Unfavorable anatomical factors influencing the success of retrograde intrarenal surgery for lower pole renal calculi.
To determine the unfavorable factors, related to lower pole anatomical characteristics (LPACs), influencing the success of retrograde intrarenal surgery (RIRS) for lower pole renal calculi (LPC). We reviewed the data of 36 patients who underwent RIRS for LPC between October 2012 and October 2013. The infundibulopelvic angle (IPA), infundibular length (IL) and infundibular width (IW) were measured on preoperative intravenous urographies. On follow-up stone-free status was defined as complete clearance at the first month kidney-ureter-bladder X-ray and computed tomography if necessary. The median stone size was 10 mm (range, 5-35). The stone-free rates according to LPACs at the first month follow-up were 100% (n = 17), 57.9% (n = 11), 90% (n = 18), 62.5% (n = 10), 90.5% (n = 19) and 60% (n = 9) for patients with IPA ≥ 70°, IPA < 70º, IL < 3 cm, IL ≥ 3 cm, IW ≥ 5 mm and IW < 5 mm, respectively. While IPA and IW were associated with success of RIRS for LPC in multivariate analysis (P = .003 and P = .046, respectively), only IW was found to be a significant factor after applying multivariate analysis (P = .05). The results of our study demonstrated that only IW had a significant effect on the success rate of RIRS for LPC.


Fluid mechanic constraints on spider ballooning.
Early investigations point to ballooning as an important mechanism for the dispersal of spiders. Most studies, however, have focused on collecting and interpreting observations with the aim of establishing the statistical characteristics of the dispersed population and their relation to biotic factors. With few exceptions, important physical factors that mechanically constrain the ballooning activity have been neglected or simply ignored. Especially important are various fluid mechanics phenomena that affect the initiation and maintenance of the ballooning activity. By reference to a simple mechanical model that simulates the essential drag characteristics of the ballooning spider-filament system, a region is defined, in terms of the relevant physical parameters, within which the ballooning activity can be initiated. Extension of the model allows a numerical investigation of the influence of vertical wind oscillations on the velocities and trajectories of ballooning spider-filament systems. Results are presented and discussed to illustrate the relative importance to ballooning of drag on the spider's body and on the silk filament to which it is attached.


Anxiety, depression and PTSD among children and their parent during 2019 novel coronavirus disease (COVID-19) outbreak in China.
Home quarantine may lead to families developing a variety of psychological distress. The purpose of this study was to examine the psychological status of children and their parent during 2019 coronavirus disease (COVID-19) outbreak in China. Data were collected from children (n = 1360) and their parent (n = 1360) in China using online survey during February 2020. Demographic information, media exposure, and psychological status including anxiety, depression and posttraumatic stress disorder (PTSD) symptoms were assessed using self-report measures. The results indicated that, for children, 1.84% experienced moderate anxiety, 2.22% experienced depression and 3.16% met the diagnostic criteria for PTSD; for parent, 1.18%, 0.01% and 3.60% experienced moderate anxiety, severe depression, and moderate depression, respectively, and 3.53% met the diagnostic criteria for PTSD. Moreover, excessive media exposure (β = -0.08 ~ 0.13, ps < 0.05) was a risk factor for anxiety and PTSD for children, a positive factor against anxiety and depression for parent. Being a mother (β = 0.07 ~ 0.21, ps < 0.01), being younger (β = -0.09 ~ -0.07, ps < 0.05), lower levels of educational attainment (β = -0.17 ~ -0.08, ps < 0.01) and family monthly income (β = -0.17 ~ -0.11, ps < 0.05) were risk factors for anxiety, depression and PTSD for parent. Findings suggested that children and their parent in non-severe area didn't suffer major psychological distress during the outbreak. Factors associated with lower levels of mental health problems were identified to inform the use of psychological interventions to improve the mental health of vulnerable groups during the pandemic.


Lipids, lipoproteins and fatty acid composition in obese adolescents undergoing a very low calorie diet.
Sixteen obese adolescents (mean +/- SD age: group I 12.5 +/- 2.1 and group II 12.0 +/- 2.5 years) were treated at least 3 weeks with two different very low calorie diet (VLCD) regimens. The VLCD in group I contained 33g proteins, 25.5g carbohydrates and 0.7g fat (240 kcal, 1004KJ) and in group II 44g protein, 33g carbohydrates and 0.9g fat (320 kcal, 1339KJ). After the 3 weeks treatment total serum cholesterol decreased from 180 +/- 34 mg/dl in group I and 184 +/- 34 mg/dl in group II respectively, to 125 + 16 mg/dl and 120 + 22 mg/dl. This fall was mainly due to the highly significant decrease of LDL-cholesterol. VLDL-cholesterol, HDL-cholesterol and triglycerides in group I remained almost unchanged. In group II triglycerides increased significantly from 81 +/- 19 mg/dl to 104 +/- 19 mg/dl and HDL-cholesterol decreased slightly. The LDL-C HDL-C- ratio in both groups improved considerably. Fatty acid composition of the serum lipids changed only slightly: In total serum linoleic acid levels declined slightly in group I and remained constant in group II. Linoleic acid content in cholesterylesters declined moderately in group I from 37.5 +/- 5.6% to 34.8 +/- 5.6% whereas arachidonic acid increased slightly in both groups. In phospholipids, oleic acid declined in both groups significantly, linoleic acid declined significantly in group I and arachidonic acid increased in group I significantly. Similar changes occurred in triglycerides. After 3 weeks treatment with a practically fat free alimentation no biochemical signs of essential fatty acid deficiency could be detected.


A pseudoreceptor docking study of 4,5-alpha-epoxymorphinans with a range of dielectric constants.
Thirteen 4,5-epoxymorphinan mu agonists with established analgesic action were docked into an Asp-Lys-His-Phe pseudoreceptor complex under a range of distance-dependent dielectric conditions. The number of compounds with potential energies of the docked complexes that agreed in rank order with corresponding analgesic potencies was determined for each condition. Two dielectric conditions, n-decane (1.991) and ethanol (24.3), enabled the greatest number of compounds to relate to their pseudoreceptors with each having 9 and 8 successes respectively. Both of these conditions demonstrated unique influences on the types of structures that were successfully docked. For example, the morphine stereoisomer alpha-isomorphine, the geometric isomer B/C trans-morphine, and the 8-position-substituted gamma-isomorphine were successes in the n-decane condition, whereas the ethanol condition produced the substituted codeine derivatives dihydrocodeinone and dihydroxycodeinone. These findings emphasize the importance of dielectric influence when developing force-field modeled quantitative structure-activity relationships for a closely related homologous series.


A systematic review evaluating the use of ultrasound in the identification of osteochondrosis in horses.
Osteochondrosis is commonly encountered in young horses, with welfare, performance, and economic effects. Consequently, pre-purchase radiographic screening for osteochondrosis is routinely performed. Ultrasonographic examination of articular cartilage and osteochondrosis lesions are described in the literature with many case series or single case reports published. This systematic review was undertaken to examine the evidence for using ultrasonography in comparison to traditional radiography, arthroscopy or necropsy findings in the detection of osteochondrosis. The systematic review identified a paucity of studies in which there was marked variation in the populations, sample size, methods and results reported. Currently, there is no strong evidence confirming the diagnostic accuracy and validity of ultrasonography in the detection of osteochondral lesions in the relevant joints in horses.


Exploring linker's sequence diversity to fuse carotene cyclase and hydroxylase for zeaxanthin biosynthesis.
Fusion of catalytic domains can accelerate cascade reactions by bringing enzymes in close proximity. However, the design of a protein fusion and the choice of a linker are often challenging and lack of guidance. To determine the impact of linker parameters on fusion proteins, a library of linkers featuring various lengths, secondary structures, extensions and hydrophobicities was designed. Linkers were used to fuse the lycopene cyclase (crtY) and β-carotene hydroxylase (crtZ) from Pantoea ananatis to create fusion proteins to produce zeaxanthin. The fusion efficiency was assessed by comparing the carotenoids content in a carotenoid-producer Escherichia coli strain. It was shown that in addition to the orientation of the enzymes and the size of the linker, the first amino acid of the linker is also a key factor in determining the efficiency of a protein fusion. The wide range of sequence diversity in our linker library enables the fine tuning of protein fusion and this approach can be easily transferred to other enzyme couples.


Plexin-B1 indirectly affects glioma invasiveness and angiogenesis by regulating the RhoA/αvβ3 signaling pathway and SRPK1.
Gliomas are one of the most common primary brain tumors in adults. They display aggressive invasiveness, are highly vascular, and have a poor prognosis. Plexin-B1 is involved in numerous cellular processes, especially cellular migration and angiogenesis. However, the role and regulatory mechanisms of Plexin-B1 in gliomas are not understood and were thus investigated in this study. By using multiple and diverse experimental techniques, we investigated cell apoptosis, mitochondrial membrane potential, cell migration and invasion, angiogenesis, PI3K and Akt phosphorylation, and also the levels of SRPK1 and αvβ3 in glioma cells and animal glioma tissues. The results indicated that Plexin-B1 expression in glioma cell lines is increased compared to normal human astrocytes. Plexin-B1 mediates RhoA/integrin αvβ3 involved in the PI3K/Akt pathway and SRPK1 to influence the growth of glioma cell, angiogenesis, and motility in vitro and in vivo. Thus, Plexin-B1 signaling regulates the Rho/αvβ3/PI3K/Akt pathway and SRPK1, which are involved in glioma invasiveness and angiogenesis. Therefore, the new drug research should focus on Plexin-B1 as a target for the treatment of glioma invasion and angiogenesis.


Current status, technology, regulation and future perspectives of essential oils usage in the food and drink industry.
Nowadays, essential oils (EOs) have a wide use in many applications such as in food, cosmetics, pharmaceutical and animal feed products. Consumers' preferences concerning healthier and safer foodstuffs lead to an increased demand for natural products, in replacement of synthetic substances, used as preservatives, flavourings etc. EOs, besides being safe, are promising alternatives as natural food additives, and much research has been carried out on their antioxidant and antimicrobial activity. The initial purpose of this review is to discuss conventional and 'green' extraction techniques along with their basic mechanism for the isolation of EOs from aromatic plants. This review aims to provide a broad overview of the current knowledge about the chemical constitution of EOs while considering the existence of different chemotypes, since bioactivity is attributed to the chemical composition - qualitative and quantitative - of EOs. Although the food industry primarily uses EOs as flavourings, an overview on recent applications of EOs in food systems and active packaging is provided. EOs exhibit poor solubility in water, oxidation susceptibility, negative organoleptic effect and volatility, restricting their use. Encapsulation techniques have been proven to be one of the best approaches to preserve the biological activities of EOs and minimize their effects on food sensory qualities. Herein, different encapsulation techniques and their basic mechanism for loading EOs are discussed. EOs are highly accepted by consumers, who are often under the misconception that 'natural' means safe. This is, however, an oversimplification, and the possible toxicity of EOs should be taken into consideration. Thus, in the final section of the current review, the focus is on current EU legislation, safety assessment and sensory evaluation of EOs. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


The Epstein-Barr virus latent membrane protein-1 (LMP1) 30-bp deletion and XhoI-polymorphism in nasopharyngeal carcinoma: a meta-analysis of observational studies.
Epstein-Barr virus (EBV) is considered to be closely associated with nasopharyngeal carcinoma (NPC), in which EBV-encoded latent membrane protein 1 (LMP1) was found to have an oncogenic role. However, the results published on the LMP1 polymorphism are inconsistent. In the present study, we performed a meta-analysis to determine the frequency of the associations and a more precise association between NPC and EBV LMP1 gene variants (30-bp deletion (del)/XhoI-loss). Eligible articles met the inclusion/exclusion criteria and were identified in the following electronic databases: PubMed, ScienceDirect, and SciELO. Consequently, the data of interest were extracted and plotted in a table to calculate the frequency and odds ratio (OR) of the outcomes of interest (30-bp del-LMP1/XhoI-loss) in patients with NPC. Study quality (Newcastle-Ottawa Scale (NOS)), publication bias, and heterogeneity were assessed. Thirty-one observational studies were included with a total of 2,846 individuals (NPC, n = 1,855; control, n = 991). The risk of bias in relation to study quality evaluated by NOS was considered low. The pooled estimate of the frequency of 30-bp del-LMP1 and XhoI-loss in patients with NPC was 77% (95% confidence interval (CI): 72 to 82) and 82% (95% CI: 71 to 92), respectively. There was an association between 30-bp del-LMP1 and NPC susceptibility (OR = 2.86, 95% CI: 1.35 to 6.07, P = 0.00). Similarly, there was an association between XhoI-loss and NPC (OR = 8.5, 95% CI: 1.7 to 41, P = 0.00). However, when we analyze the co-existence of the 30-bp del-LMP1 and XhoI-loss in patients with NPC, there was no association (OR = 1.09, 95% CI: 0.06 to 18.79, P = 0.002). Our results suggest an association between the 30-bp del-LMP1 and XhoI-loss with NPC susceptibility. However, our data should be interpreted with caution because the sample size was small, and there was heterogeneity between the studies. Thus, future studies are needed with adjusted estimates to simultaneously evaluate multiple factors involved in the development of NPC. PROSPERO CRD42014013496 .


Measurements of body image in clinical weight loss participants with and without binge-eating traits.
This study measured body image disturbances of individuals in a residential weight loss program who were identified as having binge-eating disorder (BED) traits. The study population (N=97) was a convenience sample of 74 men (76%, mean age=51.0) and 23 women (24%, mean age=49.6) in the program who completed the Eating Questionnaire-Revised (EQ-R), the Attitudes About Weight and Dieting (AAWD), the Physical Appearance State and Trait Anxiety Scale (PASTAS): State Version, and the Contour Drawing Rating Scale (CDR). Fifty-five individuals reported having binge traits (57%) while 42 (43%) had no binge traits. Individuals with the binge traits had a significantly higher BMI than nonbinge trait individuals (P=.008). The binge trait group scored higher on the total AAWD (P=.004), the AAWD factor "Fear of Fat" (P=.002), the total PASTA (P=.001), and the PASTA factor "Weight" (P=.001) than the nonbinge trait group. Logistic regression analysis indicated that the odds of having a binge trait were 1.44 times more likely for a person at a given score on the PASTA subscale Weight vs. a person at a score of 5 units less. Feelings of being unable to control eating among individuals seeking weight control is associated with several characteristics related to body image. Individuals showing greater concern about weight and dieting and specifically greater fears of becoming fat were more likely to have a problem with binge eating than those without these concerns. The results of this study suggest that a negative body image is an important factor to consider when treating individuals indicating binge-eating traits.


Acute Effect of Intravenous Sildenafil on Cerebral Blood Flow in Patients with Vasospasm After Subarachnoid Hemorrhage.
The phosphodiesterase-5 inhibitor sildenafil has been shown to attenuate delayed cerebral ischemia (DCI) and improve neurologic function in experimental subarachnoid hemorrhage (SAH). We recently demonstrated that it could improve cerebral vasospasm (CVS) in humans after SAH. However, successful therapies for DCI must also restore cerebral blood flow (CBF) and/or autoregulatory capacity. In this study, we tested the effects of sildenafil on CBF in SAH patients at-risk for DCI. Six subjects with angiographically confirmed CVS received 30-mg of intravenous sildenafil (mean 9 ± 2 days after aneurysmal SAH). Each underwent (15)O-PET imaging to measure global and regional CBF at baseline and post-sildenafil. Mean arterial pressure declined by 10 mm Hg on average post-sildenafil (8 %, p = 0.01), while ICP was unchanged. There was no change in global CBF (mean 34.5 ± 7 ml/100g/min at baseline vs. 33.9 ± 8.0 ml/100g/min post-sildenafil, p = 0.84). The proportion of brain regions with low CBF (<25 ml/100g/min) was also unchanged after sildenafil infusion. Infusion of sildenafil does not lead to a change in global or regional perfusion despite a significant reduction in cerebral perfusion pressure. While this could reflect the ineffectiveness of sildenafil-induced proximal vasodilatation to alter brain perfusion, it also suggests that cerebral autoregulatory function was preserved in this group. Future studies should assess whether sildenafil can restore or enhance autoregulation after SAH.


Effect of in vivo glucocorticoid administration on histamine metabolism in rat brain synaptosomes.
The effect of in vivo administration of acetonide triamcinolone (AT) on histamine (HA) metabolism in synaptosomes, highly purified from rat brain by discontinuous Ficoll-sucrose gradient centrifugation, was investigated. AT decreases ability of synaptosomes to actively accumulate HA precursor, L-[U-14C]histidine, measured after rapid centrifugation of synaptosomes through silicone oil, as well as lowers activity of HA catabolizing enzyme histamine N-methyltransferase (by 57%). In contrast, no changes in the level of HA, assayed by the single isotope enzymatic method, and the activity of HA synthesizing enzyme, histidine decarboxylase, were found. The results indicate that under applied conditions glucocorticoid administration may decrease turnover of neuronal pool of HA without significant effect on HA level.


Opportunities to improve reporting of rapid response in health technology assessment.
Mini health technology assessment (HTA) reports have been used to support policy makers and health systems by providing a timely summary of scientific evidence. The objective of this meta-epidemiologic study was to evaluate the quality of reporting of mini-HTA reports published in Brazil. An electronic search for all mini-HTA reports published between 2014 and March 2019 was conducted in the SISREBRATS and CONITEC databases. The study selection and data extraction were performed by two independent assessors. The following data were extracted: bibliographic data; research question; characteristics of the population, health technologies and outcomes assessed; eligibility criteria; information about searches and study selection; risk of bias assessment; quality of evidence assessment; synthesis of results; and recommendation about the technology evaluated. A descriptive analysis was used to summarize the information retrieved from all the included mini-HTA reports. We included 103 mini-HTA reports, the great majority of which (92.3 percent) focused on the coverage of the technologies in the healthcare system, with more than 60 percent being about drugs. Only five mini-HTA reports (4.8 percent) gave reasons for the choice of outcomes, and fifteen (14.5 percent) discriminated between primary and secondary outcomes. All mini-HTAs reported the databases searched and 99 percent of them reported using Medline. Sixty percent of the mini-HTA reported assessing the risk of bias, and 52 percent reported assessing the quality of evidence. The quality of reporting of the mini-HTA reports performed in Brazil is insufficient and needs to be improved to guarantee transparency and replicability.


Extracellular Iron is a Modulator of the Differentiation of Osteoclast Lineage Cells.
Osteoclasts originate from the hematopoietic stem cell and share a differentiation pathway with the cells of the monocyte/macrophage lineages. Development and activation of osteoclasts, and as a consequence regulation of bone resorption, depend on two growth factors: macrophage colony-stimulating factor and receptor activator of NF-κB ligand. Furthermore, cell development and activity are modulated by a microenvironment composed of cytokines and growth factors and of the extracellular matrix. Membrane transporters are a means for cells to interact with their environment. Within this study, the expression of proteins regulating cellular iron homeostasis in osteoclast-like cells grown from bone marrow-derived progenitors was compared to the expression of this set of proteins by monocyte/macrophage lineage cells. In differentiating osteoclasts, levels of transcripts encoding transferrin receptor 1 and divalent metal transporter 1 (Slc11A2) were increased, while levels of transcripts encoding ferroportin (Slc40A1) and natural resistance-associated macrophage protein 1 (Slc11A1) were decreased. Supplementation of the culture media with exogenous iron led to an increase in the proliferation of osteoclast progenitor cells and to the expression of a macrophage-like phenotype, while the development of osteoclasts was reduced. Upon transfer of mature OC onto a CaP substrate, iron depletion of the medium with the Fe(3+)-chelator Deferoxamine Mesylate decreased CaP dissolution by ~30 %, which could be restored by addition of exogenous iron. During the 24 h of the assay, no effects were observed on total TRAP activity. The data demonstrate transcriptional regulation of the components of cellular iron transporters during OC development and suggests that iron homeostasis may contribute to fine-tuning of the RANKL-induced OC development.


[Are artificial disorders common in palliative care? A Case report].
The main task of palliative care specialists is to focus on symptom control such as pain, nausea or fatigue. Thorough anamnesis, physical examination, laboratory examination, and differential diagnosis can ensure appropriate treatment. In an increasing number of cases psychiatric conditions like depression or anxiety increase also occur so palliative care physicians need to be more prepared to handle them. The question of this case report is, how a palliative care specialist can distinguish between a malignant disease or neurological disease progression and a presentation primarily psychiatric in etiology, as is the case in factitious disorders. We are also interested in the incidence rate of such factitious disorders. Our case study demonstrates that it is rare but not impossible that a doctor will encounter factitious symptoms in the palliative setting. This suggest being aware of evidence of psychiatric origins even in discharge letters and referrals that indicate palliative care needs, to ensure that palliative care really is the best treatment option for the patient. We do believe such cases to be rare in a palliative setting, however.


Monoclonal antibodies against an alpha-amylase inhibitor from wheat kernel.
An alpha-amylase inhibitor (called the 0.53-inhibitor, Maeda, K., Takamori, Y. and Oka, O. (1982) Agric. Biol. Chem. 41, 2873-2875) and the carboxymethylated inhibitor were used to immunize mice (strain BALB/c) according to a procedure described earlier (McMaster, W.R. and Williams, A.F., (1979) Eur. J. Immunol. 9, 426-433). After fusion of spleen cells with NS-1 myeloma cells, three stable clones producing antibodies against the inhibitor were obtained. The binding characteristics of the monoclonal antibodies, AWAI-1, AWAI-2 and AWAI-3, to the inhibitor were analyzed by radioimmunoassay. Two of these monoclonal antibodies to the alpha-amylase inhibitor did not show any binding affinity towards carboxymethylated inhibitor, suggesting that the main antigenic determinant on the native inhibitor is tertiary-structure dependent. The monoclonal antibodies obtained cross-reacted with three other alpha-amylase inhibitors (the 0.19-, the 0.36- and the 0.38-inhibitor) in wheat and these were separated together with the 0.53-inhibitor from the rest of inhibitors by immunoaffinity chromatography. One stable clone producing antibody against the carboxymethylated inhibitor was also established, AWAI-4. The antigenic determinant to this antibody was found to be included in the region of Met(5)-Lys(25) on the carboxymethylated inhibitor.


Restrictive cardiomyopathy in a child.
Restrictive cardiomyopathy in young children is rare and carries a poor prognosis. We report an 18-month-old girl with poor feeding and abdominal distension. Except for hepatomegaly, no other gastrointestinal abnormalities were found. She had normal-sized ventricles but biatrial enlargement. Echocardiography demonstrated normal systolic but impaired diastolic function. Cardiac catheterization revealed a characteristic dip-and-plateau configuration of the right ventricular pressure tracing. The diagnosis turned out to be typical restrictive cardiomyopathy. The patient was maintained on aspirin while awaiting cardiac transplant.


Cytokine gene polymorphisms in heart transplantation: association of low IL-10 production genotype with Quilty effect.
Cytokines are important modulators of post-transplant, allogeneic immune responses. In heart transplantation, endomyocardial biopsies allow monitoring of histologic and immunologic events that occur inside the graft; their correlation with risk factors condition graft outcome. Recent reports indicate that various cytokine gene allelic polymorphisms control the number of cytokines produced and may be associated with graft outcome. We studied 71 heart transplant recipients between December 1985 and December 2000. We used sequence-specific primers (SSP) polymerase chain reaction to study interleukin-10 (IL-10) polymorphisms at -1082 (G/A), -819 (C/T), and -592 (C/A); tumor necrosis factor alpha (TNF-alpha) at -308 (G/A) and -238 (G/A); transforming growth factor beta (TGF-beta) variants at codon 10 (C/T) and codon 25 (G/C); and interferon-gamma (IFN-gamma) polymorphisms at +874 (T/A). We determined the association of allele, genotype, and haplotype frequencies with the presence of histologically proven rejection episodes (according to International Society for Heart and Lung Transplantation criteria) and the presence of Quilty lesions in endomyocardial biopsy specimens. We found no association between the polymorphisms studied and the frequency and severity of acute and chronic rejection episodes. However, the gene frequency of allele A at IL-10 -1082, associated with decreased IL-10 production, was increased in patients with Quilty lesions (p = 0.0027, odds ratio = 2.98). Similarly, we found more AA homozygous individuals, compared with AG heterozygous and GG homozygous individuals (p = 0.0017), among patients with Quilty effect. The ATA and ACC IL-10 haplotypes also were associated with Quilty effect (p = 0.0051). These results suggest that genetically controlled decreased IL-10 production predisposes to the development of Quilty lesions. The decreased negative regulatory effect of IL-10 on T cells and macrophages may result in enhanced graft infiltration.


The right time for change: A report on the heterogeneity of IVB endometrial cancer and improved risk-stratification provided by new 2023 FIGO staging criteria.
We sought to provide a contemporary report on stage IVB endometrial carcinoma (2009 FIGO criteria) and applied the 2023 FIGO staging criteria to this population. Retrospective review of patients who underwent cytoreduction for stage IVB endometrial carcinoma (2009 FIGO criteria) from 2014 to 2020 was performed. Demographics, clinicopathologic factors, and outcomes were recorded. Disease burden and distribution were determined by imaging, operative notes, and pathology reports. Patients were re-staged according to 2023 FIGO staging criteria. Categorical variables were compared using χ2 or Fisher's exact test, and Kaplan-Meier curves compared survival outcomes using the log-rank test. Eighty-eight cases were included. Most patients (63.6%) were not suspected to have stage IVB (2009 FIGO criteria) disease prior to surgery. Seventy-two percent of patients underwent primary cytoreduction, and 12 (19%) were suboptimal. Median progression-free survival (PFS) was 12 months (95% CI 10-16 months), and median overall survival (OS) was 38 months (95% CI 19-61 months). Degree of cytoreduction (p = 0.0101) and pelvic-confined metastatic disease (p = 0.0149) were significant prognostic factors, while distant metastases were not associated with worse outcomes. For those patients who underwent primary cytoreduction, number (p = 0.0453) and diameter (p = 0.0192) of tumor deposits were associated with PFS. When 2023 FIGO staging criteria were applied, 58% of patients underwent change in stage, and 8% did not meet criteria for complete staging. PFS was significantly different based on 2023 FIGO staging (p = 0.0307); a trend in OS was also noted (p = 0.0550). Stage IVB endometrial carcinoma (2009 FIGO criteria) encompasses a diverse cohort of patients, where certain clinicopathologic features, tumor burden, and degree of cytoreduction are associated with outcomes. The 2023 FIGO staging criteria significantly improves our ability to risk-stratify patients.


A template for a planar tetracoordinate heavier group 14 atom: a global study of C2Si2X(q) (X = C, Si, Ge, Sn, Pb; q = +1, 0, -1).
Through a global isomeric study, we computationally identified the first structural template C2Si2X that could encompass a planar tetracoordinate X for all the heavier group 14 elements X in the 0, +1 or -1 charge state. We thus significantly expanded the traditional 16/17/18ve rules to 19/20/21ve for ptX.


Phage yield during W-reactivation of bacteriophage.
Phage production in liquid medium during W-reactivation parallels the extent of W-reactivation of infective centres on plates. The mean burst size is independent of W-reactivation; thus the reactivated phage yields a normal burst. As 8 plates, the lex- mutant shows no W-reactivation in liquid medium. It is concluded that W-reactivation is a consequence of an induced DNA repair which reactivates the damaged parental phage DNA to its full biological activity.


Interictal spiking increases with sleep depth in temporal lobe epilepsy.
To test the hypothesis that deepening sleep activates focal interictal epileptiform discharges (IEDs), we performed EEG-polysomnography in 21 subjects with medically refractory temporal lobe epilepsy. At the time of study, subjects were seizure-free for > or =24 h and were taking stable doses of antiepileptic medications (AEDs). Sleep depth was measured by log delta power (LDP). Visual sleep scoring and visual detection of IEDs also were performed. Logistic-regression analyses of IED occurrence in relation to LDP were carried out for two groups of subjects, nine with frequent IEDs (group 1) and 12 with rare IEDs (group 2). The LDP differentiated visually scored non-rapid eye movement (NREM) sleep stages (p = 0.0001). The IEDs were most frequent in NREM stages 3/4 and least frequent in REM sleep. Within NREM sleep, in both groups, IEDs were more frequent at higher levels of LDP (p < 0.05). In group 1, after accounting for the level of LDP, IEDs were more frequent (a) on the ascending limb of LDP and with more rapid increases in LDP (p = 0.007), (b) in NREM than in REM sleep (p = 0.002), and (c) closer to sleep onset (p < 0.0001). Fewer than 1% of IEDs occurred within 10 s of an EEG arousal. Processes underlying the deepening of NREM sleep, including progressive hyperpolarization in thalamocortical projection neurons, may contribute to IED activation in partial epilepsy. Time from sleep onset and NREM versus REM sleep also influence IED occurrence.


Newton on active and passive quantities of matter.
Newton published his deduction of universal gravity in Principia (first ed., 1687). To establish the universality (the particle-to-particle nature) of gravity, Newton must establish the additivity of mass. I call 'additivity' the property a body's quantity of matter has just in case, if gravitational force is proportional to that quantity, the force can be taken to be the sum of forces proportional to each particle's quantity of matter. Newton's argument for additivity is obscure. I analyze and assess manuscript versions of Newton's initial argument within his initial deduction, dating from early 1685. Newton's strategy depends on distinguishing two quantities of matter, which I call 'active' and 'passive', by how they are measured. These measurement procedures frame conditions on the additivity of each quantity so measured. While Newton has direct evidence for the additivity of passive quantity of matter, he does not for that of the active quantity. Instead, he tries to infer the latter from the former via conceptual analyses of the third law of motion grounded largely on analogies to magnetic attractions. The conditions needed to establish passive additivity frustrate Newton's attempted inference to active additivity.


Serotonergic, 5-HT2, receptor-mediated phosphoinositide turnover and mobilization of calcium in cultured rat retinal pigment epithelium cells.
Cultured rat retinal pigment epithelium cells are shown to contain serotonergic, 5-HT2, receptors associated with phosphoinositide turnover and mobilization of intracellular calcium. Serotonin at a concentration of 10 microM induced a 2.5-fold increase in [3H]-inositol phosphates (more than 75% is in the form of [3H]-inositol-1-phosphate) accumulation within 30 min in cells preincubated in [3H]-myo-inositol and exposed to 5 mM lithium chloride. The EC50 value of serotonin was approx. 0.9 microM and the saturation concentration was 100 microM. Serotonin analogues like tryptamine, 5-methoxytryptamine, alpha-methyl-serotonin and the 5-HT2 agonists quipazine and DOI (1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane) all stimulated InsPs accumulation to some degree. Carbachol, noradrenaline, isoproterenol, dopamine, tryptophan, 5-hydroxytryptophan, 8-hydroxy-2(di-n-propyl-amino) tetralin, 2-methyl-serotonin and NECA (5'-[N-ethyl]-carboxamidoadenosine) were inactive. The serotonin-induced response was blocked most effectively by ketanserin and methysergide but not by 5-HT3 or 5-HT1 antagonists. The serotonin response was attenuated by the active phorbol ester, 4 beta-phorbol 12-myristate 13-acetate and this was attenuated by the non-selective protein kinase C inhibitor, staurosporine. Pertussis toxin failed to influence the serotonin-mediated phosphoinositide turnover. Addition of serotonin to cultures loaded with Fura-2 showed a transient increase in calcium concentrations in most of the cells. This change in calcium was independent of external calcium and the serotonin response was attenuated by ketanserin but not by the 5-HT3 antagonist granisetron.(ABSTRACT TRUNCATED AT 250 WORDS)


Strain-level analysis reveals the vertical microbial transmission during the life cycle of bumblebee.
Microbial acquisition and development of the gut microbiota impact the establishment of a healthy host-microbes symbiosis. Compared with other animals, the eusocial bumblebees and honeybees possess a simple, recurring, and similar set of gut microbiota. However, all bee gut phylotypes have high strain-level diversity. Gut communities of different bee species are composed of host-specific groups of strains. The variable genomic regions among strains of the same species often confer critical functional differences, such as carbon source utilization, essential for the natural selection of specific strains. The annual bumblebee colony founded by solitary queens enables tracking the transmission routes of gut bacteria during development stages. Here, we first showed the changes in the microbiome of individual bumblebees across their holometabolous life cycle. Some core gut bacteria persist throughout different stages of development. Gut microbiota of newly emerged workers always resembles those of their queens, suggesting a vertical transmission of strains from queens to the newborn workers. We then follow the dynamic changes in the gut community by comparing strain-level metagenomic profiles of queen-worker pairs longitudinally collected across different stages of the nest development. Species composition of both queen and worker shifts with the colony's growth, and the queen-to-worker vertical inheritance of specific strains was identified. Finally, comparative metagenome analysis showed clear host-specificity for microbes across different bee hosts. Species from honeybees often possess a higher level of strain variation, and they also exhibited more complex gene repertoires linked to polysaccharide digestion. Our results demonstrate bacterial transmission events in bumblebee, highlighting the role of social interactions in driving the microbiota composition. By the community-wide metagenomic analysis based on the custom genomic database of bee gut bacteria, we reveal strain transmission events at high resolution and the dynamic changes in community structure along with the colony development. The social annual life cycle of bumblebees is key for the acquisition and development of the gut microbiota. Further studies using the bumblebee model will advance our understanding of the microbiome transmission and the underlying mechanisms, such as strain competition and niche selection. Video Abstract.


Antigen-capture ELISA for the detection of Rift Valley fever virus nucleoprotein using new monoclonal antibodies.
Monoclonal antibodies (MAbs) raised against the nucleoprotein (NP) of Rift Valley fever virus (RVFV) were developed, and an antigen-capture enzyme-linked immunosorbent assay (Ag-capture ELISA) system was developed for the detection of RVFV NP. The assay detected RVFV antigen from culture supernatants containing as little as 7.8-31.3 pfu per 100 μl. Reactivity with various truncated NPs indicated that MAb C10-54 bound only to the full-length NP, probably due to recognition of a conformational epitope, whereas MAbs G2-36 and D5-59 bound to a linear epitope ranging from amino acid residues 195-201 in the C-terminal region. Based on the alignments of the amino acid sequence of RVFV NP, the epitope regions of MAbs G2-36 and D5-59 were completely conserved among all RVFV strains. These results suggest that the MAbs are applicable to the Ag-capture ELISA for the diagnosis of RVFV infections.


Effect of continuous tolazoline infusion on cardiopulmonary response to dopamine in unanesthetized newborn lambs.
We evaluated the cardiopulmonary interaction of tolazoline and low-, medium-, and high-dose dopamine infusion (2.7, 27, and 270 micrograms/kg/min) in 11 normal, chronically instrumented, unsedated neonatal lambs. Concomitant tolazoline and dopamine infusions caused tachycardia at all dopamine doses and blocked alpha-adrenergic-mediated increases in systemic resistance and left atrial pressure caused by medium and high doses of dopamine. Moderate doses of dopamine alone increased cardiac output. During simultaneous tolazoline infusion, dopamine increased cardiac output at both moderate and high doses. The effect of dopamine on pulmonary artery pressure was not modified by tolazoline; pulmonary pressure increased similarly with dopamine alone and with dopamine plus tolazoline. Calculated pulmonary vascular resistance rose with dopamine alone, but not with infusion of tolazoline and dopamine, because pulmonary blood flow rose in proportion to pulmonary artery pressure.


Green synthesis of silver nanoparticles: an approach to overcome toxicity.
Nanotechnology, with its advent, has made deep inroads into therapeutics. It has revolutionized conventional approaches in drug designing and delivery systems by creating a large array of nanoparticles that can pass even through relatively impermeable membranes such as blood brain barrier. Like the two sides of a coin, nanotechnology too has its own share of disadvantages which in this scenario is the toxicology of these nanoparticles. Numerous studies have discussed the toxicity of various nanoparticles and the recent advancements done in the field of nanotechnology is to make it less toxic. "Green synthesis" of nanoparticles is one such approach. The review summarizes the toxicity associated with the nanoparticles and the advancement of "green" nanomaterials to resolve the toxicity issues.


Diffuse large B-cell lymphoma at risk of secondary CNS involvement: The inefficacy of intravenous high-dose methotrexate CNS prophylaxis and the importance of baseline cerebrospinal fluid analysis.
High-dose intravenous methotrexate (HD-MTX) CNS prophylaxis in high-risk diffuse large B cell lymphoma (DLBCL) remains controversial. We describe real-world CNS relapse incidence following baseline cerebrospinal fluid (CSF) analysis to exclude asymptomatic leptomeningeal involvement in newly diagnosed high-risk DLBCL patients with versus without single-route HD-MTX CNS prophylaxis. Consecutively diagnosed high-risk systemic DLBCL patients without leptomeningeal involvement by CSF analysis (noCNS) were identified retrospectively. Five-year CNS relapse incidence and survival outcomes were examined, as stratified by receipt of HD-MTX prophylaxis. Secondary analysis of survival outcomes in patients with synchronous leptomeningeal involvement (CNSinv) by CSF analysis at diagnosis were compared with the noCNS group. No significant difference in 5-year CNS relapse incidence was observed following HD-MTX prophylaxis versus no prophylaxis (total n = 445) despite similar CNS-IPI risk; 6.2% versus 5.6%, adjusted HR 1.08 (95% CI 0.41-2.85), p = .88; nor in 5-year progression free survival (PFS) or overall survival (OS) risk. Of CNSinv patients, 93.3% had ≥1 extranodal site. Increased CNS relapse/progression risk (5-year risk; HR 10.7 [95% CI 5.35-21.37], p < .0001) and inferior PFS and OS were observed in CNSinv versus all noCNS patients. The CNSinv group had superior OS compared with noCNS patients who later experienced CNS relapse (HR 0.55, p = .052). HD-MTX prophylaxis does not reduce CNS relapse risk in high-risk systemic DLBCL without leptomeningeal involvement by CSF analysis at diagnosis. Asymptomatic patients with synchronous leptomeningeal involvement on baseline CSF examination are at increased risk of further CNS disease events and inferior survival compared to patients without CSF involvement.


Suppression of the Smurf1 Expression Inhibits Tumor Progression in Gliomas.
Glioblastoma, one of the common malignant brain tumors, results in the highly death, but its underlying molecular mechanisms remain unclear. Smurf1, a member of Nedd4 family of HECT-type ligases, has been reported to contribute to tumorigenicity through several important biological pathways. Recently, it was also found to participate in modulate cellular processes, including morphogenesis, autophagy, growth, and cell migration. In this research, we reported the clinical guiding significance of the expression of Smurf1 in human glioma tissues and cell lines. Western blotting analysis discovered that the expression of Smurf1 was increased with WHO grade. Immunohistochemistry levels discovered that high expression of Smurf1 is closely consistent with poor prognosis of glioma. In addition, suppression of Smurf1 can reduce cell invasion and increase the E-cadherin expression, which is a marker of invasion. Our study firstly demonstrated that Smurf1 may promote glioma cell invasion and suppression of the Smurf1 may provide a novel treatment strategy for glioma.


Intracellular response of neurons of the caudate nucleus and putamen to intrastriatal stimulation in cat.
The purpose of this research was to determine if the different functional areas of the striatum, as defined by corticostriate connections, have excitatory and/or inhibitory interconnections. In cats anesthetized with barbiturates, an intracellular recording electrode was angled at 45 degrees such that it (1) crossed all functional areas of the striatum in a single pass and (2) traversed perpendicular to intrastriatal axonal bundles and their terminal fields. > 95% of the neurons recorded intracellularly in the head of the caudate (Cd) nucleus responded to stimulation of the rostromedial striatum (limbic area) producing an initial excitatory response in all cases. Membrane hyperpolarization and inhibition followed the initial excitatory response in approximately half of the responsive neurons. As the recording electrode approached the stimulating electrode, latencies to response onset decreased and amplitudes of the initial excitatory responses increased. Stimulation of a single site produced responses in neurons found in all functional areas of the Cd nucleus. Based on the known topography of afferents to the striatum, these results cannot be explained by stimulation of fibers en passant. Therefore, we conclude that the limbic striatum is connected to other functional areas of the Cd nucleus by intrinsic excitatory and inhibitory circuits. We speculate that intrinsic circuits are a hidden layer of organization providing connectional plasticity by which the influence of an input on striatal neurons may be expanded or contracted beyond the anatomical limits of the afferent terminal field.


Microsatellite polymorphism analysis allows the individual assignment of the rat 11 beta-hydroxylase gene (Cyp11b1) and the rat aldosterone synthase gene (Cyp11b2) to chromosome 7 using rat x mouse somatic cell hybrids and identifies differences between and within various rat strains.
Mouse hepatoma x rat hepatocyte hybrids that segregate rat chromosomes were used to determine the chromosomal location of the rat genes encoding 11 beta-hydroxylase and aldosterone synthase (Cyp11b1 and Cyp11b2 respectively). By means of species-specific restriction fragments and microsatellite markers both genes were mapped to rat chromosome 7. The Cyp11b1 microsatellite marker was subsequently found to vary in length between and within rat strains. Furthermore, we compared the sequences of Cyp11b1 markers in two genetically hypertensive strains of rat with their normotensive counterparts. Previous studies have indicated that 11 beta-hydroxylase activities in Milan and Lyon hypertensive strains are different from their respective genetic controls. The Cyp11b1 microsatellite regions from Lyon hypotensive and normotensive strains of rat were similar and were both shorter by 15 bases than that of the Lyon hypertensive strain. The Cyp11b1 marker in Milan hypertensive (MHS) and normotensive (MNS) strains differ from all the Lyon strains and from each other. The MHS marker is 12 bases shorter than that of MNS rats. These differences in microsatellite length may provide useful polymorphic markers in cosegregation studies of genetic hypertension in rats.


Is pinking susceptibility index a good predictor of white wines pinking phenomena?
The concentration of anthocyanins in white wines from different grape varieties (Prosecco, Sauvignon Blanc, Pinot Grey, Chardonnay, Síria) from diverse countries (Italy, Moldova, and Portugal) was determined. Anthocyanins, mainly malvidin-3-O-glucoside, were detected in all wines (from 0.7 to 704 μg/L). No correlation between anthocyanins concentration and the Pinking Susceptibility Index (PSI) was observed contrarily to the colour of wines exposed to oxygen (r = 0.871, p < 0.00005). The oxidation of wines with hydrogen peroxide resulted in the formation of various compounds. PSI was correlated with compounds absorbing in the 400-480 nm region, probably more related to the browning than the pinking phenomenon. The lack of correlation between the PSI and anthocyanins concentration in white wines can be due to the different chemical compositions of white wines that yield various compounds after oxidation that might not be related to the natural wine pinking phenomenon.


Attenuation of angiotensin-induced water intake in estrogen-treated rats.
Chronic treatment with either estradiol benzoate (31 and 57 microgram/kg/day) or ethynyl estradiol (30 and 72 microgram/kg/day) attenuated the drinking responses of female rats to acute administration of either isoproterenol (25 microgram/kg, SC) or synthetic angiotensin II (100 and 200 microgram/kg, IP). While these studies do not rule out the possibility that attenuation of isoproterenol-induced drink in estrogen-treated rats may be associated with a defect in renin release, attention is also apparently associated with a reduced responsiveness to angiotensin II. This may be related to reduced permeability of angiotensin II at the level of the circumventricular organs of the brain; to hyporesponsiveness of receptors for angiotensin II mediating thirst in the central nervous system, or to mechanism beyond the receptor that are responsible for the conscious behavioral changes which normally accompany angiotensin II-induced thirst.


Prevalence of pathogenic bacteria in Ixodes ricinus ticks in Central Bohemia.
Bacteria associated with the tick Ixodes ricinus were assessed in specimens unattached or attached to the skin of cats, dogs and humans, collected in the Czech Republic. The bacteria were detected by PCR in 97 of 142 pooled samples including 204 ticks, i.e. 1-7 ticks per sample, collected at the same time from one host. A fragment of the bacterial 16S rRNA gene was amplified, cloned and sequenced from 32 randomly selected samples. The most frequent sequences were those related to Candidatus Midichloria midichlori (71% of cloned sequences), followed by Diplorickettsia (13%), Spiroplasma (3%), Rickettsia (3%), Pasteurella (3%), Morganella (3%), Pseudomonas (2%), Bacillus (1%), Methylobacterium (1%) and Phyllobacterium (1%). The phylogenetic analysis of Spiroplasma 16S rRNA gene sequences showed two groups related to Spiroplasma eriocheiris and Spiroplasma melliferum, respectively. Using group-specific primers, the following potentially pathogenic bacteria were detected: Borellia (in 20% of the 142 samples), Rickettsia (12%), Spiroplasma (5%), Diplorickettsia (5%) and Anaplasma (2%). In total, 68% of I. ricinus samples (97/142) contained detectable bacteria and 13% contained two or more putative pathogenic groups. The prevalence of tick-borne bacteria was similar to the observations in other European countries.


Factors Influencing the Length of Hospital Stay in a Safety Measures Psychiatric Hospital in Romania.
A growth in the number of patients admitted to forensic psychiatric services has been reported worldwide. At the same time, an increase in the length of hospital stay of these patients was observed. To identify the factors that influence the length of hospital stay in a Romanian forensic psychiatric sample, as well as to compare the socio-demographic, clinical and criminological features of the "long stay" and "shorter stay" patients. This was a retrospective, cross-sectional study that included all patients admitted to Săpoca Psychiatry and Safety Measures Hospital according to article 110 of the Penal code (n=650) over a period of 11 years (2008-2018). Long stay was considered as a period of hospitalization greater than 5 years. The average length of hospital stay in the sample was 3.20 years. Approximately one quarter (n=154) of the patients were classified as "long stay". The variables that were significantly associated with length of stay included the main psychiatric diagnosis, social support, the severity of the offence and the perpetration of violence. Overall, our findings are in line with observations made by researchers from other countries. Our study highlights the need for further, more detailed research on the patients admitted to forensic psychiatric units in Romania.


[Microvascular anastomosis of the iliac crest transplant in mandibular reconstruction].
In 12 patients with extensive lower jaw defects following tumor removal or after radioosteonecrosis, a free osteocutaneous iliac crest flap with microvascular anastomoses was used to reconstruct the lower jaw in a single session. The results are reported in brief for this group, in many of whom conditions were not optimal for transplantation because of previous surgery, infection, or radiological tissue damage.


Effectiveness of an early, quantified, modified oral feeding protocol on nutritional status and quality of life of patients after minimally invasive esophagectomy: A retrospective controlled study.
Previous studies confirmed the safety and feasibility of oral feeding on the first postoperative day (POD) for patients with minimally invasive esophagectomy (MIE). Nonetheless, some clinical concern can lead to delays in early oral feeding on POD 1. To our knowledge, few reports have focused on resolving these clinical concerns. The aims of this study were to evaluate the effects of an early, quantified, modified oral feeding protocol for patients after MIE and to explore its effect on nutritional status and quality of life (QoL). In this prospective controlled trail, 200 patients were selected as the intervention group (IG) from March 2020 to June 2021; 115 patients hospitalized from June 2019 to February 2020 were assigned to the control group (CG). For 2 wk during the postoperative period, IG participants received an early, quantified, modified oral feeding protocol. The recovery of dietary outcomes, nutritional status, and QoL were evaluated after the intervention. There was no significant difference between the two groups in terms of demographic and clinical characteristics and baseline physical function. After the intervention, patients in the IG showed a more rapid growth in daily total oral caloric intake and the ratio of oral calorie intake to total calorie required by the body (K/R value) from POD 1 to POD 14, and less weight loss (1.5 ± 1 versus 2.1 ± 1.7 kg; P < 0.05), better serum prealbumin (193.0 ± 26.9 versus 139.3 ± 27.2 mg/L; P < 0.05) than the CG with statistical significance. By the second week of the intervention, IG patients reported higher global QoL and function scores and lower symptom scores than patients in the CG. The IG participants presented a shorter time to first flatus and bowel movement (P < 0.001), a shorter postoperative hospital length of stay, and higher activities of daily living scores (P < 0.05) the those in the CG. The findings demonstrated that the early, quantified, modified oral feeding protocol can alleviate postoperative body weight loss, improve the patient's nutritional status, and have a positive effect on QoL and early recovery for patients undergoing MIE.


Light and electron microscopic autoradiographic study of the dorsal root projections to the cat dorsal horn.
The distribution of terminals arising from dorsal root primary afferents was examined in the lumbar spinal cord of cats using light- and electron-microscopic autoradiography. Tritiated proline or leucine was injected into either the L6 or L7 dorsal root ganglion. The light-microscopic spinal cord distribution of radioactivity in the ganglia was independent of the type of amino acid used. Likewise, the length of the survival time after injection had no effect. The projections to the substantia gelatinosa and the marginal zone were consistently densest. However, the topography of the dorsal horn distribution, relative to the segment of entry, varied significantly especially in the gelatinosa, depending upon the ganglia injected. Those to the substantia gelatinosa were largely limited to the segment of entry; those to the marginal zone and nucleus proprius extended many segments beyond the level of entry. At all levels the projection was exclusively ipsilateral to the side of injection. At the electron-microscopic level the distribution of radioactivity was determined in each of the three easily recognizable areas of the dorsal horn: the marginal zone, the substantia gelatinosa and the nucleus proprius. In each dorsal horn area the total terminal population was divided into four basic categories. Each of these areas was found to contain a characteristic distribution of these four terminal categories. The difference between areas arose, primarily, as a consequence of the dorsal to ventral decreasing frequency gradient of two types of terminal: those containing large, dense-cored vesicles and the increasing gradient of those containing flattened vesicles. The terminals with small pleomorphic vesicles and those with large round vesicles were frequently encountered in all three areas without a detectable frequency gradient. Similarly the primary afferent terminal population that is the subset of the total terminal population labelled after dorsal root ganglion injection, was also characteristic of the area, and each area was dominated by a different terminal-type. In the marginal zone the terminals containing large dense-cored vesicles dominated. In the substantia gelatinosa the terminals with pleomorphic vesicles (which included the so-called 'C' type terminals) dominated. And the terminals containing large round vesicles dominated the primary afferent population in the nucleus proprius. The terminals containing flattened vesicles were never found to be specifically labeled in any of the areas examined.


Significance of peritoneal cytology in patients with potentially resectable adenocarcinoma of the pancreatic head.
Recurrence in the peritoneum occurs in up to 50% of patients after a potentially curative pancreaticoduodenectomy. Previous authors have implicated preoperative fine-needle aspiration (FNA) as a cause of intraperitoneal tumor dissemination, although prior studies of peritoneal cytology findings have largely involved patients with locally advanced disease. A consecutive series of patients referred to our institution between 1991 and 1993 with suspected or biopsy-proven adenocarcinoma of the pancreatic head was studied prospectively. All patients fulfilled criteria for resectability as assessed by computed tomography: no metastatic disease, no encasement of the superior mesenteric or hepatic arteries, and a patent superior mesenteric-portal venous confluence. Peritoneal washings were obtained at the time of staging laparoscopy and/or at subsequent laparotomy. Data regarding peritoneal cytology results, previous FNA, preoperative chemoradiation, eventual resection, pattern of disease recurrence, and survival were collected. A total of 80 peritoneal washings from 60 consecutive patients were prospectively examined. Forty-nine (82%) of 60 patients underwent FNA before peritoneal washings were obtained. A total of four patients (7%) had positive peritoneal cytology findings: three (6%) of 49 who underwent prior FNA and one (9%) of 11 with no prior FNA. Similarly, no differences in eventual peritoneal failure or short-term survival were observed for patients who underwent prior FNA compared with patients who did not. All four patients with positive peritoneal cytology findings had metastatic disease (liver, three; peritoneum, one) at a median of 4.8 months after diagnosis; three of the four died of disease at a median of 8 months. Positive peritoneal cytology findings are rare in patients with radiologically resectable adenocarcinoma of the pancreas. When found, positive peritoneal washings are an indicator of advanced disease characterized by unresectability, early metastasis, and short survival. Computed tomographic-guided FNA does not appear to increase the risk for positive peritoneal washings and represents a valid approach to the pretreatment diagnosis of patients with suspected pancreatic malignancy.


Particle Engineering for Enabling a Formulation Platform Suitable for Manufacturing Low-Dose Tablets by Direct Compression.
Maintaining good content uniformity (CU) is a significant challenge for low-dose oral tablets in particular when using direct compression (DC). Using 6 model active pharmaceutical ingredients, we show that a platform DC tablet formulation suitable for developing low-dose API with excellent CU can be developed. This platform formulation is enabled by particle engineering, where an API of interest is loaded in a suitable porous carrier to form a uniform API-carrier composite. Powder properties of such composite particles are dictated by the properties of the carrier, which are insensitive to chemical structure and loading level of the API. Powder flowability, tabletability, tablet friability, and tablet disintegration time are all excellent and only vary within a narrow range among the 6 model APIs. Nearly 100% drug can be released in water from tablets composed of the 6 model APIs. Thus, the approach described here holds the promise for broad application in developing low-dose tablet products using DC possessing excellent CU and other critical quality attributes.


Effectiveness of a patient-specific 3-dimensional printed model in Septal Myectomy of hypertrophic cardiomyopathy.
Advanced cardiovascular surgery in structural heart disease require accurate pre-operative evaluation. Most of non-invasive imaging technologies remain limited in two-dimensional and show insufficiency of visualization for procedural planning. The aim of this study was to discuss the value of patient-specific 3-dimensional (3D) printing in treatment of hypertrophic cardiomyopathy (HCM). Patient-specific 3D-printed models were constructed preoperatively in 12 consecutive HOCM patients which come to Beijing Anzhen Hospital for surgical treatment from October 2016 to March 2017. Image files were extracted from multi-slice computed tomography images, 3D models were constructed by the Mimics 19.0 software and generated by Objet350 Connex3 3D printer. The 3D-printed models were made with soft material that can be surgically performed. The modified Morrow myectomy of the model was performed before the operation. Clinical characters and echocardiographic parameters were recorded. There was no significant difference in tissue volume between the models and specimens. Preoperative and postoperative echocardiography showed the septal thickness was reduced from 18.8±4.5 mm to 12.7±3.3 mm (p<0.001), the left ventricular outflow tract obstruction was adequately relieved (83.0±27.73 mm Hg to 8.7±6.5 mm Hg, p<0.001), and the SAM disappeared completely after the operation. Cardiac function was improved in all patients (New York Heart Association functional class III to class I/II). The proposed optimal 3D-modelled septal myectomy allows intraoperative monitoring of the shape and volume of the myocardium resection to achieve the 'ideal' interventricular septum. It eliminates obstruction in the LVOT and SAM, resulting in LV remodeling with an increase in LV end-diastolic volume and diameter at early follow-up.


Genomic instability evaluation by BMCyt and telomere length in Brazilian family farmers exposed to pesticides.
Brazil is one of the largest consumers of pesticides in the world. This high consumption has resulted in higher potential health risk to agricultural farm workers due to occupational exposure. Hence, the aim of this study is to evaluate genomic instability, using Buccal Micronucleus Cytome (BMCyt) and telomere length (TL) measurement as biomarkers of occupational exposure to pesticides in rural workers living in the State of São Paulo, Brazil. Genomic instability was evaluated in 81 pesticide-exposed farm workers (69 males and 12 females) with a mean age of 49.16 ± 10.06 years and a mean time job of 30.00 ± 14.00 years,81 non-exposed individuals (62 males and 15 females) with a mean age of 47.87 ± 10.66 years. BMCyt results showed significantly higher levels of cell damage (micronuclei and binucleated cells) and cell death (karyorrhectic and condensed chromatin cells) in subjects exposed to pesticide when compared to those non-exposed (p < 0.05). Although our results did not show significant differences in TL among exposed and non-exposed groups, effects in TL due to pesticide exposure was found in a multivariable linear regression model when we stratified the groups by age (≤ 49 years and ≥ 50 years old; β = 11.21, p = 0.006). In addition, TL reduction on was identified in relation to an increase in cigarette pack consumption (β = -0.633, p = 0.045). Furthermore, exposure to specific pesticides presented different effects in TL. Cypermethrin exposure resulted in a reduction in TL (β = -18.039, p = 0.018), while abamectin exposure led to an increase in TL (β = 23.990, p = 0.007). Thus, our findings substantiate genomic instability due to pesticides exposure.


Metabolism of the cholestanol precursor cholesta-4,6-dien-3-one in different tissues.
Cerebrotendinous xanthomatosis (CTX) is a lipid storage disease where the basic defect is a lack of the mitochondrial C27-steroid 26-hydroxylase involved in bile acid synthesis (EC 188.8.131.52). Cholestanol and cholesterol accumulate in all tissues. At least part of the accumulation of cholestanol is due to a 7 alpha-dehydroxylation of early bile acid intermediates. Cholesta-4,6-dien-3-one, a proposed intermediate in this pathway, is found in increased concentrations in serum of the patients. This study shows that cholesta-4,6-dien-3-one may be metabolized to 4-cholesten-3-one and cholestanol by liver, adrenals and brain. No conversion was found in intestinal mucosa or in kidneys. The capacity to convert cholesta-4,6-dien-3-one into 4-cholesten-3-one and cholestanol varied in different tissues as well as in different species. The results are discussed in relation to the cholestanol accumulation in CTX.


Pelvic floor physical therapy and mindfulness: approaches for chronic pelvic pain in women-a systematic review and meta-analysis.
Chronic pelvic pain (CPP) in women is a complex syndrome and symptoms are associated with sexual dysfunction, musculoskeletal and myofascial disorders, and comorbid psychiatric disorders. Its widespread prevalence results in substantial expense due to therapy and lost productivity, and it is perhaps one of the most urgent and neglected medical needs. This systematic review and meta-analysis aimed to estimate the role of mindfulness and pelvic floor physical therapy (PFPT) in the treatment or management of women with CPP. This systematic review (CRD42020204987) searched for relevant publications between January 2000 and November 2020 on MEDLINE/PubMed, Web of Science, One File GALE, and Technology Research databases using the following search terms: chronic pelvic pain, pelvic floor physical therapy/physiotherapy, mindfulness, and their variants. Risk of bias and quality of evidence were evaluated. Seven clinical trials (n = 279) were included in the review, and five in the meta-analysis (n = 225). For the pain outcome and its catastrophizing, there was a statistical difference for the Pain Catastrophizing Scale after treatment and during follow-up with mindfulness and PFPT (MD = - 3.82 [- 6.97, - 0.68], p = 0.01, and MD = - 4.49 [- 7.61, - 1.37], p = 0.00, respectively). Sexual function, assessed by the female sexual function index, differed significantly during follow-up between PFPT and mindfulness (MD = - 0.72 [- 1.38, - 0.05], p = 0.03). The small number of studies applying both PFPT and mindfulness to CPP suggests that a multidisciplinary approach is required to treat women with CPP, and further studies involving these therapeutic techniques throughout the CPP cycle are needed.


Partial trisomy 8q resulting from maternal translocation t(2;8)(q373;q23).
A patient with multiple congenital malformations due to partial 8q trisomy is reported. Karyotype-phenotype correlations suggest the possibility that partial trisomy 8q is a nosologically distinct syndrome.


Solar UV-radiation, vitamin D and skin cancer surveillance in organ transplant recipients (OTRs).
The introduction of organ transplantation in clinical medicine has resulted in a constantly increasing, large population of patients that are chronically on immunosuppressive medication. It is well known that skin cancer, especially SCC, in this population has higher incidence rates, behaves more aggressively and has higher rates of metastasis. OTRs who have been treated for many years with immunosuppressive medication are at the highest risk for developing malignant skin tumors. Therefore, the intensity of surveillance for cutaneous lesions is of high importance in OTRs. A full-body skin exam at least once a year and more frequently if skin cancer or precancerous cutaneous lesions develop is recommended. Clinicians should not hesitate to biopsy or to surgically excise any suspicious skin lesion. Of high importance is also the education of OTRs about their increased risk. Protection against solar and artificial UV-radiation and monthly self-examinations are good ways to prevent and to recognize any new suspicious skin lesions. Patients are advised to always wear solar UV-radiation protection (e.g., clothing, sunscreen) before going outdoors. However, investigations have revealed that solar UV-B-exposure and serum 25(OH)D levels positively correlate with decreased risk for various internal malignancies (e.g., breast, colon, prostate and ovarian cancer) and other severe diseases. As we have shown previously, renal transplant recipients are at high risk of vitamin D deficiency. A sunscreen with a sun protection factor (SPF)-8 reduces the skin's production of vitamin D by 95%. Clothing completely blocks all solar UVB-radiation and this prevents any vitamin D production. Therefore, it is important to detect and treat vitamin D deficiency in solid organ transplant recipients. Optimal management of these patients requires communication between the transplant teams and the treating dermatologist and other clinicians. For advanced or metastatic disease, collaboration between clinicians of different disciplines, including the transplant team, dermatologists and radiation oncologists is also essential. In the future, dermatology clinics that are integrated into transplant centers may make it easier to manage and to treat OTRs, may make an interdisciplinary approach more effective and may thereby improve the clinical outcome in OTRs.


Management of the neuropathic bladder by clean intermittent catheterisation: 5 year outcomes.
Based on a telephone interview and medical record review of the urological outcomes among 40 spinal cord injury patients with a neuropathic bladder at discharge who were an average of 60 months post-injury and who were all initially managed by chronic clean intermittent catheterisation (CCIC), the following conclusions were made: Over 80% of patients using CCIC at discharge continued to use it, suggesting low morbidity and high patient acceptance; Urological complications in patients using CCIC were more frequent in the lower urinary tract than in the upper urinary tract, were more frequent in men than women, and had a low morbidity; Urological complications and hospitalisations were more frequent among the 41% of patients using CCIC who had frequent SxUTIs; SxUTIs were common in patients using CCIC but rates may be comparable with other methods; Although 44% of CCIC patients were hospitalised at least once in 5 years for urological complications, this is comparable to reported multi-centre outcomes in the U.S.A. (Young, 1982).


[Comparative studies of commercially available T4-RIA-kits (author's transl)].
The investigation of 4 commercially available T4-RIA-Kits with 350 patient sera have shown that: The separation of hypo-, eu- and hyperthyroid values is easier with kit a) and d) than with b) and c), though all kits give acceptable values under routine conditions. For the determination of the "normal range" not less than 100 patient sera are necessary. The time needed for 100 determinations is 2 to 3 hr. A general recommendation for one of the tested T4-RIA-Kits cannot be made since the choice depends also on local circumstances.


Phosphatidylinositol 3-kinase, phosphoinositide-specific phospholipase-Cgamma and protein kinase-C signal myelin phagocytosis mediated by complement receptor-3 alone and combined with scavenger receptor-AI/II in macrophages.
Complement-receptor-3 (CR3/MAC-1), scavenger-receptor-AI/II (SRAI/II) and Fcgamma-receptor (FcgammaR) can mediate phagocytosis of degenerated myelin in macrophages and microglia. However, CR3/MAC-1 and SRAI/II, but not FcgammaR, mediate phagocytosis after axonal injury. We tested for phosphatidylinositol 3-kinase (PI3K), phosphoinositide-specific phospholipase-Cgamma (PLCgamma) and protein kinase-C (PKC) signaling in myelin phagocytosis mediated by CR3/MAC-1 alone and by CR3/MAC-1 combined with SRAI/II. Phagocytosis was inhibited by PI3K inhibitors wortmannin and LY-294002, PLCgamma inhibitor U-73122, classical PKC (cPKC) inhibitor Go-6976, general PKC inhibitors Ro-318220 and calphostin-C, and BAPTA/AM which chelates intracellular Ca(2+) required for cPKC activation. PKC activator PMA augmented phagocytosis and further alleviated inhibitions induced by PI3K and PLCgamma inhibitors. Overall, altering PKC activity modulated phagocytosis 4- to 6-fold between inhibition and augmentation. PLCgamma activation did not require tyrosine phosphorylation. Thus, signaling of myelin phagocytosis mediated by CR3/MAC-1 alone and by CR3/MAC-1 combined with SRAI/II involves PI3K, PLCgamma and cPKC, the cascade PI3K-->PLCgamma-->cPKC, and wide-range modulation by PKC. This pathway may thus be targeted for in vivo modulation, which may explain differences in the efficiency of CR3/MAC-1-mediated myelin phagocytosis in different pathological conditions.


Tetraploid DNA content of Purkinje neurons of human cerebellar cortex.
Microspectrophotometric analysis of single cells in Feulgen preparations revealed tetraploid amounts of DNA in Purkinje neurons of human cerebellar cortex.


Angiotensin II-induced increase of T-type Ca2+ current and decrease of L-type Ca2+ current in heart cells.
The effect of angiotensin II (Ang II) on the T- and L-type calcium currents (I(Ca)) in single ventricular heart cells of 18-week-old fetal human and 10-day-old chick embryos was studied using the whole-cell voltage clamp technique. Our results showed that in both, human and chick cardiomyocytes, Ang II (10(-7)M) increased the T-type calcium current and decreased the L-type I(Ca). The effect of Ang II on both types of currents was blocked by the AT1 peptidic antagonist, [Sar1, Ala8] Ang II (2 x 10(-7)M). Protein kinase C activator, phorbol 12,13-dibutyrate, mimicked the effect of Ang II on the T- and L-type calcium currents. These results demonstrate that in fetal human and chick embryo cardiomyocytes Ang II affects the T- and L-type Ca2+ currents differently, and this effect seems to be mediated by the PKC pathway.


Atractylodes lancea rhizome derived exosome-like nanoparticles prevent alpha-melanocyte stimulating hormone-induced melanogenesis in B16-F10 melanoma cells.
Aberrant melanin overproduction can significantly impact an individual's appearance and cause mental and psychological distress. Current inhibitors of melanin production exert harmful side effects due to inadequate selectivity; thus a need to develop more selective melanin synthesis inhibitors is necessary. Extracellular vesicles are important agents of intercellular signalling in prokaryotes and eukaryotes. Recently, plant-derived nanoparticles, similar to mammalian exosomes, have attracted attention for their use in health research. In this study, to investigate the potential of plant-derived exosome-like nanoparticles (ELNs) as inhibitors of melanin production, we used hot water to extract ELNs from the rhizome of Atractylodes lancea (A-ELNs). The size of A-ENLs ranged from 34 to 401 nm and carried three microRNA: ath-miR166f, ath-miR162a-5p, and ath-miR162b-5p. These A-ENLs were applied to B16-F10 melanoma cells treated with α-melanocyte-stimulating hormone (α-MSH). After A-ELNs were taken up by B16-F10 cells, their melanin levels were significantly reduced. Furthermore, A-ELNs significantly reduced tyrosinase activity in B16-F10 cells and mRNA expression of microphthalmia-associated transcription factor (Mitf), tyrosinase, tyrosinase-related protein 1, and DOPA chrome tautomerase. These results suggest that A-ELN suppresses melanogenic enzymes expression by downregulating Mitf, thereby inhibiting melanin synthesis. Hence, A-ELN can be developed into a novel topical drug after additional studies and optimization.


Radiation-induced bronchiolitis obliterans organizing pneumonia (BOOP) syndrome in breast cancer patients is associated with age.
Radiation-induced bronchiolitis obliterans organizing pneumonia (BOOP) syndrome is a rarely observed phenomenon characterized by infiltration of the lungs outside of the radiation field, differentiating it from radiation pneumonitis (RP).The risk factors for radiation-induced BOOP (RT-BOOP) remain unclear and controversial. We retrospectively analyzed the incidence and risk factors for RT-BOOP associated with radiation therapy (RT) after breast conserving surgery (BCS) and post-mastectomy radiation therapy (PMRT). We analyzed 1,176 breast cancer patients treated with RT after BCS or PMRT between March 2005 and September2008 at the cancer institute hospital of the Japanese foundation for cancer research. Chest radiographs were routinely obtained every three to six months for at least 12 months after surgery, as well as when the patients experienced respiratory symptoms or fever. RT-BOOP syndrome was diagnosed in 16patients (1.4%), including12BCS patients (1.3%) and four PMRT patients (1.8%). An older age (≥52 years old) was significantly associated with the incidence of RT-BOOP syndrome in a univariate analysis (p =0.023). The type of treatment (BCS or PMRT) and irradiated lung volume at 20 Gy (V20) were not significantly associated with the incidence of RT-BOOP syndrome in the entire patient cohort. In the multivariate analysis, age and smoking were the significant factor associated with RT-induced BOOP syndrome (p =0.044 and 0.049, respectively). RT-BOOP syndrome was a rarity, and the incidence for BCT cases was similar to that for PMRT cases. The irradiated lung volume was not significantly associated with RT-BOOP syndrome. An older age can predict the incidence of RT-BOOP syndrome.


Resting multilayer 2D speckle-tracking transthoracic echocardiography for the detection of clinically stable myocardial ischemic segments confirmed by invasive fractional flow reserve. Part 1: Vessel-by-vessel analysis.
To detect stable ischemic left ventricular (LV)-segments confirmed via invasive fractional flow reserve (FFR) by quantitative longitudinal-strain (LS) determined using resting multilayer TTE. A retrospective analysis of 39 stable patients (32 males; 65.8±11.9years) with 46 coronary arteries with ≥50% stenosis confirmed by invasive coronary angiography who underwent invasive FFR measurement and TTE (Vivid E9, GE). On TTE, regional LS (absolute values) were calculated in whole, endocardial, and epicardial layers perfused by stenotic coronary arteries. Of the 46 vessels, FFR values of <0.75, ≥0.75, ≤0.80 and >0.80 were observed in 17, 29, 27 and 19 vessels, respectively. In a vessel-by-vessel analysis, the whole-layer and endocardial LS were significantly smaller in LV-segments perfused by vessels with an FFR<0.75 than in those with an FFR≥0.75, but epicardial LS was not. In ROC curves, the best cutoff values of whole-layer, endocardial and epicardial LS were, respectively, 14.0% (sensitivity, 94%; specificity 38%; area under the curve, 0.685), 10.0% (47%; 86%; 0.664) and 14.0% (100%; 24%; 0.640) to detect LV-segments with an FFR<0.75; and 14.0% (82%; 37%; 0.561), 10.0% (33%; 84%; 0.573), and 14.0% (89%; 21%; 0.538) to detect LV-segments with an FFR≤0.80. For stable subjects with coronary arteries with ≥50% stenosis, the regional whole-layer and endocardial LS were significantly smaller in LV-segments perfused by vessels with an FFR<0.75 than in those with an FFR≥0.75, but epicardial LS was not; and that the whole-layer and endocardial LS had a modest diagnostic efficiency in identifying LV-segments perfused by vessels with an FFR<0.75.


Construction of an expression vector that uses the aph promoter for protein expression in Corynebacterium glutamicum.
Corynebacterium glutamicum is an attractive host for the production of heterologous proteins despite its traditional use in fermentative production of amino acids. To enhance the expression levels of target genes, the development of useful promoters is required in the construction of expression systems. Here, we developed a new promoter, the aph promoter from aminoglycoside-3'-phosphotransferase gene, and used it to construct monocistronic and bicistronic expression systems that host different ribosome binding site (RBS) sequences. First, the expression level of the reporter protein, enhanced green fluorescent protein (EGFP), varied with changes in the RBS sequences in the constructed vectors. The results showed that the fluorescence intensities of the bicistronic group were higher than those of the monocistronic group and that RM3E showed the highest fluorescence intensity, which was 42-fold higher than the lowest (RA2E') among these groups. Next, taking advantage of the optimized aph promoter, we successfully employed this aph promoter for α-amylase and VHH (camelid antibody fragment) expression. The secretion of α-amylase improved 1.5-fold after promoter mutation. This promoter will be useful for heterologous protein production in C. glutamicum cells.


Distortion-product emissions in rabbit: II. Prediction of chronic-noise effects by brief pure-tone exposures.
In an attempt to predict the susceptibility of the cochlea to the harmful influences of excessive sound, the effects of initially exposing the same rabbits to brief pure-tones were related to the subsequent effects of octave-band noise (OBN) exposure using measures of distortion-product otoacoustic emissions (DPOAEs). The pure-tone exposure paradigm consisted of determining the rate at which a 100-dB SPL, low-frequency tone reduced the amplitude of a 1.5-kHz DPOAE, elicited by 50-dB SPL primaries. To establish the stability of the rate-reduction index, the tonal-exposure protocol was repeated on three separate occasions for each subject. Subsequently, the same rabbits were exposed chronically to a 95-dB SPL OBN, centered at 1-kHz, until DPOAE amplitudes between 1-5 kHz were diminished to noise-floor levels, i.e., by 10-30 dB, in response to 45-dB SPL primaries. The results revealed a visually apparent relation between the slope of the tonal-induced DPOAE-loss functions and the number of days required to reach the criterion decrement in emission level during chronic exposure to noise. Analysis of the frequency extent of the noise-induced changes revealed significant correlations between the previously measured rate of pure-tone induced reductions of DPOAE amplitude and the subsequent amount of decrement produced by OBN exposure. Thus, rabbits exhibiting slow rates of tonal-induced decrements in low-frequency DPOAEs were resistant to the amplitude-reducing effects of a subsequent chronic OBN exposure in that it typically took more than four days to achieve the targeted amount of DPOAE loss.(ABSTRACT TRUNCATED AT 250 WORDS)


Metabolic activation of diethylstilbestrol and aminostilbene-derivatives.
Diethylstilbestrol and trans-4-dimethylaminostilbene are metabolically activated and several of their metabolites are able to react with cellular macromolecules. Some of the problems are discussed which are encountered in linking a particular metabolite with the mutagenic and carcinogenic properties of these compounds.


Blood pressure targets in the treatment of high blood pressure: a reappraisal of the J-shaped phenomenon.
The risk that lowering blood pressure (BP) excessively increases the incidence of cardiovascular disease-the J-shaped phenomenon-has been a matter of concern endorsed by many experts, particularly in patients with coronary heart disease and diabetes. The results of the Action to Control Cardiovascular Risk in Type 2 Diabetes (ACCORD) trial strengthened the idea that it may be futile to lower BP more intensively in patients with diabetes. Nevertheless, there seems to be no direct J-shaped relation between BP-lowering treatment and outcome. Patients with normal or low BP and high or very high cardiovascular risk could have their BP reduced further by treatment. Placebo-controlled clinical trials of BP-lowering agents in patients with BP within normal values and concomitant cardiovascular disease demonstrated consistent reduction of recurrent and newer cardiovascular events. The use of BP agents in such conditions, as in patients with coronary artery disease, heart failure, diabetes and in patients recovered from a stroke has been endorsed by guidelines. Although is likely that there is a J-shaped relationship of BP with outcomes in cohort studies, clinical trials that tested more intensive versus standard goals and clinical trials done with patients with low BP demonstrated that the J-shaped phenomenon should not be a concern in the treatment of high BP.


Advances in the ultrastructural study of the implant-bone interface by backscattered electron imaging.
The biocompatibility of titanium implants in bone depends on the response shown by cells in contact with the implant surface. Several developments have been targeted at achieving successful implant treatment. The aim of this study was to develop a novel preparation procedure to evaluate the bone cell response produced at the bone-implant interface using the technique scanning electron microscopy with backscattered electron imaging (SEM-BSE). Dental prostheses with an SLA-modified or TOP-modified surface were implanted in a toothless part of the mandibula in female pigs. The animals were sacrificed 12 weeks after surgery, at which time block specimens containing the implants were obtained. These specimens were then processed for SEM-BSE by optimizing a protocol involving chemical fixation and heavy metal staining. In addition, element distribution maps for the implant-bone tissue interface were obtained using a microanalytical system based on energy-dispersive X-ray spectrometry (EDS). This novel visualisation approach enabled a comprehensive study of the extracellular matrix and cell components of the host tissues neoformed around the implant. SEM-BSE images also provided ultrastructural details of the bone cells. This technique appears to be an effective and very promising tool for detailed studies on the implant-bone tissue interface and the host response to the bone incorporation process.


P-selectin antibody reduces hemorrhage and infarct volume resulting from MCA occlusion in the rat.
We investigated the effect of an anti-P-selectin antibody (RMP-1) on ischemic cell damage and hemorrhage after transient middle cerebral artery occlusion (MCAo) in the rat. Animals were divided into four groups: (1) antibody (Ab) 1 group (n = 14) RMP-1 (2 mg/kg) was administered to rats 1 h prior to induction of 2 h of MCA occlusion; (2) control-vehicle group Ab2 (n = 12) rats were subjected to the same experimental protocol, except that an isotype-matched control antibody was administered; (3) Abl group (n = 10) rats were subjected to 2 h of MCA occlusion and RMP-1 (2 mg/kg) was administered upon reperfusion; (4) control-vehicle group Ab2 (n = 10) rats were subjected to the same experimental protocol, except that an isotype-matched control antibody was administered. Animals were sacrificed 48 h after onset of the MCAo for histological evaluation of infarction and hemorrhage, and to quantify number of neutrophils. The lesion volume was significantly smaller only in pretreated rats (RMP-1 group, 18.7+/-3.1%) compared to the vehicle-treated (31.6+/-2.6%) group (P<0.01). Total area of hemorrhage (5.94 x 10(3)+/-2.86 x 10(3) microm2) in the pre MCAo RMP-1 treated group animals was significantly reduced (P<0.02) compared to the vehicle group (6.1 x 10(4)+/-3.42 x 10(4) microm2), respectively. Our data demonstrate that administration of the anti-P-selectin antibody before transient focal cerebral ischemia in rat brain reduces ischemic cell damage and petechial hemorrhage.


Nitrogen transport and sources in urban stormwater with different rainfall characteristics.
Nitrogen pollution in urban stormwater has led to serious quality issues in urban water. Nitrogen pollution mitigation requires fully understanding the transport process and major nitrogen sources in urban stormwater. In this study, the concentrations and flux of various nitrogen forms during urban stormwater transport were analyzed. It was found that the concentration and flux of NO3--N and NH3-N decreased in the order of roof runoff, road runoff, and drainage runoff, while the concentration and flux of dissolved organic nitrogen (DON) and particulate nitrogen (PN) were found to be the highest in road runoff. Source quantification found that roof runoff (34%) and rainwater (34%) were the main contributors to nitrate pollution during light and moderate rains (<25 mm), while road runoff was identified as the major source (49%) of nitrate pollution during heavy rains (>25 mm) due to the large road runoff volume. Regarding particulate organic nitrogen (PON), the road runoff in commercial areas contributed most (23%) to PON pollution during light and moderate rains, while the runoff generated from pervious surfaces and drainage sediments were the primary two sources (22%) of PON during heavy rains. Moreover, the influence of rainfall characteristics on nitrate and PON source contributions was identified. The results show that antecedent dry periods were an important factor influencing nitrogen source contributions during light and moderate rains, while rainfall amount and intensity were critical factors impacting the nitrogen source contributions during heavy rains. Taking various transport processes, source contributions, and rainfall characteristics into consideration, several recommendations were given for the mitigation of nitrogen pollution in urban stormwater. This study can provide a useful perspective to understand the transport and sources of nitrogen, thus developing constructive strategies to control urban nonpoint source pollution management.


Myocardial perfusion imaging by contrast echocardiography with use of intracoronary sonicated albumin in humans.
Sonicated albumin has been proposed as a near ideal echocardiographic contrast agent with little myocardial toxicity or hemodynamic effect. Its use has not yet been reported in humans, partly because of difficulties in preparation. With use of the newly modified sonication method, 10 ml of 5% albumin was sonicated for 75 s with a 5.0 ml slow infusion of air. This resulted in microbubbles with a mean diameter (+/- SD) of 5 +/- microns). Fourteen patients undergoing routine coronary angiography were studied. One patient had normal coronary arteries; the other 13 had significant coronary artery disease. In a subgroup of nine patients, sonicated albumin and sonicated diatrizoate meglumine sodium (microbubble diameter 9 +/- 3 microns) were injected several minutes apart, using the same technique. Videodensity-time curves were obtained from a region of interest in the myocardium. Corrected peak contrast intensity (baseline contrast intensity subtracted from peak contrast intensity, gray scale U/pixel) for sonicated albumin and for sonicated diatrizoate meglumine sodium was 51 +/- 26 and 52 +/- 19, respectively (p = 0.89). Washout half-time (T1/2) for the two agents was 5.5 +/- 4.5 and 16.0 +/- 12.2 s, respectively (p = 0.01). One patient with unstable angina experienced transient chest pain after repeated albumin injections. No electrocardiographic changes, blood pressure changes or wall motion abnormalities were observed. Administered by intracoronary injection, sonicated 5% albumin is a safe and effective echocardiographic contrast agent for myocardial perfusion imaging, yielding excellent myocardial contrast with physiologic washout time.


Efficiency of supercritical fluid chromatography columns in different thermal environments.
The efficiency of a packed column eluted with supercritical carbon dioxide at 323K and outlet pressures from 90 to 150bar was studied with the column in two different thermal environments. The 150mm×2.0mm ID stainless steel column was packed with spherical 5-μm porous silica particles with a covalently bonded nonpolar stationary phase, and the test solutes were normal alkanes. When operated in a convective air bath the column exhibited severe efficiency losses when its outlet pressure was below 120bar. The efficiency of the same column enclosed in a shell made of foam insulation was restored at low outlet pressures down to 100bar. The van Deemter plots showed an abnormal dependence of the plate height (HETP) on the flow rate at low outlet pressures, exhibiting a maximum in the HETP at flow rates around 1mL/min and a 20-bar pressure drop. The large efficiency losses at low outlet pressures are due to radial temperature gradients associated with enthalpic expansion and cooling of the mobile phase. The separations were simulated by a numerical model that accounts for axial and radial gradients in the temperature and density along the column. The abnormal van Deemter plots arise from competing processes affecting the radial distribution of the solute migration velocity along the column. The negative impact on efficiency is greatest when the density profile of the mobile phase along the column is close to the critical isopycnic line. The efficiency improves at increased flow rates because of increased cooling at larger pressure drops and increased density along the entire length of the column. The model predicts the unusual trends in the van Deemter plots, but the calculated results at low outlet pressures are strongly influenced by small variations in the porosity distribution in the column, limiting the accuracy of the predicted HETP values. In spite of these difficulties, the model has enabled a detailed analysis of the effects of temperature, pressure and flow rate on the thermal properties of the mobile phase, and their impact on the radial distribution of the solute velocities along the column. This work provides a better appreciation of the factors that cause excess efficiency loss at low outlet pressures, a phenomenon that lacked a convincing explanation for over 40 years. Finally, a simplified form of the model, which ignores the radial gradients, provided accurate results only at the highest outlet pressure. Calculations done by the simplified model are much faster, and it can be recommended for simulation of SFC processes at sufficiently high outlet pressures.


Effect of image uncertainty on the dosimetry of trigeminal neuralgia irradiation.
Our objective was to quantify the uncertainty in localization of the trigeminal nerve (TGN) with magnetic resonance imaging (MRI) and computed tomography (CT) and to determine the effect of this uncertainty on gamma-knife dose delivery. An MR/CT test phantom with 9, 0.6-mm diameter, copper rings was devised. The absolute ring positions in stereotactic space were determined by the angiographic module of the LGP software. The standard deviation, sigma, in the difference between the absolute and MR-measured or CT-measured coordinates of the rings was determined. The trigeminal nerve in 52 previously treated patients was contoured and expanded by 1sigma and 2sigma margins to model the uncertainty in the location of the nerve. For gamma-knife treatment, a single isocenter was used and was located at the distal cisternal portion of the trigeminal nerve root. Irradiation methods included a 4-mm collimator, 90 Gy to isocenter and a 4&8-mm collimator, 70 Gy to isocenter. A patient outcome survey that sampled pain relief and morbidity was done. The MR coordinate sigma was 0.7 mm left-right, 0.8 mm anterior-posterior, and 0.6 mm superior-inferior, and the CT coordinate sigma was 0.4 mm left-right, 0.2 mm anterior-posterior, and 0.2 mm superior-inferior. A 45% higher dose line covered the TGN with the 4&8-mm method. No significant increase in pain reduction or morbidity occurred. The uncertainty of target location by MRI is more than twice that found in CT imaging. The 4&8-mm collimator method covers the trigeminal root cross section with a higher isodose line than does the 4-mm method. This higher dose did not significantly reduce pain or increase morbidity.


Splice site mutations in mismatch repair genes and risk of cancer in the general population.
We tested the hypothesis that splice site variations in MSH2 and MLH1 are associated with increased risk of hereditary non-polyposis colorectal cancer (HNPCC) and of cancer in general in the general population. In a cohort of 154 HNPCC patients with sequenced MSH2 and MLH1, we identified four possible splice-site mutations, which we subsequently genotyped in more than 9,000 individuals from the general population. Allele frequencies in the general population were 0 % for 942+3A>T in MSH2, 0.05 % for 307-19A>G, 0.005 % for 1,667+(2-8)del(taaatca);ins(attt), and 4.4 % for 1039-8T>A in MLH1. Odds ratios for HNPCC in a case-control design were 419 (95 % CI: 53-18,900) for 942+3A>T in MSH2, 19 (5-72) for 307-19A>G, 194 (21-1,768) for 1,667+(2-8)del(taaatca); ins(attt), and 0.3 (0.1-0.7) for 1,039-8T>A in MLH1. In the general population, incidence rate ratios for 1,039-8T>A carriers versus noncarriers were 0.70 (0.51-0.96) for HNPCC-related cancers combined and 0.82 (0.71-0.94) for all cancers combined in a prospective design. The three rare mutations were associated with increased risk of HNPCC. In contrast, the more common 1,039-8T>A associated with a decreased risk of HNPCC, of HNPCC-related cancers and of all cancers combined in the general population. These findings are novel and important in the counseling of HNPCC patients and their relatives.