Localized catecholamine storage associated with granules in murine neuroblastoma cells.
Catecholamine storage was examined in cultures of the murine neuroblastoma cell line, N-TD6, using histofluorescence, electron microscopic, isotopic and radioautographic criteria. This line was originally derived from uncloned, C1300 tumor cells by selection in tyrosine deficient medium. N-TD6 cells possess both tyrosine hydroxylase (tyrosine-3-monooxygenase, EC 22.214.171.124) and dopamine beta-hydroxylase (dopamine beta-monooxygenase, EC 184.108.40.206) activities. When examined for paraformaldehyde-induced histofluorescence, a small percentage of cells in the population show intense catecholamine fluorescence, often localized within discrete regions of the cellular processes. Electron microscopic examination of these cells reveals both electron lucent vesicles and more frequent, electron dense granules, 50-70 nm and 100-300 nm in diameter, respectively. The distribution of these granules and vesicles varies, but they appear most numerous near the cell surface, along processes and within process endings. By labeling cells with [3H]dopamine and then allowing the cells to release unbound label in the presence of unlabeled dopamine, the localization of catecholamine stores was visualized by radioautographic techniques. While a variety of intracellular distribution of radioactivity were observed, the most prominent concentrations were found in the processes and their terminals; no labeled material was retained when reserpine was present during uptake. The topographic coincidence of granules, catecholamine fluorescence and [3H]dopamine retention in these neuroblastoma cells suggests that catecholamines are stored within these granules in a manner analogous to that observed in normal adrenergic neurons.


Brucellosis presenting with pancytopenia due to hemophagocytic syndrome.
Reactive hemophagocytic syndrome is clinically characterized by fever, hepatosplenomegaly, pancytopenia, and coagulopathy, and is histologically characterized by excessive proliferation and activation of histiocytes or macrophages. It can occur with systemic infections, immunodeficiency, or underlying malignancy. Brucellosis is one of the rare causes of hemophagocytosis. Herein we report an 11-year-old male with pancytopenia due to hemophagocytosis during the course of brucellosis that responded favorably to therapy. Although rare, hemophagocytosis should be considered as a possible cause of pancytopenia in patients with brucellosis, especially in regions where brucellosis is frequently encountered.


Clicking for supper.
When close to prey, porpoises actively widen their sonar beam, which may make it harder for the prey to escape.


Pregnancy and functional paraganglioma.
The association of pregnancy with a catecholamine-secreting tumor is rare. The high maternal and fetal mortality rate is significantly reduced when the diagnosis is made antepartum and adequate management is started. In 1979 Burgess reviewed 42 cases with antepartum diagnosis, demonstrating the benefits of alpha-blockade (Obstet Gynecol 1979; 53:266-270). When diagnosis was made in the third trimester of pregnancy, a combined procedure of cesarean section and tumor resection was best. The best surgical approach in first- and second-trimester diagnosis, however, remains controversial. A case with second-trimester diagnosis is described. Following a period of alpha- and beta-blockade, a combined surgical procedure in the third trimester resulted in a healthy mother and infant. Follow-up procedures included a meta-iodobenzylguanidine scan of the mother. Postpartum, ultrasonography of the child's brain revealed periventricular leucomalacia. The prognosis associated with this finding is poor. Some more recent information about certain aspects of these tumors is also discussed.


Lack of correlation between lymphocyte activating determinants and HLA-DR on acute leukaemias.
The expression of allogenic lymphocyte-activating determinants (LAD) on 25 acute leukaemias has been compared with the expression of cell-surface antigens identified by HLA-DR allo- and xeno-antisera. The close correlation between LAD and DR known to occur on normal lymphocytes was not found in leukaemias. Twenty-two LAD+ leukaemias included 2 DR- cases, whilst 2 LAD- leukaemias were DR+. With the exception of 3 leukaemias all were strongly beta 2 microglobulin+. No correlation was found between the % DR+ cells and the level of lymphocyte stimulation. Separation of leukaemia cells on Ficoll gradients into fractions containing different proportions of DR+ cells did not correlate with LAD expression. Furthermore, antisera to DR antigens only partially blocked leukaemic LAD. The results support the notion that LAD on acute leukaemias are not necessarily associated with or identical to HLA-DR antigens, and that the lymphocyte activating capacity of HLA-DR may be modulated.


Adenovirus and adeno-associated virus-mediated delivery of human myophosphorylase cDNA and LacZ cDNA to muscle in the ovine model of McArdle's disease: expression and re-expression of glycogen phosphorylase.
At present there is no satisfactory treatment for McArdle's disease, deficiency of myophosphorylase. Injection of modified adenovirus 5 (AdV5) and adeno-associated virus 2 (AAV2) vectors containing myophosphorylase expression cassettes, into semitendinosus muscle of sheep with McArdle's disease, produced expression of functional myophosphorylase and some re-expression of the non-muscle glycogen phosphorylase isoforms (both liver and brain) in regenerating fibres. Expression of both non-muscle isoforms was also seen after control injections of AdV5LacZ vectors. There was up to an order of magnitude greater expression of phosphorylase after myophosphorylase vector injection than after LacZ controls (62% of sections with over 1000 positive muscle fibres, versus 7%). The results presented here suggest that the use of viral vector-mediated phosphorylase gene transfer may be applicable to the treatment of McArdle's disease and that sustained re-expression of the brain and liver isoforms should also be investigated as a possible treatment.


Uptake of Lipiodol--cytotoxic conjugates by hepatoblastoma cells.
Improvements in the management of children with hepatoblastoma have followed advances made in cytotoxic agents and treatment regimens. The aim of this study was to quantify the effect of Lipiodol, an iodinated poppy-seed oil, on the uptake of anthracyclic cytotoxic conjugates by hepatoblastoma cells in culture. Monolayer cultures of (1) a hepatoblastoma cell line generated from freshly explanted tumour tissue, (2) an immortal hepatoblastoma cell line (C3a) and (3) a human hepatocyte cell line were exposed to doxorubicin 10 microg/ml with or without 2 per cent Lipiodol for 1-72 h. The fluorescence intensity in the treated cells, which correlates with intracellular doxorubicin concentration, was measured by confocal laser scanning microscopy. Cytotoxicity was assessed by trypan blue exclusion and electron microscopy. Doxorubicin accumulated in the nucleus and cytoplasm of all the cell lines. With Lipiodol, the mean fluorescence intensity of intracellular doxorubicin was increased for up to 48 h in both hepatoblastoma lines, but not in the hepatocyte cell line. Lipiodol increased the uptake and intracellular concentration of doxorubicin in the hepatoblastoma cells in culture. Lipiodol also enhanced the cytotoxicity of doxorubicin on the cultured hepatoblastoma cells. Lipiodol significantly enhanced the uptake of doxorubicin by hepatoblastoma cells in culture. Lipiodol-doxorubicin targeted treatment of hepatoblastoma may improve the intracellular uptake and hence cytotoxicity of doxorubicin in vivo, enabling a reduction in the total dose administered and side-effects.


Dyspnea in COPD: New Mechanistic Insights and Management Implications.
Dyspnea is the most common symptom experienced by patients with chronic obstructive pulmonary disease (COPD). To avoid exertional dyspnea, many patients adopt a sedentary lifestyle which predictably leads to extensive skeletal muscle deconditioning, social isolation, and its negative psychological sequalae. This "dyspnea spiral" is well documented and it is no surprise that alleviation of this distressing symptom has become a key objective highlighted across COPD guidelines. In reality, this important goal is often difficult to achieve, and successful symptom management awaits a clearer understanding of the underlying mechanisms of dyspnea and how these can be therapeutically manipulated for the patients' benefit. Current theoretical constructs of the origins of activity-related dyspnea generally endorse the classical demand-capacity imbalance theory. Thus, it is believed that disruption of the normally harmonious relationship between inspiratory neural drive (IND) to breathe and the simultaneous dynamic response of the respiratory system fundamentally shapes the expression of respiratory discomfort in COPD. Sadly, the symptom of dyspnea cannot be eliminated in patients with advanced COPD with relatively fixed pathophysiological impairment. However, there is evidence that effective symptom palliation is possible for many. Interventions that reduce IND, without compromising alveolar ventilation (VA), or that improve respiratory mechanics and muscle function, or that address the affective dimension, achieve measurable benefits. A common final pathway of dyspnea relief and improved exercise tolerance across the range of therapeutic interventions (bronchodilators, exercise training, ambulatory oxygen, inspiratory muscle training, and opiate medications) is reduced neuromechanical dissociation of the respiratory system. These interventions, singly and in combination, partially restore more harmonious matching of excessive IND to ventilatory output achieved. In this review we propose, on the basis of a thorough review of the recent literature, that effective dyspnea amelioration requires combined interventions and a structured multidisciplinary approach, carefully tailored to meet the specific needs of the individual.


Phylogenetically and catabolically diverse diazotrophs reside in deep-sea cold seep sediments.
Microbially mediated nitrogen cycling in carbon-dominated cold seep environments remains poorly understood. So far anaerobic methanotrophic archaea (ANME-2) and their sulfate-reducing bacterial partners (SEEP-SRB1 clade) have been identified as diazotrophs in deep sea cold seep sediments. However, it is unclear whether other microbial groups can perform nitrogen fixation in such ecosystems. To fill this gap, we analyzed 61 metagenomes, 1428 metagenome-assembled genomes, and six metatranscriptomes derived from 11 globally distributed cold seeps. These sediments contain phylogenetically diverse nitrogenase genes corresponding to an expanded diversity of diazotrophic lineages. Diverse catabolic pathways were predicted to provide ATP for nitrogen fixation, suggesting diazotrophy in cold seeps is not necessarily associated with sulfate-dependent anaerobic oxidation of methane. Nitrogen fixation genes among various diazotrophic groups in cold seeps were inferred to be genetically mobile and subject to purifying selection. Our findings extend the capacity for diazotrophy to five candidate phyla (Altarchaeia, Omnitrophota, FCPU426, Caldatribacteriota and UBA6262), and suggest that cold seep diazotrophs might contribute substantially to the global nitrogen balance.


A null model of guild proportionality, applied to stratification of a New Zealand temperate rain forest.
Much ecological theory assumes that the number of species that can coexist (by 'species packing') is limited, because competitive exclusion occurs when any pair of species within a guild is too similar - 'species saturation' or 'niche limitation'. If such niche limitation occurs, the proportion of species in each guild should be relatively constant - 'guild proportionality'. This concept is applied to the guilds represented by strata in a forest. A method is produced, and used to examine a New Zealand temperate rain forest. Most strata showed no deviation from a null model of no niche limitation, i.e. no tendency to guild proportionality. The proportion of lianes was more variable than in the null model, tending to be inversely related to the proportion of epiphytes, Canopy tree proportion was significantly more constant than in the null model, but this could be interpreted as a limit caused by the size of a canopy tree individual.


Practical implementation of the Guidelines for Unstable Angina/Non-ST-Segment Elevation Myocardial Infarction in the emergency department.
In the United States each year, >5.3 million patients present to emergency departments with chest discomfort and related symptoms. Ultimately, >1.4 million individuals are hospitalized for unstable angina and non-ST-segment elevation myocardial infarction. For emergency physicians and cardiologists alike, these patients represent an enormous challenge to accurately diagnose and appropriately treat. This update of the 2002 American College of Cardiology/American Heart Association Guidelines for the Management of Patients with Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction (UA/NSTEMI) provides an evidence-based approach to the diagnosis and treatment of these patients in the emergency department, in-hospital, and after hospital discharge. Despite publication of the guidelines several years ago, many patients with UA/NSTEMI still do not receive guidelines-indicated therapy.


Multi-walled carbon nanotubes wrapped with polyvinylpyrrolidone can control the leaf yellowing of Alstroemeria cut flowers.
The rapid yellowing of the leaves on cut flowers with leafy stems severely limits their vase life and commercial value. In this study, the effect of a composite of multi-walled carbon nanotubes (MWCNTs) and polyvinyl pyrrolidone (PVP) on the longevity of cut Alstroemeria flowers (Alstroemeria hybrida) was investigated to obtain a solution to this problem. A range of MWCNTs/PVP composite concentrations (0, 3, 6, and 9 mg L-1) was applied in a vase solution (for 24 h) as pulse treatments. Our findings indicate that the composite of MWCNTs and PVP exhibits excellent dispersibility in a vase solution. The results demonstrate that a 3 mg L-1 MWCNTs/PVP concentration was the most effective, extending the vase life of cut Alstroemeria flowers by up to 27 days. Pulsing with MWCNTs/PVP delayed the onset of floret abscission and leaf yellowing by 5 and 18 days, respectively. Additionally, when MWCNTs/PVP solution was applied to cut stems, water uptake remained consistently greater than that of the control. Additionally, MWCNTs/PVP increased the total chlorophyll content, soluble protein content, and POX enzyme activity of leaves while decreasing the malondialdehyde (MDA) content. The results indicate that this composite exhibited antimicrobial activity against gram-positive and -negative bacteria, particularly at a concentration of 3 mg L-1. This study demonstrated that adding MWCNTs/PVP to a vase solution of Alstroemeria cut flowers increased their longevity with minimal leaf yellowing symptoms compared to untreated cut stems. As a result, this nanocomposite can be used safely and effectively in vase solutions and in combination with other preservatives.


Mature and activated osteoclasts exist in the synovium of rapidly destructive coxarthrosis.
We compared histological and functional findings in rapidly destructive coxarthrosis (RDC) and slowly progressive osteoarthritis (OA) to investigate whether osteoclasts contribute to the extensive bone destruction observed in RDC. A histological analysis of tissue specimens from the synovium obtained from 10 cases of RDC and 40 cases with OA of the hip was performed after staining for tartrate-resistant acid phosphatase (TRAP). The cells isolated from these tissue specimens from the synovium were cultured for 24 h, and the numbers of TRAP-positive giant cells were counted. Thereafter, we performed a resorption pit formation assay by isolated cells cultured on dentine slices for 7 days. The number of TRAP-positive multinuclear giant cells present in the synovial membrane obtained from RDC patients was significantly larger than that obtained from OA patients. Large lacunar resorption pits were only seen on the dentin slices in a culture of isolated cells from RDC patients without any stimulators. This is the first report, to our knowledge, to reveal that mature and activated osteoclasts exist only in the synovium of RDC and not in the OA synovium. This result might suggest that the underlying mechanism of RDC is therefore associated with osteoclastogenesis in the synovium.


Clonidine-induced growth hormone secretion in elderly patients with senile dementia of the Alzheimer type and major depressive disorder.
This study was undertaken to assess the value of growth hormone (GH) response to clonidine as a tool in the differential diagnosis between depression and dementia. This response is known to be blunted in depression, and neurochemical changes observed in senile dementia of the Alzheimer type (SDAT) could lead to an up-regulation of GH secretion. No difference was observed between GH response in depressed and demented patients. Together with studies on GH basal secretion in Alzheimer's disease, this finding suggests that the final consequence of SDAT-related changes in an accentuation of the effects of aging on GH reactivity.


Micro-ribonucleic acid expression signature of metastatic castration-resistant prostate cancer: Regulation of NCAPH by antitumor miR-199a/b-3p.
To identify oncogenes regulated by micro-ribonucleic acid, miR-199a/b-3p, in metastatic castration-resistant prostate cancer. Advanced ribonucleic acid sequencing technologies were applied to construct a micro-ribonucleic acid expression signature using metastatic castration-resistant prostate cancer autopsy specimens. Ectopic expression of mature micro-ribonucleic acids or small-interfering ribonucleic acids were applied to functional assays for cancer cell lines. Genome-wide gene expression and in silico database analyses were carried out to predict micro-ribonucleic acid targets. Ectopic expression of miR-199a/b inhibited cancer cell aggressiveness. The gene coding for non-structural maintenance of chromosomes condensin I complex subunit H was directly regulated by miR-199a/b-3p. High expression of condensin I complex subunit H was significantly associated with poor disease-free survival by The Cancer Genome Atlas database analysis (P < 0.0001). Overexpression of condensin I complex subunit H was detected in hormone-sensitive prostate cancer and castration-resistant prostate cancer specimens, and knockdown assays showed that its expression enhanced cancer cell migration and invasive abilities. Small ribonucleic acid sequencing of metastatic castration-resistant prostate cancer specimens showed the presence of several antitumor micro-ribonucleic acids whose targets are involved in hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer pathogenesis. Condensin I complex subunit H seems to be a promising diagnostic marker and therapeutic target for this disease. Our approach, based on the roles of anti-tumor micro-ribonucleic acids and their targets, will contribute to an improved understanding of the molecular pathogenesis of hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer.


On the asymptotic behavior of the Douglas-Rachford and proximal-point algorithms for convex optimization.
Banjac et al. (J Optim Theory Appl 183(2):490-519, 2019) recently showed that the Douglas-Rachford algorithm provides certificates of infeasibility for a class of convex optimization problems. In particular, they showed that the difference between consecutive iterates generated by the algorithm converges to certificates of primal and dual strong infeasibility. Their result was shown in a finite-dimensional Euclidean setting and for a particular structure of the constraint set. In this paper, we extend the result to real Hilbert spaces and a general nonempty closed convex set. Moreover, we show that the proximal-point algorithm applied to the set of optimality conditions of the problem generates similar infeasibility certificates.


Staging of breast cancer: what standards should be used in research and clinical practice?
Bone scan (BS), chest X-rays (CXR), liver ultrasonography (LUS) and laboratory parameters (LP) are frequently used as routine staging procedures for breast cancer patients. These procedures are not always appropriate in either clinical or research settings, regardless of the stage. The aim of this study was to identify groups of patients with differing risks for metastases in order to select more precise standard staging procedures. The staging data relating to 406 breast cancer patients consecutively referred to our institution between November 1989 and October 1996 were analysed including pathological TNN grading and biological parameters. All of the cases with a positive or suspicious pre-operatory staging and who proved to have metastatic disease before surgery or during the first six months of follow-up were considered true-positive; all of the other cases with a positive or suspicious initial staging but with no evidence of distant metastasis before surgery and with a disease-free survival longer then six months were considered false-positive. In the same way all cases with negative initial staging who relapsed during the first six months of follow-up were considered false-negative and those with negative initial staging and with a disease-free survival longer then six months were considered true-negative. Statistical analysis was performed using Fisher's exact test. BS, CXR and LUS, 388, 399 and 398 examinations respectively, were considered available, and 17 (4.38%), six (1.5%) and four (1%), respectively, proved to be true-positive. A statistically significant difference was observed when our cases were grouped according to T status (T4 vs. T1-T2-T3, P < 0.01) and nodal status (N0-N1 cases with less than three involved nodes and N1 with more than three positive lymph nodes N2 patients, P < 0.01). The present study suggests that breast cancer patients can be divided into three subgroups with different detection rates for distant metastases at staging (0.59%, 2.94% and 15.53%), and that the standard practice should be changed. In the first (T1N0 and T1N1 patients with < or = 3 positive lymph nodes--41.13% of the patients) and the second group (T2N0, T2N1 with < or = 3 positive lymph nodes, T3N0 and T3N1 patients with < or = 3 positive lymph nodes--33.49% of the patients) there is no need for a complete set of staging procedures, whereas full procedural staging is needed in the third group of patients (T4, N1 with > 3 lymph nodes and N2, 25.37% of the patients).


Late-onset cerebellar ataxia with hypogonadism and muscle coenzyme Q10 deficiency.
Two brothers had late-onset progressive ataxia, cerebellar atrophy, and hypergonadotropic hypogonadism associated with coenzyme Q10 (CoQ10) deficiency in skeletal muscle. Both patients improved on high-dose CoQ10 supplementation, stressing the importance of CoQ10 deficiency in the differential diagnosis of cerebellar ataxia, even when onset is late.


Highly sensitive HF detection based on absorption enhanced light-induced thermoelastic spectroscopy with a quartz tuning fork of receive and shallow neural network fitting.
Due to its advantages of non-contact measurement and high sensitivity, light-induced thermoelastic spectroscopy (LITES) is one of the most promising methods for corrosive gas detection. In this manuscript, a highly sensitive hydrogen fluoride (HF) sensor based on LITES technique is reported for the first time. With simple structure and strong robustness, a shallow neural network (SNN) fitting algorithm is introduced into the field of spectroscopy data processing to achieve denoising. This algorithm provides an end-to-end approach that takes in the raw input data without any pre-processing and extracts features automatically. A continuous wave (CW) distributed feedback diode (DFB) laser with an emission wavelength of 1.27 µm was used as the excitation source. A Herriott multi-pass cell (MPC) with an optical length of 10.1 m was selected to enhance the laser absorption. A quartz tuning fork (QTF) with resonance frequency of 32,767.52 Hz was adopted as the thermoelastic detector. An Allan variance analysis was performed to demonstrate the system stability. When the integration time was 110 s, the minimum detection limit (MDL) was found to be 71 ppb. After the SNN fitting algorithm was used, the signal-to-noise ratio (SNR) of the HF-LITES sensor was improved by a factor of 2.0, which verified the effectiveness of this fitting algorithm for spectroscopy data processing.


Fluoroscopic Estimation of Thoracic Dimensional Changes in Healthy Dogs.
Current methods available for assessing alterations in lung mechanics require sophisticated equipment and are of limited availability. A method that could assess lung area change with respiration might be a clinically useful surrogate for assessing lung compliance. To use fluoroscopy to determine percent change in thoracic and lung areas in healthy dogs. Forty-four client-owned dogs with no evidence of respiratory disease. Prospective study. Resting respiration was recorded fluoroscopically, and peak inspiratory and expiratory frames were captured for 3 typical respiratory cycles. The number of intrathoracic pixels in the entire thoracic cavity was measured for both inspiration and expiration, and the average percent change in intrathoracic area was determined for each dog. This process was repeated by a hemithorax measurement of lung area that excluded the mediastinum and cardiac silhouette. Proposed reference ranges (and 95% confidence intervals [CI]) were computed by a nonparametric percentile distribution. Median percent change in thoracic dimension for the total thorax measurement was 12.5% (CI, 8.9-24.0%). Median percent change for the hemithorax measurement was significantly (P < 0.001) larger (20.8%, CI, 14.3-37.6%). Both measurement techniques were correlated with body weight but not with age, sex, thoracic conformation, body condition score (BCS), or breed. Fluoroscopy allows a noninvasive and repeatable measure of lung area changes during respiration that must be corrected for body weight. Additional studies in dogs with respiratory diseases are needed to determine its utility in detecting clinically useful alterations in lung area changes.


Systematic realist synthesis of health-related and lifestyle interventions designed to decrease overweight, obesity and unemployment in adults.
Obesity and unemployment are complex social and health issues with underlying causes that are interconnected. While a clear link has been established, there is lack of evidence on the underlying causal pathways and how health-related interventions could reduce obesity and unemployment using a holistic approach. The aim of this realist synthesis was to identify the common strategies used by health-related interventions to reduce obesity, overweight and unemployment and to determine for whom and under what circumstances these interventions were successful or unsuccessful and why. A realist synthesis approach was used. Systematic literature searches were conducted in Cochrane library, Medline, SocIndex, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, and PsychInfo. The evidence from included studies were synthesised into Context-Mechanism-Outcome configurations (CMOcs) to better understand when and how programmes work, for which participants and to refine the final programme theory. A total of 83 articles met the inclusion criteria. 8 CMOcs elucidating the contexts of the health-related interventions, underlying mechanisms and outcomes were identified. Interventions that were tailored to the target population using multiple strategies, addressing different aspects of individual and external environments led to positive outcomes for reemployment and reduction of obesity. This realist synthesis presents a broad array of contexts, mechanisms underlying the success of health-related interventions to reduce obesity and unemployment. It provides novel insights and key factors that influence the success of such interventions and highlights a need for participatory and holistic approaches to maximise the effectiveness of programmes designed to reduce obesity and unemployment. PROSPERO 2020 CRD42020219897 .


[Verbal memory in patients with major depression].
Patients with major depression commonly report memory deficits but studies on this topic have shown inconsistent results. The aim of this study was to determine whether patients with major depression showed any differences in explicit verbal memory compared to healthy controls. We used the California verbal learning test (CVLT) in order to compare the explicit verbal memory of 30 patients (21 women and 9 men) to a healthy control group (23 women and 10 men). The results showed no significant differences between verbal memory performance of patients with major depression and healthy controls. Verbal memory of depressive patients with antidepressant pharmacotherapy showed no significant differences compared to a healthy control group. It can be assumed that verbal memory in depression depends on variable parameters (e.g. age, severity and duration of depression and medication). More studies with a larger number of patients should be conducted to obtain reliable results about explicit verbal memory in depression.


Double-Sided Microwells with a Stepped Through-Hole Membrane for High-Throughput Microbial Assays.
To improve the throughput of microwell arrays for identifying immense cellular diversities even at a single-bacteria level, further miniaturization or densification of the microwells has been an obvious breakthrough. However, controlling millions of nanoliter samples or more at the microscale remains technologically difficult and has been spatially restricted to a single open side of the microwells. Here we employed a stepped through-hole membrane to utilize the bottom as well as top side of a high-density nanoliter microwell array, thus improving spatial efficiency. The stepped structure shows additional effectiveness for handling several millions of nanoliter bacterial samples in the overall perspectives of controllability, throughput, simplicity, versatility, and automation by using novel methods for three representative procedures in bacterial assays: partitioning cells, manipulating the chemical environment, and extracting selected cells. As a potential application, we show proof-of-concept isolation of rare cells in a mixed ratio of 1 to around 106 using a single chip. Our device can be further applied to various biological studies pertaining to synthetic biology, drug screening, mutagenesis, and single-cell heterogeneity.


Effects of phosphate supplementation on intact and fractured femora of rats: a biomechanical study.
The production of a better and stronger healing bone has attracted the interest of many investigators in the past. Numerous substances have been used to increase both the strength and the rate of production of fracture callus. Recently phosphate, administered orally, has been suggested for this purpose. A biomechanical study was conducted with rat femora and variable doses of phosphate in this regard. Phosphate was found to benefit osteomalacic bones but to have no effect on normal bones and a toxic effect in high concentrations.


Does restaging MRI radiomics analysis improve pathological complete response prediction in rectal cancer patients? A prognostic model development.
Our study investigated the contribution that the application of radiomics analysis on post-treatment magnetic resonance imaging can add to the assessments performed by an experienced disease-specific multidisciplinary tumor board (MTB) for the prediction of pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). This analysis included consecutively retrospective LARC patients who obtained a complete or near-complete response after nCRT and/or a pCR after surgery between January 2010 and September 2019. A three-step radiomics features selection was performed and three models were generated: a radiomics model (rRM), a multidisciplinary tumor board model (yMTB) and a combined model (CM). The predictive performance of models was quantified using the receiver operating characteristic (ROC) curve, evaluating the area under curve (AUC). The analysis involved 144 LARC patients; a total of 232 radiomics features were extracted from the MR images acquired post-nCRT. The yMTB, rRM and CM predicted pCR with an AUC of 0.82, 0.73 and 0.84, respectively. ROC comparison was not significant (p = 0.6) between yMTB and CM. Radiomics analysis showed good performance in identifying complete responders, which increased when combined with standard clinical evaluation; this increase was not statistically significant but did improve the prediction of clinical response.


The interaction of adenosine and morphine on pentylenetetrazole-induced seizure threshold in mice.
Adenosine agonists or low doses of morphine exert anti-convulsant effects in different models of seizures. On the other hand, a tight interaction has been reported between morphine and adenosine in various paradigms. This study investigated the effect of the interaction of adenosine and morphine on seizure susceptibility in the intravenous mouse model of pentylenetetrazole (PTZ)-induced clonic seizures. The researchers used acute systemic administration of morphine, N(6)-cyclohexyladenosine (CHA) (a selective A1 receptor agonist), naltrexone (an opioid receptor antagonist) and 8-Cyclopentyl-1,3-dimethylxanthine (8-CPT) (a selective A1 receptor antagonist). Acute administration of morphine (0.25, 0.5 and 1 mg/kg) or CHA (0.25, 0.5, 1, 2 and 4 mg/kg) raised the threshold of seizures induced by PTZ. Non-effective dose of 8-CPT (2 mg/kg) inhibited the anticonvulsant effects of CHA (0.5 and 1 mg/kg). Combination of sub-effective doses of morphine (0.125 mg/kg) and CHA (0.125 mg/kg) increased clonic seizure latency showing the additive effect of morphine and CHA. The enhanced latency induced by combination of low doses of morphine and CHA completely reversed by 8-CPT (2 mg/kg) or naltrexone (1 mg/kg). Moreover, 8-CPT (2 mg/kg) inhibited anticonvulsant effects of morphine (0.25 and 0.5 mg/kg) and naltrexone (1 mg/kg) inhibited anticonvulsant effects of CHA (0.25, 0.5 and 1 mg/kg). Combination of low doses of 8-CPT (1 mg/kg) and naltrexone (0.5 mg/kg) inhibited the anticonvulsant effect of CHA (0.5 and 1 mg/kg). In conclusion, adenosine and morphine exhibit an additive effect on the enhancement of the pentylenetetrazole-induced seizure threshold in mice, probably through A1 or μ receptors.


Increased glomerular permeability to albumin induced by exercise in diabetic subjects.
The urinary excretion of albumin was measured in insulin-dependent diabetics under ordinary conditions of life and in response to exercise. Possible mechanisms of exercise induced albuminuria in diabetics were also investigated. Under ordinary conditions of life the insulin-treated diabetics, as a group, had a higher mean urinary albumin excretion than normal controls; however, half of the diabetics had albumin excretion rates within the control range. A given exercise load (600 kpm/min for 20 min) produced an exaggerated albumin excretion in diabetics, particularly evident in the post-exercise period. The elevated urinary albumin excretion was due to an increased transglomerular passage of albumin, not to reduced tubular reabsorption. The increase was not associated with differences in blood pressure or urine flow between controls and diabetics. This exercise test has proved to be a suitable provocation test to unmask abnormalities in the glomerular handling of albumin that might not be recognisable at rest.


A comparison of statistical methods for low dose extrapolation utilizing time-to-tumor data.
The assessment of health risks due to low levels of exposure to potential environmental hazards based on the results of toxicological experiments necessarily involves extrapolation of results obtained at relatively high doses to the low dose region of interest. In this paper, different statistical extrapolation procedures which take into account both time-to-response and the presence of competing risks are compared using a large simulated data base. The study was designed to cover a range of plausible dose response models as well as to assess the effects of competing risks, background response, latency and experimental design on the performance of the different extrapolation procedures. It was found that point estimates of risk in the low dose region may differ from the actual risk by a factor of 1000 or more in certain situations, even when precise information on the time of occurrence of the particular lesion of interest is available. Although linearized upper confidence limits on risk can be highly conservative when the underlying dose response curve is sublinear in the low dose region, they were found not to exceed the actual risk in the low dose region by more than a factor of 10 in those cases where the underlying dose response curve was linear at low doses.


Transfer of the radial branch of the superficial radial nerve to the sensory branch of the ulnar nerve for sensory restoration after C7-T1 brachial plexus injury.
Previously, we have reconstructed the motor function of patients with C7-T1 brachial plexus palsies through combined nerve and tendon transfers. However, these patients lose not only the motor function of the hand but also the sensation on the ulnar side of the hand. Without sensory recovery, the injured hand may be further damaged, particularly by burns in this contact zone. Therefore, we described a technique to restore the sensation at the ulnar aspect of the hand by performing a transfer of the radial branch of the superficial radial nerve to the sensory branch of the ulnar nerve.


A novel molluscicidal formulation of niclosamide.
Snail control by molluscicides is an important strategy for schistosomiasis control in China. Currently, only one chemical molluscicide, niclosamide, which is used as 50% wettable powder of niclosamide ethanolamine salt (WPN), is commercially available for field snail control in China. However, WPN is costly, toxic, and has a lower dispersibility and precipitates rapidly. In this paper, we describe the development of a novel formulation of niclosamide, a suspension concentrate of niclosamide (SCN). The efficacy of SCN was evaluated both in the laboratory and field. SCN showed better molluscicidal effects than conventional formulation of WPN, as determined by LC(50) for adult snails, young snails, and snail eggs. The acute toxicity of SCN to Brachdanio rerio hamiton was less than WPN. In conclusion, the novel formulation of SCN suspension is physically more stable, more effective, and less toxic. Therefore, it can be more useful for controlling snails in endemic areas of schistosomiasis in China.


Successful surgical excision of a nondysraphic holodorsal intramedullary lipoma in a 14-month-old child.
Nondysraphic intramedullary lipomas of the spinal cord are rare lesions. They are most commonly seen in the second or third decade of life. Their occurrence in the pediatric age group is even rarer. The authors describe a 14-month-old child who presented with delayed motor milestones involving the bilateral lower limbs. The child was unable to sit or stand. MRI revealed a dorsally located intramedullary lipoma extending from C7 to D12. The child underwent C7-L1 laminotomy and gross total excision of the lipoma. Postoperatively, the child improved neurologically and attained normal power in the bilateral lower limbs. Very few cases of extensive intramedullary lipomas involving the dorsal cord have previously been reported. Only two cases of pediatric extensive dorsal lipomas have been mentioned to date. The authors describe successful surgical excision of a holodorsal intramedullary lipoma in a 14-month-old child. To the best of the authors' knowledge, this is the first case being reported of a holodorsal intramedullary lipoma in the youngest patient.


The differential expression and potential roles of circular RNAs in children with anti-NMDA receptor encephalitis.
To explore the role of circular RNAs (circRNAs) in pediatric anti-N-methyl-d-aspartate (NMDA) receptor encephalitis, we assessed the profiles of circRNAs and mRNAs in blood leukocytes from anti-NMDA receptor encephalitis patients and healthy controls using microarray analysis. 1196 circRNAs and 719 mRNAs (change ≥2, p < .05) were dysregulated in anti-NMDA receptor encephalitis patients, relative to healthy controls, based on microarray data. Further bioinformatic analysis demonstrated that the host genes of dysregulated circRNAs are primarily associated with receptor internalization. In conclusion, circRNAs may be implicated in the pathogenesis of pediatric anti-NMDA receptor encephalitis.


Structural and conformational properties of 1,2-propadienylphosphine (allenylphosphine) studied by microwave spectroscopy and quantum chemical calculations.
1,2-Propadienylphosphine (allenylphosphine), H(2)C=C=CHPH(2), has been investigated by Stark and Fourier transform microwave spectroscopy. Two rotameric forms denoted syn and gauche have been assigned. The syn form has a symmetry plane (C(s)() symmetry) where the lone electron pair of phosphorus points toward the double bonds. The phosphino group is rotated roughly 120 degrees from this position in the gauche rotamer. The dipole moment of syn was determined to be mu(a) = 1.613(23), mu(b) = 2.347(24), mu(c) = 0 (for symmetry reasons), and mu(tot) = 2.848(28) x 10(-30) C m [0.854(8) D]. The energy difference between the two forms was found to be 2.1(4) kJ/mol from relative intensity measurements with syn as the more stable conformer. Extensive quantum chemical calculations have been carried out and accurate equilibrium structures have been determined for these two rotamers, as well as for the corresponding two conformers of vinylphosphine (H(2)C=CHPH(2)).


Publisher Correction: γδ TCR ligands: the quest to solve a 500-million-year-old mystery.
In the version of this article initially published, the affiliations were incorrect. The correct affiliations are as follows: "1Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK. 2Institute of Immunology and Immunotherapy, Cancer Immunology and Immunotherapy Centre, Cancer Research UK Birmingham Centre, University of Birmingham, Birmingham, UK." The reference citation at the end of the first sentence of the second paragraph of the subsection 'A perspective on current methods of ligand identification' was incorrect; the correct citation is "...ligands20-40." There is an error (en dash) in the fourth paragraph of that section; the correct text is "...specific for CD1 and phycoerythrin...". There is an error ("proposed") in the fourth paragraph of the subsection 'An emerging adaptive perspective on antigenic γδ TCR ligands'; the correct text is "...are suggested to recognize...". There is an error ("via") in the fourth paragraph of the subsection 'B7-like molecules as candidate γδ TCR ligands'; the correct text is "...in a non-clonotypic fashion are striking...". Finally, reference citations throughout the legend to Fig. 1 are incorrect; the correct citations are as follows: MHC class I free heavy chain22; HLA-B580234; I-Ek (ref. 30); MSH2 (MutShomolog 2) and HSP60 (heat-shock protein 60)24; ULBP4 (UL16-binding protein 4)27; MICA41; the herpes simplex virus glycoprotein HSVgI33; ATPase-apolipoprotein-AI39; and insulin B:9-23 peptide antigen40. The errors have been corrected in the HTML and PDF versions of the article.


Activity of deep dorsal horn neurons in the anaesthetized rat during hyperalgesia of the hindpaw induced by ultraviolet irradiation.
Thermal hyperalgesia was induced by UV irradiation of the glabrous skin of the hindpaw of adult female Sprague-Dawley rats. We have recorded single cell activity and studied excitability changes in wide dynamic range neurons in the lumbar spinal segments during the early phase (days 1-3) and late phase (days 5-7) of thermal hyperalgesia in animals under urethane anaesthesia. The proportion of spontaneously active wide dynamic range cells was increased following UV irradiation and the degree of spontaneous activity was enhanced during the course of hyperalgesia. In addition there was a significant increase in the total number of spikes evoked by standardized mechanical and noxious heat stimuli when tested at days 1-3 and days 5-7. The duration of the evoked responses was also significantly prolonged in both UV-treated groups. The noxious temperature threshold to radiant heat stimulation was significantly decreased on the UV-treated but not on the contralateral hindpaw. The average size of the receptive fields on the UV-treated paws was expanded in comparison to control. To differentiate between possible central and peripheral components of the hyperactivity of wide dynamic range cells we performed in situ dorsal rhizotomy during the recording. Cutting the dorsal roots (L2-5) evoked a significantly larger and more prolonged discharge in wide dynamic range cells in both UV-treated groups in comparison to control. Spontaneous activity in spinal wide dynamic range neurons was reduced after rhizotomy in each group. However, the decrease was only significant at days 1-3 (P < 0.05) but not at days 5-7.(ABSTRACT TRUNCATED AT 250 WORDS)


Reliable Selection and Holistic Stability Evaluation of Reference Genes for Rice Under 22 Different Experimental Conditions.
Stable and uniform expression of reference genes across samples plays a key role in accurate normalization of gene expression by reverse-transcription quantitative polymerase chain reaction (RT-qPCR). For rice study, there is still a lack of validation and recommendation of appropriate reference genes with high stability depending on experimental conditions. Eleven candidate reference genes potentially owning high stability were evaluated by geNorm and NormFinder for their expression stability in 22 various experimental conditions. Best combinations of multiple reference genes were recommended depending on experimental conditions, and the holistic stability of reference genes was also evaluated. Reference genes would become more variable and thus needed to be critically selected in experimental groups of tissues, heat, 6-benzylamino purine, and drought, but they were comparatively stable under cold, wound, and ultraviolet-B stresses. Triosephosphate isomerase (TI), profilin-2 (Profilin-2), ubiquitin-conjugating enzyme E2 (UBC), endothelial differentiation factor (Edf), and ADP-ribosylation factor (ARF) were stable in most of our experimental conditions. No universal reference gene showed good stability in all experimental conditions. To get accurate expression result, suitable combination of multiple reference genes for a specific experimental condition would be a better choice. This study provided an application guideline to select stable reference genes for rice gene expression study.


[Studies on the phenolic acids from Sarcopyramis bodinieri var. delicata].
To study the chemical constituents from Sarcopyramis bodinieri var. delicata. These compounds were isolated and purified by chromatography with silica gel column combined with Sephadex LH-20 column from high polar extracts. The structures were identified on the basis of extensive spectroscopic data analysis, and by comparison of their spectral data with those reported. Seven compounds were isolated as 3, 3'-di-O-methylellagic acid-4'-O-alpha-L-rhamnopyranoside (I), ellagic acid (II), ferulic acid (III), isoferulic acid (IV), caffeic acid (V), 3, 4-di-hydroxybenzoic acid (VI), p-hydroxycinnamic acid (VII). Compound I, III, VI, VII are isolated from the genus for the first time.


Psychiatric disorders and depression in multiple sclerosis outpatients: impact of disability and interferon beta therapy.
Associations between psychopathology and gender, duration of MS, disability and therapy with beta-interferons were studied in multiple sclerosis (MS) outpatients. A controlled descriptive epidemiological study was carried out in two Italian outpatient MS centres on 50 outpatients with clinically definite relapsing-remitting MS presenting for regular follow-up and 50 healthy controls matched for sex, age and educational level. Subjects were assessed with the Structured Clinical Interview for DSM-IV (SCID I), the Beck Depression Inventory (BDI) and the State Trait Anxiety Inventory (STAI). MS patients reported a higher prevalence of psychiatric disorders (odds ratio 3.17), with 46% (n=23) suffering from major depressive disorder. The risk of suffering from any non-mood psychiatric disorder was also higher in MS patients than in controls (odds ratio 2.67). Risk factors for depression were female sex and severity of disability, but not therapy with interferon beta or longer duration of illness. Disability level, but not therapy with beta-interferons, is a risk factor for depression in MS outpatients. Regular screening for depression in this population is appropriate.


VATS-assisted surgical stabilization of rib fractures in flail chest: 1-year follow-up of 105 cases.
Early surgical stabilization of flail chest has been shown to improve chest wall stability and diminish respiratory complications. The addition of video‑assisted thoracoscopic surgery (VATS) can diagnose and manage intrathoracic injuries and evacuate hemothorax. This study analyzed the outcome of our 7-year experience with VATS-assisted surgical stabilization of rib fractures (SSRF) for flail chest. From January 2013 to December 2019, all trauma patients undergoing VATS-assisted SSRF for flail chest were included. Patient characteristics and complications during 1-year follow-up were reported. VATS‑assisted SSRF for flail chest was performed in 105 patients. Median age was 65 years (range 21-92). Median injury severity score was 16 (range 9-49). Hemothorax was evacuated with VATS in 80 patients (median volume 200 ml, range 25-2500). In 3 patients entrapped lung was freed from the fracture site and in 2 patients a diaphragm rupture was repaired. Median postoperative ICU admission was 2 days (range 1-41). Thirty-two patients (30%) had a post‑operative complication during admission and six patients (6%) a complication within 1 year. In-hospital mortality rate was 1%. Six patients (6%) died after discharge, due to causes unrelated to the original injury. Addition of VATS to SSRF for flail chest seems helpful to diagnose and manage intrathoracic injuries and adequately evacuate hemothorax. The majority of complications are low grade and occur during admission. Further prospective research needs to be conducted to identify potential risk factors for complications and better selection for addition of VATS to improve care in the future.


Evidence of oxidative stress in mdx mouse muscle: studies of the pre-necrotic state.
Considerable evidence indicates that free radical injury may underlie the pathologic changes in muscular dystrophies from mammalian and avian species. We have investigated the role of oxidative injury in muscle necrosis in mice with a muscular dystrophy due to a defect in the dystrophin gene (the mdx strain). In order to avoid secondary consequences of muscle necrosis, all experiments were done on muscle prior to the onset of the degenerative process (i.e. during the 'pre-necrotic' phase) which lasted up to 20 days of age in the muscles examined. In pre-necrotic mdx muscle, there was an induction of expression of genes encoding antioxidant enzymes, indicative of a cellular response to oxidative stress. In addition, the levels of lipid peroxidation were greater in mdx muscle than in the control. Since the free radical nitric oxide (NO*) has been shown to mediate oxidative injury in various disease states, and because dystrophin has been shown to form a complex with the enzyme nitric oxide synthase, we examined pre-necrotic mdx muscle for evidence of NO*-mediated injury by measuring cellular nitrotyrosine formation. By both immunohistochemical and electrochemical analyses, no evidence of increased nitrotyrosine levels in mdx muscle was detected. Therefore, although no relationship with NO*-mediated toxicity was found, we found evidence of increased oxidative stress preceding the onset of muscle cell death in dystrophin-deficient mice. These results lend support to the hypothesis that free radical-mediated injury may contribute to the pathogenesis of muscular dystrophies.


First-principle calculation of the ηc→2γ decay width from lattice QCD.
We perform a lattice QCD calculation of the ηc→2γ decay width using a model-independent method that requires no momentum extrapolation of the off-shell form factors. This method also provides a straightforward and simple way to examine the finite-volume effects. The calculation is accomplished using Nf=2 twisted mass fermion ensembles. The statistically significant excited-state effects are observed and eliminated using a multi-state fit. The impact of fine-tuning the charm quark mass is also examined and confirmed to be well-controlled. Finally, using three lattice spacings for the continuum extrapolation, we obtain the decay width [Formula: see text] keV, which differs significantly from the Particle Data Group's reported value of [Formula: see text] keV (2.9σ tension). We provide insight into the comparison between our findings, previous theoretical predictions, and experimental measurements.


Enhanced uptake of gH625 by blood brain barrier compared to liver in vivo: characterization of the mechanism by an in vitro model and implications for delivery.
We have investigated the crossing of the blood brain barrier (BBB) by the peptide gH625 and compared to the uptake by liver in vivo. We clearly observed that in vivo administration of gH625 allows the crossing of the BBB, although part of the peptide is sequestered by the liver. Furthermore, we used a combination of biophysical techniques to gain insight into the mechanism of interaction with model membranes mimicking the BBB and the liver. We observed a stronger interaction for membranes mimicking the BBB where gH625 clearly undergoes a change in secondary structure, indicating the key role of the structural change in the uptake mechanism. We report model studies on liposomes which can be exploited for the optimization of delivery tools.


Validity of Self-reported Sexual Behavior Among Adolescents: Where Do We Go from Here?
Adolescents have high rates of sexually transmitted infections (STIs). Adolescents consuming alcohol and using drugs have markedly greater HIV/STI risk and are a priority population for intervention. Accurate measurement of sexual risk behavior is critical for understanding individual's risk for HIV/STI, transmission dynamics of HIV/STI, and evaluating the efficacy of interventions designed reduce HIV/STI risk. However, significant challenges to accurately measuring adolescents' self-reported sexual behavior are well-documented. Recent advances in microbiology, such as the use of less invasive specimen collection for DNA assays, can assist researchers in more accurately measuring adolescents' sexual risk behavior. However, the majority of studies of adolescents' sexual risk rely solely on self-reported behavior; therefore, methods to improve the validity of adolescents' self-reported sexual behavior are needed. In addition, integrating biologic measures to complement self-reported measures are recommended, when appropriate and feasible.


Persistent trigeminal artery variant terminating in the posterior inferior cerebellar artery: a case report.
Persistent trigeminal artery (PTA) is a rare cerebrovascular variation of remnant fetal carotid-vertebrobasilar anastomoses. The PTA variant terminates in the cerebellar artery with no direct connection to the basilar artery. We present a rare case of a PTA variant that terminated directly into the ipsilateral posterior inferior cerebellar artery.


Hyperphagia resulting from gut denervation in the sea slug, Pleurobranchaea.
Previous research suggests that gut distension by ingested bulk plays an important role in the regulation of food intake in gastropod molluscs. The present study tested whether the bilateral stomatogastric nerves which innervate the esophagus and crop in Pleurobranchaea form a neural pathway carrying information about gut distension to the central nervous system. The posterior branches of the paired stomatogastric nerves were surgically exposed and sectioned in seven experimental animals while the nerves were simply exposed and not sectioned in seven sham-operated control animals. In three, subsequent, daily feeding sessions, the experimental subjects consumed a greater amount of food in terms of percentage of body weight than the control subjects. The experimental animals also gained a greater percentage of body weight and later were found to contain much more food within their guts. The results support the hypothesis that stretch receptors which innervate the gut and which have axons in the stomatogastric nerves form an important negative feedback pathway for the control of feeding in the sea slug.


Remote sensing methods for biomass estimation of green algae attached to nursery-nets and raft rope.
Accurate estimation of the biomass of raft-attached green algae is important for predicting the scale of green-tides in the Yellow Sea, China. In this study, two different biomass estimation methods are proposed: green algae attached to nursery-net (GAAN) and green algae attached to rope (GAAR). The GAAN method involves the use of images obtained using an unmanned aerial vehicle (UAV), high-resolution satellite images, and data from a statistical yearbook. The GAAR method uses high-resolution satellite images and data from a field sample survey. The results showed that the biomass of GAAN and GAAR in the Subei Shoal during 2017 was 8868 tons and 2974 tons respectively. A longer-term study of the biomass of GAAN and GAAR could provide quantitative information for the earnings forecasts of Porphyra yezoensis and for green-tide prevention.


Intersurgeon Variability of Minimal Clinically Important Difference for Worsening Achievement Rates After Total Joint Arthroplasty.
Using the Patient-Reported Outcome Measurement Information System, we sought to evaluate surgeon performance variability via minimal clinically important difference for worsening (MCID-W) achievement rates in primary and revision total knee and hip arthroplasty. This retrospective study analyzed 3,496 primary total hip arthroplasty (THA), 4,622 primary total knee arthroplasty (TKA), 592 revision THA, and 569 revision TKA patients. Patient factors collected included demographics, comorbidities, and Patient-Reported Outcome Measurement Information System physical function short form 10a scores. Surgeon factors collected included caseload, years of experience, and fellowship training. The MCID-W rate was calculated as the percent of patients in each surgeon's cohort who achieved MCID-W. Distribution was presented via a histogram with associated average, standard deviation, range, and interquartile range (IQR). Linear regressions were performed to evaluate the potential correlation between surgeon- and patient-level factors with MCID-W rate. The average MCID-W rates of the surgeons represented in the primary THA and TKA cohorts were 12.7 ± 9.2% (range, 0 to 35.3%; IQR, 6.7 to 15.5%) and 18.0 ± 8.2% (range, 0 to 36%; IQR, 14.3 to 22.0%). The average MCID-W rates among the revision THA and TKA surgeons were 36.0 ± 22.2% (range, 9.1 to 90%; IQR, 25.0 to 41.4%) and 21.2 ± 7.7% (range, 8.1 to 37.0%; IQR, 16.6 to 25.4%). Strong correlations were not found between patient- or surgeon-level factors and MCID-W rate of the surgeon. We demonstrated variance in MCID-W achievement rates across surgeons in both primary and revision joint arthroplasty, independent of patient- or surgeon-level factors.


Laparoscopic antireflux surgery improves esophageal body motility in patients with severe reflux esophagitis.
This study was designed to clarify whether laparoscopic antireflux surgery (LARS) improves the esophageal body motility (EBM) in patients with reflux esophagitis. Thirty-five patients with gastroesophageal reflux disease (GERD) scheduled to undergo LARS were divided into a mild esophagitis group (ME; n = 18, Grade O:A:B = 7:10:1) and a severe esophagitis group (SE; n = 17, Grade C:D = 13:4), according to the Los Angeles classification of reflux esophagitis. The types of fundoplication (Nissen/Toupet) were 6/12 in the ME group and 4/13 in the SE group. Esophageal pH monitoring and manometry were performed before and 1 year after surgery. The fraction time of a pH below 4 significantly decreased after surgery in both groups. The LES pressures did not change significantly after surgery in the ME group, but significantly increased in the SE group. The peristaltic amplitudes 18 and 13 cm above the LES did not change significantly after surgery in either group. The peristaltic amplitudes 8 and 3 cm above the LES did not change significantly after surgery in the ME group, but significantly increased after surgery in the SE group. The preoperative EBM was not improved by LARS in patients with GERD and mild mucosal breaks in the esophagus, but the preoperative middle to distal EBM was improved by LARS in patients with GERD and severe mucosal breaks.


Effect of low density lipoprotein and high density lipoprotein on sodium dodecyl sulphate precipitation of very low density lipoprotein from human serum.
In the presence of low density lipoprotein, the sodium sodecyl sulphate(SDS)-very low density lipoprotein(VLDL) complex sedimented, while in the presence of high density lipoprotein the complex floated. This SDS-VLDL aggregate floats at serum triglyceride to cholesterol ratio of 0.7-0.9 and sediments at a ratio of 0.2-0.5.


Functional Brain Anatomy.
Knowledge of functional neuroanatomy is essential to design the most appropriate clinical functional MR imaging (fMR imaging) paradigms and to properly interpret fMR imaging study results. The correlation between neuroanatomy and brain function is also useful in general radiologic practice, as it improves the radiologist's ability to read routine brain examinations. Functional MR imaging is used primarily to determine the areas involved in functioning of movements, speech, and vision. Preoperative fMR imaging findings also play a key role in the neurosurgeon's decision to perform a biopsy, a subtotal resection, or a maximal resection using awake craniotomy.


Drivers of dynamic evolution in provincial production water usage: perspective of regional relevance.
With the advancement of industrialization and urbanization, the issue of water shortage has become a bottleneck for China's economic development. Based on the structural decomposition analysis and multi-regional input-output tables of China in 2002 and 2012, this paper explores the drivers of the change in China's production water usage from the regional relevance perspective. Results show a significant increase in China's production water usage during the study period. The relationship between production water usage and per capita GDP shows an inverted U-shaped curve, and the economic scale by provinces has been improved, while the trend of production water usage differs. There are rapid increases in production water usage in economically developing provinces, while it is falling sharply in developed provinces. The crucial factors promoting its growth are changes in consumption level, population scale, and regional economic patterns. The technical effect is the most important factor in curbing the growth, followed by effects of final demand sectoral and distribution structure. The provinces and sectors with more production water usage shows higher technical and final demand effects. Therefore, it is necessary to promote water-saving activities, enhance the water-saving technical effect, and optimize final demand structure to promote economic growth with low-water usage.


Corrigendum: Ultra-small molybdenum-based nanodots as an antioxidant platform for effective treatment of periodontal disease.
[This corrects the article DOI: 10.3389/fbioe.2022.1042010.].


Cervical radicular pain caused by herpes simplex virus-type 1 infection: a case report.
A case of a 16-year-old with herpes simplex virus type-1 infection with radicular arm pain is reported. The clinical implications of the case are discussed.


Methylenetetrahydrofolate reductase 677 C-T and homocysteine levels in Turkish patients with pseudoexfoliation.
The 677 C-T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with hyperhomocysteinaemia. This study aimed to investigate the frequency of MTHFR 677 C-T polymorphism and homocysteine (Hcy) levels in Turkish patients with pseudoexfoliation (PEX). This prospective study consisted of 60 patients with PEX glaucoma, 16 with PEX syndrome and 34 controls. All patients and control subjects were of Turkish origin. All participants underwent a complete ophthalmic examination. Plasma Hcy levels were measured using fluorescence polarization immunoassay (Abbott Diagnostics). Hyperhomocysteinaemia was defined as a plasma Hcy level above 14 micromol/L. MTHFR 677 C-T was genotyped by real-time polymerase chain reaction (Roche Diagnostics). There was no statistically significant difference in patient and control groups for the age and sex (P > 0.05). The mean plasma Hcy levels were 15.76, 14.98 and 17.43 micromol/L in patients with PEX glaucoma, with PEX syndrome and controls, respectively. No significant differences between Hcy levels among the three groups (P > 0.05) were found. MTHFR 677 polymorphism did not show significant differences between the total patients with PEX (PEX glaucoma + PEX syndrome) and control subjects (CC: 51.3%n = 39, CT: 40.8%n = 31, TT: 7.9%n = 6 for patients with PEX; CC: 52.9%n = 18, CT: 35.3:%n = 12, TT: 11.8%n = 4 for controls) (P > 0.05). Frequency of T allele was 28.28% and 29.41% for the total patients with PEX and controls, respectively. In Turkish patients with PEX, the authors could not find any association between Hcy levels, MTHFR 677 C-T polymorphism, and the disease.


Effects of physical exercise on the cognition of older adults with frailty syndrome: A systematic review and meta-analysis of randomized trials.
To analyze the effects of physical exercise on the cognition of community-dwelling older adults with frailty syndrome, through randomized clinical trials. Articles published until March 2020 were searched in the databases Science Direct, Scopus, Web of Science, PubMed, Lilacs, Cochrane, IEEE, EMBASE, and SciELO. Search terms included frailty, aged, exercise, rehabilitation, and cognition. For the Portuguese language, equivalent terms were used. Only randomized clinical trials that used physical exercise as an intervention method in community-dwelling older adults (≥ 60y.) with frailty syndrome, and which performed cognitive assessments before and after the intervention were included. Two authors performed data extraction using predefined data fields. The risk of bias of the six included studies was assessed using the PEDro scale. In total, 4501 studies were found. After the selection process, 6 studies were included in the systematic review and 4 studies in the meta-analysis, all with a low risk of bias. The studies included 655 community-dwelling older adults with frailty syndrome. The types of intervention varied, with multicomponent physical exercise being the most frequent. The cognitive assessments were diverse, and the Mini-mental State Examination, Trail Making Test forms A and B, and Digit Span test were the most frequently applied. A meta-analysis was performed with Global Cognition and Trail Making Test forms A and B. The data from the meta-analysis showed that physical exercise improves Global Cognition (Mean Difference = 2.26; 95% CI, 0.42 - 4.09; P = 0.02) and mental flexibility (Trail Making Test B) (Mean Difference = -30.45; 95% CI; - 47.72 - -13.19; P = 0.0005). Interventions with physical exercise promote benefits in global cognition and mental flexibility of older adults with frailty syndrome.


A DNA-intercalating compound derived from 7H-pyridocarbazole: the structure of 10-methoxy-2-methyl-7H-pyrido[4,3-c]carbazolium iodide.
C17H15N2O+.I-, Mr = 390.22, monoclinic, P21/c, a = 10.017 (2), b = 8.123 (5), c = 19.074 (4) A, beta = 95.86 (2) degrees, V = 1544 (2) A3, Z = 4, D chi = 1.67 g cm-3, mu = 2.10 cm-1, lambda (Mo K alpha) = 0.7107 A, F(000) = 768, R = 0.04 for 1236 unique reflections measured at 295 K. Dimensions of the ring system are similar to those found in 6H-pyridocarbazole analogues (ellipticine derivatives). The iodine ion and pyridocarbazolium system are linked by a hydrogen bond. The planar 7H-pyridocarbazole cations form stacks approximately parallel to b. Interactions between stacks occur by weak van der Waals forces.


Preventive effects of ME3738 on hepatic fibrosis induced by bile duct ligation in rats.
The aim of this study was to examine the preventive effects of ME3738 on hepatic fibrosis induced by bile duct ligation (BDL) in rats. ME3738 (20 mg/day) was administered orally for 21 days immediately after BDL. Fibrosis was assessed by measuring hepatic hydroxyproline (Hyp) content. Activated hepatic stellate cells (HSCs) were assessed by alpha-smooth muscle actin (alpha-SMA) immunostaining. Hepatic thiobarbituric acid-reactive substance (TBARS), 4-hydroxy-2-nonenal (4-HNE) and 8-hydroxy-2-deoxyguanosine (8-OHdG) immunostaining were used to analyze oxidative stress. The gene expressions of collagen-I, transforming growth factor-beta1 (TGF-beta1), tissue inhibitor of metalloproteinases-1 (TIMP-1), interleukin-6 (IL-6) and heme oxygenase-1 (HO-1) in the liver were examined by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Hepatic Hyp content and the area of hepatic fibrosis in BDL rats treated with ME3738 were reduced by 24% and 39% compared with non-treated BDL rats (hepatic Hyp, 9.40 +/- 2.85 vs. 12.39 +/- 3.91 mg/liver; P = 0.036; area of hepatic fibrosis, 13.1 +/- 3.8 vs. 21.5 +/- 10.9; P = 0.045). Furthermore, alpha-SMA-positive cells were significantly reduced by 40% (22.3 +/- 14.8 vs. 37.6 +/- 14.2; P = 0.011), collagen-I mRNA by 83% (6.5 +/- 2.2 vs. 38.3 +/- 9.1; P = 0.002), HO-1 mRNA by 58% (4.13 +/- 1.22 vs. 9.73 +/- 1.80; P = 0.018) and hepatic HO-1 content by 26% (2.13 +/- 0.80 vs. 2.87 +/- 0.19; P = 0.01) following ME3738 treatment. The hepatic expression of TBARS, 4-HNE, 8-OHdG and mRNA levels of TGF-beta1, TIMP-1 and IL-6 in the liver were unchanged by ME3738 treatment. Oral ME3738 administration may prevent the progression of hepatic fibrosis in BDL rats through suppression of the activation and collagen synthesis of HSC and, in part, oxidative stress. ME3738 has potential as a therapeutic drug for cholestatic liver fibrosis.


Bone mass measurement using a xenon-filled multiwire proportional counter as detector.
The application of a xenon-filled multiwire proportional counter to photon absorptiometry of bone mass is described. Performance characteristics obtained from a prototype system are discussed and future developments indicated.


Comparing the effectiveness of long-term use of daily and weekly glucagon-like peptide-1 receptor agonists treatments in patients with nonalcoholic fatty liver disease and type 2 diabetes mellitus: a network meta-analysis.
In the present network meta-analysis (NMA), we aimed to compare the effectiveness of daily and weekly treatment with glucagon-like peptide-1 receptor agonists for patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). We used Stata 17.0 for the NMA. Eligible Randomized controlled trials (RCTs) were searched in PubMed, Cochrane, and Embase databases until December 2022. Two researchers independently screened the available studies. The Cochrane Risk of Bias tool was used to assess the risk of bias in the included studies. We used GRADEprofiler (version3.6) to analyze the evidence certainty. Primary outcomes such as liver fat content (LFC), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels, as well as secondary outcomes such as γ-glutamyltransferase (γGGT) and body weight, were evaluated. Then, each intervention was ranked by the surface under the cumulative ranking curve (SUCRA). As a supplement, we drew forest plots of subgroup using RevMan (version 5.4). Fourteen RCTs involving 1666 participants were included in the present study. The NMA results showed that exenatide (bid) was the best treatment for improving LFC compared with other agents, liraglutide, dulaglutide, semaglutide (qw) and placebo), and the SUCRA values were 66.8%. Among five interventions (except exenatide (bid) and semaglutide (qw)) evaluated for AST outcome, and six interventions (except exenatide (bid)) evaluated for ALT outcome, semaglutide (qd) was the most effective drug (SUCRA (AST) = 100%, SUCRA (ALT) = 95.6%). The result of LFC in daily group was MD = -3.66, 95% CI [-5.56, -1.76] and in weekly GLP-1RAs group, it was MD = -3.51, 95% CI [-4, -3.02]. As to AST and ALT, the results in daily group versus weekly group were AST: MD = -7.45, 95% CI [-14.57, -0.32] versus MD= -0.58, 95% CI [-3.18, 2.01] and ALT: MD = -11.12, 95% CI [-24.18, 1.95] versus MD = -5.62, 95% CI [-15.25, 4]. The quality of evidence was assessed as moderate or low. The daily GLP-1RAs may be more effective in primary outcomes. And the daily semaglutide may be the most effective treatment for NAFLD and T2DM among the six interventions.


Are Australian men with psychosis spending more time homeless?
The objective of this study was to determine if homeless men with psychosis using emergency accommodation services are spending more time homeless. A 12-month accommodation history was collected from all men with psychosis referred to mental health services using two emergency accommodation services in inner Melbourne over a 5-year period. Of the 241 men referred with psychosis, 200 (81%) were able to provide a full accommodation history. In 2001 the mean total days spent in crisis accommodation was 27.0 days and in 2005 the mean number of days was 60.9. Over the 5 years, increasing time was spent homeless in the 12 months prior to assessment, most commonly in emergency accommodations. Australian men with psychosis using emergency accommodation are spending an increasing amount of time homeless.


Ovarian suppression with leuprolide acetate: comparison of luteal, follicular, and flare-up administration in controlled ovarian hyperstimulation for oocyte retrieval.
Adjunct use of leuprolide (LA) in patients undergoing controlled ovarian hyperstimulation with human menopausal gonadotropins (hMG) was evaluated by three protocols: Group F (n = 24) began LA on day 2 of the cycle and Group L (n = 38) began LA on day 23 of the cycle until ovarian suppression, at which time hMG was added. Group FL (n = 17) began LA on day 1 and hMG on day 3. Compared to FL, more ova were collected, more ova fertilized, and more pregnancies resulted per initiated cycle in groups achieving suppression before hMG stimulation. Fewer days were necessary to attain suppression for L vs F. After achieving suppression, patients were maintained on either 0.5 mg LA or 0.25 mg LA daily during hMG coadministration with similar results. Lower maintenance doses of LA during hMG did not decrease the amount of hMG needed but retained the benefits of LA. We recommend luteal initiation of LA to achieve suppression before hMG.


A new polymorphic Hemilophini Thomson, 1868 from the Tumuc Humac inselbergs, French Guiana (Coleoptera, Cerambycidae, Lamiinae).
A new Zeale Pascoe, 1866, Zeale granvillei sp. nov., is described from open areas at Mitaraka Mounts, French Guiana. The key to the species of Zeale is updated and the different forms of the new species are illustrated. A list of the material from Muséum national d'Histoire naturelle (Paris) in this genus is provided. Some aspects of its behavior are given, including its possible host plant, Ichtyothere granvillei H. Robinson (Asteraceae).


Biospecific interaction analysis using biosensor technology.
Fundamental information that enhances our understanding of biospecific interactions can be obtained using a new analytical system based on biosensor technology. The functional characteristics of biospecific interaction, such as kinetics, affinity and binding position, are examined by label-free analysis of proteins in free solution binding to an immobilized ligand at a hydrophilic sensor surface.


Ca functionalized N-doped porphyrin-like porous C60 as an efficient material for storage of molecular hydrogen.
It is widely known that decorating metal atoms on defective carbon nanomaterials is a useful approach to enhance the hydrogen storage capacity of these systems. Herein, density functional theory calculations are used to determine the H2 storage capacity of Ca functionalized nitrogen incorporated defective C60 fullerenes (Ca6C24N24). The strong binding, uniform distribution, and significant positive charges of the Ca atoms make this system effective material for storage of H2. Ca6C24N24 may adsorb a maximum of 6 hydrogen molecules per Ca atom, yielding a total gravimetric density of 7.7 wt %.


Comprehensive genome-wide analysis of Glutathione S-transferase gene family in potato (Solanum tuberosum L.) and their expression profiling in various anatomical tissues and perturbation conditions.
Glutathione S-transferases (GSTs) are ubiquitous enzymes which play versatile functions including cellular detoxification and stress tolerance. In this study, a comprehensive genome-wide identification of GST gene family was carried out in potato (Solanum tuberosum L.). The result demonstrated the presence of at least 90 GST genes in potato which is greater than any other reported species. According to the phylogenetic analyses of Arabidopsis, rice and potato GST members, GSTs could be subdivided into ten different classes and each class is found to be highly conserved. The largest class of potato GST family is tau with 66 members, followed by phi and lambda. The chromosomal localization analysis revealed the highly uneven distribution of StGST genes across the potato genome. Transcript profiling of 55 StGST genes showed the tissue-specific expression for most of the members. Moreover, expression of StGST genes were mainly repressed in response to abiotic stresses, while largely induced in response to biotic and hormonal elicitations. Further analysis of StGST gene's promoter identified the presence of various stress responsive cis-regulatory elements. Moreover, one of the highly stress responsive StGST members, StGSTU46, showed strong affinity towards flurazole with lowest binding energy of -7.6kcal/mol that could be used as antidote to protect crop against herbicides. These findings will facilitate the further functional and evolutionary characterization of GST genes in potato.


Partial purification of Drosophila Kc cell RNA polymerase III transcription components. Evidence for shared 5 S RNA and tRNA gene factors.
Class III transcription components were fractionated from Drosophila Kc cells. By the use of successive DEAE-Sephadex and CM-Sepharose column chromatographies, two fractions were identified to contain distinct positive transcription components. The reconstitution of these two fractions and RNA polymerase III was essential for faithful in vitro transcription of cloned Drosophila tRNA and 5 S RNA genes. Further chromatography of one of these fractions using phosphocellulose and DEAE-cellulose did not separate additional components required for reconstitution of transcription. These fractions may contain generalized class III transcription factors, as suggested by the cofractionation of required tRNA and 5 S RNA transcription components. We present further evidence that tRNA and 5 S RNA genes share at least one common transcription component other than RNA polymerase III by the use of stable transcription complex formation and competition experiments.


Foamy virus transactivation and gene expression.
An overview of the pattern and mechanisms of spuma or foamy virus (FV) gene expression is presented. FVs are complex retroviruses with respect to their genetic outfit and the elements used to control and regulate expression of the viral genome. The increased insight into transcriptional and posttranscriptional mechanisms has revealed that the FVs are distinct, unconventional retroviruses clearly apart from the orthoretroviruses. Although less characterized than the orthoretroviruses, FVs have several unique features that are important for construction and assembly of FV-based vectors for targeted gene delivery and vaccination purposes. Some of these distinguishing features are directly related to the FV-specific mechanisms of gene expression and include (1) the presence of an internal, functional active second transcription unit for expression of the nonstructural genes, (2) the utilization of a subgenomic, spliced transcript for Pol protein expression, and (3) distinct but not yet understood mechanisms for the nuclear exit of defined transcripts and thus an additional level of posttranscriptional control of gene expression. Finally, the interactions of the viral transactivator not only with both viral promoters but also with regulatory elements controlling the expression of defined cellular genes are an important issue with respect to vector development and the apparent apathogenicity of FVs in their natural hosts.


Hollow Square RodLike Microtubes Composed of Anatase Nanocuboids with Coexposed {100}, {010}, and {001} Facets for Improved Photocatalytic Performance.
In this study, hollow square rodlike microtubes composed of anatase nanocuboids with coexposed {100}, {010}, and {001} facets were successfully synthesized via a mild hydrothermal treatment method in the presence of NH4F by using layered H2Ti3O7 ribbons as the precursor. The precursor H2Ti3O7 ribbons were prepared from H+/Na+ ion-exchanged Na2Ti3O7. The suspension solution of protonated H2Ti3O7 ribbons was adjusted to desired pH values (0.5-13.0) prior to hydrothermal treatment. The elongated direction of the microtubes is along the b axis, according to the profile of the H2Ti3O7 ribbons. The transformation from staggered [Ti3O7]2- sheets to hollow square rodlike microtubes contained the formation and recombination of the dispersed octahedral [Ti(OH)2(OH2)4]2+ monomers, the formation and growth of the initial anatase nuclei, and the reassembly of the anatase nanocuboids along the b-axis direction during the continuous hydrothermal process. The degradation rate of pH 0.5-TiO2 was the highest at 1.66 × 10-2 min-1, which was 1.3, 1.5, 2.0, 2.3, and 18.4 folds higher than that of pH 3.0-TiO2 (1.27 × 10-2 min-1), pH 7.0-TiO2 (1.11 × 10-2 min-1), pH 5.0-TiO2 (0.83 × 10-2 min-1), P25-TiO2 (0.73 × 10-2 min-1), and the blank sample (0.09 × 10-2 min-1), respectively. Compared with P25-TiO2 and the other anatase TiO2 samples, pH 0.5-TiO2 exhibited the best photocatalytic activity, which was mainly attributed to its larger proportion of {010} (or {100}) facets, smaller crystalline size, higher band gap, and larger specific surface area.


Benign osteoblastoma of the temporal bone: MRI.
We investigated a 27-year-old woman with a retroauricular tumour. MRI revealed a signal void on T1 and T2-weighted images, and irregular enhancement with gadolinium-DTPA. The underlying dura mater also enhanced. The tumour was resected completely, and histological examination showed a benign osteoblastoma.


How individuals with spinal cord injury in the United States access and assess information about experimental therapies and clinical trials: results of a clinical survey.
An internet-based survey. To determine how individuals with spinal cord injury (SCI) access information about experimental therapies and clinical trials. To understand which factors influence receipt of and perceived trustworthiness of that information. Two academic medical centers and an SCI organization. Demographic information frequencies and percentages were calculated then analyzed using chi-square tests for independence. Fisher's exact test of independence was used to assess significance for contingency tables with categories containing expected counts below five. Three hundred sixty four persons with SCI participated in the survey. Most felt confident in their ability to evaluate SCI-specific information from a variety of sources, though SCI organizations and the medical literature were deemed the most reliable. Information from SCI specialists was deemed more credible than that from non-SCI specialists, but only 53.6% of participants had access to them. Nearly all (89.0%) respondents who had sought information about experimental therapies had found it online, while 51.4% of those who had participated in a clinical trial had been contacted by a research team. Only 8.4% of participants felt their medical teams offered them sufficient information about experimental therapies and clinical trials. Wealthier and more educated respondents were more knowledgeable about health-related resources on the internet. Nearly all participants (96.9%) expressed interest in learning more about trials related to SCI. There is an information deficit among people with SCI pertaining to experimental therapies and clinical trials. It is exacerbated by lack of income, education, and access to SCI specialists.


Pan-cancer analysis of mRNA stability for decoding tumour post-transcriptional programs.
Measuring mRNA decay in tumours is a prohibitive challenge, limiting our ability to map the post-transcriptional programs of cancer. Here, using a statistical framework to decouple transcriptional and post-transcriptional effects in RNA-seq data, we uncover the mRNA stability changes that accompany tumour development and progression. Analysis of 7760 samples across 18 cancer types suggests that mRNA stability changes are ~30% as frequent as transcriptional events, highlighting their widespread role in shaping the tumour transcriptome. Dysregulation of programs associated with >80 RNA-binding proteins (RBPs) and microRNAs (miRNAs) drive these changes, including multi-cancer inactivation of RBFOX and miR-29 families. Phenotypic activation or inhibition of RBFOX1 highlights its role in calcium signaling dysregulation, while modulation of miR-29 shows its impact on extracellular matrix organization and stemness genes. Overall, our study underlines the integral role of mRNA stability in shaping the cancer transcriptome, and provides a resource for systematic interrogation of cancer-associated stability pathways.


Aberrant pre-receptor regulation of estrogen and progesterone action in endometrial cancer.
Endometrial cancer is related to estrogen stimulation not opposed by progesterone. We have examined expression of the pre-receptor regulatory enzymes aromatase, 17beta-hydroxysteroid dehydrogenases (17beta-HSDs), 20alpha-hydroxysteroid dehydrogenases (20alpha-HSDs), sulfatase and sulfotransferase, and estrogen (ERs) and progesterone (PRs) receptors in samples of endometrial cancer and adjacent normal endometrium. No significant gene up-regulation was seen, although aromatase, AKR1C3, a 17beta-HSD and 20alpha-HSD, and AKR1C1, the major 20alpha-HSD, were up-regulated in 50% of samples. Significant down-regulation was seen for 17beta-HSD types 1 and 7, sulfotransferase, ERalpha, ERbeta, PR-AB. Western blotting revealed higher levels of AKR1C3 and PR-B and lower levels of ERalpha in cancerous endometrium, and immunohistochemistry confirmed expression of AKR1C3, PR-B and ERalpha at the cellular level. Up-regulation of aromatase in concert with AKR1C3 can lead to increased levels of estradiol, which acts via ERalpha. Up-regulation of AKR1C1 and AKR1C3 can result in lower levels of the protective progesterone, which acts mainly via PR-B.


Immune mechanisms underlying the beneficial effects of autologous hematopoietic stem cell transplantation in multiple sclerosis.
A recent phase I/II clinical trial drew serious attention to the therapeutic potential of autologous hematopoietic stem cell transplantation (AHSCT) in multiple sclerosis. However, questions were raised as to whether these beneficial effects should be attributed to the newly reconstituted immune system per se, or to the lymphoablative conditioning regimen-induced immunosuppression, given that T-cell depleting combinational drug therapies were used in the study. We discuss here the possibility that both AHSCT and T-cell depleting therapies may re-program alternatively the immune system, and why transplantation of CD34+ hematopoietic stem cells may offer AHSCT a possible advantage regarding long-term remission.


Poor quality of life in patients with and without frailty: co-prevalence and prognostic implications in patients undergoing percutaneous coronary interventions and cardiac catheterization.
We hypothesize that poor quality of life (QOL) is highly prevalent in frail older adults and is associated with worse prognosis. Predismissal standardized tests for frailty and QOL were prospectively administered to patients included in two cohorts. In Cohort 1, 629 patients ≥65 years who underwent percutaneous coronary intervention (PCI) from 2005 to 2008, frailty (Fried criteria), and QOL [SF-36 and Seattle Angina Questionnaires (SAQ)] were ascertained. Cohort 2 included 921 patients ≥55 years who underwent cardiac catheterization (535 had PCI) from 2014 to 2018 and frailty was determined by Rockwood criteria and QOL by single-item, self-reported health questionnaire. In Cohort 1, 19% were frail and 20% patients in Cohort 2 were frail with a frailty index >0.30. The median SAQ for physical limitation (58.9 vs. 82.2, P < 0.001), physical (29.5 vs. 43.9, P < 0.001), and mental (49.2 vs. 57.4, P < 0.001) component scores of SF-36 in Cohort 1 were lower and self-rating of fair/poor health (56% vs 18%, P < 0.001) in Cohort 2 was significantly higher in frail patients. As compared to patients without frailty, frail patients were five times more likely (59% vs. 11%, P < 0.001) in Cohort 1 and seven times more likely (56% vs. 8%) in Cohort 2 to be classified with poor QOL. Age- and gender-adjusted 3-year all-cause death and death or myocardial infarction (MI) was significantly higher for patients undergoing PCI with frailty; [hazard ratio (95% confidence interval) death, 4.20 (2.63-6.68, P < 0.001) and death or MI hazard ratio (HR) 2.72 (1.91-3.87, P < 0.001)] and with poor QOL [HR death 2.47 (1.59-3.84, P < 0.001)] and death or MI 1.61 (1.16-2.24, P < 0.001). There was no significant interaction between frailty and QOL (P = 0.64) and only modest attenuation was observed when considered together indicating their independent prognostic influence. In elderly patients undergoing cardiac catheterization or PCI, poor QOL is seen more frequently in frail patients. Both frailty and poor QOL had significant and independent association with long-term survival.


Brain-derived extracellular vesicles mediate traumatic brain injury associated multi-organ damage.
Traumatic brain injury (TBI) can negatively impact systemic organs, which can lead to more death and disability. However, the mechanism underlying the effect of TBI on systemic organs remains unclear. In previous work, we found that brain-derived extracellular vesicles (BDEVs) released from the injured brain can induce systemic coagulation with a widespread fibrin deposition in the microvasculature of the lungs, kidney, and heart in a mouse model of TBI. In this study, we investigated whether BDEVs can induce heart, lung, liver, and kidney injury in TBI mice. The results of pathological staining and related biomarkers indicated that BDEVs can induce histological damage and systematic dysfunction. In vivo imaging system demonstrated that BDEVs can gather in systemic organs. We also found that BDEVs could induce cell apoptosis in the lung, liver, heart, and kidney. Furthermore, we discovered that BDEVs could cause multi-organ endothelial cell damage. Finally, this secondary multi-organ damage could be relieved by removing circulating BDEVs. Our research provides a novel perspective and potential mechanism of TBI-associated multi-organ damage.


Caffeine and endurance performance.
The belief among athletes that caffeine is an ergogenic aid is common, and several governing bodies of sport have barred use of the drug during competition. At the cellular level, caffeine has been implicated to affect the translocation of calcium in muscle, promote an increase in cellular levels of cyclic AMP and cause a blockade of adenosine receptors in the central nervous system. The general systemic effect of caffeine is to cause central nervous system arousal, mobilisation of free fatty acids and other metabolites, and possibly enhance the contractile status of muscle. At present, the scientific community remains divided as to whether caffeine ingestion will indeed produce an ergogenic effect upon sport performance. Some evidence suggests that caffeine may improve performance in events relying upon strength and power; however, the lack of in vivo research in humans makes it difficult to form firm conclusions. In addition, reports concerning caffeine's effect on VO2max and performance during incremental exercise are not in agreement. On the other hand, recent studies suggest that caffeine might indeed have ergogenic potential in endurance events (e.g. marathon running). It is hypothesised that the mechanism behind these findings is related to the increased availability of free fatty acids for muscle metabolism which has a glycogen-sparing effect.


The secretome of Pichia pastoris in fed-batch cultivations is largely independent of the carbon source but changes quantitatively over cultivation time.
The quantitative changes of the secretome of recombinant Pichia pastoris (Komagataella phaffii) CBS7435 over the time-course of methanol- or glucose-limited fed-batch cultures were investigated by LC-ESI-MS/MS to define the carbon source-specific secretomes under controlled bioreactor conditions. In both set-ups, no indication for elevated cell lysis was found. The quantitative data revealed that intact and viable P. pastoris cells secrete only a low number of endogenous proteins (in total 51), even during high cell density cultivation. Interestingly, no marked differences in the functional composition of the P. pastoris secretome between methanol- and glucose-grown cultures were observed with only few proteins being specifically affected by the carbon source. The 'core secretome' of 22 proteins present in all analysed carbon sources (glycerol, glucose and methanol) consists mainly of cell wall proteins. The quantitative analysis additionally revealed that most secretome proteins were already present after the batch phase, and depletion rather than accumulation occurred during the fed-batch processes. Among the changes over cultivation time, the depletion of both the extracellularly detected chaperones and the only two identified proteases (Pep4 and Yps1-1) during the methanol- or glucose-feed phase appear as most prominent.


Perturbance analysis of nuclear determination in Tetrahymena I: background, rationale, and illustrative example, employing temperature responses.
A model based on comparative considerations, is presented for the nuclear determination of mating type in Tetrahymena thermophila. The model proposes a system of three binary control elements, each capable of stable persistence in one of two states. A general method is proposed for evaluating the model and for assigning particular mating types to particular compound states. Preliminary assignments of mating types are made from the responses of nuclei to temperature differentials.


Occipitoparietal benign osteoblastoma: should entire lesion be resected when magnetic resonance images reveal wide abnormal signal intensity in surrounding bone marrow?
Benign osteoblastoma is an uncommon primary bone tumor that usually affects long bones and the vertebral column. Its occurrence in the calvarium is rare. Despite the characteristically benign nomenclature of osteoblastoma, it sometimes recurs with the possibility of transforming into a malignant form after an incomplete resection. Therefore, radical resection is recommended whenever possible. However, it has not been clarified whether the adjacent bones should also be completely resected when magnetic resonance (MR) images reveal abnormal signal intensity in the bone marrow. Presented in this case report is a 12-year-old boy with occipital tenderness associated with occipitoparietal bone tumor. Neuroradiological studies demonstrated a solid tumor located in the occipital bone extending over the right parietal bone. Magnetic resonance images further revealed abnormal signal intensity in the bone marrow of the entire occipital and bilateral parietal bones. Macroscopically, the calvarial bone adjacent to the solid tumor appeared to be reddish, but it was not covering the entire area, contradicting the abnormal intensity found on the preoperative MR images. The resected area was determined according to macroscopic findings, and bones with normal color tone were preserved. Because histological examination did not clearly indicate tumor invasion at the margin of the resection site, no additional therapy was given. Although MR images revealed abnormal intensity in the bone marrow of the surgical margin immediately after the operation, the intensity had been normalized by degrees and there was no evidence of recurrence during a follow-up period of 34 months. This may suggest that bone marrow lesion showing abnormal intensity was edema rather than tumor invasion. The authors conclude that total resection, including a bone marrow lesion, is not always necessary for benign osteoblastoma. Macroscopic findings that show an abnormal color tone of the cortex could be a good indicator in revealing tumor activity invading bone marrow.