Congenital disorder of glycosylation type 1a in a macrosomic 16-month-old boy with an atypical phenotype and homozygosity of the N216I mutation.
We report on a 16-month-old boy with congenital disorder of glycosylation type 1a (CDG-1a; OMIM 212065) showing an atypical phenotype. Whereas failure to thrive is known to be a prominent feature in this condition, our patient developed postnatal macrosomia with increase of weight, length and occipitofrontal circumference (OFC) above the 95th percentile within his 1st year of life. Thereafter, weight and length were close to the 90th and OFC at the 50th percentiles. In contrast to other CDG-1a patients, the child did not have abnormal fat pads or inverted nipples; but unusual eyebrows were present. CDG-1a was confirmed by isoelectric focusing of serum transferrin and measurement of phosphomannomutase activity in leucocytes and cultured fibroblasts (residual activity <5% of controls). Mutation analysis of the phosphomannomutase 2 gene (PMM2) revealed homozygosity for a 647A>T (N216I) mutation in our patient and heterozygosity in his consanguineous parents. This is the first report of macrosomia and of homozygosity for the 647A>T (N216I) mutation in a patient with congenital disorder of glycosylation type 1a which may allow further phenotype/genotype comparisons.


Osteogenesis imperfecta and rheumatoid arthritis: connective issues.
The coexistence of osteogenesis imperfecta and inflammatory arthritis has been very rarely described. Nevertheless, systemic inflammation has been found in osteogenesis imperfecta. The COL1A1 mutations may affect collagen synthesis as well as post-translational modifications, extracellular matrix interactions, and receptor-mediated signaling. Major collagen binding ligands forming the interactome, such as cytokines, cell adhesion molecules, matrix metalloproteinases, proteoglycans, and other molecules, are autoimmunity targets involved in rheumatoid arthritis pathogenesis. Cross-talk between bone remodeling and inflammatory pathways involving osteoclasts is important in osteogenesis imperfecta and rheumatoid arthritis. In osteogenesis imperfecta, the structural abnormalities and repeated traumatism, including fractures, could activate locally the innate immunity and trigger arthritis, similar to post-traumatic arthritis. Currently, the therapy of osteogenesis imperfecta is a suboptimally met need. Understanding the complex putative pathogenic links between osteogenesis imperfecta and inflammatory arthritis could hopefully lead to new therapeutic targets. Raising awareness regarding a possible association between osteogenesis imperfecta and arthritis could help improve the quality of life in these patients.


Characteristics of neurogenic voiding dysfunction in cerebellar stroke: a cross-sectional, retrospective video urodynamic study.
Voiding dysfunctions are common neurological complications after a stroke, yet there are few urodynamic studies of patients with cerebellar stroke. We report the video urodynamic findings of 15 patients with cerebellar stroke, including eight patients with ischemic and seven with hemorrhagic stroke. Their mean age was 75 ± 13.4 years and the mean interval from stroke to video urodynamic study was 11.2 ± 17.9 months. At urodynamic study, four (50 %) patients with ischemic stroke had urinary incontinence as did two (28 %) patients with hemorrhagic stroke. Detrusor overactivity (DO) was found in eight (53 %) patients, dyssynergic urethral sphincter in six (40 %), and nonrelaxing urethral sphincter in seven (47 %). DO occurred in six (75 %) of patients with ischemic stroke and in two (28.6 %) of patients with hemorrhagic stroke (p = 0.072). While DO was not found in five of the 15 patients within 2 months after the stroke, it was more frequently detected in eight (80 %) of the 10 remaining patients 2 or more months after stroke (p = 0.007). Four (80 %) of the five stroke patients had nonrelaxing sphincter and urinary retention within 2 months after stroke. Two or more months after their strokes, coordinated sphincter function was noted in two (20 %) patients and dyssynergic sphincter was found in six (60 %); two (20 %) remained with nonrelaxing sphincter. Thus, lower urinary tract dysfunction caused by cerebellar stroke may change with time. Knowledge of video urodynamic findings should help us better manage voiding dysfunction in patients with cerebellar stroke.


Multi-Functional Bio-HJzyme: Revolutionizing Diabetic Skin Regeneration with its Glucose-Unlocked Sterilization and Programmed Anti-Inflammatory Effects.
Antibacterial dynamic therapy (ADT) triggered by reactive oxygen species (ROS) is promising for diabetic infectious disease treatment. However, the limited local O2 /H2 O2 production and post-treatment inflammation remain long-standing issues. To address these challenges, a novel H2 -evolving bio-heterojunction enzyme (Bio-HJzyme) consisting of graphite-phase carbon nitride/copper sulfide (CN/Cu2-x S) heterojunction and glucose oxidase (GOx) is created. The Bio-HJzyme offers glutathione peroxidase (GPx), peroxidase (POD), and catalase (CAT) mimetic activities; provides anti-pathogen properties via programmed light activation; and effectively promotes diabetic wound healing. Specifically, its GPx-mimetic activity and the presence of GOx significantly enhance the yield of H2 O2 , which can be catalyzed through POD-mimetic activity to produce highly germicidal •OH. The H2 O2 can also be catalyzed to H2 O and O2 , assisted by the CAT-mimetic activity. The catalyzed products can then be catalyzed into germicidal •OH and •O2 - under NIR light irradiation, giving enhanced ADT. Further, CN can split water to form H2 under solar light, which dramatically suppresses the inflammation caused by excessive ROS. In vivo evaluation confirms that Bio-HJzyme promotes the regeneration of diabetic infectious skin through killing bacteria, enhancing angiogenesis, promoting wound bed epithelialization, and reinforcing anti-inflammatory responses; hence, providing a revolutionary approach for diabetic wounds healing.


Production of 10-hydroxystearic acid from oleic acid by whole cells of recombinant Escherichia coli containing oleate hydratase from Stenotrophomonas maltophilia.
A putative fatty acid hydratase from Stenotrophomonas maltophilia was cloned and expressed in Escherichia coli. The recombinant enzyme showed the highest hydration activity for oleic acid among the fatty acids tested, indicating that the enzyme is an oleate hydratase. The optimal conditions for the production of 10-hydroxystearic acid from oleic acid using whole cells of recombinant E. coli containing the oleate hydratase were pH 6.5, 35°C, 0.05% (w/v) Tween 40, 10 g l(-1) cells, and 50 g l(-1) oleic acid. Under these conditions, whole recombinant cells produced 49 g l(-1) 10-hydroxystearic acid for 4 h, with a conversion yield of 98% (w/w), a volumetric productivity of 12.3 g l(-1) h(-1), and a specific productivity of 1.23 g g-cells(-1) h(-1), which were 18%, 2.5-, and 2.5-fold higher than those of whole wild-type S. maltophilia cells, respectively. This is the first report of 10-hydroxystearic acid production using recombinant cells and the concentration and productivity are the highest reported thus far among cells.


Neuropathic pain after brachial plexus avulsion--central and peripheral mechanisms.
The pain that commonly occurs after brachial plexus avulsion poses an additional burden on the quality of life of patients already impaired by motor, sensory and autonomic deficits. Evidence-based treatments for the pain associated with brachial plexus avulsion are scarce, thus frequently leaving the condition refractory to treatment with the standard methods used to manage neuropathic pain. Unfortunately, little is known about the pathophysiology of brachial plexus avulsion. Available evidence indicates that besides primary nerve root injury, central lesions related to the abrupt disconnection of nerve roots from the spinal cord may play an important role in the genesis of neuropathic pain in these patients and may explain in part its refractoriness to treatment. The understanding of both central and peripheral mechanisms that contribute to the development of pain is of major importance in order to propose more effective treatments for brachial plexus avulsion-related pain. This review focuses on the current understanding about the occurrence of neuropathic pain in these patients and the role played by peripheral and central mechanisms that provides insights into its treatment. Pain after brachial plexus avulsion involves both peripheral and central components; thereby it is characterized as a mixed (central and peripheral) neuropathic pain syndrome.


Association of low meal frequency with decreased in vivo Alzheimer's pathology.
Little is known about the association between meal frequency and Alzheimer's disease (AD) in humans. We tested the hypothesis that low meal frequency (LMF) is associated with reduced in vivo AD pathology in human brain, and additionally investigated the mediation of serum ghrelin, a hunger-related hormone, for the association. A total of 411 non-demented older adults were systematically interviewed to identify their dietary patterns including meal frequency and underwent multi-modal neuroimaging for cerebral beta-amyloid (Aβ) and tau deposition, glucose metabolism, and cerebrovascular injury. LMF (less than three meals a day) was significantly associated with lower Aβ deposition compared to high meal frequency (HMF). In addition, both LMF and reduced Aβ deposition were significantly related to elevated serum ghrelin. Our findings suggest that LMF may be related to the lower risk of AD through reduced brain amyloid deposition. Additionally, ghrelin appears mediate the association between LMF and lower amyloid deposition.


Examination of Patients' Regular Participation at an Obesity Center to Evaluate the Effects on Mental Status and Blood Parameters.
Obesity is the main cause of type 2 diabetes, coronary artery disease, musculoskeletal disorders, some cancers, and mental disorders, and many other diseases leading to mortality. The aim of this study was to determine the effects of participation in an obesity center on patient mental status and blood parameters within 3 months and to show the relationship of this participation with depression, anxiety, and other parameters. This was a descriptive and cross-sectional study. Of 2,591 patients admitted to an obesity center between November 1, 2018 and November 1, 2019, 317 met the inclusion criteria. This study was a descriptive and cross-sectional study of the data from those 317 patients. Of the patients enrolled in the study, 90.5% were female and 9.5% were male. Weight, occupation, body mass index, body fat percentage, waist circumference, hip circumference, glycosylated hemoglobin (HbA1c), Beck Depression Scale, and Beck Anxiety Scale were important determinants in our univariate analyses associated with the regular receipt of center education. HbA1c (odds ratio, 1.661; 95% confidence interval, 1.140-2.421; P=0.008) was shown to be multivariate predictors of amount of participation in center education. These results support that regular participation in obesity center education has a positive effect on patients mental status, blood parameters, and anthropometric measurements. Thus, increasing the number of obesity centers is of great importance in treating obesity and improving obese patient mental status.


HoxB4 confers definitive lymphoid-myeloid engraftment potential on embryonic stem cell and yolk sac hematopoietic progenitors.
The extent to which primitive embryonic blood progenitors contribute to definitive lymphoid-myeloid hematopoiesis in the adult remains uncertain. In an effort to characterize factors that distinguish the definitive adult hematopoietic stem cell (HSC) and primitive progenitors derived from yolk sac or embryonic stem (ES) cells, we examined the effect of ectopic expression of HoxB4, a homeotic selector gene implicated in self-renewal of definitive HSCs. Expression of HoxB4 in primitive progenitors combined with culture on hematopoietic stroma induces a switch to the definitive HSC phenotype. These progenitors engraft lethally irradiated adults and contribute to long-term, multilineage hematopoiesis in primary and secondary recipients. Our results suggest that primitive HSCs are poised to become definitive HSCs and that this transition can be promoted by HoxB4 expression. This strategy for blood engraftment enables modeling of hematopoietic transplantation from ES cells.


Lipid peroxidation and antioxidant vitamins C and E in hypertensive patients.
Lipid peroxidation is a free radical process which is implicated in the formation of atherosclerosis. Vitamins C and E are important natural antioxidants which inhibit lipid peroxidation and a high intake of these vitamins, particularly vitamin E, is related to a reduced incidence of ischaemic heart disease. Hypertension is an independent risk factor for atherosclerosis and its relationship to antioxidant status is undetermined. In this study, we investigated free radical activity by measuring plasma malondialdehyde (MDA) using high-performance liquid chromatography (HPLC), vitamin C status measured as plasma ascorbic acid and vitamin E status measured as plasma lipid standardized alpha-tocopherol and erythrocyte alpha-tocopherol. We compared 28 patients with essential hypertension to 31 healthy subjects. Results showed that in comparison with the healthy subjects, the hypertensive patients had significantly higher plasma MDA levels (0.95 +/- 0.28 vs 0.69 +/- 0.21 mumol/l, mean +/- SD, p < 0.001) and significantly lower levels of plasma ascorbic acid (34.83 +/- 12.88 vs 51.76 +/- 13.34 mumol/L, p < 0.01). In addition, erythrocyte alpha-tocopherol concentration, which may reflect vitamin E protection in cell membranes, was significantly lower in hypertensive patients when compared with the normotensive controls (3.87 +/- 0.53 vs 4.82 +/- 1.01 mumol/l, p < 0.001), although plasma alpha-tocopherol levels were similar in the two groups (25.07 +/- 10.45 vs 23.96 +/- 6.07 mumol/l). Our results suggest that hypertensive patients may have increased lipid peroxidation and reduced protection from vitamins C and E. This may contribute to the propensity in such patients to develop atherosclerosis.


Localization of flotillins in human brain and their accumulation with the progression of Alzheimer's disease pathology.
To clarify (1) the localization of flotillins in human brain tissue and (2) the relationship between senile plaque formation and flotillins localization, we performed Western blotting and immunohistochemical analysis. Flotillins 1 and 2 were shown as 48 and 42 kDa bands, respectively, in human brain. The cerebral cortex showed a broad band-like labeling in entire layers. Flotillins were abundant in pyramidal neurons and astrocytes in the white matter. The intensity of the band-like labeling throughout the cortex became stronger with the development of senile plaque formation, and strongest in Alzheimer's disease. These findings suggest that flotillins are associated with progression of Alzheimer pathology.


Studies on regeneration of central nervous system and social ability of the earthworm Eudrilus eugeniae.
Earthworms are segmented invertebrates that belong to the phylum Annelida. The segments can be divided into the anterior, clitellar and posterior parts. If the anterior part of the earthworm, which includes the brain, is amputated, the worm would essentially survive even in the absence of the brain. In these brain amputee-derived worms, the nerve cord serves as the primary control center for neurological function. In this current work, we studied changes in the expression levels of anti-acetylated tubulin and serotonin as the indicators of neuro-regenerative processes. The data reveal that the blastemal tissues express the acetylated tubulin and serotonin from day four and that the worm amputated at the 7th segment takes 30 days to complete the regeneration of brain. The ability of self-assemblage is one of the specific functions of the earthworm's brain. The brain amputee restored the ability of self-assemblage on the eighth day.


The comparison of remimazolam and midazolam for the sedation of gastrointestinal endoscopy: a meta-analysis of randomized controlled studies.
Remimazolam and midazolam are used for the sedation of gastrointestinal endoscopy, but their efficacy remains controversial. We conduct a systematic review and meta-analysis to compare the sedation of remimazolam with midazolam for gastrointestinal endoscopy. PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched. Randomized controlled trials (RCTs) assessing the influence of remimazolam versus midazolam on gastrointestinal endoscopy were included. Two investigators independently have searched articles, extracted data, and assessed the quality of included studies. This meta-analysis was performed using the random-effect model. Three RCTs involving 528 patients were included in the meta-analysis. Compared with midazolam for gastrointestinal endoscopy, remimazolam was associated with higher procedure success (OR=9.78; 95% CI=1.48 to 64.71; P=0.02), lower need for rescue medication (OR=0.09; 95% CI=0.01 to 0.80; P=0.03), shorter total recall (Std. MD=0.93; 95% CI=0.15 to 1.72; P=0.02) and delayed recall (Std. MD=0.44; 95% CI=0.05 to 0.83; P=0.03), reduced incidence of hypotenson (OR=0.39; 95% CI=0.25 to 0.62; P<0.0001) and adverse events (OR=0.36; 95% CI=0.17 to 0.79; P=0.01), but had no obvious influence on fully alert (Std. MD=-0.75; 95% CI=-1.58 to 0.08; P=0.08). Remimazolam demonstrated better efficacy and safety for the sedation of gastrointestinal endoscopy compared to midazolam.


[Hemispheric dominance in schizophrenics as determined on extrapyramidal side effects of neuroleptics].
Phenomena observed during treatment with neuroleptics were clinically measured in an attempt to determine the difference in vulnerability of the two hemispheres and the relation between this difference and schizophrenic diseases. In the group of systematic schizophrenias the increase in tonus was significantly higher in the dominant hemisphere. This finding is considered a verification of the nosological hypothesis of schizophrenias.


Cardiomyocyte count in rat myocardium under the effect of antitumor agents cyclophosphamide and triterpenoids.
Structural reorganization of the myocardium in response to antitumor agents (cyclophosphamide, betulonic acid and its amide) was studied. Cardiotoxic effects of these chemicals manifested in cardiomyocyte contracture and lytic injuries and by significant hemodynamic disorders. The most pronounced lytic and necrobiotic changes in cardiomyocytes were detected after injection of cyclophosphamide followed by betulonic amide; this led to a more pronounced decrease in heart weight as a result of a decrease in total cardiomyocyte count. Antitumor drugs differently changed the ratio of mono- to binuclear cardiomyocytes, which differ by their regeneratory and compensatory adaptive potential.


[The effect isometric exertion on left ventricular function in patients after myocardial infarct].
24 patients, after transmural cardiac infarction, were exposed to isometric exercise ("handgrip"). The haemodynamic response was checked by means of impedance plethysmography. The stroke volume decreased on average from 64 +/- 14 to 60 +/- 15 ml (p less than 0.05), cardiac output increased from 4.8 +/- 1.0 to 5.4 +/- 1.2 l/min. (p less than 0.01). Peripheral resistance significantly increased and left ventricular performance was non-significantly reduced. Compared with a group of healthy control, their stroke and cardiac output and cardiac work kept increasing during isometric exercise. Isometric exercise is an adequate means of checking left ventricular performance.


A Statistical Timetable for the Sub-2-Hour Marathon.
Breaking the sub-2-h marathon in an official event has attracted growing interest in recent times with commercial and international momentum building. Here it is shown that predicting how likely and when the sub-2-h barrier will be broken are statistically coupled considerations. Using a nonlinear limiting exponential model and calculating prediction intervals, a statistical timetable for the sub-2-h event is produced over a range of likelihoods. At the benchmark odds level (1 in 10, or 10% likely), the expected sub-2-h arrival time is found to be May 2032. By estimating the model for male and female world record progressions, I find that limiting marathon times for males and females (at 1 in 10) are 1 h 58 min 5 s and 2 h 5 min 31 s, respectively. These times equate to a performance gap of 2.9% and 8.6%, respectively. The male estimate has remarkable similarity (~7 s) to Joyner's 1991 limiting human physiological estimate. Finally, I provide an estimate of the equivalent "sub-2-h" threshold for females and argue that a threshold of 130 min ("sub-130") could be an appropriate choice. The study is the first to address all three related aspects of world record marathon performance (sub-2 h, limits, gender equivalence) in a single, unified modeling framework and provides many avenues for further exploration and insight.


Transcatheter closure of a patent arterial duct in a patient on veno-arterial extracorporeal membrane oxygenation.
The presence of a patent arterial duct may complicate the course of the patient on veno-arterial extracorporeal membrane oxygenation (ECMO). While surgical ligation has been traditionally used as a definitive treatment for this problem, transcatheter closure may have advantages. This is the first report of transcatheter occlusion of a patent arterial duct in an infant on ECMO support.


Phenotypic selection on leaf functional traits of two congeneric species in a temperate rainforest is consistent with their shade tolerance.
Several studies across species have linked leaf functional traits with shade tolerance. Because evolution by natural selection occurs within populations, in order to explain those interspecific patterns it is crucial to examine variation of traits associated with shade tolerance and plant fitness at an intraspecific scale. In a southern temperate rainforest, two climbing plant species coexist but differ in shade tolerance. Whereas Luzuriaga radicans is most abundant in the shaded understory, L. polyphylla typically occurs in intermediate light environments. We carried out an intraspecific approach to test the hypothesis of differential selection patterns in relation to shade tolerance in these congeneric species. The probability of showing reproductive structures increased with specific leaf area (SLA) in L. polyphylla, and decreased with dark respiration in L. radicans. When reproductive output of fertile individuals was the fitness variable, we detected positive directional selection on SLA in L. polyphylla, and negative directional selection on dark respiration and positive directional selection on leaf size in L. radicans. Total light radiation differed between the microsites where the Luzuriaga species were sampled in the old-growth forest understory. Accordingly, L. radicans had a lower minimum light requirement and showed fertile individuals in darker microsites. L. radicans showed lower dark respiration, higher chlorophyll content, and greater leaf size and SLA than L. polyphylla. Results suggest that in more shade-tolerant species, established in the darker microsites, selection would favor functional traits minimizing carbon losses, while in less shade-tolerant species, plants displaying leaf traits enhancing light capture would be selected.


Factors associated with perceived health in elderly medical inpatients: a particular focus on personal coping recourses.
We wanted to unveil associations between perceived health and physical health, function in activity of daily living, anxiety, depression and coping resources in terms of sense of coherence (SOC) in elderly (≥65 years) in-hospital patients without cognitive impairment. In a cross-sectional study, we evaluated 217 hospitalized elderly patients with an age range 65-95 (mean 77.9) years. Perceived health was rated on a four-point scale. Physical health was measured with the Charlson index; functional status was rated using the Lawton and Brody's scale for self-maintaining and instrumental activities of daily living; and, anxiety and depression were rated using the Hospital Anxiety and Depression scale. Finally, the 13-item version of the SOC scale was used to assess coping, and cognitive state was assessed using the Mini-mental State Examination. In all, 40% of the patients reported good perceived health. In an adjusted logistic regression analysis, the main outcome good perceived health was associated with increasing age: odds ratio (OR) 1.06 (95% CI 1.01-1.11); good physical health: OR 2.49 (95% CI 1.22-5.07); and, medium high and high SOC: OR 2.48 (95% CI 1.20-5.13), and OR 2.43 (95% CI 1.11-5.28), respectively. Explained variance was 22.2%. Good coping resources and low severity of co-morbid disorders are the two most important factors that explain why elderly inpatients rate their health as good. Since coping may be equally important as poor physical health for perception of health, coping should be recognized and measured in clinical practice.


Glial granules contain germline proteins in the Drosophila brain, which regulate brain transcriptome.
Membraneless RNA-protein granules play important roles in many different cell types and organisms. In particular, granules found in germ cells have been used as a paradigm to study large and dynamic granules. These germ granules contain RNA and proteins required for germline development. Here, we unexpectedly identify large granules in specific subtypes of glial cells ("glial granules") of the adult Drosophila brain which contain polypeptides with previously characterized roles in germ cells including scaffold Tudor, Vasa, Polar granule component and Piwi family proteins. Interestingly, our super-resolution microscopy analysis shows that in the glial granules, these proteins form distinct partially overlapping clusters. Furthermore, we show that glial granule scaffold protein Tudor functions in silencing of transposable elements and in small regulatory piRNA biogenesis. Remarkably, our data indicate that the adult brain contains a small population of cells, which express both neuroblast and germ cell proteins. These distinct cells are evolutionarily conserved and expand during aging suggesting the existence of age-dependent signaling. Our work uncovers previously unknown glial granules and indicates the involvement of their components in the regulation of brain transcriptome.


Changes in behavior and amino acid neurotransmitters in the brain of rats with seizure induced by IL-1beta or IL-6.
To explore the mechanism of epilepsy induced by IL-1beta and IL-6, the changes of glutamic acid (Glu) and GABA immunoreaction in the cerebral cortex and hippocampus of rats with seizure induced by IL-1beta or IL-6 were studied. Rats were randomly divided into 3 groups: control group (intracerebroventricular injection (icv) of NS), IL-1beta group (icv injection of IL-1beta) and IL-6 group (i. c. v. injection of IL-6). 120 min after the icv injection of reagents of IL-1beta or IL-6, behavioral changes were observed and Glu and GABA in the cerebral cortex and hippocampus were examined by means of immunohistochemistry. Our results showed that no seizure developed in the control group, while moderate seizure was observed in IL-1beta group and IL-6 group. Compared with the controls, the immunoreaction of Glu was significantly increased, while GABA was obviously decreased in IL-1beta group and IL-6 group after 120 min. Our study suggested that the IL-1beta and II-6 might promote and induce epilepsy by increasing Glu and decreasing GABA in the cerebral cortex and hippocampus.


Effectiveness and safety of monoamine oxidase inhibitor treatment for bipolar depression versus unipolar depression: An exploratory case cohort study.
Patients with bipolar disorder spend most of their clinical lifetime in the depressive phase of their illness. However, antidepressants are discouraged in the treatment of bipolar depression due to concerns over manic induction and drug ineffectiveness. Some reports suggest that monoamine oxidase inhibitors (MAOIs) may be safe and effective compared to other antidepressants in treating bipolar depression. The present study compared the safety and effectiveness of MAOI therapy in patients with bipolar versus unipolar depression. Data were collected from approximately 2500 clinical research charts of patients treated with MAOI therapy at a university mood disorder clinic between 1983 and 2015. A mixed-effects model was created with patient entered as the random effect. The model included the primary diagnosis (i.e., either unipolar or bipolar depression) and other clinical covariates as fixed-effect predictors. Patients with bipolar depression demonstrated lower post-treatment clinical global impressions/severity scores versus patients with unipolar depression (p = 0.04). Neither group demonstrated a full syndromal manic or hypomanic episode. A higher proportion of patients with bipolar depression reported myoclonic tics and tremors, which may have resulted from concomitant lithium use. Amongst the covariates, only the number of prior antidepressant trials predicted poorer outcomes from MAOI therapy. MAOIs may be more effective-and as safe-for patients with bipolar depression versus unipolar depression. Future studies should explore this possible advantage using a larger sample size.


Dose-dependent antinociceptive action of neurotensin microinjected into the rostroventromedial medulla of the rat.
Microinjection of neurotensin into the rat rostroventromedial medulla produces dose-dependent inhibition of the tailflick reflex (ED50 of 2.06 nmol/animal (1.33-3.19)). The peak effect occurs 15-20 min following injection and, at the highest dose used, lasts up to 70 min.


Anterior chamber lenses. Part I: Complications and pathology and a review of designs.
Clinicopathologic data to assist ophthalmologists in choosing a safe and efficacious anterior chamber intraocular lens (IOL) are rapidly becoming available. Two important factors that have led to an increased success rate with some anterior chamber IOL styles are (1) attention to lens design and (2) attention to modern manufacturing and lens finishing techniques. We now know much more about how to achieve appropriate lens flexibility, which decreases the need for perfect sizing. Increased attention has been given to the anterior-posterior vaulting characteristics of IOLs. This has reduced the incidence of various complications such as the intermittent touch syndrome and the uveal chafing syndrome. We recognize several design flaws in some lens styles. For example, there is now a considerable decrease in the number of small-diameter, round-looped anterior chamber IOLs being implanted, particularly those with a closed-loop configuration. Several problems have been and continue to be caused by some poorly manufactured anterior chamber lenses with sharp optic and haptic edges. Technology to assure smooth lens finishing and polishing is available and readily accessible to all manufacturers. Defective lenses should soon be a thing of the past.


Behavior of vascular resistance undergoing various pressure insufflation and perfusion on decellularized lungs.
Bioengineering of functional lung tissue by using whole lung scaffolds has been proposed as a potential alternative for patients awaiting lung transplant. Previous studies have demonstrated that vascular resistance (Rv) could be altered to optimize the process of obtaining suitable lung scaffolds. Therefore, this work was aimed at determining how lung inflation (tracheal pressure) and perfusion (pulmonary arterial pressure) affect vascular resistance. This study was carried out using the lungs excised from 5 healthy male Sprague-Dawley rats. The trachea was cannulated and connected to a continuous positive airway pressure (CPAP) device to provide a tracheal pressure ranging from 0 to 15cmH2O. The pulmonary artery was cannulated and connected to a controlled perfusion system with continuous pressure (gravimetric level) ranging from 5 to 30cmH2O. Effective Rv was calculated by ratio of pulmonary artery pressure (PPA) by pulmonary artery flow (V'PA). Rv in the decellularized lungs scaffolds decreased at increasing V'PA, stabilizing at a pulmonary arterial pressure greater than 20cmH2O. On the other hand, CPAP had no influence on vascular resistance in the lung scaffolds after being subjected to pulmonary artery pressure of 5cmH2O. In conclusion, compared to positive airway pressure, arterial lung pressure markedly influences the mechanics of vascular resistance in decellularized lungs.


Functionalized ultra-low fouling carboxy- and hydroxy-functional surface platforms: functionalization capacity, biorecognition capability and resistance to fouling from undiluted biological media.
The non-specific binding of non-target species to functionalized surfaces of biosensors continues to be challenge for biosensing in real-world media. Three different low-fouling and functionalizable surface platforms were employed to study the effect of functionalization on fouling resistance from several types of undiluted media including blood plasma and food media. The surface platforms investigated in this work included two polymer brushes: hydroxy-functional poly(2-hydroxyethyl methacrylate) (pHEMA) and carboxy-functional poly(carboxybetaine acrylamide) (pCBAA), and a standard OEG-based carboxy-functional alkanethiolate self-assembled monolayer (AT-SAM). The wet and dry polymer brushes were analyzed by AFM, ellipsometry, FT-IRRAS, and surface plasmon resonance (SPR). The surfaces were functionalized by the covalent attachment of antibodies, streptavidin, and oligonucleotides and the binding and biorecognition characteristics of the coatings were compared. We found that functionalization did not substantially affect the ultra-low fouling properties of pCBAA (plasma fouling of ~20 ng/cm(2)), a finding in contrast with pHEMA that completely lost its resistance to fouling after the activation of hydroxyl groups. Blocking a functionalized AT-SAM covalently with BSA decreased fouling down to the level comparable to unblocked pCBAA. However, the biorecognition capability of blocked functionalized AT-SAM was poor in comparison with functionalized pCBAA. Limits of detection of Escherichia coli O157:H7 in undiluted milk were determined to be 6×10(4), 8×10(5), and 6×10(5) cells/ml for pCBAA, pHEMA, and AT-SAM-blocked, respectively. Effect of analyte size on biorecognition activity of functionalized coatings was investigated and it was shown that the best performance in terms of overall fouling resistance and biorecognition capability is provided by pCBAA.


Spatial patterns and environmental controls of particulate organic carbon in surface waters in the conterminous United States.
Carbon cycling in inland waters has been identified as an important, but poorly constrained component of the global carbon cycle. In this study, we compile and analyze particulate organic carbon (POC) concentration data from 1145 U.S. Geological Survey (USGS) gauge stations to investigate the spatial variability and environmental controls of POC concentration. We observe substantial spatial variability in POC concentration (1.43 ± 2.56 mg C/L, mean ± one standard deviation), with the Upper Mississippi River basin and the Piedmont region in the eastern U.S. having the highest POC concentration. Further, we employ generalized linear models (GLMs) to analyze the impacts of sediment transport and algae growth as well as twenty-one other environmental factors on the POC variability. Suspended sediment and chlorophyll-a explain 26% and 17% of the variability in POC concentration, respectively. At the national level, the twenty-one environmental factors combined can explain ca. 40% of the spatial variance in POC concentration. At the national scale, urban area and soil clay content show significant negative correlations with POC concentration, whereas soil water content and soil bulk density correlate positively with POC. In addition, total phosphorus concentration and dam density correlate positively with POC concentration. Furthermore, regional scale analyses reveal substantial variation in environmental controls of POC concentration across eighteen major water resource regions in the U.S. The POC concentration and associated environmental controls also vary non-monotonically from headwaters to large rivers. These findings indicate complex interactions among multiple factors in regulating POC concentration over different spatial scales and across various sections of the river networks. This complexity, together with the large unexplained uncertainty, highlights the need for considering non-linear interplays of multiple environmental factors and developing appropriate methodologies to track the transformation and transport of POC along the terrestrial-aquatic interfaces.


Hypertension and renovascular disease: follow-up on 100 renal vein renin samplings.
The clinical value of renal vein renin sampling (RVRS) as a prognostic tool in the treatment of renovascular hypertension was evaluated. One hundred consecutive patients were included over a 4-year period of time. About half of the patients (49%) were treated interventionally by PTRA (21%), nephrectomy (20%), or vascular surgery (8%). Seven patients (15%) were cured and 15 (32%) had improved (reduction in antihypertensive medicine) after 6 months follow-up, whereas three patients (6%) were cured and 12 (26%) improved after 3-4 years follow-up. Thus, the number of patients cured or improved is comparable with the results from our department reported 20 years ago. However, in the present report, more than twice as many patients were enrolled, leading to double costs. Different indices of lateralisation of the renin generation were calculated for the use in cases of a shrunken kidney (functional share < or =15%). None of the indices clearly discriminated between the patients who did benefit from intervention, and those who did not. The only positive finding was that a peripheral renin concentration lower than 8 mlU/l predicted no effect of intervention, which might lead to the exclusion of 11% of the patients before entering the diagnostic programme. We conclude that the RVRS demands a very restrictive referral pattern if it should be of prognostic value for the blood pressure outcome after intervention. No indices of lateralised renin concentrations proved high predictive value. However, a peripheral renin concentration low in the normal range seems useful as an indicator of no benefit from intervention.


Efficient fat suppression by slice-selection gradient reversal in twice-refocused diffusion encoding.
Most diffusion imaging sequences rely on single-shot echo-planar imaging (EPI) for spatial encoding since it is the fastest acquisition available. However, it is sensitive to chemical-shift artifacts due to the low bandwidth in the phase-encoding direction, making fat suppression necessary. Often, spectral-selective RF pulses followed by gradient spoiling are used to selectively saturate the fat signal. This lengthens the acquisition time and increases the specific absorption rate (SAR). However, in pulse sequences that contain two slice-selective 180 degrees refocusing pulses, the slice-selection gradient reversal (SSGR) method of fat suppression can be implemented; i.e., using slice-selection gradients of opposing polarity for the two refocusing pulses. We combined this method with the twice-refocused spin-echo sequence for diffusion encoding and tested its performance in both phantoms and in vivo. Unwanted fat signal was entirely suppressed with this method without affecting the water signal intensity or the slice profile.


Bacterial Chromosome Dynamics by Locus Tracking in Fluorescence Microscopy.
Bacterial chromosomes have been shown in the last two decades to have remarkable spatial organization at various scales, and also well-defined movements during the cell cycle, for example, to reliably segregate daughter chromosomes. More recently, various labs have begun investigating the short-time dynamics (displacements during time intervals of 0.1-100 s), which one hopes to link to structure, in analogy to "microrheology" approaches applied successfully to study mechanical response of complex fluids. These studies of chromosome fluctuation dynamics have revealed differences of fluctuation amplitude across the chromosome, and different characters of motion depending on the time window of interest. The highly nontrivial motion at the shortest experimentally accessible times is still not fully understood in terms of physical models of DNA and cytosol. We describe how to carry out tracking experiments of single locus and how to analyze locus motility. We point out the importance of considering in the analysis the number of GFP molecules per fluorescent locus.


MCQ and higher examinations as exemplified by the primary Fellowship of the Faculty of Anaesthetics, Royal College of Surgeons of England.
A major problem of the use of multiple choice examinations is the inherent difficulty of the questions, a fact which cannot be assessed in relation to questions not previously used. Questions which have been used during previous examinations, however, will have an available measure of the difficulty in the form of candidates' previous scores. The performance of candidates in a current examination can be compared with that in a previous examination. On the strength of these differences it is possible to decide whether the candidates in any single examination are better prepared than their predecessors or less well prepared. Pass marks can be appropriately adjusted.


The effect of carbachol and isoprenaline on cell division in the exocrine pancreas of the rat.
The effect of muscarinic cholinergic receptor stimulation on pancreatic acinar cell division has been investigated. Muscarinic receptor stimulation, in addition to causing a 50% depletion of amylase in the pancreas after 4 h, resulted in a 400% increase in the incorporation of [6(-3)H]thymidine 27 h after drug administration. This increase in incorporation was dose-dependent. Autoradiography showed this increase to be due to an increased acinar cell labelling. Isoprenaline also increased the incorporation of [6(-3)H]thymidine into the pancreas but did not reduce enzyme levels. However, with isoprenaline there was no increase in acinar cell labelling. The possibility of a relationship between secretion and hyperplasia of acinar cells in the rat pancreas is discussed.


Interannual and cyclone-driven variability in phytoplankton communities of a tropical coastal lagoon.
One of the main challenges in phytoplankton ecology is to understand their variability at different spatiotemporal scales. We investigated the interannual and cyclone-derived variability in phytoplankton communities of Chilika, the largest tropical coastal lagoon in Asia and the underlying mechanisms in relation to environmental forcing. Between July 2012 and June 2013, Cyanophyta were most prolific in freshwater northern region of the lagoon. A category-5 very severe cyclonic storm (VSCS) Phailin struck the lagoon on 12th October 2013 and introduced additional variability into the hydrology and phytoplankton communities. Freshwater Cyanophyta further expanded their territory and occupied the northern as well as central region of the lagoon. Satellite remote sensing imagery revealed that the phytoplankton biomass did not change much due to high turbidity prevailing in the lagoon after Phailin. Modeling analysis of species-salinity relationship identified specific responses of phytoplankton taxa to the different salinity regime of lagoon.


Self-monitoring of health data by patients with a chronic disease: does disease controllability matter?
There is a growing emphasis on self-monitoring applications that allow patients to measure their own physical health parameters. A prerequisite for achieving positive effects is patients' willingness to self-monitor. The controllability of disease types, patients' perceived self-efficacy and health problems could play an essential role in this. The purpose of this study is to investigate the relationship between patients' willingness to self-monitor and a range of disease and patient specific variables including controllability of disease type, patients' perceived self-efficacy and health problems. Data regarding 627 participants with 17 chronic somatic disease types from a Dutch panel of people with chronic diseases have been used for this cross-sectional study. Perceived self-efficacy was assessed using the general self-efficacy scale, perceived health problems using the Physical Health Composite Score (PCS). Participants indicated their willingness to self-monitor. An expert panel assessed for 17 chronic disease types the extent to which patients can independently keep their disease in control. Logistic regression analyses were conducted. Patients' willingness to self-monitor differs greatly among disease types: patients with diabetes (71.0%), asthma (59.6%) and hypertension (59.1%) were most willing to self-monitor. In contrast, patients with rheumatism (40.0%), migraine (41.2%) and other neurological disorders (42.9%) were less willing to self-monitor. It seems that there might be a relationship between disease controllability scores and patients' willingness to self-monitor. No evidence is found of a relationship between general self-efficacy and PCS scores, and patients' willingness to self-monitor. This study provides the first evidence that patients' willingness to self-monitor might be associated with disease controllability. Further research should investigate this association more deeply and should focus on how disease controllability influences willingness to self-monitor. In addition, since willingness to self-monitor differed greatly among patient groups, it should be taken into account that not all patient groups are willing to self-monitor.


Elderly at time of COronaVIrus disease 2019 (COVID-19): possible role of immunosenescence and malnutrition.
The unprecedented COVID-19 pandemic is rapidly and unpredictably evolving and the majority of deaths are occurring in older people. A partial description of the magnitude of the scenario is provided by numbers and statistics, which probably underestimate the ongoing tragedy. In the present opinion paper, we have focused our attention on the evidence of the relationship among malnutrition, immunosenescence, and the higher morbidity and mortality in elderly patients. In particular, we propose the intriguing hypothesis that correction of nutritional deficits may attenuate the age-dependent alterations of the innate and adaptive immune system which participate in the increased susceptibility and worse outcome observed in the elderly COVID-19 patients.


Colon hydrotherapy plus Traditional Chinese Medicine to treat non-alcoholic fatty liver disease: a pilot study.
To demonstrate the potential to treat non-alcoholic fatty liver disease (NAFLD) with colon hydrotherapy (CHT) plus Traditional Chinese Medicine (TCM). A total of 20 patients were enrolled into the study and received CHT with TCM for 2 weeks. Body mass index (BMI) and levels of serum triglycerides (TG) and total cholesterol (TC) were compared between pre-treatment and post-treatment. Two-week treatment with CHT plus TCM significantly lowered BMI and reduced blood lipids. BMI decreased from 29.5 4.3 to 25.4 1.0, while mean TG levels decreased by 0.70 mmol/L on average from baseline and mean TC levels decreased by 0.37 mmol/L. Forty-five percent of patients exhibited TC decreasing by more than 10% from baseline and 25% of patients exhibited TC decreasing by more than 20%. Sixty percent of patients exhibited TG decreasing by more than 20% and 20% of patients exhibited TG decreasing by more than 40%. However, high-density and low-density lipoprotein cholesterol levels did not change significantly after intervention. No serious adverse events were reported. Our findings suggest that CHT plus TCM to treat NAFLD is promising and it might be a new treatment strategy for management of NAFLD.


Isolation and partial characterization of binding proteins for immobilized delta endotoxin from solubilized brush border membrane vesicles of the silkworm, Bombyx mori, and the common cutworm, Spodoptera litura.
1. Brush border membrane vesicles (BBMV) were prepared from the Bombyx mori, and Spodoptera litura, midguts. BBMV was solubilized. 2. Activated delta endotoxin from Bacillus thuringiensis were immobilized. 3. Solubilized BBMV proteins were applied to the toxin column and the proteins bound were analyzed by SDS-PAGE. 4. In the case of B. mori M(r) = 220,000, 150,000 and 130,000 and in the case of S. litura 160,000 bands were detected. 5. The bindings were inhibited by N-acetyl galactosamine and mannose. 6. The binding proteins applied onto a Con A column and eluted by 0.1 M methyl-alpha-glucose, suggesting that hybrid type sugar sidechain may involve in the interaction.


Ptp61F integrates Hippo, TOR, and actomyosin pathways to control three-dimensional organ size.
Precise organ size control is fundamental for all metazoans, but how organ size is controlled in a three-dimensional (3D) way remains largely unexplored at the molecular level. Here, we screen and identify Drosophila Ptp61F as a pivotal regulator of organ size that integrates the Hippo pathway, TOR pathway, and actomyosin machinery. Pathologically, Ptp61F loss synergizes with RasV12 to induce tumorigenesis. Physiologically, Ptp61F depletion increases body size and drives neoplastic intestinal tumor formation and stem cell proliferation. Ptp61F also regulates cell contractility and myosin activation and controls 3D cell shape by reducing cell height and horizontal cell size. Mechanistically, Ptp61F forms a complex with Expanded (Ex) and increases endosomal localization of Ex and Yki. Furthermore, we demonstrate that PTPN2, the conserved human ortholog of Ptp61F, can functionally substitute for Ptp61F in Drosophila. Our work defines Ptp61F as an essential determinant that controls 3D organ size under both physiological and pathological conditions.


Radioprotective effect of mistletoe extract on intestinal toxicity: in vivo study using adult zebrafish.
The intestine is a dose-limiting organ in the treatment of intra-abdominal cancer. We previously reported that the extract of mistletoe parasites on Quercus had a more potent radioprotective effect than amifostine in reducing the developmental toxicities of zebrafish embryos. In this study, radioprotection against intestinal toxicity was investigated in adult zebrafish. Wild-type adult AB zebrafish were exposed to 45-50 Gy of photon beam irradiation and/or treated with mistletoe extract orally 1 h before. The main endpoints of the study were survival and degree of deformation of the intestinal villi. The median follow-up period was 10 d post-irradiation (range: 7-11 d). A total of 105 zebrafish were used, including 42 in the radiation alone, 42 in the radiation and mistletoe arms, and 21 control subjects (mistletoe alone, mock-irradiated arm). The rate of both significant deformity and death was 53% in the radiation-alone arm, whereas the corresponding rate was 30% in the radiation and mistletoe arms. Significant deformity-free survival rates at 10 d post-irradiation in the radiation alone, and radiation and mistletoe arms were 44.7% (95% confidence interval [CI]:20-54.3) and 68.4% (95% CI:53.8-86.8), respectively (p=.046). The radiation and mistletoe arms showed decreased expression of two of three inflammatory genes (IL-1β and IL-6) compared to the radiation alone group (p<.05). The radioprotective effect against intestinal toxicity was successfully shown in an adult zebrafish model. This result suggests the possibility of clinical use of mistletoe extract for the treatment of abdominal cancers.


Effect of thermal acclimation on the tolerance of the peach fruit fly (Bactrocera zonata: Tephritidae) to heat and cold stress.
Understanding the thermal biology of insects is of increasing importance for predicting their geographic distribution, particularly in light of current and future global temperature increases. Within the limits set by genetic makeup, thermal tolerance is affected by the physiological conditioning of individuals (e.g., through acclimation). Considering this phenotypic plasticity may add to accurately estimating changes to the distribution of insects under a changing climate. We studied the effect of thermal acclimation on cold and heat tolerance of the peach fruit fly (Bactrocera zonata) - an invasive, polyphagous pest that is currently expanding through Africa and the Middle East. Females and males were acclimated at 20, 25 and 30 °C for up to 19 days following adult emergence. The critical thermal minimum (CTmin) and maximum (CTmax) were subsequently recorded as well adult survival following acute exposure to chilling (0 or -3 °C for 2 h). Additionally, we determined the survival of pupae subjected for 2 h to temperatures ranging from -12 °C to 5 °C. We demonstrate that acclimation at 30 °C resulted in significantly higher CTmax and CTmin values (higher heat resistance and lower cold resistance, respectively). Additionally, adult recovery following exposure to -3 °C was significantly reduced following acclimation at 30 °C, and this effect was significantly higher for females. Pupal mortality increased with the decrease in temperature, reaching LT50 and LT95 values following exposure to -0.32 °C and -6.88 °C, respectively. Finally, we found that the survival of pupae subjected to 0 and 2 °C steadily increased with pupal age. Our findings substantiate a physiological foundation for understanding the current geographic range of B. zonata. We assume that acclimation at 30 °C affected the thermal tolerance of the flies partly through modulating feeding and metabolism. Tolerance to chilling during the pupal stage probably changed according to temperature-sensitive processes occurring during metamorphosis, rendering younger pupae more sensitive to chilling.


Engineering pectin-based hollow nanocapsules for delivery of anticancer drug.
Multifunctional capsules have great applications in biomedical fields. In this study, novel polysaccharide-based nanocapsules were prepared via a layer-by-layer technique using silica as the templates. The shell was constructed based on the electrostatic interactions between pectin and chitosan. The pectin-chitosan nanocapsules ((Pec/Cs)3Pec) could keep good colloidal stability within 96h in PBS solution and 48h in BSA solution. Meanwhile, the nanocapsules exhibited a high drug loading and pH-sensitive release property for doxorubicin hydrochloride. Moreover, (Pec/Cs)3Pec nanocapsules had no cytotoxicity to both human hepatocellular carcinoma cells (HepG2 cells) and mouse fibroblast cells (L929 cells). More importantly, (Pec/Cs)3Pec nanocapsules could be more easily uptaken by HepG2 cells when compared with L929 cells. In vitro anticancer activity tests indicated the carriers could effectively kill HepG2 cells. Overall, (Pec/Cs)3Pec nanocapsules have great potential as a novel anticancer drug carrier as a result of their pH-sensitivity, good colloidal stability and anticancer activity.


Markers of polychlorinated biphenyl (PCB) degradation in highly contaminated soil of Central Russia.
The highly polychlorinated biphenyl (PCB)-contaminated historical soil is located in the Serpukhov region (Central Russia). This study evaluates the processes of PCB degradation in the soil under natural conditions. Compositions of industrial mixtures (Sovol, Sovtol, and trichlorodiphenyl) were compared with PCB-contaminated soil from different depths. An increased number of dichlorobiphenyls (6 congeners) were determined in the deeper soil horizons (40-60 cm) in comparison with the surface layer (1 congener). Non-associated with industrial mixture congener, PCB 11 was determined in some soil layers with concentrations reaching 3.6 mg/kg. PCB 11 can be considered as a potential marker of activated degradation processes in highly contaminated soils with industrial mixtures. Aegopodium podagraria reduced total PCB concentrations in the contaminated soil to 25% during pot experiments. Prospective precursors of PCB 11 were significantly depleted (62-88%) after phytoremediation, but this did not increase PCB 11 concentration in the soil.


The Patient-Derived Cancer Organoids: Promises and Challenges as Platforms for Cancer Discovery.
The cancer burden is rapidly increasing in most countries, and thus, new anticancer drugs for effective cancer therapy must be developed. Cancer model systems that recapitulate the biological processes of human cancers are one of the cores of the drug development process. PDCO has emerged as a unique model that preserves the genetic, physiological, and histologic characteristics of original cancer, including inter- and intratumoral heterogeneities. Due to these advantages, the PCDO model is increasingly investigated for anticancer drug screening and efficacy testing, preclinical patient stratification, and precision medicine for selecting the most effective anticancer therapy for patients. Here, we review the prospects and limitations of PDCO compared to the conventional cancer models. With advances in culture success rates, co-culture systems with the tumor microenvironment, organoid-on-a-chip technology, and automation technology, PDCO will become the most promising model to develop anticancer drugs and precision medicine.


Cytotoxic and genotoxic effects of [Ru(phi)3]2+ evaluated by Ames/Salmonella and MTT methods.
In this work, we synthesized and evaluated the cytotoxic effect of [Ru(phi)(3)](2+), on rat C6 glioma cell line. Cell viability was determined by assay with 3-(4-5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). The mutagenicity of [Ru(phi)(3)](2+) was studied in vitro by using two strains of Salmonella typhimurium with frameshift mutation (TA98) and base-pair substitution mutation (TA100) were used in plate incorporation assay in the absence of metabolic activation. According to the results, the Ru compound is not toxic but mutagenic, and it shows cytotoxic effect towards C6 rat glioma cells in 100 microM.


Active matrix metalloproteinase-7 is associated with invasion in buccal squamous cell carcinoma.
Protein microarrays have shown that matrix metalloproteinase-7 is upregulated in head and neck squamous cell carcinomas, but its role in local tissue invasion is still uncertain. We investigated the expression of active matrix metalloproteinase-7, using tissue microarray, immunohistochemistry, and western blotting, in oral tissues from 24 patients with buccal squamous cell carcinoma, and correlated the findings with clinicopathological features. Normal buccal tissue samples from the same patients, obtained at sites at least 1 cm from tumor tissue, served as normal controls. Total matrix metalloproteinase-7 was detected on western blots in 9 of 15 (60%) tumor tissue samples and in 2 of 15 (13%) normal mucosal samples; this difference was significant (P=0.008). Moreover, the active matrix metalloproteinase-7 was expressed only in eight of the nine (89%) tumor samples that expressed matrix metalloproteinase-7, and in none of the normal tissue samples, regardless of the expression status of the pro-matrix metalloproteinase-7. Immunostaining of matrix metalloproteinase-7 was observed histologically in both tumor and nonneoplastic epithelium, but immunostaining of active matrix metalloproteinase-7 was present only in tumor nests. Expression of active matrix metalloproteinase-7 was associated with larger tumor size (P=0.022) and was significantly higher in buccal squamous cell carcinoma with adjacent skin or bone invasion (P=0.036). In conclusion, active matrix metalloproteinase-7 expression was associated with more aggressive buccal squamous cell carcinomas.


Clinical utility of hereditary cancer panel testing: Impact of PALB2, ATM, CHEK2, NBN, BRIP1, RAD51C, and RAD51D results on patient management and adherence to provider recommendations.
Although management guidelines exist for several genes associated with a 2-fold to 5-fold increase in the relative risk for certain cancers, the value of testing for them remains controversial. De-identified personal and family history data for 654 individuals with pathogenic variants (PVs) in PALB2, ATM, CHEK2, NBN, BRIP1, RAD51C, and/or RAD51D were analyzed for pretest and post-test candidacy for guideline-recommended management of cancer risk. These individuals were invited to complete a survey about provider recommendations and their adherence. Twenty-four percent of CHEK2, ATM, PALB2, or NBN PV carriers were appropriate for consideration of annual breast magnetic resonance imaging screening before genetic testing, with the remaining 76% appropriate only after testing. No BRIP1, RAD51C, or RAD51D PV carriers were appropriate for consideration of risk-reducing salpingo-oophorectomy before genetic testing; 100% were appropriate only after testing. Seventeen percent of CHEK2 PV carriers were appropriate for earlier and more frequent colonoscopy before genetic testing, with the remaining 83% appropriate only after testing. Provider recommendations for annual breast magnetic resonance imaging, consideration of risk-reducing salpingo-oophorectomy, and earlier and more frequent colonoscopy were reported by 42%, 26%, and 66% of breast, ovarian, and colorectal cancer risk PV carriers, respectively, before genetic testing, versus 82%, 79%, and 81%, respectively, after testing. Nearly all respondents had planned or undertaken provider-recommended management. Testing for PALB2, ATM, CHEK2, NBN, BRIP1, RAD51C, and RAD51D changed management for those carrying PVs. Provider recommendations were aligned with guidelines, and patients adhered to recommendations, both of which are critical for reducing both long-term cancer morbidity and mortality.


Root extract of Hemsleya amabilis Diels suppresses renal cell carcinoma cell growth through inducing apoptosis and G2/M phase arrest via PI3K/AKT signaling pathway.
Hemsleya amabilis Diels, belongs to cucurbitaceae, was traditional Chinese medicine (TCM). It is widely used to treat various diseases. However, these diseases may contribute to the development of RCC. investigated the anticancer activities of root extract of Hemsleya amabilis Diels (HRE), and elucidated the underlying molecular mechanism in vivo and in vitro. Dried Hemsleya amabilis Diels roots were extracted by ethyl acetate and used to treat RCC4, OS-RC-2 and ACHN cells. UHPLC-MS was used to analyze the chemical composition of the extract. CCK-8 and colony formation assay were used to investigate proliferation. PI staining was used to detect cell cycle. Annexin-V-FITC, AO/EB and TEM were used to evaluate apoptosis. Transwell and wound healing assays were used to evaluate migration and invasion. RNA-seq, Network pharmacology, autodocking for virtual screening and molecular dynamics simulation were used to analyze potential molecular mechanisms and active components of HRE inhibiting proliferation of RCC. LY294002 and UC2288 were used to inhibit PI3K and P21 expression, respectively. IGF-1 was used to activate PI3K. Xenograft tumor model was established to evaluate its anti-tumor potential in vivo. Immunohistochemistry and Western blot were used to test protein expression levels. H&E staining was used to explore the side effects of HRE in vivo. Applying bioinformatics to analyze the effect of P21 on RCC. HRE consists of 739 compounds. CCK-8 and colony formation assay showed that HRE significantly inhibited RCC cells proliferation. PI staining indicated that HRE caused G2/M phase arrest. Annexin-V-FITC, AO/EB and TEM experiments revealed that HRE significantly promoted apoptosis of RCC cells. Transwell and wound healing assays showed that HRE can inhibit the migration and invasion of RCC cells. RNA-seq showed that HRE induced 230 gene changes. Network pharmacology analysis found the relationship between HRE-component-target-RCC. Auto-docking found that Epitulipinolide diepoxide in HRE can stably bind to PIK3CA (-7.22 kJ/mol), and molecular dynamics simulation verified the combination between Epitulipinolide diepoxide of PIK3CA. In RCC4 cells, pretreatment with IGF-1, attenuated HRE-induced apoptosis and G2/M arrest. When pretreated with PIK3 inhibitor LY294002, the opposite result appears. Pretreatment with CDKN1A (P21) inhibitor UC2288 attenuated HRE-induced G2/M arrest. Xenograft tumor model showed that HRE inhibited tumor growth. Western blot analysis indicated that HRE can regulating Bax, Bcl-2, PARP, cleared-PARP, Caspase-9, Caspase-8, Caspase-3, Survivin, Cyclin-B1, CDK1, N-cadherin, snail, slug, E-cadherin, MMP-9. Immunohistochemical staining showed that in the treated group, expression of E-cadherin, Bax, P21 was up-regulated, while N-cadherin, PI3K, AKT and Bcl-2 were down-regulated. H&E staining showed that compared to control groups, the main organs in the HRE-treated groups showed no histological abnormalities. The overall survival rate of RCC patients in the high-expression group of P21 was higher than in the low-expression group of P21 on bioinformatics analysis. HRE inhibited RCC migration and invasion through EMT, and inhibited proliferation in vivo and in vitro. In addition, HRE inhibited proliferation through promoting apoptosis and P21-induced G2/M phase arrest via PI3K/AKT signaling pathway. Overall, these results suggest that HRE may be a promising chemotherapy agent for RCC.


Six-minute walking distance in healthy Chinese people older than 60 years.
The six-minute walking test (6MWT) is a tool that plays a key role in evaluating the functional exercise capacity, prognosis and evaluation of treatment response of patients with various cardiopulmonary diseases. However, standard reference equations are currently unavailable for the six-minute walking distance (6MWD) for people aged 60-85 years in China. The purpose of this study was to 1) measure the 6MWD of healthy Chinese people aged 60-85 years, 2) establish reference equations for predicting the 6MWD, and 3) compare our reference equations with equations reported in previously published studies. We obtained informed consent from each participant prior to the test, and the research design was approved by the Ethics Committee of Wenzhou People's Hospital. The demographic and anthropometric data and the 6MWD of healthy Chinese subjects aged 60-85 years old were measured using a standardized protocol. Every subject completed two 6MWTs, and the longest 6MWD further analyzed. Two hundred sixty-six subjects (128 males and 138 females) completed the 6MWT, and the mean walking distance was 518 ± 72 m. Males achieved a longer walking distance than females (518 ± 72 m vs. 487 ± 70 m; p < 0.0001), and active subjects achieved a longer walking distance than nonactive subjects (512 ± 76 m vs. 485 ± 63 m; p < 0.0001). According to the univariate analysis, the 6MWD was significantly associated with age, height, body mass index (BMI), heart rate and blood pressure after exercise and changes in heart rate before and after exercise. The stepwise multivariate regression analysis identified age, height and BMI as independent predictors of the 6MWD. The reference equations for Caucasians and South Americans tended to overestimate the 6MWD of our subjects, while the equations for Asian and African populations tended to underestimate the 6MWD. This study is the first to describe the 6MWD of healthy Chinese people aged 60-85 years, and reference prediction equations were proposed. These findings will help to improve the evaluation of Chinese patients with diseases that affect exercise capacity.


Bindings of toxic shock syndrome toxin-1 and staphylococcal enterotoxins A, B, and C to rabbit spleen cells.
Toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxins (SE) A, B, and C were studied on binding to rabbit spleen cells. The toxins showed remarkable mitogenic effects on the cells. Among them, SEA and TSST-1 had much stronger mitogenic activities than SEB and SEC. Binding study showed that labeled TSST-1 and SEA bound considerably to cells, but that labeled SEB or SEC was not observed to bind at a detectable level under the same conditions as TSST-1 and SEA. Competitive binding analysis between toxins to cells proved that TSST-1 and SEA clearly competed with each other in binding. Scatchard plots for TSST-1 and SEA in binding were linear at the doses used. The Scatchard analysis for TSST-1 and SEA gave a dissociation constant of 2.5 X 10(-9) M and 7.6 X 10(-8) M and the number of binding sites per cell of 5.3 X 10(3) and 1.0 X 10(5), respectively.


Dose-dependent renoprotection efficacy of sglt2 inhibitors in type 2 diabetes: systematic review and network meta-analysis.
To compare the relative effects of different dosages of sodium-glucose cotransport inhibitors (SGLT2i) for renoprotection in Type 2 diabetes mellitus. The study searched different databases (PubMed, Embase, Scopus, and Web of Science) for studies comparing dose-dependent renoprotective efficacy defined as a decline in eGFR with the different "-flozins namely Empagliflozin, Canagliflozin, Dapagliflozin, Ertugliflozin, Ipragliflozin, Luseogliflozin, Remogliflozin and Sotagliflozin. The studies were compared with the Bayesian approach of network meta-analysis coupled with the random-effect model using the Cochrane risk of bias tool (RoB 2.0), and the surface under the cumulative ranking curve (SUCRA) score was allotted to each dosage of different SGLT-2i. A total of 43,434 citations were identified, out of which forty-five randomized trials with 48,067 patients, mentioning the flozin dose and eGFR as an endpoint, were found to be eligible for further analysis. The median duration of the follow-up in the trials was 12 months (IQR 5.5-16 months). Canagliflozin 100 mg demonstrated distinct eGFR benefit with an odds ratio of 2.3 (CI 0.72-3.9) compared to placebo. A statistically non-significant eGFR benefit was observed with all other "-flozins." Canagliflozin 100 mg drug dose category showed the highest sucra rank probability score of 93%, followed by the Canagliflozin 300 mg and Dapagliflozin 5 mg with sucra rank probability scores of 69% and 65%, respectively. The Flozin-dose assessment against eGFR was similar to the albumin-creatinine ratios as the secondary endpoint in the SUCRA ranking. The renoprotective efficacy of SGLT2i is independent of the incremental doses suggesting lower doses may suffice for renal outcomes.


Alteration of BAFF and APRIL in the cerebrospinal fluid based on the therapeutic response in primary central nervous system B-cell lymphoma.
We evaluated the cerebrospinal fluid (CSF) levels of the B-cell activating factor of the tumor necrosis factor family (BAFF) and A proliferation-inducing ligand (APRIL) in two cases of primary central nervous system B-cell lymphoma (PCNSBL) before and after treatment. One patient achieved clinical remission, and demonstrated decrease in the CSF levels of both BAFF and APRIL after treatment. Meanwhile, the other patient with insufficient therapeutic response showed increase in the BAFF levels despite decrease in APRIL levels. This report suggests that the combination of BAFF and APRIL levels could be useful in estimating the therapeutic efficacy in treating PCNSBL as reliable CSF markers.


Mechanical stretch aggravates vascular smooth muscle cell apoptosis and vascular remodeling by downregulating EZH2.
Enhancer of zeste homolog 2 (EZH2) was recently found to play an important role in cardiovascular disease. However, the role of EZH2 in vascular remodeling induced by mechanical stretch is poorly understood. The aim of the present work was to investigate the role of EZH2 in regulating smooth muscle cell function through mechanical stretch assays and to explore the underlying mechanisms. WT C57BL/6 J mice underwent sham surgery or abdominal aortic constriction. The level of EZH2 expression was determined by Western blotting and immunohistochemical staining. We demonstrated the thickness of vascular remodeling by HE staining. JASPAR was used to predict transcription factors that could affect EZH2. Chromatin immunoprecipitation was used to substantiate the DNAprotein interactions. Promoter luciferase assays were performed to demonstrate the activity of the transcription factors. We found that in vivo, AAC significantly reduced EZH2 protein levels in the thoracic aorta. Smooth muscle-specific overexpression of EZH2 was sufficient to attenuate the AAC-induced reduction in trimethylation of Lys-27 in histone 3 and thickening of the arterial media. Administration of GSK-J4 (an inhibitor of H3K27me3 demethylase) induced the same effects. In addition, we found that mechanical stretch regulated the expression of EZH2 through the Yes-associated protein (YAP)- transcriptional factor TEA domain 1 (TEAD) pathway. TEAD1 bound directly to the promoter of EZH2, and blocking the YAP-TEAD1 interaction inhibited EZH2 downregulation due to mechanical stretch. This study reveals that mechanical stretch downregulates EZH2 through the YAP-TEAD1 pathway, thereby aggravating smooth muscle cell apoptosis and vascular remodeling.


Heart transplantation for end-stage heart failure due to cardiac sarcoidosis.
Cardiac sarcoidosis with end-stage heart failure has a poor prognosis without transplantation. The rates of sarcoid recurrence and rejection are not well established after heart transplantation. A total of 19 heart transplant recipients with sarcoid of the explanted heart were compared with a contemporaneous control group of 1,050 heart transplant recipients without cardiac sarcoidosis. Assessed outcomes included 1st-year freedom from any treated rejection, 5-year actuarial survival, 5-year freedom from cardiac allograft vasculopathy (CAV), 5-year freedom from nonfatal major adverse cardiac events (NF-MACE), and recurrence of sarcoid in the allograft or other organs. Patients with sarcoidosis were maintained on low-dose corticosteroids after transplantation. There were no significant differences between the sarcoid and control groups in 1st-year freedom from any treated rejection (79% and 90%), 5-year posttransplantation survival (79% and 83%), 5-year freedom from CAV (68% and 78%), and 5-year freedom from NF-MACE (90% and 88%). Causes of death (n = 5) in the sarcoid group were coccidioidomycosis, pneumonia, rejection, hemorrhage, and CAV. No patient had recurrence of sarcoidosis in the cardiac allograft. Three of 19 patients (16%) experienced recurrence of extracardiac sarcoid, with no mortality. Patients with cardiac sarcoidosis undergoing heart transplantation have acceptable long-term outcomes without evidence of recurrence of sarcoidosis in the allograft when maintained on low-dose corticosteroids. Progression of extracardiac sarcoid was uncommon, possibly related to immunosuppression. In patients with cardiac sarcoidosis, heart transplantation is a viable treatment modality.


Identification of low frequency knockout mutants in Dictyostelium discoideum created by single or double homologous recombination.
Generation and characterization of knockout clones is a widely used approach to evaluate the specific function of a gene product in Dictyostelium discoideum. The mutant clones are generally obtained by double homologous recombination in the target gene. A frequent limitation to obtaining mutants is the low frequency of homologous recombination. Here we present an easy method to identify rare mutants, based on PCR analysis of pools of clones. This method also allows the isolation of functional knockout mutants created by a single homologous recombination event, which can be more frequent than a double recombination event.


A test system for the determining of the fate of pesticides in surface water. Protocol and comparison of the performance for parathion of ecocores and micro ecosystems from two sources.
Protocols are described for constructing laboratory micro-ecosystems (MES), incubating them with radiolabelled pesticides and then using a routine test procedure to ascertain the fate of these pesticides in surface water. The performance of fresh ecocores and acclimated MES from two sources was compared. The influence of the duration of the acclimation to room temperature and a light cycle on the fate of parathion was studied. The variation between replicates of MES was less than that between ecocores. The eutrophic ecocores and MES performed similarly, the oligotrophic ecocores transformed parathion faster than the oligotrophic MES. In eutrophic systems, reduction to aminoparathion was much faster than in oligotrophic systems. The sandy oligotrophic MES needed a longer acclimation to laboratory conditions than the eutrophic MES to produce reproducible results. The results of year-to-year experiments were also more reproducible for the eutrophic MES.


NADH fluorescence in vivo: changes in cerebral oxidative metabolism and perfusion induced by pentobarbital, indomethacin, and salicylate.
The effects of two prostaglandin synthesis inhibitors on brain oxidative metabolism and cerebral blood volume were studied by the nicotinamide adenine dinucleotide (reduced) (NADH) fluorescence technique in rats. Indomethacin (5, 10, and 15 mg/kg) and sodium salicylate (50, 100, and 300 mg/kg) were administered intravenously to groups of rats anesthetized with either nitrous oxide or pentobarbital (40 mg/kg, i.p.). The effects of pentobarbital alone were also examined: pentobarbital induced a progressive reduction in blood volume 4 min following intraperitoneal administration. A reduced NADH fluorescence (oxidation) was noted approximately 9 min after pentobarbital treatment. In N2O-anesthetized rats, the effects of salicylate were dose-dependent. Low doses (50 and 100 mg/kg) decreased both blood volume and NADH fluorescence; in contrast, salicylate at 300 mg/kg increased blood volume and NADH fluorescence. Following pentobarbital, the effects of salicylate (50 and 100 mg/kg) were reversed: increases in both blood volume and NADH fluorescence were seen. In the absence of pentobarbital, it would appear that salicylate induces a cerebral vasoconstriction, an effect that may be obscured by a central stimulation provoked by this drug. Under N2O anesthesia, indomethacin, in a dose-related manner, induced a decrease in blood volume that was accompanied by a dose-related increase in NADH fluorescence (reduction). The changes induced by the highest dose of indomethacin (15 mg/kg) were essentially abolished by pentobarbital. These results support those studies in which indomethacin-induced cerebral vasoconstriction could be abolished by barbiturates. Furthermore, our experiments demonstrate, following indomethacin infusion, a decrease in brain oxidative metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)


Case report: further upward migration of a misplaced double-J ureteral stent.
A 45-year-old man was referred to our hospital for the removal of a misplaced double-J ureteral stent. The lower end of the stent shortly after insertion was at the level of sacroiliac joint. However one week later the stent was further migrated upwards to the level of 4th lumbar vertebra. Immediate ureterorenoscopy was performed to prevent further migration of the stent to the renal pelvis and the stent was removed by the grasping forceps under direct vision successfully.


Blood clots in COVID-19 patients: Simplifying the curious mystery.
The universal phenomenon of blood clotting is well known to be protective in external cellular/ tissue injury. However, the emergence of unusual thrombotic presentations in COVID-19 patients is the real concern. Interaction of the spike glycoprotein with ACE2 receptor present in the host cell surface mediates the entry of SARS-CoV-2 causing COVID-19 infection. New clinical findings of SARS-CoV-2 pathogenesis are coming out every day, and one such mystery is the formation of mysterious blood clots in the various tissues and organs of COVID-19 patients, which needs critical attention. To address this issue, we hypothesis that, high ACE2 expression in the endothelium of blood vessels facilitates the high-affinity binding of SARS-CoV-2 using spike protein, causing infection and internal injury inside the vascular wall of blood vessels. This viral associated injury may directly/indirectly initiate activation of coagulation and clotting cascades forming internal blood clots. However, the presence of these clots is undesirable as they are responsible for thrombosis and need to be treated with anti-thrombotic intervention.


Why Are Orphaned Adolescents More Likely to Be HIV Positive? Distinguishing Between Maternal and Sexual HIV Transmission Using 17 Nationally Representative Data Sets in Africa.
Why do orphans have higher rates of HIV infection than nonorphaned peers? Research consistently assumes that orphans acquire HIV primarily through sexual behavior, but infections may instead be due to maternal transmission. Although these two pathways have very different implications for HIV programs and policies, their relative contribution has not been previously examined. In this research, we compare the contribution of maternal and sexual transmission to HIV infection among orphans in Africa. We use Demographic and Health Survey data for 21,463 women and 18,359 men from 17 countries. We propose a conceptual framework linking orphanhood to HIV, and use mediation analysis and structural equation modeling to compare the potential contribution of maternal transmission (measured through direct pathways from orphanhood to HIV) and sexual transmission (measured through reports of risky sexual behavior) to orphan HIV infection. Our results suggest that maternal transmission is the predominant pathway of HIV infection among orphaned adolescents: there is strong evidence for a direct pathway from maternal (odds ratio [OR]: 2.45; 95% confidence interval [CI]: 1.72-3.51 for females and OR: 2.45; 95% CI: 1.53-3.90 for males) and double orphanhood (OR: 2.69; 95% CI: 1.97-3.66 and OR: 2.53; 95% CI: 1.68-3.82, respectively) to HIV; greater excess HIV risk in maternal versus paternal orphans. The contribution of sexual behavior is largely not significant. We do not observe correspondingly high orphan disparities in other sexually transmitted diseases. Maternal transmission is a more likely explanation than sexual transmission for heightened HIV infection among orphans. These results suggest that programs designed to address HIV infection among adolescents should focus on reducing maternal transmission and on identifying and testing undiagnosed HIV among orphans.


Polymyxin-B hemoperfusion inactivates circulating proapoptotic factors.
To test the hypothesis that extracorporeal therapy with polymyxin B (PMX-B) may prevent Gram-negative sepsis-induced acute renal failure (ARF) by reducing the activity of proapoptotic circulating factors. Medical-Surgical Intensive Care Units. Sixteen patients with Gram-negative sepsis were randomized to receive standard care (Surviving Sepsis Campaign guidelines) or standard care plus extracorporeal therapy with PMX-B. Cell viability, apoptosis, polarity, morphogenesis, and epithelial integrity were evaluated in cultured tubular cells and glomerular podocytes incubated with plasma from patients of both groups. Renal function was evaluated as SOFA and RIFLE scores, proteinuria, and tubular enzymes. A significant decrease of plasma-induced proapoptotic activity was observed after PMX-B treatment on cultured renal cells. SOFA and RIFLE scores, proteinuria, and urine tubular enzymes were all significantly reduced after PMX-B treatment. Loss of plasma-induced polarity and permeability of cell cultures was abrogated with the plasma of patients treated with PMX-B. These results were associated to a preserved expression of molecules crucial for tubular and glomerular functional integrity. Extracorporeal therapy with PMX-B reduces the proapoptotic activity of the plasma of septic patients on cultured renal cells. These data confirm the role of apoptosis in the development of sepsis-related ARF.


Target Volume Delineation Training in Radiation Oncology in India : A Survey Evaluating Its Status, the Need for Educational Programs and the Utility of Virtual Teaching.
The complexity of modern-day radiotherapy techniques calls for greater accuracy in target volume delineation which requires intensive training and expert guidance. In this study, we intend to evaluate the status of training in target delineation across radiation oncology curriculums in India and utility of webinars in teaching it. We organized daily webinars on the topics of radiological anatomy and target volume delineation in common sites of cancer over a period of 2 weeks. At the end of the program, a 35 item survey questionnaire was shared with the participants. The responses were analysed and are reported here. Out of the 797 participants that registered for the course, 356 radiation oncologists responded to the survey questionnaire. Majority (96%) of our respondents believe that there is a need for additional training in target volume delineation. Ninety percent of the participants felt that radiation oncology curriculum requires a formal radiology training but only 6.7% reported that their training consisted of a dedicated rotation and regular lectures in radiological anatomy. Majority (97%) responded that they were likely to incorporate the points learnt from the webinar sessions in their daily practice. Forty eight percent of respondents opted for attending a webinar to an in-person event in the future while 34% would like to have the option to choose between the two. Ninety four percent agreed that online webinars should be conducted routinely even after the pandemic ends. Our survey results suggest that target volume delineation training in India is deficient and virtual teaching programs can be a practical and effective way to improve it.


Effect of synthetic neuromedin C, a decapeptide of gastrin-releasing peptide (GRP [18-27]), on blood flow and exocrine secretion of the pancreas in dogs.
Neuromedin C, the smaller molecular form of gastrin releasing peptide (GRP [18-27]), has been recently identified from canine intestinal muscle and porcine spinal cord. This study was conducted to determine if this newly identified peptide retains biological activity on canine pancreas in vivo. Intravenous injection of graded doses of synthetic Neuromedin C caused a marked increase of systemic blood pressure and initial reduction of pancreatic blood flow in eleven anesthetized dogs, as measured by Laser Doppler Flowmetry. Flow volume and protein output of pancreatic juice were also increased by Neuromedin C in a dose-related manner in six dogs. These results suggest that this peptide is one of the biologically active forms of mammalian bombesin-like peptides and may possess physiological significance as a novel neuropeptide.


Synaptology and sources of vasoactive intestinal polypeptide and substance P containing axons of the cat celiac ganglion. An experimental electron microscopic immunohistochemical study.
We have examined the possible origin of vasoactive intestinal polypeptide (VIP) and substance P-containing axons and the synapses formed by these axons in the celiac ganglion of the cat, by means of ultrastructural immunohistochemistry combined with various surgical lesions. Axons containing VIP as well as those immunopositive for substance P, formed axo-dendritic and axosomatic synapses with principal ganglion cells. After transection of the superior mesenteric nerve numerous degenerated axonal profiles could be found in the celiac ganglion. Some of these contained VIP immunoreactivity. By contrast in alternate sections stained with substance P antibody only intact axons were labelled. Bilateral vagotomy resulted in the appearance of degenerating axonal profiles in the celiac ganglion, some of which could be stained with substance P antiserum but not with VIP antiserum. Following removal of dorsal root ganglia (Th6-Th12) from both sides, a large number of degenerated axons were found, many of which were immunopositive for substance P but not for VIP. We conclude that the peripheral input to the celiac ganglion contains VIP fibers which form synapses with principal ganglion cells. Substance P-containing fibers reach the celiac ganglion via the vagal nerve as well as from the dorsal root ganglia, and they form synapses with the principal ganglion cells. It is proposed that the VIP and the substance P-containing axons are involved in two different peripheral reflex loops.


Changes of δ15N values during the volatilization process after applying urea on soil.
Ammonia (NH3) volatilized from soils plays an important role in N cycle and air pollution, thus it is important to trace the emission source and predict source contributions to development strategies mitigating the environmental harmful of soil NH3 volatilization. The measurements of 15N natural abundance (δ15N) could be used as a complementary tool for apportioning emissions sources to resolve the contribution of multiple NH3 emission sources to air NH3 pollution. However, information of the changes of δ15N-NH3 values during the whole volatilization process under different N application rates are currently lacking. Hence, to fill this gap, we conducted a 15-day incubation experiment included different urea-N application rates to determine δ15N values of NH3 during volatilization process. Results showed that volatilization process depleted 15N in NH3. The average δ15N value of NH3 volatilized from the 0, 20, 180, and 360 kg N ha-1 treatment was -16.2 ± 7.3‰, -26.0 ± 5.4‰, -34.8 ± 4.8‰, and -40.6 ± 5.7‰. Overall, δ15N-NH3 values ranged from -46.0‰ to -4.7‰ during the whole volatilization process, with lower in higher urea-N application treatments than those in control. δ15N-NH3 values during the NH3 volatilization process were much lower than those of the primary sources, soil (-3.4 ± 0.1‰) and urea (-3.6 ± 0.1‰). Therefore, large isotopic fractionation may occur during soil volatilization process. Moreover, negative relationships between soil NH4+-N and NH3 volatilization rate and δ15N-NH3 values were observed in this study. Our results could be used as evidences of NH3 source apportionments and N cycle.


Survey of sugar beet (Beta vulgaris L.) hAT transposons and MITE-like hATpin derivatives.
Genome-wide analyses of repetitive DNA suggest a significant impact particularly of transposable elements on genome size and evolution of virtually all eukaryotic organisms. In this study, we analyzed the abundance and diversity of the hAT transposon superfamily of the sugar beet (B. vulgaris) genome, using molecular, bioinformatic and cytogenetic approaches. We identified 81 transposase-coding sequences, three of which are part of structurally intact but nonfunctional hAT transposons (BvhAT), in a B. vulgaris BAC library as well as in whole genome sequencing-derived data sets. Additionally, 116 complete and 497 truncated non-autonomous BvhAT derivatives lacking the transposase gene were in silico-detected. The 116 complete derivatives were subdivided into four BvhATpin groups each characterized by a distinct terminal inverted repeat motif. Both BvhAT and BvhATpin transposons are specific for species of the genus Beta and closely related species, showing a localization on B. vulgaris chromosomes predominantely in euchromatic regions. The lack of any BvhAT transposase function together with the high degree of degeneration observed for the BvhAT and the BvhATpin genomic fraction contrasts with the abundance and activity of autonomous and non-autonomous hAT transposons revealed in other plant species. This indicates a possible genus-specific structural and functional repression of the hAT transposon superfamily during Beta diversification and evolution.


Pregnancy Outcomes Following Letrozole Use in Frozen-thawed Embryo Transfer Cycles: A Systematic Review and Meta-analysis.
While widely used for ovulation induction in assisted reproductive technology, the clinical efficacy of letrozole for endometrial preparation prior to frozen-thawed embryo transfer (FET) cycles remains yet to be elucidated. We performed a meta-analysis to compare pregnancy outcomes after letrozole use with those of other endometrial preparation protocols in patients undergoing FET. PubMed, Scopus, Embase and the Cochrane Library were searched for eligible studies. Clinical pregnancy rate (CPR), live birth rate (LBR) and birth defect rate (BDR) were analysed using odds ratio (OR) and 95% confidence interval (CI). A total of 10 studies representing 75 968 FET cycles were included. Comparable CPR and LBR were observed when comparing letrozole administration with natural cycle (OR 1.24, 95% CI: 0.69 - 2.24; OR 1.18, 95% CI: 0.60 - 2.32), artificial cycle (OR 1.46, 95% CI: 0.87 - 2.44; OR 1.39, 95% CI: 0.77 - 2.52), and artificial cycle with gonadotropin-releasing hormone agonist suppression (OR 1.11, 95% CI: 0.78 - 1.59; OR 1.18, 95% CI: 0.82 - 1.68). Pooled results of the limited studies comparing letrozole with human menopausal gonadotropin demonstrated a similar CPR between groups (OR 1.46, 95% CI: 0.29 - 7.21, two studies), but the letrozole group had a statistically lower LBR (OR 0.67, 95% CI: 0.52 - 0.86, one study). No increased BDR was observed in the letrozole group compared to natural cycles or artificial cycles (OR 0.98, 95% CI: 0.60 - 1.61; OR 1.39, 95% CI; 0.84 - 2.28). This pooled analysis supports the use of letrozole as an efficacious and safe alternative to mainstream regimens for endometrial preparation in FET cycles.


Genetic abnormalities detected in ependymomas by comparative genomic hybridisation.
Using comparative genomic hybridisation, we have analysed genetic imbalance in a series of 86 ependymomas from children and adults. Tumours were derived from intracranial and spinal sites, and classified histologically as classic, anaplastic or myxopapillary. Ependymomas showing a balanced profile were significantly (P<0.0005) more frequent in children than adults. Profiles suggesting intermediate ploidy were common (44% of all tumours), and found more often (P<0.0005) in tumours from adults and the spinal region. Loss of 22q was the most common specific abnormality, occurring in 50% of spinal (medullary) ependymomas and 26% of tumours overall. Genetic profiles combining loss of 22q with other specific abnormalities--gain of 1q, loss of 6q, loss of 10q/10, loss of 13, loss of 14q/14--varied according to site and histology. In particular, we showed that classic ependymomas from within the cranium and spine have distinct genetic profiles. Classic and anaplastic ependymomas with gain of 1q tended to occur in the posterior fossa of children and to behave aggressively. Our extensive data on ependymomas demonstrate significant associations between genetic aberrations and clinicopathological variables, and represent a starting point for further biological and clinical studies.


Change in cervical length in cases resulting in threatened preterm labor.
To determine the predisposing changes in cervical length (CL) and the critical range of CL in which significant uterine contractions emerge resulting in threatened preterm labor (TPL). Sixty-eight uncomplicated singleton pregnancies where the CL was <25 mm before 31 weeks were divided into cases with TPL (n = 23) or without (n = 45). CL and uterine contractions were monitored sequentially starting between 16 and 20 weeks. The gestational ages when a CL of <25 or <15 mm was first observed, the interval between these two measurements, and the CL value at TPL diagnosis were analyzed retrospectively. (1) The gestational ages when a CL of <25 and <15 mm was first detected were lower in the TPL group (25 (median); 18-30 (range) and 28; 25-33 weeks, respectively) than in the non-TPL group (27; 20-30 and 33; 26-35 weeks; P = 0.030 and P < 0.001). (2) The interval between the two measurements was shorter in the TPL group (2.5; 0-15 weeks) than in the non-TPL group (5.5; 0-13 weeks, P = 0.034). (3) The CL value at TPL diagnosis was 13 mm (median), ranging from 7 to 18 mm. Cases with early onset and subsequent rapid CL shortening before 31 weeks resulted in TPL when CL decreased below the range 7-18 mm.


Design of exceptionally strong and conductive Cu alloys beyond the conventional speculation via the interfacial energy-controlled dispersion of γ-Al2O3 nanoparticles.
The development of Cu-based alloys with high-mechanical properties (strength, ductility) and electrical conductivity plays a key role over a wide range of industrial applications. Successful design of the materials, however, has been rare due to the improvement of mutually exclusive properties as conventionally speculated. In this paper, we demonstrate that these contradictory material properties can be improved simultaneously if the interfacial energies of heterogeneous interfaces are carefully controlled. We uniformly disperse γ-Al2O3 nanoparticles over Cu matrix, and then we controlled atomic level morphology of the interface γ-Al2O3//Cu by adding Ti solutes. It is shown that the Ti dramatically drives the interfacial phase transformation from very irregular to homogeneous spherical morphologies resulting in substantial enhancement of the mechanical property of Cu matrix. Furthermore, the Ti removes impurities (O and Al) in the Cu matrix by forming oxides leading to recovery of the electrical conductivity of pure Cu. We validate experimental results using TEM and EDX combined with first-principles density functional theory (DFT) calculations, which all consistently poise that our materials are suitable for industrial applications.