Manipulation of nitrogen leaching from tea field soil using a Trichoderma viride biofertilizer.
With the increasing use of chemical fertilizers, negative environmental impacts have greatly increased as a result from agricultural fields. The fungus Trichoderma viride used as a biofertilizer can efficiently reduce nitrous oxide (N2O) emissions from subtropical tea fields in southern China. In this paper, it was further found that T. viride biofertilizer could alleviate nitrogen (N) leaching in tea fields. Gross N leaching was 1.51 kg ha-1 year-1 with no external fertilizer input, but when 225 kg N ha-1 year-1was applied, it increased to 12.38 kg ha-1 year-1 using T. viride biofertilizer but 53.46 kg ha-1 year-1 using urea. Stepwise linear regression analysis identified the factors responsible for N leaching to be soil nitrate concentration and soil interflow, simulated here using the water balance simulation model (WaSiM-ETH). Finally, mass-scale production of T. viride biofertilizer from waste reutilization using sweet potato starch wastewater and rice straw was found to be cost-effective and feasible. These procedures could be considered a best management practice to reduce N leaching from tea fields in subtropical areas of central China and to reduce pollution from other agricultural waste products.


Spray drying of budesonide, formoterol fumarate and their composites--I. Physicochemical characterisation.
The objective of this work was to examine the physicochemical properties of spray dried budesonide, formoterol fumarate and their mixtures at two different weight ratios: 100:6 and 400:6 of budesonide and formoterol fumarate, respectively. A comparison of the thermal properties, crystalline/amorphous nature and particle size of the starting micronised as well as processed materials was carried out. The micronised drugs on their own and the physical mixtures were crystalline in contrast to the spray dried counterparts which were shown to be amorphous. The glass transition temperatures (T(g)s) of the processed actives were determined and appeared at 89.5 and 88 degrees C for budesonide and formoterol fumarate, respectively. As for the spray dried composites, an indication of miscibility and/or interactions between the components was indicated by differential scanning calorimetry and infrared analysis. The spray drying in all cases resulted in smooth, spherical microparticles of sizes suitable for inhalation.


Additional value of associating aortic valve calcification to coronary calcium as a gatekeeper for coronary tomography angiography.
Aortic valve calcification shares risk factors with coronary artery disease. Coronary calcium has been used has a gatekeeper to performing coronary tomography angiography. The aim of this study was to evaluate aortic valve calcification as a predictor of obstructive coronary artery disease by computed tomography, and its possible usefulness, alongside with coronary calcium, to improve the decision of whether or not to proceed with computed tomography angiography. Transversal case-control study including 154 consecutive patients (62 ± 12 years, 57.6 % female, without known coronary or valve disease) undergoing calcium scoring and angiography through computed tomography (Phillips Brilliance, 16-slice). Predictors of aortic valve calcification and obstructive coronary artery disease were identified. Usefulness of aortic valve calcification when added to calcium score for prediction of obstructive coronary artery disease was assessed by binary logistic regression and net reclassification index. Aortic valve calcification was associated with higher coronary calcium, extent and prevalence of obstructive coronary disease, which was identified in 22.1 % of patients and was discriminated by aortic valve calcium with an area under curve 0.749 (p < 0.001, Youden index: 61). A higher discriminative power was achieved with a model based on coronary and aortic valve calcification (AUC 0.900, p < 0.001). Compared with calcium score >400 as a gatekeeper to angiography, the association of aortic calcium >61 allowed a net reclassification index of +7.7 % of patients. Aortic valve calcification is associated with the prevalence and extent of obstructive coronary artery disease by computed tomography angiography and is an easy, fast and useful method to improve the selection of patients for angiography.


Human SPRY2 inhibits FGF2 signalling by a secreted factor.
Growth factor signalling pathways and their inhibitors coordinate the formation of three-dimensional patterns of vertebrates and invertebrates. Temporal and spatial restriction of the response to a few well-defined cells is crucial and needs the integration of positive and negative signals. Recently, Spry has been identified as an inhibitor of fibroblast growth factor (FGF) signalling during Drosophila trachea development. Spry has been described as an intracellular protein that can exert its function in a cell autonomous or a paracrine manner. Here we describe the role of SPRY2, a human homologue of Spry, in human FGF2 signalling. We show that in primary human dermal endothelial cells (MVEC) SPRY2 mRNA is transiently upregulated in response to FGF2. Overexpression of SPRY2 in A375 cells leads to the secretion of a soluble factor that inhibits FGF2- but not VEGF-stimulated proliferation of MVEC. Direct administration of recombinant SPRY2 protein has no effect on MVEC proliferation. However, SPRY2 protein binds the intracellular adaptor protein GRB2, indicating an intracellular localization. A SPRY2/GFP fusion protein remains in the cell, further supporting the intracellular localization of SPRY2. So the intracellular protein SPRY2 is involved in the non-cell autonomous inhibitory effect indirectly, via regulating the secretion of an inhibitor of FGF2 signalling in vertebrates, the evidence of which is presented here for the first time.


Methylenetetrahydrofolate reductase gene polymorphisms: genomic predictors of clinical response to fluoropyrimidine-based chemotherapy?
Fluorouracil (5-FU) is widely used in the treatment of colorectal cancer. Methylenetetrahydrofolate reductase (MTHFR) may play a central role in the action of 5-FU, an inhibitor of thymidylate synthase, by converting 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. The aim of this study was to ascertain whether two polymorphisms in the MTHFR gene (677C>T and 1298 A>C) could be used as genomic predictors of clinical response to fluoropyrimidine-based chemotherapy (in combination with irinotecan or oxaliplatin). Ninety-four patients diagnosed with metastatic colorectal cancer and undergoing 5-FU-containing chemotherapy as a first line treatment were studied. The results suggest that the MTHFR genotype cannot be considered as an independent factor of outcome in colorectal cancer patients under 5-FU-based chemotherapy.


Fe/Co redox and surficial hydroxyl potentiation in the FeCo2O4 enhanced Co3O4/persulfate process for TC degradation.
A magnetic FeCo2O4/Co3O4 nanocomposite was successfully synthesized by a facile hydrothermal method as an efficient activator for persulfate (PS) activation to degrade tetracycline (TC) in an aqueous solution. TC removal and mineralization efficiencies reached up to 91.63% and 43.57% in 120 min in the FCC-3/PS system, respectively. The mixed-valence of Fe/Co in the nanocomposite catalyst was beneficial for electrons transfer between Co and Fe elements and enhanced the redox circulation of Fe and Co in between divalent and trivalent. Surficial analysis and phosphate adsorption test confirmed the existence of -OH groups on the surfaces of FeCo2O4/Co3O4 nanocomposite. Fe/Co redox and surficial hydroxyl in the catalyst played significant roles in the TC potentiation degradation, which was contributed by the plenty of adsorbed -OH groups and excellent dispersity of FeCo2O4 in the FeCo2O4/Co3O4 composite. The sulfate radicals were major species followed by the hydroxyl radicals, and the surficial adsorbed hydroxyl made great contributions to radical generation. The cycling test and intermediate toxicity analysis indicated that the nanocomposite was considered stable and practicable in water treatment. This work demonstrated that the FeCo2O4/Co3O4 nanocomposite was an effective and environ-friendly catalyst towards PS activation for removing organic pollutants from water.


Pain and thyroid hormones.
The role of endocrine systems in chronic pain mechanisms is slowly getting increasing experimental and clinical consideration. Many painful conditions appear to be directly and/or indirectly induced, reduced or, in some cases, modulated by hormones. We have done much work in trying to understand the relationship between hormones and pain, with particular attention to the hypothalamus-pituitary-gonadal axis. To expand our knowledge of this field, we have directed our attention to another axis, the hypothalamus-pituitary-thyroid (HPT). The literature on thyroid functions is vast but very few studies have focused on the HPT axis and pain. The few available data are considered in the present review to stimulate interest in the possible interactions between the HPT axis and pain.


Reinnervation of hind limb extremity after lumbar dorsal root ganglion injury.
Loss of dorsal root ganglion neuron, or injury to dorsal roots, induces permanent somatosensory defect without therapeutic option. We explored an approach to restoring hind limb somatosensory innervation after elimination of L4, L5 and L6 dorsal root ganglion neurons in rats. Somatosensory pathways were reconstructed by connecting L4, L5 and L6 lumbar dorsal roots to T10, T11 and T12 intercostal nerves, respectively, thus allowing elongation of thoracic ganglion neuron peripheral axons into the sciatic nerve. Connection of thoracic dorsal root ganglion neurons to peripheral tissues was documented 4 and 7 months after injury. Myelinated and unmyelinated fibers regrew in the sciatic nerve. Nerve terminations expressing calcitonin-gene-related-peptide colonized the footpad skin. Retrograde tracing showed that T10, T11 and T12 dorsal root ganglion neurons expressing calcitonin-gene-related-peptide or the neurofilament RT97 projected axons to the sciatic nerve and the footpad skin. Recording of somatosensory evoked potentials in the upper spinal cord indicated connection between the sciatic nerve and the central nervous system. Hind limb retraction in response to nociceptive stimulation of the reinnervated footpads and reversion of skin lesions suggested partial recovery of sensory function. Proprioceptive defects persisted. Delayed somatosensory reinnervation of the hind limb after destruction of lumbar dorsal root neurons in rats indicates potential approaches to reduce chronic disability after severe injury to somatosensory pathways.


The hormone-sensitive lipase gene and body composition: the HERITAGE Family Study.
To investigate whether the C-60G polymorphism and other markers in the hormone-sensitive lipase (LIPE) gene are associated with baseline body composition and free-fatty acid (FFA) concentrations measured at rest and during low-intensity exercise in white and black subjects participating in the HERITAGE Family Study. Adult sedentary white (245 men and 258 women) and black (91 men and 185 women) subjects. body mass index (BMI); fat mass (FAT); percentage body fat (%FAT); fat-free mass (FATFR); sum of eight skinfolds (SF8); subcutaneous (ASF), visceral (AVF) and total (ATF) abdominal fat areas assessed by CT scan; plasma FFA concentrations measured at rest (FFAR), at a power output of 50 W (FFA50) and at a relative power output of 60% of VO(2max) (FFA60%); and fasting insulin (INS). Association between the C-60G polymorphism of the LIPE gene and each phenotype was tested separately in men and women using ANCOVA with the effects of age and race as covariates and with further adjustment for FAT for ASF, AVF, ATF, FFAR, FFA50 and FFA60%. Secondly, owing to significant gene-by-race interaction, associations were investigated separately in each of the two race groups. Linkage was tested with the C-60G polymorphism, a dinucleotide repeat polymorphism in the intron 7 of the LIPE gene and two microsatellites markers (D19S178 and D19S903) flanking the LIPE gene. There were no race differences in the allele frequencies of the C-60G polymorphism of the LIPE gene. No association or gene-by-race interaction was observed in men. However, in women, strong gene-by-race interactions were observed for BMI (P=0.0005), FAT (P=0.0007), %FAT (P=0.0003), SF8 (P=0.0001), ASF (P=0.03) and ATF (P=0.01). When the analysis was performed separately in each race, white women carriers of the -60G allele exhibited lower %FAT (P=0.005) and SF8 (P=0.01) than non-carriers, while in black women, the -60G allele was associated with higher BMI (P=0.004), FAT (P=0.009), %FAT (P=0.01) and SF8 (P=0.0009). These associations were no longer significant after adjusting for INS. Evidence of linkage was observed in whites with ATF, FFAR, FFA50 and FFA60%. These results suggest that the C-60G polymorphism in the LIPE gene plays a role in determining body composition and that its effect is sex-, race- and insulin-dependent.


Key components and IT assistance of participant management in clinical research: a scoping review.
Managing participants and their data are fundamental for the success of a clinical trial. Our review identifies and describes processes that deal with management of trial participants and highlights information technology (IT) assistance for clinical research in the context of participant management. A scoping literature review design, based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement, was used to identify literature on trial participant-related proceedings, work procedures, or workflows, and assisting electronic systems. The literature search identified 1329 articles of which 111 were included for analysis. Participant-related procedures were categorized into 4 major trial processes: recruitment, obtaining informed consent, managing identities, and managing administrative data. Our results demonstrated that management of trial participants is considered in nearly every step of clinical trials, and that IT was successfully introduced to all participant-related areas of a clinical trial to facilitate processes. There is no precise definition of participant management, so a broad search strategy was necessary, resulting in a high number of articles that had to be excluded. Nevertheless, this review provides a comprehensive overview of participant management-related components, which was lacking so far. The review contributes to a better understanding of how computer-assisted management of participants in clinical trials is possible.


Phosphorylation of CpgA protein enhances both its GTPase activity and its affinity for ribosome and is crucial for Bacillus subtilis growth and morphology.
In Bacillus subtilis, the ribosome-associated GTPase CpgA is crucial for growth and proper morphology and was shown to be phosphorylated in vitro by the Ser/Thr protein kinase PrkC. To further understand the function of the Escherichia coli RsgA ortholog, CpgA, we first demonstrated that its GTPase activity is stimulated by its association with the 30 S ribosomal subunit. Then the role of CpgA phosphorylation was analyzed. A single phosphorylated residue, threonine 166, was identified by mass spectrometry. Phosphoablative replacement of this residue in CpgA induces a decrease of both its affinity for the 30 S ribosomal subunit and its GTPase activity, whereas a phosphomimetic replacement has opposite effects. Furthermore, cells expressing a nonphosphorylatable CpgA protein present the morphological and growth defects similar to those of a cpgA-deleted strain. Altogether, our results suggest that CpgA phosphorylation on Thr-166 could modulate its ribosome-induced GTPase activity. Given the role of PrkC in B. subtilis spore germination, we propose that CpgA phosphorylation is a key regulatory process that is essential for B. subtilis development.


THE STORM (acute coronary Syndrome in paTients end Of life and Risk assesMent) study.
Elderly patients with coexisting frailty and multiple comorbidities frequently present to the emergency department (ED). Because non-cardiovascular comorbidities and declining health status may affect their life expectancy, management of these patients should start in the ED. This study evaluated the role of Gold Standards Framework (GSF) criteria for identifying patients with acute coronary syndromes (ACS) approaching end of life. All consecutive patients admitted to the ED and hospitalised with a diagnosis of ACS between May 2012 and July 2012 were included. According to GSF criteria, patients were labelled as positive GSF status when they met at least one general criterion and two heart disease criteria; furthermore, traditional cardiovascular risk scores (the Global Registry for Acute Coronary Events (GRACE) score and the Age, Creatinine and Ejection Fraction (ACEF) score) were calculated and WHOQOL-BREF was assessed. Mortality and repeat hospitalisation due to cardiovascular and non-cardiovascular causes were evaluated at 3-month and 12-month follow-up. From a total of 156 patients with ACS enrolled, 22 (14%) had a positive GSF. A positive GSF was associated with higher rate of non-cardiovascular events (22.7% vs 6.7%; p=0.03) at 3 months and higher rates of both cardiovascular and non-cardiovascular events (36% vs 16.4%; p=0.04 and 27.3% vs 6.7%; p=0.009, respectively) at 12 months. In multivariate analysis, an in-hospital GRACE score was a predictor of cardiovascular events, while a positive GSF independently predicted non-cardiovascular events. The GSF score independently predicts non-cardiovascular events in patients presenting with ACS and may be used along with traditional cardiovascular risk scores in choosing wisely the most appropriate treatment. The present results need to be externally validated on larger samples.


Acute otitis media in children: are decongestants or antihistamines necessary?
This study was designed to investigate the efficacy of a decongestant-antihistamine preparation in combination with antibiotic treatment of acute otitis media. The effectiveness of a new Dimetapp (DIM) preparation was assessed in comparison with each of its components (brompheniramine maleate [BPM] and phenylephrine hydrochloride [PEH] as well as a placebo (PL) vehicle in the treatment of acute otitis media. In a randomized double blind study, 98 children were treated in the emergency department or outpatient medical clinics at Children's Hospital of Michigan with amoxicillin and either DIM, BPM, PEH, or PL. They were evaluated at two weeks by clinical examination, pneumatoscopy, and tympanometry. Fifty-eight patients (59%) continued to have evidence of fluid in the middle ear. These patients were continued on the test medications for another two weeks and then reevaluated. There were significant differences between the treatment groups (DIM, BPM, and PEH) and the control PL group; the patients receiving Dimetapp or placebo fared better than those receiving BPM or PEH. However, there was no difference in the overall response between Dimetapp and placebo. Antihistamine-decongestant therapy does not appear to be necessary in the treatment of acute otitis media in children.


Inspiratory-activated and inspiratory-inhibited airway vagal preganglionic neurons in the ventrolateral medulla of neonatal rat are different in intrinsic electrophysiological properties.
This study investigates the firing properties of the inspiratory-activated and inspiratory-inhibited airway vagal preganglionic neurons located in the external formation of the nucleus ambiguus. The results showed that inspiratory-activated and inspiratory-inhibited neurons are distributed with different density and site preference in this area. Inspiratory-inhibited neurons exhibit significantly more positive resting membrane potential, more negative voltage threshold and lower minimal current required to evoke an action potential under current clamp. The afterhyperpolarization in inspiratory-activated neurons was blocked by apamin, a blocker of the small-conductance Ca(2+)-activated K(+) channels; and that in inspiratory-inhibited neurons by charybdotoxin, a blocker of the large-conductance Ca(2+)-activated K(+) channels. Under voltage clamp, depolarizing voltage steps evoked tetrodotoxin-sensitive rapid inward sodium currents, 4-aminopyridine-sensitive outward potassium transients and lasting outward potassium currents. 4-Aminopyridine partially blocked the lasting outward potassium currents of inspiratory-activated neurons but was ineffective on those of inspiratory-inhibited neurons. These findings suggest that inspiratory-activated and inspiratory-inhibited neurons are differentially organized and express different types of voltage-gated ion channels.


Diverse Effects of Women's Employment on Fertility: Insights From Italy and Poland: Diverses conséquences de l'emploi des femmes sur la fécondité: quelques informations à partir des cas de l'Italie et de la Pologne.
In this paper, we look into how country-specific factors shape the interrelationship between childbearing and women's labor supply. To this end, we compare Italy and Poland, two low-fertility countries where the country-specific obstacles to work and family reconciliation are similarly strong but which differ in the history of women's labor supply and the extent to which couples' material aspirations are satisfied by men's earnings. Our findings show that women's employment clearly conflicts with childbearing in Italy, while in Poland women tend to combine the two activities, despite the similar difficulties they face. These results challenged the standard microeconomic explanations and point to the importance of other country-specific factors, apart from conditions for work and family reconciliation, in shaping women's employment and fertility decisions, such as economic incentives or culturally rooted behavioral patterns. Overall, our study provides thus foundations for explaining the variation in the relationship between women's employment and fertility in an enlarged Europe.


Can LBC Completely Replace Conventional Pap Smear in Developing Countries.
A number of screening techniques have been developed to reduce the incidence of cervical cancer, most common of which is conventional Pap smear (CPS) being overtaken by liquid-based cytology (LBC) in most of the developed countries. There are a number of studies with conflicting results, and no method has been shown superior in terms of all parameters. LBC was introduced in our hospital in 2014, and we planned to do a study and compare results of the two techniques. This study aims to compare the two methods in terms of sensitivity, specificity, positive predictive value and negative predictive value, turnover time, cost-effectiveness, sample adequacy. This study has been done in 100 women with unhealthy cervix to increase the output. This was a prospective observational study. A total of 100 women fulfilling the inclusion criteria were subjected to screening test. In first 50 cases, first conventional Pap smear was taken and then LBC, and in remaining 50 cases, first LBC and then conventional Pap smear were taken; this was done to remove bias. The number of unsatisfactory slides was reduced with LBC, and turnover time was less for LBC. The detection of ASCUS was increased with LBC, but the detection of higher-grade lesions (HSIL and SCC) was equal with both tests. The superiority of LBC with respect to reduction in the number of unsatisfactory slides and less turnover time is being offset with increased detection of low-grade lesions subjecting women to further testing increasing the cost of programme and anxiety among women. It is difficult to say that it can completely replace conventional Pap smear in low-resource settings.


Oxidative Stress, Disrupted Energy Metabolism, and Altered Signaling Pathways in Glutaryl-CoA Dehydrogenase Knockout Mice: Potential Implications of Quinolinic Acid Toxicity in the Neuropathology of Glutaric Acidemia Type I.
We investigated the effects of an acute intrastriatal QUIN administration on cellular redox and bioenergetics homeostasis, as well as on important signaling pathways in the striatum of wild-type (Gcdh +/+ , WT) and knockout mice for glutaryl-CoA dehydrogenase (Gcdh -/- ) fed a high lysine (Lys, 4.7 %) chow. QUIN increased lactate release in both Gcdh +/+ and Gcdh -/- mice and reduced the activities of complex IV and creatine kinase only in the striatum of Gcdh -/- mice. QUIN also induced lipid and protein oxidative damage and increased the generation of reactive nitrogen species, as well as the activities of the antioxidant enzymes glutathione peroxidase, superoxide dismutase 2, and glutathione-S-transferase in WT and Gcdh -/- animals. Furthermore, QUIN induced DCFH oxidation (reactive oxygen species production) and reduced GSH concentrations (antioxidant defenses) in Gcdh -/- . An early increase of Akt and phospho-Erk 1/2 in the cytosol and Nrf2 in the nucleus was also observed, as well as a decrease of cytosolic Keap1caused by QUIN, indicating activation of the Nrf2 pathway mediated by Akt and phospho-Erk 1/2, possibly as a compensatory protective mechanism against the ongoing QUIN-induced toxicity. Finally, QUIN increased NF-κB and diminished IκBα expression, evidencing a pro-inflammatory response. Our data show a disruption of energy and redox homeostasis associated to inflammation induced by QUIN in the striatum of Gcdh -/- mice submitted to a high Lys diet. Therefore, it is presumed that QUIN may possibly contribute to the pathophysiology of striatal degeneration in children with glutaric aciduria type I during inflammatory processes triggered by infections or vaccinations.


Posterior-only debridement, internal fixation, and interbody fusion using titanium mesh in the surgical treatment of thoracolumbar tuberculosis with spinal epidural abscess: a minimum 5-year follow-up.
To investigate the clinical efficacy and feasibility of posterior-only debridement, internal fixation, and interbody fusion using titanium mesh in the surgical treatment of thoracolumbar tuberculosis (TB) with spinal epidural abscess. From January 2008 to January 2014, a total of 45 patients (27 male and 18 female) were reviewed. The patients were diagnosed with thoracolumbar TB with spinal epidural abscess. The patients underwent posterior-only debridement, internal fixation, and interbody fusion using titanium mesh. Hence, we assessed the intraoperative and postoperative complications, disease recurrences, kyphosis deformity correction, and neurological improvement following the American Spinal Injury Association (ASIA). We used SPSS 22.0 for the statistical analyses. An independent Student's t-test was used for the analysis of preoperative and postoperative continuous variables. The value of P (P < 0.05) was considered statistically significant. The mean age of patients was 37.76 ± 10.94 years (17-59 years). The mean follow-up time was 82.76 ± 12.56 months (60-128 months). The mean kyphosis Cobb angle preoperative was 29.36 ± 13.29° (5-55°) and postoperative was 3.58 ± 5.44° (- 6-13°), given the value of P (P < 0.001). According to the neurological score by the ASIA scale, there were 3 cases of grade B, 11 cases of grade C, 16 cases of grade D, and 15 cases of grade E preoperatively. The neurological score improved by 1 ~ 2 grades. All patients achieved pain relief and the VAS score significantly reduced at the last follow-up (P<0.05). While 1 patient had cerebrospinal fluid leakage, 1 had a neurological complication, 1 had delayed surgical wound healing, and 1 had a disease recurrence. No pseudoarthrosis or implant failure occurred in our patients. All patients achieved solid bone graft fusion. For thoracolumbar TB patients with spinal epidural abscess, posterior-only debridement, internal fixation, and interbody fusion using titanium mesh are safe and effective surgical treatments.


Incidence of Adverse Pregnancy Outcomes Based on the Degree of Short Interpregnancy Interval in Urban Milwaukee Population.
Short interpregnancy interval is defined as conception occurring within 18 months of a previous live birth. Studies show increased risks of preterm birth, low birth weight, and small for gestational age with short interpregnancy intervals; however, it is unclear if these risks are higher for all short interpregnancy intervals or only for those less than 6 months. The objective of this study was to evaluate prevalence of adverse pregnancy outcomes among people with short interpregnancy intervals, stratified by degree: less than 6 months, 6 to 11 months, and 12 to 17 months. We conducted a retrospective cohort study of people with 2 singleton pregnancies between 2015 and 2018 at a single academic center. The following outcomes were compared between patients with interpregnancy intervals of less than 6 months, 6 to 11 months, 12 to 17 months, and 18 months or more; hypertensive disorders of pregnancy (gestational hypertension and preeclampsia), preterm birth at less than 37 weeks, low birth weight ( < 2500 g), congenital anomalies, and gestational diabetes. Bivariate and multivariate analyses were done to examine the independent role of the degree of short interpregnancy interval and each outcome. A total of 1,462 patients were included in the analysis, with 80 pregnancies occurring at interpregnancy intervals less than 6 months, 181 at 6 to 11 months, 223 at 12 to 17 months, and 978 at 18 months or more. In unadjusted analysis, patients with interpregnancy intervals less than 6 months had the highest rate of preterm birth at 15.0%. In addition, patients with interpregnancy intervals less than 6 months and 12 to 17 months had higher rates of congenital anomalies versus those with interpregnancy intervals of 18 months or more. In multivariate analysis, controlling for sociodemographic and clinical confounding factors, interpregnancy intervals less than 6 months were associated with 2.3 higher odds of preterm birth (95% CI, 1.13-4.68), and those 12 to 17 months were associated with 2.52 higher odds of congenital anomalies (95% CI, 1.22-5.20). The odds of gestational diabetes were lower with interpregnancy intervals of 6 to 11 months compared to those 18 months or more (aOR 0.26; 95% CI, 0.08-0.85). In this single-site cohort, people with interpregnancy intervals less than 6 months had higher odds of preterm birth, while those with interpregnancy intervals 12 to 17 months had higher odds of congenital anomalies, compared with the control group with interpregnancy intervals greater than or equal to 18 months. Future research should focus on identifying modifiable risk factors for short interpregnancy intervals and interventions to reduce them.


Straight wire: the next generation.
Frequently, the anticipated results of treatment are not achieved by using preadjusted appliances and straight wires. This is due to inaccurate bracket placement, variations in tooth structure, variations in the maxillary/mandibular relationships, tissue rebound, and mechanical deficiencies of edgewise orthodontic appliances. Clearly, one preadjusted appliance prescription cannot fit all orthodontic patients. Individualized prescriptions for preadjusted orthodontic appliances can be fabricated once all of these reasons are recognized. From the cephalogram and visual treatment objective, the desired position of maxillary and mandibular incisors can be determined according to the maxillary/mandibular relationships. The torque angle of the labial surface of maxillary and mandibular incisors relative to the arch wire plane can be measured with an incisor torque template. The development and refinement of a system to vary the orientation of the bracket arch wire slot relative to the labial surface of each tooth provides a solution to these problems. Beyond the accuracy or inaccuracy of bracket placement and the fact that brackets are placed away from the center of resistance, orthodontic appliances have two additional significant mechanical deficiencies; play between the arch wire and the arch wire slot, and force diminution. These deficiencies cannot be eliminated from current appliances, however, they can be minimized by using reasonably stiff arch wires approximating the size of the arch wire slots. The amount of play plus the amount of force diminution inherent in your appliance can be added to or subtracted from the torque, tip, rotation, and height parameters for each bracket to deliver the teeth to the desired positions. Therefore treatment goals can be achieved with maximum efficiency.


Glass microstructure capping and bonding techniques.
The capping of microfluidic features fabricated in glass substrates is achievable by various technological methods. Of the entire spectrum of possibilities (gluing, glass bonding via intermediate layers, pressure or plasma-assisted glass bonding, etc.) a detailed description of three techniques is presented here. The first is a low temperature PDMS-glass adhesion bonding, the second is medium temperature pressure assisted glass-glass bonding, and finally, high temperature glass-glass fusion bonding. All these protocols allow completion of the manufacturing process for a fully enclosed microfluidic chip. Nevertheless, as they are complementary rather than competing methods, they effectively extend the range of tools available to fabricate lab-on-a-chip microdevices. Each has its own merits and each could feasibly be used at different developmental stages of a given microfluidic device.


Comparative in vitro activities of twelve antimicrobial agents against Campylobacter species.
The in vitro susceptibility of 27 Campylobacter jejuni, 31 Campylobacter coli, and 30 Campylobacter fetus subsp. fetus strains to 12 antimicrobial agents was determined. Ciprofloxacin, a new quinoline derivative, was the most active agent tested. Antimicrobial susceptibility differed among the three species tested.


The Juggling Act of Supervision in Community Mental Health: Implications for Supporting Evidence-Based Treatment.
Supervisors are an underutilized resource for supporting evidence-based treatments (EBTs) in community mental health. Little is known about how EBT-trained supervisors use supervision time. Primary aims were to describe supervision (e.g., modality, frequency), examine functions of individual supervision, and examine factors associated with time allocation to supervision functions. Results from 56 supervisors and 207 clinicians from 25 organizations indicate high prevalence of individual supervision, often alongside group and informal supervision. Individual supervision serves a wide range of functions, with substantial variation at the supervisor-level. Implementation climate was the strongest predictor of time allocation to clinical and EBT-relevant functions.


Seed mass and emergence time effects on performance of Panicum dichotomiflorum Michx. across environments.
The effects of seed mass and emergence time on growth and reproduction of the annual, C4 grass, Panicum dichotomiflorum Michx., were investigated in an experimental field study. Individual seeds of P. dichotomiflorum of known mass were sown into marked plots in four newly-abandoned fields that differed in soil nutrient availability, soil moisture and the time of the year in which they were abandoned. Seedling emergence was monitored daily for four weeks following sowing. In none of these fields was there any relationship between seed mass and emergence time. Analyses of covariance indicated that the effects of seed mass and emergence date on plant performance varied among fields. Seed mass affected performance in one field (SOUTH EARLY) where abiotic stress after emergence was high. In contrast, later emergence significantly reduced performance in all four fields. We used a path analysis to decompose the direct and indirect effects of seed mass and emergence time on plant performance in each field. The path analysis revealed that in all four fields, final weight had a significant positive effect on seed production. The effect of seed mass and emergence time had variable (and often opposite effects) on these traits. Seed mass only had a significant positive, direct effect on seed production in the most abiotically stressful field (SOUTH LATE). In the other fields, the effects of seed mass on fecundity were mediated by the effect on final weight. Thus, the effects of seed mass and emergence time on growth and reproduction in P. dichotomiflorum vary across environments.


Evaluation of the change in efficacy of erenumab when used long-term for migraine prevention after initial established benefit in a veteran population.
With the increased use of erenumab and other calcitonin gene-related peptide antagonists for migraine prevention, increased evidence on long-term efficacy and real-world effectiveness is needed. Some reports of a wearing-off effect or waning efficacy over time have been observed with erenumab use. This study evaluated the change in efficacy of erenumab after initial established benefits for migraine prevention in a veteran population. This retrospective chart review evaluated patients who were prescribed erenumab for migraine prevention at a Veterans Affairs neurology clinic between June 1, 2018, and May 31, 2021. Patients with an initial 50% or greater reduction in mean monthly headache days (MHDs) by 12 weeks after erenumab 70 mg initiation were then followed forward to determine the change in MHDs until erenumab dose was increased, changed to galcanezumab, or by November 30, 2021, to ensure a minimum 6-month follow-up for all patients. Ninety-three patients were included for analysis. A significant reduction in mean MHDs from 16.1 to 5.7 days was found by 12 weeks after erenumab 70 mg initiation (p < 0.0001). Following this initial response to erenumab, 69% of patients experienced a significant increase in MHDs over an average time of 7.8 months and required a subsequent dose increase to erenumab 140 mg or change to galcanezumab. The remaining 31% of patients continued erenumab 70 mg monthly with a further nonstatistically significant decline in MHDs. A decrease in efficacy with the long-term use of erenumab was observed for the majority of patients evaluated in this analysis. This suggests that patients with initial benefits on lower dose erenumab should be monitored for change to effectiveness.


Anti-angiogenic therapy for ovarian cancer.
Angiogenesis is a known hallmark in cancer and plays a crucial role in ovarian cancer carcinogenesis and invasion. Anti- angiogenic agents are active in ovarian cancer treatment either as monotherapy or combined with chemotherapy, immunotherapy or poly ADP ribose polymerase (PARP) inhibitors. We review the mechanism of action, clinical activity and safety profile of the most important drugs either in the actual treatment or in current evaluation in the ovarian cancer treatment scenario (neoadjuvant, first line and relapse).


Modulatory effects of substance P on norepinephrine induced vasoconstrictor responses in the rat mesentery.
1. The role of substance P (SP) in adrenergic transmission has been studied in the isolated perfused rat mesentery. 2. Intra-arterial perfusion of SP (4 x 10(-9) to 4 x 10(-7)M) produced a dose dependent potentiation of norepinephrine (NE) induced vasoconstrictor responses and a shift of the log dose--response curve to the left. 3. Saralasin, a specific antagonist of angiotensin II (ang. II) when perfused at a concentration of 3 x 10(-9)M did not change the NE responses as such. However, the potentiating effect of SP could not be demonstrated in the presence of saralasin. 4. Indomethacin, a prostaglandin (PG) synthetase inhibitor, when perfused at a concentration of 2.8 x 10(-6)M, markedly attenuated the vascular responses to NE, which could not be normalized by the addition of SP. 5. It appears that SP's potentiating effect on NE responses in the perfused rat mesentery simulates ang. II and not prostaglandins. A direct non-specific post synaptic sensitizing effect of SP on vascular smooth muscle cell, for its potentiating property, cannot be ruled out.


Bioinspired Dry Adhesives for Highly Adaptable and Stable Manipulating Irregular Objects under Vibration.
For dry adhesive-based operation, highly adaptable and stable manipulation is important but also challenging, especially for irregular objects with complex surface (such as abrupt profile and acute projection) under vibration-inducing environments. Here, a multi-scale adhesive structure, with mechanically isolated energy-absorbing backing, based on the synergistic action of microscale contact end (seta), mesoscale supporting layer (lamella), and macroscopic backing (muscle tissues) of gecko's sole, is proposed. Top layer of mushroom-like micro tips provides dry adhesion via mimicking gecko's seta, and bottom layer of physical cuts and porous feature achieves the interfacial mechanical decoupling and crack inhibition via mimicking the non-continuous distributing of lamella and compliance of muscle. The proposed dry adhesive exhibits excellent adaptable adhesion to various objects with curved or irregular surfaces, even for that with abrupt contours, as well as an amazing stable anti-vibration ability, opening a new avenue for the development of dry adhesive-based device or system.


Determination of sugars in honey by liquid chromatography.
Honey is a rich conventional natural resource of sweetness and energy for human beings. A protocol for the determination of two important monosaccharide sugars (fructose and glucose) in honey was established in the current study by using normal phase partition liquid chromatography and 1-5% combined working standard of glucose, fructose and sucrose.


The continuous performance test, identical pairs version: II. Contrasting attentional profiles in schizophrenic and depressed patients.
The Continuous Performance Test-Identical Pairs version was administered to 14 schizophrenic patients, 17 depressed patients, and 28 normal controls. The task was divided into verbal and spatial stimuli, as well as no-distraction and distraction (verbal and auditory) conditions. Both patient groups displayed attentional impairments compared to normal subjects, but they differed from each other in specific profiles. Schizophrenic patients were characterized by a global impairment and a particular inability to focus on the critical stimuli, whether verbal or spatial. They also made an excess of random responses throughout the task but showed no evidence that attention declined from its initial level over time. Depressed patients did not display a global attentional deficit but did show a specific inability to attend to spatial as compared to verbal stimuli and, in particular, a confusion when the spatial stimuli were only slightly different. Performance on a secondary task in response to a change in expectation improved dramatically for depressed but not schizophrenic patients, suggesting a more efficient allocation strategy, a greater reserve of processing capacity, or more dependence on motivational factors in depressed patients. Schizophrenic and depressed patients were alike in extent of distractibility. Whereas normal controls improved with the onset of external distraction, schizophrenic and depressed patients deteriorated to an equal extent. Distractibility was thus concluded to be a correlate of acute psychiatric illness and not specific for schizophrenia.


Lump on the scalp of a child arising over a previous parietal fracture: growing skull fracture or post-traumatic lipoma?
A young girl was referred to our Institution for the appearance of a painless soft swelling in the right parietal region of the scalp. In the same site, the patient had a parietal bone fracture 1 year ago. In the suspicion of a growing skull fracture, the patient underwent radiological investigations. Ultrasound showed a soft, poorly vascularised swelling with parenchymatous content. The skull X-ray showed an apparent healing of the previous fracture. CT scan and MRI confirmed the correct healing of the fracture and described the presence of a lipomatous mass. The mass was surgically removed and histology confirmed the diagnosis of encapsulated lipoma. The postoperative period was uneventful, with no evidence of infections or recurrence in the 6-month follow-up.


Galloyl flavonoids from Acacia farnesiana pods possess potent anthelmintic activity against Haemonchus contortus eggs and infective larvae.
Acacia farnesiana (L.) Willd is a shrub legume used as condiment, medicinal plant and bioactive herbage. This species is used in traditional medicine of several countries to relieve the symptoms of gastrointestinal diseases, diarrhoea, stomach pain and typhoid as well as astringent, antidysenteric and anthelmintic. Some studies have shown that this plant displayed anthelmintic activity against several gastrointestinal nematode parasites of livestock, and also against parasites of human beings, such as malaria. This work describes the isolation and chemical identification of the anthelmintic compounds of Acacia farnesiana pods against eggs and infective larvae of the sheep parasitic nematode Haemonchus contortus. The bio-guided chemical fractioning of A. farnesiana pods using ethyl acetate against H. contortus eggs and infective larvae allowed for the identification of naringenin 7-O-(6″-galloylglucoside) (flavonol group) as the compound responsible for the anthelmintic activity against this important parasitic nematode. Anthelmintic activity was assessed using the egg hatching inhibition assay (EHI) and mortality tests. A complete hydroalcoholic extract (HA-E) at 12.5-50 mg/mL, an aqueous fraction (Aq-F) at 3.12-25 mg/mL and an ethyl acetate fraction (EtOAc-F) at 3.12-25 mg/mL were analysed in the first selection phase. The purification of compounds through the chromatographic separation of the organic fraction resulted in nine less complex mixtures (C1F1, C1F2, C1F3, C1F4, C2F1, C2F2, C2F3, C2F4 and C2F5) that were assessed at 0.62-5 mg/mL concentrations. In addition, thiabendazole (0.6 mg/mL) and ivermectin (5 mg/mL) were used as positive controls. Likewise, distilled water and 4% methanol were used as negative controls. The bioactive compounds of EtOAc-F were obtained and characterised through chromatographic processes like open column chromatography, thin layer chromatography (TLC), high performance liquid chromatography (HPLC), ultra-performance liquid chromatography (UPLC) and gass chromatography-mass detection (GC-MS). Bioactive compounds were identified by spectroscopy (1H and 13C NMR) and mass spectrometric analysis. Additionally, the H. contortus eggs and infective larvae exposed to the bioactive compounds were observed through environmental scanning electron microscopy (ESEM) and confocal laser scanning microscopy (CLSM). Data were analysed based on a completely randomised design using ANOVA through a general linear model. The EtOAc-F fraction showed the highest ovicidal and larvicidal activities, at close to 100% at 3.12 and 6.25 mg/mL, respectively. The treatments C1F2, C1F3 and C2F3 displayed the main ovicidal activity (80-100%) at 2.5 mg/mL. The major compounds found in these sub-fractions were identified as galloyl derivatives and flavanones, including gallic acid (1), methyl gallate (2), ethyl gallate (3), naringin (4), naringenin 7-O-(4″, 6″-digalloylglucoside) (5), naringenin 7-O-(6″-galloylglucoside) (6) and naringenin (7). Likewise, the ESEM and CLSM images showed that the assessed compounds adhered to the eggshell and the external cuticle of the larvae. These results indicate that A. farnesiana pods contain nematocidal compounds and might be promising natural anthelmintic agents against H. contortus. This leguminous plant could be used as a nutraceutical food source for the control of gastrointestinal nematodes in small ruminants.


Rickets--a complication of ifosfamide chemotherapy for Wilms tumor.
Recent reports of metabolic bone disease occurring as a result of drug induced Fanconi syndrome due to ifosfamide have appeared in the pediatric literature. Ifosfamide is a chemotherapeutic agent used for treatment of pediatric solid tumors. We present an additional case of ifosfamide induced rickets, the first in the radiologic literature.


The Effects of In Vitro Incubation of Asthenoteratozoospermic Semen after Density Gradient Centrifugation at Room Temperature and 37°C on Sperm Parameters, Chromatin Quality and DNA Fragmentation in a Short Time Period.
Sperm quality is an important factor in assisted reproductive technology (ART) that affects the success rate of infertile couples treatment. In vitro incubation of sperm can influence its parameters and DNA integrity. The present study focused on the effect of different incubation temperatures sperm parameters on asthenoteratozoospermia semen prepared with density gradient centrifugation at different times. Twenty-seven samples were collected and prepared. Then, the suspension was divided into two parts. One part was incubated at room temperature (RT), and another was incubated at 37°C. Immediately and after 2 hr (2H) and 4 hr (4H), spermatozoa were evaluated regarding motility, viability, morphology, sperm protamine deficiency, chromatin and DNA fragmentation. Statistical analysis was performed using paired t-test and repeated measures. The p<0.05 was considered statistically significant. Our results showed that following 2 and 4 hr of incubation at RT, sperm progressive motility and viability decreased significantly. Sperm DNA fragmentation increased significantly following 2 and 4 hr of incubation at RT and 37°C. The Trend analysis confirmed that there were no significant differences between sperm parameters and DNA fragmentation after different times at RT and 37°C. Incubation of sperm at RT in comparison to 37°C didn't preserve sperm parameters and DNA efficiently. Therefore, IVF, ICSI and IUI procedure should be performed in the soonest possible time after sperm preparation.


Outperformance of interleukin-6 over placental alpha microglobulin-1 in predicting preterm delivery in symptomatic women.
Threatened preterm labor is the major cause of hospital admission during the second half of pregnancy. An early diagnosis is crucial for adopting pharmacologic measures to reduce perinatal mortality and morbidity. Current diagnostic criteria are based on symptoms and short cervical length. However, there is a high false-positive rate when using these criteria, which implies overtreatment, causing unnecessary side effects and an avoidable economic burden. This study aimed to compare the use of placental alpha microglobulin-1 and interleukin-6 as vaginal biomarkers combined with cervical length and other maternal characteristics to improve the prediction of preterm delivery in symptomatic women. A prospective observational study was conducted in women with singleton pregnancies complicated by threatened preterm labor with intact membranes at 24+0 to 34+6 weeks of gestation. A total of 136 women were included in this study. Vaginal fluid was collected with a swab for placental alpha microglobulin-1 determination using the PartoSure test, interleukin-6 was assessed by electrochemiluminescence immunoassay, cervical length was measured by transvaginal ultrasound, and obstetrical variables and newborn details were retrieved from clinical records. These characteristics were used to fit univariate binary logistic regression models to predict time to delivery <7 days, time to delivery <14 days, gestational age at delivery ≤34 weeks, and gestational age at delivery ≤37 weeks, and multivariate binary logistic regression models were fitted with imbalanced and balanced data. Performance of models was assessed by their F2-scores and other metrics, and the association of their variables with a risk or a protective factor was studied. A total of 136 women were recruited, of whom 8 were lost to follow-up and 7 were excluded. Of the remaining 121 patients, 22 had a time to delivery <7 days and 31 had a time to delivery <14 days, and 30 deliveries occurred with a gestational age at delivery ≤34 weeks and 55 with a gestational age at delivery ≤37 weeks. Univariate binary logistic regression models fitted with the log transformation of interleukin-6 showed the greatest F2-scores in most studies, which outperformed those of models fitted with placental alpha microglobulin-1 (log[interleukin-6] vs placental alpha microglobulin-1 in time to delivery <7 days: 0.38 vs 0.30; time to delivery <14 days: 0.58 vs 0.29; gestational age at delivery ≤34 weeks: 0.56 vs 0.29; gestational age at delivery ≤37 weeks: 0.61 vs 0.16). Multivariate logistic regression models fitted with imbalanced data sets outperformed most univariate models (F2-score in time to delivery <7 days: 0.63; time to delivery <14 days: 0.54; gestational age at delivery ≤34 weeks: 0.62; gestational age at delivery ≤37 weeks: 0.73). The performance of prediction of multivariate models was drastically improved when data sets were balanced, and was maximum for time to delivery <7 days (F2-score: 0.88±0.2; positive predictive value: 0.86±0.02; negative predictive value: 0.89±0.03). A multivariate assessment including interleukin-6 may lead to more targeted treatment, thus reducing unnecessary hospitalization and avoiding unnecessary maternal-fetal treatment.


Augmented internalisation of ferroportin to late endosomes impairs iron uptake by enterocyte-like IEC-6 cells.
Absorption of iron occurs by duodenal enterocytes, involving uptake by the divalent metal transporter-1 (DMT1) and release by ferroportin. Ferroportin responds to the hepatocyte-produced 25-amino-acid-peptide hepcidin-25 by undergoing internalisation to late endosomes that impair iron release. Ferroportin is also expressed on the apical membrane of polarised Caco-2 cells, rat intestinal cells and in IEC-6 cells (an intestinal epithelial cell line). A blocking antibody to ferroportin also impairs the uptake, but not the release, of iron. In this study IEC-6 cells were used to study the mechanism of impairment or recovery from impairment produced by the blocking antibody and the fate of DMT1 and ferroportin. Uptake of 1 muM Fe(II) was studied by adding the antibody from time 0 and after adding or removing the antibody once a steady state had been reached. Surface binding, maximum iron transport rate V(max) and transporter affinity (K(m)) were measured after impairment of iron uptake. Ferroportin and DMT1 distribution were assessed by immunofluorescence microscopy. Antibody-mediated impairment, or recovery from impairment, of Fe(II) uptake occurred within minutes. Impairment was lost when the antibody was combined with the immunizing peptide. DMT1 and ferroportin undergo internalisation to late endosomes and, in the presence of the antibody, augmented internalisation of DMT1 and ferroportin caused swelling of late endosomes. Surface binding of Fe(II) and iron transport V(max) were reduced by 50%, indicating that the antibody removed membrane-bound DMT1. The ferroportin antibody induced rapid turnover of membrane ferroportin and DMT1 and its internalisation to late endosomes, resulting in impaired Fe(II) uptake.


ROS1 Alterations as a Potential Driver of Gliomas in Infant, Pediatric, and Adult Patients.
Gliomas harboring oncogenic ROS1 alterations are uncommon and primarily described in infants. Our goal was to characterize the clinicopathological features and molecular signatures of the full spectrum of ROS1 fusion-positive gliomas across all age groups. Through a retrospective multi-institutional collaboration, we report a collection of unpublished ROS1 fusion gliomas along with the characterization and meta-analysis of new and published cases. A cohort of 32 new and 58 published cases was divided into the following 3 age groups: 19 infants, 40 pediatric patients, and 31 adults with gliomas. Tumors in infants and adults showed uniformly high-grade morphology; however, tumors in pediatric patients exhibited diverse histologic features. The GOPC::ROS1 fusion was prevalent (61/79, 77%) across all age groups, and 10 other partner genes were identified. Adult tumors showed recurrent genomic alterations characteristic of IDH wild-type glioblastoma, including the +7/-10/CDKN2A deletion; amplification of CDK4, MDM2, and PDGFRA genes; and mutations involving TERTp, TP53, PIK3R1, PIK3CA, PTEN, and NF1 genes. Infant tumors showed few genomic alterations, whereas pediatric tumors showed moderate genomic complexity. The outcomes were significantly poorer in adult patients. Although not statistically significant, tumors in infant and pediatric patients with high-grade histology and in hemispheric locations appeared more aggressive than tumors with lower grade histology or those in nonhemispheric locations. In conclusion, this study is the largest to date to characterize the clinicopathological and molecular signatures of ROS1 fusion-positive gliomas from infant, pediatric, and adult patients. We conclude that ROS1 likely acts as a driver in infant and pediatric gliomas and as a driver or codriver in adult gliomas. Integrated comprehensive clinical testing might be helpful in identifying such patients for possible targeted therapy.


Adverse outcomes in clear cell renal cell carcinoma with mutations of 3p21 epigenetic regulators BAP1 and SETD2: a report by MSKCC and the KIRC TCGA research network.
To investigate the impact of newly identified chromosome 3p21 epigenetic tumor suppressors PBRM1, SETD2, and BAP1 on cancer-specific survival (CSS) of 609 patients with clear cell renal cell carcinoma (ccRCC) from 2 distinct cohorts. Select sequencing on 3p tumor suppressors of 188 patients who underwent resection of primary ccRCC at the Memorial Sloan-Kettering Cancer Center (MSKCC) was conducted to interrogate the genotype-phenotype associations. These findings were compared with analyses of the genomic and clinical dataset from our nonoverlapping The Cancer Genome Atlas (TCGA) cohort of 421 patients with primary ccRCC. 3p21 tumor suppressors are frequently mutated in both the MSKCC (PBRM1, 30.3%; SETD2, 7.4%; BAP1, 6.4%) and the TCGA (PBRM1, 33.5%; SETD2, 11.6%; BAP1, 9.7%) cohorts. BAP1 mutations are associated with worse CSS in both cohorts [MSKCC, P = 0.002; HR 7.71; 95% confidence interval (CI)2.08-28.6; TCGA, P = 0.002; HR 2.21; 95% CI 1.35-3.63]. SETD2 are associated with worse CSS in the TCGA cohort (P = 0.036; HR 1.68; 95% CI 1.04-2.73). On the contrary, PBRM1 mutations, the second most common gene mutations of ccRCC, have no impact on CSS. The chromosome 3p21 locus harbors 3 frequently mutated ccRCC tumor suppressor genes. BAP1 and SETD2 mutations (6%-12%) are associated with worse CSS, suggesting their roles in disease progression. PBRM1 mutations (30%-34%) do not impact CSS, implicating its principal role in the tumor initiation. Future efforts should focus on therapeutic interventions and further clinical, pathologic, and molecular interrogation of this novel class of tumor suppressors.


Revealing metastatic castration-resistant prostate cancer master regulator through lncRNAs-centered regulatory network.
Metastatic castration-resistant prostate cancer (mCRPC) is an aggressive form of cancer unresponsive to androgen deprivation therapy (ADT) that spreads quickly to other organs. Despite reduced androgen levels after ADT, mCRPC development and lethality continues to be conducted by the androgen receptor (AR) axis. The maintenance of AR signaling in mCRPC is a result of AR alterations, androgen intratumoral production, and the action of regulatory elements, such as noncoding RNAs (ncRNAs). ncRNAs are key elements in cancer signaling, acting in tumor growth, metabolic reprogramming, and tumor progression. In prostate cancer (PCa), the ncRNAs have been reported to be associated with AR expression, PCa proliferation, and castration resistance. In this study, we aimed to reconstruct the lncRNA-centered regulatory network of mCRPC and identify the lncRNAs which act as master regulators (MRs). We used publicly available RNA-sequencing to infer the regulatory network of lncRNAs in mCRPC. Five gene signatures were employed to conduct the master regulator analysis. Inferred MRs were then subjected to functional enrichment and symbolic regression modeling. The latter approach was applied to identify the lncRNAs with greater predictive capacity and potential as a biomarker in mCRPC. We identified 31 lncRNAs involved in cellular proliferation, tumor metabolism, and invasion-metastasis cascade. SNHG18 and HELLPAR were the highlights of our results. SNHG18 was downregulated in mCRPC and enriched to metastasis signatures. It accurately distinguished both mCRPC and primary CRPC from normal tissue and was associated with epithelial-mesenchymal transition (EMT) and cell-matrix adhesion pathways. HELLPAR consistently distinguished mCRPC from primary CRPC and normal tissue using only its expression. Our results contribute to understanding the regulatory behavior of lncRNAs in mCRPC and indicate SNHG18 and HELLPAR as master regulators and potential new diagnostic targets in this tumor.


DNA methylation in chicken brain and liver.
Adult chicken brain DNA is subject to a developmental alteration of methylation at HpaII sites flanking 4, 1, 0.8 and 0.7 kilobase sequences. This change is not evident in adult chicken liver DNA and 1-day-old chick brain and liver DNAs, suggesting tissue specificity and age-dependency in DNA methylation.


C-reactive protein induces pro- and anti-inflammatory effects, including activation of the liver X receptor alpha, on human monocytes.
Non-specific markers of inflammation such as C-reactive protein (CRP) are associated statistically with an increased risk of atherosclerosis through mechanisms that have not yet been fully elucidated. We investigated the effects of CRP on several aspects of human monocyte biology, a cell type involved in the initiation and progression of atherosclerosis. Blood monocytes isolated from healthy men and premenopausal women (n = 9/group) were exposed to purified CRP (25 microg/ml) for 12 hours. Changes in gene expression were analyzed using a custom-made array containing oligonucleotide sequences of 250 genes expressed by activated monocytes and confirmed by quantitative PCR. CRP increased significantly the expression of the cytokines interleukin (IL)-1alpha, IL-1beta and IL-6, and the chemokines GRO-alpha, GRO-beta and IL-8. CRP also displayed anti-inflammatory effects through upregulation of liver X receptor (LXR) alpha and activin receptor expression, and down-regulation of alpha 2-macroglobulin expression. Increased LXRalpha mRNA expression in both monocytes and the monocytic cell lineTHP-1 was associated with increased LXRalpha protein expression and nuclear translocation, as well as increased ABCA1 mRNA expression, a target gene of LXRalpha. Western blot analysis revealed CRP-induced nuclear translocation of NF-kappaB and activation of p42/44, MAP and Akt kinases. CRP-induced LXRalpha mRNA expression was inhibited by anti-CD64 (FcgammaRI) antibodies and by p42/44 and PI3 kinase inhibitors. This hypothesis-generating study demonstrates that CRP modulates the expression of genes that contribute to both pro- and anti-inflammatory responses in human monocytes. Among these novel anti-inflammatory effects, we show clearly that CRP activates the LXRalpha pathway.


Protocol for quantitative analysis of RNA 3'-end processing induced by disassociated subunits using chromatin-associated RNA-seq data.
Sequencing chromatin-associated RNA using libraries from the chromatin fraction makes it possible to characterize RNA processing driven by disassociated subunits. Here, we present an experimental strategy and computational pipeline for processing chromatin-associated RNA-seq data to detect and quantify readthrough transcripts. We describe steps for constructing degron mouse embryonic stem cells, detecting readthrough genes, data processing, and data analysis. This protocol can be adapted to various biological scenarios and other types of nascent RNA-seq, such as TT-seq. For complete details on the use and execution of this protocol, please refer to Li et al. (2023).1.


Effect of ensilation of potato on viability of Taenia hydatigena eggs.
A Taenia hydatigena model was used to assess the effect 0, 7, 14, 21, and 28 days of ensilation of minced potato on viability of tapeworm eggs. For infection of lambs, 2,000 T. hydatigena eggs were ensiled for 0, 7, 14, 21 and 28 days in minced potato at 22°C and fed to recently weaned lambs (29.9±0.76 kg). At slaughter, no cysticerci were recovered from lambs infected with eggs ensiled for 28 days while a mean of 5.0±5.0 cysticerci (0.25% of the initial egg dose) were recovered from lambs infected with eggs ensiled for 21 days. For lambs fed eggs ensiled for 0 days (control), 359.3±55.6 cysticerci were recovered (18.0% of the initial egg dose). Regression analysis revealed that a 99.9% reduction in viability was attained after 18.59 days of ensilation.


Global analysis of a time fractional order spatio-temporal SIR model.
We deal in this paper with a diffusive SIR epidemic model described by reaction-diffusion equations involving a fractional derivative. The existence and uniqueness of the solution are shown, next to the boundedness of the solution. Further, it has been shown that the global behavior of the solution is governed by the value of [Formula: see text], which is known in epidemiology by the basic reproduction number. Indeed, using the Lyapunov direct method it has been proved that the disease will extinct for [Formula: see text] for any value of the diffusion constants. For [Formula: see text], the disease will persist and the unique positive equilibrium is globally stable. Some numerical illustrations have been used to confirm our theoretical results.


Radiotherapy versus radiotherapy enhanced by cisplatin in stage III non-small cell lung cancer.
Between January 1987 and June 1991, 173 patients with inoperable non-small cell lung cancer, Stage III, were entered into a randomized trial comparing radiotherapy only (RT) (45 Gy/15 fractions/3 weeks) (arm A) versus RT and a daily low dose of cDDP (6 mg/m2) (arm B). An overall response rate of 58.9% was observed in arm A and 50.6% in arm B, respectively. No differences in the pattern of relapse were noted between the two treatment groups. Median time to progression was 10.6 months for arm A and 14.2 months for arm B. Median survivals were 10.3 months and 9.97 months, respectively. Toxicity was acceptable and no treatment-related death occurred in either treatment schedule. In this study no significant advantage of the combined treatment over radiation therapy only was found. The encouraging results achieved in some trials together with the intractability of the disease suggest that further efforts should be made to optimize clinical trial protocols, perhaps by reviewing the radiobiological and pharmacological basis of the combined treatment.


The bacterial secondary metabolite 2,4-diacetylphloroglucinol impairs mitochondrial function and affects calcium homeostasis in Neurospora crassa.
The bacterial secondary metabolite 2,4-diacetylphloroglucinol (DAPG) is of interest as an active ingredient of biological control strains of Pseudomonas fluorescens and as a potential lead pharmaceutical molecule because of its capacity to inhibit growth of diverse microbial and non-microbial cells. The mechanism by which this occurs is unknown and in this study the filamentous fungus Neurospora crassa was used as a model to investigate the effects of DAPG on a eukaryotic cell. Colony growth, conidial germination and cell fusion assays confirmed the inhibitory nature of DAPG towards N. crassa. A number of different fluorescent dyes and fluorescent protein reporters were used to assess the effects of DAPG treatment on mitochondrial and other cellular functions. DAPG treatment led to changes in mitochondrial morphology, and rapid loss of mitochondrial membrane potential. These effects are likely to be responsible for the toxicity of DAPG. It was also found that DAPG treatment caused extracellular calcium to be taken up by conidial germlings leading to a transient increase in cytosolic free Ca(2+) with a distinct concentration dependent Ca(2+) signature.


Observational Surveillance Approach to Detect Novel Work-Related Diseases and Hazards: An Application to a Belgian Occupational Health and Safety Database.
Rapid changes in working conditions give rise to new occupational health risks. We applied the Spectrosome approach, a network-based analysis, to investigate associations between disease and multiple occupational exposures. We investigated work and health's associations in a specific sector: the agricultural sector and for a specific and frequent health complaint: sore throat; using PRECUBE dataset of the Belgian Occupational Health and Safety, containing 381.615 occupational health observations. We compared the results of the spectrosome with classic frequency analyses. Spectrosome approach reports more significant signals of multiple associations of agents compare to the frequency analysis. This difference justifies the usefulness of taking into account the multiplicity of causes leading to a health event, which is a clear asset of the Spectrosome method.


Introducing medical students to radiology as paid emergency department triage assistants.
The aim of this report is to provide a detailed description of a program employing medical students to assist with triaging off-hour diagnostic imaging studies at a major academic medical center. Current and former participants of the Medical student Emergency Department (ED) Radiology Triage Program were interviewed regarding the inception, development, and impact of this program. Student participation and triage activities were compiled and tabulated from scheduling records and triage assistant call logs. Opportunities for medical students to obtain an intensive, well-organized experience in radiology are often absent or occur relatively late during medical school, which can be problematic for developing basic imaging literacy and for making timely, well-informed decisions regarding radiology as a career path. The authors describe a program that provides students with a rigorous, hands-on experience in radiology relatively early in their training by employing medical students to assist the emergency department radiology staff with managing off-hour radiology workflow. Students work with the off-hour emergency department radiologists and staff members answering phone calls and help to facilitate the ordering and protocoling of studies and the dissemination of results to clinicians. The employment of medical student triage assistants provides in-depth exposure to clinical radiology relatively early in medical school, while providing an effective system to help streamline the off-hour workflow for attending radiologists, residents, technicians, and support staff members.


Generation of two induced pluripotent stem cell lines (NHLBIi001-A and NHLBIi001-B) from a healthy Caucasian female volunteer with normal cardiac function.
Human-derived induced pluripotent stem cells (iPSCs) have proven to be indispensable in cardiovascular drug development, disease modeling, and developmental biology research. For this reason, it is particularly useful to develop wild-type iPSC lines to be used in experimental or control conditions. Here, we present two such cell lines generated from a sample of peripheral blood mononuclear cells (PBMCs) from a healthy patient with normal cardiac function.


Dominance from the perspective of gene-gene and gene-chemical interactions.
In this study, we used genetic interaction (GI) and gene-chemical interaction (GCI) data to compare mutations with different dominance phenotypes. Our analysis focused primarily on Saccharomyces cerevisiae, where haploinsufficient genes (HI; genes with dominant loss-of-function mutations) were found to be participating in gene expression processes, namely, the translation and regulation of gene transcription. Non-ribosomal HI genes (mainly regulators of gene transcription) were found to have more GIs and GCIs than haplosufficient (HS) genes. Several properties seem to lead to the enrichment of interactions, most notably, the following: importance, pleiotropy, gene expression level and gene expression variation. Importantly, after these properties were appropriately considered in the analysis, the correlation between dominance and GI/GCI degrees was still observed. Strikingly, for the GCIs of heterozygous strains, haploinsufficiency was the only property significantly correlated with the number of GCIs. We found ribosomal HI genes to be depleted in GIs/GCIs. This finding can be explained by their high variation in gene expression under different genetic backgrounds and environmental conditions. We observed the same distributions of GIs among non-ribosomal HI, ribosomal HI and HS genes in three other species: Schizosaccharomyces pombe, Drosophila melanogaster and Homo sapiens. One potentially interesting exception was the lack of significant differences in the degree of GIs between non-ribosomal HI and HS genes in Schizosaccharomyces pombe.


Somatostatin Type 2 Receptor Antibody Enhances Mechanical Hyperalgesia in the Dorsal Root Ganglion Neurons after Sciatic Nerve-pinch Injury: Evidence of Behavioral Studies and Bax Protein Expression.
Our previous study has indicated that somatostatin potently inhibits neuropathic pain through the activation of its type 2 receptor (SSTR2) in mouse dorsal root ganglion and spinal cord. However, the underlying mechanism of this activation has not been elucidated clearly. The aim of this study is to perform the pharmacological studies on the basis of sciatic nerve-pinch mice model and explore the underlying mechanism involving SSTR2. On the basis of a sciatic nerve-pinch injury model, we aimed at comparing the painful behavior and dorsal root ganglion neurons neurochemical changes after the SSTR2 antibody (anti- SSTR2;5μl,1μg/ml) administration in the mouse. After pinch nerve injury, we found that the mechanical hyperalgesia and severely painful behavior (autotomy) were detected after the application of SSTR2 antibody (anti-SSTR2; 5μl, 1μg/ml) on the pinch-injured nerve. The up-regulated phosphorylated ERK (p-ERK) expression and the apoptotic marker (i.e., Bax) were significantly decreased in DRGs after anti-SSTR2 treatment. The current data suggested that inhibitory changes in proteins from the apoptotic pathway in anti-SSTR2-treated groups might be taking place to overcome the protein deficits caused by SSTR2 antibody and supported the new therapeutic intervention with SSTR2 antagonist for neuronal degeneration following nerve injury.


Ebola protein analyses for the determination of genetic organization.
Amino-acid sequencing of the purified major nucleoprotein (NP), VP35 and VP40 from purified Ebola virus proved that they are the protein products of the first three genes, and that the open reading frame (ORF) of the NP begins at nucleotide 470. Because of the many unusual features of the ORFs of Ebola virus, we thought that our conclusions should be substantiated. Comparisons of in vitro-translation products to purified viral proteins were used to demonstrate conclusively that the NP, VP35 and VP40 were the protein products of genes one, two, and three, respectively. Studies using antibodies to synthetic peptides matching the N- and C-termini of the deduced sequences from these genes confirmed these conclusions and that the ORF for the NP begins at nucleotide 470. Subsequent studies confirmed that VP30 is encoded by the fifth gene.


Present concept of the relevance of steroid receptors for prostatic cancer.
Suitable assays for nuclear androgen-receptors in human prostatic cancer tissue have been presented. Correlations between NAR-content and response to hormonal therapy are demonstrated. The methods are time consuming and require expensive equipment as well as experience. Individual laboratory standards seem to determine response rates. The earlier methodological difficulties are replaced by a new set of problems for which as yet no single solution is available. As there is a tendency to use aspiration cytology more and more for diagnosis as well as follow-up of prostatic cancer, a cytochemical method would be extremely valuable. Research in that direction should be pursued.


A numerical method for guiding the design of surgical meshes with suitable mechanical properties for specific abdominal hernias.
Abdominal hernia is a common disease, and the most effective treatment of it is using surgical meshes. However, it was found that due to the mismatch of the mechanical properties between the mesh and the tissues around the hernia, there was still a recurrence rate of more than 33% and a high probability of postoperative discomfort. Currently, because of the complex mechanical environment provided by the abdominal tissues and the lack of quantitative research, it is still difficult to select a mesh with suitable mechanical properties for a hernia with specific position and size. Therefore, the purpose of this study is to use numerical models to evaluate the mechanical behavior of both abdominal wall and meshes after repair, and to determine the most suitable mechanical properties of meshes for specific hernias, including elastic modulus and tensile strength. To realize that purpose, defects with different locations and sizes were considered, including defects of 20 mm and 40 mm in diameter on linea alba (LA20 and LA40) and on rectus abdominis (RA20 and RA40), and laparoscopic repair was simulated. The mechanical properties of the most suitable mesh we determined are as follows: suitable modulus for LA20, LA40, RA20 and RA40 are 1 MPa, 3 MPa, 2 MPa and 4 MPa, respectively; suitable tensile strength for LA20, LA40, RA20 and RA40 are 0.35 MPa, 0.89 MPa, 0.77 MPa and 1.43 MPa, respectively. These data could give a standard of mechanical properties which can be referenced in mesh design and evaluation and provide surgeons with treatment advice for specific patients.


[Research on the chemical composition and aspects of the pharmacological action of the essential oil of Kochi thyme (Thymus kotschyanus Boiss)].
In experiments on white mice, guinea pigs and rabbits it was found that ethereal oil of Kochi thyme is non-toxic. At concentrations of 0.5-5.0% (1 mg/kg) it produced in rabbits hypotensive and cardiotonic effects.


Schistosoma mansoni and S. japonicum: comparison of levels of ultraviolet irradiation for vaccination of mice with cercariae.
When cercariae of Schistosoma mansoni and of S. japonicum were irradiated with various levels of u.v. light at 254 nm, their development to perfusable worms was reduced to below 1% at about 200 microW min cm-2. Cercariae attenuated with about 300 microW min cm-2 induced partial resistance against an homologous challenge infection in mice. No differences were observed between the two schistosome species when the same treatment was given to the cercariae. Thus the same u.v. dose can confer immunizing ability to cercariae of both S. mansoni and S. japonicum.


In vivo clonal expansion and phenotypes of hypocretin-specific CD4+ T cells in narcolepsy patients and controls.
Individuals with narcolepsy suffer from abnormal sleep patterns due to loss of neurons that uniquely supply hypocretin (HCRT). Previous studies found associations of narcolepsy with the human leukocyte antigen (HLA)-DQ6 allele and T-cell receptor α (TRA) J24 gene segment and also suggested that in vitro-stimulated T cells can target HCRT. Here, we present evidence of in vivo expansion of DQ6-HCRT tetramer+/TRAJ24+/CD4+ T cells in DQ6+ individuals with and without narcolepsy. We identify related TRAJ24+ TCRαβ clonotypes encoded by identical α/β gene regions from two patients and two controls. TRAJ24-G allele+ clonotypes only expand in the two patients, whereas a TRAJ24-C allele+ clonotype expands in a control. A representative tetramer+/G-allele+ TCR shows signaling reactivity to the epitope HCRT87-97. Clonally expanded G-allele+ T cells exhibit an unconventional effector phenotype. Our analysis of in vivo expansion of HCRT-reactive TRAJ24+ cells opens an avenue for further investigation of the autoimmune contribution to narcolepsy development.


Randomized noninferiority trial of reduced high-dose volume versus standard volume radiation therapy for muscle-invasive bladder cancer: results of the BC2001 trial (CRUK/01/004).
To test whether reducing radiation dose to uninvolved bladder while maintaining dose to the tumor would reduce side effects without impairing local control in the treatment of muscle-invasive bladder cancer. In this phase III multicenter trial, 219 patients were randomized to standard whole-bladder radiation therapy (sRT) or reduced high-dose volume radiation therapy (RHDVRT) that aimed to deliver full radiation dose to the tumor and 80% of maximum dose to the uninvolved bladder. Participants were also randomly assigned to receive radiation therapy alone or radiation therapy plus chemotherapy in a partial 2 × 2 factorial design. The primary endpoints for the radiation therapy volume comparison were late toxicity and time to locoregional recurrence (with a noninferiority margin of 10% at 2 years). Overall incidence of late toxicity was less than predicted, with a cumulative 2-year Radiation Therapy Oncology Group grade 3/4 toxicity rate of 13% (95% confidence interval 8%, 20%) and no statistically significant differences between groups. The difference in 2-year locoregional recurrence free rate (RHDVRT - sRT) was 6.4% (95% confidence interval -7.3%, 16.8%) under an intention to treat analysis and 2.6% (-12.8%, 14.6%) in the "per-protocol" population. In this study RHDVRT did not result in a statistically significant reduction in late side effects compared with sRT, and noninferiority of locoregional control could not be concluded formally. However, overall low rates of clinically significant toxicity combined with low rates of invasive bladder cancer relapse confirm that (chemo)radiation therapy is a valid option for the treatment of muscle-invasive bladder cancer.


Geographical distribution of host's specific SARS-CoV-2 mutations in the early phase of the COVID-19 pandemic.
To assess, if the SARS-CoV-2 mutate in a similar pattern globally or has a specific pattern in any given population. We report, the insertion of TTT at 11085, which adds an extra amino acid, F to the NSP6 at amino acid position 38. The highest occurrence of TTT insertion at 11,085 position was found in UK derived samples (65.97%). The second and third highest occurrence of the mutation were found in Australia (8.3%) and USA (4.16%) derived samples, respectively. Another important discovery of this study is the C27945T mutation, which translates into the termination of ORF-8 after 17 amino acids, reveals that the SARS-CoV-2 can replicate without the intact ORF-8 protein. We found that the 97% of C27945T mutation of global occurrence, occurred in Europe and the USA derived samples. Two of the reported mutations (11085TTT insertion and C27945T nonsense), which seemed to reduce Type I interferon response are linked to specific geographical locations of the host and implicate region-specific mutations in the virus. The findings of this study signify that SARS-CoV-2 has the potential to adapt differently to different populations.


Comparative analysis between different methods for calculating on-board ship's emissions and energy consumption based on operational data.
With the aim of more reliably measuring ships' fuel consumption and emissions several different estimation methods have been put forward and are in use but there is ongoing debate still on the best way to measure maritime emissions. Fuel and emissions monitoring are already a common practice in the shipping industry. But there are currently neither harmonised guidelines nor legal requirements that clearly define the method and the rules to follow to monitor on-board fuel consumption for each situation during navigation. In this context, this article describes and compares four existing methods (EPA, IMO, Jalkanen and MAN) for calculating energy consumption and emissions, and presents a more realistic method, based on a case study. The purpose is to examine the differences between all of these methods, in order to propose the most suitable method of obtaining the data needed for better energy management, and a method that can be applied to any type of ship. The case study was carried out on Ro-Pax ships, comparing these four different methods through the application of a bottom-up integrated system approach. The study describes in detail and applies the most complete methodology for calculating energy consumption and emissions during cruising, operating in a Speed Reduction Zone (SRZ), manoeuvring and berthing. Application of the new improved method proposed in this paper could be the first step in implementing operational measures for detecting both abnormal high emissions and abnormal fuel consumption. The application of this method does not, in itself, reduce fuel use or improve efficiency, but it should be the necessary first step to establish uniform operational measures that will improve the management of energy on board ship and monitor accurately the performance of the fleet.


NG2-glia cell proliferation and differentiation by glial growth factor 2 (GGF2), a strategy to promote functional recovery after ischemic stroke.
Stroke is the leading cause of adult disability. Spontaneous functional recovery occurs after ischemic stroke, but it is very limited. Therefore, it is urgent to find a strategy to promote functional recovery after stroke in clinical setting. Gray matter damage has received extensive attention owing to the important roles of the gray matter in synaptic plasticity, cognitive, and motor function. However, stroke also causes white matter damage, which accounts for half of the infarct volume and can be aggravated by blood brain barrier damage. Disruption of white matter integrity, which is characterized by death of oligodendrocytes (OLs), loss of myelin, and axonal injury, greatly contributes to impaired neurological function. Impaired proliferation and differentiation of OL precursor cell (OPC, NG2-glia cells) play an important role in limited functional recovery after ischemic stroke and inhibitor of differentiation 2 (ID2) is a key factor controlling NG2-glia cells differentiation. It has been reported that the number of NG2-glia cells in the peri-infarction area significantly increases after ischemic stroke and glial growth factor (GGF2) administration promotes the proliferation and differentiation of NG2-glia cells as well as functional recovery after spinal cord injury. On the basis of the important roles of GGF2 in functional recovery and those of ID2 in NG2-glia cell proliferation and differentiation, we propose that after binding with the ErBb receptor on the surface of NG2-glia cells, GGF2 promotes NG2-glia cell proliferation and differentiation, thereby repairing BBB and white matter integrity and promoting neural functional recovery after ischemic stroke.


Trends in incidence and prevalence of type 1 diabetes between 1999 and 2019 based on the Childhood Diabetes Registry of Saxony, Germany.
The Childhood Diabetes Registry of Saxony has been existing since 1999. The aim of this study was to investigate the incidence rates, cohort and point prevalence, and the trends of type 1 diabetes among children and adolescents based on the registry data over the past 21 years. A completeness check of the Childhood Diabetes Registry of Saxony for the observation period 2012-2019 was performed using the capture-recapture method. The age-standardized incidence rates per 100,000 person years (PY) were estimated for the observation period 1999-2019. Prevalence was estimated per 100,000 children and adolescents as the point prevalence of five consecutive years, and as a cohort prevalence for the birth cohorts, which result from the difference of age and year at diagnosis. Trend analyses were executed using join point regression. A completeness of 98% (95% CI 89-100) was determined for the period from 2012 to 2019. The standardized incidence rate of type 1 diabetes among children and adolescents increased from 17.1 per 100,000 PY in 1999 to 24.7 per 100,000 PY in 2019. If this trend continues, the incidence rate will increase to 34.8 (95% CI 24.4-49.6) per 100,000 PY in 2030. The point prevalence of 5 consecutive years did not show a continuous trend over time. According to this method, the prevalence reached a plateau in the last segment (2013-2019). The calculation of cohort prevalence indicated a continuous increase from 2013 to 2019 with no significant statistical difference in terms of sex. The point prevalence and the last incidence rates indicate that type 1 diabetes of children and adolescents is slowing down or has reached a plateau in Saxony. Nevertheless, the cohort prevalence predicts a steady increase. Future studies should continue investigating these trends in a longer observation period and consider including possible correlating environmental factors.


Feasible and clinical relevant outcome measures for adults with mitochondrial disease.
There is no consensus on clinical outcome measures that reflect function, activities and participation which are suitable for adults with mitochondrial diseases (MD). The aim of this study was to determine feasible and clinically relevant outcome measures for patients with MD . In 156 adult patients with MD, endurance, balance, strength and mobility tests were evaluated. All tests showed a negative deviation to healthy reference values. Balance tests were feasible and significantly correlated with clinical severity. The Åstrand cycle test was not feasible in 55%, whereas the feasibility of the 6 min walking test is unclear in patients with MD.


MRI for Diagnosing Intrauterine Adhesions.
To prospectively assess the diagnostic accuracy of MRI and transvaginal ultrasound (TVS) as well as the prognostic value of MRI for intrauterine adhesions (IUAs), using hysteroscopy as the reference standard. Prospective observational study. Tertiary medical centre. Ninety-two women with amenorrhea, hypomenorrhea, subfertility, or recurrent pregnancy loss who underwent MRI and in whom Asherman's syndrome was suspected upon TVS. MRI and TVS were conducted approximately 1 week before hysteroscopy. Ninety-two patients suspected of having Asherman's syndrome were examined by MRI and TVS within 7 days of an upcoming hysteroscopy. All hysteroscopy procedures were performed during the early proliferative phase of the menstrual cycle. All hysteroscopic diagnoses were performed by an experienced expert. All MRIs were read by 2 experienced, blinded radiologists. MRI was highly accurate (94.57%), sensitive (98.8%), and specific (42.9%) for diagnosing IUAs with a positive predictive value of 95.5% and a negative predictive value of 75%. The diagnostic values of MRI and TVS were significantly different according to McNemar tests. Junctional zone signal and junctional zone alterations correlated with the stage of IUAs. MRI is markedly superior to TVS in terms of diagnostic accuracy for IUAs, with total agreement with hysteroscopic findings. However, the main advantage of MRI is that, unlike TVS and hysterosalpingography, it can be used to assess the risk of hysteroscopy and to predict postoperative recovery and future pregnancy based on the uterine junctional zone.


Increasing incidence and survival of a rare skin cancer in the Netherlands. A population-based study of 2,220 cases of skin adnexal carcinoma.
The aim of this study was to describe the epidemiology and treatment of skin adnexal carcinoma (SAC) in the Netherlands and to identify prognostic factors for survival in patients with SAC. We used population-based nationwide data from the Netherlands Cancer Registry with cases diagnosed during 1989-2010 and followed up to February 1st, 2012. A total of 2,220 SACs were diagnosed during 1989-2010 (age-standardized incidence rate 5.3 per million). Incidence increased by 2.7% and 1.7% annually in males and females, respectively. Fifteen different morphological types were registered. The 5-year relative survival rate increased from 80% in 1989-1994 to 91% in 2006-2010. The majority of all patients (91%) received surgery. Adjuvant radiotherapy and/or lymph node dissection was performed in only a minority of cases. The risk of death was significantly higher in patients who did not receive surgery. The rising incidence of SAC together with the predilection for the head and neck region suggests a role for UV radiation in the carcinogenesis of SAC. Furthermore, we found an improved survival of SAC in the Netherlands between 1989 and 2010. In view of the low proportion of patients receiving adjuvant therapy there may be further room for improving survival.


Study of habitat quality assessment using geospatial techniques in Keoladeo National Park, India.
Wetlands are one of the most productive ecosystems on the Earth. They are generally considered a transitional state between terrestrial-aquatic habitats and provide numerous vital ecosystem services to mankind. Wetlands are under a tremendous pressure due to growing human interference, urbanization, conventional agriculture, industrial expansions, and overexploitation of ecological services. The Keoladeo National Park (KNP) is a manmade wetland, world heritage site and a designated Ramsar site in India, widely known for its avian biodiversity. Due to insufficient amount of water supply and widespread invasion of Prosopis juliflora, notable spatio-temporal changes are observed in the land cover affecting habitat quality of the park. The present study is designed to highlight the importance of very high-resolution satellite data for characterization of the wetland ecosystem. It assesses the spatio-temporal dynamics of land use/land cover (LULC) and habitat quality, a model built in the InVEST (Integrated Valuation of Ecosystem Services and Tradeoffs) tool, is utilized to analyze the effect of land cover changes and increase in P. juliflora on habitat quality in the park. The study concludes that drastic changes in LULC and rampant spread of P. juliflora have deteriorated the quality of habitat for bird species. Furthermore, it highlights importance of geospatial tools in mapping, monitoring, and managing wetland ecosystems.


Leukotriene modifiers as potential therapeutics for cardiovascular disease.
Owing to their anti-inflammatory properties, leukotriene modifiers have been the primary therapeutics in asthma management for several years. Although blocking the inflammatory component of human disease is a long-standing and established concept, the use of leukotriene modifiers in treating the inflammatory component of cardiovascular disease encompassing atherosclerosis, myocardial infarction, stroke and aortic aneurysm has, surprisingly, only been seriously contemplated in the past few years. As reviewed here, several exciting studies have recently contributed to this expanding area of interest, and so far one leukotriene modifier has entered Phase II clinical trials to assess its potential for reducing the risk of heart attacks.


Maternal hemodynamics and impaired fetal growth in pregnancy-induced hypertension.
Twenty-one subjects with pregnancy-induced hypertension were investigated with regard to the relationship between maternal hemodynamics and fetal growth. Five of the infants were small for gestational age (SGA) (less than tenth percentile) and 16 were appropriate for gestational age (AGA) (greater than tenth percentile). Mean arterial blood pressure, cardiac output, and stroke volume were significantly lower in the group of mothers with SGA infants than in the group with AGA infants (102 +/- 3 versus 115 +/- 3 mmHg, 5.8 +/- 0.2 versus 8.2 +/- 0.3 L/minute, and 76 +/- 7 versus 100 +/- 5 mL, respectively). The results of this investigation suggest that the hemodynamic background to the blood pressure increase in pregnancy-induced hypertension ranges from a low cardiac output, high vascular resistance condition to a high-output, low-normal resistance variant. The former subtype is often associated with the birth of an SGA infant.


Hodgkin's disease.
The outlook for patients with Hodgkin's disease has improved dramatically over the past 20 years. The question is no longer whether cure is possible, but rather, how can cure be best achieved. With better understanding of the biology of Hodgkin's disease and with continued evolution of treatment approaches, the goal of curing all patients with Hodgkin's disease is clearly within reach. This article provides a summary of current concepts in the biology and management of Hodgkin's disease. Staging, treatment options, and complications of therapy are discussed.


Fluorescent compounds as retrograde tracers compared with horseradish peroxidase (HRP). II. A parametric study in the peripheral motor system of the cat.
Fluorescent compounds which are currently used as retrograde tracers were tested in the cat peripheral motor system and compared with horseradish peroxidase (HRP). The tracers were either injected into forelimb muscles or applied to the proximal end of transected forelimb nerves. The remaining muscles of the limb has been carefully denervated. Following intramuscular injection all fluorescent compounds labeled spinal cord motoneurons, the DAPI compounds labeled endothelial cells in addition. In the nerve application mode tracer positive motoneurons were only observed when propidium iodide (PI) and the DAPI compounds were used, whereas bisbenzimide (BB), nuclear yellow (NY) and primuline did not label any cells. The fluorescence of BB labeled motoneurons were predominantly located in the cytoplasma. NY positive motoneurons showed a different localization of the fluorescent label between the different neurons of the same motornucleus: in some neurons it was exclusively located in the nucleus, in others predominantly in the cytoplasma, in the majority in both compartments. The intracellular distribution of the BB and the NY label was independent of the pH of the fixation fluid. The fluorescent tracers labeled the motoneuronal cell columns in their complete rostrocaudal extent and in a position identical to the one obtained with HRP. However, some substances (PI, fast blue) labeled less motoneurons of a motornucleus than did HRP, none of the fluorescent tracers labeled more. The results are discussed under several aspects: use of the investigated fluorescent compounds as single tracers; use of several tracers in the same animal to map collateral projections of one and the same neuron; use of several tracers in the same animal to establish the topographical relation between several independent neuronal populations.