Design, development, and use of molecular primers and probes for the detection of Gluconacetobacter species in the pink sugarcane mealybug.
Molecular tools for the species-specific detection of Gluconacetobacter sacchari, Gluconacetobacter diazotrophicus, and Gluconacetobacter liquefaciens from the pink sugarcane mealybug (PSMB) Saccharicoccus sacchari Cockerell (Homiptera: Pseudococcidae) were developed and used in polymerase chain reactions (PCR) and in fluorescence in situ hybridizations (FISH) to better understand the microbial diversity and the numerical significance of the acetic acid bacteria in the PSMB microenvironment. The presence of these species in the PSMB occurred over a wide range of sites, but not in all sites in sugarcane-growing areas of Queensland, Australia, and was variable over time. Molecular probes for use in FISH were also designed for the three acetic acid bacterial species, and shown to be specific only for the target species. Use of these probes in FISH of "squashed" whole mealybugs indicated that these acetic acid bacteria species represent only a small proportion of the microbial population of the PSMB. Despite the detection of Glac. sacchari, Glac. diazotrophicus, and Glac. liquefaciens by PCR from different mealybugs isolated at various times and from various sugarcane-growing areas in Queensland, Australia, these bacteria do not appear to be significant commensals in the PSMB environment.


Interactive effects of fire and large herbivores on web-building spiders.
Altered disturbance regimes are a major driver of biodiversity loss worldwide. Maintaining or re-creating natural disturbance regimes is therefore the focus of many conservation programmes. A key challenge, however, is to understand how co-occurring disturbances interact to affect biodiversity. We experimentally tested for the interactive effects of prescribed fire and large macropod herbivores on the web-building spider assemblage of a eucalypt forest understorey and investigated the role of vegetation in mediating these effects using path analysis. Fire had strong negative effects on the density of web-building spiders, which were partly mediated by effects on vegetation structure, while negative effects of large herbivores on web density were not related to changes in vegetation. Fire amplified the effects of large herbivores on spiders, both via vegetation-mediated pathways and by increasing herbivore activity. The importance of vegetation-mediated pathways and fire-herbivore interactions differed for web density and richness and also differed between web types. Our results demonstrate that for some groups of web-building spiders, the effects of co-occurring disturbance drivers may be mostly additive, whereas for other groups, interactions between drivers can amplify disturbance effects. In our study system, the use of prescribed fire in the presence of high densities of herbivores could lead to reduced densities and altered composition of web-building spiders, with potential cascading effects through the arthropod food web. Our study highlights the importance of considering both the independent and interactive effects of disturbances, as well as the mechanisms driving their effects, in the management of disturbance regimes.


Parallel sparse and dense information coding streams in the electrosensory midbrain.
Efficient processing of incoming sensory information is critical for an organism's survival. It has been widely observed across systems and species that the representation of sensory information changes across successive brain areas. Indeed, peripheral sensory neurons tend to respond densely to a broad range of sensory stimuli while more central neurons tend to instead respond sparsely to a narrow range of stimuli. Such a transition might be advantageous as sparse neural codes are thought to be metabolically efficient and optimize coding efficiency. Here we investigated whether the neural code transitions from dense to sparse within the midbrain Torus semicircularis (TS) of weakly electric fish. Confirming previous results, we found both dense and sparse coding neurons. However, subsequent histological classification revealed that most dense neurons projected to higher brain areas. Our results thus provide strong evidence against the hypothesis that the neural code transitions from dense to sparse in the electrosensory system. Rather, they support the alternative hypothesis that higher brain areas receive parallel streams of dense and sparse coded information from the electrosensory midbrain. We discuss the implications and possible advantages of such a coding strategy and argue that it is a general feature of sensory processing.


Vitamin B12 deficiency in an infant with neurological and hematological findings: A case report.
It is important for pregnant and breastfeeding women who adhere to a strict vegetarian diet to take appropriate steps to avoid vitamin B12 deficiency in their infants. Vitamin B12 deficiency is rare during infancy. The initial symptoms of this deficiency are subtle and may include irritability, failure to thrive with a decline in growth rate, apathy, anorexia, refusal of solid foods, megaloblastic anemia, and developmental regression. The case presented here involves an 8-month-old male infant who showed neurological symptoms such as decreased activity, increased drowsiness, and reduced interaction with parents, which were ultimately linked to a deficiency of cobalamin (vitamin B12). Early recognition of this condition is critical because it is reversible. Therefore, pregnant and lactating women who follow a strict vegetarian diet should take necessary measures to prevent vitamin B12 deficiency in infants.


Transplantation to the brain--a new therapeutic principle or useless venture?
On the basis of remarkable results from transplantation experiments in animals, the author in 1979 suggested autologous transplantation of catecholamine tissue to the brain as tentative treatment for parkinsonism. Experiences from four patients thus treated are reported comprehensively. Transitory rewarding effects were seen when the transplant was deposited in the putamen. The potential prospects for this principally new therapeutic paradigm are discussed, as well as possible improvements in the method.


Chemotherapy responsiveness of human breast tumors in the 6-day subrenal capsule assay: an update.
Feasibility of utilizing the 6-day subrenal capsule (SRC) assay to screen drugs against fresh surgical explants of human tumors was confirmed by testing six clinically active chemotherapeutic agents against 141 human breast cancers. Response rates of the six drugs obtained in the assay compared favorably with clinical response rates for the same drugs as reported by Carter (5). The evaluable assay rate for breast tumors was 92% as compared to 89% for gynecologic tumors. Innate drug resistance was indicated with 16 of 57 tumors (28%) which did not respond to any of the six agents tested. Differences in responsiveness of tumors to each agent in a potential three-drug combination of either CMF or CAF suggest that the effectiveness of multiagent therapy might be enhanced if the individual agents of a potential drug combination were selected on the basis of tumor sensitivity to each of the agents in a predictive assay. Although cross-resistance between L-PAM and cytoxan was demonstrated and was statistically significant, 31% of these tumors responded individually to either one or the other agent, suggesting caution in extrapolating concomitance in activity between these two alkylators.


Lower effectiveness of facet joint infiltration in patients with concurrent facet joint degeneration and active endplate changes.
Facet joint degeneration (FJD) and disc degeneration (DD) with associated endplate (EP) changes, specifically Modic 1 changes, might occur concurrently and therefore pose a challenge in the treatment of lower back pain (LBP). The aim of the present study was to investigate if the presence of active EP changes (Modic 1) would alter the effect of facet joint infiltrations (FJI) for the treatment of concurrent FJD. Prospective cohort study, Level III. 42 patients (Male:20, Female:22) with an average of 58±14 years with FJD on conventional magnetic resonance imaging (MRI) receiving a FJI for treatment of lower back pain were included. The pain score at baseline, 15 min, 1 day, 1 week and 1 month following FJI as well as the reduction of pain were analyzed. Furthermore, active EP changes on conventional MRI and increased EP metabolic activity on PET/MRI were evaluated and compared. All the patients underwent a (18F)-NaF PET/MRI, conventional MRI and FJI for symptomatic FJD. Active EP changes on conventional MRI and increased EP metabolic activity on PET/MR were analyzed for conformity. The pain score as well as the pain reduction at the above-mentioned time points were compared between patients with and without increased EP metabolic activity in PET/MRI. The LBP reduction was significantly different between patients with (n=20) and without (n=22) active EP changes at 15 minutes (1.3±2.4 vs. 2.9±2.4, p=.03) and 1 month (0.9±2.3 vs. 2.8±2.9, p<.001) following FJI. The minimal clinically important difference for LBP reduction was reached significantly more often in the absence of active EP changes (73%) compared with patients with active EP changes (35%) 1 month following FJI (p=.03). FJI is less effective in LBP reduction of patients with FJD and concurrent active EP changes (eg Modic 1).


Recent trends of phosphorus-containing flame retardants modified polypropylene composites processing.
Polypropylene has been used for applications requiring high mechanical properties, good adhesion, chemical stability and insulation. Whereas, Polypropylene itself is flammable, and its limiting oxygen index (LOI) is low, which cannot pass the UL-94 combustion test. Therefore, extensive use will cause a serious threat to human life and property. With the wide application of thermoplastic polypropylene in industry, the development of environmentally friendly flame retardant materials has become an important research direction. For the past dozen years, researchers have been exploring flame retardants with high flame retardant efficiency, low toxicity, less smoke or other excellent performance flame retardants. This paper reviews the research progress of some phosphorus-containing flame retardants on the flame retardant properties of polypropylene in recent years. Phosphorus flame retardant is a flame retardant with high flame retardant efficiency, good stability and wide application. The types and flame retardant properties of phosphorus flame retardant will be introduced, and the future research of phosphorus flame retardant is summarized, direction and development opportunities.


Partial trisomy 22 resulting from rearrangements between chromosomes 11/22 and 16/22: a report of two cases.
Two male infants with partial trisomy 22 resulting from a rearrangement between chromosomes 11/22 and 16/22 were admitted to the Children's Hospital of the University of Leipzig within the space of two months. The characteristic phenotype of the infants is described and compared with the data on liveborn infants with trisomy 22, as reported in the literature. One of the infants reported here showed a prenatally detected hygroma colli. To the best of our knowledge this is the first description of a hygroma colli in this chromosomal disorder. Infants with trisomy 22 can present with variable phenotypes. It is important to bear the phenotype of chromosome 22 infants in mind.


The amygdala's role in human mnemonic processing.
The possible role played by the human amygdaloid complex in the processing of mnemonic information is examined. First, evidence is reviewed from case reports in which amygdaloid damage occurred due to surgical intervention or pathological or age-related changes. Then, studies are evaluated in which the amygdala was stimulated or in which electrical potentials were recorded from it. Based on this survey an hypothesis on the possible involvement of the amygdala in mnemonic information processing is proposed. In essence, it is argued that the human amygdala is responsible for activating or reactivating those mnemonic events which are of an emotional significance for the subjects' life history and that this (re-)activation is performed by charging sensory information with appropriate emotional cues. Supportive evidence for this hypothesis is given based on human case reports, on studies in animals in which information processing was determined following amygdaloid lesions, and on evidence of neuroanatomical connections of the primate amygdala.


Carbon monoxide poisoning.
This paper illustrates the remarkable fall of carbon monoxide poisoning due to the abolition of coal gas in the 1970 era and a corresponding decrease in suicide deaths. It enfolds the varying forms of suicide and accident according to age, sex and circumstance.


[Hodgkin's disease and glomerulonefritis (author's transl)].
A case of infradiaphragmatic Hodgkin's disease (mixed pattern) associated with glomerulonephritis in the childhood is reported. The pathogenic relationship between Hodking's disease and the renal lesion is discussed.


Unexpected brain lesions in lactating Sprague-Dawley rats in a Two-generation Inhalation Reproductive Toxicity Study with pentafluoropropane (HFC-245fa).
The study presented was conducted following the reproductive study guideline OECD Guideline 416 Two-Generation Reproduction Toxicity Study. Sprague-Dawley rats were exposed to 2000, 10,000 and 50,000 ppm of HFC-245fa. There was an unexpected mortality of lactating dams in the medium and high dose group beginning at day 10 of lactation. Statistically significant histopathological alterations were observed in the cerebellum of a total of 9/30 females of the high dose group of the F0-generation and in 10/27 females of the high dose group of the F1-generation. In contrast there were no brain lesions found in males or non-pregnant females of all dose groups. Neuronal necrosis and degeneration in the cerebellar cortex were observed as the most severe finding. Furthermore vacuolation of the neuropil in different degrees was diagnosed in 7/30 females of the F0-generation and in 9/30 females of the F1-generation. Acute hemorrhages - in particular perivascular - occurred in 5/30 females of the F0- and in 5/30 females of the F1-generation indicating a disturbed vascular integrity. The main lesions found in the cerebrum were glial scars in the corpus callosum and restricted to 2/30 females of the F0-generation of the high dose group. The increased incidence of myocardial fibrosis and mononuclear cell infiltration in males - indicating myocarditis - was only seen in the F0-generation of the high dose group. Females of the F1-generation of the high dose group showed an increased incidence of minimal myocardial fibrosis. In summary, histopathology revealed that the brain, particularly the cerebellum, and to a minor degree the heart turned out to be the toxicological target organs of the substance. Presumably substance-related energy deprivation may be responsible for the observed changes. One of the metabolites, 3,3,3-trifluoropropanoic acid has been shown to be capable of causing this effect.


Simulations of Amyloid-Forming Peptides in the Crystal State.
There still is little treatment available for amyloid diseases, despite their significant impact on individuals and the social and economic implications for society. One reason for this is that the physical nature of amyloid formation is not understood sufficiently well. Therefore, fundamental research at the molecular level remains necessary to support the development of therapeutics. A few structures of short peptides from amyloid-forming proteins have been determined. These can in principle be used as scaffolds for designing aggregation inhibitors. Attempts to this end have often used the tools of computational chemistry, in particular molecular simulation. However, few simulation studies of these peptides in the crystal state have been presented so far. Hence, to validate the capability of common force fields (AMBER19SB, CHARMM36m, and OPLS-AA/M) to yield insight into the dynamics and structural stability of amyloid peptide aggregates, we have performed molecular dynamics simulations of twelve different peptide crystals at two different temperatures. From the simulations, we evaluate the hydrogen bonding patterns, the isotropic B-factors, the change in energy, the Ramachandran plots, and the unit cell parameters and compare the results with the crystal structures. Most crystals are stable in the simulations but for all force fields there is at least one that deviates from the experimental crystal, suggesting more work is needed on these models.


Steroid production by ovarian follicles of the viviparous guppy (Poecilia reticulata) and its regulation by precursor substrates, dibutyryl cAMP and forskolin.
Production in vitro of estradiol-17 beta, testosterone, 17 alpha-20 beta-dihydroxy-4-pregnen-3-one (17 alpha,20 beta-P), 17 alpha-hydroxyprogesterone, and progesterone by follicles of the guppy at various stages of oocyte growth and gestation was investigated. Basal production of estradiol-17 beta was highest in 0.8- and 1.2-mm follicles, whereas that of testosterone and 17 alpha,20 beta-P was highest in 1.6-mm (postvitellogenic) follicles. Levels of these steroids declined after fertilization and were undetectable in late gestation and postpartum follicles. 17 alpha-Hydroxyprogesterone and progesterone levels were low at all stages. Thus, none of these steroids appears to be involved in maintaining gestation. Regulation of estradiol-17 beta and 17 alpha,20 beta-P secretion by vitellogenic (1.0 mm) and postvitellogenic follicles by precursor substrates, dbcAMP (0.1 to 10 mM) and forskolin (1 to 100 microM), was also investigated. Vitellogenic follicles synthesized increased quantities of estradiol-17 beta in the presence of exogenous testosterone, whereas estradiol-17 beta production by postvitellogenic follicles was not altered by testosterone. These results suggest decreased aromatase activity in the postvitellogenic follicles. Dibutyryl cAMP and/or forskolin stimulated testosterone and estradiol-17 beta production by vitellogenic follicles but did not stimulate conversion of testosterone to estradiol-17 beta, suggesting that the adenylate cyclase system stimulates estradiol-17 beta production by stimulating testosterone production but does not mediate conversion of testosterone to estradiol-17 beta. Postvitellogenic follicles synthesized increased quantities of 17 alpha,20 beta-P in response to 17 alpha-hydroxyprogesterone in a dose-dependent manner. Although 1 microM of forskolin stimulated 17 alpha,20 beta-P production by postvitellogenic follicles in the absence of exogenous 17 alpha-hydroxyprogesterone, 100 microM of forskolin inhibited 17 alpha,20 beta-P production. Dibutyryl cAMP, however, did not affect 17 alpha,20 beta-P production. In the presence of 50 ng of 17 alpha-hydroxyprogesterone, dbcAMP (10 mM) and forskolin (1 to 100 microM) suppressed 17 alpha,20 beta-P production. It is suggested that cAMP mediates 17 alpha,20 beta-P production up to a certain threshold level, beyond which it inhibits 17 alpha,20 beta-P production.


Quantitative study of various factors influencing the migration of lymphocytes in vitro: glucocortico-steroid, PHA, cyclosporin A and heparin.
Various agents known to influence the lymphocyte recirculation in vivo were investigated for their effect on the migration of lymphocytes in 3-D collagen gel. Both glucocortico-steroid and cyclosporin A were shown to inhibit the migration in a dose dependent manner. In contrast heparin and PHA treated lymphocytes migrated at a significantly faster rate.


Living Donor Liver Transplantation for Adults With High Model for End-stage Liver Disease Score: The US Experience.
Outcomes after living-donor liver transplantation (LDLT) at high Model for End-stage Liver Disease (MELD) scores are not well characterized in the United States. This was a retrospective cohort study using Organ Procurement and Transplantation Network data in adults listed for their first liver transplant alone between 2002 and 2021. Cox proportional hazards models evaluated the association of MELD score (<20, 20-24, 25-29, and ≥30) and patient/graft survival after LDLT and the association of donor type (living versus deceased) on outcomes stratified by MELD. There were 4495 LDLTs included with 5.9% at MELD 25-29 and 1.9% at MELD ≥30. LDLTs at MELD 25-29 and ≥30 LDLT have substantially increased since 2010 and 2015, respectively. Patient survival at MELD ≥30 was not different versus MELD <20: adjusted hazard ratio 1.67 (95% confidence interval, 0.96-2.88). However, graft survival was worse: adjusted hazard ratio (aHR) 1.69 (95% confidence interval, 1.07-2.68). Compared with deceased-donor liver transplant, LDLT led to superior patient survival at MELD <20 (aHR 0.92; P = 0.024) and 20-24 (aHR 0.70; P < 0.001), equivalent patient survival at MELD 25-29 (aHR 0.97; P = 0.843), but worse graft survival at MELD ≥30 (aHR 1.68, P = 0.009). Although patient survival remains acceptable, the benefits of LDLT may be lost at MELD ≥30.


Histochemical evidence for lysosomal storage of acid glycosaminoglycans in splenic cells of rats treated with tilorone.
Tilorone, an agent with antiviral and antitumor activities, has previously been reported to produce clear cytoplasmic vacuoles in many cell types of the rat. The present study on rat spleen was planned to investigate the ultrastructural and histochemical features of the tilorone-induced vacuoles occurring in sinus endothelium, trabecular smooth muscle cells, and macrophages of the red pulp. Evidence was obtained that the vacuoles represent lysosomes overloaded with acid glycosaminoglycans (aGAG). The main purpose of the present study was to overcome the technical difficulties of preserving the intralysosomal storage materials which were highly water-soluble and non-fixable by aldehyde fixatives. Preservation, at least for the light microscopical level, was achieved by freeze drying and by means of cationic dyes which served also to characterize the storage materials on the basis of their acidities. Tissue slices were used to determine the critical MgCl2 concentration necessary to abolish Alcian blue staining; cartilage and mast cells served as references. For the storage material in sinus endothelium, the critical MgCl2 concentration was found to be greater than 0.7 M, as compared to greater than 0.5 M for cartilage and greater than 0.9 M for mast cells. The storage materials in trabecular cells and macrophages were slightly less acidic than cartilaginous matrix and more heterogeneous than that in sinus endothelium. Ultrastructurally, positive staining with high iron diamine (HID) confirmed the presence of aGAG within the tilorone-induced vacuoles.


[Management of vaginal carcinoma in patients over 70 years old: advantage of a radiotherapy-brachytherapy association].
Report and discuss the management of the primitive vaginal cancer in elderly adults at a single institute. Data from patients more than 70 year-old treated for a primitive vaginal cancer at the Institut de Cancérologie de la Loire Lucien-Neuwirth was retrospectively collected. From August 1999 to January 2009, 9/24 patients treated for a primitive vaginal cancer had more than 70 year-old. The median age was 81 years (7-94 years). Most patients had a performance status less or equal to 1 (n=6), a squamous cell carcinoma (n=7) and a FIGO stage less or equal to II (n=6). All patients were treated with 3D external beam radiation, 3 received concurrent chemotherapy, 3 had a supplementary brachytherapy, and 6 had a colpohysterectomy. Among 7 evaluable patients, there were 4 complete responses, 2 partial responses and one progression. Main acute toxicities were gastrointestinal (n=5), urinary (n=3), general (n=3) and cutaneous (n=2). Three patients experienced late toxicities. Four patients had a local recurrence after a mean delay of 10.8 months. At last news, 4 patients were still alive and 4/5 deaths were related to the cancer. All (n=3) patients who received the combination of radiotherapy - brachytherapy were alive and disease-free. Median overall survival was 18 months. Primitive vaginal cancers are rare and aggressive tumours. Our results suggested the feasibility of the combination of radiotherapy and brachytherapy for elderly patients. Prospective trials remain needed to better define and validate the optimal strategy, especially in elderly adults.


Identification of biological targets of therapeutic intervention for clear cell renal cell carcinoma based on bioinformatics approach.
We aimed to discover the potential microRNA (miRNA) targets and to explore the underlying molecular mechanisms of clear cell renal cell carcinoma (ccRCC). Microarray data of GSE16441 was downloaded from Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially expressed miRNAs between ccRCC tumors and matched non-tumor samples were analyzed. Target genes of differentially expressed miRNAs were screened. Besides, functional enrichment analysis of DEGs was performed, followed by protein-protein interaction (PPI) network construction and sub-module analysis. Finally, the integrated miRNA-DEGs network was constructed. A total of 1758 up- and 2465 down-regulated DEGs were identified. Moreover, 15 up- and 12 down-regulated differentially expressed miRNAs were screened. The up-regulated DEGs were significantly enriched in pathways such as cell adhesion molecules and focal adhesion. Besides, the down-regulated DEGs were enriched in oxidative phosphorylation, and citrate cycle (TCA cycle). Moreover, eight sub-modules of PPI network were obtained. Totally, eight down-regulated miRNAs were identified to significantly regulate the DEGs and miRNA-200c that could regulate collagen, type V, alpha 2 (COL5A2) as well as COL5A3 was found to be the most significant. Additionally, 10 up-regulated miRNAs were identified to be significantly associated with the DEGs. Thereinto, miRNA-15a that could regulate ATPase, H(+) transporting, lysosomal 21 kDa, V0 subunit b (ATP6V0B) and miRNA-155 were found to be the most significant. miRNA-200c that could regulate COL5A2 and COL5A3, miRNA-15a that could regulate ATP6V0B and miRNA-155 may play key roles in ccRCC progression. These miRNAs may be potential targets for ccRCC treatment.


RapidPlan for Knowledge-Based Planning of Malignant Pleural Mesothelioma.
Treatment planning for malignant pleural mesothelioma is a challenging task due to the relatively large size of the target and the need to spare critical organs that overlap with or are within the target volume. We aimed to develop a knowledge-based model using RapidPlan (RP) for patients with 2 intact lungs. Data from 57 patients treated with volumetric modulated arc therapy were chosen for training the dose estimation model at a single dose level. The prescription dose was 50.4 Gy in 1.8 Gy fractions. The model was validated on 23 new patients by comparing the clinical plan to the RP. Time taken to plan the RP was compared with that for the clinical plan. For similar target coverage and plan inhomogeneity, RP significantly improved the sparing of the contralateral lung, heart, stomach, esophagus, and ipsilateral kidney. On average, the contralateral lung V5 Gy and V10 Gy were reduced by 13.9% (P < .001) and 7.9% (P < .001), respectively. The mean heart dose was reduced by 5 Gy (P < .001) and V30 Gy by 9.1% (P < .001). Mean dose to the stomach and esophagus were both reduced by 5 Gy (P < .001), and the ipsilateral kidney V18 Gy by 4.1% (P < .001). Mean total lung dose was reduced by 0.8 Gy with RP, which enabled an increase in prescription dose by 1 fraction Absolute volume of ipsilateral lung was adequately spared by both techniques, while sparing of all other organs, namely the cord, liver, and bowel, was not compromised with RP. Time taken with RP was 20 minutes, 45 seconds versus at least 4 hours for an experienced treatment planner. The RP model for malignant pleural mesothelioma showed improved sparing of critical organs with a reduced treatment planning time and increased prescription dose.


Interactions between lymphocytes and hematopoietic progenitor cells in normal and leukemic human bone marrow (phase contrast observations).
Single cell observations of normal and of leukemic human bone marrow cells demonstrated cell-cell interactions of lymphocytes with hematopoietic progenitor cells. In all cases lymphocytes and target cells were from the same individual. Lymphocyte-target cell interactions occurred more frequently with normal committed progenitor cells and leukemic blast cells from acute myeloid leukemia than with precursor cells of the proliferative cell pool, including myeloblasts, promonocytes, erythroblasts and megakaryocytes. Both induction of mitosis and degeneration of the progenitor cells occurred after cell-cell interaction with almost the same frequency. Acute myeloid leukemic blast cells degenerated after contact with lymphocytes with the same frequency as normal progenitor cells (i. e. in 16% of cell contacts), but especially during mitosis. In contrast, normal and regenerating bone marrow progenitor cells from myeloproliferative diseases demonstrated no degeneration after cell-cell interaction with lymphocytes during mitosis. Otherwise the induction of mitoses by lymphocyte-target cell interactions was more frequently observed in normal progenitor cells than in leukemic blasts.


A glimpse on the function of chitosan as a dental hemostatic agent.
Managing a bleeding patient can be a challenge during dental surgery. Profuse hemorrhage due to platelet defects, coagulation disorders, vascular anomalies, medication-induced patients, as well as inherited bleeding ailments result in soft tissue hematoma, septic shock, compromised airway, and in some severe cases, death could occur. A vast array of surgical hemostatic agents are available to stop bleeding, including chitosan-based hemostatic agents. Chitosan has an advantage over other topical hemostatic materials for its ability to promote shorter bleeding times and assist in healing. Massive behind-the-scene research and development efforts are ongoing to increase the performance of chitosan as a hemostatic agent. Numerous studies on chitosan use in dental hemostasis have registered it as being safe, biodegradable, biocompatible, promoting healing, antimicrobial and bioactive. This article reviews the application of chitosan in managing hemostasis in dental patients.


Protective effects of colchicine in an experimental model of necrotizing enterocolitis in neonatal rats.
The pathophysiology of necrotizing enterocolitis (NEC) includes the massive production of endogenous cytokines with exaggerated activation of inflammatory pathways. Colchicine has been used as an anti-inflammatory agent. The aim of this study was to investigate the possible beneficial effects of colchicine in a neonatal rat model of NEC. We randomly divided rat pups into three groups: a control group, a saline-treated NEC group, and a colchicine-treated NEC group. We induced NEC by hyperosmolar enteral formula feeding and exposure to hypoxia/reoxygenation after cold stress. Intestinal samples were harvested for biochemical and histopathologic analyses. The grade of intestinal injury of pups in the saline-treated NEC group was significantly higher than in the control and colchicine-treated groups (P < 0.001 and 0.003, respectively). The median level of intestinal malondialdehyde was significantly higher in the saline-treated NEC group compared with the control group (P = 0.006) or the colchicine-treated NEC group (P = 0.015). We observed significantly higher activity levels of intestinal superoxide dismutase and glutathione peroxidase in the colchicine-treated NEC group compared with the saline-treated NEC group (P = 0.033 and 0.030, respectively). The tissue levels of tumor necrosis factor-α and interleukin-1β were significantly higher in the saline-treated NEC group compared with the colchicine-treated NEC group (P < 0.001 and 0.003, respectively). We observed that in this model of NEC, colchicine had favorable effects on intestinal histologic and biochemical changes.


Pan-colonic field defects are detected by CGH in the colons of UC patients with dysplasia/cancer.
BAC arrays were used to evaluate genomic instability along the colon of patients with ulcerative colitis (UC). Genomic instability increases with disease progression and biopsies more proximal to dysplasia showed increased instability. Pan-colonic field copy number gain or loss involving small (<1Mb) regions were detected in most patients and were particularly apparent in the UC progressor patients who had dysplasia or cancer. Chromosomal copy gains or losses affecting large regions were mainly restricted to dysplastic biopsies. Areas of significant chromosomal losses were detected in the UC progressors on chromosomes 2q36, 3q25, 3p21, 4q34, 4p16.2, 15q22, and 16p13 (p-value⩽0.04). These results extend our understanding of the dynamic nature of pan-colonic genomic instability in this disease.


Conformational homologies among cytokines: interleukins and colony stimulating factors.
Some 30 cytokine amino acid sequences (mainly interleukins, colony stimulating factors and tumor necrosis factors) have been examined for evidence of secondary structure as well as longer-range interactions of a type likely to lead to stable alpha-helical bundles. Most, though not all, of the cytokines examined have a high predicted alpha-helical content (40-60%) and quasi-repeating heptads containing i/i + 3 apolar periodicities. This major subset of the cytokines is predicted to be characterized by molecules in which 4-alpha-helical bundles with an average length of 25A are the most marked conformational features. Based on these conclusions, we suggest structures for huG-CSF, huGM-CSF and muIL-5 in which defined loop segments at the ends of helical bundles are the most likely sites for binding and recognition by specific cell receptors. As such, they provide a means for testing or refining the three working models we have defined, using currently available methods of site-directed substitution and deletion mutagenesis, as well as synthetic peptides corresponding to the proposed loop sequences and the use of monoclonal antibodies of defined epitopic specificity. The structure arrived at for huGM-CSF is consistent with the limited data currently available concerning the residues which are important for binding and activity.


A simplified and efficient procedure for the purification of apolipoprotein AI from human serum high-density lipoprotein-3 by preparative isoelectric focussing on polyacrylamide gel beads.
An improved method is described for the purification of milligram amounts of apolipoprotein AI from serum apo-HDL3 by isoelectric focussing on polyacrylamide gel beads. The procedure involves a single focussing over a narrow (1.3 unit) pH gradient, and permits isolation of apo-AI of exceptional purity and in high yield (75% recovery of HDL3 protein, ca. 50% corresponding to pure apo-AI). The electrophoretic mobility, pI values, molecular weight, antigenicity and amino acid composition of such apo-AI were indistinguishable from those reported in the literature. A rabbit antiserum to apo-AI isolated by focussing exhibited similar immunological reactivity to one prepared from an antigen isolated by gel filtration chromatography; moreover, apo-AI purified by the respective procedures reacted identically with both antisera. We conclude that isoelectric focussing on a support of polyacrylamide gel beads (as Bio-Gel P60) presents certain advantages for the isolation of highly purified apo-AI over both conventional chromatographic procedures and isoelectric focussing on a Sephadex support.


Nurses' perspectives of pain assessment and management in dementia care in hospital.
To explore nurses' perspectives and generate recommendations for nursing practice of pain assessment and management in dementia care in a hospital setting. Semi-structured face-to-face interviews were conducted with nurses who had experience in dementia care from two care units of a regional hospital. Data were analysed using six phases of reflexive thematic analysis. Eight nurses from two inpatient units of a local district hospital were interviewed. Five themes were identified: (1) ways of understanding, (2) practicality of pain assessment tools, (3) usefulness of pain scores, (4) analgesia use and (5) limitations to practice. Nurses perceived pain tools did not sufficiently help to assess pain in people with dementia, and adaptation was often needed when scoring pain. Overuse of analgesia, trial-and-error practice and delayed prescriptions for analgesia limited pain management effectiveness for people with dementia during hospitalisation. Pain tools are preferably used as a complementary method in addition to nurses' intuitional judgement. Reporting pain via scores requires a more complete narrative description from the source of pain reports to allow clinicians to accurately report a persons' pain. Clinicians must minimise trial-and-error practice in analgesia by conducting comprehensive pain assessments. Health-care organisations need to foster timely collaboration between clinicians to support nurses' practice limitations for effective analgesia administration in dementia care.


Human testis cytosol and ovarian follicular fluid contain high amounts of interleukin-1-like factor(s).
Human testicular cytosol and ovarian follicular fluid were analyzed for the presence of interleukin-1 (IL-1)-like factors. Both the follicular fluid and testis cytosol preparations exhibited significant IL-1-like activity as determined by the murine thymocyte proliferation bioassay. The dose-response lines obtained with the gonadal preparations were parallel to each other and to those obtained with monocyte-derived IL-1 and the activity of the gonadal IL-1 could be neutralized by specific IL-1 antibodies. After gel chromatography of human follicular fluid (hFF) and human testis cytosol (hTC) proteins, IL-1 activity was found in the molecular weight region between 30 and 50 kilodaltons (kDa). Chromatofocusing of IL-1 from hFF and hTC revealed that the major part of IL-1 in both cases exhibited similar charge properties (pI less than 6.0). However, two extra peaks (pI 7.0 and greater than 9.0, respectively) were observed in hFF preparations. After isoelectrofocusing (IEF), IL-1 activity of hFF was also found in two different pH regions; a broad area of activity was localized between pH 5.5 and 7.0, while a sharp peak was observed with an approximate pI value of 9.5. Re-chromatofocusing or IEF of alkaline IL-1-like activity resulted in a heterogeneous profile of IL-1-like activity suggesting that the alkaline material may represent either a precursor or an aggregated form of the acidic IL-1. None of the IL-1 peaks obtained from hFF or hTC exhibited IL-2 activity as assessed in a specific IL-2 bioassay. The results of the present study indicate that both gonads may produce high amounts of IL-1-like factor(s) which might play a regulatory role in normal gonadal function.


Typing of Saccharomyces cerevisiae and Kloeckera apiculata strains from Aglianico wine.
Kloeckera apiculata and Saccharomyces cerevisiae yeast species are dominant, respectively, at the early and at the following stages of wine fermentation. In the present study, PCR fingerprinting and NTS region amplification and restriction were applied as techniques for monitoring yeast population performing Aglianico of Vulture grape must fermentation. Thirty S. cerevisiae and 30 K. apiculata strains were typed by PCR fingerprinting with (GAC)5 and (GTG)5 primers and by complete NTS region amplification followed by restriction with HaeIII and MspI enzymes. S. cerevisiae strains generated two patterns with (GAC)5 primer, while (GTG)5 primer yielded a higher genetic polymorphism. Conversely, in K. apiculata Aglianico wine strains (GAC)5 and (GTG)5 primers generated the same profile for all strains. Restriction analysis of the amplified NTS region gave the same profile for all strains within the same species, except for one strain of S. cerevisiae. The PCR fingerprinting technique was useful in discriminating at strain level S. cerevisiae, particularly with the primer (GTG)5. RFLP patterns generated from the NTS region of the two species can be more easily compared than the patterns resulting from PCR fingerprinting, thus RFLP is more suitable for the rapid monitoring of the species involved in different stages of fermentation. The molecular techniques used allow discrimination of S. cerevisiae at strain level and monitoring of the ratio of S. cerevisiae/K. apiculata during the fermentation process. Thus, their application can assure technological adjustments in a suitable time.


[Analysis of mutation frequency following continuous and fractionated application of ethyleneimine and ethyl methanesulfonate to male sex cells of Drosophila melanogaster].
The increase in the frequency of recessive lethal sex-linked mutations induced by fractionated effect of ethylene imine (EI) an ethylmethanesulphonate (EMS) on mature sperm of Drosophila melanogaster was observed and compared uith prolonged treatment (8h) and with the additive effect. This effect of dose fractionation was observed in the case of the treatment of sperms in male gonads and in female spermathecas. The increase of the mutation frequency was noted by brood-pattern method after fractionated treatment of spermatocytes and spermatogonia only with EMS. This increase was not observed under the effect of EI on spermatocytes and spermatogonia because of the high sierilization activity of EI. Possible mechanisms of the effects observed are discussed.


Serologic response against cardiolipin and enterobacterial common antigen in young patients with acute myocardial infarction.
Elevation of anticardiolipin antibodies has been observed in myocardial infarction and in many infections. To elucidate this topic, paired serum specimens from 40 patients with acute myocardial infarction were tested for anticardiolipin antibodies (solid-phase enzyme immunoassay) and enterobacterial common antigen antibodies (indirect hemagglutination test). Forty-one randomly selected individuals and 30 patients with chronic coronary heart disease served as controls. All individuals were males whose maximum age was 50 years. In patients with acute myocardial infarction the levels of anticardiolipin antibodies in paired sera rose significantly in all immunoglobulin classes (18% in the IgG class, 26% in the IgA class, and 43% in the IgM class), whereas no elevations occurred in the other groups. Fifteen of the acute myocardial infarction patients also showed at least a fourfold increase in enterobacterial common antigen antibodies, as compared with only one such increase in the two other groups combined. The increases were less marked than those seen in pronounced enterobacterial infections. These two reactions were closely associated.


IVF, acupuncture and mental health: a qualitative study of perceptions and experiences of women participating in a randomized controlled trial of acupuncture during IVF treatment.
Infertility treatments such as in-vitro fertilization (IVF) are stressful and challenging to mental health and well-being. The use of alternative therapies adjunct to IVF treatment, such as acupuncture, is common and women hope to improve their chance of pregnancy and live birth. While many women engage in acupuncture adjunct to IVF in Australia, few qualitative studies of women's motivations and experiences have been conducted in this field. A qualitative study was nested within a randomized controlled trial of acupuncture during IVF treatment in order to explore women's perceptions of acupuncture, its effects in the context of IVF treatment, and how acupuncture is perceived in relation to the outcome of IVF. Fifty women randomized into both acupuncture and sham acupuncture groups were interviewed using a semi-structured format. In-depth interviews were transcribed, coded and categorized in a theoretical thematic analysis. Two primary themes emerged: 'psychological benefit' and 'perceived influence of acupuncture on fertility/medical outcome'. Regardless of randomization, women in both groups described similar psychological effects suggesting that a placebo effect was present. They were not convinced that acupuncture could enhance their treatment outcome through biomedical pathways. Rather, they perceived that acupuncture or sham acupuncture gave them a psychological advantage through increased relaxation, reduced psychological stress, and enhanced well-being and self-efficacy. In conclusion, there are significant features associated with a placebo effect in acupuncture that might be exploited to provide psychological benefit for women undertaking IVF.


Fish oil n-3 polyunsaturated fatty acids selectively affect plasma cytokines and decrease illness in Thai schoolchildren: a randomized, double-blind, placebo-controlled intervention trial.
To determine whether very long-chain n-3 polyunsaturated fatty acids (PUFAs) affect illness and selected plasma cytokines in schoolchildren. Thai schoolchildren aged 9 to 12 years consumed milk containing placebo (soybean) oil (n = 86) or fish oil (n = 94) on 5 days per week for 6 months; the latter provided 200 mg eicosapentaenoic acid plus 1 g docosahexaenoic acid daily. Episodes and duration of illness were recorded, and plasma interleukin (IL)-2 receptor, IL-6, IL-10, and transforming growth factor (TGF)-beta1 concentrations and the fatty acid profile of plasma phosphatidylcholine determined. After intervention, very long-chain n-3 PUFAs were higher in plasma phosphatidylcholine in the fish oil group than in the placebo group (P < .001). The fish oil group showed fewer episodes (P = .014) and shorter duration (P = .024) of illness (mainly upper respiratory tract) than the placebo group. Plasma IL-2 receptor, IL-10, and IL-6 were not affected by either treatment. Plasma TGF-beta1 increased in both groups, but the increase was smaller in the fish oil group, and at the end of supplementation TGF-beta1 concentration was lower in the fish oil group (P < .001). Very long-chain n-3 PUFAs reduce illness, mainly infections, in healthy Thai schoolchildren.


Engineering the Ovarian Hormones Inhibin A and Inhibin B to Enhance Synthesis and Activity.
Ovarian-derived inhibin A and inhibin B (heterodimers of common α- and differing β-subunits) are secreted throughout the menstrual cycle in a discordant pattern, with smaller follicles producing inhibin B, whereas the dominant follicle and corpus luteum produce inhibin A. The classical function for endocrine inhibins is to block signalling by activins (homodimers of β-subunits) in gonadotrope cells of the anterior pituitary and, thereby, inhibit the synthesis of FSH. Whether inhibin A and inhibin B have additional physiological functions is unknown, primarily because producing sufficient quantities of purified inhibins, in the absence of contaminating activins, for preclinical studies has proven extremely difficult. Here, we describe novel methodology to enhance inhibin A and inhibin B activity and to produce these ligands free of contaminating activins. Using computational modeling and targeted mutagenesis, we identified a point mutation in the activin β A-subunit, A347H, which completely disrupted activin dimerization and activity. Importantly, this β A-subunit mutation had minimal effect on inhibin A bioactivity. Mutation of the corresponding residue in the inhibin β B-subunit, G329E, similarly disrupted activin B synthesis/activity without affecting inhibin B production. Subsequently, we enhanced inhibin A potency by modifying the binding site for its co-receptor, betaglycan. Introducing a point mutation into the α-subunit (S344I) increased inhibin A potency ~12-fold. This study has identified a means to eliminate activin A/B interference during inhibin A/B production, and has facilitated the generation of potent inhibin A and inhibin B agonists for physiological exploration.


Histone Deacetylase 3-Directed PROTACs Have Anti-inflammatory Potential by Blocking Polarization of M0-like into M1-like Macrophages.
Macrophage polarization plays a crucial role in inflammatory processes. The histone deacetylase 3 (HDAC3) has a deacetylase-independent function that can activate pro-inflammatory gene expression in lipopolysaccharide-stimulated M1-like macrophages and cannot be blocked by traditional small-molecule HDAC3 inhibitors. Here we employed the proteolysis targeting chimera (PROTAC) technology to target the deacetylase-independent function of HDAC3. We developed a potent and selective HDAC3-directed PROTAC, P7, which induces nearly complete HDAC3 degradation at low micromolar concentrations in both THP-1 cells and human primary macrophages. P7 increases the anti-inflammatory cytokine secretion in THP-1-derived M1-like macrophages. Importantly, P7 decreases the secretion of pro-inflammatory cytokines in M1-like macrophages derived from human primary macrophages. This can be explained by the observed inhibition of macrophage polarization from M0-like into M1-like macrophage. In conclusion, we demonstrate that the HDAC3-directed PROTAC P7 has anti-inflammatory activity and blocks macrophage polarization, demonstrating that this molecular mechanism can be targeted with small molecule therapeutics.


An extensive data set related to micro-drilling of Al-SiC-B4C hybrid composite through µECM using GRA coupled PCA.
The emerging technique of micro electro mechanical systems throws a lot of challenging in the micro and nanoscale of machining. The present research explores the development of hybrid aluminium composite with hard particles boron carbide and silicon carbide in 10% volume fraction, and drilling of micro-holes using micro Electro Chemical Machining (µECM) process. The experiments were conducted based on Taguchi's design of experiments. The chief drilling parameters considered for electrochemical drilling were frequency, voltage, current, and electrolyte concentration. The machining duration and electrode wear were observed as the machining responses. After the experimental trials, the observed machining responses were transformed into equivalent Multi Response Performance Index (MRPI) through Grey Relational Approach (GRA) approach. This MRPI were further analysed through Principal Component Analysis (PCA) so as to determine the exact interaction effect of each parameter on the machining responses. The supply current and electrolyte concentration were found to impact the responses at a bigger level, but frequency and voltage were at the meagre level. The research declared the purposeful finding of optimized micro-drilling parameters of 30 Hz frequency, 8 V voltage, 16A current, and 0.4 mol of electrolyte concentration. The data presented in the articles are highly contributed to enhancing the micro-drilling process in terms of good process capability.


In-line probing of RNA G-quadruplexes.
Although the majority of the initial G-quadruplex studies were performed on DNA molecules, there currently exists a rapidly growing interest in the investigation of those formed in RNA molecules that possess high potential of acting as gene expression regulatory elements. Indeed, G-quadruplexes found in the 5'-untranslated regions of mRNAs have been reported to be widespread within the human transcriptome and to act as general translational repressors. In addition to translation regulation, several other mRNA maturation steps and events, including mRNA splicing, polyadenylation and localization, have been shown to be influenced by the presence of these RNA G-quadruplexes. Bioinformatic approaches have identified thousands of potential RNA G-quadruplex sequences in the human transcriptome. Clearly there is a need for the development of rapid, simple and informative techniques and methodologies with which the ability of these sequences, and of any potential new regulatory elements, to fold into G-quadruplexes in vitro can be examined. This report describes an integrated methodology for monitoring RNA G-quadruplexes formation that combines bioinformatic algorithms, secondary structure prediction, in-line probing with semi-quantification analysis and structural representation software. The power of this approach is illustrated, step-by-step, with the determination of the structure adopted by a potential G-quadruplex sequence found in the 5'-untranslated region of the cAMP responsive element modulator (CREM) mRNA. The results unambiguously show that the CREM sequence folds into a G-quadruplex structure in the presence of a physiological concentration of potassium ions. This in-line probing-based method is easy to use, robust, reproducible and informative in the study of RNA G-quadruplex formation.


Assessment of brain dopamine metabolism from plasma HVA and MHPG during debrisoquin treatment: validation in monkeys treated with MPTP.
Homovanillic acid (HVA) is formed from dopamine that escapes conversion to norepinephrine in noradrenergic neurons throughout the body as well as from dopamine synthesized in dopaminergic neurons that are mainly in brain. Debrisoquin has been used to diminish peripheral formation of dopamine to enhance the value of plasma HVA as an index of brain dopaminergic activity. This enhancement may be improved if the residual HVA formed in noradrenergic neurons could be estimated. By use of simultaneously measured plasma levels of the major metabolite of norepinephrine, the degree of residual catecholamine formation in noradrenergic neurons can be estimated. By extrapolating to zero MHPG levels the linear relationship of plasma HVA to plasma MHPG, an estimate of HVA formed solely from brain dopaminergic neurons can be obtained. This method was tested by administering debrisoquin to monkeys before and after destruction of brain dopaminergic neurons with MPTP. After MPTP treatment there were decreases in plasma HVA that were relatively greatest when considered in relation to MHPG. The results support the view that the plasma HVA levels at extrapolated zero MHPG levels improves precision in assessing brain dopamine metabolism.


Adjunctive with versus without intravitreal bevacizumab injection before Ahmed glaucoma valve implantation in the treatment of neovascular glaucoma.
Neovascular glaucoma (NVG) is a refractory disease which is difficult to manage. This study aimed at evaluating the efficacy and safety of adjunctive intravitreal bevacizumab (IVB) injection in conjunction with Ahmed glaucoma valve implantation (AGVI) in the management of NVG. This was a retrospective study of patients with NVG in whom AGVI was performed between October 2008 and May 2012. The sample was divided into two groups according to the pretreatment: with adjunctive IVB injection (the IVB group, n = 25 eyes) and without adjunctive IVB injection (the control group, n = 28 eyes). The surgical success rate, number of antiglaucoma medications used, best-corrected visual acuity (BCVA), postoperative complications, regression, and recurrence of iris neovascularization (NVI) were analyzed between the groups. The surgical outcomes of the two groups were compared. The complete success rates in the IVB and control groups were 84.0% and 64.3% at 12 months and 80.0% and 53.6% at 18 months, respectively. There was a significant difference between the two groups (P = 0.041). Mean postoperative intraocular pressures, mean number of postoperative antiglaucoma medications, and BCVA were not significant between the two groups. The NVI in 22 (88.0%) eyes had completely regressed within 2 - 8 days after IVB. However, NVI recurred in 10 eyes (40.0%) 2 - 9 months later after IVB. The IVB group had only 1 case (4.0%) of hyphema out of 25 eyes, while there were 8 (28.6%) cases of hyphema out of 28 eyes in the control group (P = 0.026). This study showed that preoperative IVB injection reduced NVI remarkably, decreased hyphema, and led to higher surgical success rates. Pre-operative IVB injection may be an effective adjunct to AGVI in the management of NVG.


Occurrence of different classes of perfluorinated compounds in Greek wastewater treatment plants and determination of their solid-water distribution coefficients.
The concentrations of eighteen perfluorinated compounds (PFCs: C5-C14 carboxylates, C4, C6-C8 and C10 sulfonates and 3 sulfonamides) were determined in wastewater and sludge samples originating from two different wastewater treatment plants (WWTPs). The analytes were extracted by solid phase extraction (dissolved phase) or sonication followed by solid phase extraction (solid phase). Qualitative and quantitative analyses were performed by LC-MS/MS. According to the results, perfluoropentanoic acid (PFPeA), perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) were dominant in wastewater and sludge samples from both plants. The average concentrations in the raw and treated wastewater ranged up to 75.7 ng L(-1) (perfluorotridecanoic acid, PFTrDA) and 76.0 ng L(-1) (PFPeA), respectively. Concentrations of most PFCs were higher in effluents than in influents, indicating their formation during wastewater treatment processes. In sewage sludge, the average concentrations ranged up to 6.7 ng g(-1) dry weight (PFOS). No significant seasonal variations in PFCs concentrations were observed, while higher concentrations of PFOA, PFOS and perfluorononanoic acid (PFNA) were determined in the WWTP receiving municipal and industrial wastewater. Significantly different distribution coefficient (Kd) values were determined for different PFCs and different type of sludge, ranging between 169 L kg(-1) (PFHxS) to 12,922 L kg(-1) (PFDA).


[Discussion about the application of risk management to medical devices].
Safety and effectiveness of medical devices is a focus of people's attention, which is also a central work for the government's administration. Carrying out safety standards of medical devices, implementing the quality system standards and risk management standards are supplemented with each other. The risk management is an indispensable part to the quality management system of medical devices.


The circular RNA circFARSA sponges microRNA-330-5p in tumor cells with bladder cancer phenotype.
Circular RNAs (circRNAs) modulate gene expression in various malignancies. However, their roles in the occurrence of bladder cancer (BC) and their underlying mechanisms of action are currently unclear. We measured levels of the circRNA phenylalanyl-tRNA synthetase subunit alpha (circFARSA) and target microRNAs (miRNAs/miRs) in BC tissues and cell lines using quantitative polymerase chain reactions. The functions of circFARSA in tumor formation were examined in mice with BC xenografts in vivo and in BC cells via determination of their proliferation, activity, apoptosis, metastasis, and invasion in vitro using cell counting kit-8 assays, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, flow cytometry, western blotting, Transwell assays, and cell wound healing assays. Interactions between miR-330 and circFARSA were predicted and confirmed by bioinformatic processing and dual-luciferase reporter gene assays, respectively. Expression profiles of miR-330 targets in BC cells were assessed via western blotting. circFARSA expression was markedly upregulated in BC tissues and cell lines compared with that in normal bladder samples. Silencing circFARSA expression decreased BC cell proliferation, invasion, and migration but induced their apoptosis in vitro. Downregulating circFARSA expression slowed tumor growth in vivo and directly sponged miR-330 and inhibited its function in BC cells in vitro. Inhibiting miR-330 expression abolished the regulatory effects of circFARSA silencing on the tumor phenotypes of BC cells. circFARSA expression is upregulated and exerts oncogenic functions in BC by sponging miR-330.


Intravascular coagulation in fresh-water submersion: report of three cases.
We describe three cases of fresh-water drowning that were complicated by disseminated intravascular coagulation. Close observation for clinical bleeding, laboratory investigation of the coagulation system, and therapy for disseminated intravascular coagulation, when appropriate, seem indicated in patients hospitalized after fresh-water immersion.


A label-free and signal-on supersandwich fluorescent platform for Hg2+ sensing.
A label-free supersandwich fluorescent assay was demonstrated for the first time by taking Hg(2+) as a detection candidate. The principle of the proposed supersandwich fluorescent platform is based on the formation of supersandwich structure by T-Hg(2+)-T coordination and the fluorescence enhancement of the intercalated Genefinder (GF) in double strand DNA (dsDNA). Such supersandwich fluorescent DNA sensor exhibits a linear range of 10-300 nM for the detection of Hg(2+), with a detection limit of 2.5 nM on the basis of the 3σ/slope (σ represents the standard deviation of the blank samples), which is well below the permit of the U.S. Environmental Protection Agency (<10 nM). The detection can be fulfilled in less than 10 min. The proposed mix-and-detect fluorescent platform exhibits excellent sensitivity, selectivity, and convenient manipulation. The assay was successfully used to detect Hg(2+) in the lake water samples, which suggested its potential in practical samples.


A mathematical analysis of the generation and termination of calcium sparks.
Calcium sparks are local regenerative releases of Ca(2+) from a cluster of ryanodine receptors on the sarcoplasmic reticulum. During excitation-contraction coupling in cardiac cells, Ca(2+) sparks are triggered by Ca(2+) entering the cell via the T-tubules (Ca(2+)-induced Ca(2+) release). However under conditions of calcium overload, Ca(2+) sparks can be triggered spontaneously. The exact process by which Ca(2+) sparks terminate is still an open question, although both deterministic and stochastic processes are likely to be important. In this article, asymptotic methods are used to analyze a single Ca(2+) spark model, which includes both deterministic and stochastic biophysical mechanisms. The analysis calculates both spark frequencies and spark duration distributions, and shows under what circumstances stochastic transitions are important. Additionally, a model of the coupling of the release channels via the FK-binding protein is analyzed.


The Aureochrome Photoreceptor PtAUREO1a Is a Highly Effective Blue Light Switch in Diatoms.
Aureochromes represent a unique type of blue light photoreceptors that possess a blue light sensing flavin-binding LOV-domain and a DNA-binding bZIP domain, thus being light-driven transcription factors. The diatom Phaeodactylum tricornutum, a member of the essential marine primary producers, possesses four aureochromes (PtAUREO1a, 1b, 1c, 2). Here we show a dramatic change in the global gene expression pattern of P. tricornutum wild-type cells after a shift from red to blue light. About 75% of the genes show significantly changed transcript levels already after 10 and 60 min of blue light exposure, which includes genes of major transcription factors as well as other photoreceptors. Very surprisingly, this light-induced regulation of gene expression is almost completely inhibited in independent PtAureo1a knockout lines. Such a massive and fast transcriptional change depending on one single photoreceptor is so far unprecedented. We conclude that PtAUREO1a plays a key role in diatoms upon blue light exposure.


Monitoring land-use change effects on soil carbon in New Zealand: quantifying baseline soil carbon stocks.
We designed a soil carbon monitoring system for New Zealand using country-specific land use and soil carbon information. The system pre-stratifies the country by soil type, climate, and land use. Soils were placed in six IPCC soil categories; Podzols were added as they are widespread throughout New Zealand. Temperature was stratified into two categories, each spanning 7 degrees C. Moisture categories were based on water balance, and included five categories. Temperature and moisture stratification was based on the USDA Soil Classification system. Land use (10 categories) was based on 1980s survey data. Overall, 39 combinations of these three factors (cells) described 93% of the New Zealand landscape. Geo-referenced soil carbon data (carbon concentration and bulk density) were used to quantify average soil carbon for each of the 39 cells. Aggregating the polygons gave an estimated 1990 soil carbon baseline of 1152+/-44, 1439+/-73, and 1602+/-167 Mt C (mean+/-S.D.) for the 0-0.1, 0.1-0.3, and 0.3-1.0 m depth increments (not including forest floor carbon). The system described could also be used to quantify equilibrium changes in soil C associated with land-use change if land use is updated periodically.


Cytoplasmic peptide:N-glycanase (PNGase) in eukaryotic cells: occurrence, primary structure, and potential functions.
A cytoplasmic peptide:N-glycanase has been implicated in the proteasomal degradation of newly synthesized misfolded glycoproteins exported from the endoplasmic reticulum. The gene encoding this enzyme (Png1p) has been identified in yeast. Based on sequence analysis, Png1p was classified as a member of the 'transglutaminase-like superfamily' that contains a putative catalytic triad of amino acids (cysteine, histidine, and aspartic acid). More recent studies in yeast indicate that Png1p can bind to the 26S proteasome through its interaction with the DNA repair protein Rad23p. A mouse homologue of Png1p (mPng1p) bound not only to the Rad23 protein, but also to various proteins related to ubiquitin and/or the proteasome through an extended amino-terminal domain. This NH2 terminus of mPng1p, which is not found in yeast, contains a PUB domain predicted to be involved in the ubiquitin-related pathway. This review will focus on the primary structure and potential functions of the cytoplasmic PNGases.


Linear correlation between patellar positioning and rotation of the lower limb in radiographic imaging: a 3D simulation study.
The purpose of this study was to quantify changes in rotation of the lower limb between image pairs based on patellar position. Additionally, we investigated the differences in alignment between centralized patellar and orthograde-positioned condyles. Three-dimensional models of 30 paired legs were aligned in neutral position with condyles orthogonal to the sagittal axis and then rotated internally and externally in 1° increments up to 15°. For each rotation, the deviation of the patella and the subsequent changes in alignment parameters were calculated and plotted using a linear regression model. Differences between neutral position and patellar centralization were analysed qualitatively. A linear relationship between lower limb rotation and patellar position can be postulated. The regression model (R2 = 0.99) calculated a change of the patellar position of - 0.9 mm per degree rotation and alignment parameters showed small changes due to rotation. The physiological lateralization of the patella at neutral position was on average - 8.3 mm (SD: ± 5.4 mm). From neutral position, internal rotation that led to a centralized patella was on average - 9.8° (SD: ± 5.2°). The approximately linear dependence of the patellar position on rotation allows an inverse estimation of the rotation during image acquisition and its influence on the alignment parameters. As there is still no absolute consensus about lower limb positioning during image acquisition, data about the impact of a centralized patella compared to an orthograde condyle positioning on alignment parameters was provided. IV.


Cocktail biosynthesis of triacylglycerol by rational modulation of diacylglycerol acyltransferases in industrial oleaginous Aurantiochytrium.
Triacylglycerol (TAG) is an important storage lipid in organisms, depending on the degree of unsaturation of fatty acid molecules attached to glycerol; it is usually used as the feedstock for nutrition or biodiesel. However, the mechanism of assembly of saturated fatty acids (SFAs) or polyunsaturated fatty acids (PUFAs) into TAGs remains unclear for industrial oleaginous microorganism. Diacylglycerol acyltransferase (DGAT) is a key enzyme for TAG synthesis. Hence, ex vivo (in yeast), and in vivo functions of four DGAT2s (DGAT2A, DGAT2B, DGAT2C, and DGAT2D) in industrial oleaginous thraustochytrid Aurantiochytrium sp. SD116 were analyzed. Results revealed that DGAT2C was mainly responsible for connecting PUFA to the sn-3 position of TAG molecules. However, DGAT2A and DGAT2D target SFA and/or MUFA. There are two specific TAG assembly routes in Aurantiochytrium. The "saturated fatty acid (SFA) TAG lane" primarily produces SFA-TAGs mainly mediated by DGAT2D whose function is complemented by DGAT2A. And, the "polyunsaturated fatty acid (PUFA) TAG lane" primarily produces PUFA-TAGs via DGAT2C. In this study, we demonstrated the functional distribution pattern of four DGAT2s in oleaginous thraustochytrid Aurantiochytrium, and provided a promising target to rationally design TAG molecular with the desired characteristics.


Chronic Otitis Media and its Correlation with Unilateral Sensorineural Hearing Loss in a Tertiary Care Centre of North India.
Relation between chronic otitis media and sensorineural hearing loss is controversial. Otitis media can cause threshold shift in high frequency range. Also this correlation with patient's age, disease duration and normal ear is of importance for early prevention of hearing loss. The aim of this study was to evaluate relationship between sensorineural hearing loss and chronic otitis media. We also studied association of bone conduction between diseased ear and contralateral normal ear. In this study, 840 patients of unilateral COM were included. Audiometry was done and data analyzed. Majority of patients showing SNHL had COM for over a period of 5 years. Squamosal disease showed early progression to SNHL than mucosal disease. Higher frequencies were found to be more affected and maximum bone gap was seen at 4000 Hz. There was significant difference in mean bone conduction threshold between diseased ear and normal ear at all frequencies (p value < 0.001). Contradicting studies have emerged about association of SNHL with COM. Studies suggest that SNHL does not change with age but with duration. Bone conduction threshold tends to increase with increasing frequency. Few authors also pointed that this may be due to Carhart's effect and not due to disease damaging inner ear.


Cutaneous Wound Generation in Diabetic NOD/SCID Mice and the Use of Nanofiber-Expanded Hematopoietic Stem Cell Therapy.
Despite significant advances in diabetic wound management, diabetic wounds remain a significant global problem that decreases patient's quality of life, and chronic wounds may lead to amputation and death to the patients. To develop a potential regenerative therapy, a xenogeneic transplantation compatible laboratory model needs to be developed. This procedure demonstrates how to isolate hematopoietic stem cells (CD133+) from human umbilical cord blood, expand CD34+ stem cells using a nanofiber scaffold (polyether sulfone-coated and amino group-treated), induce diabetes in immunocompromised (NOD/SCID) mice, induce a cutaneous wound in mice, and how to treat the wound with the nanofiber-expanded CD34+ stem cells. This protocol also shows how to measure wound healing.


Neonatal Streptococcus Pneumoniae pneumonia induces airway SMMHC expression through HMGB1/TLR4/ERK.
Our previous study showed that neonatal S. pneumoniae pneumonia promoted airway smooth muscle myosin heavy chain (SMMHC) expression and AHR development. Researches demonstrated HMGB1, TLR4 and ERK are involved in smooth muscle contractile protein expression, so we hypothesis that HMGB1/TLR4/ERK pathway participated in airway SMMHC overexpression in neonatal S. pneumoniae pneumonia model. Neonatal (1-week-old) BALB/c mice were intranasal inoculated with D39 to establish non-lethal S. pneumoniae pneumonia model. TLR4 was inhibited 2 weeks after infection with TLR4 specific inhibitor (TAK-242). Five weeks after infection, the bronchoalveolar lavage fluid (BALF) and lungs of neonatal S. pneumoniae pneumonia and mock infection mice with or without TLR4 inhibition were collected to assess the expressions of HMGB1, TLR4 and p-ERK1/2. Airway Hyperresponsiveness (AHR) of the three groups was determined by whole-body plethysmograph. Our results demonstrated that neonatal S. pneumoniae pneumonia promoted HMGB1/TLR4 production, SMMHC expression and AHR development significantly, with ERK1/2 phosphorylation decreased remarkably. TLR4 inhibition after pneumonia significantly increased ERK1/2 phosphorylation, reversed airway SMMHC overexpression and alleviated AHR. Neonatal S. pneumoniae pneumonia promotes airway SMMHC expression and AHR through HMGB1/TLR4/ERK.


Degradation of human apolipoprotein B-100 by apolipoprotein(a).
Human plasma low density lipoproteins (LDL) contain a very high molecular weight protein termed apoB-100 (M(r) = 550,000). In many samples of LDL, minor components designated as apoB-74 (M(r) = 407,000) and apoB-26 (M(r) = 145,000) are present. It has been shown that they can arise as a result of proteolytic degradation of apoB-100. Our earlier studies demonstrated that the active forms of lipoprotein(a) (LP(a)) and apolipoprotein(a) (apo(a)) possess proteolytic activity. In the present study we investigated the possibility of apoB-100 degradation in the presence of activated apo(a). LDL were incubated with the purified apo(a) and analyzed by SDS-polyacrylamide gel electrophoresis. It was found that apoB is cleaved by apo(a) with formation of proteolytic fragments including B-74 and B-26. The physiological significance of apoB degradation under the action of apo(a) is considered.


Role of Socioeconomic Factors on Physical and Mental Distress Reported by Alabama Adults with COPD.
Educational attainment, income, and race play significant roles in managing and treating patients with chronic obstructive pulmonary disease (COPD). The purpose of this study was to evaluate the impact of these socioeconomic factors and others on the physical and mental distress reported by patients with COPD living in Alabama. A cross-sectional analysis was completed of Alabama Behavioral Risk Factor Surveillance System 2015-2019 data collected from 4123 respondents who reported that a health professional told them they had COPD, chronic bronchitis, or emphysema. Univariate analyses examined descriptive differences in physical and mental distress among racial groups. Multivariable logistic regression models were used to assess physical and mental distress as a function of race and demographic variables (age, sex, employment status, household income, education level), controlling for dichotomous healthcare access variables (enrollment in a health insurance plan, having a usual source of care, routine check-up in the past 2 years). Most Alabama adults with COPD from 2015 to 2019 were female (64%) and older than 45 years (88%). Annual incomes were low, with >40% of respondents (43.84%) earning <$20,000/year; adults making between $35,000 and $49,999 were less likely (odds ratio 0.60, 95% confidence interval 0.38-0.96) to experience mental distress. Younger Alabama adults with COPD (25-64 years) were approximately two times more likely than respondents ages 65 and older to report mental distress. African Americans were less likely to report physical distress as compared with Whites (odds ratio 0.61, 95% confidence interval 0.44-0.83). Alabama adults who could not work were more likely than those with COPD who were employed/self-employed, out of work, retired, or identified as homemakers to report physical distress. Public health and healthcare practitioners across Alabama should use these analyses to direct more targeted, high-yield interventions that will address existing health disparities among state residents living with COPD.


The progression of an infundibulum to aneurysm formation and rupture: case report and literature review.
Infundibula (IFs) are funnel-shaped symmetrical enlargements that occur at the origins of cerebral arteries and are apparent on 7 to 25% of otherwise normal angiograms. They are frequently considered as normal anatomic variants of no pathogenic significance. We report the case of a ruptured posterior communicating artery aneurysm that had developed at the site of a previously known IF in a 49-year-old hypertensive woman. She had a poor conscious level at admission, with widespread subarachnoid hemorrhage and obstructive hydrocephalus. The patient was immediately ventilated, and an external ventricular drain was inserted. The aneurysm was successfully clipped; however, secondary hemorrhage occurred both before and during craniotomy. She developed marked hypernatremia and subsequently died. This is the 11th case of IF-to-aneurysm progression reported. It suggests that in certain cases, serial investigations may be indicated with IFs to detect aneurysm formation and preempt rupture.


Transcriptome sequencing reveals Cnaphalocrocis medinalis against baculovirus infection by oxidative stress.
Cnaphalocrocis medinalis granulovirus (CnmeGV) is a potential microbial agent against the rice leaffolder. Innate immunity is essential for insects to survive pathogenic infection. Therefore, to clarify the immune response of Cnaphalocrocis medinalis to the viral colonization, the gene expression profile of C. medinalis infected with CnmeGV was constructed by RNA-seq. A total of 8,503 differentially expressed genes (DEGs) were found including 5,304 up-regulated and 3,199 down-regulated unigenes. Gene enrichment analysis indicated that these DEGs were mainly linked to protein synthesis and metabolic process as well as ribosome and virus-infection pathways. Specifically, a significantly up-regulated PiggyBac-like transposon gene was identified suggested that the enhancement of transposon activity is related to host immunity. Further, the DEGs encoding oxidative stress related genes were identified and validated by RT-qPCR. Overall, 9 antioxidant enzyme genes and 4 antioxidant protein genes were up-regulated, and the extensive glutathione S-transferase genes were down-regulated. Our results provide a basis for understanding the molecular mechanisms of baculovirus action and oxidative stress response in C. medinalis and other insects.


Duodenal and rectal obstructions due to urothelial cancer infiltration from recurrent renal pelvic cancer in the bladder wall: An autopsy case.
Duodenal and rectal obstructions due to urological malignancies are relatively uncommon. We report an autopsy case of an 83-year-old man with a history of renal pelvic cancer who presented these obstructions. Autopsy revealed that urothelial cancer infiltrated the bladder wall, duodenal wall, rectal wall, and prostate and widely spread in the retroperitoneal lymphatic vessel. We concluded that renal pelvic cancer recurred in the bladder wall and then infiltrated into each organ because of lymphatic dissemination. The gastrointestinal obstructions due to urinary tract cancer were lethal. Further knowledge and clinical experience regarding these types of obstructions are crucial.


Recurrence and complications of pterygium extended removal followed by extended conjunctival transplant for primary pterygia.
To study the recurrence rate and complications after primary pterygium removal using pterygium extended removal followed by extended conjunctival transplant. Sixty-eight eyes of 57 consecutive patients with primary pterygia underwent pterygium removal using pterygium extended removal followed by extended conjunctival transplant between April 2010 and October 2014. The follow-up period lasted for at least 36 months after the procedure. No recurrences were reported after a mean follow-up period of 40.0 ± 5.7 months (minimum of 36 months). One case (1.4%) developed Tenon granuloma at the donor site 2 weeks after surgery, and it was surgically removed. Transient graft swelling was observed in 22% of the cases, and transient diplopia was observed in 17.6%. Both graft swelling and diplopia resolved gradually in all cases during the early postoperative period. Loss of corrected distance visual acuity was not reported. Pterygium extended removal followed by extended conjunctival transplant is an effective technique for primary pterygia and resulted in a 0% recurrence rate with minimal intraoperative and postoperative complications.


Acute ST-segment elevation myocardial infarction: critical care perspective.
More than 1.2 million patients suffer from new or recurrent ischemic events occur annually. This includes an estimated 565,000 cases of first and 300,000 cases of recurrent myocardial infarction (MI). Although mortality from acute MI has declined in recent years, it still remains high at 25% to 30%. Despite its high mortality, prognosis can be improved with timely and effective use of evidence-based treatment in the acute setting. This review outlines the critical care management strategies for ST-segment MI (STEMI).


Bone remodeling in hip fracture.
Hip fracture incidence has shown strong upward secular trends in many societies with wide differences in age adjusted incidence between nations. Falls and reduced physical activity have emerged as the strongest risk factors in epidemiological studies, while clinical investigations have pointed to secondary hyperparathyroidism as an important candidate cause of the loss of femoral cortical bone in old age. Until recently there have been few studies performed directly on the region of interest in the proximal femur. Non-invasive methodology using 85Sr has now been developed by our group for measuring bone formation and (with concurrent serial DXA densitometry) resorption in the femoral neck. Bone turnover averaged about 8% annually in controls. A group of younger cases of femoral fracture showed similar indices of total and regional bone formation to a control group; but their resorption was higher. To further investigate this, a femoral neck bone biopsy technique has been developed which can be applied to fracture cases treated by arthroplasty. Preliminary studies have established that the anatomical asymmetry of the neck in cross-section is considerable and imposes restraints on the interpretation of smaller or incomplete femur biopsies. Prospects are quite good that, in the absence of tetracycline pre-labeling, mineralization can be studied by assessment of alkaline phosphatase-positive surfaces in cryostat sections. Moreover, such sections will permit study of other anatomically localized metabolic activities as well as antigen expression and osteocyte viability. Candidate mechanisms for the regional decline in bone quality as well as bone mass in subjects suffering hip fracture can now be investigated more effectively.


Functional characterization and expression of endothelin receptors in rat carotid artery: involvement of nitric oxide, a vasodilator prostanoid and the opening of K+ channels in ETB-induced relaxation.
We aimed to functionally characterize endothelin (ET) receptors in the rat carotid artery. mRNA and protein expressions of both ETA and ETB receptors, evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and Western immunoblotting, were detected in carotid segments. Immunohistochemical assays showed that ETB receptors are expressed in the endothelium and smooth muscle cells, while ETA receptors are expressed only in the smooth muscle cells. In endothelium-denuded vessels, levels of ETB receptor mRNA were reduced. Vascular reactivity experiments, using standard muscle bath procedures, showed that ET-1 induces contraction in endothelium-intact and -denuded carotid rings in a concentration-dependent manner. Endothelial removal enhanced ET-1-induced contraction. BQ123 and BQ788, selective antagonists for ETA and ETB receptors, respectively, produced concentration-dependent rightward displacements of the ET-1 concentration-response curves. IRL1620, a selective agonist for ETB receptors, induced a slight vasoconstriction that was abolished by BQ788, but not affected by BQ123. IRL1620-induced contraction was augmented after endothelium removal. ET-1 concentration dependently relaxed phenylephrine-precontracted rings with intact endothelium. The relaxation was augmented in the presence of BQ123, reduced in the presence of BQ788 and completely abolished after endothelium removal. IRL1620 induced vasorelaxation that was abolished by BQ788 and endothelium removal, but not affected by BQ123. Preincubation of intact rings with N(G)-nitro-L-arginine methyl ester (L-NAME), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), indomethacin or tetraethylammonium (TEA) reduced IRL1620-induced relaxation. The combination of L-NAME, indomethacin and TEA completely abolished IRL1620-induced relaxation while sulfaphenazole did not affect this response. 4-aminopyridine (4-AP), but not apamin, glibenclamide or charybdotoxin, reduced IRL1620-induced relaxation. The major finding of this work is that it firstly demonstrated functionally the existence of both ETA and ETB vasoconstrictor receptors located on the smooth muscle of rat carotid arteries and endothelial ETB receptors that mediated vasorelaxation via NO-cGMP pathway, vasodilator cyclooxygenase product(s) and the activation of voltage-dependent K+ channels.


Three-dimensional collimated self-accelerating beam through acoustic metascreen.
We report the generation of three-dimensional acoustic collimated self-accelerating beam in non-paraxial region with sourceless metascreen. Acoustic metascreen with deep subwavelength spatial resolution, composed of hybrid structures combining four Helmholtz resonators and a straight pipe, transmitting sound efficiently and shifting fully the local phase is evidenced. With an extra phase profile provided by the metascreen, the transmitted sound can be tuned to propagate along arbitrary caustic curvatures to form a focused spot. Due to the caustic nature, the formed beam possesses the capacities of bypassing obstacles and holding the self-healing feature, paving then a new way for wave manipulations and indicating various potential applications, especially in the fields of ultrasonic imaging, diagnosis and treatment.


Comparison of titanium and Robinson stainless steel stapes piston prostheses.
Although stainless steel stapes prostheses have generally been considered magnetic resonance imaging safe, there is concern that this may change with the development of more powerful imaging systems. The objective of the study was to determine whether a titanium piston stapes prosthesis would be audiometrically and surgically equivalent to a Robinson stainless steel piston for stapedectomy. Retrospective chart review. Private otology practice. In all, 50 patients underwent stapedectomy with a Gyrus titanium piston prosthesis. These patients were matched on the basis of age and preoperative bone-conduction scores with patients who underwent stapedectomy with a Robinson stainless steel piston prosthesis. Audiometric results are analyzed, and surgical complications noted. There was no significant difference between groups in hearing improvement or postoperative air-bone gap. The mean four-frequency hearing improvement was 27.7 dB for the stainless steel group and 27.8 dB for the titanium group. The mean postoperative air-bone gap was 2.65 dB for the stainless steel group and 2.60 for the titanium group. Neither group had a surgical complication. The titanium stapes prosthesis is a good alternative to a stainless steel prosthesis.


Effects of low doses of cholinesterase inhibitors on behavioral performance of robot-tested marmosets.
To investigate at which dose levels undesirable effects started, behavioural performance and several physiological parameters were measured in marmosets (Callithrix jacchus) after soman (1.75 and 3.5 micrograms/kg), sarin (3 and 6 micrograms/kg), physostigmine (10 and 20 micrograms/kg), and pyridostigmine (200 and 400 micrograms/kg). Effects on performance were investigated with a discrete-trial, two-choice visual discrimination task and a hand-eye coordination task. The former test appeared more sensitive to disruption than the hand-eye coordination task. "Motor speed" was not disrupted by any of the four compounds. However, "choice time" as well as "no attempts" increased and were clearly more disturbed by soman and physostigmine than by sarin and pyridostigmine. All effects had disappeared after 24 h. Except for a small effect of sarin on heart rate and blood pressure, none of the cholinesterase (ChE) inhibitors affected a number of physiological parameters at behavioural effective does that caused a profound ChE inhibition in blood. Take together, these results strongly suggest that both soman and physostigmine may interfere with higher CNS functions at low dose levels. These effects may go undetected because physical signs are absent.


Quantity Metrics and Proxy Indicators to Estimate the Volume and Appropriateness of Antibiotics Prescribed in French Nursing Homes: A Cross-sectional Observational Study Based on 2018 Reimbursement Data.
Antibiotic resistance is an increasing threat to public health globally. Indicators on antibiotic prescribing are required to guide antibiotic stewardship interventions in nursing homes. However, such indicators are not available in the literature. Our main objective was to provide a set of quantity metrics and proxy indicators to estimate the volume and appropriateness of antibiotic use in nursing homes. Recently published articles were first used to select quantity metrics and proxy indicators, which were adapted to the French nursing home context. A cross-sectional observational study was then conducted based on reimbursement databases. We included all community-based nursing homes of the Lorraine region in northeastern France. We present descriptive statistics for quantity metrics and proxy indicators. For proxy indicators, we also assessed performance scores, clinimetric properties (measurability, applicability, and room for improvement), and conducted case-mix and cluster analyses. A total of 209 nursing homes were included. We selected 15 quantity metrics and 11 proxy indicators of antibiotic use. The volume of antibiotic use varied greatly between nursing homes. Proxy indicator performance scores were low, and variability between nursing homes was high for all indicators, highlighting important room for improvement. Six of the 11 proxy indicators had good clinimetric properties. Three distinct clusters were identified according to the number of proxy indicators for which the acceptable target was reached. This set of 15 quantity metrics and 11 proxy indicators may be adapted to other contexts and could be used to guide antibiotic stewardship programs in nursing homes.


Effectiveness of an inactivated SARS-CoV-2 vaccine in children and adolescents: a large-scale observational study.
Policymakers urgently need evidence to adequately balance the costs and benefits of mass vaccination against COVID-19 across all age groups, including children and adolescents. In this study, we aim to assess the effectiveness of CoronaVac's primary series among children and adolescents in Chile. We used a large prospective national cohort of about two million children and adolescents 6-16 years to estimate the effectiveness of an inactivated SARS-CoV-2 vaccine (CoronaVac) in preventing laboratory-confirmed symptomatic SARS-CoV-2 infection (COVID-19), hospitalisation, and admission to an intensive care unit (ICU) associated with COVID-19. We compared the risk of individuals treated with a complete primary immunization schedule (two doses, 28 days apart) with the risk of unvaccinated individuals during the follow-up period. The study was conducted in Chile from June 27, 2021, to January 12, 2022, when the SARS-CoV-2 Delta variant was predominant but other variants of concern were co-circulating, including Omicron. We used inverse probability-weighted survival regression models to estimate hazard ratios of complete immunization over the unvaccinated status, accounting for time-varying vaccination exposure and adjusting for relevant demographic, socioeconomic, and clinical confounders. The estimated adjusted vaccine effectiveness for the inactivated SARS-CoV-2 vaccine in children aged 6-16 years was 74.5% (95% CI, 73.8-75.2), 91.0% (95% CI, 87.8-93.4), 93.8% (95% CI, 87.8-93.4) for the prevention of COVID-19, hospitalisation, and ICU admission, respectively. For the subgroup of children 6-11 years, the vaccine effectiveness was 75.8% (95% CI, 74.7-76.8) for the prevention of COVID-19 and 77.9% (95% CI, 61.5-87.3) for the prevention of hospitalisation. Our results suggest that a complete primary immunization schedule with the inactivated SARS-CoV-2 vaccine provides effective protection against severe COVID-19 disease for children 6-16 years. Agencia Nacional de Investigación y Desarrollo (ANID) Millennium Science Initiative Program and Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias (FONDAP).


The Efficacy of Adjuvant Targeted Therapy in Patients with Advanced Renal Cell Carcinoma: A Systematic Review and Meta-Analysis.
The aim of this systematic evaluation and meta-analysis was to analyze the efficacy and adverse effects of adjuvant targeted therapy regimens in advanced or metastatic renal cell carcinoma (RCC). Studies eligible for the efficacy of adjuvant targeted therapy regimens in advanced or metastatic RCC published before December 2021 in PubMed, Embase, Cochrane Clinical Trials Database (CENTRAL), and Web of Science were searched for (1) patients with locally advanced renal cell carcinoma (RCC) who received adjuvant postoperative targeted therapy versus those not receiving active treatment; (2) primary endpoint outcomes of disease-free survival (DFS), overall survival (OS), and adverse events (AEs); and (3) design: randomized controlled trial (RCT) as inclusion criteria. Data on DFS and OS were extracted or recalculated by meta-analysis as hazard ratios (HRs), and AEs were compared using a dominance ratio (OR). This systematic evaluation will provide evidence on the effectiveness and adverse effects of adjuvant targeted therapy in patients with advanced RCC. The results of meta-analysis showed that all of the three adjuvant targeted therapeutic drugs (sorafenib, sunitinib, and pazopanib) did not benefit from the adjuvant targeted therapy for DFS and OS and even increase the incidence of AEs compared to the placebo. The aim of this study was to summarize data on DFS, OS, and AEs in patients with advanced RCC treated with targeted therapies. The evidence provided by this systematic evaluation and meta-analysis will help guide clinical decision-making and provide insight into the future management of patients with advanced RCC.


Metal co-ordination in rat liver metallothionein-2 prepared with or without reconstitution of the metal clusters, and comparison with rabbit liver metallothionein-2.
Possible origins of the different metal co-ordination topologies in the recently determined structures of rat metallothionein-2 (MT2) in single crystals and rabbit MT2 in solution were investigated. A complete structure determination for rat MT2 in solution by nuclear magnetic resonance (n.m.r.) showed that the differences in the spatial structures cannot be attributed to the different primary structures of the two species. Comparison of [113Cd7]MT2 obtained by reconstitution of the apoprotein in vitro with preparations using a different procedure showed, moreover, that the metal co-ordination observed in solution by n.m.r. is not an artefact of the protein reconstitution. Solutions of high-pressure liquid chromatographically homogeneous biosynthetic preparations of [113Cd, Zn]MT2 were obtained from rat liver following injection of 113Cd into rats in vivo, without further metal exchange after protein isolation. They contain a mixture of several forms of MT2 with different relative metal compositions, giving rise to an increased number of 113Cd resonances. For the components of the four-metal cluster, the major one of these different forms exhibits patterns in the two-dimensional [1H, 113Cd]-correlated spectra that are indistinguishable from those of [113Cd7]MT2, thereby implying identity of cluster coordination and topology. These results are discussed with regard to continued investigations into the differences between the solution structure and crystal structure of MT2.