which a variety of tunable devices can be fabricated for specific medical procedures and site-specific indications. The guide was designed to rapidly disassemble within the intestinal lumen after use, reliably degrading while maintaining sufficient mechanical rigidity and stability to support manipulation during complex surgical procedures. The nature of the device's disassembly makes it suitable for use in hollow structures that discharge their contents, resulting in their elimination from the body. A swine model of intestinal anastomosis was utilized to validate the use and function of the device.


Selection criteria for endoscopic retrograde cholangiopancreaticography (ERCP) in patients with gallstone disease.
Endoscopic retrograde cholangiopancreatography (ERCP) has been used in patients referred to cholecystectomy when clinical information, biochemical values, or ultrasonography (clinical characterization) have indicated possible presence of common bile duct stones. A retrospective study of 599 patients treated for gallstone disease was used to develop a characterization procedure for predicting common bile duct stones by a discriminant analysis procedure. The variables selected by the analysis as the best combination for CBDS prediction were age (years), the values of bilirubin (micromol/l), ALAT (U/l) and gamma GT (U/l). The characterization was false positive in 22 cases (3.7%) and false negative in 11 cases (1.8%), compared to 198 false positive cases (33.1%) and three false negative cases (0.5%) by the clinical characterization. A leaving-one-out correction did not change the results. In a test set of 157 cholecystectomy patients, clinical characterization was false positive in 44.6% of the patients, compared to 4.5% false positive results when using the discriminant analysis procedure. The discriminant analysis procedure would have missed one patient with common bile duct stones. Selection by the discriminant analysis characterization procedure seems to reduce the frequency of preoperative ERCP significantly without an increase in undetected common bile duct stones.


Using liquefied biomass hydrogel to mitigate salinity in salt-affected soils.
Salinity affects over 33% of irrigated farmland globally. Developing a low-cost, safe, and effective material as a soil salinity mitigation option would be of significant importance. This study proposed to synthesize a hydrogel using liquefied biomass from sugarcane bagasse, polyvinyl alcohol, and sodium tetraborate decahydrate. The effectiveness of the produced hydrogel in mitigating soil salinity was evaluated based on an incubation experiment at two salinity levels (5 and 10 dS m-1). The experiment was conducted by mixing liquefied hydrogel with soil at four application rates (0, 1, 2, and 3% w/w) with three replications. Porewater and soil samples were tested for pH and electrical conductivity (EC). Soil samples were also analyzed for selected cations and anions. The results demonstrated that hydrogel significantly reduced porewater EC at both 5 and 10 dS m-1 salt solutions. In addition, hydrogel reduced Cl-, P, Ca2+, and Al3+ concentrations in soil samples with maximum reductions observed from 3% hydrogel treatment. However, pH of porewater showed a consistent increase with hydrogel application. The application of hydrogel also increased NH4-N at high salt level. Overall, hydrogel has shown promising results in reducing soil salinity and could potentially be used as a soil amendment for saline soils.


The diagnostic value of computed tomography in temporomandibular joint synovial chondromatosis.
Synovial chondromatosis of the temporomandibular joint was diagnosed and location of dens particles was assessed by means of computed tomography. Based upon the data collected, the joint was operated conservatively and most of the calcifications were removed leaving the patient symptom free. The importance of an accurate preoperative diagnosis of synovial chondromatosis by use of CT scan is stressed in view of numerous unnecessary condylectomies and parotidectomies reported in the literature.


Long term effects of septohippocampal lesions and intrahippocampal grafts on acetylcholine concentration, muscarinic stimulated formation of inositol phospholipids and electrically evoked release of neurotransmitters in the rat hippocampus.
Long Evans female rats sustained aspirative lesions of the septohippocampal pathways; subsequently, they received intrahippocampal suspension grafts of fetal septal-diagonal band or hippocampal tissue. The long term (8-10 months post-surgery) effects of these treatments were examined in the hippocampus for the following variables: concentration of hippocampal acetylcholine (ACh), muscarinic-stimulated (carbachol) formation of inositol monophosphate, accumulation of tritiated choline, noradrenaline (3H-NA) and serotonin (3H-5-HT), electrically evoked release of 3H-acetylcholine (3H-ACh), 3H-NA and 3H-5-HT, and choline acetyltransferase (ChAT) activity. The lesions decreased the levels of endogenous ACh, the accumulation of 3H-choline and 3H-5-HT and the evoked release of both 3H-ACh and 3H-5-HT as well as the ChAT activity, but they failed to significantly affect the muscarinic-stimulated formation of inositol monophosphate and the accumulation and release of 3H-NA. Grafts of hippocampal cells were found to be ineffective on all lesion-induced effects. In contrast, grafts of septal-diagonal band origin attenuated the deficit of hippocampal concentrations of ACh and accumulation of 3H-choline without, however, improving release of 3H-ACh, accumulation and release of 3H-5-HT, and ChAT activity. These observations suggest that: (i) denervation-induced hippocampal muscarinic supersensitivity might not be long-lasting or the lesions, which in some cases spared the lateral edges of the fimbria, failed to induce any muscarinic supersensitivity, (ii) intrahippocampal grafts rich in cholinergic neurons do not foster recovery from the lesion-induced noncholinergic deficits we assessed, (iii) recovery of function may be expressed by some but not all biochemical or pharmacological cholinergic variables and (iv) graft-derived hippocampal reinnervation may be less efficient than the endogenous innervation of intact rats as indicated by the restoration of only some of the variables related to cholinergic function by intrahippocampal septal-diagonal band grafts.


Clinical Outcomes and Prognosis Analysis of Younger Bladder Cancer Patients.
Generally, little is known about prognostic factors in bladder cancer patients under 40 years of age. We therefore performed a retrospective study to identify prognostic factors in these younger bladder cancer patients. We collected clinicopathological data on bladder cancer patients ≤40 years old diagnosed between 1975 and 2018 from the Surveillance, Epidemiology, and End Results (SEER) database. Survival curves were generated using the Kaplan-Meier method, and the differences between groups were analyzed using the log-rank test. Univariate and multivariate Cox hazards regression analyses were performed to define hazard ratios (HRs) for cancer-specific survival (CSS). There were statistical differences in race, histological type, cancer stage, tumor size, and surgery treatment groups between overall survival and CSS. Only tumor size and cancer stage were significant independent prognostic risk factors in younger bladder cancer patients for the prediction of CSS. Tumors greater than 30 mm in size and a more advanced stage of bladder cancer were indicative of a poor prognosis in bladder cancer patients ≤40 years old, and long-term follow-up is suggested.


Rapid start-up of photo-granule process in a photo-sequencing batch reactor under low aeration conditions: Effect of inoculum AGS size.
The photo-granule process is an effective and economically feasible alternative for wastewater treatment, but little information is available regarding how to speed up the photo-granulation process. In this study, the effect of inoculum aerobic granular sludge (AGS) size on the start-up of the photo-granule process was investigated under low aeration conditions (superficial gas velocity of 0.5 cm/s). For this purpose, the inoculum AGS was sorted into various size-categories (0.4-0.8 mm, 0.8-1.4 mm, 1.4-2.2 mm, and > 2.2 mm) to serve as individual inoculum sludge. The excellent settling properties (SVI5 of 39.3 mL/g), strong mechanical strength, efficient nutrient removal (COD: 94.2-97.1%; TN: 80.1-84.8%; TP: 60.4-91.5%), and high biodiesel yields (12.11 mg/g MLSS) were rapidly achieved in the system inoculated with 0.8-1.4 mm AGS. The granulation process was facilitated by filamentous algae as the nucleus, extracellular polymeric substances as the backbone, and the enrichment of functional bacteria (such as Thauera and Sphingorhabdus). Furthermore, the inherent influencing mechanisms of inoculum AGS size on the photo-granulation were revealed from cellular hydrophobicity, surface thermodynamics, and sludge aggregation behavior. This study provides a novel start-up approach of the photo-granule process by inoculating with the optimal AGS size, which is convenient, practically feasible and significantly reduced the aeration consumption.


The adsorption-release behavior of sediment phosphorus in a typical "grass-algae" coexisting lake and its influence mechanism during the transition sensitive period.
In the early stage of eutrophication, the coexistence of "grass and algae" in lakes is obvious. Understanding the P sorption-desorption behavior in natural sediments during the ecologically sensitive transition period has important scientific value for predicting the deterioration of lake ecosystems and formulating restoration measures, but the related mechanisms are still unclear. In this study, the analysis results of sedimentary dissolved organic matter (DOM) fractions, extractable Fe (hydr)oxide fractions and P adsorption experiments showed that sedimentary DOM fractions, especially the tyrosine-like protein fractions and microbial humic-like fractions, played a part in determining the EPC0 and Kd values of sediments in the plateau lake environment. The compound effect of amorphous Fe (hydr)oxides and sedimentary OM affected the increase of sedimentary P adsorption. Interestingly, these phenomena were strongly correlated with water depth. Furthermore, the distribution of water depth to aquatic plants indirectly regulated the values of sedimentary EPC0 and Kd. Meanwhile, the ability of submerged plants to control the sedimentary EPC0andKd values will be forced to shift shallowly, thereby forcing a significant reduction of areas with low EPC0 and high Kd values. This not only enhanced the risk of endogenous P release in lakes, but also accelerated the further deterioration of aquatic ecosystems. Therefore, studying the long-term scale changes of sedimentary EPC0 and Kd values can help to understand the duration of the lake ecological transition period and prevent the transitional deterioration of ecosystem.


Ligand discovery using small molecule microarrays.
Small molecule microarrays have recently been used to identify ligands for several proteins, and several themes regarding screening strategies and limitations have emerged. In this review, some of the technical issues related to the manufacture and screening of small molecule microarrays, as well as prospects for small molecule microarrays in several areas of drug discovery and chemistry, are discussed.


Oceanicoccus sagamiensis gen. nov., sp. nov., a gammaproteobacterium isolated from sea water of Sagami Bay in Japan.
A gram-negative, motile, coccoid- and amorphous-shaped, non-pigmented chemoheterotrophic bacterium, designated strain PZ-5(T), was isolated from sea water of Sagami Bay in Japan and subjected to a polyphasic taxonomic study. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the novel isolate could be affiliated with the class Gammaproteobacteria. Strain PZ-5(T) showed below 93.9% similarity with validly published bacteria and demonstrated the highest sequence similarity to Dasania marina KOPRI 20902(T) (93.9%). Strain PZ-5(T) formed a monophyletic group with D. marina KOPRI 20902(T). The DNA G+C content of strain PZ-5(T) was 49.8 mol%. The major isoprenoid quinone was Q-8 and predominant cellular fatty acids were C(15:0) ISO 20H (19%), C(16:1) ω7c (17.4%), C(17;1) ω8c (16.2%), C(11:0) 3OH (7.5%), and C(15:1) ω8c (6.5%). Based on evidence from a polyphasic taxonomical study, it was concluded that the strain should be classified as representing a new genus and species of the class Gammaproteobacteria, for which the name Oceanicoccus sagamiensis gen. nov., sp. nov., (type strain PZ-5(T) =NBRC 107125(T) =KCTC 23278(T)) is proposed.


Design of (Nb, Mo)40Ti30Ni30 alloy membranes for combined enhancement of hydrogen permeability and embrittlement resistance.
The effect of substitution of Nb by Mo in Nb40Ti30Ni30 was investigated with respect to microstructural features and hydrogen dissolution, diffusion and permeation. As-cast Nb40-xMoxTi30Ni30 (x = 0, 5, 10) alloys consist of primary bcc-Nb phase and binary eutectic (bcc-Nb + B2-TiNi). The substitution of Nb by Mo reduces the hydrogen solubility in alloys, but may increase (x = 5) or decrease (x = 10) the apparent hydrogen diffusivity and permeability. As-cast Nb35Mo5Ti30Ni30 exhibits a combined enhancement of hydrogen permeability and embrittlement resistance as compared to Nb40Ti30Ni30. This work confirms that Mo is a desirable alloying element in Nb that can contribute to a reduction in hydrogen absorption and an increase in intrinsic hydrogen diffusion, thus improving embrittlement resistance with minimal permeability penalty.


Crystal forms of naproxen.
The objective of this work was to investigate the existence of polymorphs and pseudopolymorphs of naproxen and the transformation of crystal forms. Four crystal forms of naproxen have been isolated by recrystallization and characterized by differential scanning calorimetry, powder X-ray diffractometry and thermogravimetric analysis. The differential scanning calorimetry and powder X-ray diffractometry patterns of the four crystal forms were different respectively. In the dissolution studies in pH 6.8 ± 0.05 buffer equilibrated at 37 ± 0.5°C, the solubility of four crystal forms was similar (within the error range). After storage of 1 month at 0% RH (silica gel, 20°C), 52% RH (saturated solution of Na(2)Cr(2)O(7.2)H(2)O/20°C) and 95% RH (saturated solution of Na(2)HPO(4)/20°C), Form 2 and Form 4 were transformed to Form 1, but Form 3 and Form 1 were not transformed and they were shown to have a good physical stability at room temperature for 1 month.


Transatrial stenting for long-term management of cardiac tumor obstruction of the right atrium in 3 dogs.
Venous obstruction in dogs caused by large intracardiac masses can result in severe morbidity with few safe treatments. Retrospective study to report results after transatrial stent placement in dogs with naturally occurring cardiac masses causing venous obstruction. Three client-owned dogs diagnosed with large cardiac masses. Retrospective study of patients that received transatrial stents extending from the caudal vena cava, across the right atrium, and into the cranial vena cava (CrVC). Procedures, complications, and outcomes were recorded based upon medical records, referring veterinarians, and client communications. Two dogs had similar clinical signs suggestive of congestive hepatopathy including marked ascites and lethargy. One dog had clinical signs of CrVC syndrome including head and neck swelling with pitting edema and pleural effusion. After stent placement, venous pressure gradients were decreased and repeat angiography confirmed that vascular patency was reestablished. Resolution of clinical signs was marked in all 3 dogs with only mild complications including tachyarrhythmias and hypertension in 1 dog during the perioperative period. Two dogs that required additional transatrial stent placement for reobstruction 6 and 14 months later improved after the second stent implantation. Survival times poststenting for the dogs were 3, 21, and 37 months, with cause of death related to the cardiac tumor in all dogs. Endovascular transatrial stenting may provide a long-term palliative treatment option for dogs with clinical signs attributable to tumor-induced venous obstruction when more traditional treatments are declined or not indicated.


Self-reports of salt intake by 10- to 18-year-olds: relationship to urinary sodium excretion.
Our data indicated that self-reports of consumption of salty foods by children and adolescents were associated with 24-hour urinary sodium excretion. Specifically, youths 10 to 18 years of age who selected a poster depicting high-sodium foods excreted significantly more sodium than youths who selected a poster depicting low-sodium foods. Future research is needed to refine simplified self-report measures, to corroborate the validity of the measures, and to extend the studies to other samples, e.g., younger children.


Vindesine, prednisone, and daunomycin in acute lymphoblastic leukemia in relapse.
Patients with resistant or recurrent acute lymphoblastic leukemia were treated with vindesine 3 mg/m2/IV weekly X 4, daunomycin 25 mg/m2/IV weekly X 4, and prednisone 40 mg/m2/PO daily X 28. Seventeen (44%) of 38 evaluable patients achieved complete remission. Fifty-one percent of 31 patients in first relapse achieved complete remission, while only one of five in second or third relapse and neither of two resistant to first induction achieved complete remission. The major toxicity was hematologic. The median duration of complete remission was only 6 weeks and median survival from start of the study, 3 months, with 22% patients remaining alive at 10 months. We conclude that the vindesine, prednisone, and daunomycin combination is no more effective than vincristine, prednisone, and daunomycin in achieving remission of relapsed acute lymphoblastic leukemia patients, and is more toxic than the latter regimen.


Choice reaction time performance in hospitalized schizophrenic patients and depressed patients.
The choice reaction time performances of matched groups of hospitalized patients diagnosed schizophrenic or depressed were compared with normal controls to test a hypothesis concerning thought disorder specific to schizophrenia. Both patient groups were abnormal compared to controls providing evidence inconsistent with the diagnostic specificity issue. The results are discussed in terms of cognitive dysfunction in depression, the effects of institutionalization and the problems of diagnostic heterogeneity.


Purification of human serum vitamin D-binding protein by 25-hydroxyvitamin D3-Sepharose chromatography.
25-Hydroxyvitamin D3-Sepharose was prepared by coupling 25-hydroxyvitamin D3-3 beta-(1,2-epoxypropyl)-ether to thio-activated Sepharose CL-6B, forming a protease-resistant linkage between the sterol and the matrix. Vitamin D-binding protein from human plasma was obtained 85-92% pure after ligand affinity chromatography. Subsequent hydroxylapatite chromatography provided homogeneous protein. The purified vitamin D-binding protein was fully active in regard to 25-hydroxyvitamin D3 and actin binding capabilities.


Prevention of tumor recurrence and distant metastasis formation in a breast cancer mouse model by biodegradable implant of 131I-norcholesterol.
Brachytherapy has many potential roles in cancer therapy. However, major constraints are associated with placement and removal procedures of the brachytherapy machinery. An attractive approach would be the use of a biodegradable implant loaded with a radioisotope, thus enabling targeted radiotherapy, while reducing the need for surgical procedures for the removal of brachytherapy hardware. In this study, crosslinked chitosan (Ct) hydrogels were prepared and loaded with (131)I-norcholesterol ((131)I-NC). The radioactive hydrogels ((131)I-NC-Ct) were implanted adjacent to 4T1 cell-induced tumors in two different xenograft mice models either as primary therapy or surgical adjuvant therapy of breast cancer. Non-treated mice and mice implanted with naive (non-radioactive) hydrogels served as control groups. In the primary therapy model, the progression rate of the tumor was delayed by two weeks compared with the non-treated and the naive-implant control animals, resulting in a one-week extension in the survival of the treated animals. In the adjuvant therapy model, for the treatment of minimal residual disease, (131)I-NC-Ct implants were able to prevent 69% of tumor recurrence, and to prevent metastatic spread resulting in long-term survival, compared with 0% long-term survival of the non-treated and the naive control groups. Imaging of the hydrogel's in vivo elimination revealed a first order process with a half-life of 14 days. The degradation was caused by oxidation of the Ct as was assessed by in vitro H&E stain. Biodegradable radioactive implants are suggested as a novel platform for the delivery of brachytherapy. This radiotherapy regimen may prevent locoregional recurrence and metastatic spread after tumor resection.


Effects of continuous light and darkness on the eyes of the troglobitic salamander Typhlotriton spelaeus.
Larval Typhlotriton spelaeus collected from five caves in Pulaski Co., Missouri, were kept as larvae or induced to transform in darkness or continuous fluorescent illumination. Larvae maintained in darkness for 215 and 279 days had smaller eyes, smaller rod inner and outer segments, and fewer metaphase figures in the germinative zone of the neural retina than comparable larvae maintained in light (258 lux). Except for visual cell size, differences were small and for each characteristic exceptions were observed. One larva kept in light showed early retinal degeneration comparable to that in transformed adults to T. spelaeus. All larvae exhibited optomotor behavior both before and after the experiment. Among animals induced to transform by L-thyroxin and maintained in darkness 111 to 366 days, visual cell and pigment epithelium degeneration was more extensive and more frequent than in animals kept for the same length of time in light (237-298 lux). In darkness the frequency of animals with retinal degeneration increased between 111 and 366 days. In light some animals exhibited pigment epithelium reduction with normal visual cells, and others had free, pigmented cells in the subretinal space. These effects were not comparable to degeneration in darkness. Eyelids covered the eyes of only a few animals in both light and dark treatments. The extent of eyelid encroachment over the eye greater in darkness than in light. Most animals exhibited optomotor responses after experiments, but responses of animals kept in darkness were impaired in comparison to those of animals kept in light.


Forebrain overexpression of type 1 adenylyl cyclase promotes molecular stability and behavioral resilience to physical stress.
The ability to cope with stress is essential for emotional stability and mental health. It is also hypothesized that factors promoting resilience to stress may offer treatment strategies for maladaptive disorders such as anxiety and depression. Here, we find that physical restraint reduces the expression of type 1 adenylyl cyclase (Adcy1), a neurospecific synaptic enzyme that positively regulates the cAMP signaling cascade. Conversely, an increase of forebrain Adcy1 expression in transgenic mouse (i.e., Adcy1 tg mouse) predisposes individuals to molecular stability and behavioral resilience. Transgenic overexpression of Adcy1 prevents the physical restraint-induced down-regulation of brain-derived neurotrophic factor (BDNF) and neuropeptide Y (NPY). Further, Adcy1 tg mice maintain regular locomotive activity in novelty exploration and voluntary wheel running following physical restraint. Adcy1 tg mice show higher corticosterone and lower basal glucocorticoid receptor (GR) expression, along with a higher MR (mineralocorticoid receptor) to GR ratio in the hippocampus. Further, Adcy1 tg mice show reduced immobility under acute physical stress conditions in the forced swimming test and are more sensitive to the antidepressant desipramine. Our results demonstrate a novel function of Adcy1 in stress coping and suggest Adcy1 as a potential target to antagonize stress vulnerability and promote antidepressant efficacy.


Association of FXR gene variants with cholelithiasis.
Impairment of bile acid homeostasis is the most important risk factor of gallstone disease. Thereby the bile acid sensor farnesoid X receptor (FXR) plays a pivotal role in hepatic and intestinal bile acid metabolism. In this explorative study, the FXR gene was investigated to identify gene variants, associated with gallstone formation in a Caucasian population. Sequencing of the FXR gene was conducted in a randomly selected cohort of gallstone carriers (n=30) and control subjects (n=16) from Stuttgart, Germany. Genomic DNA was obtained from blood leukocytes. Genotype frequencies were established in the total cohort (controls: n=133, gallstone carriers: n=74). For expression analysis, total RNA and protein were isolated from ileal biopsies. The sequencing showed the sole appearance of 10 SNPs in gallstone carriers. Further genotype analysis revealed significant gender- and weight-dependent frequency differences of 3 SNPs between gallstone carriers and controls in males (rs35724: OR=4.73, P=0.022) and normal weight subjects (rs11110385: OR=3.67, P=0.027; rs11110386: OR=3.67, P=0.027) applying the 11+12<>22 allele model. Furthermore, rs11110385 carriers showed a significantly decreased FXR protein expression (11+12<>22: P=0.003). Significant mRNA expression differences between lean rs11110385 carriers and non-carriers were observed in FXR target genes (decrease: ILBP: P=0.042, OSTalpha: P=0.071, FGF19: P=0.011. Increase: LRH1: P=0.044). Three FXR gene variants (rs35724, rs11110385, rs11110386) were identified as potential susceptibility factors for cholelithiasis in a German cohort in gender- and weight-dependent manners. Thereby the tag SNP rs11110385 seemed to influence the activation of the FXR gene.


Topoisomerase Assays.
Topoisomerases are enzymes that play essential roles in DNA replication, transcription, chromosome segregation, and recombination. All cells have two major forms of DNA topoisomerases: type I enzymes, which make single-stranded cuts in DNA, and type II enzymes, which cut and decatenate double-stranded DNA. DNA topoisomerases are important targets of approved and experimental anti-cancer agents. Provided in this article are protocols to assess activities of topoisomerases and their inhibitors. Included are an assay for topoisomerase I activity based on relaxation of supercoiled DNA; an assay for topoisomerase II based on the decatenation of double-stranded DNA; and approaches for enriching and quantifying DNA-protein covalent complexes formed as obligatory intermediates in the reactions of type I and II topoisomerases with DNA; and assays for measuring DNA cleavage in vitro. Topoisomerases are not the only proteins that form covalent adducts with DNA in living cells, and the approaches described here are likely to find use in characterizing other protein-DNA adducts and exploring their utility as targets for therapy. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Assay of topoisomerase I activity Basic Protocol 2: Assay of topoisomerase II activity Basic Protocol 3: In vivo determination of topoisomerase covalent complexes using the in vivo complex of enzyme (ICE) assay Support Protocol 1: Preparation of mouse tissue for determination of topoisomerase covalent complexes using the ICE assay Support Protocol 2: Using recombinant topoisomerase standard for absolute quantification of cellular TOP2CC Basic Protocol 4: Quantification of topoisomerase-DNA covalent complexes by RADAR/ELISA: The rapid approach to DNA adduct recovery (RADAR) combined with the enzyme-linked immunosorbent assay (ELISA) Basic Protocol 5: Analysis of protein-DNA covalent complexes by RADAR/Western Support Protocol 3: Adduct-Seq to characterize adducted DNA Support Protocol 4: Nuclear fractionation and RNase treatment to reduce sample complexity Basic Protocol 6: Determination of DNA cleavage by purified topoisomerase I Basic Protocol 7: Determination of inhibitor effects on DNA cleavage by topoisomerase II using a plasmid linearization assay Alternate Protocol: Gel electrophoresis determination of topoisomerase II cleavage.